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correlation between maternal and fetal plasma levels of glucose and free
fatty acids .                                                           
  correlation coefficients have been determined between the levels of   
glucose and ffa in maternal and fetal plasma collected at delivery .    
significant correlations were obtained between the maternal and fetal   
glucose levels and the maternal and fetal ffa levels . from the size of 
the correlation coefficients and the slopes of regression lines it      
appears that the fetal plasma glucose level at delivery is very strongly
dependent upon the maternal level whereas the fetal ffa level at        
delivery is only slightly dependent upon the maternal level .           
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changes of the nucleic acid and phospholipid levels of the livers in the
course of fetal and postnatal development .                             
  we have followed the evolution of dna, rna and pl in the livers of rat
foeti removed between the fifteenth and the twenty-first day of         
gestation and of young rats newly-born or at weaning . we can observe   
the following facts..                                                   
  1. dna concentration is 1100 ug p on the 15th day, it decreases from  
the 19th day until it reaches a value of 280 ug 5 days after weaning .  
  2. rna concentration is 1400 ug p on the 15th day and decreases to 820
during the same period .                                                
  3. pl concentration is low on the 15th day and during foetal life (700
ug) and increases abruptly at birth .                                   
  4. the ratios rna cyto/dna and pl cyto/dna increase regularly from the
18th day of foetal life .                                               
  5. nuclear rna and pl contents are very high throughout the           
development .                                                           
  6. these results enable us to characterize three stages in the        
development of the rat liver.. - from the 15th day to the 18th day of   
foetal life.. stage of growth through hyperplasia without hypertrophy,  
  - from the 19th day of foetal life to the 3rd day of post-natal life,.
stage of cellular reorganisation,                                       
  - after the 3rd day of post-natal life.. stage of growth through      
hyperplasia and hypertrophy .                                           
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surfactant in fetal lamb tracheal fluid .                               
  lambs delivered by cesarean section with intact fetal circulation have
a fluid filling the trachea . analysis revealed that this fluid         
contained material high in surface activity in lambs delivered near     
term, but less surface activity in premature lambs .                    
  administration of 10 per cent oxygen to the ewe for 1 hour prior to   
delivery did not alter the surfactant properties of the fetal tracheal  
fluid .                                                                 
  two analyses of the fetal tracheal fluid revealed it to contain 146   
and 198 mg. of lipid per 100 ml., 30 to 40 per cent of which was        
phospholipid, part of the active component of surfactant .              
  the investigations reported here offer a model for further research   
into possible intrauterine factors in the pathogenesis of hyaline       
membrane disease .                                                      
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placental and cord blood lipids.. comparison in a set of double ovum    
twins, a stillborn and a live-born .                                    
  1. determinations of phospholipid, total and free cholesterol,        
triglyceride and nefa have been made on placental tissue and cord blood 
in a set of double ovum twins, one stillborn and one live-born .        
  2. similarities occurred in all fractions studied except the cord     
blood triglyceride and nefa levels .                                    
  3. the serum of the stillborn infant contained one-third as much      
triglyceride and 21/2 times as much nefa as did the live-born infant .  
  4. the phospholipid content and the total lipid content of the        
stillbirth placenta were the highest studied in this laboratory which   
includes determinations on 26 live births .                             
  5. the suggestion is made that increased lipoprotein lipase activity  
in the cord blood may accompany intrauterine fetal death .              
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free fatty acid concentration in maternal plasma and fetal body fat     
content .                                                               
  subcutaneous injection of 200 u.s.p. units of heparin into female     
sprague-dawley rats produced large and sustained elevations of plasma   
free fatty acids but no significant change in blood glucose . a group of
pregnant rats received such injections of heparin 3 times daily         
throughout pregnancy . the fetuses from mothers of this group, at 191/2 
and 211/2 days of gestation, had significantly more body fat than the   
fetuses from uninjected mothers . the hypothesis is presented that the  
maternal free fatty acid concentration in part determines fetal fat     
accumulation . it is proposed that the body composition changes noted in
babies of mothers with diabetes might thus be ascribed to abnormally    
high maternal plasma free fatty acid concentrations .                   
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the concentration of non-esterified fatty acids in maternal and fetal   
plasma in intact, alloxan-diabetic and x-ray-irradiated rats .          
  determinations of the non-esterified fatty acids in the plasma of     
pregnant rats showed that there do not exist any increases in the       
concentrations depending on pregnancy during the period from the 20th - 
22nd day of pregnancy . in the fetal plasma the concentrations of       
non-esterified fatty acids only amounted to 40 - 50 per cent of the     
maternal values .                                                       
  with alloxan diabetes produced 2 days prior to the test the           
concentration in the maternal plasma increased three- to fivefold, while
at the same time a significant rise was absent in fetal plasma with     
slightly increased average values .                                     
  whole-body x-ray exposures (dose.. 400r, dose output.. 40r/min) of    
non-pregnant female and of pregnant rats beginning on the 17th day of   
pregnancy did not result in any changes of the concentration of         
non-esterified fatty acids immediately after irradiation .              
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lipid metabolism in toxemia and normal pregnancy .                      
  the amount and fatty acid composition of total lipid extract from     
serum were examined in normal pregnant women in the first, second, and  
third trimesters, and early postpartum period, and in patients with mild
and severe preeclampsia and with essential hypertension . placentas at  
term were also examined for total lipid and its fatty acid composition .
in the normal women, total serum lipid increased during pregnancy . the 
rise was less pronounced in those with preeclampsia or hypertension .   
serum palmitate was mildly but significantly elevated in preeclampsia . 
total lipid and arachidonic acid were elevated in the placentas of      
preeclamptic women . the findings are compared with those obtained from 
animals developing eclampsia on an experimental basis .                 
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essential fatty acids and acids with trans-configuration in the         
subcutaneous and visceral fat of the newborn .                          
  we made an investigation of the subcutaneous and visceral fat in the  
newborn . we estimated the contents of linolic and linolenic acid and of
acids with trans-configuration spectrophotometrically .                 
  we were able to show the penetration of these acids through the       
placental barrier . the essential fatty acid contents of fat in the     
newborn is low . in immature ones about 7-14 g, there is a rising trend.
.I 9
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acetoacetate formation by livers from human fetuses aged 8-17 weeks .   
  slices and homogenates from livers of human fetuses aged 8-17 weeks   
have a low rate of acetoacetate formation which can be raised by        
addition of acetate or octanoate to the incubation medium . it was not  
possible to demonstrate acetoacetate formation by isolated liver        
mitochondria from 17-week-old fetuses, probably because mitochondria are
injured during isolation .                                              
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changes in blood glucose and non-esterified fatty acids in the foetal   
and newborn lamb after injection of adrenaline .                        
  changes in blood glucose and non-esterified fatty acids after         
intravenous adrenaline were measured in foetal, newborn and adult sheep 
in the foetus and immediately after birth there was very little       
increase in either blood glucose or non-esterified fatty acids after    
adrenaline . the response of blood glucose to adrenaline had reached    
adult levels at twenty-four hours of age . the response of non-esterifi-
ed fatty acids to adrenaline increased gradually over the first week .  
.I 11
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electron-microscopic observatations on transference of fat through the  
human placenta .                                                        
  from the results of our previous and present studied on the           
transportation of fat through the human placenta by means of electron   
microscopy, we obtained the following conclusions .                     
  1) neutral fat can permeate through the human placenta without        
dissociation .                                                          
  2) almost all processes of fat permeation seem to be due to the       
biological activity . pinocytosis is most representative, but the       
authors newly found several facts such as dissolution-like change in the
basement membrane and transport via the stroma cell . the authors       
believe that these results will bring a clue to explain the mechanism of
biological transportation of materials through the placenta .           
.I 12
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the content of phosphatides, triglycerides and cholesterol in placentas,
maternal, fetal and new-born liver of the white rat .                   
  thin-layer-chromatographic examinations in the maternal rat liver     
showed different rise of the triglycerides and a significant increase of
the esterified cholesterol, however, no striking changes in the content 
of free cholesterol and lipid phosphorus with the fractions examined    
(lecithin, colamine cephalin, sphingomyelin and lysolecithin) .         
  as compared to the liver of adult rats, the fetal liver contains a    
little less than 50 per cent lipid phosphorus . the difference is       
conditioned by the concentrations of lecithin, and colamine cephalin .  
on the 19th day the content of triglycerides is lower than in the mother
rat . referred to the dry weight, there results a decrease of all       
phosphatide fractions, as well as of the free cholesterol and a slight  
rise of the triglycerides from the 19th to the 22nd day .               
  the rise of the phosphatide concentrations to the values of adult rats
occurs immediately after birth under the influence of milk food, which, 
moreover, leads to a considerable increase of the triglyceride values . 
phospholipid- and triglyceride concentrations of the placenta correspond
to those of the fetal liver . solely the content of free cholesterol is 
higher at the end of pregnancy . the content of triglyceride drops      
towards the 22nd day .                                                  
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analysis of mammalian lens proteins by electrophoresis .                
  lens proteins of different mammalian species were analyzed by         
two-dimensional starch gel electrophoresis . the number of fractions    
detected by this means varied from 11-20 . a-crystallin was resolved    
into two to three components, b-crystallin into 5-11, and y-crystallin  
into three to five components . this technique provides a sensitive     
method for the fractionation of lens proteins and for analyzing species 
differences .                                                           
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an autoradiographic study on cell migration in the eye lens epithelium  
from normal and alloxan diabetic rats .                                 
  lenses from normal and alloxan diabetic rats with and without cataract
were investigated by autoradiography 4 hours, 4 days and 8 days after an
intraperitoneal injection of h3-thymidine (0.4 uc/g body weight) . the  
rats were made diabetic 8 days prior to the injection of thymidine at an
age of 4 weeks . the position of labelled nuclei of the lens epithelium 
was noted and their grain numbers counted . the diabetic rats had a     
lower frequency of labelled nuclei than the controls but after 4 hours  
their grain counts were equal . frequency diagrams of labelled nuclei   
are given for each of the three experimental periods . a predominant    
peak appears after 4 hours at a distance of 30-60 cells in front of the 
beginning of the nuclear arc . a successive shift towards this area was 
observed for the longer experimental periods . the shift of the peaks   
was more restricted in the diabetic animals . this result may best be   
interpreted as an effect of an increased time of cell generation .      
  as an appendix a histotechnique for the eye lens is given in          
collaboration with mrs. gertraude moewis .                              
.I 15
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lens development.. the differentiation of embryonic chick lens          
epithelial cells in vitro and in vivo .                                 
  the behavior of lens epithelial cells from six-day chick embryos was  
studied in three different experimental situations.. (a) explantation   
into several different fluid culture media, (b) explantation followed by
reimplantation into lensectomized embryonic eyes, and (c) explantation  
followed by reimplantation into the embryonic coelomic cavity .         
specimens were examined histologically, and the total volume of the lens
material of each specimen was determined from the planimetry of serial  
sections . the results were interpreted as follows..                    
  1. with a small amount of protein supplement in the culture medium,   
embryonic lens epithelial cells are capable of a limited amount of      
independent cytodifferentiation . without protein supplement they fail  
to undergo any fiber formation .                                        
  2. when returned to the eye environment, cultured epithelial explants 
will respond with a resumption of growth, with further cellular         
differentiation, and with at least some of the morphogenetic changes    
necessary to form a lens . the embryonic coelom will not support these  
responses .                                                             
  3. the initiation of the formation of lens fibers is not sufficient   
for their complete autonomous maturation .                              
  4. the internal architecture of the developing lens is not the only   
determinant of its overall shape .                                      
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treatment of active chronic hepatitis and lupoid hepatitis with         
6-mercaptopurine and azothioprine .                                     
  6-mercaptopurine or azothioprine ('imuran') was used successfully in 3
patients with active chronic hepatitis and 2 with lupoid hepatitis, for 
periods up to 1 year . these drugs allowed modification and even        
abolition of discomforting corticosteroid regimes . their action in     
chronic hepatitis may be analogous to their anti-immune action in       
suppressing homograft rejection .                                       
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treatment of collagen diseases with cytostatics .                       
  22 patients with collagen diseases and 3 patients with other          
immunological diseases were treated with the cytostatic antimetabolites 
('purinethol') 6-mercaptopurine and ('imuran') azathioprine for an      
average period of four months (range one to eleven months) . improvement
was obtained in 17 patients,. and, in 20 out of 22 patients who had been
on long-term glucocorticoid medication, the steroid therapy could be    
permanently discontinued . serious complications occurred, in the form  
of two deaths from pancytopenia and sepsis . the treatment requires     
careful supervision of the patients, and should only be instituted, on  
strict indications, when the alternative is long-term glucocorticoid    
medication .                                                            
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bilateral popliteal cysts in a patient with rheumatoid arthritis .      
  a case of bilateral popliteal cysts and multiple joint subluxations in
a patient with rheumatoid arthritis on corticosteroid medication for    
many years is reported . the effect of long-term corticosteroid therapy 
on all periarticular connective tissue structure and the relationship of
articular disease and popliteal knee cysts to this therapy have been    
discussed .                                                             
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systemic lupus erythematosus and renal transplantation.. report of two  
cases .                                                                 
  two cases of systemic lupus erythematosus along with terminal uremia  
secondary to lupus nephritis are presented . both patients were treated 
with renal hemodialysis and transplantation . certain mechanical,       
infectious, and immunologic problems were responsible for their death . 
there was no evidence of resurgence of lupus erythematosus in either    
patient, and the transplanted kidneys did not show evidence of lupus    
nephritis . renal transplantation should be considered as a last resort 
in treatment of patients with terminal lupus nephritis .                
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arteritis and localised periosteal new bone formation .                 
  1. three patients with localised periosteal new bone formation        
associated with periosteal arteritis and other evidence of systemic     
lupus erythematosus are described .                                     
  2. systemic steroid therapy was valuable in the management of this    
condition .                                                             
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fine structure of subtilis phage sp-50 .                                
  some structural details and anomalous forms of subtilis phage sp-50   
are described .                                                         
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genetic transcription during morphogenesis .                            
  messenger rna's from bacillus subtilis undergoing sporulation,        
germination, or step-down transition have been characterized and        
compared . hybrid competition experiments indicate that these messengers
are derived from distinct genetic loci . the results are consistent with
the hypothesis that differential transcription of the genome occurs     
during morphogenesis . the data also complement previously observed     
changes in morphology and enzymatic activity in sporulating bacteria .  
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renal amyloidosis a clinicopathological study .                         
  the clinical and histopathological data from 40 cases of renal        
amyloidosis diagnosed by percutaneous renal biopsy are presented .      
  twenty-two cases were labelled as 'secondary' amyloidosis, as definite
aetiological factors responsible for renal amyloidosis could be         
discovered . the predisposing disease states leading to amyloid deposits
in the kidney in the order of frequency were fibrocaseous pulmonary     
tuberculosis, bronchiectasis, lung abscess, and ileocaecal tuberculosis 
five cases were labelled as suspected 'primary' amyloidosis as a      
definite evidence of the predisposing disease could not be obtained     
although the skiagram of chest revealed minimal healed foci . no cause  
could be determined in thirteen cases, which were, therefore, labelled  
as 'primary' amyloidosis .                                              
  albuminuria was a constant feature in all the cases and 32 cases      
presented as nephrotic syndrome . the rest of the cases presented with  
hypertension or renal failure in addition to albuminuria .              
  the ancillary procedure, viz., congo-red test, gingival and liver     
biopsies proved to be of limited value in the diagnosis of renal        
amyloidosis .                                                           
  the importance of percutaneous renal biopsy as a diagnostic tool has  
been emphasised .                                                       
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idiopathic autoimmune hemolytic anemia and idiopathic thrombocytopenic  
purpura associated with diffuse hypergammaglobulinemia, amyloidosis,    
hypoalbuminemia and plasmacytosis .                                     
  a case is reported of a sixty-nine year old woman with severe,        
idiopathic, autoimmune hemolytic anemia which was initially controlled  
by splenectomy . a relapse associated with the development of severe,   
autoimmune, thrombocytopenic purpura failed to respond to large doses of
prednisone, but was controlled to a variable degree with imuran .       
  associated features included diffuse hypergammaglobulinemia, excessive
gamma-u proteins in the urine, idiopathic hypoalbuminemia with a greatly
reduced total exchangeable albumin pool, amyloidosis in the spleen and  
other organs, and diffuse plasmacytosis of the bone marrow, lymph nodes,
and thoracic and peritoneal fat . these features and their              
interrelationships are discussed . there was no deficiency in the       
synthesis of specific neutralizing antibodies against viruses,          
indicating that a qualitative immune deficiency did not exist .         
  the frequency of occurrence of thrombocytopenic purpura in such a case
is discussed, as is the prognosis . the mechanism of action of          
antimetabolites in inducing a remission in autoimmune hemolytic anemia, 
as well as the etiology of the disease, is reviewed .                   
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corticosteroid therapy of amyloid nephrotic syndrome .                  
  the results of treatment with prolonged adrenal corticosteroids in 26 
adults with amyloid nephrotic syndrome are presented . eight subjects   
were observed in this series, and 18 additional cases were summarized   
from the literature . twenty-two of the patients were male and four were
female . the diagnosis was established by renal biopsy in 19 instances  
and by autopsy in the others, with 18 patients considered to have       
primary amyloidosis and 8, secondary amyloidosis .                      
  the majority of the subjects died in renal failure with an average    
survival after onset of the disease of 17.6 months . the renal disease  
was indistinguishable from that seen in other forms of the nephrotic    
syndrome, with the possible exceptions of (a) a high incidence of       
purpuric skin lesions, (b) a low or negligible incidence of hypertension
(at times actual hypotension was prominent), and (c) a rapid and        
inexorable progression of azotemia despite persistence of the clinical  
and biochemical characteristics of the nephrotic syndrome . amyloidosis 
was found by percutaneous renal biopsy in 12 per cent of 83 adults with 
the nephotic syndrome .                                                 
  corticosteroids did not appear to affect the progress of the disease  
and were neither beneficial nor detrimental . in view of the high       
incidence of deleterious side effects of prolonged corticosteroid       
therapy and the availability of potent diuretic agents which may be     
helpful in relieving edema in this disorder, it is felt that            
corticosteroids are contraindicated in the treatment of amyloid         
nephrotic syndrome .                                                    
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renal amyloidosis.. a biopsy study .                                    
  the relationship of the amount of amyloid deposition in the kidney to 
the clinical picture is reviewed in 14 cases of renal amyloidosis       
diagnosed by renal biopsy . the large percentage of patients who had the
nephrotic syndrome (11 patients) probably reflects the criteria for     
renal biopsy at this institution . the etiology of the amyloid          
deposition did not seem to be clearly correlated with either the amount 
of amyloid deposition in the kidney or the severity of the clinical     
renal disease . all patients had deposits in the glomerulus, and the    
heavier the deposition the severer the renal disease . of 7 patients who
had biopsy of the bone marrow, all had abnormal types or numbers of     
plasma cells . the age range in primary amyloidosis appeared to be about
the same as that in amyloidosis secondary to myeloma . amyloidosis      
should be suspected in patients with proteinuria, the nephrotic         
syndrome, or renal failure .                                            
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amyloid goitre a case report .                                          
  a case of amyloid goitre in an indian female, aged 27 years, occurring
as a sequelae to pulmonary tuberculosis, is reported .                  
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amyloid.. starch gel electrophoretic analysis of some proteins extracted
from amyloid .                                                          
  proteins extracted by strong urea from washed tissue of patients with 
amyloidosis secondary to several diseases or associated with familial   
mediterranean fever have common major electrophoretic components . in   
hearts of primary amyloidosis one component in common with the secondary
amyloid may be present . however, primary amyloid is much more difficult
to dissolve and does not regularly give the components observed when the
secondary amyloid is extracted . the big question remains as to what    
constituent or constituents comprise the fibrils now known to be a part 
of amyloid .                                                            
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selectivity of protein excretion in patients with the nephrotic syndrome.
  with a gel diffusion precipitin technique and commercially prepared   
antisera, urine/plasma ratios of specific proteins were determined .    
individual protein clearances, expressed as a percentage of transferrin 
clearance, were plotted as ordinates against respective molecular       
weights on a log-log graph . a straight line was evident graphically,   
its constants were estimated by the method of least squares, and the    
slope, expressed as , was determined . the slope of the line may be said
to express the degree of glomerular selectivity to protein excretion .  
sixty-five determinations were performed in 48 patients . 45 satisfying 
the usual criteria of the nephrotic syndrome .                          
  1) those patients with primary renal disease and the nephrotic        
syndrome who displayed high selectivity types of proteinuria ( greater  
than the average for the group + 1 sd) usually respond initially to     
steroid therapy, regardless of the acute or subacute glomerular changes 
observed on renal biopsy .                                              
  2) those patients with chronic renal disease and the nephrotic        
syndrome display an average and frequently a low selectivity type of    
proteinuria .                                                           
  3) there appears to be no characteristic type of selectivity for a    
given pathologic group of patients with the nephrotic syndrome .        
  4) the degree of selective protein excretion is not related to the    
total daily amount of protein being excreted at any one time and remains
fairly constant despite fluctuation in the amount of protein being      
excreted .                                                              
  5) there is a slight correlation of borderline significance between   
the degree of selective protein excretion and the duration of the       
disease, and the initial para-aminohippuric acid clearance .            
  6) a statistically significant correlation exists between the initial 
blood urea nitrogen or inulin clearance and the selectivity type of     
protein excretion . those patients who were not azotemic and had        
initially near-normal inulin clearances had an average selectivity type 
or better .                                                             
  7) it is suggested that if the adult patient is initially azotemic and
has a grossly abnormal inulin clearance, response to therapy is         
unlikely, whereas if the blood urea nitrogen is normal and the inulin   
clearance is near normal, response to therapy cannot be predicted with  
any degree of accuracy . further studies of adult patients with the     
nephrotic syndrome are required to substantiate this premise .          
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some aspects of haemostasis after open-heart surgery .                  
  synopsis in two groups of patients undergoing extracorporeal          
circulation with hypothermia, changes were found in the coagulation     
mechanism which were probably due to the dosage of polybrene            
administered .                                                          
  the role of heparin and polybrene and the concept of activation of the
coagulation mechanism in the production of bleeding after perfusion are 
discussed .                                                             
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a case of interventricular septal defect with dextrocardia and situs    
inversus treated by surgery .                                           
  a case of interventricular septal defect associated with situs        
inversus and dextrocardia in twenty year old male patient was presented 
along with discussion on three types of dextrocardial complexes and with
emphasis on the rarity of occurrence of the intracardiac anomalies in   
true /mirror-image/ dextrocardia with total situs inversus . a comment  
was also made on kartagener's syndrome which was excluded by appropriate
radiographic procedures in this case .                                  
  the closure of the interventricular septal defect with extracorporeal 
circulation was successfully performed under moderate hypothermia .     
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excretion patterns of urinary metabolites of estradiol-4-c14 in         
postmenopausal women with benign and malignant disease of the breast .  
  a study of the excretion patterns of the urinary metabolites of       
estradiol-4-c1j administered to a group of 43 postmenopausal women, 38  
with advanced mammary carcinoma prior to endocrine therapy and 5 with   
benign mammary dysplasia, is reported . a chromatographic method was    
employed for the determination of estradiol, estrone, and estriol and   
other estrogen metabolites . the urinary excretion pattern is defined by
(a) the extent of excretion of isotope in each of 3 successive 24-hr.   
collection periods, (b) the percentage of the urinary radiometabolites  
enzymatically hydrolyzed, (c) the relative concentration of the several 
metabolites in the hydrolyzed fraction . wide subject-to-subject        
variations were found . the metabolites other than estradiol, estrone,  
and estriol comprised a large portion of the total estrogens excreted . 
a significantly lower amount of estradiol was noted in the group of     
women with mammary carcinoma as compared to the amount found in the     
group of women with benign mammary dysplasia, suggesting that the former
group metabolizes more rapidly the administered estradiol . although the
excretion patterns of patients who failed to respond to estrogen        
treatment (nonresponders) differed the greatest from the patterns       
associated with benign disease, distinctive patterns of the urinary     
excretion of isotopic estrogens which allowed a statistically           
significant or clinically useful separation between responders and      
nonresponders to subsequent estrogen therapy were not discovered .      
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the localizing significance of limited simultaneous visual form         
perception .                                                            
  a patient presenting with an isolated /spelling dyslexia/ and         
impairment in picture interpretation (simultanagnosia) was shown by     
tachistoscopic studies to have a pathological limitation of simultaneous
form perception . at autopsy a localized lesion was found within the    
inferior part of the left occipital lobe .                              
  these findings are discussed in relation to the problem of the        
disorder of function underlying /agnosic alexia/ .                      
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visual anosognosia in cortical blindness anton's symptom .              
  denial of blindness in a case of bilateral hemianopia is presented to 
acquaint ophthalmologists with this symptom which is well-known to      
neurologists but is rarely seen by opthalmologists .                    
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the development of social attachments in infancy .                      
  this report is devoted to the formation and development of social     
attachments in infancy . it is suggested that the core of the attachment
function is represented by the tendency of the young to seek the        
proximity of certain other members of the species and that the most     
suitable operational definition may be found in the behavior of the     
individual when deprived of such proximity .                            
  the study takes the form of a longitudinal follow-up, in which 60     
infants were investigated at four-weekly intervals from the early weeks 
on up to the end of the first year and again at 18 months of age . with 
the use of an attachment scale, based on seven everyday separation      
situations, the following three main parameters were explored.. the age 
at onset of specific attachments, the intensity of such attachments, and
the number of objects to whom attachments are formed . a measure of     
fear-of-strangers was also included .                                   
  results indicate that the age at onset of specific attachments is     
generally to be found in the third quarter of the first year, but that  
this is preceded by a phase of indiscriminate attachment behavior,. that
the intensity of specific attachment increases most in the first month  
following onset and that thereafter fluctuations occur in individual    
cases which make long-term prediction difficult,. and that multiplicity 
of objects can be found in some instances at the very beginning of the  
specific attachment phase, becoming the rule in most of the remaining   
cases very soon thereafter . correlations between the attachment        
variables, as well as with the fear-of-strangers measure, are presented,
and an examination is also made of the conditions eliciting protest at  
proximity loss, of the manner in which protest is expressed, and of the 
conditions necessary to terminate protest .                             
  individual differences with regard to the three main parameters were  
explored in a subgroup of 36 infants . a number of variables were       
examined in relation to these individual differences, and suggestions   
made regarding the conditions which affect the manifestation of the     
attachment function .                                                   
  the data are discussed in relation to four themes which emerged from  
the findings.. the nature of the attachment function, its developmental 
origins, its developmental trends, and the influence of the social      
setting .                                                               
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separation anxiety as a cause of early emotional problems in children . 
  in summary, three cases of disturbed behavior in children have been   
discussed, with particular emphasis on disturbances in feeding,         
sleeping, and motility . some of the hypotheses have been presented of  
why such behavior should develop,. the significance of attachment       
behavior and separation anxiety in infants has been particularly        
stressed . difficulties in mothering care are threatening to the child's
sense of security and lead to greater experience of separation anxiety, 
which may then be reflected in various disturbances or alterations in   
his behavior . this experience of separation anxiety is the result of   
early life experience, may reach pathologic proportions, and may account
for many later problems in children and adults .                        
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the production of malignant tumours by nickel in the rat .              
  powdered metallic nickel when injected intramuscularly into rats      
produced tumours of striated muscle origin, most of which were very well
differentiated .                                                        
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studies of nickel carcinogenesis fractionations of nickel in            
ultracentrifugal supernatants of lung and liver by means of dextran gel 
chromatography .                                                        
  chromatographic fractionations have been performed on the             
ultracentrifugal supernatants of homogenates of rat lung and liver by   
the use of columns of dextran gel (sephadex g-100) . a major proportion 
of nickel in these tissue supernatants has been demonstrated to be      
firmly bound to macromolecular constituents . following acute and       
chronic inhalation of carcinogenic levels of nickel carbonyl, the       
predominant increases in the concentrations of nickel have been observed
in the macromolecular fractions . these findings are consistent with the
previous demonstration of nickel in purified preparations of ribonucleic
acids (rna) from several rat tissues, and with the observation of       
increased concentrations of nickel in high-molecular weight rna from    
lung and liver following the inhalation of nickel carbonyl .            
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a study of the inhibitory effect of ethylenediaminetetra-acetic acid on 
the thrombin-fibrinogen reaction .                                      
  1. ethylenediaminetetra-acetic acid reversibly inhibits the           
thrombin-fibrinogen reaction by means of a time-dependent diminution in 
fibrinogen reactivity .                                                 
  2. this alteration of fibrinogen is due to some property of the edta  
molecule in an unchelated form, and is not due to the removal of trace  
metal ions .                                                            
  3. possible explanations for this phenomenon are discussed .          
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intradermal test using cobalt chloride .                                
  selected groups of patients with cobalt allergy and nickel allergy as 
well as normal controls were tested intradermally with cobalt chloride  
in the dilutions 10 to 10 . reactions of the wheal and flare type appear
during the first hours and make the 24-hour reading misleading . the    
papular response to cobalt chloride 10, when read 48 to 96 hours after  
the injection, appears to be a reliable test for cobalt allergy .       
patients with combined nickel-cobalt allergy were excluded from the     
study, and the question of group reactions is not discussed . nickel    
allergics give a somewhat stronger reaction than controls to the        
slightly impure cobalt chloride . it would be preferable if the degree  
of purity of the cobalt chloride were ten times greater .               
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measurements of nickel in biological materials by atomic absorption     
spectrometry .                                                          
  an atomic absorption procedure has been developed which facilitates   
quantitative measurements of nickel in biological materials, including  
urine, ribonucleic acids (rna), and serum proteins .                    
  the sensitivity of detection of nickel by the atomic absorption       
spectrometer (0.10 p.p.m.) was insufficient to permit direct            
measurements of nickel in normal urine . therefore, it was necessary to 
employ a dimethylglyoxime extraction procedure to concentrate the       
nickel, prior to atomic absorption spectrometry .                       
  the coefficients of variation of measurements of nickel in urine and  
human b- globulins were 6.3 and 5.9 per cent, respectively . the        
recovery of nickel added to urine averaged 96 per cent, with a range    
from 94 to 97, and the recovery of nickel added to human b-globulin     
averaged 101 per cent, with a range from 96 to 104 .                    
  the mean concentration of nickel in 24-hr. collections of urine from  
17 normal subjects was 1.8 ug. per 100 ml. (s.d. = 0.8), with a range   
from 0.4 to 3.1 . the mean urinary excretion of nickel was 19.8 ug. per 
24 hr. (s.d. = 10.0), with a range from 7.2 to 37.6 .                   
  the mean concentration of nickel in 5 preparations of ribonucleic     
acids from ultracentrifugal supernatants of homogenates of rat lung was 
48 ug. of ni per gm. of rna, with a range from 34 to 64 . the mean      
concentration of nickel in 5 preparations of rna from ultracentrifugal  
supernatants of homogenates of rat liver was 29 ug. of ni per gm. of    
rna, with a range from 21 to 39 .                                       
  measurements of nickel were performed upon fractions of human serum   
proteins, prepared by continuous-flow electrophoresis, and by           
cold-ethanol precipitation . the highest concentrations of nickel were  
found in preparations of serum b-globulins .                            
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properties of activity of 5'-nucleotidase in human serum, and           
applications in diagnosis .                                             
  the influence of mg , ni , and l-histidine on purified preparations of
bone and intestinal alkaline phosphatases and 5'-nucleotidase, and on   
various mixtures of these enzymes has been studied . the extent to which
these findings can be utilized in the quantitative assay of             
5'-nucleotidase in serum has been evaluated . results are presented on  
the possible utilization of l-histodine in the simultaneous evaluation  
of serum alkaline phosphatase and 5'-nucleotidase activity .            
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some 2-iminoselenazolidin-4-ones and related compounds .                
  a series of 2-iminoselenazolidin-4-ones, selenazolidine-2,4-diones and
some 2-alkylidenehydrazones have been synthesised . wide-range screening
for biological activity failed to reveal any compounds of promise .     
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the influence of methemoglobinemia on the lethality of some toxic       
anions, 1. azide .                                                      
  the time course and extent of the methemoglobinemia induced by        
intraperitoneal sodium nitrite and p-aminopropiophenone (papp) have been
characterized in female mice . the peak methemoglobin formation (34 ) is
achieved in about 40 minutes . comparable levels from papp (15 mg/kg)   
are achieved more quickly (between 5 and 10 minutes) but decline more   
rapidly to normal . both nitrite- and papp-induced methemoglobinemia    
afford a significant degree of protection against poisoning by sodium   
azide when administered in an appropriate time sequence . it was not    
possible under the same circumstances to protect mice against death from
fluoride, cyanate, thiocyanate, selenate, or borate, although some      
prolongation of survival time was seen after fluoride . the formation of
the azide-methemoglobin complex has been demonstrated within intact     
mouse red blood cells, and small amounts of the complex were identified 
in vivo in an antidotal situation . we think it important that the      
protective action of methemoglobinemia has been demonstrated to date    
only against established inhibitors of cytochrome oxidase .             
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selenium as a trace element .                                           
  an account is given of the discovery of selenium by berzelius and gahn
the toxic behaviour of large selenium quantities in soils upon        
vegetation, animals, and man is surveyed . a review is also given of the
role of trace amounts of selenium in the prevention of myopathies in    
animals . finally, some recent theories on the importance of retinal    
selenium to vision are mentioned .                                      
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toxicity of inorganic selenium salts to chick embryos .                 
  the effects of selenite and selenate treatment by air cell injection  
on mortality and growth of 14-day chick embryos during a 64-68 hour     
period were studied . the ld for selenite-se was about 0.5 ppm, based on
weight of the egg contents, and that for selenate-se about 1.8-2.0 ppm .
growth depression was evident from these treatments, but other gross    
effects were not prominent . the treatment of embryos with selenite and 
sulfate together caused a greater mortality than treatment with selenite
alone .                                                                 
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lesions of the islets of langerhans during injections of sodium selenite
administered intravenously .                                            
  sodium selenite was administered intravenously in rabbits and in dogs 
  repeated injections can lead to the development of a diabetic syndrome
in the rabbit .                                                         
  the histological examination of the pancreas in the poisoned animals  
(dogs and rabbits) has shown the existence of lesions of the islets of  
langerhans, mostly of the b cells which lose their granules partly or   
completely .                                                            
  these changes seem analogous to the ones produced by alloxan,. these  
two poisons act at first by inactivating the sh groups, which leads to a
deficiency to which the b cells are very sensitive .                    
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toxicity of sulfur-35, selenium, and tellurium to avian embryos .       
  continuous internal irradiation of chick embryos with sulfur-35       
administered on the 4th or 8th day of incubation produced abnormalities 
similar to those observed in selenium toxicosis of avian embryos . the  
highest level of sulfur-35 (1600 uc) injected into eggs containing 4-day
embryos produced morphological abnormalities more severe than those     
produced by the same level of radiosulfur administered to 8-day embryos,
or by any level of stable selenium tolerated . selenium at levels       
greater than 30 ug killed all the embryos within 24 hours after         
injection . nearly 20 times more tellurium than selenium was required to
kill all the embryos within 24 hours.. no abnormalities were observed in
the tellurium-injected embryos .                                        
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the effect of selenium on the upper respiratory passages .              
  results are reported of examination of workers exposed to selenium,   
with special reference to chronic changes in the respiratory passages . 
the findings are the same as reported in the literature . we emphasize  
the occurrence of teleangiectasias on the uvula and on the posterior    
palatinal arcs and on the epiglotis . we describe the occurrence of the 
first poisoning with selenium xyde in this country . the poisoning      
healed within a few days under symptomatic treatment . the patient had  
however to be transferred into another shop owing to frequent symptoms  
due to toxic effect of selenium . we report also on secondary findings  
in examination of chronic changes and we emphasize particularly the     
finding of profesional selenium external otitis .                       
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the influence of small selenite doses upon the toxic fatty degeneration 
of the liver .                                                          
  sodium selenite (10 ug/kg) manifests a lipotropic effect after        
toxication of the rat by tetrachlorocarbon . this effect is absent when 
the selenite dose is increased to 50 ug/kg . the level of the total     
lipides of the liver after ethionine toxication is not significantly    
influenced by 10 ug selenite/kg . it is increased by 50 ug selenite/kg. 
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selenium-caused tumours .                                               
  in 10 out of 23 heterozygous rats administered 10 mg na seo per 1 kg  
food (containing 12 protein) and surviving for 18 months, cancer of the 
liver (with metastases in the lungs) along with sarcoma and adenoma was 
recorded . in another series of the yet incompleted experiment the      
animals were fed higher quantities of protein and selenium . toward     
14-19 months in three of them sarcoma was noted.. in two sarcoma of the 
lymphatic nodes, and in one- of the mediastinum .                       
  it is suggested that the changes caused by selenium compounds are to  
some extent due to their antagonistic relationship with methionine .    
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blood and bone marrow damage caused by drugs .                          
  drug side effects on blood and bone marrow are briefly reviewed . they
embrace a wide variety of symptoms and pathogenetic mechanisms, and in  
recent years study of these effects has made important contributions to 
our knowledge of the immunology, biochemistry and metabolism of the     
blood cells .                                                           
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hypothermia.. physiologic effects and clinical application .            
  a survey of the background, physiologic effects, indications,         
technique and complications of hypothermia is presented . the           
application of this technique is straightforward and safe when used at  
the proper levels with the proper indications .                         
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ehrlich ascites tumor cells agglutination.. the interference exerted by 
epsilonaminocaproic acid (eac) and its acetyl derivative (eaca) .       
  the activity of epsilon-aminocaproic acid (eac) and of its acetyl     
derivative (eaca) was studied on antigen-antibody reactions, membrane   
antigens and immune globulins .                                         
  in vitro eac and eaca do not affect immune globulins, but they do     
alter the membrane antigens of ehrlich ascites tumor cells and inhibit  
the agglutination reaction induced by a specific antiserum . inhibition 
is only partially due to the antigenic alteration observed, and it      
represents more prominently a direct interference at the level of the   
antigen-antibody reaction .                                             
  the membrane antigen alternations induced by the drugs and by nitrogen
mustard were compared, taking into account their toxicity.. eac and eaca
were found to be much more active and more specific than nitrogen       
mustard .                                                               
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study on the behavior of tumor tissue in diffusion chambers against     
penetrating host cells in tumor-resistant rats .                        
  tumour cells in diffusion chambers, which were implanted in           
tumour-resistant rats, were only destroyed by penetrating immunized host
cells when membrane filters of large pore size were used, whereas with  
filters of small pore size the tumour cells survived and remained       
virulent .                                                              
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current status of hypothermia .                                         
  moderate hypothermia has been recommended for many and varied         
conditions . today its value is being questioned in the light of        
controlled groups of patients . at the moment its use is justified in   
certain cardiac and other operations where circulation may be           
interrupted for short periods.. in general surgical procedures where    
massive, sudden blood loss may be anticipated.. in neurosurgical        
operations where a /relaxed/ brain is required.. following acute hypoxia
such as seen in cardiac arrest.. and perhaps in the therapy of acute    
septicemic shock .                                                      
  profound hypothermia in association with extracorporeal circulation   
rests on shakier premises, but can be of value in major cardiac         
operations where asystole is required and in certain neurosurgical      
procedures where complete interruption of circulation is indicated .    
  there is a great hazard in the development of inadvertent or          
unrecognized hypothermia in the anesthetized patient . monitoring of    
body temperature is an important feature of the care of the patient in  
the operating theater and in the recovery room .                        
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hyperglycemic coronary perfusion.. effect of hypothermia on myocardial  
function during cardiopulmonary bypass .                                
  in a series of 84 animal experiments hyperglycemic perfusion of the   
heart gave significant protection to the anoxic heart . this protection 
was evaluated by ventricular function and contractile force studies and 
was observed after aortic occlusion at 37, 28 and 10 degrees c .        
  metabolic data revealed a considerable myocardial glucose uptake,     
higher coronary ph, higher po and lower pco in the glucose-perfused     
groups as compared to controls .                                        
  a hypothesis for the protective effect may be an alteration in        
metabolic pathway and support of the myocardial enzyme systems          
associated with high glucose concentration and utilization .            
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specific carcinoembryonic antigens of the human digestive system .      
  a wide variety of human adult and fetal tissues were studied by       
immunodiffusion techniques in agar gel to determine whether they        
contained the tumor-specific antigen(s) previously found in colonic     
cancers . in the adult tissues it was demonstrated that identical       
antigens were present in all tested specimens of malignant tumors of the
entodermally derived epithelium of the gastro-intestinal tract and      
pancreas, but were absent from all other tested adult tissues . the     
common antigenic constituents, therefore, represent system-specific     
cancer antigens of the human digestive system . system-specific cancer  
antigens have not previously been demonstrated in humans .              
  experiments with fetal tissues demonstrated that identical antigens   
were also present in fetal gut, liver, and pancreas between 2 and 6     
months of gestation . these components were named /carcinoembryonic/    
antigens of the human digestive system . on the basis of the present    
findings and the recent work regarding control of the expression of     
genetic potentialities in various genetic potentialities in various     
types of cells, it was concluded that the carcinoembryonic antigens     
represent cellular constituents which are repressed during the course of
differentiation of the normal digestive system epithelium and reappear  
in the corresponding malignant cells by a process of                    
derepressive-dedifferentiation .                                        
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the course of influenza virus infection in mice.. organ tissues of      
infected mice tested by electron microscope .                           
  using the electron microscope the presence of inclusions could be     
shown in the lungs and liver of mice infected with the pr 8 strain . the
inclusions contained particles of size and shape closely resembling the 
most frequently seen forms of influenza virus . the presence of         
inclusions in liver tissue might perhaps speak for the possibility of   
virus multiplication in this organ .                                    
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comparative bone marrow study using two aspiration needles and two      
biopsy sites .                                                          
  bone marrow aspiration is now widely used in the diagnosis of         
hematologic diseases and many conditions not primarily affecting the    
blood system . a number of techniques have been devised by which a      
suitable specimen of marrow can be obtained with relatively little      
discomfort to the patient . the two needle sets described in this paper 
have been found to be equally reliable in obtaining bone marrow for     
microscopic study and diagnosis . comparative studies of bone marrow    
aspirated simultaneously from the iliac crest and the sternum in 26     
patients show no significant difference . however, there were four      
instances of dry tap at the iliac site . this fact, in addition to the  
observation that less discomfort was experienced by the patient when the
sternum was used, might indicate that the sternal area is a more        
reliable and efficient site for obtaining bone marrow .                 
  it was also observed during this study that patients experienced less 
discomfort when the university of illinois needle was used . the major  
objection to the use of this needle is the inability to obtain a bone   
core for biopsy .                                                       
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cell populations in the bone marrow of the normal guinea-pig .          
  quantitative data have been obtained for cell-populations in the bone 
marrow of the normal 400g guinea-pig based on a study of 25 animals .   
there was good agreement between two independent groups of observations 
and an average of 1880000 nucleated cells per c. mm. was found . of this
total, 27 were lymphocytes, 31 granulocyte precursors and 26 nucleated  
erythrocyte precursors . whole body populations have been computed and  
the implications of the findings discussed .                            
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pneumocystis carinii pneumonia.. case studies with electron microscopy .
  this paper deals with the clinicopathologic findings in 2 patients    
with pneumocystis carinii pneumonia . the first example was in a        
51/2-month-old white female infant without an underlying disease . the  
second occurred, in association with cytomegalic inclusion disease of   
the lungs, in a 46-year-old white woman who had received steroid        
therapy, cytotoxic agents, and irradiation to the thorax for hodgkin's  
disease . an electron microscope was used for the study of the          
morphology of the organisms in tissue removed at autopsy .              
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the effect of dehydroepiandrosterone on the dehydroxycorticosteroids in 
the plasms in various stages of breast cancer and mastopathy .          
  the depressing effect of dehydroepiandrosterone on plasma             
corticosteroids is, on an average, shortened in advanced breast cancer  
(stage iv) . the lowest corticosteroid values have been found with the  
three groups of patients 6 hours after infusion of                      
dehydroepiandrosterone phosphate . the effect of dehydroepiandrosterone 
being, still provable after 12 hours with the group suffering from      
mastopathy, the breast cancer group of stage iv had at this time already
reached the level of the initial values . the breast cancer group of    
stage iv had at this time already reached the level of the initial      
values . the breast cancer group of stage i/ii behaved intermediately . 
the less lasting effect of dehydroepiandrosterone is attributed to its  
accelerated transformation in advanced breast cancer .                  
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the meaning of ph at low temperatures during extra-corporeal circulation
  a review of the temperature gradients occurring during profound       
hypothermia is made in regard to acid base changes in general, and to ph
readings in particular . it is concluded that terms such as 'body',     
'mean', 'average' and 'core' temperature should be discarded and that   
when a temperature is quoted it should be referred to the site at which 
it was measured .                                                       
  the main circumstances in which blood ph is measured at a temperature 
different from that at which the blood is equilibrated with respiratory 
gases are reviewed by describing the changes which occur during         
tonometry experiments . in this way fundamental changes can be          
understood before considering the more complicated sequences of events  
taking place in the living body .                                       
  the alterations that occur in the concentrations of protein and       
bicarbonate ion when whole blood is cooled are reviewed, together with  
their influence on 'correction factors' . the reasons why these factors 
should not be applied to blood when the living body is undergoing       
hypothermia involving the use of an extra-corporeal circulation are     
discussed .                                                             
  examples of the numerical values for blood ph during the two main     
methods for producing profound hypothermia, one using autogenous lung   
perfusion and the other a pump-oxygenator are given, with reference to  
the influence of pco2 upon these values .                               
  the existing methods of acid-base measurement appear to be            
sufficiently accurate to reflect the metabolic component during profound
hypothermia .                                                           
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induced tumour resistance in rats .                                     
  the human sarcoma hs has been grown in weanling rats treated with     
cortisone . this growth was modified by prior injection of various      
tissue antigens . active /immunity/ was produced by using human placenta
or embryonic tissue as antigen, and similar results were obtained using 
suspensions of rapidly growing human tumours .                          
  the response to other human tissues varied.. foetal muscle and spleen 
were active, whereas adult plasma was inactive except from some patients
with extensive malignant disease .                                      
  passive protection was produced by using certain human sera at the    
time of challenging with hs . sera from five women who aborted showed   
this characteristic . where the pregnancy continued to term,            
antisubstances were not found,. and they were present in the puerperium 
in only two out of fifty cases .                                        
  further groups of rats were given rat embryonic tissues as antigen,   
and the tumour challenge was then made with walker tumour,. the results 
were variable .                                                         
  with a benzpyrene-induced tumour in a pure line of /wag/ rat the      
effect was not obtained except in isolated cases .                      
  in experiments in mice, using as challenge an irondextran induced     
mouse sarcoma, prior injection with embryonic mouse liver or placenta   
increased the resistance to the growth of the tumour, but the tumour has
not as yet been produced in a pure-line mouse . on the other hand mouse 
experiments, using as challenge the crocker tumour, proved negative .   
  it is suggested that immune reactions may play a part in causing some 
abortions .                                                             
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urinary steroid estimations in the prediction of response to            
adrenalectomy or hypophysectomy .                                       
  a clinical trial has been carried out to test the use of the          
discriminant in assessing the suitability of patients with advanced     
breast cancer for hypophysectomy or adrenalectomy .                     
  patients with positive discriminants submitted to hypophysectomy have 
a much better prognosis than patients with negative discriminants       
submitted to adrenalectomy .                                            
  patients selected for adrenalectomy because of negative discriminants 
have a significantly worse response to the operation than patients      
selected by random sample .                                             
  patients selected for hypophysectomy because of positive discriminants
tend to have a better response to the operation than do patients        
selected by random sample, but the difference is not significant .      
  adrenalectomy is not recommended for patients with negative           
discriminants .                                                         
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primary epidermoid cancer of the lung.. ultrastructural study .         
  the early epidermoidic epithelioma of the human lung are initiated by 
the proliferation of body cells whose structure is analogical to that of
the medium cells and/or the modificated basal cells of the normal       
bronchial wall .                                                        
  the presence of desmosomes and tonofibrils in the cells of the stratum
germinativum of the bronchial epithelium and in the cells derived from  
it, allows us a better understanding of the malpighian metaplasis of    
this wall and gives account of the epidermoidic evolution of the        
bronchial epithelioma .                                                 
  certain nuclear and cytoplasmic modifications suggest the possibility 
of a causal virus .                                                     
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biosynthesis of glycoproteins i. incorporation of glucosamine- c into   
liver and plasma proteins of the rat .                                  
  it has been shown that glucosamine-1- c administered intravenously to 
fed rats is rapidly removed from the blood stream and appears first as  
trichloroacetic acid-soluble derivatives in the tissues . this is       
followed by a conversion to macromolecules . at least 80 of the         
administered compound can be recovered in tissues . the liver is by far 
the most active organ in accumulating glucosamine . this is rapidly     
converted to protein-bound components of the liver particulate fraction 
(microsomes and mitochondria) and is then released to the plasma without
appreciable accumulation in the soluble proteins of the liver . it is   
concluded that the glucosamine is transferred to the peptide chains of  
glycoproteins at some stage before these proteins are released from the 
liver particulate fraction .                                            
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acute experimental pneumococcal (type i) pneumonia in the mouse.. the   
migration of leucocytes from the pulmonary capillaries into the alveolar
spaces as revealed by the electron microscope .                         
  in this preliminary study of experimental pneumococcal pulmonary      
pneumonia in the mouse the leucocytes were observed to pass from the    
capillaries into the interstitial tissue and eventually into the        
alveolar spaces through the intercellular junctions of the endothelial  
and epithelial cell membranes .                                         
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a light and electron microscope study of developing respiratory tissue  
in the rat .                                                            
  1. light microscopic observations on the development of the rat lung  
have shown the presence of glandular, canalicular and alveolar stages . 
  2. these same three stages can be identified by electron microscopy   
and all may be present in different parts of the lung at one time, e.g. 
at 40 and 45 mm. c.r. length .                                          
  3. in the glandular stage, the lung tissue itself has an immature     
appearance by light microscopy and by electron microscopy individual    
cells also are immature in respect of organelles . glycogen is present  
in immature cells .                                                     
  4. during the canalicular stage, lung tissue becomes more vascular .  
  5. throughout all stages of development, the 'duct' or 'air' spaces   
are always lined by a continuous and complete epithelium, and blood     
vessels by a complete endothelium .                                     
  6. lamellated inclusion bodies are present in epithelial (endodermal) 
cells at an early stage of development .                                
  7. micropinocytotic vesicles are present in large numbers in both     
epithelial and endothelial cytoplasm and it is suggested that in the    
foetus they may indicate absorption of amniotic fluid from alveolar     
spaces .                                                                
  8. the mechanism of alveolar distension is discussed and its nature   
remains uncertain .                                                     
  9. respiratory tissue of the rat is not fully differentiated at birth 
and the importance of this fact in human infants is discussed .         
  10. the adult blood-air barrier, consisting of epithelium, zona       
diffusa and endothelium, varies in thickness .                          
  this project was performed whilst both of us were in receipt of grants
from the medical research council of canada, for which gratitude is     
expressed . our gratitude is also expressed to miss sylvia smith for    
typing the manuscript .                                                 
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the pathogenesis of viral influenzal pneumonia in mice .                
  the pathogenesis of influenzal pneumonia in mice was studied by       
electron microscopy . mice were inoculated with 1.5 ld of pr8 influenza 
virus and killed at varying intervals after inoculation . observations  
by light microscopy were correlated with those by electron microscopy in
order to evaluate the lesions produced .                                
  at the periphery, the earliest lesions were focal areas of edema of   
alveolar lining cells, the capillary endothelium and the interposed     
basement membrane . this caused an appreciable thickening of the        
blood-air pathway . hypertrophy, degeneration and desquamation of the   
alveolar lining and proliferation of alveolar macrophages resulted in   
complete consolidation, which was progressive up to 1 week after        
infection .                                                             
  the central areas of the lung were affected somewhat differently . at 
3 days after infection, the nonciliated bronchiolar cells showed        
considerable hyperplasia of endoplasmic reticulum and apical cytoplasmic
edema . viral particles matured at the lumen surface of these cells and 
were then released into the bronchiolar lumen . the bronchiolar cells,  
both ciliated and nonciliated, underwent degeneration and sloughed into 
the bronchiolar lumen . the regenerating epithelium was stratified, and 
the surface cells were elongated and flattened . the peribronchiolar    
interstitial tissue gradually became totally infiltrated by cells,      
mostly of the mononuclear type .                                        
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studies on aging with horse crystalline lens gel as a contribution to   
biomorphosis of the mammalian crystalline lens .                        
  the effects of biomorphosis -dash the continuous material change in   
the chemical composition of the organs and tissues -dash are studied on 
the horse crystalline lens in respect of its amino acid content subject 
to substantial variations in the course of life . it is shown by        
electrophoretic and paperchromatographic methods that the qualitative   
composition of horse crystalline lenses remains quite the same, but that
within the individual age stages there occur quantitative variations    
between the individual amino acids .                                    
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the role of alveolar inclusion bodies in the developing lung .          
  the developing alveolar epithelium of man and rat contains            
characteristic inclusion bodies which are heterogeneous structures but  
basically consist of a system of membranous profiles and a limiting     
membrane of the unit type .                                             
  inclusion bodies appear to result from focal cytoplasmic degradation  
which occurs in the rapidly changing cuboidal alveolar epithelium . some
inclusion bodies in the developing rat lung are similar to the so-called
/lamellar transformed mitochondria./ however, evidence is presented     
suggesting that alteration of all cytoplasmic membranes may be involved 
in the process of inclusion body formation . certain images associated  
with the golgi complex are interpreted as early forms of inclusion      
bodies . there is also evidence that inclusion bodies enlarge by        
accretion of membranes which finally are extruded into the alveolar     
space . inclusion bodies are formed and /secreted/ in greater number    
late in fetal life and in early infancy, i.e., at the time when the     
cuboidal alveolar epithelium is differentiating to the mature flattened 
type . the latter contains no inclusion bodies .                        
  on the basis of the morphologic characteristics of the inclusion      
bodies and the distribution of the acid phosphatase reaction, it is     
concluded that inclusion bodies are lysosomal structures active during  
remodeling of the developing alveolar epithelium .                      
  the possible interrelationship of inclusion bodies and pulmonary      
surfactant is discussed .                                               
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retinal detachment, cataract, keratoconus as ocular symptom complex in  
endogenous eczema .                                                     
  with reference to personal observations the authors describe the      
ovular changes encountered in endogenous eczema . besides the cataract  
which has been known to occur already for a long time, retinal          
detachment, keratoconus and keratoconjunctivitis do still belong to the 
symptom complex .                                                       
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postural changes in blood distribution and its relation to the change in
cardiac output .                                                        
  (1) cardiac output and the blood content indices of the several parts 
of the body were measured in 18 subjects including patients with various
diseases using external radioisotope counting techniques . changes in   
these 2 parameters induced by standing were compared with each other .  
  (2) average changes in blood distribution produced by standing were as
follows . decrease in blood content in the /lung/ (-25 ) and in the     
/heart/ (-26 ) and increase in the /thigh/ (+56 ) were statistically    
significant . no significant change was revealed in the /head/, /palm/, 
/liver/ and /abdomen/ .                                                 
  (3) cardiac output and stroke volume decreased by standing in most of 
the cases . recent data were added to those reported previously and were
treated statistically . average decrease in cardiac output was -13 in 6 
control cases, -35 in 16 cases with neurocirculatory asthenia and -35 in
10 cases with hyperthyroidism . the difference was significant between  
control and neurocirculatory asthenia . standing induced a substantial  
increase in cardiac output in a case of idiopathic nodal rhythm,        
although there remains a doubt whether it is the ordinary response in   
this disease .                                                          
  (4) significant linear correlation was revealed between per cent      
change of blood content in the /thigh/ or in the /lung/ and that of     
cardiac output or stroke volume induced by standing . minimal blood     
shift was observed when the latter was extreme, and vice versa . this   
implies as follows.. reactivity of the heart might be influenced by     
posture, and transmural pressure of veins and or capillaries is probably
adjusted, as in arterioles, to compensate for changes in cardiac output 
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comparative studies of the glycogen content of heart, liver and brain   
before and after iodine treatment and under conditions of asphyxia .    
  blood sugar level and glycogen concentration in the heart, brain and  
liver of rabbits after treatment with inorganic iodine, depot insulin,  
iodine and insulin combined, hostacortine and hostacortine and iodine   
combined are being examined . a control group remains untreated . in a  
second test series the glycogen determination under asphyxia (the       
trachea is being pinched off for three minutes) is repeated .           
  contrary to the brain the glycogen content of the heart muscle is not 
dependent upon the blood sugar level . after iodine treatment a lowering
of the blood sugar becomes noticeable, but also an increase in heart    
glycogen . the liver glycogen shows greater variations . the levels     
achieved in these test series therefore show no significant differences 
during asphyxia there is a significant lowering of glycogen in all    
three organs . preliminary treatment with iodine succeeds in stopping   
the lowering of glycogen in the heart muscle and the brain . the        
possible causes for this phenomenon are being discussed .               
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altered immunologic activity in sarcoidosis .                           
  studies in 16 patients with sarcoidosis revealed evidence of          
immunologic alterations other than impaired delayed hypersensitivity .  
transient impairment of the response of lymphocytes cultured from       
patients with sarcoidosis to phytohemagglutinin stimulation was found to
parallel the clinical severity of the disease . the hemolytic activity  
of serum complement was increased . a disproportionate increase in serum
iga was found characteristic of the hyperglobulinemia of sarcoidosis .  
these observations indicate that an altered immune response may be      
important in the pathogenesis of sarcoidosis . a simple hypothesis as to
the specific kind of interaction of infectious agent and immunity which 
might result in the immunologic alterations observed is formulated and  
presented .                                                             
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electron microscopy of cytoplasmic inclusions within /macrophages/ of   
human tissue .                                                          
  the fine structure of inclusions found within the cytoplasm of        
macrophages of human lung, spleen, skin, lymph node, and rectum has been
described .                                                             
  the inclusions appear as concentric or whorled lamellae arranged      
around a core . each lamella is constructed of discrete, parallel       
filaments . the inclusions do not resemble currently described viruses  
or virus-like particles, nor do they resemble asbestos bodies or other  
known atmospheric pollutants or ingestants .                            
  there is some resemblance to lipid phase systems as well as mast cell 
granules,. possibly the inclusions represent partial intracellular      
digestion of phagocytized tissue membranes or ingested mast cell        
granules, respectively . differences and similarities exist between the 
inclusion bodies of macrophages and the granules of mast cells . such   
variations could be due to alterations in mast cell granule morphology  
before or after macrophage ingestion .                                  
  cytologic distinctions between macrophages laden with mast cell       
granules and mast cells proper, remains obscure and requires additional 
experimental evidence for clear electron microscopic differentiation of 
these two cell types .                                                  
  the exact nature of these highly structured bodies remains speculative
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histological research on the lens in condition of hypoxia, changes in   
the mitotic activity of the epithelium .                                
  the effect of hypoxia on the mitotic activity of the cells of the lens
epithelium was studied in 24 rats of the same strain and weight . the   
hypoxia was obtained in the decompression chamber .                     
  the results show that the mitotic activity of the lens epithelium is  
depressed at any of the examined altitudes (6.500, 8.000, 9.500 m),. in 
particular, a marked reduction in the number of the prophases and an    
accumulation in metaphase was observed .                                
  the results were examined from the statistical standpoint and         
discussed .                                                             
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rate of change of carbon dioxide tension in arterial blood, jugular     
venous blood and cisternal cerebrospinal fluid on carbon dioxide        
administration .                                                        
  1. the rate of change of p in arterial blood and cisternal c.s.f., was
measured following 5 percent co administration in eight anaesthetized   
patients undergoing routine air encephalography . ventilation was       
maintained constant throughout the procedure by a respirator . in three 
of the experiments the rate of change of p in the jugular venous blood  
was also measured .                                                     
  2. the rise in p varied between 25.7 and 14.8 mm hg . the final       
samples of blood and c.s.f. were taken 20-25 min after the start of co  
administration in five experiments . at this time the mean rise in p was
65.9 (maximum range 68.1-61.6 percent) of the rise in p . in the        
remaining three experiments the final samples were taken at 15 min when 
the rises in p were 53.2, 39.4 and 38.1 percent of the arterial change .
  3. the increases in p were 57.5, 76.2 and 76.1 percent of those in the
arterial blood . the changes in p in the c.s.f. were smaller than in the
jugular venous blood in all three experiments . in two of the           
experiments the final samples were taken 15 min after the start of co   
administration when the increases of p in the c.s.f. were 68.5 percent  
and 50 percent of those in jugular venous blood . in one experiment     
where the final samples were taken at 20 min the increase in p was 89   
percent of the rise in p .                                              
  4. there was a delay, following the start of co administration, in the
rise of p in jugular venous blood and in the c.s.f . this delay was     
about 1 min in the jugular venous blood but in the c.s.f. it varied from
1.6 to 4.2 min (mean 2.3) .                                             
  5. the rise of p in blood and c.s.f. was exponential . the rise in p  
in all experiments consisted of a fast component with time constants    
which varied between 0.2 and 0.9 min (mean 0.5) and a slow component    
with time constants varying between 6.7 and 14.7 (mean 11.6) .          
  the rise in p and p consisted of only one component . the time        
constants for the changes in jugular venous blood were 2.1, 3.8 and 4.3 
min, whilst in the c.s.f. they varied between 6.7 and 14.7 (mean 11.6) .
  6. it is probable that about 40 percent of the increase in ventilation
following co administration is due to stimulation of an area in the     
antero-lateral surface of the medulla sensitive to changes in ph or p   
(mitchell et al. 1963) . this area is superficial and ventilation is    
affected by changes in the p of the overlying c.s.f . it can be         
predicted from our experiments that the rise in p on co administration  
will take some 30 min to be complete . this may explain the slow rise in
ventilation on co breathing when compared with the rate of rise of      
arterial and jugular venous p .                                         
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studies on the compound lipids from x-ray irradiated animal, ii.        
biological and biochemical properties of the compound lipids in the     
x-ray irradiated rabbit organs .                                        
  for the purpose to clarify the causes of x-ray disturbances a series  
of experiments have been conducted on biological and biochemical        
properties of compound lipids extracted from normal and x-ray irradiated
rabbit organs with a special reference to the p -labeled compound lipids
uptake, inhibitory action to l cell proliferation and uncoupling of     
oxidative phosphorylation, and the following results have been obtained 
  the compound lipids (lysophosphatide rich fraction) isolated from the 
x-ray irradiated rabbit organ have been found to possess a strong       
hemolytic action and also an action to inhibit the cell proliferation as
well as to accelerate the respiration of the mitochondria in the rabbit 
liver and spleen . it has also been proven that they act as to induce a 
marked swelling of mitochondria, to impede the formation of high energy 
phosphate as well as to act as an uncoupler of oxidative phosphorylation
in vivo . in the test to see the uptake of p -labeled compound lipids by
various organs, a marked uptake has been observed in spleen, bone       
marrow, and liver of both irradiated and non-irradiated groups .        
further, the uptake of p -labeled compound lipids in the rabbits given  
intravenous injections of compound lipid fraction for 30 consecutive    
days previously has been found to be greatest in pancreas followed by   
bone marrow, spleen, liver in the order mentioned in male group, whereas
it is greatest in spleen, followed by liver and bone marrow in the      
female group .                                                          
  with these results the discussion was conducted concerning the        
relation between the lipid metabolism and x-ray disturbances .          
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cesium-131 uptake and distribution in the human heart.. an analysis of  
cardiac scans in 104 patients .                                         
  when properly used, cesium-131 is a satisfactory agent for the study  
of cardiac morphology by photoscanning, which we believe is a useful    
adjunctive diagnostic procedure in patients for whom the results of     
other methods of evaluation are at variance with the clinical symptoms  
of cardiac disease . the studies reported here suggest that perhaps     
infarction of a subclinical type, size, or location may occur earlier   
than has been previously thought and that the damage it leaves may not  
be detectable by any means other than autopsy or a technique such as    
scanning . we have not yet been able to measure the actual concentration
of cesium-131 in the heart at autopsy so that the cold and cool areas   
could be examined by histologic sections .                              
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oxygen consumption of paralysed men exposed to cold .                   
  1. oxygen consumption and carbon dioxide output were measured when    
human subjects were cooled for 80-210 min . two subjects were normal,   
one had been almost completely paralysed below the neck by              
poliomyelitis, and two were unconscious as a result of intracranial     
damage and were observed with and without paralysing doses of muscle    
relaxants (d-tubocurarine and gallamine) .                              
  2. when normal subjects and unconscious subjects receiving no drugs   
were cooled, oxygen consumption and carbon dioxide output rose .        
  3. when subjects paralysed by disease or drugs were cooled, oxygen    
consumption and carbon dioxide output were not increased .              
  4. these observations are consistent with the view that in man the    
increase in metabolism on cooling for periods up to 31/2 hr occurs      
solely in skeletal muscle .                                             
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heparin levels during and after hypothermic perfusion .                 
  1. perfusion-temperature influences the rate of heparin-loss during   
extracorporeal circulation, and therefore, the requirement of           
re-heparinization .                                                     
  2. heparin half-lives of approximately 13/4 hours and 21/2 hours were 
calculated during perfusions conducted at average temperatures of 31.5  
and 22.6 c. respectively .                                              
  3. the rate of heparin-loss during extracorporeal circulation is      
inconstant in an individual, and variable between individuals, so that  
exact neutralization requires an accurate estimation of the heparin     
concentration present at the end of perfusion .                         
  4. the protamine titration test provides a crude but simple and       
satisfactory means of monitoring free-heparin levels .                  
  5. complete neutralization of heparin is an important factor in       
minimizing postoperative blood losses .                                 
  6. protamine is a less efficient neutralizing agent than polybrene at 
the same dosage level . it may be most effective in divided dosage .    
  7. /rebound/ was detected in 5 of 45 cases studied, although in only  
one instance was it of a degree likely to be significant .              
  8. significant prolongation of the clotting-time resulting from excess
neutralizing agent, was not evident in this study .                     
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platelet sequestration in man . i. methods .                            
  current methods of labeling platelets with chromium using             
ethylenediamine tetraacetate (edta) as an anticoagulant were found to   
cause rapid hepatic sequestration of nearly all the transfused platelets
about 50 returned to the circulation but then were partially destroyed
in the spleen . less than one-third survived . evidence is presented    
which indicates that edta is injurious to platelets .                   
  when an acid-citrate medium that buffered plasma at ph 6.5 was used as
an anticoagulant, 36 to 85 of the labeled platelets survived (average,  
62 ), and marked temporary sequestration did not occur . studies in     
thrombocytopenic persons showed that circulating platelet cr activity   
measures the true survival of such transfused platelets .               
  the survival and sequestration of platelets were studied in normal    
subjects . the survival data support the concept that platelets die     
chiefly by a process of senescence . external scintillation scanning of 
the various organs suggests that normally the majority of platelets is  
destroyed in the liver .                                                
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acute leukemia associated with phenylbutazone treatment.. a review of   
the literature and report of a further case .                           
  the possible toxic reactions to phenylbutazone have been listed, and a
review of the literature of haematological complications has shown that 
16 deaths attributable to agranulocytosis, aplastic anaemia and         
thrombocytopenia have been recorded . the association between leukaemia 
and phenylbutazone first suggested by bean (1960) has been amplified by 
further reports, which have been reviewed .                             
  a further case history has been presented . of the 15 patients with   
acute leukaemia in which the association has been recorded, there were  
other possible leukaemogenic factors in three, and in a further three   
the drug had been given for only a short time before the leukaemia was  
diagnosed . however, in the remaining nine, the histories are such that 
the phenylbutazone ingestion may have been associated with the          
development of the leukaemia . further studies, which should include    
matched controls, are indicated, and will be required before a definite 
opinion can be given as to any causal relationship between the drug and 
the disease .                                                           
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absorbed radiation dose and excretion of cesium-131 in humans .         
  data relating to the effective half-life, absorbed dose of radiation, 
and excretion rates of cesium-131 have been presented . cesium-131 is an
excellent material for cardiac scanning, since a very low amount of     
radiation is absorbed -dash a dose of the order of one twentieth that   
received in diagnostic x-ray studies of the gastrointestinal tract .    
absorption of radiation can be reduced further by the administration of 
a thiazide type of diuretic and, probably, by catharsis after the scan .
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radiocardiography.. principles and methods .                            
  the aa show the importance of radiocardiography, as a method to       
evaluate the cardiac output, the ventricular volumes and the pulmonary  
blood volume .                                                          
  in this first paper, they are particulary concerned with some         
technical aspects, which are very important to collect data .           
  the position of the collimator on the precordium, the injection of    
isotopes through a catheter, just behind the ventricle near the         
tricuspid valve, the selection of ratemeter constants the velocity of   
paper on the recorder and the way to read the area of the curve, were   
specially discussed .                                                   
  finally, they present the formula used to calculate cardiac output,   
ventricular volumes and pulmonary blood volumes .                       
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reaction of the adrenal cortex during controlled experimental           
hypothermia .                                                           
  the stress reaction caused by hypothermia was studied in rabbits      
subjected to controlled hypothermia by immersion in an icebath . some of
the animals were re-warmed . to anesthetize the animals, pentobarbitone 
sodium (nembutal) was given intraperitoneally, and, in some cases,      
followed by ether anesthesia . further, the stress reaction produced by 
pentobarbitone alone was studied in five animals, and that of ether     
anesthesia alone in three . no anesthesia was given to the three rabbits
placed in the refrigerator . the variation in distribution and amount of
adrenocortical lipids served as an indicator for evaluation of the      
stress reaction .                                                       
  in all the hypothermia tests there occurred changes in the            
distribution and amount of cortical lipids, denoting a stress reaction  
brought about by hypothermia . in rabbits, the barbiturate did not seem 
to inhibit the stress reaction . this may be attributed partly to the   
test animal, as such and partly to the fact that shivering of some      
extent always occurred during the hypothermia experiments .             
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use of a cross-circulation technique in studying respiratory responses  
to co .                                                                 
  the effect of hypercapnia and hypocapnia on ventilation was           
investigated in cross-circulated dogs in which the recipient dog's head 
and neck regions were perfused by blood from a donor dog . hypercapnia  
of the donor dog was produced by administering co -o -n gas mixtures in 
the inspired air . hypocapnia was produced by hyperventilating the donor
dog with the aid of a respiratory pump . when the donor dog was         
hyperventilated, the ventilation of the recipient was maintained at or  
just below its resting level and it was independent of the arterial pco 
of the donor . the donor dog was apneic when the artificial             
hyperventilation was suspended and this response was not abolished by   
vagotomy . bilateral vagotomy caused an increase in ventilation in the  
recipient when its head was perfused by hypocapnic blood . bilateral    
removal of the carotid receptors did not influence the response to co   
qualitatively although there was some reduction in the ventilation of   
the recipient to cephalic hypercapnia . the ventilation of the recipient
dog was best correlated to the ph and pco of its cerebrospinal fluid in 
both hypercapnic and hypocapnic states .                                
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action of phytohaemagglutinin in vitro on the lymphocytes of chronic    
lymphoid leukaemia .                                                    
  the in vitro action of phytohaemagglutinin has been the subjects of a 
comparative investigation of the lymphocytes of 13 normal subjects and  
of 15 cases of chronic lymphatic leukaemia .                            
  in both groups there is cellular change shown by the appearance of    
large basophil nucleolated cells showing mitotic activity .             
  in all the cases of lymphatic leukaemia the percentage of cells       
undergoing such change is lower than in normal subjects, and the        
transformation occurs more slowly .                                     
  the two phenomena are more striking the higher the initial            
leucocytosis .                                                          
  these results suggest, in chronic lymphatic leukaemia, the cells      
affected by the transformation are residual normal lymphoid elements .  
leukaemic lymphoid cells appear to be incapable of this transformation .
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demonstration of ventricular aneurysms by radioisotope scanning .       
  radioisotope scanning of the cardiac blood pool after the intravenous 
injection of i -labeled iodipamide was carried out in 14 patients with  
ventricular aneurysm . in 4, the aneurysm could be demonstrated on      
neither the anteroposterior chest roentgenogram nor the scan . in 5, the
aneurysm was apparent on the radiograph, but the blood pool did not     
enter the area, suggesting a thrombus within the aneurysm . in 5, the   
aneurysm was detectable on the film and was also seen to be filled with 
radioactivity on the scan . presumably these findings showed that a     
thrombus had not yet formed . blood pool radioisotope scanning appears  
to be another tool in the diagnosis of ventricular aneurysm, useful also
in demonstrating in some patients the presence or absence of an         
intraluminal clot within the aneurysm .                                 
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propagation of lactic dehydrogenase-elevating virus in cell culture .   
  primary cultures of adult mouse lung, spleen, and liver and of mouse  
embryo support the multiplication of the lactic dehydrogenase-elevating 
virus . such cultures produced virus continuously until they had been   
subcultured 2-3 times . this corresponded to 20 weeks in the case of    
lung and spleen and to 2-3 weeks with cultures of embryo . viral        
multiplication was not accompanied by cytologic alterations in the cells
or by changes in their rate of synthesis of nucleic acids or protein .  
infection did not cause detectable changes in either the production of  
ldh or in its release from cells .                                      
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transformation of bovine cells in vitro after inoculation of simian     
virus 40 or its nucleic acid .                                          
  cells of bovine embryonic lung tissue in culture were inoculated with 
simian virus 40 (sv 40) or a phenol extract of a high titer suspension  
of sv 40 . both the virus and the nucleic acid preparation induced      
proliferative morphological changes characteristic for sv 40            
transformation . non-infected control cultures and cultures which were  
inoculated with a preparation of nucleic acid exposed to dnase and      
maintained under the same conditions as infected cultures showed a      
regular fibroblastic growth .                                           
  cell lines of rapidly growing transformed cells have been obtained .  
most attempts to isolate virus from the transformed cells were negative,
but minute amounts of virus were recovered from occasional passages .   
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rapid transformation of human fibroblast cultures by simian virus 40 .  
  the risk of systemic embolism is assessed in a group of 754 patients  
with chronic rheumatic heart disease followed over a period of 5,833    
patient-years .                                                         
  the incidence of embolism was 1.5 per patient-year for the whole group
it was seven times higher in atrial fibrillation than in sinus rhythm 
when the duration of atrial fibrillation was known, it was found that 
one-third of the emboli occurred within one month and two-thirds within 
12 months after the onset of atrial fibrillation . the incidence of     
embolic recurrences was 8 per patient-year, irrespective of the nature  
of the cardiac rhythm, but 66 of the recurrences took place within 12   
months of the initial embolic episode .                                 
  mitral valvotomy did not eliminate the danger of embolism . it is     
questionable whether it reduced its incidence .                         
  anticoagulant treatment reduced the incidence of embolic recurrences .
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the tissue reaction to hyperbaric oxygen .                              
  hyperbaric oxygen damages tissues exposed in vitro, but their         
sensitivity varies . if exposure is limited some tissues may recover .  
the effect appears to depend on oxygen tension rather than raised       
pressure per se . the tissue reaction may be involved in the clinical   
application of hyperbaric oxygen .                                      
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attitudinal factors in congenital heart disease .                       
  this study considers the behavioral implications of congenital heart  
disease for the pediatric patient, his siblings, and his parents . the  
effects of a disease on the child, on his siblings, and on his parents  
and the interplay among these individuals are explored . the impact of  
the physician's diagnosis is illustrated by the induced significant     
changes in family attitudes, which are not necessarily related to       
disease severity or child incapacity .                                  
  poorer adjustment and anxiety in the cardiac child related more highly
to maternal anxiety and pampering than to his degree of incapacity .    
maternal protectiveness and pampering were significantly greater in the 
cardiac than in the normal group and were highest in the cyanotic group 
the best predictor of maternal protectiveness was maternal anxiety,   
and it was found that the addition of other variables such as incapacity
and child dependence failed to improve prediction substantially .       
maternal anxiety seemed related to the presence rather than to the      
severity of the heart condition .                                       
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maternal anxiety during pregnancy and adequacy of mother and child      
adjustment eight months following childbirth .                          
  fifty pregnant women were administered a battery of psychological     
tests . on the basis of scores obtained from the manifest anxiety scale,
these pregnant women were dichotomized into a /high anxiety/ group and a
/low anxiety/ group . eight months following childbirth, the mothers and
children were seen for a psychological assessment . it was found that   
the women in the /high anxious/ group evidenced significantly more      
negative childrearing attitudes . that is, the /high anxious/ mothers   
obtained significantly higher scores on the hostility and control       
factors measured by the pari . on the basis of the examiner's ratings of
the mother's personality traits, it was found that the women who were   
highly anxious during pregnancy received much less favorable personality
ratings at the time of the 8-month assessment . moreover, there was a   
significant difference in the proportions of mothers in the two groups  
who received a favorable rating from the examiner on the basis of his   
observation of the mother-child interaction during the session . in     
studying the children of these mothers, it was found that the children  
of the /low anxious/ mothers received a significantly higher            
developmental quotient on the infant mental scale . in keeping with this
finding, they also obtained a higher developmental quotient on the motor
scale, although on this aspect of the intellectual assessment the       
difference was not statistically significant . also, the children from  
the /low anxious/ mothers tended to receive a score indicative of a more
favorable general emotional tone than did the offspring of the /high    
anxious/ mothers . this difference between the two groups of children   
was not statistically significant . in general, the findings were       
consistent with the predictions that the children who were being reared 
by women who had been highly anxious during pregnancy would fare less   
well on tests of intellectual development and indices of emotional      
adjustment . the findings also were in keeping with the prediction that 
the highly anxious women during pregnancy would evidence less desirable 
parental attitudes during their child's early development and that they 
would present a less favorable personality picture at a time            
approximately 8 months following pregnancy .                            
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maternal separation in the rhesus monkey .                              
  the present study involved separation of eight monkey mother-infant   
pairs for a period of two weeks and measurement of the behavior of the  
infants before, during and after reunion with their mothers, and of the 
mothers before and after reunion . all infants showed emotional         
disturbance in response to separation and drastic decreases in play and 
other complex social behaviors while separated .                        
  it is clear that infant-mother separation produces emotional          
disturbance in both human and macaque infants and that the patterns of  
responses following separation are similar in both species . the results
obtained in studies of monkey infant-mother separation indicate that    
sheer physical separation is the crucial aspect of maternal separation  
for monkeys . undoubtedly other factors associated with separation from 
the mother are vitally important for human children, and may account in 
part for the absence or rarity of the detachment stage (as seen in human
response pattern) in separated monkey infants . the overall results show
considerable similarity in the responses of human children and infant   
monkeys to separation from the mother .                                 
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the ophthalmologist's role in the management of dyslexia .              
  dyslexia is a clinical entity characterized by subnormal reading      
ability in a person of average or above average intelligence .          
  it is a disease which has different causes in different children . the
causes include brain damage in the /language area,/ hereditary          
predisposition and such ophthalmic factors as hyperopia, muscle         
imbalance, aniseikonia or visual immaturity . emotional disturbances,   
educational immaturity and cerebral dominance may also play some role in
the etiology of this condition .                                        
  the universal symptom is poor reading ability . however, these cases  
frequently have other associated symptoms such as poor writing,         
difficulty in reading and writing numbers, inability to read or write   
musical notes and disorientation for left and right . many of these     
patients develop personality maladjustments . visual fields often reveal
a hemianopia .                                                          
  in any group of poor readers, a large percentage will have ocular,    
neurologic, psychiatric or psychologic abnormalities and/or a strong    
hereditary tendency . the degree to which reading can be learned depends
upon the ability of the individual to adjust to the psycho-physiologic  
needs that are present at the time he reaches /reading age/ in school . 
if compensating abilities are present, and if the child's reaction is a 
favorable one, he may read well in spite of unfavorable factors,. if    
not, he may become a /poor reader/ . these children should be recognized
in their first year of school .                                         
  a complete medical work-up should be managed by an ophthalmologist . a
complete ophthalmic examination should first be performed and all       
possible visual anomalies should be corrected . the ophthalmologist may 
want a psychometric evaluation, a neurologic opinion to determine the   
role of organic brain damage, psychiatric consultation for evaluation of
emotional disturbances, pediatric consultation for evaluation of the    
status of the general health and/or consultation by an otolaryngologist 
to determine the patient's hearing ability . with all the necessary     
information at hand, the ophthalmologist will be able to recommend      
corrective medical therapy and to advise the parents and teachers about 
available remedial reading aids .                                       
  the prognosis is good for most patients since they are of average or  
above average intelligence,. nearly all cases can be helped .           
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unusual course of internal carotid artery accompanied by bitemporal     
hemianopia .                                                            
  a case is reported with bitemporal relative hemianopia, craniotomy    
showing internal carotid arteries to have an unusual course,            
corresponding to the carotid siphon, with resultant change in shape of  
the optic nerves .                                                      
  abnormalities of the carotid siphons could not be detected on         
reviewing the carotid angiograms . evaluation of the optic nerve's      
relationship, as can be measured on the pneumograms, indicated that the 
optic nerves in this case were exposed to compression from the abnormal 
arteries .                                                              
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frontal lobes and vision .                                              
  the influence of the frontal lobe on vision is discussed based on the 
presentation of a rather unusual case . after the operation of a right  
frontal brain abscess, which never had led to papilledema, there was a  
pronounced diminution of the visual capacities of the patient,.         
gradually these disturbances regressed to the point of return of full   
visual acuity,. but there remained a hemianopic field defect . this and 
psychological defects in the sense of a partial visual agnosia (which   
latter are also regressing very well) prompted a discussion of those    
neuroanatomical and neurophysiological observations pertinent to the    
findings in this patient . the many data on the fronto-occipital        
connections in subhuman primates point to the role of the frontal lobe  
(area 8) in the development of visual disturbances in the sense of a    
temporary hemianopia with partial visual agnosia and some intellectual  
deficits . contrary to a single observation in an anthropoid ape, our   
case would seem to indicate that the aforementioned combination of      
symptoms may originate in the frontal lobe,. and we hope it will prompt 
other long-term follow-up studies of similar patients . the continued   
observation of this patient and perhaps of others will give a           
possibility to gain insight into the role of the frontal lobe in vision,
as has been assumed for animals .                                       
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physiologic bitemporal hemianopsia in pregnancy .                       
  a severe case of bitemporal hemianopsia occurring late in pregnancy is
presented . the patient illustrated a typical rapidly progressive course
and rapid recovery with complete return of visual fields and visual     
acuity after delivery was accomplished . the presumed pathologic        
physiology of this entity is briefly reviewed .                         
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evoked response in visual disorders .                                   
  1. erg and ver have been recorded from eyelid and lateral occipital   
electrodes in response to diffuse stroboscopic stimulation . in 45      
normal subjects ver was found to be composed of an early triphasic      
potential arising from the occipital region . wave i was present in 67  
percent of subjects, wave ii in 97 percent, and wave iii in 100 percent 
later waves were inconstant and contained components from the vertex  
reference . no overall asymmetry in ver from right to left was found in 
normal subjects, although average asymmetry with smaller side compared  
to larger was 19 percent 12.5 . on monocular stimulation the            
contralateral ver was regularly larger than the ipsilateral reflecting  
predominant retinal representation of the temporal field .              
  2. a statistically determined criterion of 50 percent depression in   
wave ii successfully identifies most patients with hemianopic defects   
involving the central 10 percent of visual field on tangent screen      
campimetry .                                                            
  latency asymmetry of six msec. or more and grossly asymmetrical       
aberrant wave forms are seen in some patients with diffuse cerebral     
disease and hemianopic defects .                                        
  3. severe or diffuse retinal disease is associated with alteration or 
loss of erg and ver on stimulation of the involved eye .                
  4. optic nerve disease is indicated by bilateral loss or suppression  
of ver on stimulation of the involved eye . erg is normal .             
  5. bilateral prechiasmal involvement is associated with complete      
suppression of ver . if only waves i and ii are lost, disease is        
probably, but not conclusively, demonstrated .                          
  6. involvement of nasal retinal fibres is indicated by reversal of the
normal contralateral preponderance of ver on monocular stimulation .    
these changes are observed in chiasmal disease .                        
  7. retrogeniculate blindness is associated with loss of early ver and 
preservation of late response . nonspecific projections are felt to     
contribute to the late cortical response to photic stimulation .        
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optokinetic nystagmus and occipital lesions .                           
  six cases are presented to invalidate the rule that horizontally      
symmetric optokinetic responses indicate a vascular etiology in patients
with occipital lobe type hemianopias . the converse of this rule is, in 
our experience, still a valuable observation . that is, asymmetry of    
horizontal optokinetic responses accompanying an occipital type field   
defect is a strong indication of a mass lesion . optokinetic nystagmus  
may be helpful, therefore, as corroborative evidence in diagnosing      
occipital lobe tumor but not in ruling it out .                         
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anaphylactoid shock induced by oral penicillin and resulting in         
gerstmann's syndrome .                                                  
  an anaphylactoid reaction to oral penicillin in a 46-year-old woman is
described.. after hours of unconsciousness and weeks of confusion she   
was left with a residual gerstmann's syndrome . these reactions are less
rare than is generally supposed . symptomatology, treatment, diagnosis, 
and mechanism are discussed, and some of the relevant literature is     
briefly reviewed .                                                      
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disturbances of the verbal body image.. a particular syndrome of sensory
aphasia .                                                               
  1. the pto syndrome of the dominant hemisphere varies according to the
extent and depth of the lesion in the angular and supramarginal areas . 
the mildest clinical syndrome consists of a vague contralateral sensory 
impairment associated with dyscalculia, dysgraphia, dyslexia and        
difficulty in naming . a more extensive lesion is needed to cause the   
wide variety of classical signs described in parietal lobe disease,     
among them being gerstmann's syndrome, which is usually found in        
association with other manifestations of parietal loss (case 1) . an    
even more extensive corticosubcortical lesion in the area leads to      
complete disintegration of naming and understanding of speech (cases 3, 
4 and 5) .                                                              
  2. attention is drawn to the difficulties arising from lack of        
differentiation between the concrete gnostic body image and the abstract
verbal body image in investigation of these patients . the aphasic      
syndrome should be differentiated from disturbances of gnosis by        
application of separate, non-verbal methods of testing to elicit the    
impairment of the gnostic body image . the latter may be well           
compensated for and it is apparently unimpaired in the presence of an   
aphasic syndrome limited to the verbal body image .                     
  3. disturbances of speech in pto lesions if investigated along        
quantitative scales of impairment of repetition, understanding and      
naming, show a regular interrelation . nomination is the most affected, 
understanding is less affected . repetition is the best preserved       
function (cases 1-4) . the same interrelation of these functions is     
found with regard to the verbal body image . however, understanding and 
naming of parts of the body show far greater disintegration than        
understanding and naming of any other categories of words (all cases    
presented here) . if the aphasic syndrome is subsiding, finger aphasia  
with some other minor disturbances of verbal body image associated with 
acalculia may persist (case 1) . thus gerstmann's /finger agnosia/ may  
represent a partial impairment of the verbal body image and be limited  
to finger aphasia .                                                     
  4. it is assumed that the verbal body image differs from other        
categories of verbal symbols owing to the mainly proprioceptive,        
vestibular and tactile experience forming its specific physiologic      
background . telereceptive experience is of minor importance in the     
initial development of the understanding of words defining the body     
image .                                                                 
  in the patients described here, the selectively worse aphasic         
impairment of the verbal body image, as compared with other categories  
of words, seem to confirm this assumption .                             
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chromosomal patterns in cancer patients during treatment .              
  radiation damages the chromosomes of human cells, and through         
short-term cultures of white blood cells some of this damage can be     
assessed . patients with cancer were selected for this study because of 
the large portions of the blood-forming tissues irradiated in the course
of treatment . chromosomal damage may be quantitative with variations   
from the normal number of 46, or qualitative, thereby showing structural
aberrations . counting the chromosomes in cells from cultures grown     
prior to therapy and at intervals during treatment enables us to        
determine the variation .                                               
  stained preparations examined microscopically allow us to recognize   
these abnormalities which are apparent before, during, and after        
radiotherapy . the damage appears to be largely random in the           
chromosomes affected in the different cancers, and the specific         
aberrations differ from cell to cell . however, there does seem to be   
some correlation between the appearance of persistent aberrant          
chromosomes and their frequency . while the peak incidence or /plateau/ 
may remain unchanged, the frequency may change .                        
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a few interesting neurologic manifestations of migraine .               
  migraine is a complex vascular phenomenon presumably of genetic origin
which, through changes induced by either vasoconstriction or            
vasodilitation, can produce interference with the neurologic system and 
result in many bizarre and alarming clinical pictures . a few examples  
of the more interesting neurologic manifestations have been shown .     
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visual neglect .                                                        
  clinical trainees in nursing and in psychology from boston college and
simmons college, boston, mass., collected data and observed patients    
under the direction of the authors in a pilot program designed to       
measure visual spatial neglect and to develop rehabilitative material . 
these measurements and exercises might also be used by nurses in their  
care of those patients who have had cerebral vascular accidents .       
  the diversity of daily activities in which the patient becomes        
involved during his hospitalization should provide some indication of   
the extent to which the compensatory visual neglect therapeutics have   
been effective . more formal estimates can be obtained by               
re-administering the battery of visual neglect tests at periodic        
intervals . nursing personnel adopting a program of therapeutics such as
this must bear in mind that patients suffering cerebral insult are      
usually less adaptive than their nonbrain-injured peers . they develop  
new habit patterns slowly and regression often will follow apparent     
fixation at a more adaptive level of response habituation(11) . however,
experimental inquiry has shown that the dimension of behavioral         
difference between the brain-injured adults and normal adults is one of 
degree rather than kind -dash a difference that skilled nursing can     
often reduce(12) .                                                      
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respiratory changes after open-heart surgery .                          
  patients who undergo cardiac surgery with extracorporeal circulation  
develop significant alveolar-arterial oxygen tension differences and    
venous admixture in the early post-operative period . up to 50 of this  
abnormality is due to anatomical right to left shunting through the     
lungs.. the remainder is most likely to be due to ventilation-perfusion 
inequality . the changes appear to be completely reversible . the       
cardiopulmonary bypass procedure may be responsible for initiating the  
underlying pathology, since changes of this magnitude were not found in 
cardiothoracic surgery patients in whom this technique was not required 
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cardiac malformations associated with ventricular septal defect .       
  in this study, 46 necropsy-proved cases of ventricular septal defect  
associated with another anomaly but not part of a recognized complex    
were selected .                                                         
  the associated anomalies were classified as (1) obstructive or        
positional anomalies of the great vessels, (2) anomalies responsible for
additional shunts, (3) anomalies causing intraventricular obstruction   
and (4) aortic valvular insufficiency .                                 
  clinical findings were often those of the ventricular septal defect,  
and the findings related to the associated lesion were frequently       
obscure . even with special studies, including cardiac catheterization  
and angiocardiography, there was often failure to arrive at a complete  
diagnosis . the findings which led to an erroneous or incomplete        
diagnosis have been presented . when a complete diagnosis was made      
preoperatively, the procedures leading to it have been outlined . while 
the diagnostic approach varies with the malformations which may coexist 
with ventricular septal defect, it was observed that aortography and    
selective left ventricular angiocardiography were most commonly helpful 
in identifying occult malformations associated with ventricular septal  
defect . it is therefore recommended that complete studies, including   
left-sided cardiac catheterization with left ventricular                
angiocardiography and aortography, should be considered in all cases in 
which the clinical, electrocardiographic, and right-sided cardiac       
catheterization studies are not entirely typical for isolated           
ventricular septal defect .                                             
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anatomic types of single or common ventricle in man morphologic and     
geometric aspects of 60 necropsied cases .                              
  in 60 necropsied cases of single or common ventricle in man, four     
major unrelated ventricular malformations were found.. (1) absence of   
the right ventricular sinus, in 47 cases (78 percent), designated type  
a,. (2) absence of the left ventricular sinus, in 3 cases (5 percent),  
type b,. (3) absence or rudimentary development of the ventricular      
septum, in 4 cases (7 percent), type c,. and (4) absence of both        
ventricular sinuses and of the ventricular septum, in 6 cases (10       
percent), type d .                                                      
  three types of relationship between the great arteries were present.. 
a normal (solitus) interrelationship, in 9 cases (15 percent),          
designated type 1,. d-transposition, the transposed aortic valve lying  
to the right (dextro, or d), relative to the transposed pulmonary valve,
in 25 cases (42 percent), type ii,. and l-transposition, the transposed 
aortic valve lying to the left (levo or l), relative to the transposed  
pulmonary valve, in 26 cases (43 percent), type iii . in none was the   
inversus interrelationship, type iv, displayed .                        
  three types of visceral and atrial situs were found.. solitus, or     
normal, in 50 cases (83 percent),. inversus, an exact apparent mirror   
image of normal, in 2 cases (3 percent),. and heterotaxy, the uncertain 
visceral and atrial situs associated with asplenia, in 8 cases (13      
percent) .                                                              
  the 60 cases were classified segmentally, according to the anatomy of 
the three cardiac segments.. the great arteries, the ventricular        
sinuses, and the atria .                                                
  the classic single ventricle with a rudimentary outlet chamber was    
found morphologically to be a large left ventricle with a right         
ventricular infundibulum, the sinus of the right ventricle being absent 
(type a) .                                                              
  the myocardium of the right ventricular infundibulum, of the right    
ventricular sinus, and of the left ventricular sinus was identified by  
the distinctive gross morphologic characteristics of each .             
  the planes of the atrial and ventricular septa, and the relationships 
between the great arteries at the semilunar valves, were measured as    
projections upon the horizontal plane, relative to the anteroposterior  
line .                                                                  
  an approach to cardiac anatomy is presented which is segmental,       
morphologic and geometric . this approach has angiocardiographic,       
electrocardiographic and embryologic applications .                     
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congenital heart disease in the adult .                                 
  events in the natural course of 310 adult patients with proved        
significant congenital cardiac anomalies have been reviewed to determine
incidence, longevity, complications and cause of death .                
  atrial septal defect and patent ductus arteriosus were the most       
frequently encountered lesions and comprised over one third of the      
entire series . ventricular septal defect and pulmonic stenosis made up 
almost a quarter of the group . twenty-two instances of the eisenmenger 
syndrome secondary to a variety of shunting lesions are included .      
  bacterial endocarditis, sudden death and cardiac decompensation were  
the greatest threats to these patients . symptoms were minimal until the
appearance of heart failure, which was the most common cause of death,  
especially with older patients . sudden death occurred most often in    
patients with ventricular septal defect .                               
  although the clinical features are usually characteristic of a        
congenital malformation, young adults with acyanotic congenital heart   
disease are often misdiagnosed as rheumatic,. and in older patients,    
presenting manifestations are frequently attributed to arteriosclerotic 
heart disease . at times an associated acquired cardiovascular disorder 
may alter the basic syndrome .                                          
  three quarters of the patients survive and continue under observation 
the ability of many to live active, productive lives and to withstand 
stress, surgery, both cardiac and non-cardiac, and pregnancy was        
impressive . further observation of the patient with congenital heart   
disease but without surgical intervention is essential for accurate     
evaluation of the long term efficacy of cardiac surgery .               
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a study of ventricular septal defect associated with aortic             
insufficiency .                                                         
  clinical, electrocardiographic, radiographic, and hemodynamic findings
in 12 children with the combination of a ventricular septal defect and  
aortic insufficiency are presented . the left-to-right shunt was        
determined to be small or moderate in all, and significant aortic       
insufficiency was documented by aortography in 11 patients . clinical   
indication of aortic insufficiency as manifested by an aortic diastolic 
murmur first appeared at an average age of 6 years in 7 patients, with  
concomitant widening of the pulse pressure in 4 . progressive left      
ventricular hypertrophy was noted electrocardiographically, with        
progressive cardiac hypertrophy and aortic dilatation on x-ray          
examination in 2 patients . progression of the hemodynamic disability   
does not appear to be common in childhood, however .                    
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ventricular septal defect and aortic regurgitation clinical, hemodynamic
and surgical considerations .                                           
  the clinical, hemodynamic, angiographic and anatomic findings in      
fifteen patients with ventricular septal defect complicated by aortic   
regurgitation are presented . in this combination of malformations the  
aortic regurgitation is acquired and results from prolapse of an aortic 
valve leaflet into the septal defect . the strategic location of the    
septal defect in relation to the aortic leaflets appears to be more     
important to the development of this complication than the size of the  
defect or the magnitude of the shunt through it . the onset of aortic   
regurgitation occurs during early childhood and, once present, tends to 
become more severe . careful observation of patients with these defects 
is indicated following the appearance of aortic regurgitation since     
rapid progression to severe left ventricular failure is not uncommon .  
ventricular septal defect and aortic regurgitation must be distinguished
from other cardiovascular abnormalities producing a wide pulse pressure 
with a continuous or to-and-fro murmur . cardiac catheterization and    
thoracic aortography are the diagnostic procedures most helpful in this 
differentiation . the operative treatment of ventricular septal defect  
and aortic regurgitation is reviewed and, on the basis of the present   
and previously reported results, suggested plans for surgical management
are presented .                                                         
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current techniques in the surgical approach to aortic and mitral        
valvular disease .                                                      
  1. the aortic and mitral valves can be operated upon successfully and 
totally replaced with a prosthetic device of the ball-valve type with   
good long-term results . seventy-four cases are reported .              
  2. in aortic valvular disease the outcome in the immediate            
postoperative period is influenced primarily by the presence of calcific
aortic stenosis as well as the presence or absence of disease in the    
coronary arteries .                                                     
  3. we have significantly decreased the appearance of a low-output     
syndrome postoperatively in patients who are suffering from severe      
mitral disease by leaving the papillary muscle-chordae tendineae-mural  
leaflet relationship intact . we feel this adds strength to each        
contraction .                                                           
  4. there have been no late deaths in the follow-up period to date     
(thirty months) in any patient with replacement of aortic or mitral     
valves with the ball-valve prosthesis .                                 
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effects of aortic regurgitation on left ventricular performance direct  
determinations of aortic blood flow before and after valve replacement .
  the volume of regurgitant blood flow and its effects on the           
performance of the left ventricle were assessed at operation in 14      
patients with varying degrees of aortic regurgitation . instantaneous   
forward and regurgitant flows in the ascending aorta were measured with 
a sine-wave electromagnetic flowmeter simultaneously with left          
ventricular and aortic pressures . in eight patients who had aortic     
regurgitation without associated stenosis, 63 to 75 percent of the total
forward stroke volume regurgitated during the succeeding diastole . the 
calculated regurgitant orifice areas ranged from 0.13 to 0.44 cm /m .   
after replacement of the aortic valve with a starr-edwards prosthesis,  
the absence of regurgitant flow was proved in every patient, and the    
records of aortic blood flow closely resembled those seen in patients   
with normal aortic valves . net forward blood flow increased by an      
average of 60 percent, total left ventricular stroke volume fell 42     
percent, and the mean aortic pressure rose 29 percent . the pressure    
work of the left ventricle was elevated preoperatively in five of the   
eight patients (average 89 g-m stroke/m ) and fell significantly to an  
average of 34 g-m stroke m after valve replacement . kinetic ventricular
work was high in seven of the eight patients and comprised 10 percent of
total work before replacement but only 4.8 percent afterward .          
  similar observations were made in five patients with aortic stenosis  
and associated aortic regurgitation, ranging in severity from 24 to 72  
percent of total forward stroke volume . in four patients in whom the   
valve was replaced, no residual regurgitation was present afterward, and
net forward flow rose an average of 49 percent . kinetic left           
ventricular work was extremely high in every patient and averaged 26    
percent of total work preoperatively and 13 percent after valve         
replacement . in this group, pressure work was variable both before and 
after operation .                                                       
  the studies described provide definitive information concerning the   
effects of aortic valve disease on left ventricular performance in man  
and document the favorable changes in flow, pressure, and left          
ventricular work which immediately follow aortic valve replacement .    
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the absorption and hepatic uptake of orally ingested radioactive vitamin
b in hepato-splenic bilharziasis .                                      
  the absorbed plasma radioactivity and hepatic uptake of orally        
ingested vitamin b tagged with co were measured in 52 subjects, 26      
normals and 26 suffering from bilharziasis .                            
  the results of the present work indicate that the absorption and      
hepatic uptake of this vitamin are within normal limits in hepatosplenic
bilharziasis irrespective of the stage of the disease, the size of the  
organs affected and the presence or absence of associated peripheral    
neuritis .                                                              
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early effects of digitalis on central hemodynamics in normal subjects . 
  the intravenous administration of lanatoside c in 7 normal subjects   
had the following effects..                                             
  1. an early significant reduction of heart rate .                     
  2. a significant transient reduction of cardiac output .              
  3. a significant increase of the stroke volume initially accompanied  
by a significant rise of the end-diastolic volume with unchanged        
systolic rate of emptying . the increase of end-diastolic volume seems  
to be related to the lengthening of the diastolic filling period . later
on, the systolic emptying rate increases, and the ventricular volumes   
decrease, suggesting an inotropic effect of the drug .                  
  4. a significant increase of pulmonary blood volume, parallel to the  
increase of the stroke volume, suggestive of a passive relation between 
the two variables .                                                     
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measurement of pericardial fluid correlated with the i -cholografin and 
ihsa heart scan .                                                       
  in 23 patients undergoing open-heart surgery in whom the pericardial  
contents were accurately measured, and in 11 additional patients        
examined at autopsy or by pericardiocentesis, isotopic photoscans of the
heart were made and the results were correlated .                       
  the most accurate means of diagnosis of pericardial effusion was found
to be the ratio of the maximum transverse cardiac diameters on scan and 
roentgenogram . in patients with less than 100 cc of pericardial fluid  
this ratio was greater than 0.80, and it was less than this in cases of 
effusion of 200 cc or more .                                            
  measurement of the difference of these diameters, and visible         
separation of the cardiac blood pool from the pulmonary vasculature and 
liver aided in the diagnosis .                                          
  pericardial effusions of 200-300 cc or greater can be detected by     
isotopic photoscanning . although cardiac dilatation and/or hypertrophy 
decrease the sensitivity of the technique somewhat, a definite diagnosis
of pericardial effusion can be made even when cardiomegaly exists .     
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aneurysm of the membranous septum .                                     
  1. aneurysms of the membranous septum are relatively rare lesions     
presumably developing on a congenital basis . these aneurysms originate 
in the left ventricle immediately beneath the aortic valve and bulge    
into the right ventricle, the septal leaflet of the tricuspid valve or  
into the right atrium .                                                 
  2. many of these aneurysms do not produce symptoms . others may cause 
right ventricular outflow tract obstruction or may rupture and result in
a septal defect . the resulting shunt will be from the left ventricle   
into the right atrium or ventricle .                                    
  3. an aneurysm of the membranous septum may be an isolated abnormality
or be associated with other congenital cardiac defects, particularly    
aortic valvular insufficiency . membranous septal aneurysms may be the  
site of bacterial endocarditis or thrombus formation .                  
  4. aneurysms resembling those arising from the membranous septum may  
occur as part of the complex of deformities produced by an endocardial  
cushion defect . however, the angiographic features diagnostic of a     
cushion defect can still be recognized .                                
  5. the presence of a septal aneurysm can be established only by       
angiocardiography . the diagnostic features as seen on the left         
ventricular angiocardiogram are presented .                             
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distribution of transfused tritiated cytidine-labeled leukocytes and red
cells in the bone marrow of normal and irradiated rat .                 
  in normal rats and after total body irradiation with 550 r of x-rays, 
the fate in the bone marrow of labeled nucleated and red cells of       
transfused peripheral blood was observed autoradiographically .         
  labeled nucleated cells, most of which were lymphocyte-like cells,    
readily migrated into the marrow parenchyma in normal animals (2 cells/ 
1,000 parenchymal cells/hr.) . following irradiation to at least 27-51  
hr., this migration appeared to be relatively increased . beyond this   
time, parenchymal areas were more difficult to be defined as such .     
  labeled red cells were rarely observed to enter parenchyma despite the
presence of nonlabeled erythrocytes within the parenchymal structure    
after irradiation .                                                     
  the vascular bed following irradiation increased greatly as the       
parenchyma diminished to a minimum of less than 10 percent control at 75
hr . despite these changes in the architecture of the marrow, the       
average density of labeled cells per area of marrow corresponded to     
values expected on the assumption of a free-flowing circulation . the   
technique used at present did not allow us to distinguish, at all times,
between a free-flowing circulation through intact sinusoids or through  
areas in which the sinusoidal wall, as such, was destroyed .            
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factors limiting survival after circulatory occlusion under hypothermia 
and hyperbaric oxygenation .                                            
  thirty minutes of circulatory occlusion with mild hypothermia and     
hyperbaric oxygen ventilation resulted in a mortality of 83.3 percent in
animals . when coronary perfusion from a reservoir was added, the       
mortality rate was 22 percent . ventricular fibrillation was much more  
easily reversed after coronary perfusion . there was no evidence of     
brain damage in survivors which leads to the conclusion that the brain  
tolerates circulatory arrest better than the heart under these          
conditions .                                                            
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the effect of hypothermia on circulatory reflexes in the human .        
  total circulatory occlusion and release result in hemodynamic         
phenomena which provide an index of integrity of some cardiovascular    
reflexes . these include carotid sinus and aortic baroceptors,          
arteriolar vasomotor tone, and venomotor reactivity .                   
  baroceptor depression appears at a more moderate level of cooling than
does the sympathetic, vasomotor, depression . below 28 degrees c. both  
are significantly depressed, although probably not totally abolished .  
  the level of 28 degrees c. is a critical physiological level and may  
represent an important limit in the clinical use of hypothermia .       
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studies in perfusion hypothermia with special reference to /deep        
hypothermia/ and circulatory arrest .                                   
  1. perfusion hypothermia produces large temperature gradients within  
the body since organs are cooled roughly in proportion to their basal   
blood flows . the difference between the coldest and the warmest portion
of the body after 30 minutes of perfusion exceeds 25 c .                
  2. the average body temperature, which provides a proper measure of   
total body cooling, may be calculated from the arteriovenous temperature
difference and the extracorporeal flow rate .                           
  3. true /deep/ hypothermia is not obtainable by reasonable periods of 
perfusion alone .                                                       
  4. an important rise of core temperatures occurs during circulatory   
arrest in hypothermia because of relatively high average body           
temperature .                                                           
  5. high average body temperatures lead to continuing production of    
lactic acid in muscle tissue, whereas low core temperatures impair      
lactic acid metabolism . thus metabolic acidosis is progressive in      
prolonged perfusion hypothermia, and is accentuated by total circulatory
arrest . progressive acidosis may be minimized by uniform profound      
cooling by combining external with perfusion hypothermia .              
  6 diluents appear to have little effect on total body heat exchange   
during perfusion cooling .                                              
  7. perfusion warming has a differentially greater effect on core      
organs . though these are readily brought to a normal range, much of the
animal may remain cold .                                                
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application of the emission spectrograph to the analytical needs of the 
industrial hygiene laboratory .                                         
  examples of unique applications of the principles of emission         
spectroscopy to industrial hygiene problems are provided . a discussion 
of qualitative, semiquantitative and quantitative methods of            
spectrographic analysis is presented . these methods include            
representative applications which are made for the analysis of the      
metallic constituents of body tissues and fluids from human and animal  
subjects, industrial process materials, ores, and environmental dusts   
and fumes . brief descriptions of sample preparation techniques required
for successful analyses are also presented .                            
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nickel carbonyl.. its detection and potential for formation .           
  recent recommendations for control of nickel carbonyl exposures have  
been considered in the design of a simple, sensitive field method for   
sampling nickel carbonyl in air and process gases . the method involves 
collection in dilute aqueous hcl, ph adjustment, nickel complex         
development with alpha-furildioxime, and extraction with chloroform .   
color intensity is compared visually (or for greater accuracy,          
spectrophotometrically) with liquid standards . sensitivities on the    
order of 0.001 ppm are obtainable . a detailed development of the       
thermodynamics associated with the formation of nickel carbonyl is also 
presented to show the maximum concentrations of nickel carbonyl that may
be formed over a wide range of co concentrations, temperatures and      
pressures .                                                             
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polarographic determination of heavy metals in air samples .            
  the polarograph possesses the required sensitivity and specificity to 
make it the method of choice for analysis for a variety of heavy metals 
in air . two commercial polarographs are compared and both found        
adequate on the basis of analysis for lead . determinations may be made 
for antimony, copper, lead, cadmium, chromium, nickel, cobalt,          
manganese, and others .                                                 
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the inorganic constituents of human teeth and bone examined by x-ray    
emission spectrography .                                                
  x-ray emission spectrography has been applied to study of the         
elemental composition of human teeth, enamel, dentine and bone . the    
material consisted of eight crushed teeth, enamel and dentine powder    
separated from eighteen teeth, and four pieces of buccal cortical       
mandibular bone . the teeth did not have fillings . the whole material  
contained nineteen elements, of which the main ones were calcium and    
phosphorus . in all the samples of tooth material, there were found ca, 
p, cl, fe, zn, sr and k, and the bone also contained ni . the time      
needed for a semi-quantitative analysis compares very favourably with   
that needed for other methods .                                         
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a kinetic study of nickel(ii), complexes of sulfur-containing amino acid
  the rate expression for the ethylenediaminetetraacetic acid (edta)    
ligand exchange reaction with nickel(cysteine) is.. rate = k(complex) + 
kedta (complex)(edta) . this two-term rate expression is characteristic 
of square planar complexes and agrees with the square planar            
configuration of ni(cysteine) reported on the basis of spectral studies 
the edta-independent term of the rate expression is an acid-catalyzed 
term and can be written k (h) (complex) . the value of kn is 2.5 x 10 m 
sec while the value of kedta is only on the order of 10 -10 m sec . the 
edta reaction with ni(cysteine) methyl ester) is very similar to the    
reaction with ni(cysteine) . when the sulfur-containing amino acid      
ligand contains a thiol ether, the kinetic differences are striking .   
  ligand exchange reactions of edta, triethylenetetramine, and          
diethylenetriamine with nickel-methionine complexes are several orders  
of magnitude faster and give products that are mixed-ligand complexes . 
the results of this kinetic study of amino acid complexes containing    
sulfhydryl and thiol ether sulfur groups support other studies at       
equilibrium which suggest sulfur coordination and square planar         
complexes for the sulfhydryl groups and octahedral complexes with no    
sulfur coordination for thiol ethers .                                  
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the action of metal ions on tobacco mosaic virus ribonucleic acid .     
  added transition metal ions stabilize the secondary structure of      
tobacco mosaic virus ribonucleic acid (tmv-rna) as evidenced by a       
reduction in the absorbancy change of heated nucleic acid solutions . in
spite of this stabilization of secondary structure, heating in the      
presence of metal ions results in the loss of biological activity due to
the hydrolysis of phosphodiester bonds . thus, all heavy metal ions of  
the iib and first-transition elements studied caused a rapid loss of    
biological activity of tmv-rna at ph 6.5 and 65 . calcium and magnesium 
ions, while not affecting secondary structure at 65 and ph 8.5, caused a
rapid loss of biological activity . at ph 5.8 and room temperature lead 
ions catalyzed the hydrolysis of rna to i'(3')- mononucleotides,. on    
long standing, nucleosides were formed .                                
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chromium, lead, cadmium, nickel and titanium in mice.. effect on        
mortality, tumors and tissue levels .                                   
  about 700 mice were given throughout their lives 5 ppm cadmium, lead, 
chromium, nickel or titanium in drinking water while fed a diet         
deficient in cadmium and low in other metals . tissue concentrations    
comparable to those of man were observed . sex differences appeared .   
mortality of females was unaffected . mortality of males on cadmium,    
lead and nickel was increased compared with that of the chromium group, 
and of those on cadmium and lead compared with the controls . longevity 
of the oldest 10 of both sexes was less in lead and titanium groups, and
of males in cadmium group, compared with controls . no metal was        
carcinogenic,. incidence of tumors in males on cadmium and lead, and in 
females given nickel was decreased . body weights at death were greater 
in titanium, chromium and lead groups . large increments of titanium,   
moderate increments of cadmium and nickel, and lesser increments of     
chromium and lead were observed in 5 organs, compared with controls .   
higher concentrations of cadmium and titanium occurred in younger mice  
and the other metals did not increase markedly in tissues with age . all
metals except chromium exhibited one or more signs of innate toxicity . 
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synergistic effects between antioxidants and selenium or vitamin e .    
  several antioxidants when fed to chicks at relatively high levels in  
an experimental diet were ineffective in preventing the exudates and    
mortality from a combined deficiency of selenium and vitamin e . some of
the compounds were toxic, as evidenced by sudden death or subcutaneous  
hemorrhages . when amounts of either selenite or a-tocopheryl acetate,  
which individually had little or no effect on symptoms, were given with 
the antioxidants signs of deficiency and mortality were prevented, and  
toxicity also was eliminated .                                          
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the expression of urine analysis results -dash  observations on the use 
of a specific gravity correction .                                      
  urine analyses are very useful for measuring the extent of exposure to
certain toxic substances . the types of specimen obtainable from persons
employed in industry, and the effect of concentration variations are    
discussed . in expressing the results of analysis it is shown that a    
concentration correction is essential . the correction based on specific
gravity is the easiest to apply . the mean specific gravity for persons 
resident in the u.k. has been found to be around 1.016, a figure        
considerably lower than the mean of 1.024 used by many workers          
(particularly in the u.s.a.) . the implications of this on the results  
of urine analysis are indicated .                                       
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activation and inactivation of p-hydroxyphenylpyruvate hydroxylase .    
  1. p-hydroxyphenylpyruvate hydroxylase (ec 1.99.1.14) is reversibly   
inactivated by dialysis, storage, purification involving ammonium       
sulfate fractionation, and treatment with oxidizing agents . the        
inactive enzyme is reactivated by various reducing agents .             
  2. metal-chelating agents inhibited enzyme activity . 1,10-           
phenanthroline and 4,7-diphenyl-1,10-phenanthroline (fe sensitive)      
strongly inhibited, but 2,9-dimethyl-1,10-phenanthroline (cu specific)  
did not . 1,10-phenanthroline-treated p-hydroxyphenylpyruvate hydroxyl- 
ase was reactivated specifically by fe in the presence of a reducing    
agent, indicating a role for fe in enzyme activity .                    
  3. nonoxidative sulfhydryl reagents did not materially inhibit the    
enzyme activity under various conditions .                              
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responses of b. subtilis (atcc 558) to streptomycin .                   
  to observe in detail the influence of streptomycin on the growth of sm
dependent type, the author chose b. subtilis (atcc 558) and made        
experiments on its responses to streptomycin, with special reference to 
the relation of the sm concentration with spore formation of its sm     
dependent type together with germination and outgrowth of the spores    
formed . the results are as follows .                                   
  1. among 18x10 cells of wild type of b. subtilis (atcc 558) about     
3,200 cells of sm resistant and one cell of sm dependent are found as   
its mutant .                                                            
  2. b. substilis (atcc 558) shows normal growth at sm concentration    
below 10 r/ml, but the growth declines rapidly between sm 10 r/ml-20 r/m
l, and the growth stops entirely at sm concentration 20 r/ml .          
  3. sm resistant type grows well between sm 0.1 r/ml-sm 2,000 r/ml, the
growth declines rapidly at about sm 10,000 r/ml .                       
  4. sm dependent type shows normal growth between sm 10,000 r/ml-20 r/m
l, the growth get worth below sm 10 r/ml, and the cell shape elongates  
several times, at sm below 1 r/ml each cell becomes filamentous form and
has several ten times length of normal cell, as if the cells have       
stopped to divide at low sm concentration .                             
  6. the germination and outgrowth of spores of the sm dependent type   
slow down with decline of sm concentration, but the germinated spores   
grow in normal forms until sm concentration reaches 7.8 r/ml, then the  
germination becomes much slower, and the cells grow in filamentous forms
or irregular forms . at extremely low sm concentration both germination 
and outgrowth nearly stop .                                             
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phospholipids of the bovine, rabbit, and human lens .                   
  the phospholipids of bovine, rabbit, and human lenses contain cephalin
lecithin, and sphingomyelin but their distribution differs with each    
species . there is suggestive evidence that there may also be           
plasmalogen in the lens, but, if so, it represents a minor phospholipid 
component . the fatty acid composition of each phospholipid differs in  
each species, with most of the differences centering around 16..0,      
18..1, and 24..1 .                                                      
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surgical aspects of heart disease in pregnancy .                        
  the ideal management of the pregnant woman with heart disease is      
medical, if feasible . the operative experience with mitral valvulotomy 
in pregnancy has expanded . this procedure is now indicated when        
progressive cardiac disability develops during the first or second      
trimester and when the proven dominant lesion is mitral stenosis . when 
other lesions are present, especially those requiring pump oxygenator   
perfusion, the risk must be carefully measured . damage to the fetus may
result from reduced placental blood flow .                              
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traumatic lesions of the optic chiasma.. a report of four cases .       
  case histories of four patients who suffered severe head trauma       
resulting in complete bitemporal hemianopia are presented . the optic   
chiasm was visualized in only one patient . it was markedly swollen and 
disintegrated . this appearance was consistent with multiple minute     
tears of the crossed fibres in the median sagittal plane . other        
theories to explain the bitemporal field defect are discussed .         
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lung cancer.. an evolutionary approach .                                
  lung cancer is presented as an example of somatic mutation . in       
contrast to previous theories the following are defined.. (a) the major 
growth controlling mechanism,. (b) the mutation found in cancer,. and   
(c) the environmental changes in the lungs of patients who smoke        
cigarettes which can select this mutant .                               
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the effects of electrophoretically separated lens proteins on lens      
regeneration in diemyctylus viridescens .                               
  in the present study, lenses were removed from the eyes of adult      
anesthetized newts, macerated in 0.03 m borate buffer at ph 8.6, and    
separated by starch gel electrophoresis . upon staining with amido black
10-b, seven distinct staining areas appeared in the blocks . three bands
moved toward the anode, and three toward the cathode . in addition, a   
seventh moiety represented by a smear of material moved toward the anode
one millimeter times five tenths millimeter plugs were removed from   
each of these areas and were placed into freshly lentectomized eyes .   
plugs from most strongly positive and most weakly negative proteins     
inhibited lens regeneration . in addition, plugs from the area          
containing the weakly negative protein induced either lenses with       
aberrant polarity or double centered lenses with centers of opposed     
polarity . all other protein bands had no significant effect on         
regeneration .                                                          
  in addition to the above experiments, homogenates and                 
proteinasedigested homogenates of lenses were injected into eyes        
following lentectomy . three 5-ul samples were injected in each case    
over a six day period . injection of the plain homogenate stimulated    
lens regeneration markedly, while the proteinase destroyed the          
stimulatory activity .                                                  
  theoretical considerations of the above data are discussed .          
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enzymic synthesis of deoxyribonucleic acid xviii. the repair of         
partially single-stranded dna templates by dna polymerase .             
  a partially single-stranded dna, prepared by limited digestion of each
strand with exonuclease iii, can be restored to its native, fully       
double-stranded structure by escherichia coli dna polymerase . the rate 
of synthesis observed in the repair of such a partially degraded primer 
in the polymerase system is faster than that seen with a native dna .   
the newly synthesized dna is covalently attached to the primer . the    
fully repaired dna resembles the original native dna as judged by its   
appearance in electron micrographs, cscl density-gradient analysis,     
denaturability and genetic activity . dna synthesis which follows the   
repair phase produces a structure that is not covalently linked to the  
primer and resembles, in its nondenaturability, branched appearance, and
lack of genetic activity, the product obtained with a native dna primer 
(schildkraut, richardson + kornberg, 1964) .                            
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on the mechanism of genetic recombination in transforming bacillus      
subtilis .                                                              
  the molecular fate of transforming dna in competent bacillus subtilis 
has been studied . the physical differentiation of transforming dna and 
the genetic material of recipient bacteria was effected by employing the
isotopes n and p . competent bacteria labeled with n and p were allowed 
to incorporate n p-labeled transforming dna intracellularly . dna was   
isolated from these recipient cells and centrifuged in cesium chloride .
analysis of drop fractions collected at equilibrium showed the presence 
of radioactivity in a region of density corresponding to recipient dna .
material contribution from donor dna to the resident dna did not occur  
when genetically inert bacillus cereus dna was substituted for          
homologous dna . it was concluded that radioactivity appearing in the   
unlabeled resident dna was not the result of degradation of input (     
p)dna and subsequent incorporation by normal metabolic processes . since
single-stranded dna of donor origin was not detected, nor was there     
evidence for the non-specific aggregation of donor and recipient dna, it
was concluded that the observed physical association of transforming and
recipient dna occurs as a result of genetic recombination in transformed
b. subtilis .                                                           
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physical and biological studies on transforming dna .                   
  bacillus subtilis transforming dna prepared by the method described,  
has an average molecular weight of 11.6 million . the dna is            
heterogeneous, as judged by chemical composition, thermo-spectral and   
pyenographic properties . these properties have been used to fractionate
some of the biologically active molecules which show higher specific    
activities in transforming respective auxotrophs .                      
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comparison of mutation and inactivation rates induced in bacteriophage  
and transforming dna by various mutagens .                              
  inactivation and mutation rates were measured for t4 phages and       
bacillus subtilis transforming dna treated by low ph, nitrous acid, or  
hydroxylamine at different temperatures . the frequency of mutants      
increased linearly with time for all three agents, whereas the logarithm
of survival gave a linear plot only for nitrous acid and low ph . an    
arrhenius plot showed the same slopes for both inactivation and mutation
rates after treatment with low ph or nitrous acid,. for the latter agent
the slope remained unaltered even when the dna was treated in the       
denaturated state . in contrast, mutation rates obtained after the      
exposure to hydroxylamine differed greatly for native or denatured dna, 
phage t4 being intermediate .                                           
  treatment by low ph or nitrous acid interrupted the genetic linkage   
between tryptophan and histidine, the interrupting hits being about 1/3 
as frequent as lethal hits, independent of the temperature .            
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autolysis of bacillus subtilis by glucose depletion .                   
  in cultures in minimal medium, rapid lysis of cells of bacillus       
subtilis was observed as soon as the carbon source, e.g. glucose, had   
been completely consumed . the cells died and ultraviolet-absorbing     
material was excreted in the medium . the results suggest that the cells
lyse because of the presence of autolytic enzymes . in the presence of  
glucose the damage to the cell wall caused by these enzymes is repaired 
immediately .                                                           
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plasma 17-hydroxycorticosteroids and 17-oxosteroids in patients with    
breast cancer and in normal women .                                     
  (1) 17-hydroxycorticosteroids (17-ohcs) and 17-oxosteroids were       
measured in the plasma of normal women, patients with early breast      
cancer and in patients with advanced metastatic disease .               
  (2) the mean plasma 17-ohcs level was found to be normal in the early 
stages of the disease but was raised in the advanced disease . in both  
groups of patients the variance was significantly greater than in normal
women .                                                                 
  (3) the mean plasma 17-oxosteroid level in both early and advanced    
breast cancer was not significantly different from the normal level but 
the variance was increased .                                            
  (4) there is a significant correlation between the plasma 17-ohcs and 
17-oxosteroids in normal women which was not found in the cancer        
patients .                                                              
  (5) in patients with advanced breast cancer, the levels of plasma 17- 
oxosteroids were significantly correlated with the amounts of 11-deoxy- 
17-oxosteroids found in the urine . there was no correlation between    
plasma and urinary 17-ohcs .                                            
  (6) the physiological significance of these findings is discussed .   
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hormone therapy in metastatic breast cancer.. clinical response and     
urinary gonadotrophins .                                                
  the total urinary gonadotrophin output of a group of post menopausal  
women with metastatic breast carcinoma undergoing hormone therapy, which
in every case initially consisted of treatment with diethylstilboestrol,
des (ca. 20 mg/d), has been studied for periods varying from seven      
months to 31/2 years .                                                  
  no correlation between gonadotrophin output and clinical response was 
found, except that in all cases showing objective regression urinary    
gonadotrophin remained low throughout the remission period . a low level
of gonadotrophin output was not, however, necessarily indicative of a   
good clinical remission . following withdrawal of des, and independent  
of the period of therapy, recovery to pre-treatment levels was the rule 
rather than the exception .                                             
  a small group of patients maintained on a lower dose of des (3-5 mg/d)
showed the same degree of suppression of urinary output as those        
receiving 20 mg/d, and several of these exhibited objective remissions .
  the study has emphasised the importance of site specificity in the    
response to hormone therapy, and underlines the difficulties of relating
the clinical response of the patient as a whole to changes in hormonal  
environment .                                                           
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plasma androgens in women i. normal and non-hirsute females,            
oophorectomized and adrenalectomized patients .                         
  1. in a group of 20 normal non-hirsute females age 17 to 38, 18 non-  
hirsute patients with varied genito-urinary disorders, 8 oophorectomized
and or adrenalectomized patients plasma testosterone was measured by the
method of finkelstein et al. (1961) . conjugated androsterone and       
conjugated dhea were determined by a modified method of migeon + plager 
(1955) .                                                                
  2. mean baseline values in normal females were .11 .06 ug/100 ml      
testosterone, 11.8 5.5 ug/100 ml conjugated androsterone, and 29.5 15.5 
ug/100 ml conjugated dhea . no significant response to hcg could be seen
dexamethasone affected the conjugated dhea significantly, but did not 
seem to affect conjugated androsterone or testosterone .                
  3. the non-hirsute patients showed essentially the same pattern . an  
effect of dexamethasone on the levels of conjugated androsterone was    
demonstrated .                                                          
  4. oophorectomized women had baseline values for the conjugates in the
range of normals . testosterone, however, was low with an average of    
 .016 ug/100 ml . in the adrenalectomized patients no androgens were     
detectable .                                                            
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oophorectomy and cortisone treatment as a method of eliminating         
oestrogen production in patients with breast cancer .                   
  the urinary excretion of oestrone, oestradiol-17b, oestriol, and 17-  
hydroxycorticosteroids has been estimated in 55 premenopausal and 91    
postmenopausal women with breast cancer at various stages of the disease
before therapy . the depletion of oestrogen excretion caused by         
oophorectomy combined with cortisone treatment was studied in the       
patients with metastasising breast tumours (32 premenopausal and 56     
postmenopausal subjects) .                                              
  patients with disseminating breast cancer excreted significantly      
larger quantities of oestriol than healthy women of the same age,       
whether pre- or postmenopausal . the excretion of oestrone and          
oestradiol-17b was similar in cancer patients and healthy women of      
corresponding age .                                                     
  oophorectomy reduced the oestrogen excretion not only in premenopausal
subjects but also in quite a number of postmenopausal patients,         
particularly in those who were still excreting significant amounts of   
oestrogens . this decrease in the oestrogen output was transient and was
followed by a compensatory increase, possibly of adrenal origin .       
  cortisone administered within a month after the oophorectomy at a     
dosage of 50 mg per day rapidly depressed the secondary rise in the     
oestrogen output to a level of about 4 to 5 ug/24 h irrespective of the 
age of the patient . this excretion level was unchanged as long as      
cortisone was given in an adequate dose, but increased rapidly when the 
cortisone treatment was discontinued .                                  
  oophorectomy combined with adequate cortisone treatment seems to offer
an alternative to the extensive surgical porcedures undertaken to       
eliminate oestrogen production in breast cancer patients .              
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some reactions of cytotoxic antibodies against previously unknown mouse 
isoantigens .                                                           
  the antiserum produced in c3h/he against c3h/st lymphosarcoma 6c3hed  
contains a mixture of at least two antibodies of different properties   
and specificities . anti h-5a is a hemagglutinating antibody removed by 
absorption with red cells and many tissues . anti v is a cytotoxin      
reacting with c3h/st tissue and 6c3hed but not with red cells.          
  the reciprocal antiserum c3h/st anti c3h/he sarcoma mc1m is more      
complex . it contains the hemagglutinin anti h-6a and a variety of      
cytotoxins . one appears to be specific for c3h/he tissues and the      
   tumor mc1m . another reacts with antigens on the c3h/go carcinoma    
bp8. two additional cytotoxins may also be present .                    
  immunization between sublines of the same inbred strain can result in 
the production of a variety of antibodies directed against unrelated    
antigens present on even long transplanted cells . the significance of  
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on the value of thymectomy in adult mice as a means of potentiating the 
immunosuppressive action of melphalan (l-phenylalanine mustard) .       
  thymectomy has been found to be ineffective as a means of potentiating
the immunosuppressive action of melphalan in adult cba-p mice challenged
with a-strain mammary carcinoma transplants . this was true when the    
thymectomy was performed 2 days, 4 weeks or 7 weeks prior to injection  
of a single dose (15 mg/kg body weight) of melphalan, administered 24   
hours prior to tumour transplantation, and also when thymectomy was     
combined with multiple doses of melphalan given before and after tumour 
transplantation . these findings are discussed .                        
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studies on the kinetics of transplantation immunity .                   
  using the parameter of the number of tumor cells necessary to produce 
s.c. tumors in allogeneic animals at varying intervals after antigenic  
stimulation, immunity was found to be in force as early as 2 days after 
primary antigenic stimulation . it reached a peak at 8-10 days and had  
largely subsided by the end of a month . this method was also applied to
the quantitative study of the onset, degree, and duration of immunity   
elicited by skin grafts . the results obtained with inocula of large    
numbers of tumor cells (10 percent) were comparable to those obtained   
with massive skin grafts .                                              
  the differences in the degree of antigenic stimulation resulting from 
different routes of inoculation were studied . it was found that the    
intradermal (i.d.) route of inoculation resulted in a more intense      
antigenic stimulation than the s.c. route . when both routes of         
inoculation were used simultaneously the pattern of growth of the s.c.  
tumor was influenced by the i.d. inoculation.. an i.d. inoculum given 24
or 48 hr earlier caused marked suppression of growth of the s.c. tumor, 
while when an i.d. inoculation was preceded by an s.c. inoculation,     
although there was an appreciable effect on the growth size, the growth 
curves of the 2 tumors were always parallel .                           
  there was no correlation between cytotoxic activity and the degree of 
immunity in force at a given time .                                     
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evidence for an immunological reaction of the host directed against its 
own actively growing primary tumor .                                    
  cells isolated from primary benzo(a)pyrene-induced fibrosarcomas in   
rats of a pure line were tested for their ability to grow as autografts 
when injected back into the autochthonous host . the autograft did not  
take if the primary tumor had been removed but grew occasionally in     
animals in which the major part of the tumor was left . in every        
instance the sarcoma cells grew when injected into syngeneic recipients 
in these recipients the growth of the sarcoma cells was prevented or  
retarded when they were mixed in vitro, prior to injection, with spleen 
cells from animals that had been immunized against the tumor .          
autochthonous spleen cells taken from the animal with the tumor behaved 
in this test like those from immunized animals as long as the spleen was
taken 3 weeks after removal of the tumor . when the spleen and tumor    
were removed at the same time, however, autochthonous spleen cells did  
not behave like spleen cells from immunized animals and did not         
interfere with the growth of the tumor . the results of both the        
autograft and spleen cell experiments suggest that rats react actively  
against their own growing primary tumors, but that the tumor exhausts   
the supply of lymphocytes responsible for this reaction . after the     
tumor is removed, the concentration of antitumor lymphocytes in the     
spleen builds up and the animals can reject an autograft .-j nat cancer 
inst 36.. 29-35, 1966 .                                                 
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a comparison of the cytologic effects of leurosine methiodide and       
vinblastine in tissue culture .                                         
  comparison of the degree and duration of arrest of metaphases in      
tissue culture cells by leurosine methiodide and vinblastine was made,. 
colchicine and demecolcine were included for reference purposes . all   
four drugs produced a similar cytologic effect, but vinblastine was most
active and remained active for the longest period of time .             
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comparison of central aortic and peripheral artery pressure curves .    
  brachial artery and central aortic pressures were compared in 50      
consecutive patients subjected to retrograde left heart catheterization 
in order to re-emphasize the fact that the two pressures are not        
necessarily identical . in 43 cases the systemic systolic pressure peaks
exceeded those in the central aorta while in seven these pressures were 
equal . the average pressure difference was 22.6 mm. hg . the greatest  
differences occurred in cases of aortic regurgitation and could be      
extreme, the brachial artery systolic pressure exceeding that in the    
aorta by more than 100 mm. hg in some instances . the least differences 
occurred in cases of aortic stenosis but significant differences        
occasionally existed, leading to erroneous estimation of valve orifice  
size if the systemic rather than the aortic systolic pressure was used .
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changes in sphingosine and fatty acid components of the gangliosides in 
developing rat and human brain .                                        
  rat brain increases in weight after birth in three stages.. (i)       
rapidly for the first 2 weeks, (ii) at a lower rate from 2 to 5 weeks,  
and (iii) at a still lower rate from 5 weeks to 5 months . during the   
succeeding period, designated iv, it maintains constant weight up to 1  
year of age . brain ganglioside content increased linearly during i and 
ii, more slowly during iii, and diminished during iv . the appearance of
measurable amounts of brain sphingomyelin and cerebroside succeeded that
of ganglioside .                                                        
  ceramide with c -sphingosine and c fatty acid was found in a large    
proportion of all three sphingolipids upon their first appearance in    
measurable quantity . c fatty acid in cerebroside rapidly declined to a 
negligible level, while in gangliosides and sphingomyelin it declined   
slowly but remained the major fatty acid component .                    
  cerebrosides and sphingomyelin contained c -sphingosine almost        
exclusively at all stages of rat brain growth . gangliosides contained c
-sphingosine almost exclusively at birth, but subsequently accumulated c
-sphingosine until they had nearly equal quantities of each base type . 
  changes in human brain gangliosides resemble those in rat . in        
tay-sachs disease, gangliosides have c -sphingosine predominantly, and a
high content of c fatty acid .                                          
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studies of the generalized shwartzman reaction induced by diet vi.      
effects of pregnancy on lipid composition of serum and tissues .        
  pregnancy induced profound alterations in the lipid composition of    
serum and tissues . (1) there is an elevation of total serum lipid,     
phospholipid, triglyceride, free fatty acid and cholesterol,. (2) while 
the total lipid of the liver and kidney are increased, that of the depot
fat is decreased,. (3) palmitate and oleate are increased in serum and  
liver,. (4) arachidonate and stearate are decreased in serum and liver,.
and (5) placentas contain more stearate than the other organs of the    
pregnant rat and also have a higher water content . the decrease in     
depot total fat,. elevation of serum, liver and kidney total fat,. and  
elevation of serum free fatty acids suggest that pregnancy induced      
mobilization of depot fat . the increase in proportion of liver and     
serum palmitate suggests that pregnancy induces increased lipogenesis   
from the acetate pool . the appearance of an increased amount of        
long-chain fatty acids in the liver may be due to the increased intake  
of dietary fat . the decrease in arachidonate and stearate in serum and 
liver suggests a relative decrease in mitochondrial fatty acid synthesis
.I 160
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electron microscopy of the bovine lung.. the normal blood-air barrier . 
  lungs of 20 healthy, mature cattle were fixed in oso , embedded in a  
polyester resin, and studied via electron microscopy . the blood-air    
barrier was widely variable in thickness and consistency . there was a  
continuous epithelial alveolar lining . the cytoplasm of some of the    
epithelial cells contained membrane-bound aggregates of granules which  
may be secretory structures . the epithelium rested on a basement       
membrane, which in turn was continuous with or rested on an adjacent    
capillary endothelial basement membrane, or continued into merging      
connective tissue . the capillary endothelium was not fenestrated,. it  
was a continuous cellular membrane . both the epithelium and endothelium
contained numerous caveolae and pinocytotic vesicles . cells of the     
alveolar wall included fibroblasts, lymphocytes, macrophages, and an    
occasional mast cell . very little elastin was observed .               
.I 161
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a sensitive and specific fluorescence assay for tissue serotonin .      
  a sensitive and specific method for the estimation of serotonin in    
biological materials is described . in this method, serotonin is reacted
with ninhydrin to form a product whose fluorescence is eight times more 
intense than the native fluorescence of serotonin in strong acid        
solution . with this method it is possible to measure serotonin in      
organs in which endogenous serotonin had not been previously detected   
and to study the subcellular distribution of this amine in the rat      
pineal and adrenal glands .                                             
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effects of ruminal insufflation on cerebral circulation and metabolism  
in the goat .                                                           
  the effects of nitrogen insufflation of the cannulated rumen were     
studied in 10 goats . parameters which were measured included cerebral  
blood flow, mean carotid arterial pressure, pressure in the confluence  
of sinuses, cerebrospinal fluid pressure, blood oxygen and carbon       
dioxide contents, packed cell volume (pcv), and hemoglobin concentration
values for cerebrovascular resistance and cerebral o utilization were 
calculated .                                                            
  increased ruminal pressure had little effect on cerebral blood flow   
and cerebrovascular resistance . cerebral o utilization was decreased   
when the intraruminal pressure was increased . this decrease was caused 
by a reduction in arterial o content and a consequent decrease in       
cerebral arteriovenous o difference . mean arterial, venous sinus, and  
cerebrospinal fluid pressures were increased as the intraruminal        
pressure was increased . increases in pcv and hemoglobin concentration  
were not related to the elevated intraruminal pressure .                
  central nervous system signs in goats with acute ruminal tympany may  
be caused by cerebral hypoxia . the nature of the hypertensive changes  
associated with increased ruminal pressure were demonstrated, but due to
the influence of multiple factors on fluid compartments, no conclusions 
could be made about the mechanism of these pressure responses .         
mechanical factors, however, may be involved .                          
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a comparison between inhaled dust and the dust recovered from human     
lungs .                                                                 
  experiments on the loss of dust particles during breathing indicate   
total deposition in the respiratory tract,. subjection of the results to
qualitative arguments may give information about alveolar deposition .  
measurements of insoluble dust recovered post mortem from human lungs   
give the absolute retention of dust which was deposited in the alveoli  
and subsequently shifted, probably to a large extent, to the lymphatic  
vessels of the lungs .                                                  
  experimental results for total deposition and absolute retention are  
discussed in connection with the health risk due to inhaling insoluble  
particles, such as plutonium dioxide .                                  
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dual cation activation of bovine lens autolysis .                       
  the autolytic activity of bovine lens extracts at 55 c. and ph 7.4 has
been shown to be markedly influenced by the simultaneous presence of    
mono- and divalent cations . of the cations tested, na at 2.5 to 5 mm . 
and mg at 5 to 10 mm. produce the best activation . the stimulation is  
synergistic . on the basis of results obtained here and in other        
laboratories, the suggestion is made that this combination of cations   
may be required for activation of the neutral proteinase of the lens .  
in the presence of mg and average physiologic lenticular levels of both 
na and k , autolysis is suppressed to the basal level obtainable in the 
presence of mg alone .                                                  
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nucleic acid metabolism in the lens iii. effect of x-radiation .        
  a previous communication reported an increased in vivo incorporation  
of p-32 into the albuminoid rna fraction of the rat lens 6 hours after  
the animal had been exposed to x-radiation (1,500 r) .                  
  in the present study, the in vitro uptake of p-32 and c-14-adenine by 
albuminoid, ribosomal, and soluble rna fractions of normal and x-       
irradiated rat lenses was measured . the rna fractions were extracted by
sodium dodecyl sulfate in 0.9 per cent nacl . the specific rna fractions
were also hydrolyzed, chromatographed (on paper), and the activity of   
the individual nucleotides (as well as the specific rna fractions) was  
determined . an experiment was also performed in which the capsules were
removed (after the 3 hour incubation period) and the activities         
determined in the nucleic acids extracted from the capsules and in the  
three rna fractions of the remaining lens matter .                      
  the results of these experiments indicate that the incorporation of   
p-32 and c-14-adenine into albuminoid rna was markedly stimulated 1 hour
after 1,500 r whole body radiation . there was no significant effect on 
ribosomal or soluble fractions .                                        
  the effect of formaldehyde and heating on x-irradiated albuminoid rna 
was much less than on the albuminoid rna derived from control animals . 
.I 166
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changes in dna, rna, and protein synthesis in the developing lens .     
  lens cell dna, rna, and protein synthesis in the developing mouse eye 
were studied with the use of tritium-labeled thymidine, uridine, and l- 
leucine and autoradiographic techniques . in the mouse embryonic lens,  
epithelial cells undergoing dna synthesis were found over the entire    
anterior lens surface . from birth and until the eyes opened the        
percentage of epithelial cells undergoing dna synthesis rapidly         
decreased . later the percentage of epithelial cells undergoing dna     
synthesis was nearly constant as the germinative zone became localized  
in the lens equator region . rna synthesis occurred in all nucleated    
cells of the developing lens from the embryonic stage until the eyelids 
opened . with lens maturity the h uridine was incorporated into the rna 
of only the more superficial cells . a similar pattern of tritium       
incorporation was seen with h l-leucine .                               
.I 167
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amino acid transport in the lens in relation to sugar cataracts .       
  the steady state distribution of free amino acids between the lens and
aqueous humor is significantly reduced in diabetic rabbits and also in  
rats fed rations containing high concentrations of xylose or galactose .
  the reduction in the level of amino acids in the lens is apparently a 
direct effect of the high concentration of sugars, but it is doubtful   
whether it is related to cataract formation .                           
.I 168
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visco-elastic properties of the lens .                                  
  the dynamic visco-elastic properties of human, monkey and rabbit      
lenses have been measured with a dynamic rheometer . the value for the  
apparent elastic modulus (young modulus) of the lens was found to be 10 
-10 dyne/cm in humans and 10 -10 dyne/cm in monkeys and rabbits . the   
value for the loss tangent was 0.3-0.4 in the human lens and 0.3-0.6 in 
rabbit and monkey lenses .                                              
  elastic moduli and loss tangents of the lenses showed poor dependence 
on temperature at 15 -55 c and on frequency of oscillation at 0.01-25 c/
s . the lenses showed linear visco-elasticity when the amplitude of     
oscillation was below 0.02 mm, and they showed nonlinear visco-         
elasticity when the amplitude exceeded 0.03 mm .                        
.I 169
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carbonic anhydrase distribution in rabbit lens .                        
  the distribution of carbonic anhydrase activity in the mature rabbit  
lens was determined . the activities in nucleus, cortex, epithelium with
anterior capsule, anterior capsule, and posterior capsule were,         
respectively, 2484 ( 256), 1571 ( 87), 545 ( 93), 159 ( 39) and 65 ( 49)
moles co /kg wet tissue wt per hr at 0 c . it was concluded, on the     
basis of the available evidence, that carbonic anhydrase cannot play a  
primary role in the cation transport system of the lens .               
.I 170
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changes in weight and adenosine triphosphate content in the lens of the 
xylose-fed rat .                                                        
  xylitol and sorbitol accumulated in the lens of the xylose-fed rat two
days before loss of adenosine triphosphate, and cataractous changes,    
were apparent . the maximum degree of cataract occurred when the level  
of the polyols was at its highest . regression of cataract was          
accompanied by decrease in polyol concentration and restoration of the  
level of atp . the lens of the xylose-fed rat did not usually increase  
in weight .                                                             
.I 171
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identification of species-specific and organ-specific antigens in lens  
proteins .                                                              
  the species-specific and organ-specific antigens of lens were         
investigated by gel diffusion and immunoelectrophoresis techniques . it 
was found that rabbit antiserum to bovine lens showed cross reaction    
with other bovine tissues . these cross-reacting antigens were the b- - 
and y-crystallins . there were two major and a minor organ-specific     
antigen in lens . both the major antigens had a mobility and were       
identified as the a-crystallin of lens .                                
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an electron microscopic study of wolffian lens regeneration in the adult
newt .                                                                  
  changes in the morphology of cells during the regenerative tissue     
transformation of the pigmented epithelium of the iris into lens in the 
adult newt triturus viridescens were studied in ultrathin sections using
the electron microscope . in addition, quantitative analyses with       
electron micrographs were performed . the cells of the normal iris are  
characterized by an abundance of melanin granules, an extensive smooth--
surfaced endoplasmic reticulum, and irregular indentations of the       
nuclear membrane . after lens removal, the first visible changes are    
detected in nuclei of the mediodorsal iris cells and involve an increase
in the number of primary nucleoli . later, the nuclei enlarge and become
spherical, and prominent nucleoli appear . these nucleoli can be        
distinguished from the normal nucleoli by the presence of the granular  
cortex surrounding the fibrous core . the pigment granules seem to be   
completely extruded into the intercellular spaces and subsequently taken
up by leucocytes . the endoplasmic reticulum disintegrates gradually and
finally almost disappears . there is a significant increase of ribosomes
in the cytoplasm . later, the cytoplasmic matrix also acquires fibrous  
elements (about 50 a wide) of low density, probably corresponding in    
nature to the main components of a normal lens cell . these and other   
changes in the transforming cells are discussed .                       
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growth of several human cell lines in newborn rats .                    
  when injected intravenously into newborn rats, eight human            
tissue-cultured cancer cell lines -dash h.ep. 2, detroit 6, j-111, rp   
41, rp 212, adeno cx 1, ovary 2, and mac 21 -dash grew progressively in 
lung and other organs of more than 50 per cent of the animals and       
commonly caused death after 5-8 weeks . two other human cell lines -dash
the carcinoma h.ep. 1 and the presumably normal amnion b -dash grew less
frequently and rarely caused death or illness .                         
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the human tumor-egg host system iii. tumor-inhibitory properties of     
tenuazonic acid .                                                       
  the fermented broth of a culture of alternaria tenuis auct. inhibited 
the growth of the human adenocarcinoma (h.ad. 1) in the embryonated egg 
with the aid of studies in the egg-tumor system the active agent was  
isolated and identified as tenuazonic acid . tenuazonic acid was        
produced by a number of alternaria isolates and by an aspergillustamarii
and a phoma sp . compared with tenuazonic acid, on a molar basis, about 
20 times as much hadacidin or 6-mercaptopurine, 2 times as much         
azaserine, but only 1/20 as much triethylenemelamine (tem) were required
to achieve the same inhibition of h.ad. 1 tumor growth in the egg .     
tenuazonic acid was more effective against h.ad. 1 than against another 
transplantable human tumor, a-42 . tenuazonic acid, compared with       
puromycin, more specifically inhibited tumor growth in the egg-tumor    
system .                                                                
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the occurrence of biologic crystals in tumor and nontumor cultures of   
c3h/hej mice .                                                          
  crystalline structures of various types have been found in primary    
tissue cultures of neoplastic and non-neoplastic tissues from c3h/hej   
mice . all of the cultures of mammary carcinoma tissue contained the    
crystals . the crystals were found in varying incidence in the cultures 
of several other tissues with the exception of those from the kidney . a
'dialysis compartment' was not essential for the formation of the       
crystals . the development of the crystals was accelerated by a         
modification of the culture medium .                                    
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a comparison of the fine structure of cultured mac-21 and hela cell .   
  the fine structure of a cultured mucoid adenocarcinoma cell of human  
lung (mac-21) is described and compared with the fine structure of the  
hela cell . the differences in fine structure between the two strains   
are primarily quantitative . the mac-21 cell differed, however, in the  
following respects.. a spindle-shaped cell with larger nucleus and      
increased nuclear membrane invaginations, and considerably larger       
amounts of perinuclear golgi apparatus . the cytoplasm contained areas  
of low density, undefined by a limiting membrane, which are thought to  
be accumulations of mucin .                                             
  the two cell strains contained numerous multivesicular bodies, some   
with lamellae in various stages of development, suggesting that these   
organelles may be involved in the formation of the lipide-rich,         
myelinated structures observed in both hela and mac-21 cells . the      
number of myelinated bodies was found to be inversely proportional to   
the ph of the medium .                                                  
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effect of parathyroid and other human tumors and tissues on bone        
resorption in tissue culture .                                          
  mouse calvaria were grown in tissue culture in combination with single
or multiple fragments of a variety of human tumors and glandular tissues
to determine their capacity to enhance bone resorption . single         
fragments of parathyroid adenoma tissue consistently enhanced resorption
in both the frontal and the parietal bones . except for one squamous--  
cell carcinoma of the lung which had some activity all other tissues    
tested as single fragments had no enhancing effect . on the other hand, 
all human tissues enhanced resorption when multiple fragments were      
placed in a halo around the calvarium, suggesting the presence of lesser
amounts of resorption-enhancing factors in other human tissues .        
.I 178
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limited growth period of human lung cell lines transformed by simian    
virus 40 .                                                              
  summary--infection of human cell strains with simian virus 40 induced 
virus replication and cell transformation with the changes in morphology
and cytology described by previous investigators . although             
transformation greatly enhanced growth potentials of the strains, only 2
of 23 transformed cultures appear to have attained autonomous growth.--j
nat cancer inst 33.. 227-236, 1964 .                                    
.I 179
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bacteriophages that lyse mycobacteria and corynebacteria, and show      
cytopathogenic effect on tissue cultures of renal cells of cercopithecus
aethiops.. a preliminary communication .                                
  bacteriophages isolated from sputum and resection specimens of pa-    
tients suffering from carcinoma of the lung were found to lyse coryne-  
bacteria and mycobacteria, and to produce a cytopathogenic effect on    
certain cells in tissue cultures . from the same and other patients with
neoplastic disease, bacteria were isolated and described as coryne-my-  
cobacteria because of bacteriological features they shared with both    
species . these bacteria, which either were sensitive to mycobacterio-  
phages and corynebacteriophages or were phage-immune lysogenic bacteria,
could be induced to produce lytic particles with phagolytic activity on 
corynebacteria and mycobacteria and a cytopathogenic effect on hela     
cells and on the renal cells of cercopithecus .                         
.I 180
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gel filtration of the soluble proteins from normal and cataractous human
lenses .                                                                
  the soluble proteins of normal and cataractous lenses were separated  
according to their molecular size on the polysaccharide gel sephadex    
g-100 . in cataractous as well as in normal lenses 4 different compo-   
nents were obtained . during the evolution of cataract there is a pre-  
ferential decrease of the low molecular weight proteins of the lens .   
these disappeared completely in mature and hypermature cataract . on the
other hand, the proteins of high molecular weight (e.g., -crystallin)   
are very resistant to the pathological process . the electrophoretic    
pattern of the low molecular weight proteins in the normal lens revea-  
led several fractions distributed over a large mobility area . after    
immunoelectrophoresis, 3 different precipitin lines were obtained .     
.I 181
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the insoluble proteins of bovine crystalline lens .                     
  the insoluble lens proteins, the albuminoids, of the adult bovine lens
cortex can be rendered soluble by raising the ph of their washed        
suspension in 0.9 nacl to 10.5 and then reducing it again to ph 7.4 .   
the sedimentation constant of the dissolved protein is 10.8 s,. its     
molecular weight is estimated to be 360,000 12,000 . the amino acid     
composition is approximately the same as that of the soluble -crysta-   
llin fraction, a kinship which is also apparent from their immunochemi- 
cal properties . it is suggested that the initial insoluble protein is a
molecular aggregate of -crystallin, which is dissociated in alkaline    
solutions to molecules exhibiting a sedimentation constant of 10.8 s .  
.I 182
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glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase  
in lens and blood of different species .                                
  the activities of glucose 6-phosphate and 6-phosphogluconate dehydro- 
genase were measured in the lens and erythrocytes of man and several    
other species . there is a wide variation between individuals of the    
same species, but there seemed no correlation between the activity of   
either enzyme in the lens and their activity in the erythrocytes of the 
same species . there is a wide range of activity of both glucose 6-phos-
phate dehydrogenase and 6-phosphogluconate dehydrogenase in the lens and
in the blood of different species . several species had glucose 6-phos- 
phate dehydrogenase activity in erythrocytes below the level considered 
/deficient/ in man . the sorbitol content of the lens was not correla-  
ted with glucose 6-phosphate dehydrogenase activity .                   
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nucleic acid metabolism in the lens iii. effect of x-radiation .        
  a previous communication reported an increased in vivo incorporation  
of p-32 into the albuminoid rna fraction of the rat lens 6 hours after  
the animal had been exposed to x-radiation (1,500 r) .                  
  in the present stody, the in vitro uptake of p-32 and c-14-adenine by 
albuminoid, ribosomal, and soluble rna fractions of normal and          
x-irradiated rat lenses was measured . the rna fractions were extracted 
by sodium dodecyl sulfate in 0.9 per cent nacl . the specific rna       
fractions were also hydrolyzed, chromatographed (on paper), and the ac- 
tivity of the individual nucleotides (as well as the specific rna frac- 
tions) was determined . an experiment was also performed in which the   
capsules were removed (after the 3 hour incubation period) and the      
activities determined in the nucleic acids extracted from the capsules  
and in the three rna fractions of the remaining lens matter .           
  the results of these experiments indicate that the incorporation of   
p-32 and c-14-adenine into albuminoid rna was markedly stimulated 1 hour
after 1,500 r whole body radiation . there was no significant effect on 
ribosomal or soluble fractions .                                        
  the effect of formaldehyde and heating on x-irradiated albuminoid rna 
was much less than on the albuminoid rna derived from control animals . 
.I 184
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an investigation of mitotic control in the rabbit lens epithelium .     
  a water soluble substance which inhibits mitosis in the rabbit lens   
epithelium has been found to be present in young and old rabbit lenses .
it has a high molecular weight and is relatively stable at room tempera-
ture . the inhibitory factor is associated with the y-crystallin frac-  
tion and exists throughout the young lens, although the activity in the 
nuclear region (on a wet weight basis) is less than half that of the    
cortex and epithelium .                                                 
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the identification of lysosomal enzymes in bovine lens epithelium .     
  biochemical studies are described for the isolation of lysosomes      
(identified as such by the activities of their enzymes) in the cells of 
the bovine lens epithelium . the various fractions assayed for lysosomal
enzymes showed contamination of mitochondrial and soluble cytoplasmic   
material in the two isolation procedures employed .                     
.I 186
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protein synthesis and polyribosomes in the calf lens .                  
  a cell-free system capable of incorporating amino acid into protein   
has been isolated from calf lens . polyribosomes have been shown to be  
present in the ribosomal fraction and to be responsible for most of the 
protein-synthesizing capacity of this fraction . the polyribosomes have 
been examined by electron microscopy and appear to be composed of long  
strands of ribonucleic acid, ranging from 7,000 a to 20,000 a, and con- 
taining a large number of ribosomes with an average diameter of about   
140 a .                                                                 
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measurement of oxygen tensions in cerebral tissues of rats exposed to   
high pressures of oxygen .                                              
  brain and cerebrospinal oxygen tensions have been measured in rats    
breathing air or in various high pressures of oxygen (ohp) . addition of
5 percent co2 to the inspired oxygen raised cerebral oxygen tensions    
when rats were exposed to 2 atm abs or above . inhibition of 75         
hemoglobin saturation by para-aminopropriophenone lowered cerebral po in
rats breathing air, but not in rats exposed to ohp . the rate of rise of
cerebral po to a steady level after rapid compression was found to be   
faster than the rate of fall to a steady level following decompression .
addition of co to the inspired gas mixture increased the rate of rise of
cerebral po . the anesthetics urethane and pentobarbital sodium did not 
affect cerebral po in rats breathing air or oxygen at 4 atm . the       
results are discussed in relation to factors contributing to oxygen     
poisoning at high pressures .                                           
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release of free fatty acids from adipose tissue obtained from newborn   
infants .                                                               
  summary the role played by mobilization of free fatty acids (ffa) from
adipose tissue in producing the typically high serum ffa levels of human
infants has been studied . ffa concentrations in the serum and subcuta- 
neous adipose tissue from the gluteal region were determined during     
postnatal development . a maximum level was reached within 24 hr after  
birth, after which there was a gradual fall . in serum the ffa level at 
the end of 12 months was still higher than that in adults, while the ffa
level in adipose tissue was lower at 3 months than in adults .          
  incubation of small pieces of adipose tissue in krebs-ringer phosphate
buffer containing 4 albumin led to release of ffa into the medium . this
release could be suppressed by the addition of glucose (200 mg/100 ml)  
for tissue from all age groups except the youngest (0-15 hr after birth)
.I 189
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detection of pericardial effusion by radioisotope heart scanning .      
  a marked difference between the cardiac silhouette on the six-foot    
chest roentgenogram and the cardiac blood pool, determined by radioiso- 
tope scanning, has been shown to be consistent with pericardial effusion
and/or thickening . it has also been observed that the cardiac blood    
pool is separated from the liver margin by the interposition of peri-   
cardial fluid and/or thickening . this separation was not demonstrated  
in the presence of a normal pericardium . to appreciate these features, 
400 c. of radioiodinated human serum albumin and 50 c. of colloidal     
radiogold were used for scanning . the former outlined the blood pool   
and the latter demonstrated the position of the liver .                 
.I 190
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on the mechanism of erythropoietin-induced differentiation iv. some     
characteristics of erythropoietin action on hemoglobin synthesis in     
marrow cell culture .                                                   
  some of the characteristics of the erythropoietin stimulation of hemo-
globin synthesis by rat marrow cells in culture have been studied . the 
relationship between cell number and rate of hemoglobin synthesis at va-
rious levels of erythropoietin is sigmoid rather than linear suggesting 
a cooperative action among the sensitive cells . the magnitude of the   
erythropoietin effect on the cells increases with time of contact with  
the hormone,. at the time of one-half maximal effect there is no discer-
nible loss of erythropoietin from the culture medium . a previously des-
cribed lag time in the response to erythropoietin appears to be largely 
due to the conditions of culture and disappears when the cells are pre--
incubated for 9 h . replacement of a large fraction of the medium at    
24-h intervals enabled the cells to continue hemoglobin synthesis for an
additional 24 h .                                                       
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the occurrence of megakaryocytes in the peripheral blood of dogs .      
  a study of megakaryocytes in buffy coat smears from 26 dogs revealed  
that no unusual characteristics were consistently associated with appea-
rance of megakaryocytes in the peripheral blood .                       
.I 192
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moderate hypothermia in man.. haemodynamic and metabolic effects .      
  studies were performed on four patients undergoing intracranial opera-
tion during the induction and reversal of surface hypothermia to 30 c . 
oxygen uptake decreased an average of 26 per cent from 34 to 30 c to a  
mean value of 48 per cent of predicted basal uptake . at the same time, 
cardiac output decreased only 11.5 per cent, resulting in a consistent  
rise in calculated mixed venous oxygen saturation from a mean of 76 to  
81 per cent at 30 c . as a result of this and the effect of cooling on  
oxygen dissociation, the estimated tension of oxygen in mixed venous    
blood remained virtually unchanged . when shivering was allowed to occur
in two patients, oxygen uptake increased approximately 50 per cent      
without any concomitant increase in cardiac output . observed right     
atrial and svc oxygen saturations correlated well with calculated mixed 
venous oxygen saturations with regard to direction and magnitude of     
change with change in temperature .                                     
.I 193
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the spectrum of lupus nephritis .                                       
  fifty cases of sle have been collected over a ten year period and the 
incidence and clinical picture of ln reviewed in the light of other     
published data .                                                        
  lupus nephritis, like sle, has a variable pattern of its own with a   
wide spectrum of renal involvement -dash evaluation of therapy and      
prognosis will have to be conducted against this background .           
  lupus nephritis may present as a renal syndrome only, without any of  
the other manifestations of sle .                                       
  renal involvement in sle is common, but this does not necessarily     
indicate a poor short-term prognosis . in the peter bent brigham        
hospital series a sustained raised blood pressure and the onset of renal
insufficiency influenced the prognosis adversely .                      
.I 194
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comparison of ultraviolet sensitivity of bacillus subtilis bacteriophage
spo2 and its infectious dna .                                           
  deoxyribonucleic acid extracted from a clear plaque mutant of the     
temperate phage, spo2, was infectious when incubated with competent     
cultures of bacillus subtilis 168 m . the relationship between numbers  
of infectious centers and dna concentration was linear .                
  the sensitivity of the infectious dna to ultraviolet light was much   
greater than that of the free phage when b. subtilis 168 m was used as  
host . acriflavin, which inhibits host cell reactivation, increased the 
rate of ultraviolet inactivation of the free phage so that it approached
the inactivation rate of the phage dna . acriflavin had little effect on
the survival curves of the infectious dna .                             
  non-host reactivating mutants (hcr ) of b. subtilis 168 m were        
isolated . the survival curves of spo2 phage were much steeper when the 
hcr mutant was used as a host than those obtained when the hcr parental 
strain was used as a host .                                             
  ultraviolet sensitivity of the phage dna was still greater than that  
of the free phage even when b. subtilis hcr was used as host, but the   
difference in sensitivity was much less than the difference obtained    
with b. subtilis hcr as a host .                                        
  possible explanations for the greater ultraviolet sensitivity of the  
infectious dna are discussed .                                          
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the isolation and morphology of some new bacteriophages specific for    
bacillus and acetobacter species .                                      
  the best natural habitat for bacteriophages is probably a semi-solid  
medium containing actively dividing host bacteria . such conditions are 
provided for bacillus and acetobacter species in rotting grass and      
apples, respectively . the bacillus phages found included one with a    
large head and a contractile tail, and also a so-called killer particle,
which had a 350 a head and a long contractile tail . this particle had  
the property of killing but not multiplying within a sensitive cell . a 
new morphological type of virulent bacillus phage was also isolated,.   
its head was oblong and the tail consisted of a short needle and a plate
the one acetobacter phage found resembled coliphage t3 but was of     
particular interest because of the prominence of the head capsomeres and
the three-pronged tail .                                                
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characterization of bacillus subtilis bacteriophages .                  
  brodetsky, anna m. (university of california, los angeles), and w. r. 
romig . characterization of bacillus subtilis bacteriophages . j.       
bacteriol. 90..1655-1663. 1965.--a group of six phages, sp5, sp6, sp7,  
sp8, sp9, and sp13, which use the marburg strain of bacillus subtilis as
host was characterized . these phages, referred to as group 1, were     
examined for the following properties.. host range, plaque morphology,  
stability, adsorption kinetics, one-step growth characteristics, calcium
requirements, serum neutralization, thermal inactivation, and           
inactivation by ultraviolet irradiation . five unrelated b. subtilis    
phages, sp3, sp10, pbs1, sp alpha, and sp beta, were included in the    
studies . when first isolated, none of the group 1 phages was able to   
replicate efficiently on b. subtilis sb19, a mutant of the /transforming
/ b. subtilis 168 . host range mutants capable of growth in sb19 were   
isolated for all of the group 1 phages except sp13, and are designated  
the /star/ phages (sp5 through sp9 ) . for characterization, sb19 was   
used as host for the star phages, and another b. subtilis mutant, 168b, 
was host for sp13 .                                                     
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transduction in bacillus subtilis .                                     
  (i) comparative examinations have shown that the temperate subtilis   
phages can be divided into two groups . b. subtilis strain nrs 231 was  
an adequate common host sensitive to all the examined temperate phages .
  owing to certain technical advantages this strain was found suitable  
for the titration subtilis phages .                                     
  (ii) some cultural differences have been revealed among substrains of 
b. subtilis 168 ind auxotrophs maintained in various laboratories .     
cells in one of these cultures were partly capable and partly incapable 
of using ammonia . ammonia assimilation was transducible to ammonia     
negative bacteria .                                                     
  (iii) after mitomycin c or ultraviolet ray induction the examined b.  
subtilis strains liberated /bacteriocin/-like principles . this finding 
is probably analogous to that of seaman et al. concerning pbsx defective
phages . on the basis of bacteriocin production the examined strains    
were divided into two groups .                                          
  (iv) several temperate phages isolated in our laboratory were         
presumably identical with phage pbs 1 . phage sp 10 differed from these 
agents both in antigenic structure and in host range .                  
  (v) transduction by some lysates of pbs 1-type phages was observed at 
frequencies of the order of 10 . considerably more and less effective   
phage materials were yielded by some lysogenic transductants . thus     
transducing phages active in the order of 10 were prepared .            
  (vi) transduction frequency, in addition to the properties of the     
phage, was influenced by the physiological condition of bacteria .      
  (vii) transduction of indole and histidine loci was studied by use of 
his derivatives of strain 168 ind .                                     
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the carrier state of bacillus subtilis infected with the transducing    
bacteriophage sp10 .                                                    
  bacteriophage sp10 may infect bacillus subtilis to form a carrier     
system . the infected bacteria give rise to infected organisms after six
or more successive single-colony isolations . about 60 of the spores    
derived from such an infected culture yield clones that produce phage,  
and such spores retain their ability to produce phage even after        
treatment with antiserum and heating at 80 . four hours' incubation of  
carrier spores in nutrient broth yields cultures having more than 10    
infective centers per bacterium . cultivation of infected organisms in  
medium containing sp10 antiserum leads to loss of phage and loss of     
immunity to phage infection . dna with a density characteristic of viral
dna can be detected in infected bacteria . extracts of infected bacteria
contain a phage-induced deoxyribonuclease activity which attacks both   
phage and bacterial dna in vitro . the phage-bacterial complex is       
therefore best described as a carrier state .                           
  the dna of the phage and of b. subtilis are chemically different .    
enzymatically prepared complementary virus rna has no homology with     
bacterial dna . the lack of homology of this transducing phage dna with 
the dna of its host and the failure to form a truly lysogenic           
relationship reinforce previous conclusions that transducing bacterial  
dna is incorporated into the sp10 virus particle without any            
recombination between viral and bacterial dna .                         
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infectivity of dna isolated from bacillus subtilis bacteriophage, sp82 .
  sp82, a newly isolated bacteriophage of bacillus subtilis, is         
described . sp82 is closely related to sp8, but differs from sp8 in the 
density of its denatured dna and in its plating effciency on b. subtilis
strain sb-1 .                                                           
  dna isolated from this phage can be recovered in molecular weight     
equivalent to the amount contained in a single phage (approximately 130 
x 10 daltons) . dna of this molecular weight, but not half pieces, is   
infective in competent b. subtilis . the response of plaque-forming     
ability to dna concentration suggests that four whole molecules are     
required to initiate an infective center . recombination studies with   
mixed dna's of two non-allelic temperature-sensitive mutants confirm the
existence of an obligatory co-operative infective process . a second    
infective procedure that utilizes extracted phage dna is described . in 
this system, low concentrations of wild-type dna are exposed to the     
cells . at these concentrations the multiple-event nature of phage dna  
infection precludes the formation of unaided plaques . however, by      
subsequently superinfecting the dna-infected cells with a               
temperature-sensitive mutant and plating under selective conditions,    
genetic rescue of the infecting dna is accomplished and detected .      
infective centers elicited by this /marker rescue/ phenomenon are       
directly proportional to dna concentration . the time of attainment of  
dnase resistance by phage dna infective centers that have irreversibly  
adsorbed dna can be measured . phage dna infective centers require at   
least 13 minutes to become totally dnase resistant . the reasons for the
failure of single phage dna molecules to carry out an infection are     
discussed in terms of a specific breakage-reunion                       
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psychology of children's dental treatment .                             
  the communication deals with influences involved in the development of
the child's attitude to dental treatment . they are extrinsic           
(educational etc.) and intrinsic (constitutional and hereditary) . their
understanding helps to determine the correct psychological policy for   
the management of the child in the surgery .                            
  the aim of psychology applied in dentistry is to discover a mode of   
treatment procedure which would ensure that the child will not be       
subject to any psychic traumatization (psychophylaxis) . its second aim 
is the management of the so called difficult child and his treatment .  
  to understand better the child's frame of mind during dental treatment
the situation in the surgery is dealt with step by step as the child    
experiences it through his senses and his psyche . beside the basic     
senses -dash hearing and seeing -dash others are also affected.. touch  
(pressure sensation), smell and taste .                                 
  children during dental treatment are nearly always in a state of      
raised emotional tension and are susceptible to anxiety reactions .     
according to the degree of fear which they manifest children may be     
classed into categories of cooperating and difficult patients . the     
psychological procedure for the treatment of children of both groups is 
based on the principles summarized in the section 'psychophylaxis in    
dentistry' . in difficult children it is often necessary to employ yet  
other psychological measures-psychotherapy, suggestion etc . in         
extremely exacting cases premedication helps sometimes to find contact  
with the child .                                                        
  the experimental part of the work demonstrates the following findings 
 1. dental treatment consists of a series of interdependent           
traumatizing impulses . many of them appear only after a close analysis 
of the situation . 2. the adverse response similar to that elicited by  
pain may be due also to sensory impressions with a negative emotional   
background . 3. psychic traumatization of the child during dental       
treatment can be prevented by relatively simple psychological measures .
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relation of emotional changes during pregnancy to obstetric             
complications in unmarried primigravidas .                              
  this study was designed to assess the psychological changes           
experienced by white unmarried primigravidas during pregnancy, the      
relationship between manifest anxiety and clinical factors such as labor
time and mean birth weight, and the personality differences between     
/normal/ and /abnormal/ obstetric cases . the kent egy intelligence     
scale, the taylor manifest anxiety scale, and the mmpi were administered
to 160 obstetric patients at the beginning of the third trimester of    
pregnancy, with the mmpi and taylor being readministered post partum .  
reliable group personality changes observed from pre- to postdelivery   
supported the contention that pregnancy is a time of emotional upset .  
  following delivery, each patient was classified as normal or abnormal 
dependent on the clinical course of parturition, delivery, and condition
of the offspring . there were no significant differences between these  
groups with respect to age or intelligence . reliable differences were  
found, however, for manifest anxiety and total labor times . in         
addition, a positive relationship was found between manifest anxiety and
birth weights . personality differences found at predelivery between the
subgroups were largely attributable to the abnormal group's greater     
neuroticism, anxiety, and use of the ruminative ego defenses .          
  post partum, the personality characteristics of the subgroups were    
quite similar . both groups showed greater personality stability        
following delivery, with the most striking changes from predelivery     
demonstrable in the abnormal group . the magnitude of these changes were
interpreted as emotional lability and related to obstetric complications
by activation of various physiological regulator systems .              
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stranger and separation anxiety in infancy .                            
  anxiety responses to strangers and to separations from mother were    
studied longitudinally in 19 infants between the ages of three and 23   
months by direct observations and by interviews with the mother .       
benjamin's hypotheses concerning the differentiation and immediate      
dynamics of infantile stranger and separation anxiety were supported by 
the findings . differences in onset, period of highest intensity,       
termination, and ratios in individuals were found between the two       
anxieties . tests of the relationship between the two anxieties were    
supportive of deductive predictions made by benjamin . sex differences  
in intensity of the two anxieties were found .                          
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mental retardation related to hypercalcaemia .                          
  for more than 20 years a number of retarded children and adolescents  
have been observed who show points of striking similarity . we recognise
in them a well-defined type that is clearly distinguishable from other  
forms of mental deficiency . they are therefore described in detail .   
some of the children have had infantile hypercalcaemia but it is assumed
that other aetiological factors are also involved .                     
  there is a characteristic facies and usually congenital heart disease 
ordination is poor . there is a constant failure to thrive in infancy,
with episodes of vomiting, often with constipation . mentally the       
children also show great similarities . their iq is about 40-50 but they
show outstanding loquacity and a great ability to establish interper-   
sonal contacts . this stands against a background of insecurity and     
anxiety .                                                               
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psychological effects of circumcision .                                 
  in order to evaluate the psychological effects of circumcision, a     
small study was arranged in which twelve children, from average and low 
socio-economic level, were given goodenough dam test, cat, rorschach and
two sets of stories, prior to the operation and following it . the      
results of the tests showed that circumcision, performed around the     
phallic stage is perceived by the child as an act of aggression and     
castration . it has detrimental effects on the child's functioning and  
adaptation, particularly on his ego strength . by weakening the         
controlling and defensive mechanisms of the ego, and initiating         
regression, it loosens the previously hidden fears, anxieties, and      
instinctual impulses, and renders a feeling of reality to them . what is
expressed following the operation is primitive, archaic, and            
unsocialized in character . as a defensive control and protection       
against the surge of the instinctual forces coming from within and the  
threats coming from outside, the ego of the child seeks safety in total 
withdrawal, thus isolates and insulates itself from disturbing stimuli .
  the results of the study raised some questions concerning certain     
psychoanalytic formulations, for which further research was suggested . 
possibilities for future research were also discussed .                 
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changes in children's behavior after hospitalization some dimensions of 
response and their correlates .                                         
  changes in 387 children's behavior following hospitalization were     
evaluated by means of a questionnaire sent to parents a week after      
discharge . factor analyses revealed that children's responses to       
hospitalization and illness were of six types.. (i) general anxiety and 
regression, (ii) separation anxiety, (iii) anxiety about sleep, (iv)    
eating disturbance, (v) aggression toward authority, and (vi)           
apathy-withdrawal . scores for these six factors (types of responses) as
well as a total score, were analyzed by univariate and, in most cases,  
multivariate analyses of variance . four variables -dash sex, prior     
hospitalization, degree of pain experienced during hospitalization, and 
birth order -dash were essentially unrelated to any type of response by 
any analysis . age, duration of hospitalization, and occupational status
were each significantly related to one or more types of responses .     
comparison of the mean factor and total scores for the full sample with 
the levels indicative of no overall change indicated that the           
combination of illness and hospitalization is a psychologically         
upsetting experience for children in general, resulting in increased    
separation anxiety, increased sleep anxiety, and increased aggression   
toward authority .                                                      
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isozymes of lactic dehydrogenase.. sequential alterations during        
development .                                                           
  applications of isozymes in various biological contexts have been     
reviewed . diagnosis of several disease states has been facilitated by  
examination of the serum isozyme pattern which has been shown to        
correlate in some conditions with the isozyme pattern of pathologically 
involved tissues . physico-chemical studies of human ldh isozymes have  
revealed differences among isozymes in affinity for a given substrate . 
comparative studies of ldh isozymes within the erythrocyte from various 
vertebrate species demonstrated a marked species variation in the number
of ldh isozymes, in the distribution of total ldh activity among them,  
and in their electrophoretic mobilities . during development of chick,  
rabbit, and human tissues characteristic sequential alterations in the  
ldh isozyme pattern occurred and consisted for liver and muscle in loss 
of the most rapidly migrating anodal bands and increased activity in the
cathodal bands and slower migrating anodal bands . in heart the reverse 
changes were observed . if high enough ldh activities of early fetal    
tissue extracts were applied to the gel the full complement of ldh      
isozymes was observed,. however, in lower concentrations the cathodal   
bands, which in the starch gel disappear more rapidly on dilution than  
do the anodal bands, were not observed . a species-specific isozyme     
pattern is obtained in long term culture of rabbit, chick, and human    
cells . independently of the tissue of origin, there occurs in cells in 
culture a sequential series of isozyme alterations characterized by     
decreased intensity of rapidly migrating anodal bands . the shift toward
prominence of cathodal isozymes during both fetal development and tissue
culture can be explained by postulating the increased activity of the   
gene producing one of the subunits of ldh with a concomitant decrease in
the activity of the gene producing the second subunit . practical       
applications of the study of isozymes in tissue culture were discussed .
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establishment of a cell line in vitro from a case of human lung cancer .
  1) one cell line has been established from the pneumonectomized       
specimen of a case with lung cancer, which was diagnosed as             
undifferentiated cell carcinoma and partially adenocarcinoma by its     
histological findings and was characterized with intracytoplasmic fat   
droplets in them .                                                      
  2) the morphological changes of the cells were repeated but they have 
been stabilized to their epithelial shapes after the 35th transfer . the
cell atypy of the culture was remarkable . phagocytosis of the cell line
has not been observed . it was characterized that the intracytoplasmic  
droplets found in the original cancer cells have been maintained in the 
cultured cells, even in their mitotic stage, throughout the cultural    
course .                                                                
  3) concerning the chromosomal constitution diploid cells were only 15 
per cent . the range of chromosome number did not show sharp peak,      
forming two groups of near diploid and near tetraploid ranges .         
  4) transplanting the cell to cheekpouches of golden hamsters, the     
implanted cells grew from the inoculum of 10 cells in conditioned animal
but did not show the invasiveness to neighbour tissue and metastasis to 
other organs .                                                          
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factors influencing development of tumors in frogs .                    
  (1) study of 75 spontaneous tumors of vermont frogs showed three      
pathological grades of malignancy present.. aggressive renal            
adenocarcinoma in some 30 per cent, medium adenocarcinoma in 50 per     
cent, and lower grade mixed with tumors of undetermined origin in the   
remaining 20 per cent .                                                 
  (2) correlation with parasite infections (trematodes) was demonstrable
in only few cases in the kidney . hyperplasias and neoplasias grading   
into lung primary carcinoma have been found in the lung in r. pipiens . 
temperatures below 15 c. protected animals from lung as well as kidney  
disease . higher temperatures disturbed the host-parasite relationships 
and led to higher incidence of malignancy . in the bullfrog, precancer  
was clearly associated with the worm attachment discs .                 
  (3) other histological types of tumors in vermont frogs included      
lymphosarcomas, liposarcoma, mesothelioma, epithelioma, and adrenal and 
cartilage tumors of uncertain malignancy .                              
  (4) improved methods of obtaining tumor filtrates allowed greater     
probability of inducing malignancy with direct renal injection . in 106 
frogs 37 per cent developed histologically provable cancers in the      
ranges of three to seven months . twenty-six per cent showed some       
pre-cancer response and 43 per cent were negative . within the series   
receiving filtrate from high malignancy donors one group yielded 100 per
cent positive, the others 50 and 38 per cent, respectively .            
  (5) among animals injected with /low/ malignancy filtrate, fewer      
tumors resulted . some of these were clearly vesicular carcinomas and   
could be classed as lung tumors .                                       
  (6) improved tissue culture methods allowed explants to live in liquid
media under perforated cellophane up to one year . slower growth, aided 
by lower temperatures (16 c.) improved the microecology of cell types   
and allowed detailed daily observations of each cell's intranuclear and 
intranucleolar physiology for extended time-lapse cine-photography .    
  (7) mechanisms for malignant transformation are related to increased  
activity and production of nucleolar dna and rna . the infective dna    
hypothesis is not classical virus theory, but it does offer detailed    
support .                                                               
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mitotic lymphocytes in primary tissue cultures of normal and neoplastic 
human lung .                                                            
  normal and tumor tissue explants from 33 resected human lungs were    
studied in vitro . lymphocyte mitoses were observed in tissue cultures  
derived from 12 of the lungs . the ability of lymphocytes to undergo    
mitotic division in human lung tissue culture has not been reported     
previously . in the autologous systems used lymphocyte mitoses were much
more common in cellular outgrowths derived from non-neoplastic tissue   
than they were in the outgrowths derived from cancer-bearing explants . 
no differences were observed in the total number of nondividing         
lymphocytes present in the non-neoplastic and neoplastic preparations . 
the in ritro systems employed are promising tools for further           
contributions to an already well established clinicopathologic          
relationship between lymphocytes and cancer cells .                     
  phase contrast and time-lapse cinephotomicrographic records were      
obtained of the mitotic process and special attention was paid to the   
structural details . certain findings were of particular interest,      
namely the formation of a dense chromatin ring during telophase, the    
variable occurrence of cytoplasmic bubbling, and the death of           
lymphocytes during early metaphase (/exploding/ metaphase) . an         
elaboration and discussion of these findings have been presented .      
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studies on transformation of syrian hamster cells by simian virus 40    
(sv40).. acquisition of oncogenicity by virus-exposed cells apparently  
unassociated with the viral genome .                                    
  lines of syrian hamster lung and liver cells originally exposed as    
primary cultures to large doses of sv40 exhibited increased growth rate,
high plating efficiency, morphological transformation, and, in some     
instances, oncogenic potential after unusually long intervals . in at   
least two lines acquisition of oncogenic potential occurred             
independently of morphological transformation . in none of a total of 11
cell lines studied in detail was conclusive evidence for the presence of
the sv40 genome obtained .                                              
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eye and kidney tissue reactions to heterologous anti-uveal antibodies . 
  the uvea, lens capsule and kidney glomerulus in the albino wistar rat 
have a common antigenic component(s) . the uvea and lens capsule in the 
pigmented bovine eye also have a common antigenic component(s) . these  
results were demonstrated by the immunofluorescence technique . the     
common antigenic sites in the uvea were assumed to be the basement      
membrane surrounding the vascular trees in the tissues . the possibility
of the basement membrane participation as an antigenic source for       
inducing sympathetic ophthalmia is discussed .                          
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experiments dealing with the role played by the aqueous humor and retina
in lens regeneration of adult newts .                                   
  1. these three groups of experiments involve approximately 140 eyes of
adult newts, triturus v. viridescens . they were devised to examine     
what, if any, role the aqueous humor plays during lens regeneration from
the dorsal iris .                                                       
  2. many daily injections of aqueous humor from normal eyes were made  
in lentectomized eyes for as long as 96 days in some cases . as controls
some lensless eyes were daily injected with holtfreter's solution . in  
others aqueous humor was merely withdrawn .                             
  3) procedures for the injection experiments are difficult to control .
however, the most successful cases showed varying degrees of inhibition 
and retardation of lens regeneration .                                  
  4. pairs of eyes were united at large adjacent wound openings to      
provide a common reservoir of aqueous humor bathing both lenses and     
dorsal irises . in some cases the eyes were placed on the side of the   
body . in others more successful unions were made by fusing a           
transplanted eye to the right eye of a host .                           
  5. approximately three months after operation one of two large lens   
regenerates in a pair of perfectly fused eyes was removed . six weeks   
later a new large lens regenerate reappeared in most of the             
lentectomized units in the presence of the intact lens of the other unit
  6. there is a strong possibility that the more than normal amount of  
neural retina present provided a more powerful retinal factor for lens  
regeneration than the inhibiting influence of the intact lens in the    
environment .                                                           
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correlation between the mast cells and histamine content of the eye in  
cattle .                                                                
  the authors have examined the mast cell content of the eyes of cattle 
and have established that most of the mast cells are contained in the   
conjunctiva, the optic nerve and the ocular muscles,. fewer occur in the
sclera and iris, and least in the ciliary body and choroid . cornea,    
lens and retina do not contain mast cells . the histamine content of the
ocular tissues and their mast cell contents generally run parallel .    
however, the cornea is exceptional in that its histamine does not occur 
in a bound state but in some form which is readily available to a mild  
process of extraction (tyrode solution at 4 c) .                        
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studies in sickle cell anemia xxi. clinico-pathological aspects of      
neurological manifestations .                                           
  neurologic manifestations are frequent in patients who have sickle    
cell disease . these manifestations may be the earliest presenting signs
and symptoms and they are so variable that the patient may be           
erroneously diagnosed as having conditions such as meningitis,          
poliomyelitis, subdural hematoma, neoplasm, subarachnoid hemorrhage,    
lead encephalitis, subacute bacterial endocarditis, and congenital      
malformations of the brain . furthermore, development of these          
manifestations cannot be predicted on the basis of the type of crisis   
involved .                                                              
  prognosis following neurological involvement is unpredictable, but    
recurrent episodes, together with abnormal electroencephalographic      
readings suggest a poor outcome . such patients die or are the victims  
of rather severe neurological deficits .                                
  neurological examination of these patients suggests diffuse           
involvement of the cerebral hemispheres . examination of the            
pathological material, however, often fails to reveal thromboses . the  
striking findings are infarcts in the white matter and perivascular     
hemorrhages .                                                           
  the thesis that the abnormal neurological findings in these patients  
are actually due to sickle cell disease is supported by the fact that   
all such symptoms appear in association with clinical circumstances     
known to induce sickling . these include surgery and anesthesia, fever  
and infection .                                                         
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attenuation curves of the human eye under normal and pathological       
conditions .                                                            
  a method is described which allows the determination of /attenuation  
curves/ of the human eye . those curves are obtained by plotting the    
critical depth of modulation (cmd) as a function of the critical fusion 
frequency (cff) . routine experiments were carried out for a 2 test     
field showing a sinusoidal periodical variation of its luminance,       
surrounded by an extensive area with a luminance equal to the average   
luminance of the test field . attenuation curves were obtained for      
normal observers under different experimental conditions and for a      
number of patients . it is shown that this method affords us information
which cannot be obtained by means of the classical methods for measuring
the cff .                                                               
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central nervous system manifestations of periarteritis nodosa .         
  in the 114 cases of pathologically proved periarteritis nodosa        
reviewed, 53 patients (46 percent) had symptoms and signs of central    
nervous system or cranial nerve involvement . thirty-nine patients had  
both cerebral manifestations and neuropathy, 38 had neuropathy alone,   
and 14 had only cerebral symptoms and signs .                           
  the most common cerebral manifestation was that of mental derangement,
usually an organic psychosis or confusional state . headache,           
convulsions, blurred vision, vertigo, and sudden unilateral visual loss 
were the most common symptoms referable to the central nervous system . 
the most common abnormalities on examination were retinopathy,          
hemiparesis, and signs of a brainstem lesion . there was no difference  
in duration of life, after onset of disease, in those with and those    
without central nervous system involvement .                            
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see-saw nystagmus an unusual sign of lesions near the third ventricle . 
  a case of see-saw nystagmus in a child with craniopharyngioma and     
bitemporal hemianopsia is described, and reference is made to previous  
case reports . the basis for this curious sign is not clear, but the    
site of the lesion must be considered to be in the region of the third  
ventricle, since bitemporal hemianopsia is a necessary part of the      
syndrome . the sign is not common but when present points to a lesion   
near the third ventricle .                                              
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implications of gerstmann's syndrome .                                  
  of 465 consecutive patients subjected to a standardized battery of    
neuropsychological tests, 111 had one or more components of gerstmann's 
syndrome . each of these 111 patients had some evidence of organic brain
dysfunction in addition to gerstmann components . as the number of      
gerstmann components increased, the responsible brain lesions tended to 
be larger, more highly destructive of tissue, and to cause greater      
neurological impairment . every patient with four gerstmann components  
had associated evidence of severe impairment of brain functions and the 
lesion or underlying disease was likely to compromise survival of the   
patient . the syndrome is not to be regarded as an autonomous entity,   
but merges with numerous other neurological deficits, notably dysphasia 
in agreement with benton, we find no justification for singling out   
the four gerstmann components as a separate syndrome, unless one is also
prepared to recognize that any other arbitrary groups of concurrent     
deficits are also separate syndromes .                                  
  in at least three of 23 patients with all four gerstmann components,  
the angular gyrus, as shown by necropsy examination, was not involved by
the lesion . however, the probability that the left hemisphere contained
a lesion increased with the number of gerstmann components, and the     
probability of involvement of the left posterior parasylvian area also  
increased with the increase in the number of gerstmann components . with
two, three, or four gerstmann components, the lesions were never        
restricted to the angular gyrus but tended to spread widely over the    
parietal, temporal, and occipital lobes . as to localizing significance,
gerstmann's syndrome has approximately the same degree of cogency as    
dysphasia .                                                             
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alterations of visual evoked response in the presence of homonymous     
visual defects .                                                        
  the visual evoked response (ver) was studied by means of computer     
averaging in 32 normal subjects, nineteen patients without visual       
disorder but with unilateral cerebral lesions, and 30 patients with     
homonymous visual field defects . an early negative-positive-negative   
complex was recorded between laterally placed occipital electrodes and a
vertex reference . latencies were prolonged in the hemianopic patients .
some amplitude asymmetries were noted in the brain-damaged controls but 
were more pronounced in patients with visual defects . the recordings in
the hemianopic patients were differentiated from those in both control  
groups by the presence of aberrant wave forms (2 cases),. prolonged     
latencies (3 cases),. and amplitude depression of greater then 50 per   
cent of the positive wave on the abnormal side (16 cases) . pathologic  
verification was obtained in three patients and demonstrated a          
correspondence between alterations in the ver and the presence of       
lesions of the geniculocalcarine system .                               
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cerebro-vascular lesions and livedo reticularis .                       
  extensive livedo reticularis has been observed in one man and five    
women who have suffered from a series of cerebrovascular lesions . the  
neurological disabilities have included aphasia, homonymous hemianopia  
and hemiplegia but have been remarkable for the degree of recovery which
has occurred . it is presumed that the livedo which has been found in   
only one patient without neurological lesions is related to the         
cerebrovascular incidents . investigations have failed to show any      
evidence of polyarteritis nodosa, disseminated lupus erythematosus and  
thrombocythaemia and an arteritis of unrecognized type is suggested as  
the etiology .                                                          
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seesaw nystagmus case report elucidating the mechanism .                
  the eighth recorded case of see-saw nystagmus is reported . features  
in this case are analyzed and evidence to suggest that this form of     
nystagmus is ocular rather than central in origin is offered . see-saw, 
nystagmus, unlike true vertical nystagmus, is not of itself indicative  
of a brain stem lesion .                                                
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supratentorial paratransversal meningiomas .                            
  the author describes 6 cases of supratentorial paratransversal        
meningioma . clinically, the development of these tumours is slow and   
the chief neurological signs are.. homonymous hemianopia, contralateral 
hemiparesis and speech disorders when the tumour is on the dominant side
radiologically, carotid angiography permits identification of these   
tumours easily . surgically, the tumours were removed completely and,   
although in 2 cases the transverse sinus had to be resected, this caused
no damage . one patient, who was operated on twice and whose            
histological specimen on the second occasion showed that the meningioma 
was malignant, died seven months after the second operation . the other 
patients are well and free of neurological deficits from 1 to 12 years  
after operation .                                                       
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life span and lymphoma-incidence of mice injected at birth with spleen  
cells across a weak histocompatibility locus .                          
  newborn cogenic c h mice receiving injections across a weak (h-i h-i )
histocompatibility barrier exhibited life-shortening and a high         
incidence of lymphomatous disease during mid-adult life . in control    
experiments (h-i h-i ) lymphomatous disease developed much later life . 
both mouse strains when not given injections as new-borns manifest only 
a negligible incidence of lymphoma or leukemia . these findings are     
variably interpretable in terms of oncogenic virology, and of the       
immunologic theories of aging and cancer by analogy with transplantation
disease mechanisms .                                                    
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the heterogeneity of rheumatoid factors and the genetic control of      
polypeptide chains of globulin .                                        
  (1) evidence is presented that most rf proteins are heterogeneous in  
their antigenic composition although occasional ones are homogeneous and
thus resemble the paraproteins .                                        
  (2) studies pointing out some of the difficulties encountered with    
currently available preparations of polypeptide chains in the genetic   
mapping of globulin are described .                                     
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progynon, a depot preparation with oestrogenic action, in the treatment 
of prostatic carcinoma .                                                
  a derivative of a natural oestrogen -dash oestradiol undecylate,      
progynon-depot -dash was given in depot form by injection to a group of 
patients with prostatic carcinoma . the study showed progynon-depot to  
reduce the excretion of androgen metabolites in the urine . the results 
suggest that the preparation reduced the testicular production of       
androgens but probably not that of the adrenal glands . the depot effect
and clinical action of the preparation are described briefly .          
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/urinary 17-ketosteroid excretion study in radiation induced menopause  
in carcinoma breast./ .                                                 
  (1) urinary 17-ketosteroid estimation results are given in 11 patients
subjected to radiotherapeutic sterilisation .                           
  (2) a high dosage level was used in all these cases .                 
  (3) results indicate some suppression of ovarian function within 2    
weeks of sterilisation .                                                
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prostatic cancer of a young person with primary hypogonadism .          
  the prostatic carcinoma of a 34 years old man with primary            
hypogonadism was presented . endocrine environment of relative          
estrogenic excess is suspected to have played the leading part in       
pathogenesis of this case .                                             
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urinary excretion of neutral 17-ketosteroids and pregnanediol by        
patients with prostatic cancer and benign prostatic hypertrophy .       
  urinary neutral 17-ketosteroid fractions and pregnanediol excreted by 
21 patients with prostatic cancer, 17 patients with benign hypertrophy, 
and 59 clinically well subjects were assayed to determine whether       
differences exist .                                                     
  patients with prostatic cancer and those with benign hypertrophy      
excreted significantly less androsterone than the clinically well       
subjects . a disproportionately lower level of androsterone than        
etiocholanolone resulted in a significantly lower                       
androsterone/etiocholanolone ratio in both groups .                     
  the specificity of the findings is discussed . the lower levels of    
androsterone excreted by patients with benign hypertrophy were          
associated with an extended period of hospitalization . patients        
hospitalized less than 5 days excreted androsterone at levels not       
significantly different from the clinically well subjects .             
  lower levels of androsterone excreted by patients with prostatic      
cancer were not explained by the presence of metastasis, the duration of
hospitalization, loss of appetite, or other definable differences, when 
each was considered singly . the possible interrelationships of clinical
differences prevent assigning lower excretion levels to the cancer state
alone .                                                                 
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i. urinary excretion of neutral 17-ketosteroids and pregnanediol by     
patients with breast cancer and benign breast disease .                 
  urinary levels of neutral 17-ketosteroid fractions and pregnanediol   
excreted by 114 women, 56 premenopausal and 58 postmenopausal, were     
determined . subjects studied were included in 4 premenopausal groups   
(breast cancer 6, benign breast disease 18, sick control 8, well control
24) and 3 postmenopausal groups (breast cancer 21, sick control 17, well
control 20) .                                                           
  levels of androsterone and etiocholanolone excreted by premenopausal  
patients with breast cancer were significantly less than levels excreted
by other premenopausal groups, and they did not differ significantly    
from levels excreted by postmenopausal patients with breast cancer .    
  disproportionately lower levels of the 11-desoxy-17-ketosteroids than 
11-oxy-17-ketosteroids excreted by premenopausal patients with cancer   
resulted in significantly lower ratios than those found in other        
premenopausal groups . ratios associated with premenopausal patients    
with cancer did not differ significantly from those of postmenopausal   
patients with cancer .                                                  
  lower levels of androsterone and etiocholanolone were not explained by
debilitation .                                                          
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the morphologic demonstration of an alveolar lining layer and its       
relationship to pulmonary surfactant .                                  
  the presence of an alveolar lining layer was histologically           
demonstrated in animal lungs by ultraviolet microscopy . this layer     
appeared as a thin fluorescent line at the air-tissue interface .       
  the fluorescent lining layer could be abolished from lung sections by 
extraction with chloroform..methanol and was diminished by digestion    
with cl.welchii a-toxin lecithinase, suggesting that the structure was a
lecithin-containing lipid . an alveolar lining structure was also       
identified by the use of phosphatide and polysaccharide stains,         
suggesting that the lipid was a phosphatide, but that a                 
mucopolysaccharide component might also be present .                    
  bilateral cervical vagotomy resulted in diminution or loss of the     
fluorescent alveolar lines and abnormal surface tension properties of   
lung extracts . this suggested that the presence of the fluorescent     
material was associated with the surface activity of the lung .         
  alveolar lining structure could not be demonstrated by electron       
microscopy, even with special staining techniques .                     
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experimental emphysema basis, review, and critique .                    
  normal lung structure has been described as a rich capillary bed in a 
finely partitioned airspace with unique surface-active effects .        
morphologic criteria of the lesions of human pulmonary emphysema include
evidence of destruction, residual vascular remnants, the absence of     
significant amounts of fibrosis, and altered conducting airways without 
anatomic obstruction .                                                  
  experimental studies relating to the pathogenesis of emphysema have   
been reviewed and critically evaluated . stress has been placed on the  
necessity to control the biologic factors influencing the action of any 
specific etiologic agent .                                              
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alveolar lining cells and pulmonary reticuloendothelial system of the   
rabbit .                                                                
  complete freund's adjuvant was injected intravenously into rabbits and
the cellular response in the lungs was investigated . the population of 
cells within the alveolar spaces was contributed to by monocytes of the 
circulation, mesenchymal cells of the alveolar walls and epithelial     
lining cells of the alveoli . the abnormal epithelial lining during the 
proliferative phase was the result of an increase in size and number of 
the cells that line the normal alveoli . as healing progressed, a       
structurally normal alveolar lining was found .                         
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time course of changes in surface tension and morphology of alveolar    
epithelial cells in co2-induced hyaline membrane disease .              
  atelectasis and hyaline membranes produced by exposure of guinea pigs 
to 15 percent co2 were found to be associated with disappearance of     
lamellar bodies in the large alveolar lining cells (granular            
pneumocytes) and an associated decrease in surfactant as indicated in   
the rise of minimal surface tension of the lungs . this process is      
limited to the uncompensated phase of respiratory acidosis and is       
reversed during the compensatory phase . the parallel time course in    
changes of surface tension and alterations of lamellar bodies in the    
granular pneumocytes provides additional evidence for the identification
of the latter as the cells responsible for the secretion of surfactant .
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some observations on myelin-glial relationships and on the etiology of  
the cerebrospinal fluid exchange lesion .                               
  the present paper presents cytological observations from developing   
kitten spinal cord and from spinal cord white matter reacting to injury 
it also presents some recent experiments on the mechanism of etiology 
of the csf exchange lesion . drawing on these various sources, the      
authors propose specific functions for some of the cell types present in
spinal cord white matter .                                              
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lactate and pyruvate in the brain of rats during hyperventilation .     
  experiments on anesthetized and curarized rats under artificial       
ventilation show that during hyperventilation lactate and pyruvate are  
markedly increased both in blood and in brain . the lactate/pyruvate    
ratio which remains in blood the same as in control conditions, is      
systematically decreased in brain . during hypoxia (ventilation with 7  
oxygen in nitrogen) lactate rises markedly in blood and in brain . the  
lactate/pyruvate ratio which is strongly increased in blood shows a     
small rise in brain . these observations could indicate that a different
mechanism is responsible for the rise of lactate in brain during hypoxia
and hyperventilation . the important augmentation of lactate in brain   
during hyperventilation can give an explanation for the delayed rise    
which is seen in the lactate level in cerebrospinal fluid in these      
conditions .                                                            
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cisternal fluid oxygen tension in man .                                 
  using a beckman micro-oxygen-electrode we have studied the oxygen     
tension simultaneously in the cisterna magna, the internal jugular vein 
and in arterial blood under various conditions . the results suggest    
that the cisternal oxygen tension to some degree reflects the average   
oxygen tension of the surrounding brain tissue and besides reflecting   
the available free oxygen to the brain it registrates changes of short  
duration in the cerebral blood flow .                                   
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ventricular septal defect with prolapsed aortic valve and outflow tract 
obstruction .                                                           
  a case of ventricular septal defect combined with aortic valvular     
lesion and infundibular pulmonic stenosis is described . the right      
coronary cusp of the aortic valve, protruding through the ventricular   
septal defect, was demonstrated by right ventricular angiocardiography  
as a polyp-like mass in the right ventricular outflow tract . cardiac   
catheterization and angiocardiography showed progressive right          
ventricular outflow obstruction .                                       
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functional adaptations of the right ventricular outflow tract in        
congenital heart disease .                                              
  functional adaptations in the right ventricular outflow tract have    
been discussed in relation to the development of acquired /pulmonary    
stenosis/ .                                                             
  it is concluded that physical forces as well as structural            
abnormalities may greatly influence both the clinical picture and the   
life history of many patients with congenital heart lesions .           
  the importance of further serial haemodynamic studies to provide a    
fuller understanding of the natural course of many lesions is stressed, 
so that better advice about prognosis and the optimal time for surgical 
treatment may be given .                                                
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mitral atresia associated with pulmonary venous anomalies .             
  pulmonary venous anomalies were observed in 5 among 29 specimens with 
mitral atresia . in 4 of these 5 the anomalous pulmonary veins took the 
form of anomalous pulmonary venous connexion . in the remaining case the
pulmonary venous anomaly was represented by cor triatriatum . in 3      
(group i), mitral atresia and premature closure of the foramen ovale    
coexisted . the anomalous pulmonary venous connexions in this group     
provided collateral routes for the flow of pulmonary venous blood, and  
can be understood as developing en response to obstruction at the       
foramen ovale when the mitral valve is atretic . in the remaining 2     
(group ii) no such causative factor could be invoked . in one of the    
latter group total anomalous pulmonary venous connexion coexisted with a
common atrium . in the other, cor triatriatum coexisted with a patent   
foramen ovale .                                                         
  pulmonary venous obstruction occurred in each of the 5 cases .        
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basal metabolic rate after cardiovascular surgery .                     
  the basal metabolic rate and respiratory equivalent of patients were  
determined during 8 days of convalescence from cardiovascular surgical  
operations performed with or without cardiopulmonary bypass . the       
results were compared in patients who had undergone operation for       
different diseases . metabolic rate in the majority of cases was        
increased but was commensurate with body temperature . some patients,   
particularly those requiring open operation on the aortic valve, had    
raised metabolic rates which could not be explained solely by pyrexia . 
  all types of patients in this series had elevated respiratory         
equivalents which persisted throughout convalescence . these equivalents
were greater in patients treated with cardiopulmonary bypass than in    
patients treated without bypass .                                       
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surgical treatment of ventricular septal defect .                       
  the surgical technique of closure of ventricular septal defects in 80 
cases (37 cases of isolated defects and 43 cases of tetralogy of fallot)
is discussed in the light of the follow-up results . the use of a patch 
for closure has reduced the incidence of recurrence to 4 percent, com-  
pared with 18 percent when direct suture was performed . the incidence  
of heart block also decreased from 15 percent, when direct suture was   
used, to 4 percent with a patch . the transatrial approach is preferred 
for isolated ventricular septal defects,. the ventricular approach is   
preferred for cases with tetralogy of fallot . in cases combined with   
aortic insufficiency only small defects are closed through the aorta .  
larger defects are closed in the usual way at a first stage operation,  
and a total valve prosthesis is introduced at a second operation . there
was an operative mortality of 6 percent in isolated ventricular septal  
defects, compared with 27 percent in cyanotic patients with tetralogy of
fallot .                                                                
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some hemodynamic observations in congenital heart disease with special  
reference to pressure curves in ductus arteriosus .                     
  hemodynamic observations in 100 congenital heart disease cases are    
made based on data in the department of pediatrics, kyoto university    
between may 1961 and december 1963 . we have classified these 100 cases 
according to the malformation from the hemodynamic view point . our     
cases were classified into the following groups .                       
  (1) ventricular septal defect                             35 cases    
      small ventricular septal defect                       20          
      moderate ventricular septal defect                     9          
      marked ventricular septal defect                       4          
      ventricular septal defect with pulmonary stenosis      2          
  (2) patent ductus arteriosus                              21          
  (3) atrial septal defect                                  19          
      atrial septal defect                                  14          
      atrial septal defect with pulmonary stenosis           5          
  (4) pulmonary stenosis                                     5          
  (5) tetralogy of fallot                                   14          
  (6) aortic stenosis                                        3          
  (7) aortic insufficiency                                   3          
      aortic insufficiency with ventricular septal defect    2          
      aortic insufficiency with pulmonary stenosis           1          
  in sonre small ventricular septal defect, we tried the vasoactive     
drugs . phenylephrine was injected slowly into the right ventricle via  
the catheter, a rapid rise in femoral arterial pressure associated with 
bradycardia and intensiffication of the systolic murmur was observed .  
after the administration of amyl nitrite, a rapid fall in femoral       
arterial pressure associated with tachycardia and softening of the sys- 
tolic murmur was observed .                                             
  in patent ductus arteriosus, when the cardiac catheter is withdrawn   
slowly from the aorta into the pulmonary artery, the outstanding        
pressure curve is recorded in ductus arteriosus . the systolic pressure 
curve in the ductus arteriosus is the same as the systolic pressure in  
the aorta and the diastolic pressure curve in the ductus arteriosus has 
a diastolic dip followed by a late diastolic pressure peak .            
  in patent ductus arteriosus, when the cardiac catheter is withdrawn   
from the left pulmonary artery to the right ventricle, the pressure     
curve reveals a considerable characteristic rise in pulmonary arterial  
pressure which is regarded as an effect of the transmission of systemic 
pressure through the ductus arteriosus .                                
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a study on the direction of inscription of the vectorcardiographic      
t-loop in left and right ventricular hypertrophy .                      
  (1) frank lead vectorcardiogram was recorded in 30 normal persons and 
in 323 cases with hypertension and acquired and congenital heart disease
the t-loop was classified into 8 types according to the directions of 
inscription in 3 planar projections . frequently observed types were    
examined with the direction of the maximal t vector .                   
  (2) in majority of normal cases, the t-loop was inscribed             
counterclockwise in horizontal and clockwise in sagittal planes .       
  (3) in left ventricular hypertrophy, abnormal inscription of the      
t-loop was observed with abnormal rightward and superior deviation of   
its maximal vector and the t-loop oriented more than 120 in horizontal  
plane was usually accompanied by abnormal inscription . percentage of   
abnormal inscription was higher in cases with cardiac complaints .      
  (4) in right ventricular hypertrophy, directional change of the t-loop
was relatively small but changes in inscription of it were common . the 
t-loop was always inscribed abnormally in cases with abnormal           
inscription of the qrs-loop .                                           
  (5) the concept of the polar vector was found to be valuable in       
studying the inscription and the direction of the t-loop . significance 
of changes in inscription of the t-loop was discussed .                 
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pulmonary vascular plexiform lesion pathogenetic studies .              
  an attempt was made to test the theory that in pulmonary arterial     
hypertension, the plexiform lesion is a jet lesion beyond points of     
arterial stenosis resulting from nonspecific intimal thickening .       
  in 39 subjects with such congenital communications as are associated  
with pulmonary arterial hypertension, the lungs were studied            
histologically . in each, there was an additional element of pulmonary  
venous obstruction . it is likely that in the absence of pulmonary      
venous obstruction, adult patients with only the congenital             
communication would have developed plexiform lesions .                  
  in the three adult patients in the study, no plexiform lesions were   
identified . among the 36 infants or children, one subject showed       
plexiform lesions, a 53-day-old girl with mitral atresia, ventricular   
septal defect, and patent ductus arteriosus .                           
  while the findings in the three adult subjects support the theory     
regarding the genesis of plexiform lesions, the findings in the one     
infant with plexiform lesions appear to contradict it .                 
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renal hemosiderosis (blue kidney) in patients with valvular heart       
disease .                                                               
  anatomic evidence of intravascular hemolysis, i.e., renal             
hemosiderosis, was found at necropsy in 4 of 132 patients who died of   
severe valvular heart disease . the aortic valve in each of these 4     
patients was heavily calcified, immobile, and portions of the calcific  
deposits were in direct contact with the blood . hemolysis in each      
patient was attributable to direct trauma to erythrocytes traversing the
stenotic valve, and the frequency of trauma was increased by an         
associated regurgitant flow . renal hemosiderosis was not observed in   
any patient with isolated mitral valve disease, or in those with        
combined mitral and tricuspid valve malformations .                     
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tumor scanning with radioactive cesium .                                
  fourteen patients with cancer were scanned 10 minutes to 48 hours     
after injection of radioactive cs. and satisfactory scans of the tumors 
were obtained in seven . positive scans were obtained in large,         
superficial tumors, in a pulmonary lymphoma, and in a carcinoma of the  
upper third of the esophagus . the negative scans were all in abdominal 
tumors . correlations were made with data obtained from external        
counting and by well scintillation counting of biopsy specimens . two   
modes of uptake are suggested.. (a) early uptake due to vascularity and 
probably not proportional to stable cesium content.. and (b) a later    
uptake based upon greater alkali metal content of tumors than of normal 
tissue .                                                                
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lung scanning with colloidal risa .                                     
  the use of colloidal risa injected intravenously in a particle size of
10.50 microns followed by lung photoscanning offers a practical,        
atraumatic method of visualizing pulmonary artery occlusions in the dog 
the fact that the particles have a relatively short biological        
half-life appears to decrease the radiation dose delivered and the      
duration of occlusion of pulmonary capillaries as compared to ceramic   
microspheres . work is in progress to apply this technique to the study 
of pulmonary artery occlusion in the human .                            
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multivariate comparison of results of treatment in chronic lymphocytic  
and chronic granulocytic leukemia .                                     
  the results of several clinical trials have been analyzed by          
multivariate procedures which rely completely on laboratory findings and
do not involve scoring specific changes or subjective evaluations .     
statistically significant differences among drugs after three months of 
therapy were demonstrated . a relationship between the multivariate     
method and the subjective evaluation was demonstrated which indicates   
that if the subjective evaluation is an estimate of the physiologic     
state or prognosis of the patient, then so are the completely objective 
techniques used here .                                                  
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oxacillin--apparent hematologic and hepatic toxicity .                  
  bone marrow depression and hepatocellular dysfunction developed in an 
allergic woman receiving 3.0 gm. of sodium oxacillin by mouth daily for 
nearly three months . discontinuing the drug and administering          
corticosteroids and antibiotics resulted in apparent recovery . the     
toxic potentialities of oxacillin should be appreciated .               
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drugs and neonatal jaundice .                                           
  this paper is not intended as an exhaustive review of bilirubin       
metabolism nor of the many factors which may result in exaggerated      
physiologic jaundice.. for such a review the interested reader is       
referred to the excellent articles by zuelzer and brown . brief mention 
has been made of the mechanism by which certain drugs may contribute to 
the development of hyperbilirubinemia . a few drugs, the water-soluble  
vitamin k derivatives, sulfasoxazole (gantrisin), the salicylates, and  
novobiocin have been unequivocally shown to affect adversely the newborn
infant's ability to handle bilirubin . in time other compounds will     
definitely be incriminated .                                            
  it is important to remember that the administration of a drug to a    
mother just prior to delivery may result in appreciable concentrations  
of the compound in the infant's serum, and that drugs administered to   
the nursing mother may be excreted in breast milk and thereby absorbed  
by the infant . careful consideration of the drugs given not only to the
newborn but also to the mother is therefore essential if we are to avoid
what may be termed iatrogenic hyperbilirubinemia .                      
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amputation in patients over 80 years of age .                           
  although patients over 80 years of age can be expected to have poor   
physical reserve and many co-existing diseases, our observations show   
that nevertheless they can be subjected to surgical procedures without  
undue mortality . the mortality rate can be maintained at a minimum if  
the surgeon considers the factors that contribute to its increase in the
elderly . this necessitates.. 1) careful evaluation of the patient and  
treatment of any pre-existing or co-existing disease, 2) proper control 
of electrolytes, 3) avoidance of infection, 4) prompt correction of any 
postoperative hypotension, 5) postoperative pulmonary ventilation and   
tracheal cleansing, and 6) avoidance of prolonged surgical procedures . 
  a group of 26 patients past the age of 80 years underwent amputation  
of a lower extremity, without undue mortality (9 deaths) .              
  lumbar sympathectomy is not considered advisable in these aged pa-    
tients .                                                                
  the standard mid-thigh operation can be questioned in the younger     
patient, but it is the procedure of choice for removal of a gangrenous  
extremity in patients over 80 years of age .                            
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radical operation for ventricular septal defect in infancy .            
  ventricular septal defect is the most common congenital anomaly of the
heart in infancy, and has a poor prognosis . we have operated upon 18   
infants all under one year of age for ventricular septal defect . there 
has been successful repair in 16 cases .                                
  at present, hypothermia with a surface cooling method has proved to be
superior to the artificial heart-lung machine because of the simplicity 
and the good operative results with its use . in addition, early        
operation during the infantile period will cause less psychological     
impact on infants . these advantages are sufficient for us to advocate  
radical operation of ventricular septal defect in infancy, even         
including the severely ill children .                                   
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specific suppression of tumor growth by isolated peritoneal macrophages 
from immunized mice .                                                   
  methods were presented by which macrophages may be isolated from the  
peritoneal cell population of mice . these cells, and for comparison    
peritoneal lymphocytes and lymph node cells, were tested for immunologic
activity by injecting a mixture of the test cells and tumor cells       
subcutaneously into irradiated mice . each cell type, when obtained from
immunized mice, was capable of suppressing the growth of the specific   
tumor cells . the results are discussed with respect to a possible      
specific immunologic function for macrophages in graft rejection .      
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effect of heterologous antiserum and complement on glycolysis of tumor  
cells .                                                                 
  the effect of heterologous antiserum and complement on glucose        
metabolism of rat ascites tumor cells was examined to clarify the       
mechanism of the cytotoxic effect of antibody .                         
  1. lactate-production of the target cells was inhibited by the        
cooperation of antiserum and complement, while no inhibition was        
observed when the cells were subjected to either antiserum or complement
alone . the inhibition of lactate-production was observed under both    
acrobic and anacrobic conditions . no effect of the antiserum and       
complement was observed on the oxygen consumption of the cells .        
  2. the amount of antiserum necessary for the inhibition of            
lactate-production of the cells was determined in the presence of a     
definite amount of complement, and it was found that the degree of      
inhibition was not in parallel with the concentration of antiserum      
beyond a certain threshold . on the other hand, a parallelism was       
observed between the amount of complement and the rate of inhibition of 
lactate-production when different amounts of complement were added to a 
definite amount of antiserum .                                          
  3. similar inhibitory effects of the antiserum and complement on      
lactate-production of the cells from glucose, fructose-1, 6-diphosphate,
and pyruvate suggested that the inhibition occurred toward the final    
step of glycolytic process of the cells .                               
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soluble tissue antigens in human brain tumor and cerebrospinal fluid .  
  an a-2 globulin antigen present in human glioblastomas and            
immunologically identical with antigens present in human brain, liver,  
spleen, and metastatic carcinoma cyst fluid has been described . this   
protein antigen is not present in plasma, wbc, or normal csf . it has   
been demonstrated in the csf of three of 27 patients with tumors of the 
central nervous system . when present, it may represent a specific      
tissue protein fraction contributed by either the tumor itself or the   
adjacent cns tissue . the major protein components of normal and        
abnormal csf are derived from, or, at least, antigenically identical to,
the plasma proteins .                                                   
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the apparent immunofluorescence of tissue mast cells .                  
  both rat mast cells and rat cosinophils exhibited fluorescence in blue
violet light after treatment with fitc-conjugated rabbit anti-rat       
g-globulin and in each cell this fluorescence was immunologically       
nonspecific .                                                           
  whereas cosinophils fluoresced after treatment with fluorescein alone,
mast cells fluoresced only after treatment with a protein conjugate     
containing g-globulin .                                                 
  the phenomenon was observed in cells from different organs and the    
fluorescence was seen to be associated with the cytoplasmic granules    
normally present in these cells .                                       
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the determinants of cerebrospinal fluid po2 the effects of oxygen and   
carbon dioxide breathing in patients with chronic lung disease .        
  the lumbar cerebrospinal fluid po2 of some hypoxemic hypercapnic      
patients with chronic lung disease is the same as that of patients      
without chronic lung disease . breathing 95 oxygen with 5 carbon dioxide
increased lumbar cerebrospinal fluid po2 more than breathing 95 oxygen  
with 5 nitrogen . the change in cerebrospinal fluid po2 is closely      
related to the change in arterial pco2, and this relationship is similar
to the relationship between arterial pco2 and cerebral blood flow in    
patients with and without hypercapnia . interpretation of these         
observations must be qualified by the following.. cisternal             
cerebrospinal fluid po2 differs from lumbar cerebrospinal fluid po2 in  
its response to breathing oxygen with carbon dioxide,. regulation of    
blood flow to the spinal cord and nerve roots is not known to be        
comparable to that of the brain,. and factors other than blood flow may 
have contributed to the changes of cerebrospinal fluid po2 .            
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the behavior of lymphocytes in primary explants of human lung cancer in 
vitro .                                                                 
  the activity of lymphocytes within outgrowths from explanted tissue   
fragments of 20 human lung cancers has been studied . the study included
cancer-bearing tissue explants from all cases and noncancerbearing lung 
tissue from 4 of the 20 cases . five major categories of lymphocytic    
behavior were derived from the study, namely.. (1) emigration and       
migration of lymphocytes from the explant,. (2) clustering of           
lymphocytes around /target/ cells,. (3) ameboid transformation of       
lymphocytes,. (4) lymphocytic congregation,. and (5) emperipolesis .    
criteria for these different lymphocytic activities have been amplified 
or introduced .                                                         
  findings of particular interest were.. (1) the frequency of both via  
ble and nonviable lymphocytes within the vacuoles of other cells . this 
observation is considered to be an absolute criterion for the recogni-  
tion of emperipolesis . a subsequent /inclusionbody/ appearance of the  
dead lymphocytes has been observed . (2) the intimate relationship of   
ameboid forms of lymphocytes to selected cells, resulting in a          
juxtanuclear and frequently unipolar crowding of one cell by numerous   
lymphocytes while nearby cells were totally devoid of ameboid           
lymphocytes . reasons are given to support the impression that this     
phenomenon is re lated to sensitization . there is also the possibility 
that the phenomenon may indicate that the lymphocyte is /conditioned/ . 
(3) the apparent entry of the lymphocyte into the cell has been recorded
by timelapse cinematography .                                           
  a lymphocyte relationship to cancer cells was infrequently found      
although explants of 15 of the 20 cases produced identifiable cancer    
cells and lymphocytes emigrated from the explants of all 20 cases . it  
is not apparent from this limited study whether this is a significant   
finding .                                                               
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ventricular septal defect with aortic insufficiency a clinical and      
hemodynamic study of 18 proved cases .                                  
  eighteen patients with the combination of ventricular septal defect   
and aortic insufficiency were studied . nine also had infundibular      
pulmonary stenosis . seventeen were treated by open-heart operations .  
  the physical findings were those of a typical ventricular defect      
murmur and thrill together with an aortic insufficiency blow and a wide 
pulse pressure . a systolic murmur at the upper left sternal border with
thrill is strongly suggestive of the additional lesion of infundibular  
pulmonary stenosis, but the presence or absence of infundibular         
pulmonary stenosis was indicated most accurately at cardiac             
catheterization and on inspection at operation . it was not of          
sufficient severity for signs of additional right ventricular           
hypertrophy to appear on the electrocardiogram .                        
  retrograde aortography serves to demonstrate the severity of the      
aortic regurgitation .                                                  
  the problem of the surgical correction of these lesions will be the   
subject of a separate communication .                                   
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radioisotope photoscanning as a diagnostic aid in cardiovascular disease
a safe, simple method for diagnosing pericardial effusion and aneurysm .
  radioisotope scanning is a safe, simple, and useful method for the    
diagnosis of pericardial effusion and aortic aneurysm . the whole-body  
radiation dose, approximately 25 millirads from 300 of i 131-sodium     
iodipamide, is no greater than the dose received from a standard        
posteroanterior chest roentgenogram or a blood volume determination .   
there are no side effects or complications from the procedure, and it is
well tolerated by the patient . the scan can be repeated at intervals to
assess progress of the disease or response to treatment . cardiovascular
scanning with radioactive isotopes can be recommended as a useful and   
safe diagnostic tool .                                                  
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studies of hematology and bone marrow morphology in vitamin e-deficient 
pigs .                                                                  
  forty-four pigs were used in two experiments whose purpose was to     
produce a deficiency of vitamin e . the anemia and changes in bone      
marrow morphology occurring in the vitamin e-deficient state are        
described . the hematologic disorders include low hemoglobin and        
hematocrit values, leucocytosis and granulocytosis . nuclear            
abnormalities were observed in the erythroid precursors in the bone     
marrow, many of the cells being multinucleated . giant multinucleated   
cells of megakaryocyte type were frequently found .                     
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surgical treatment of atrial septal defect under hypothermia .          
  the technique of inflow occlusion under 30 c. hypothermia was adopted 
for direct visual correction in 133 consecutive cases of atrial septal  
defect of the secundum variety and the associated anomalies .           
  the use of extracorporeal circulation combined with hypothermia was   
reserved for the repair of two cases of ostium primum defects .         
  the over-all operative mortality was 4 .                              
  post-operative evaluation showed that the results have been good in   
almost all patients, including those with pulmonary hypertension .      
  since an ostium primum defect requires cardio-pulmonary bypass for its
closure, the pre-operative recognition of the defect is highly desirable
in the selection of patients for operation and in planning the procedure
itself .                                                                
  the information derived from the clinical examination and appropriate 
diagnostic studies has been found to be consistently accurate in the    
pre-operative differentiation of the primum from the secundum defect .  
therefore, the unexpected discovery of a primum defect at operation was 
not a problem .                                                         
  in our experience, open-heart surgery under 30 c. hypothermia for the 
repair of an atrial septal defect of the secundum type and the          
associated anomalies is a safe and practical technique and effectively  
corrects the anomaly with minimal risk .                                
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internal cooling for general hypothermia .                              
  a further presentation is offered on the advantageous use of          
intragastric temperature control as an adjunct in general hypothermia . 
a device is described which accomplishes this end with no encountered   
deleterious side effects, minimal technical involvement, and minor      
expense . observations are recorded on rates of temperature change      
according to sex, weight, and type of surgery performed .               
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late effects of regional renal hypothermia .                            
  in summary, one can safely conclude that no deleterious effects were  
created in dogs observed over a period of 3 years following renal       
ischemia of 6 hours' duration protected by hypothermia . the blood      
pressure failed to climb, there was no evidence of azotemia, and careful
microscopic studies failed to reveal histological evidence of renal,    
vascular or cardiac damage . renal function, as demonstrated by         
creatinine and pah, was preserved and there was no delay in wound       
healing .                                                               
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mesenteric vascular response to hypothermia .                           
  1. total and segmental resistances were studied in the mesenteries of 
37 dogs, and the effects of hypothermia, changes in blood viscosity and 
epinephrine on these resistances were compared .                        
  2. cooling to 15 c. caused an increased mesenteric resistance in 94   
per cent of animals with approximately 90 per cent of the resistance    
rise contributed by the arterial segment . small vessel resistance      
increased in 52 per cent . there was no evidence of venous constriction 
  3. blood viscosity appeared to play a minor role .                    
  4. it is suggested that hemorrhagic necrosis of the bowel wall is due 
to intense vasoconstriction in the precapillary vessels with subsequent 
distal anoxia and cellular damage .                                     
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2803. effect of dosage on endotoxin-induced changes in the reticuloendothelial
system of rabbits
tissues were removed from rabbits 4
and 24 hr. following an i.v. injection of 5,
25, or 200 ug of endotoxin.  explants of
tissues from normal and injected animals
were grown in a coagulated plasma medium
and in medium containing 1 ug/ml of
endotoxin.  the migration and growth of cells
were observed during the following week
of incubation.  the inhibition or stimulation
of cells of the reticuloendothelial system
(res) at different host sites after endotoxin
administration depended on the dosage
and on the known capacity of different organs
to take up circulating endotoxin.  macro-
phage migration was suppressed in cultures
of spleen removed 4 hr. after a dose of
hibited by 200 ug, but macrophages in
lymph node, testis, and thymus showed an in-
crease in numbers, in extent of migration
and in phagocytic activity.  widespread
res stimulation was seen in tissues removed
24 hr after the largest dose.  in ad-
dition to the restoration of re cell activity in
spleen and lung there was a marked
increase in the migration of large phagocytic
cells from bone marrow, as well as
other organs.  macrophages from endotoxin-injected
animals were as sensitive as
normal macrophages to added endotoxin in vitro.
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3075. vaccinia pneumonia in mice.  a light and electron microscopic and viral
assay study
swiss white mice between 2 and 4 days of age
developed generalized vaccinia viral
infection 2 to 7 days after intranasal inoculation.
gross and histologic evidence of
pneumonia was seen in more than 80% of
approximately 300 mice.  virus was re-
covered in relatively high titers from the
lungs (10   pfu per g) during the per-
iod when pneumonia developed; viremia
was also present, but virus titers in the
blood stream remained much below those
in the lungs.  histologically, vaccinia
pneumonia was characterized by large swollen
mononuclear cells giving rise to
marked widening of alveolar septa.  only
scattered neutrophils were noted, usually
in association with cell necrosis.  exudation
of edema fluid and red cells into al-
veoli was considered the result of viral
replication and cytopathic effect on cells
comprising alveolar septa.  various forms
of vaccinia virus were observed by elec-
tron microscopy within both 'type i' and
'type ii' alveolar lining cells, capillary
endothelial cells, and interstitial cells
within alveolar walls.  these infected inter-
stitial cells were probably derived from
fixed macrophages and were noted also
around bronchioles.  virus particles were
similarly observed in bronchiolar epi-
thelium and surrounding smooth muscle
cells.  the earliest pathologic ultrastruc-
tural change noted in virus infected cells
was intracellular edema, evidenced by
low electron density of the background
cytoplasmic material and dilatation of the
endoplasmic reticulum.  more extensive
changes resulted in cell necrosis with
release of virus particles into the extracellular space.
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1560. the ultrastructure of the lungs of lambs.  the relation of osmiophilic
inclusions and alveolar lining layer to fetal maturation and experimentally
produced respiratory distress
the lungs in 69 fetal and newborn lambs
were studied.  osmiophilic inclusion bodies
first appeared at about 121 days gestation
and their total number increased with
maturation.  normal surface activity of
lung extracts was detectable a few days
following the appearance of inclusion
bodies.  the excretory nature of the type ii
alveolar epithelial cell, the phospholipid
nature of the inclusion body content, the
decrease in the number of inclusion
bodies and their loss of density associated
with respiratory distress and with the
loss of normal surface activity of lung ex-
tracts provide strong evidence that
inclusion bodies are the source of pulmonary
surfactant.  a dense osmiophilic alveolar
lining layer in mammals is described.
since the presence of such a layer is
well correlated with surface tension values
and the number of inclusions, it is
suggested that this layer consists of surface
active substances.  the difficulty in
detecting such an osmiophilic layer in other
mammals is thought to be, at least
in part, due to species differences in the compo-
sition of materials constituting the
pulmonary surfactant.  cytologic immaturity
exists until lamb fetuses reach 135
days gestation.  this is considered to be the
basis for the susceptibility of immature
lambs to respiratory distress.  fibrin with
230 a periodicity is a component,
although a small one, of hyaline membranes in
lambs.  in view of the fact that mature
fibrin appearing as bundles of fibrils is rare-
ly found, it is suggested that the bulk
of the hyaline membrane is not a mature fi-
brin, but probably consists of polymers
of fibrinogen and serum protein.
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3831. lysosomes in the rat sciatic nerve following crush
peripheral nerves undergoing degeneration
are favorable material for studying the
types, origins, and functions of lysosomes.
the following lysosomes are described
(a) autophagic vacuoles in altered schwann
cells.  within these vacuoles the myelin
and much of the axoplasm which it encloses
in the normal nerve are degraded (wal-
lerian degeneration).  the delimiting
membranes of the vacuoles apparently form
from myelin lamellae.  considered as
possible sources of their acid phosphatase are
golgi vesicles (primary lysosomes), lysosomes
of the dense body type, and the endo-
plasmic reticulum which lies close to the vacuoles.
(b) mebranous bodies that accu-
mulate focally in myelinated fibers in a zone extending
2 to 3 mm distal to the crush.
these appear to arise from the endoplasmic reticulum
in which demonstrable acid
phosphatase activity increases markedly within 2 hours
after the nerve is crushed.
(c) autophagic vacuoles in the axoplasm of fibers
proximal to the crush.  the break-
down of organelles within these vacuoles may have
significance for the reorganization
of the axoplasm preparatory to regeneration.
(d) phagocytic vacuoles of altered
schwann cells.  as myelin degeneration begins, some
axoplasm is exposed.  this
is apparently engulfed by the filopodia of the schwann
cells, and degraded within the
phagocytic vacuoles thus formed.  (e) multivesicular
bodies in the axoplasm of myelina-
ted fibers.  these are generally seen near the nodes of ranvier.
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2431. histochemistry of surface epithelial and pleural mucins in mammalian
lung.  the demonstration of sialomucin in alveolar cuboidal epithelium
sialo- and sulfomucins have been demonstrated
histochemically in the surface
layer of the lung and pleura from rabbit,
syrian hamster, guinea pig, mouse, and
man.  sialomucin predominates in the distal
bronchial tree and covers the alveolar
epithelial surface.  the possible significance
of these observations is discussed.
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454. xanthogranuloma (xanthoma) of choroid plexus.  the origin of foamy
(xanthoma) cells
a case of a 3-month-old infant with intense pro-
liferation of choroidal epithelium with foamy cells, a
second similar case in a 9-month-old infant with gener-
alized glycogen storage disease and a case of a 51-year-
old male with bilateral xanthogranuloma of choroid
plexus and proliferation of the choroidal epithelial cells
are discussed.  the pathogenesis of the foamy xanthoma
cells in the stroma of the choroid plexus, particularly,
is discussed.  the authors believe that the origin of foamy
cells and the mode of formation of such a xanthogranuloma
can be explained by the proliferative capability and the
phagocytic activity of the choroid epithelium.  choroidal
epithelial cells can be regarded as fixed macrophages
which becomes wandering phagocytes after detachment.
disintegration of these foamy cells then releases the
lipid content into the interstitium and provokes a re-
sponse of macrophages and multinucleated giant cells
of the foreign-body type.  hemorrhage is also considered
as a factor involved in the formation of xanthogranuloma.
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4. mixed hematopoietic and pulmonary origin of 'alveolar macrophages' as
demonstrated by chromosome markers
the origin of alveolar macrophages was investiga-
ted in mouse chimeras in which the hematopoietic cells
could be identified by marker chromosomes.  by chro-
mosome analysis it was found that in both normal lungs
and in lungs exposed to an irritant, approximately two-
thirds of the dividing cells which could be recovered by
lung washing arose from the hematopoietic system and
one-third were of pulmonary origin.
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632. pulmonary alveolar proteinosis.  a study using enzyme histochemistry,
electron microscopy, and surface tension measurement
lung biopsies from 4 patients with pulmonary al-
veolar proteinosis were studied using histochemical me-
thods, electron microscopy, and surface tension mea-
surement.  the lipid-rich intraalveolar fluid contained
material with the staining reactions and ultrastructure
of phospholipid.  although many alveoli were lined by
enzymatically active, secreting granular pneumonocy-
tes, extracts of proteinotic tissue were not surface
active, and, in fact, inhibited normal surfactant.  some
of the cells free in the intraalveolar material were de-
generating sloughed granular pneumonocytes.  at the
margins of the lesions were lipid-filled macrophages
which appear to play a role in the removal of the mate-
rial.  these observations indicate that alveolar protein-
osis is not a primary overproduction of surfactant and
are consistent with the concept that the alveolar clear-
ing process is defective in this disease.
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1689. alterations in pulmonary surface active lipids during ex-
posure to increased oxygen tension
the syndrome of progressive respiratory
distress, pulmonary edema, and increased
pulmonary surface tension was induced in
8 dogs by exposure to oxygen tensions
greater than 550 mm hg for 44.5 and 52
hours.  pulmonary surfactant was extracted
by endobronchial washing for measurement
of lipid composition and surface activity.
five dogs developed respiratory distress
without pulmonary edema.  in these dogs
endobronchial wash surface tension was
normal or slightly increased, and total
lipid distribution was essentially normal.
esterified fatty acids in the lecithin frac-
tion were consistently altered with a
reduction in palmitate and total saturated fatty
acids.  three dogs developed pulmonary
edema with increased surface tension, in-
creased total lipid and protein, and
relatively decreased total phospholipid in the
endobronchial washings.  esterified
fatty acids in the lecithin fraction were marked-
ly altered with palmitate levels about
1/3 normal.  esterified arachidonate was pre-
sent that was attributed to intra-alveolar
plasma.  electron micrographs of the lung
after oxygen exposure showed thickening
of alveolar basement membrane and altera-
tions in the structure of the lamellar bodies
of the type ii alveolar epithelial cells.
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3805. cisternal fluid oxygen tension in man
measurement of cerebral oxygen tension
in man has been hampered by technical dif-
ficulties.  the authors present a method
in which a beckman microelectrode was
introduced into the cisterna magna and
oxygen tension measured, the hypothesis
being that measurement of oxygen tension
in a fluid which equilibrates with the
average cerebral oxygen tension should
give reliable measure of cerebral oxygen
tension.  in their subjects, inhalation of
pure oxygen produced an increase in the
oxygen tension in the cisternal fluid as
well as in the arterial blood without any
alteration of the oxygen tension in the
bulb of the internal jugular vein, whereas
inhalation of 95% oxygen and 5% carbon
dioxide increased the oxygen tension in the
cisternal fluid as well as in the arterial
and venous blood.  5% carbon dioxide in
air produced an increase in the cisternal
oxygen tension; a fall in arterial blood
pressure associated with the introduction
of the suboccipital needle was accom-
panied by a decrease in cisternal oxygen
tension which then rose simultaneously with
the increase in arterial blood pressure
that followed infusion of dextran.  intravenous
injection of xanthinol niacinate induced
in all patients a more or less pronounced fall
in arterial blood pressure and at the
same time the cisternal oxygen tension fell;
administration of aramine was associated
with a rise in arterial blood pressure
plus a rise in cisternal oxygen tension.
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4181. cerebrospinal fluid in man native to high altitude
csf ph was shown in a prior report to
remain essentially constant during 8 days
of acclimatization to 3,800 m.  in order
to further evaluate the possible role of
csf acid-base equilibria in the regulation
of respiration, 20 peruvian andean na-
tives were studied at altitudes of 3,720-4,820 m.
in 10 subjects at 3,720 m, means
were  csf ph 7.327, pco, 43, hco3-21.5,
na+136, k+2.6, cl-124, lactate 30 mg/
100 ml.  arterial blood  ph 7.43, pco, 32.5,
hco3-21.3, na+136, k+4.2, cl-107,
hematocrit 49, sao, 89.6.  in 6 subjects at
4,545 m and 4 at 4,820 m csf values
were not significantly different; mean arterial
pco, was 32.6 and 32.3, respectively.
the only significant variations with altitude
were the expected lowering of pao, to
47 and 43.5 mm hg, and of sao, to 84.2 and
80.7, and increase of hematocrit to
67% and 75%, respectively.  the natives
differed from recently acclimatized sea-
level residents in showing less ventilation
(higher pco,) in response to the ex-
isting hypoxia, and less alkaline arterial
blood.  the difference appears to relate
to peripheral chemoreceptor response
to hypoxia rather than central medullary
chemoreceptor.
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1116. na, k, ca, mg, and cl concentrations in choroid plexus fluid
and cisternal fluid compared with plasma ultrafiltrate
in 7 cats the concentrations of na,
k, ca, mg, and cl were measured in plasma
ultrafiltrate, newly formed choroid
plexus fluid, and cisterna magna fluid.  the
choroid plexus fluid did not differ
from plasma ultrafiltrate in cl and k concentra-
tion but contained higher na, markedly
higher mg, and lower ca concentrations
than the ultrafiltrate.  cisterna magna
fluid differed from the ultrafiltrate with
respect to all 5 electrolytes, containing
higher concentrations of cl, na, and mg
and lower concentrations of k and ca.
it differed from choroid plexus fluid in con-
taining a higher concentration of cl but
lower concentrations of k, ca, and mg.
hco3-concentration, calculated on the
basis of the charge balance, was 7 mm/kg
h2o higher in choroid plexus fluid than
in cisterna magna fluid, suggesting an ele-
vated ph at the former site.  without
measurement of the potential difference be-
tween the csf and plasma, definitive
conclusions could not be drawn as to which
cations were actively transported.  the fact
that the distribution ratio between cerebro-
spinal fluid and ultrafiltrate of one divalent
cation was in the opposite direction
from that of the other, and that this was
also true of the monovalent cations, was
taken as evidence that the mechanisms
involved in cation transfer are quite selec-
tive.  though not proven, active transport
was considered the most likely explana-
tion of these findings.  the data suggest
that these specific transfer mechanisms
subserve a homeostatic function with
regard to mg and k in the cerebrospinal fluid.
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3230. cerebral hemodynamics, blood gases, and electrolytes
during breath-holding and the valsalva maneuver
continuous recordings of arterial and
internal jugular blood oxygen tension, oxy-
gen saturation, carbon dioxide tension,
ph, sodium and potassium, together with
peco2, blood pressure, and
electroencephalogram were obtained to compare the
effects of inspiratory and expiratory
breath-holding and the valsalva maneuver on
the cerebral circulation and cerebral
oxygen availability in man.  during the inter-
val of tolerated breath-holding for
69 seconds or less, jugular venous oxygen tension
was increased owing to increased
cerebral blood flow resulting from an increase
of arterial carbon dioxide tension.
there was a statistically significant correlation
between changes in jpo2 and paco2,
which proved to be more or less linear for
both increases and decreases of paco2 4 mm.
above and below control levels.  no
threshold was found for changes in paco2
altering effective cerebral perfusion and
cerebral venous po2, extremely small
changes in paco2 (less than 1 mm. hg)
altered cerebral oxygen availability within
10 to 20 seconds.  during the valsalva
maneuver a consistent reduction of jugular
oxygen tension was found associated
with the sudden fall in arterial blood
pressure and reduction of arterial carbon
dioxide tension.  the rapid changes in
cerebral hemodynamics and cerebral oxy-
gen availability during the procedure
are briefly discussed.
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2344. respiratory and cardiovascular changes during rapid spon-
taneous variations of ventricular fluid pressure in pa-
tients with intracranial hypertension
in patients with intracranial hypertension
the ventricular fluid pressure (vfp)
curve is characterized by 3 main forms
of spontaneous variations.  two of these
forms are of a rhythmical nature, and
are here called 1-per-minute waves and 6-
per-minute waves, respectively, in
accordance with the dominating frequency.
the third form - irregularly appearing
waves of large amplitude and duration -
is called plateau waves in accordance
with the usual shape of the fluctuations.
respiratory and cardio-vascular changes
accompanying these variations of the vfp
were studied by simultaneous recording,
in various combinations, of the vfp, the
pulmonary ventilation, the pco2 of the
expiratory air, the arterial and the venous
blood pressure, and the pulse frequency.
it was found that the rhythmic vfp vari-
ations of the 1-per-minute type occurred
synchronously with the respiratory peri-
ods in cheyne-stokes breathing.
synchronously appearing variations in systemic
blood pressure, in pulse frequency,
as well as in consciousness and in muscular
tone of the limbs were also noted.  the
respiratory midposition shifted towards the
inspiratory side during the periods of
hyperpnoea.  the 6-per-minute waves were
entirely synchronous with variations
in the systemic arterial blood pressure of the
traube-hering-mayer type.  long
sequences of these waves were observed only
when the vfp level was considerably
elevated.  the plateau waves were not accom-
panied by corresponding elevations of
the arterial or venous systemic blood pres-
sure.  simultaneously with the crests
of the plateau waves sudden changes often
occurred in the pulse frequency (from
bradycardia to tachycardia), and in the res-
piratory pattern, sometimes also in the
degree of consciousness and in the muscu-
lar tone.  there were also long sequences
of 6-per-minute waves.  the deep, irre-
gular breathing seen in this stage induced
a considerable hypocapnia preceeding
the final critical fall in the vfp ending the
plateau wave.  in most instances, how-
ever, this fall did not begin until several
minutes after the appearance of the hypo-
capnia.
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747. electrode size and tissue po2 measurement in rats exposed
to air or high pressure oxygen
a comparison has been made of values of
po2 recorded in several rat tissues with
60-u or 330-u flexible gold electrodes.
although qualitatively both sizes of elec-
trodes give similar results, the quantitative
values of po2 differ.  such large differ-
ences as are found in some cases between
electrodes varying only in physical di-
mensions are thought to reflect the amount
of trauma caused in the tissue under in-
vestigation due to electrode insertion.
errors in po2 estimations due to tissue da-
mage are considered to outweigh any other
errors such as those due to electrode
calibration.  soft, highly vascular tissues,
such as liver, kidney and spleen, which
show macroscopic bruising over quite a
large area when electrodes are inserted,
show the greatest difference in estimations
of the po2 value.  recordings of tissue
po2 were made while animals breathed air
and when compressed to 4 or 5 atm. in
pure oxygen, and the pattern of response of
tissue po2 to such exposure of the ani-
mal to high pressures of oxygen is described.
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10642. the effects of antioxidants on high pressure oxygen toxicity
several commonly used antioxidants have
been tested for their effect against poison-
ing due to high pressures of oxygen (ohp).
the tests used were preconclusive pe-
riod and survival time of mice at 5 atm
absolute oxygen, lung damage in rats ex-
posed to 5 atm oxygen for 1 hr., and post
ohp paralysis in rats following deep
pentobarbital-na anesthesia and ohp at 4
atm for 30 min.  2,5-bis (1,1-dimethyl-
propyl) hydroquinone gave excellent
protection against ohp toxicity in all tests,
and several other antioxidants also
protected against ohp toxicity but their potency
and effectiveness varied for the
different criteria of oxygen poisoning tested in the
experiments.
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3716. glycolytic control mechanisms. i. inhibition of glycolysis
by acetate and pyruvate in the isolated, perfused rat heart
acetate or pyruvate had similar effects
on the over-all metabolism of glucose.  gly-
colytic flux was decreased in both the
presence and absence of insulin, glucose
oxidation was greatly decreased, and
the conversion of glucose to glycogen and lac-
tate was promoted.  glucose phosphorylation
was decreased in the presence but not
in the absence of insulin.  hexokinase,
phosphofructokinase, glyceraldehyde phos-
phate dehydrogenase, and pyruvic kinase
are far displaced from equilibrium, while
the other enzymic steps of glycolysis
are maintained either at equilibrium or fairly
close to equilibrium.  in different metabolic
situations, glycolytic flux may be affec-
ted by those steps which are far displaced
from equilibrium.  increased levels of
the hexose monophosphates, and decreased
levels of the other glycolytic inter-
mediates between fructose 1,6-diphosphate
and pyruvate after the addition of 10 mm
acetate indicate that glycolytic flux was
decreased by inhibition of phosphofructo-
kinase.  after the addition of 10 mm pyruvate,
fructose 1,6-diphosphate, and triose-
phosphate accumulated as a result of an
inhibition of either glyceraldehyde phosphate
dehydrogenase or phosphoglyceric kinase.
acetate had little effect on the total con-
tent of oxidized or reduced di- or
triphosphopyridine nucleotides, but slightly de-
creased the ratio of nad to nadh2
in the cytoplasm, as estimated from the ratios
of lactate to pyruvate and a-glycerophosphate
to dihydroxyacetone phosphate.  pyru-
vate increased the total content of nadh2
and nadph2 as shown both by an increase
of fluorescence in the intact heart, and by
tissue analyses, but the ratio of nad to
nadii2 in the cytoplasm was greatly
increased.  these results demonstrate com-
partmentation of pyridine nucleotides
between cytoplasm and mitochondria in the
intact cell.  after the addition of acetate,
citrate was the only intermediate of the
citric acid cycle which increased greatly
in amount, while oxaloacetate levels de-
creased.  after the addition of pyruvate,
the levels of citrate, a-ketoglutarate, ma-
late, and oxaloacetate were all greatly
elevated.  the glutamic-oxaloacetate trans-
aminase reaction as measured from the
total contents of the reactants in the tissue
remained close to equilibrium.  changes
in the concentrations of the adenine nu-
cleotides were insufficient to account for
the inhibition of phosphofructokinase, but
the results are consistent with control at this
step being mediated by citrate.
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244. oxygen tension in human malignant disease under hyperbaric
conditions
oxygen tensions were recorded continuously
in tumours and normal tissues of 34 pa-
tients pressurized in pure oxygen to 4 atmospheres
absolute.  mean rises to 620 mm.
hg and 320 mm. hg for tumours and normal tissues
respectively were recorded.
with patients breathing air at atmospheric
pressure 22/90 (24%) of tumour elec-
trodes registered po2values of less than 4 mm. hg
compared to only 2/39 (5%) of normal
tissue electrodes.  the results obtained
suggest that oxygen polarography as a meth-
od for determining po2 in 'solid' tissues
in vivo is complicated by many artefacts -
particularly tissue damage due to electrode
trauma - which reduce its value to clin-
ical research concerned with accurate
information of absolute po2 values in intact
tissues.
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8914. the effect of hypoxia on oxygen consumption of cerebral
cortex, liver slices and of diaphragm in vitro during post-
natal development of the rat
oxygen consumption of slices from the liver
and cerebral cortex and of the cut dia-
phragm was determined in rats aged 5, 10,
14, 20 and 25 days and in adult animals.
under hypoxic conditions (gas phase 10%
oxygen, 90% nitrogen) oxygen consumption
of liver slices and diaghragm is decreased
by about 25% in all age groups.  hypoxia,
however, did not affect oxygen consumption
of slices of the cortex from 5-day-old
rats and its inhibitory effect only appeared
later as the normal oxygen consumption
started to rise.  the inhibitory effect of
hypoxia was greatest in adult animals.
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3917. plasma free fatty acid and blood sugar levels in newborn
infants and their mothers
simultaneous plasma free fatty acid (ffa)
and blood sugar levels were determined
for fasting newborn infants during the first
24 hours of life, for their cord bloods,
and for their mothers at delivery.  the
following observations were made.  in con-
trol infants the mean ffa level rose about
three times the cord level after birth
and was accompanied by a 25% drop in the
mean blood sugar level.  thereafter, the
mean blood sugar level remained relatively
constant, but the mean ffa level varied
from 2.5 to 3 times the cord level.  there
was no significant correlation between the
length of maternal fasting prior to delivery
and the infant ffa level; there was,
however, a significant negative correlation
between the length of maternal fasting
prior to delivery and the infant blood sugar
level at 24 hours of age.  high ffa levels
occurred in the infants of obese mothers
and low levels were observed in infants with
delayed respirations, in infants of preeclamptic
mothers, and in infants of diabetic
mothers.
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2933. the essential fatty acid requirement of infants and the
assessment of their dietary intake of linoleate by serum
fatty acid analysis
the content of polyunsaturated fatty acids
in serum total fatty acids was related
to the dietary intake of linoleate in 243 infants
two to four months of age and in 197
infants eleven to twelve months of age.  the
curves relating triene tetraene ratio
to dietary linoleate indicated approximately
1 per cent of total calories as minimal
linoleate requirement.  the exponential
equations relating dienoic, trienoic and
tetraenoic acids to dietary linoleate were
derived by computer methods.  these
yielded constants from which the minimal
nutrient requirement could be calculated.
the best estimates were obtained from the
triene and tetraene data for two to four
months' old infants and were found to be
approximately 1.4 per cent of the caloric
intake.  the nutritive status with respect to
linoleate may be estimated by means
of logarithmic regression equations.  the
equation for two to four months' old infants
is  log 10 dietary linoleate = -1.087 + 0.0432
(di - tri + tetra).  the data for eleven to
twelve months' old infants were found to have
greater scatter and give lower triene
tetraene ratios at comparable linoleate intakes.
the scatter and displacement are
considered to be due to supplements of solid food
to the basic diet not considered in
the calculated dietary linoleate.
.I 306
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74. analytic study of the a- and b-lipoprotein micellar groups
and of nonesterified fatty acids of the plasma in normal pregnancy
an analytical study has been made on 39
patients, using a chemical method which
allows the simultaneous detailed evaluation
of the lipidic and a- and b-liproproteinic
fractions of the plasma.  in addition the
non-esterified fatty acids have been titrated,
the b-proteins and the uric acid assayed,
and numerous indices and deducible ratios
made from the data obtained.  the existence
of quantitative dyslipidemia has been
proven, starting gradually, especially in the
4th-5th month of pregnancy, and most-
ly regarding the b-lipoproteins, prevalently
the slow subfractions, greater increase
of glycerides than phosphatides and cholesterol,
but with a non-proportional in-
crease of b-proteins (lower proteinic content).
it has, moreover, been noted that
there is a prevalent rise of free cholesterol in
the fraction of b-lipoproteins with
a reduction of the total esterification coefficient.
the morphological picture of the
lipidic rate in pregnancy shows characteristics
which, according to the authors,
are like those to be seen in the lipidic rate of
male presenility.
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75. behavior of polyunsaturated fatty acids in physiological
pregnancy
by the enzymatic lipoxidase method of
macgee et al., the author measured polyun-
satured fatty acids (p.f.a.) in healthy
pregnant women at full term of pregnancy.
before labour there are in the blood 75-95
mg.% of p.f.a., i.e. 10-15% more
than in non-pregnant women; during labour
p.f.a. increase very much, 100-137
mg.%, about 50% more than before labour.
.I 308
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5196. effects of nutritional deficiency of unsaturated fats on
the distribution of fatty acids in rat liver mitochondrial phospholipids
the fatty acid composition of liver mitochondrial
phospholipids from rats rendered
deficient in essential unsaturated fatty acids
has been determined, and compared
with that of rats fed a diet containing corn oil.
in addition to marked reductions in
the amounts of linoleic and arachidonic acids
esterified at the b-position of ethanol-
amine-, inositol-, and choline glycerophosphatides,
the deficiency resulted in ex-
tensive changes in the distribution of saturated
acids at both the a- and b-positions.
palmitoleic and oleic acids were increased in
amount in fat deficiency, and large
amounts of docosatrienoic acids appeared in
these 3 phospholipids.  the fatty acids
of the sphingomyelins were not altered as a
result of essential fatty acid deficiency.
the data demonstrate that each phospholipid
is unique in the way in which its fatty
acid moieties change in response to feeding
a fat deficient diet.
.I 310
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2579. measurement of aortic regurgitation by upstream sampling with continuous
infusion of indicator
a direct and theoretically valid method
for the measurement of aortic regurgitation
involves the recording of indicator concentrations
from the left ventricle and a down-
stream site during aortic root injection.  however,
this method has yielded erratic
results when applied to man in the authors'
laboratory when using the sudden in-
jection technique.  therefore, the upstream
sampling method, using continuous in-
fusion of indicator, was evaluated in 18 patients
with aortic regurgitation during
retrograde aortic and transseptal left ventricular
catheterization.  the continuous
infusion technique was compared with the technique
of sudden injection in 10 patients
and with aortic valvulography in 14 patients.
measurements of forward flow obtained
with continuous infusions into the aortic root
were not significantly different from
measurements obtained with sudden injections
into the pulmonary artery.  recordings
of indicator concentrations from the left ventricle,
during continuous infusions into
the aortic root, demonstrated readily evident
equilibrium plateaus.  the resultant
measurements of regurgitant flow were highly
reproducible and not impaired by
nonsimultaneity of upstream and downstream
sampling.  the percentage error of
estimate at 95% confidence limits was 22% of
the measurement for regurgitant flow,
13% for total flow, and 9% for the regurgitant
fraction of total flow.  the correspond-
ing errors of estimate for the sudden injection
technique were 4 times larger.  re-
gurgitant flow by the continuous infusion method
ranged from 0.8-30.0 l/min, total
flow from 3.0-36.0 l/min, and the regurgitant
fraction of total flow from 12-86%.
ranking of patients by the magnitudes of regurgitant
and total flow did not correspond
to ranking by angiographic criteria of severity.
however, an excellent correlation
prevailed between angiographic grade and the regurgitant
fraction of total flow,
demonstrating that this variable is the most meaningful
expression of severity.  the
correlation (0.997) between the angiographic grade and
the regurgitant fraction
measured by the continuous infusion technique was
clearly superior to that obtained
with the sudden injection technique (0.894).  mild
regurgitation was equivalent to
a regurgitant fraction of <25%, moderate
regurgitation to a fraction of 25-50%,
moderately severe regurgitation to a fraction
of 50-75% and severe regurgitation to
a fraction of >75%.  it is concluded that the
upstream sampling method during con-
tinuous infusion of indicator, because of its
sensitivity, reliability, applicability to
multiple measurements, and validity in the
presence of mitral regurgitation is the
most useful method for quantifying aortic
regurgitation in man.
.I 311
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2950. aortico-left ventricular tunnel.  a cause of massive aortic regurgitation
and of intracardiac aneurysm
the clinical, roentgenographic, hemodynamic
and pathologic findings in a 14-year-
old boy with aortico-left ventricular tunnel are
presented.  the accessory channel
between the aorta and left ventricle resulted in
massive aortic regurgitation, and
the portion of the tunnel which traversed the
ventricular septum was aneurysmal,
displaced the posterior wall of the right
ventricle and caused severe obstruction
to right ventricular outflow.  the presence
of associated cardiovascular anomalies,
in this and previously reported cases,
suggests that the malformation is congenital
rather than acquired.  the clinical and
hemodynamic manifestations of aortico-left
ventricular tunnel are indistinguishable
from those observed with the more common
forms of aortic regurgitation, and the
correct diagnosis can be established only by
thoracic aortography.  the malformation
is usually recognized in childhood; since
aortic regurgitant flow can be abolished by
simple closure of the aortic ostium,
and without aortic valve replacement, the
indications for operative treatment
differ from those which apply in aortic
regurgitation due to a valvular anomaly.
.I 312
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502. the haemodynamic implications of the bisferiens pulse
a bisferiens carotid arterial displacement pulse
was recorded in 10 patients with
severe aortic valvular disease.  the braunwald
test indicated that moderately severe,
severe, or gross aortic regurgitation was present
in each.  the absence of a peak
systolic aortic pressure gradient in certain cases,
particularly in those with the
most severe regurgitation, suggested their freedom
from an element of stenosis.
the anacrotic wave and the peak of the aortic
pressure pulse were found to coincide
with the percussion and the tidal waves of the
simultaneously recorded carotid ar-
terial displacement curves.  it is suggested that
amplitude of the peak of the anacro-
tic wave is proportional to the rate of change of
momentum of the ejected blood, and
that the amplitude of the corresponding percussion
wave of displacement is modified by
the distensibility of the artery.  the depth and shape
of the trough between the two
peaks is thought to depend upon the magnitude and
slope of the two waves rather than
upon a venturi effect.  it is suggested that the condition
of the arterial wall, the dia-
stolic blood pressure, and the stroke volume can
influence the pulse sufficiently to
preclude its use as a simple guide to the nature of
the aortic valve lesion.
.I 313
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2753. left ventricular function following replacement of the
aortic valve.  hemodynamic responses to muscular exercise
evaluations of left ventricular myocardial
function were carried out in 14 patients
4-16 mth after stenotic or regurgitant
malformations of the aortic valve had been
corrected by valve replacement.  the
circulatory responses to exercise, judged by
the increases in cardiac output in relation
to the increases in oxygen consumption,
were normal or only mildly reduced in 12
patients.  in 5 patients the relationships
between the change in the left ventricular
end-diastolic pressure and the alteration
in the stroke volume were also normal, a
fall or an increase in left ventricular
end-diastolic pressure of less than 3 mm
hg being accompanied by an increase in
stroke volume.  in 8 patients, however,
abnormal increases in the left ventricular
end-diastolic pressure occurred during
exercise, and in 4 the left ventricular end-
diastolic pressure was increased to levels
above 12 mm hg.  variable alterations in
the stroke volume accompanied these increases
in end-diastolic pressure.  it is
suggested that in the 3 patients who exhibited
simultaneous increases in left ven-
tricular end-diastolic pressure and stroke
volume, the changes were either a mani-
festation of the frank-starling mechanism,
or primarily the result of a positive
inotropic influence.  in the 5 patients who
exhibited increases in left ventricular
end-diastolic pressure, but no change or a
fall in stroke volume, it is proposed
that a distinct depression of left ventricular
performance was present.  thus, while
the cardiac output response was adequate to
meet the stress of exercise in the
majority of the patients studied following aortic
valve replacement, determination
of the relationship between the left ventricular
end-diastolic pressure and the stroke
volume permitted the detection of abnormalities
in the function of the left ventricle.
.I 314
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2497. pulmonary atresia with intact ventricular septum
when the pulmonary valve is atretic and
the ventricular septum intact, the right
ventricle usually consists of a small chamber
with a very thick wall capable of de-
veloping high pressure.  this pathologic picture
is associated with clinical findings
similar to those in tricuspid atresia-cyanosis,
decreased pulmonary flow, left ven-
tricular preponderance on the electrocardiogram,
and early death.  the diagnosis
may be confirmed by heart catheterization and
selective angiocardiography with in-
jection into the right ventricle, but the risk is
great.  surgery has never been suc-
cessful in the past; but because of the equally
hopeless prognosis on medical treat-
ment, attempts should continue to be made.
anastomosis of the superior vena cava
to the right pulmonary artery appears to offer
hope of success in the future.
.I 315
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1635. intra-atrial pressure measurement and electrocardiography in the
detailed diagnosis of atrial septal defect
after discussing the possibilities and
limitations of different methods for identifying
the anatomical type of atrial septal
defect, the authors suggest a more useful new
method.  this consists in simultaneous
recording of both the pressure curve and
endocavitary electrocardiogram during
withdrawal of the catheter from the left into
the right atrium.  in the ostium primum
type, the septal foramen has no infe-
rior margin, and the point of the catheter
during retraction (unlike in the ostium
secundum type) rests on the intermediate
section of the atrioventricular septum.
the endocavitary electrocardiogram in the
zone of passage between the two atria
shows the typical pattern of the intermediate
section of the atrioventricular septum;
the pressure curve may show a pattern of the
atrial of intravalvular type.
.I 316
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1636. ventricular septal aneurysms.  a report of two cases
two cases of ventriuclar cuptal aneurysm
are reported, one in the membranous and one
in the muscular portion.  the diagnosis was
made by selective left ventricular angiogra-
phy.  it is suggested that these cases represent
spontaneous closure of a ventricular septal
defect with weakness and aneurysmal formation
due to the high left ventricular pressure.
both are asymptomatic and hemodynamically
within normal limits.  surgical repair
of the aneurysms is not considered necessary.
.I 317
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1642. electrode catheters and the diagnosis of ebstein's anomaly
of the tricuspid valve
the successful surgical treatment of ebstein's
anomaly calls for accurate pre-ope-
rative assessment of the nature and severity of
the tricuspid valvular lesion.  the
increased risk of cardiac catheterization in this
condition has been matched by in-
creased experience of intracardiac techniques,
and provided the examination is in
skilled hands, patients with ebstein's anomaly
should be investigated in the same
way as those with any other serious congenital
heart lesion for whom surgery is con-
templated.  the diagnostic value of electrode
catheters is discussed, and the intra-
cardiac electrocardiographic features of ebstein's
anomaly are illustrated.  false
positive and false negative records are demonstrated
and the mechanism of their
production is explained.  it is concluded that, though
helpful, intracardiac electro-
cardiographic evidence should be regarded as confirmatory
rather than diagnostic.
records made with electrode catheters during cardiac
catheterization should be con-
sidered only along with the other clinical,
electrocardiographic, and radiological
features of the case, and should not be relied upon
as the definitive method in the
diagnosis of ebstein's anomaly.
.I 318
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3326. unusual aneurysm of the membranous interventricular septum
the case of a patient with a huge aneurysm of the
membranous interventricular
septum is presented.  this is believed to be the
first such patient to have undergone
successful resection.
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934. laevocardia with situs inversus.  a case report and a review of literature
a case of levocardia, with
inversion of the cham-
bers of the heart and
transposition of the great vessels
and situs inversus, has been described.
gross cyanosis
and clubbing were present and were due
to a veno-arteri-
al shunt through a right-sided superior
vena cava open-
ing into the arterial atrium and
passage of venous blood
into the aorta through a ventricular
septal defect.  the
case was complicated with right-sided
hemiplegia and
with the development of a liver abscess.
a review of the
literature with prognosis and possible
etiology of the
condition has also been made.
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2431. the natural history of arrhythmias following septal defect reapir
the repair of 191 atrial and ventricular septal
defects between 1955 and 1961 was
reviewed to determine the incidence and prognosis
of arrhythmias related to operation.
cases included 90 ventricular septal defects, 61
atrial defects of the ostium secundum
type, and 40 of the ostium primum variety.
nodal rhythms, second degree blocks,
complete heart block, and flutter or fibrillation that
persisted after completion of operation
were analyzed, while intermittent ectopic beats,
sinus tachycardia, and bundle branch
blocks were excluded.  fifteen per cent of the
patients with ventricular defects, 17%
with ostium primum defects, and 35% with ostium
secundum defects developed abnormal
rhythms associated with repair.  of 18 patients whose
arrhythmias began during operation,
there were 8 deaths; no fatalities occurred in the 24
patients who developed arrhythmias
in the postoperative period.  seven deaths were
associated with complete heart block and
one with second degree block.  although only one
half of the patients who developed
arrhythmias had pulmonary artery pressure greater
than 30 mm. hg systolic, all fatalities
occurred in this group.  four of the deaths followed
surgery with the use of the pump
oxygenator in children under 30 months of age.
thirty-eight per cent of the abnormal
rhythms that began in the postoperative period
were nodal.  flutter and fibrillation
were common following repair of atrial secundum
defects in patients over 15 yr. of age
but did not occur in younger patients.  deaths from
heart block occurred in the first 30 days
following operation except one, 5 months later.
survivors of complete heart block reverted
to a less serious arrhythmia or normal rhythm
within 3 months.
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4105. free fatty acid metabolism in chinese hamsters
in normal chinese hamsters (cricetulus
griseus) the mean concentration of free
fatty acids (ffa) in serum varied from
group to group, but was (1) consistently 4
to 9 times greater than in rats, dogs,
or man; (2) slightly higher than in syrian
hamsters; (3) two- to four-fold higher
than in fasting or alloxan-diabetic rats.  the
epididymal adipose tissue of the chinese
hamster (1) had initial concentrations of
ffa comparable to those in the rat and
syrian hamster; (2) released, in the same
time interval, 8- to 10-fold more ffa
in vitro than this tissue of the rat; (3) had
higher concentrations of ffa after incubation
than the incubated tissue of the rat.
the retroperitoneal (perirenal) adipose tissue
of the chinese hamster was less ac-
tive in release of fatty acids in vitro than the
epididymal, but was, however, more
active than the epididymal adipose tissue of
the rat.  these characteristics of ffa
metabolism in the chinese hamster were
apparently attributable to species, not to
age, diet, or sex.  in the chinese hamster,
the weight of the epididymal adipose tis-
sue per gram of body was relatively high.
it appears that in this species the rate of
release of fatty acids from adipose tissue
is great, leading to high ffa concentra-
tions in serum.  in chinese hamster and rat
adipose tissues in vitro, glucose and in-
sulin (separately) reduced the rate of release
of ffa and the amount of ffa in the
tissues, but glucose and insulin together
produced the greatest reduction.  the net
reduction in ffa release by glucose and
insulin in vitro was greater in tissue from
the chinese hamster.  insulin markedly
increased glucose uptake by the adipose tis-
sues of both species.  the possible relation
of the results to spontaneous diabetes in
the chinese hamster is discussed.
.I 328
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3294. epinephrine infusions in normal and toxemic pregnancies.
ii. plasma glucose, nonesterified fatty acid, and epineph-
rine-norepinephrine alterations
seven controls and 9 preeclamptic patients
were infused with different amounts of
epinephrine.  plasma nefa, glucose and
catecholamines were determined before,
during and after epinephrine infusion.  the
toxemic patient responds to the metabolic
effects of infused epinephrine in a manner
similar to that of the normal pregnant
patient.  the increased levels of nefa in
pregnant patients are explained by a com-
plicated biochemical mechanism involving
an increased availability of cortisone-like
steroids, slightly increased amounts of thyroid,
hormones, etc., resulting in an
alteration of carbohydrate utilization.  the study
leads to the conclusion that epi-
nephrine is not an etiologic agent in toxemia of pregnancy.
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377. experimental study of sensitization to nickel
sensitization was effected by epicutaneous
application of nickel sulfate in
15 guinea-pigs.  it was confirmed by the
appearance of eczematiform lesions in
skin tests with nickel sulfate.  for maintenance
of the animals in good general
condition it was necessary to add vit. c and
antiinfective agents to the diet.
for this reason the allergenicity of the ni
salt had to be augmented by the use
of adjuvants (freund's complete adjuvant or alum).
such adjuvants act by
stimulating the res.  the method for
sensitization of guinea-pigs to metal salts
having been worked out, it is now proposed
to study the mechanism of such
sensitization, the biological disturbances
involved and the possible existence
of cross-sensitizations.
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2285. some remarks on the nickel dermatitis
by non-occupational contact
this dermatitis represents 2% of the
skin diseases observed at the
allergologic outpatients department of
the dermatological clinic of milan.
the disorder is more frequent in women
and prefers the thighs (girdles, keys)
and the wrist (watch); its incubation
period is generally long and a peculiar
papulo-vesicular follicular and lichenoid eruption often follows.
.I 336
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3200. studies on the binding of protein by nickel.
with special reference to
its role in nickel sensitivity
the reaction between nickel and proteins
was studied using the technique of
equilibrium dialysis.  in most of the experiments
crystalline bovine serum
albumen was used.  the nickel-protein complex
was of low stability, the quantity
of nickel bound by the protein being dependent
on the concentration of free
nickel ions, the ph, and the particular protein used.
the sites of binding of
the nickel ions were primarily carboxyl and amino
groups.  the author concluded
that it was unlikely that nickel behaved as a
hapten capable of initiating an
allergic response.
.I 337
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2596. experimental nickel contact sensitization in man
in 16 of 172 male prisoners contact-type
delayed hypersensitivity was induced
experimentally by repeated application of
25% nicl2 in a 0.1% sodium lauryl
sulphate solution on the skin.  test reactions
with 5% nicl2 with occlusion
were found to be irritating.  no experimentally
sensitized subject demonstrated
clinical sensitivity to the metal in his environment.
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189. influence of age, sex and glandular extirpation on muscle carcinogenesis
in rats
the carcinogenic effect of a single intramuscular injection of nickel sulphide
in an aqueous suspension to which penicillin g had been added was compared
in male and female castrated, hypophysectomized or intact, rats of different
ages.  the response seemed most marked in intact females injected when 2 mth.
old.  castrated or hypophysectomized 2-month old females were less
responsive.  one-month old intact males were more responsive than 2-month or
3-month old intact males, 1-month old castrated males, or 1-month old
intact females.  more data would be required before firm conclusions could be
drawn from these results.
.I 344
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3176. studies of trace metal metabolism  electron paramagnetic resonance of
manganese in ribonucleic acids
the electron paramagnetic resonance spectrum pattern of manganese was
readily detected in all of the samples of rna.  the resonance patterns
indicate that manganese is present in rna in a divalent state and suggest
that manganese is located at the center of a distorted octahedron of oxygen
atoms.  from the intensity of nominally forbidden resonances, the crystal
field splitting parameter d was estimated to be 0.02 cm -1.
.I 345
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4790. metal chelates as potential reactivators of organic phosphate poisoned
acetylcholinesterase
as part of a study to investigate metal chelates as possible reactivators
of phosphate poisoned acetylcholinesterase, it is shown that chelates act
as inhibitors of the enzyme.  in addition, copper and nickel chelates of
2-pyridinealdoxime catalyze the decomposition of dfp and sarin.  compared to
2-pam, however, these chelates are very poor reactivators, probably because
of an improper alignment of the oxine oxygen in the chelate-enzyme complex.
.I 347
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2302. the carcinogenic activities of n-hydroxy-2-acetylaminofluorene and its
metal chelates as a function of retention at the injection site
the carcinogenic activities of s.c. administered
n-hydroxy-2-acetylaminofluorene
(n-hydroxy-aaf) and a variety of its metal chelates indicate that greater
activity locally is associated with a longer retention of the chelates at the
site of injection with a slow release of n-hydroxy-aaf to the surrounding
tissue.  no tumors were obtained at the sites of 4 injections of n-hydroxy-aaf
(3.2 mg. /injection), but 4 and 16 of 20 rats developed sarcomas at the
sites of 8 and 16 injections, respectively.  the nickelous, cobaltous, ferric,
or cupric chelates induced moderate to high incidences of sarcomas with 1 or 4
injections; in these cases one-half of the administered n-hydroxy-aaf was
retained at the injection site for 4-50 days.  the manganous and zinc chelates
and the potassium salt were less active at the injection site; the
half-retention times for these ranged from 2.5 hr. to 2.5 days.  the comparable
half-retention time for n-hydroxy-aaf was about 2 hr.  injection of the metal
derivatives s. c. with short half-retention times resulted in higher incidences
of mammary tumors than injection of the derivatives with half-retention
times of 4 or more days.  when administered in the food the cupric chelate
of n-hydroxy-aaf induced the same spectrum of tumors as n-hydroxy-aaf,
but the incidences were lower.  while the prolonged retention of the material
at the injection site may account for the greater carcinogenic activities of
the metal chelates, serious consideration must also be given to the possible
importance of chelation of carcinogens or their metabolites to cellular
constituents.
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1287. agnostic alexia and constructive apraxia with regressive evolution in
a child of 12 yr. of age
after an acute encephalopathy, the etiology of which could not be determined,
a boy of 11 yr. and 10 mth. of age developed a syndrome of agnostic alexia
and constructive apraxia which was remarkably pure.  the intellectual
functions were normal as determined by iq tests, speech was not disturbed
either.  the child could not read or copy a text, but was fully able to write
(both freely and dictated).  the patient could not read what he had written.
this shows the characteristic features of agnostic apraxia.  motor activity and
performance were normal, but the child had extreme difficulty in constructing
geometric forms, even elementary, either spontaneously or by copying.
this remarkable syndrome disappeared, and during its involution it was
followed up.
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1288. the symptomatology of the parietal cerebral syndrome of the dominant
hemisphere.  parietal dyslexia and conduction aphasia
this is a very comprehensive study on a patient.  in the beginning there was
a pronounced gerstmann's syndrome, with autotopagnosia for parts of the face,
dyspraxia and constructive apraxia and dyslexia.  the autotopagnosia and mild
left-right disturbances showed marked regression.  actual hemianopsia was
not observed, but tachistoscopy revealed that perception of the right field of
vision was poor.  audiometric examination showed a conduction deafness and
disturbed binaural word synthesis.  the disturbances were examined
meticulously and tested for symptom relationships, which became evident
in the various factors concerned with creative ability.
.I 351
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4544. observations on colour agnosia
a 56-year-old right-handed man, following the formation of a left posterior
subdural hematoma developed 'spelling dyslexia' and impaired picture
interpretation, which resolved, and color agnosia, which persisted.  the latter
impaired the use both of color information and of the names of the colors.
this may be explained as a disorder impairing the recollection and formation
of associations between color names and other types of information, with
resulting interference in any task in which colors or their names have
to be placed in a specific context.  the alternative views of willbrand (1887)
that here a limited dysphasia, and of sittig (1921) that a recognition defect
is simultaneously present, cannot be excluded.  in the present and in
previously reported cases the causative lesion seems to have been posteriorly
located in the dominant hemisphere, in the borderland between the area
receiving visual input and the language or verbal recording area.
.I 352
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652. bitemporal hemianopia
two stages can be distinguished in the development of bitemporal hemianopia
in hypophyseal tumors.  the first stage is the consequence of direct pressure
of the tumor on the lower side of the chiasma.  hence its start with upper
quadrantic field defects.  in this stage the visual disorder is amenable to
prompt and complete restoration.  with progressing growth of the tumor the
second stage follows as consequence of constriction by the circle of vessels.
in this stage nerve fibers are being destroyed.  therefore, after pressure
relieving operation no restoration occurs, or to a limited extent only.
.I 354
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1774. the speed of reading.  basis for a clinical function test
as an easily comprehensible measure for the capability of reading, the author
recommends the determination of the reading speed for supplementation of the
ocular function tests.  the method in question constitutes a senso-motor
efficiency test which is of value in the appraisal of haemianopias, paracentral
and central defects of the visual field, in squint amblyopias and in
spontaneous nystagmus.
.I 360
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1384. importance of campimetry and carotid and vertebral angiography in
thrombosis of the posterior cerebral artery
the authors report a case of thrombosis of the posterior cerebral artery which
presented only lateral homonymous hemianopia and stress the importance of
campimetry and of carotid angiography beside vertebral angiography.
.I 364
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2120. thioguanine in the treatment of certain autoimmune, immunologic and
related diseases
the therapeutic effectiveness of 6-thioguanine has been evaluated over the past
3 years in 19 patients with diverse syndromes.  only patients with severe
debilitating disease unresponsive to conventional therapy were treated.
remissions occurred in 2 of 5 patients with systemic lupus erythematosus, in 1
patient each with dermatomyositis and necrotizing angiitis, 2 patients with
psoriasis and 2 of 4 patients with atopic disease.  improvement occurred in
other patients with these diseases and in 2 of 4 patients with
neurodermatitis.  two patients with scleroderma experienced only
equivocal benefit.  significant toxicity attributable to the drug
was observed in 5 patients.  assessment of the eventual value of
these agents in therapy requires further study.  hypotheses regarding the
mechanism of action of these agents and the significance of clinical
response are discussed.
.I 368
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198. early experiences with azathioprine in ulcerative colitis.  a note of
caution
azathioprine was administered to 10 patients with ulcerative colitis classified
as 'very severe' in 2,'moderately severe' in 7 and 'relatively mild' in 1
patient, in conjunction with 'standard' therapy and adrenal corticosteroids in
8 of the 10 patients.  the possible beneficial therapeutic effects of
azathioprine in this small series cannot be evaluated definitively because of
the concurrent medication and the preliminary uncontrolled observations.
however, clinical improvement was apparent in 8 of the 10 patients; and in 2
patients, the favorable course occurred in the absence of steroid therapy.  in
2 additional patients, the favorable course was maintained during the
administration of azathioprine following the discontinuance of prolonged
steroid therapy.  in 1 patient, the administration of azathioprine was
associated with amelioration of an arthritis and pyoderma gangrenosum which did
not respond to the use of steroids and other medication.  immuno-suppressive
observations were limited.  the established delayed hypersensitivity response,
as reflected in various skin tests, was unchanged during the administration of
azathioprine.  azathioprine had no discernible toxic effects upon the kidneys
or the liver in 2 patients, 1 with postnecrotic cirrhosis and the other with
serum hepatitis.  gastro-intestinal symptoms (anorexia, epigastric discomfort,
and nausea) occurred in 8 patients.  mild to moderate leukopenia developed in 8
patients and, in 2 individuals, was accompanied by thrombocytopenia.  temporary
alopecia occurred in 1 woman.  the hematopoietic effects developed within 2 or
3 wk of therapy with azathioprine at a dosage level of 4-6 mg/kg/day.
azathioprine does not exert the rapid beneficial effect in ulcerative colitis
noted with corticotropin and adrenal corticosteroids.  therefore, its use in
severe ulcerative colitis requiring intensive therapy probably is undesirable.
azathioprine, on the basis of these initial observations, may be considered for
moderately severe ulcerative colitis, under circumstances permitting controlled
and prolonged therapeutic trial as adjunct medication, but with careful
supervision for prevention of toxicity, especially leukopenia.
.I 369
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1281. effect of fluoropyrimidines on delayed cutaneous hypersensitivity
the ability to express delayed cutaneous hypersensitivity was assessed in 51
patients with carcinoma.  evidence is presented that 5-fluorouracil and
5-fluoro-2'-deoxyuridine paradoxically potentiate this parameter of immune
responsiveness.
.I 370
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248. data on etiology, pathogenesis, treatment results and survival period in
560 patients with cirrhosis of the liver
statistics were compiled from a total of 560 cases chosen at random, of
cirrhosis of the liver.  the figures refer to the age and sex of the patients,
as well as to the etiology and the hepatic morphology.  as the date of death of
304 of the subjects was known, it was possible to calculate the survival time
after the diagnosis was made.  only 36% survived the time of diagnosis by 1
year, 16% by 3 years, and 8% by 5 years.  these figures show that modern
therapy of liver cirrhosis has up to now not succeeded to prolong the life of
the majority of the victims.  in many cases, however, it is possible to a large
extent to relieve the patients' suffering by improving the appetite and the
general condition and by eliminating ascites and periods of hemorrhage and
stupor.  particular attention should be paid to the prophylaxis of the disease
and, by studying the survival time assessments and therapeutic reports, to the
method of selection of the subjects.
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897. chronic renal diseases and pregnancy  a review
a review is given of the reciprocal relationships between chronic renal disease
and pregnancy.  after a short review of the most important changes in renal
function due to normal pregnancy, the diagnosis of chronic renal disease is
discussed.  subsequently, the following complications of pregnancy are
discussed individually  chronic pyelonephritis, chronic glomerulonephritis,
lupus erythematosus, the nephrotic syndrome, diabetic nephropathy and
polycystic disease of the kidney.  the paper is concluded by a discussion on
the influence of pregnancy on the different renal affections.
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4193. the occurrence to cytomegalovirus infections in childhood leukemia.
report of three cases
cytomegalic inclusion disease (cmid) presented the following clinical findings
in three children with acute leukemia  persistent high temperature, cough,
vomiting, diarrhea, hepatosplenomegaly, rales, and terminal icterus.
pancytopenia was present in all, including two children in leukemic remission.
roentgenographic evidence of pneumonia did not appear until the third week
after the onset of symptoms.  abnormalities in liver function tests were late
findings.  intranuclear inclusions were seen in urine sediments of two
patients.  in neither of these patients were intranuclear inclusions
demonstrable in the sputa.  virus culture from urine was done in one of these
patients and cytopathogenic changes characteristic of cytomegalovirus (cmv)
were demonstrated.  cmid was the cause of death in these three children, all
of whom had received chemotherapy with agents known to have immunosuppressive
properties.
.I 373
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   . on chorea, lupus erythematosus, and cerebral arteritis
a woman aged 33 developed chorea 10 yr after the onset of systemic lupus
erythematosus (sle).  she had experienced an asymptomatic interval of
8 yr.  the abnormal movements persisted for 5 mth, but then subsided
after short-term administration of 6-mercaptopurine.  there are 11 previous
descriptions of chorea patients with sle.  in 3 out of 4 autopsied cases,
extensive cerebral lesions due to diffuse arteritis were found.  the cns
changes were quite similar to those found in chorea minor.
.I 374
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1878. pharmacologic actions on cellular immunity
the following chapters of interest in the field of drugs and immunity processes
are included  manifestations of cellular immunity.  states of reduced
immunologic reactivity.  present status of pharmacologic immunosuppression.
tests for susceptibility of tuberculin reactions to pharmacologic action.
tests for susceptibility of transplantation immunity to pharmacologic action.
comparative susceptibilities of tuberculin and skin homotransplantation
reactions to pharmacologic action.
.I 375
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2625. chromosome aberrations in human cells following treatment with imuran
five women with various collagen diseases were studied.  bone marrow aspirates
were obtained from each patient before and 12 to 24 days after start of imuran
(azothioprine) therapy.  fifty metaphases from each sample were counted.  in
patients nos. 1 and 2 the increase in cells with structural abnormalities
during therapy is significant.  the aberrations found were mostly breaks of the
chromatid and chromosomal type.  a few abnormal chromosomes were seen,
among which a ring chromosome.  in patient no. 1 chromatid exchanges were
seen in three cells.
.I 376
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3645. autoimmune hepatitis
in 30% of 301 patients with cirrhosis, the cause was uncertain.  of these 90
cases the clinical picture of active chronic hepatitis could be recognized in
69, and 26 of these were characterized as lupoid hepatitis.  the relationship
between active chronic hepatitis, lupoid hepatitis and sle was studied in 3
groups of 25 cases each.  a comparison was then made between the possible
etiological factors, the systemic manifestations, the survival rate, the
histological appearances, the biochemical tests, the autoimmune reactions
and the results of the immunosuppressive drugs.  from this study a concept
emerged according to which a proportion of cases of cirrhosis occurring in
adequately nourished individuals can be attributed to the end result of an
autoimmune reaction.
.I 377
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766. a comparison of the effects of selected cytotoxic agents on the primary
agglutinin response in rats injected with sheep erythrocytes
a comparative study was made of the effects of several cytotoxic agents, given
at maximally tolerable doses, on the primary agglutinin response in rats
immunized with sheep erythrocytes given intraperitoneally.  antigen was given
before, at the beginning, or in the middle of a 5-day course of drug
treatment.  chlormethine (mechlorethamine), 5-fluorouracil, and
5-fluoro-2'-deoxyuridine did not suppress the primary response
significantly.  methotrexate, 6-mercaptopurine, 6-mercaptopurine roboside
and 2-amino-6-((1-methyl-4-nitro-5-imidazolyl) thio) purine
prolonged induction time and suppressed peak titer maximally
when immunization was performed one to three days prior
to drug treatment.  vinblastine did not affect peak titer, but did prolong
induction time when antigen was given 2 days prior to drug treatment.
cyclophosphamide markedly prolonged induction time and suppressed peak titer
irrespective of the time of antigen administration.  the antimetabolites
appeared to suppress maximally the intermediate stage of the primary response.
cyclophosphamide appeared to suppress all stages.
.I 378
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1959. analysis of mechanism of immunosuppressive drugs in renal
homotransplantation
dammin g. j.
a long-term study of the mechanism of action of immunosuppressive drugs has
been completed in bilaterally nephrectomized dogs with kidney homotransplants.
over 1,000 test animals with 24 different drug protocols have been analyzed.
increasing numbers of long surviving animals have posed many questions
regarding the status treated host.  the current drug protocol of azathioprine
and diazoacetylserine ('azaserine') has produced 90% 50-day survivors and 50%
100-day survivors.  the following observations have been documented  all
animals on prolonged drug therapy are immunologically competent; drug therapy
can be stopped successfully in some but not all animals; long surviving kidneys
apparently are protected in some way in the new environment because a
second donor kidney can be rejected while the first survives; retransplantation
of a long surviving kidney back to its original host did not lead to a decrease
in renal function; long surviving kidneys successfully retransplanted back
to their original donors are rejected when transplanted to third party,
non-drug treated recipients; immune paralysis does not account for the
prolonged survival because the second donor kidney which constitutes a double
dose of antigen is rejected while the first continues to survive; absorption or
metabolism of the drug does not account for the variation in results because
two kidneys, each from separate donors, can be rejected differentially in the
same drug treated host; and all hosts are sensitized against the recipient and
this sensitization continues even in those animals successfully weaned from
drugs.  additional analyses of the relationship of skin homografts and kidney
homografts reveal the following  skin homografts are universally rejected
within 20 days by hosts treated with the drug regimen which protects kidney
homografts sometimes permanently.  when skin and kidney homografts from the
same donor are placed simultaneously skin survival is prolonged while kidney
survival is shortened.  this paradoxical effect probably is explained by the
production of antibodies by skin which are absorbed by the rejecting kidney.
additional observations indicate that drug-treated animals, male and female,
are fertile and that multiple rejection processes can produce generalized
immunological picture in the host similar to an autoimmune disease process.
.I 379
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3083. myocardial toxicity of contrast agents used in angiography
the myocardial toxicity of many current and
some experimental contrast agents
has been studied in dogs, by use of a previously
unreported method of occlusion
retrograde coronary venography as well as the
familiar technique of selective
coronary arterial catheterization.  the following
conclusions appear justified in
the light of the experiments   not only the
iodine-containing radicals with which the
contrast agents are so often identified (acetrizoates,
diatrizoates, iothalamates,
etc.), but also the final salification products appear
to be responsible for the widely
divergent degrees of myocardial toxicity of contrast
agents, to the point that differ-
ent salts of the same compound behave as entirely
different agents both chemically
and biologically.  the results seem to indicate the
dominance of sodium ion and/or
the protective effect of methylglucamine salts with
respect to the myocardial toxi-
city of current radiopaque media.  reported,
yet unexplained, electrocardiographic
changes occurring within one to two seconds
from the beginning of massive caval
high-pressure injections appear to find a
causal relationship in the myocardial ir-
ritability induced by the distention of the
coronary veins and the myocardial infiltra-
tion which is intentionally enhanced with
our retrograde injection techniques.  a pe-
culiar trait, shared in varying degrees by
all radiopaque agents tested, is their
ability to increase coronary blood flow.
the clinical significance of this phenome-
non, however, remains to be established.
these studies re-emphasize the limita-
tions of the standard toxicity studies conducted
in animals.  it should be clear from
the results reported that agents to be
administered into the coronary circulation
demand investigation in regard to their
potential toxicity by the methods described
herein or variations thereof.  in fact,
similar tests should be carried out for all or-
gans to be subjected to radiographic
examination via the vascular bed.  the authors
hope that this presentation will stimulate
renewed investigation, particularly in view
of the growing clinical applications of
selective cardiovascular opacification tech-
niques.
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2476. studies on cardiac dimensions in intact,
unanesthetized man. i. description of techniques and their
validation. ii. effects of respiration. iii. effects of
muscular exercise
a method is described which permits
measurement of relative changes in the exter-
nal dimensions of individual cardiac
chambers throughout the cardiac cycle in intact,
unanaesthetized man.  it consists of
suturing multiple radiopaque silver-tantalum
clips to the surface of the heart at the
time of cardiac operations.  in the postopera-
tive period, cineradiograms are
obtained and the distances between clips are mea-
sured on each individual frame.
this technique has been found to be safe and has
been employed in 68 patients without
any complications.  as a result of studies in 8
patients utilizing biplane serial exposures,
the effects of rotation of the heart in the
sagittal plane during the cardiac and
respiratory cycles were determined precisely.
if clips were properly placed on the heart,
the possible errors resulting from such
rotation were found to be quite small.
during inspiration right ventricular dimen-
sions increased, while the opposite occurred
during expiration and during the val-
salva manoeuvre.  left ventricular dimensions
exhibited little change during normal
respiration.  during deep, slow inspiration,
the changes in dimensions of the left
ventricle lagged behind those of the right
ventricle by 1 to 5 (generally 2 or 3) car-
diac cycles; the magnitude of the changes in
the dimensions of the left ventricle was
smaller than that which occurred in the right
ventricle.  the effects on ventricular
dimensions of light muscular exercise performed
in the supine position were studied
in 9 patients.  the end-diastolic dimensions
decreased by an average of 6.0% of con-
trol in the right ventricle, and by an average of
5.1% in the left ventricle.  end-sys-
tolic dimensions decreased by an average of 5.6%
of control in the right ventricle
and by an average of 6.5% in the left ventricle.
these decreases are considered to
approximate one-half of the resting stroke volume.
in the 4 patients in whom the
rate of right ventricular pressure rise was determined
continuously, exercise re-
sulted in an elevation of dp/dt while ventricular
end-diastolic dimensions decreased.
these data are interpreted to indicate that an
increase in myocardial contractility
occurs during muscular exercise in man.
.I 381
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3765. radioactive isotope determination of myocardial blood
flow by surface counting and ratio formula
wilkinson d.
the results presented here have a large
scale error and a large scatter, so that
the authors recommend that further clinical
use of this method should not be at-
tempted.  if the coronary portion of the flow
rate curve exists, then a change in the
present instrumentation is needed to allow
use of the technique of sevelius and
johnson in defining a coronary portion of the
flow rate.  an attempt is made to
evaluate the possible source of errors.
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1379. risa-ventriculography and risa-cisternography
some general experience of the authors with
risa-ventriculography and risa-cis-
ternography is related.  they conclude that the
former technique may be particularly
useful in detecting intraventricular tumors and
internal hydrocephalus as well as
assessing the efficiency of surgical shunts; the
latter technique may be useful in
the study of normal csf circulation as well as
in cases of csf leaks, arachnoiditis
and external hydrocephalus.
.I 383
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3485. measurement of the cardiac output and ventricular
volumes by radiocardiography
cardiac output was measured by external
counting after injection of radioisotopes
(rihsa and erythrocytes-cr51).  the results
in 113 subjects, including 16 normals,
are presented and compared with the results
by other methods.  cardiac output at
rest and after exercise was compared in 65 subjects.
the principle of ventricular
volume measurement by radioisotope-cardiography is
discussed.  the results of
measurement of the ventricular volume in 17 normal
subjects and 90 patients, and
of measurement of the ventricular volume in 57 patients,
are presented.
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3762. aberrant left coronary artery
five cases of aberrant coronary artery are
presented, with emphasis on the angio-
graphic features and differentiation from
endocardial fibroelastosis.  clinical and
electrocardiographic features may suggest
the proper diagnosis, but only angio-
graphy can conclusively demonstrate the
continuity between the pulmonary artery
and the left coronary artery.  in these cases,
blood flow was from the pulmonary
artery to the coronary artery (forward) in 2
cases, and from the coronary artery
to the pulmonary artery (retrograde) in the
other 3.  when the diagnosis of aberrant
coronary artery is suspected, selective
left-sided angiocardiography should be the
angiographic procedure of choice.  the differentiation
from endocardial fibroelas-
tosis and other myocardiopathies is usually not a
problem with such a study, but
may be more difficult with intravenous angiocardiography.
with this latter type of
study, the coronary arteries are not generally visible,
but a persistently thin la-
teral aspect of the left ventricular wall should suggest
the proper diagnosis.  sub-
sequent confirmation by a left-sided injection is advisable.
.I 385
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4159. detection of heart shunts by means of i 125
external scintillation detection of a pure dilution
curve originating in the right ven-
tricle has been pursued by investigators for many
yr.  the use of the soft photons
of 125 i offers an improved method of determination
by allowing excellent collimation
through 2 mechanisms  (1) a small half value layer
of 2 cm in tissue, and (2) uni-
directionality, in part due to all-or-none photoelectric
absorption of these photons
as compared with the pluridirectionality due to compton
scatter in the case of 131 i.
in 30 normal individuals, externally detected dilution
curves from the right heart
ventricle and arterial dilution curves obtained by arterial
puncture are compared.
five hundred microcuries of 125 i are injected into an
antecubital vein.  the amount
of radiation absorbed from a 500 uc dose in an adult of
70 kilos is 1000 to 2000
mrads when injected in the form of 125 i iodide.  the use
of 125 i orthoiodohippu-
rate is advised due to its short biological half-period and
the integrated whole-body
radiation exposure is decreased 100-fold in comparison
with the 125 i iodide.  the
shape of the right heart curve is very similar to the arterial
dilution curve with a
13   5% excess of counts originating outside the right ventricle
area.  the descending
segment of the right ventricle curve has a minimum count rate
of only 12   2% of the
peak of the curve as compared with the arterial curve of 10
   2.5%.  a mean t 1/2
of the descending down slope of the right ventricle is 1.52
   0.45 sec. for the right
heart curve and 2.4   0.65 sec. for the arterial curve.
the clinical usefulness of this
procedure in 20 patients with atrial septal defects and 9
patients with ventricular sep-
tal defects is analyzed.  it seems possible to perform selective
right-heart radiocardio-
graphy by means of external precordial detection of 125 i.  the
method is simple and
reproducible.
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4160. clinical applications of quantitative radiocardiography. i.
results in normal subjects and changes with age
a technique is described for routine determinations
at the bedside of blood volume,
cardiac output and pulmonary blood volume by means
of the method of quantitative
radiocardiography.  the instrumentation is simple,
the technique is easy to perform
and causes little trouble to the patients, only one
injection of about 50 uc of rihsa
being needed.  thirty-nine patients aged 17-83 yr.,
free of cardiovascular or re-
spiratory disorders, were studied.  the results
obtained are in close agreement with
previous reports.  only the cardiac index showed a
significant decrease with age,
while the reduction of blood volume and of pulmonary
blood volume was slight.  a close
statistical correlation was found between pbv and sv,
and was interpreted as a
dependence of pbv on sv.
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2725. demonstration of myocardial infarction by photoscans of
the heart in man
intravenously injected radioiodinated oleic acid
was incorporated into heart muscle
in sufficient concentration to permit recording photoscans
of the heart in man.  in
3 fatal cases of massive septal myocardial infarction,
injection of the radioiodin-
ated fatty acid (rifa) was made during life; at necropsy
photoscans of the excised
heart showed a discrete area of absent radioactivity
corresponding to the infarcted
interventricular septum.  photoscans of the heart were
made during life in 42 pa-
tients, 9 of whom had suffered recent myocardial infarction.
there were definite
areas of deceased radioactivity corresponding to the location
of the infarction,
judged by the electrocardiogram, in 4, and probable areas of
decreased radioactivity
in 2, of the 9 cases of myocardial infarction.  the technic as
presently employed
just approaches the limits of definition of infarction in acute
cases.  modification of
the biochemical principles or further development of the
y-camera may bring the
method to a level of diagnostic usefulness.
.I 388
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2716. y-angiocardiography
recordings were made, simultaneously with
the y-cardiogram, of a pulmonary an-
giogram by means of a collimator placed in
the left scapular region and of carotid
angiogram by a collimator centered on the axis
of the external auditory canal.  the
3 curves yielded very interesting information on
the chronology of the various car-
diac cycles.  the pattern of the pulmonary and
carotid y-angiograms was valuable
in several pathologic conditions.  it is more logical
to measure the cardiac output
on the carotid curve than on the y-cardiogram,
especially if there are shunts.  the
pulmonary curve allows rectification of the time
constant of emptying of the left
cavities of the heart.  as regards chronologic
information on cardiac cycles, atten-
tion is drawn to the fact that in the pulmonary
circulation long and short circuits
can be demonstrated.  the characteristic times
can be measured.  between the time
that the radioactive material appears in the left
cavities and the time that it leaves
the carotid, there is an interval of 3-4 systoles,
which represents the time neces-
sary for left circular filling.  the validity of
calculation of the cardiac output with
the stewart-hamilton formula is discussed.
this is valid if the collimator covers
a small volume of the principal channel.  it remains
to be shown if such a calculation
is valid for larger cavities, or for 2 cavities, through
which the radioactive material
passes successively, and which have different c (t)
functions as well as for all tissue
'seen' by the collimator, some of which are not yet
irrigated with the radioactive
blood, while in other areas recirculation has already
started.  these aspects, and
their application to the pulmonary angiogram, are
discussed in detail.  with the
authors' technique, y-angiogram is
especially valuable, as correc-
tion for the time constant of the decrease of the left
peak is based on the lengthening
of this curve.  this again serves as a basis for
determining the left ventricular
volume.
.I 394
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information.
2724. primary epidermoid cancers of the lung.  electron micro-
scopic study
an electron microscopic study was made
of 8 squamous cell, 3 undifferentiated,
and 3 alveolar carcinomas of the lung on
biopsy specimens embedded in methacryl-
ate.  the squamous cell carcinomas were
found to contain cylindrical cells with
glycogen granules, scanty mitochondria,
a reticular endoplasm which was chiefly
vesicular, numerous free ribosomes,
and bundles of confluent fibrils in the desmo-
somes.  the authors also observed in
the center of the tumor nodes, cells richer
in tonofibrils which enveloped the
nucleus, and cells in which all the cytoplasmic
organelles had almost disappeared
except for tonofibrils or cells packed with
keratohyalin and even lipid granules
sometimes arranged in lamellar formations
of the myelin type.  the picture as a
whole was that so often seen in the optic
microscope tumor foci formed of
slightly differentiated cells at the periphery
which became more differentiated
as one approaches the center.  the undifferenti-
ated cells resembled more the
intermediate bronchial cells than the basal cells.
the paper does not describe the
undifferentiated and alveolar carcinomas.
.I 395
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1375. loss of neoplastic properties in vitro. ii. observations on
kb sublines
ten sublines of the kb cell line obtained from
a number of different laboratories
were reexamined with respect to chromosome
number and heterotransplantability
to the syrian hamster cheek pouch.  twelve
clonal cultures derived from 2 of these
sublines were similarly examined.  three
sublines differed from one another and
from the kb cell line originally studied,
which was heterotransplantable with inocula
of circa 10 cells.  only 2 of the sublines
could be heterotransplanted with inocula
of less than 10 4 cells; 5 were heterotransplantable
with inocula of 10 4-10 6 cells; and
2 failed to heterotransplant, even with
inocula of 10 6 cells.  similar differences in
heterotransplantability were observed
among the clonal derivatives of 2 of these
sublines.  although the modal numbers of
these sublines and clonal derivatives were
basically similar, ranging from 73 to 80,
a few lines had a chromosome of sufficient-
ly distinctive morphology to serve as a
marker.  there was, however, no apparent
correlation between these minor karyotypic
differences and heterotransplantability.
possible differences between non-heterotransplantable
and heterotransplantable
sublines with respect to the pattern of
variability in cytoplasmic protein and cyto-
plasmic ribonucleic (rna) content per cell
remain to be studied in detail.  for i of this
series of articles see exc. medica cancer, 1965, abstr. no. 2378.
.I 396
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1377. establishment of a tissue culture strain jtc-14 from actino-
mycin-induced ascites sarcoma, and its biological characters
cell line jtc-14 has been maintained for more
than 2 yr. and subcultured 93 times.
cells from the 10th subculture on subcutaneous
injection into mice produced tumors
identical with those produced by the original
cells.  judged by the time taken to kill
mice on intraperitoneal injection the tissue
culture cells were not as malignant as
the original tumor cells.  after passage in
animals the cells were easily re-established
in culture in vitro.
.I 398
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31
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2413. the presence of lymphocytes in long term cultures of
newborn mouse thymic epithelium
thymic epithelial cells derived from newborn
mouse thymic fragments were cultured
in vitro for over 22 mth.  subcultures were
started by transferring minute cell
sheets obtained by mechanical scraping of
the original culture when it was 14 mth
old or older.  lymphocytes, many of them
with the morphological appearance of
plasma cells, were seen in the subcultures.
intact lymphocytes, as well as mitotic
figures were seen within cytoplasmatic vacuoles
of the epithelial cells.  the possible
bearing of these observations on the origin of the
thymic lymphocytes is briefly
discussed.
.I 401
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31
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133. demonstration, purification, and partial characterization of ab-
normal (hsl) antigens in stable human cell lines
the existence of abnormal human stable
line (hsl) antigens common to a
number of stable human cell lines, but
absent from normal human tissues and
normal human diploid cell strains in tissue
culture, was demonstrated by agar gel
microimmunodiffusion.  hsl was detected
in hela-sj, hela-mba, hela-s3,
chang conjunctiva, syverton's embryo
esophagus, chang liver, and j-iii.  it
was not detected in henle's human intestine
or detroit-6.  it was absent from two
normal diploid strains, wi-38 and sj-dhl,
and was not found in a variety of
concentrated extracts of fresh human
organs.  hsl was not associated with
contamination by pleuropneumonia-like
organisms (pplo) of cell lines.  the
purest hsl preparations obtained from hela-sj
by ammonium sulfate fractiona-
tion yielded absorption spectra characteristic of
protein and were inactivated by
trypsin.  sephadex chromatography indicated a
particle weight of approximately
150,000; hsl was not sedimented at 125,000 x g.
in 0.02 m po4 buffer, activity
was virtually completely eliminated after 2 minutes
at 50 c., 8 minutes at 45 c.,
or 80 minutes at 40 c.  preliminary studies with
fluorescent anti-hsl globulin
indicated that hsl was not a surface antigen;
rabbit antisera to purified hsl
fractions were not cytotoxic to hela cells.
the best preparations of hsl still
contained a trace of common human antigen
and appeared to consist of multiple
components active in immunoprecipitation.
electrophoresis indicated the in-
homogeneity of this material.
.I 402
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31
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1696. further comparative studies on two isogenic cell lines of autologous
origin, one of which is tumor-producing
a single explant of normal lung tissue
from an adult female mouse c57bl provided
2 cell lines.  one remained normal
and is referred to as pg, the other became
malignant and is designated as pt.
with successive in vitro passages by tryp-
sinization the tumour-inducing capacity
of the pt line considerably decreased its
tumour-producing capacity as well
as its acrobic glycolysis coefficient, while the
pg line showed no appreciable
change.  results of chromosome studies are de-
scribed, but proved inconclusive.
similar experiments were also carried out on
cell lines derived from the pt line
and their results are discussed.
.I 403
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31
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1202. characteristics of human adenovirus type 12 induced hamster tumor
cells in tissue culture
characteristics of a human adenovirus
type 12 induced hamster tumor serially pro-
pagated in vitro are described.  these
include small cell size, epithelioid appear-
ance, rapid growth rate, resistance to
superinfection with a-12, and transplant-
ability to weanling hamsters.  these cells grew
either as monolayers or as balls of
aggregated cells detached from the glass,
depending on whether calf serum or horse
serum was added to the eagle's medium.  attempts
to demonstrate virus activity by
subculture of supernatant fluids and lysed cells into
hela cells, mixed culture with
human and hamster cells, electron microscopy,
and inoculation of newborn
hamsters with irradiated tumor cells were negative.
.I 407
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31
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2774. pitfalls in the clinical and histologic diagnosis of broncho-
genic carcinoma
a necropsy study of 380 cases of extrathoracic
carcinoma revealed that pulmonary
metastases occurred in almost 50% of the
cases and bronchial metastases in over
25%.  there were 39 cases (10.3%) in the
series with clinical features simulating
bronchogenic carcinoma and in 24 (62%)
of these cases there was cytologic and/or
histologic confirmation.  carcinomas of
the pancreas presented the greatest source
of diagnostic error accounting for more
than one-third of the 39 cases; the primary
site second in frequency was carcinoma
of the kidney.  bronchial metastases were
chiefly responsible for the clinical,
cytologic, and histologic findings compatible
with the diagnosis of bronchogenic
carcinoma.  secondary growths in the lungs may
present roentgenologically as solitary
tumors indistinguishable from primary lung
cancer.  metastatic lesions in lymph
nodes, bronchi, and lung may exhibit pleomor-
phic features simulating squamous
cell carcinoma.  the diagnosis of bronchioloalveo-
lar carcinoma in resected lung tissue
is a presumptive conclusion inasmuch as the
identical morphological features may
be reproduced by metastases from duct or
glandular carcinomas.  the simulation
of bronchogenic carcinoma by metastatic tum-
ors occurs with sufficient frequency to
challenge the diagnostic accuracy of deaths
certified as bronchogenic carcinoma
with necropsy exclusion of other primary sites.
.I 410
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31
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464. cardiac performance in hypothermia.  an experimental study of left
ventricular power, oxygen consumption, and efficiency in dogs
multiple cardiac parameters have been measured
in 30 dogs cooled to 20 c. aortic
blood temperature.  the parameters have been
expressed both as absolute values
and as percentages of normothermic values.
at normothermia, dogs with closed
chest had an ascending aorta flow of 154%
and a left ventricular external power of
183% of the corresponding values for dogs
with open chest.  both ascending aorta
flow and left circumflex coronary artery flow
were reduced to 25% of normothermic level
at 20 c.  aortic arch mean pressure was
reduced to 50% of normothermic level
at 20 c.  total peripheral resistance was
increased to 205% of normothermic level
at 20 c.  left ventricular external power
was decreased to 11% of normothermic
level at 20 c.  left ventricular oxygen
consumption was decreased to 31% of nor-
mothermic level at 20 c.  mechanical
efficiency of the left ventricular myocardium
was decreased to 39% of normothermic level at 20 c.
.I 411
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31
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3270. tolerance of dogs to deep hypothermia.  controlled and maintained with a
pump oxygenator
the advantages of hypothermia of below 10 c for 2 hr,
induced and maintained by
extracorporeal circulation of 200 min.,
were compared to partial bypass of the
same duration during normothermia.
in the normothermic group 9 dogs out of 12
lived.  in the hypothermic group 6 dogs
out of 15 (40%) survived when perfused at
the high flow of 55 cc/kg/min.  eleven
dogs out of 15 (70%) survived when the flow
rate was reduced to 25 cc/kg/min when
the temperature was below 10 c.  the death
in the high flow group were due mainly
to postperfusion lung changes even when low
pulmonary venous pressure was assured
by venting in the left atrial chamber.  me-
tabolic acidosis occurred in all groups;
though greater in the high flow, with the
low flow intermediate between the former
and the normothermic group.  this change
to a great degree, can be explained by the lung changes.
.I 413
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31
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4088. the use of hypothermia and dehydration in the treatment of severe
cerebral hypoxia
the rational for using hypothermia or
cerebral dehydration is to suppress or re-
verse progressive or delayed cerebral
damage after hypoxia.  it is suggested that
damage of this nature results from injury
to the astroglia and oligodendroglia,
especially the former.  experimental and
clinical evidence favors lowering of the
body temperature immediately after any
episode of hypoxia accompanied by impor-
tant damage to the brain.  the rational
for using dehydration is insecure and its
results are uncertain.  this treatment
should probably be reserved for cases in
which a raised cerebrospinal fluid pressure
has been proved, and in which other
measures, especially hypothermia,
are either not available or have failed.
.I 414
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7828. selective cerebral hypothermia  physiology and technic
a safe, suitable technique for producing
selective brain cooling by a perfusion
method is described.  of 15 dogs, 7 survived.
the salient features aiding survival
are discussed.  the use of a direct vasodilator
(papaverine) in the perfusate to
relieve vasospasm markedly reduced cooling time
and represented the most signi-
ficant technical advance over previously
described methods.  an acid base analysis
utilizing the siggaard-andersen curve nomogram
was performed on 4 dogs and no
significant acidosis noted during selective brain
cooling.  a definite arteriovenous
lactic acid difference developed at hypothermic
temperatures indicating the brain
may metabolize this substance in preference to
glucose at lowered brain tempera-
tures, the reasons for which were discussed.
the rate of disappearance of physi-
cally dissolved oxygen (po2) was measured
in the brain following ischemia at dif-
ferent temperatures.  the average rate of
disappearance at 20 c. was 40% of the
rate at 37 c.  the discrepancy between this
finding and the in vitro oxygen utili-
zation rate at the same temperature was discussed.
.I 416
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31
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946. respiration in hypothermia.  i. respiratory pattern and
acid-base balance in the blood
mongrel dogs, under light pentobarbital anesthesia,
were made hypothermic by im-
mersing them in ice water and then normothermic
in warm water.  in the course of
cooling, the respiratory rate and pulmonary
ventilation, after an initial increase,
were reduced as the rectal temperature fell,
and spontaneous respiration was ar-
rested at rectal temperatures of 21-25 c.
alveolar pco2 was increased, after an
initial slight lowering, with the progress of
hypothermia.  arterial ph and standard
bicarbonate (jorgensen and astrup) decreased,
and the alkalinity of the blood coh/
ch (winterstein) decreased markedly during hypothermia.
these findings suggest
both respiratory and metabolic acidosis as the
mechanisms concerned.  in the course
of rewarming all these changes disappeared rapidly
and completely though the venti-
latory stimulation observed as an initial transitory
phenomenon during cooling failed to occur.
.I 417
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31
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896. studies on blood viscosity and its significance in anesthesia
the principles for measuring blood viscosity
have been discussed.  although blood
does not behave in a newtonian manner,
the data obtained in in vitro measurement
are useful.  a modified simple method for
measuring blood viscosity relative to nor-
mal saline has been described.  there is
essentially no difference in viscosity be-
tween fresh blood and heparinized blood and between plasma and serum.
viscosity varies with the quantity and nature of proteins
in plasma and the cellular concentra-
tion.  halothane and thiopental sodium reduce
blood viscosity and seem to be indicat-
ed in conditions in which there is hemoconcentration
and a tendency for red blood
cells to aggregate.  cyclopropane, hypothermia,
and norepinephrine tend to raise
blood viscosity and would seem to be contraindicated
when the microcirculation is failing.
.I 418
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31
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4612. flow considerations in regional cerebral hypothermia
it is suggested that low flows are dangerous
and may cause anoxia either directly
or by interfering with cooling.  sixty dogs
have been subjected to local cerebral
hypothermia by the method of femoral to
carotid cooling of arterial blood with per-
fusion at a predetermined pressure rather
than predetermined flow rate.  the cir-
cuit is described and its advantages for
clinical use mentioned together with its in-
accuracies as a method of scientific investigation.
these are chiefly concerned
with maintenance of systemic blood pressure
which may require the injection of
pressor agents.  evidence for reduction in flow
at low temperatures is discussed
and evidence presented that this is not only due
to increase in viscosity but that
there is an active spasm, manifested by
'rewarming humps' which occur in the
cooling graphs.  mean carotid flow rates
were determined by a revolution counter
attached to a pump of fixed stroke volume,
the output of which was linked to the per-
fusion pressure and thus determined by the resistance.
the place of added co2
is discussed particularly in relation to the fall
in partial pressure which accompa-
nies the cooling of the blood.  the addition of 5% co2
did not increase total carotid
flows.  halothane had been used as an anesthetic
because of its sympatholytic ac-
tion.  it has increased flows by 37% and
abolished 'rewarming humps'.  rheomacro-
dex used as a priming fluid instead of blood
produced increased flow averaging 75%
but did not abolish spasm.  it is suggested that
cooling faster than 1 c. per minute
is not intrinsically dangerous if spasm is prevented
and high flow maintained by the methods described.
.I 419
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31
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4613. selective brain cooling produced by cerebral ventricular perfusion
hypothermic cerebral ventricular perfusion
was applied to dogs.  shivering appear-
ed to be directly related to the cns temperature
rather than the peripheral body
temperature.  selective heating of the brain-stem
produced panting.  rewarming
of the body was retarded by the initiation of heat
loss mechanisms controlled cen-
trally when hyperthermic perfusion was used.
shivering disappeared but panting
was unaffected by pentobarbital anesthesia.
cooling of one or both frontal areas and
the anterior part of the third ventricle did not
significantly affect the respiratory
or circulatory systems but brain-stem hypothermia
produced distinct respiratory
and circulatory reactions.  it is suggested that
cooling of the 3rd and 4th ventricu-
lar areas may be utilized for anesthetic purposes.
.I 423
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31
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3194. systemic hypothermia via gastric cooling
eight dogs underwent gastric cooling for
systemic hypothermia.  each dog was cooled
with the balloon filled with a 'safe' volume
based on weight (20 ml/kg) and subjected
to cooling with the balloon filled maximally,
but safely to a pressure of 10 mm hg.
consistently, the latter procedure was far
more efficient, averaging 2.6 times as
rapid for all degrees of hypothermia.  a
decrease in core temperature by 7 c re-
quired an average of only 28.4 minutes.
on comparison with clinical reports of hy-
pothermia induced by the usual gastric
cooling, an improved efficiency of two-fold
to three-fold is still noted.
.I 424
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31
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3820. the dubious haemopoietic
stem cell function of the lym-
phoid cells of the blood.
autoradiographic studies on
dogs
the migration, fate and turnover of
lymphoid cells in blood and bone marrow of
irradiated and non-irradiated dogs were
studied by serial autoradiography with co-
ping of the hind legs during the plasma
clearance time of h3-thymidine injected into
an anterior vein.  in irradiated dogs,
the h3-thymidine injection procedure was car-
ried out during the early recovery phase
following 250 r whole body x-irradiation.
conclusive evidence of transformation of
hematogenous bone marrow lymphoid cells
into hemopoietic precursors was not found.
however, in the light of the individual
grain counts transformation of a few lymphoid
cells into hemopoietic cells cannot be
ruled out.  the data obtained from a dog in the
very early recovery phase following
whole body irradiation strongly indicate such
a transformation.
.I 425
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31
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3927. studies on growth and cytomorphosis
in the thymo-lympha-
tic systems - with special
reference to the influence of
the thymus and the thyroid
in guinea-pigs
migratory streams of lymphocytes between
different parts of the thymo-lymphatic
system were evaluated by comparisons between
lymphocyte populations in thoracic-
duct lymph and arterial and venous blood,
especially thymic venous blood.  by re-
cording organ weights in sham-operated and
thymectomized guinea-pigs, treated
with thyroxin or untreated, the importance
of the thymus and the thyroid for growth
and regeneration in the thymo-lymphatic
system was studied.  the main results are
as follows.  there is a considerable venous
output of lymphocytes with low mito-
chondrial content (small lymphocytes) from
the thymus in normal young guinea-pigs.
this explains the much higher incidence of
small lymphocytes in blood than in tho-
racic-duct lymph.  neonatal thymectomy
causes lymphatic hypotrophy with defi-
ciency of lymphocytes and pyroninophilic
cells in relation to reticular ones.  body
growth and survival of the animals are not
affected.  in the thymus, exogenous
thyroxin most probably promotes differentiation
of large basophilic cells to small
lymphocytes, resulting in an increased output of
small lymphocytes.  in the lymph
nodes, thyroxin promotes differentiation of large
pyroninophilic cells ('transitional
cells') into immature and mature plasma cells.
the effects of thyroxin on dif-
ferentiation are followed by an increased growth
of the thymo-lymphatic organs,
characterized by an increased incidence of large
basophilic cells and increased weight
of the lymphatic organs.  growth of the thymus and
lymph nodes precedes that of
the red splenic pulp.  this delayed splenic response
is not due to a transformation
of an increased number of immigrated thymic
lymphocytes, as neonatal thymectomy
does not prevent the thyroxin-stimulated
occurrence of large basophilic cells in the
red splenic pulp.  the thyroxin-stimulated
growth of the lymphatic system is ac-
companied by an increased output of larger
lymphocytes through the thoracic
duct, resulting in an increased number of
larger lymphocytes in the blood.  in
postnatally thymectomized animals, having a
normal (or above normal) amount of
circulating small lymphocytes, thyroxin produces
a drastic decrease in the number of
small blood lymphocytes, indicating a decreased
delivery and/or increased disappear-
ance of these cells to and from the blood, respectively.
this decrease in number of small
lymphocytes is not seen in sham-operated animals.
as judged by studies of organ
weights, the thyroxin-stimulated growth and
regeneration of the lymphatic tissue
are influenced antagonistically by thymectomy
and synergistically by local factors
in involuted tissue.
.I 426
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31
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815. the origin of macrophages
from bone marrow in the rat
skin windows' and subcutaneous coverslips
were applied to rats in a study designed
to identify the tissues in which the precursors
of macrophages proliferate.  lympho-
cyte-depletion by either chronic drainage from
the thoracic duct or 400 rads of x-
irradiation failed to suppress the emigration of
macrophages or to reduce the pro-
portion of them which became labelled after an
injection of tritiated thymidine.  x-
irradiation with 750 rads suppressed
the emigration and the labelling of the exudate
macrophages.  both were restored to
normal when the tibial marrow was shielded
during irradiation.  radioactively-labelled
cell suspensions obtained from thoracic
duct lymph, lymph nodes, thymus, spleen
and bone marrow were transfused into
syngeneic recipients.  the emigration of
labelled macrophages on to coverslips
could be demonstrated only in recipients
of labelled bone marrow and spleen cells.
labelled monocytes were found in the blood
of rats which had received injections
of labelled bone marrow.  it was concluded
that in the rat, bone marrow, and to a
lesser extent spleen, are major sources of
the macrophages which emigrate into
foci of acute, non-bacterial inflammation.
.I 427
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31
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1786. studies of the
leucocyte compartment
in guinea-pig bone
marrow after acute
haemorrhage and
severe hypoxia  evidence
for a common stem-cell
after a large acute hemorrhage,
the absolute le-
vels of neutrophils, eosinophils, and
basophils in guinea
pig bone marrow are considerably
reduced.  all stages
of differentiation are involved, the
decline in myelo-
blasts and promyelocytes being
particularly marked.
exposure to severe hypoxia also
temporarily depresses
the number of marrow granulocytes.
bone marrow
lymphocytes are only slightly reduced
after a single he-
morrhage but in the later stages of
severe hypoxia their
numbers are greatly reduced.
assuming the supply of
stem cells in the bone marrow
is not unlimited, the de-
crease in marrow granulocytes
and lymphocytes follow-
ing marked erythropoietic stimulation
appears to favor
a monophyletic theory of hemopoiesis;
a heavy demand
for stem cells to differentiate into the
erythron may
temporarily restrict the
number entering the leukon.  the
hypoxic animals showed
a considerable loss of body weight
and the notable reduction
of marrow lymphocytes in the
later stages of hypoxia
may be specifically related to a
generalized atrophy of
lymphoid tissue.  using h3-thymi-
dine there is evidence
of active dna synthesis in guinea
pig metamyelocytes.
although dna-synthesis was found
in metamyelocytes of
normal marrow, after hemorrhage
these cells form a much
larger proportion of the total
synthesizing cells in the
granulocyte compartment and
also the ratio of labeled
metamyelocytes to myelocytes
is considerably increased.
microspectrophotometric
measurements of the feulgen
dna-content of metamyelo-
cytes after hemorrhage show
that there are 2 populations
of these cells.  one group has
values typical of resting or
nonsynthesizing cells but a 2nd
group shows a complete
range of dna-values up to levels
characteristic of those
found in dividing cells.  certain
small mononuclear cells
with minimal but deeply basophilic
cytoplasm are a dis-
tinctive group of dna-synthesizing
cells in marrow af-
ter hemorrhage.  morphologically,
there appears to be a
complete sequence between these
cells and procrythro-
blasts.
.I 428
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31
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3831. relative ability of parental
marrow to repopulate lethal-
ly irradiated f1 hybrids
lethally irradiate (c57bl x 101)f1 mice
injected with a mixture of 10 million
c57bl and 10 million 101 bone-marrow
cells were repopulated only by the 101
bone-marrow cells.  experiments with other
cell mixtures indicated that the 101
marrow was relatively nine times as efficient
as c57bl marrow in repopulating
lethally irradiated (c57bl x 101)f1 mice.
results from additional strain combina-
tions suggested that the behavior of the
donor marrows was not determined solely
by h-2 factors.  c57bl marrow, which
frequently regresses in irradiated f1 mice,
has shown to be relatively less capable
of repopulating the recipient than regularly
retained parental marrow.  the differences
in the relative abilities of parental mar-
rows to repopulate f1 mice cannot as yet be
fully explained.  they might be corre-
lated with physiological differences between
the parental marrows or with a micro-
environmental advantage of one hematopoietic
cell type over another in the irradiated
recipient.  immunological and physiological factors
that might favor this selective
growth are discussed.
.I 429
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31
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3832. pluripotent stem cell function
of the mouse marrow
'lymphocyte'
bone marrow from normal and polycythemic
mice was filtered through glass wool
columns to remove cells other than 'lymphocytes'.
for a given number of nucleated
cells, filtered marrow was more efficient than
the original marrow in repopulating
the spleen of an isogenic recipient previously
exposed to lethal irradiation.  the
proliferative capacity of both the filtered and
unfiltered marrow suspensions ap-
peared to be a constant function of the number
of small and medium 'lymphocytes'
present and not of any other cell type.
.I 430
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31
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2045. the effect of
unilateral limb shield-
ing on the haemopoietic
response of the
guinea-pig to gamma
irradiation
guineapigs were exposed to
150 r  -irradiation
whilst approx. 1/5 of the total bone
marrow was protect-
ed by shielding 2 limbs.  quantitative
cell counts of both
the shielded and irradiated marrow
were combined with
observations on the thymus, spleen
and blood during the
recovery period, and compared
with the effects of whole-
body irradiation.  following
whole-body irradiation
(150 r) the thymus shows a
delayed secondary cellular
depletion coinciding with a
marked splenic hyperplasia.
both phenomena were eliminated
by limb shielding.  the
lymphocytes in the irradiated
marrow of partially shiel-
ded animals continued to show
both the overshoot and the
secondary fall in numbers which
characterize recovery
from whole-body irradiation
(150 r).  after an initial fall
in numbers of erythroid and
granulocytic precursors,
the shielded marrow showed
a temporary increase in
granulocytopoiesis coinciding
with an abortive phase of
granulocytopoiesis in the irradiated
marrow.  there was
no evidence of any effective colonization
of irradiated
marrow by cells from the shielded marrow.
the signi-
ficance of these findings is discussed.
.I 431
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31
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4311. studies on intravenous transfusion
of thymus cells and
lymphnode cells.  iii. influence of
transfused thymus cells
and lymphnode cells on the bone
marrow
in rabbits transfused with thymus cells and
lymphnode cells the peripheral blood and
bone marrow were studied.  the transfusion
of thymus cells caused a peripheral
lymphocytosis and a diminution of lymphoid
cells in the bone marrow of both young
and adult rabbits.  the transfusion of lymphnode
cells resulted in a peripheral lympho-
penia, and an initial increase and a subsequent
diminution of lymphoid cells in the
bone marrow.  it is suggested that lymphoid cells
in the bone marrow may be lympho-
cytes which are stored or discharged according
to a variety of conditions.  further-
more, thymus cells are thought to mobilize
lymphocytes from the bone marrow to
the peripheral blood.
.I 432
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31
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5041. studies on hypoxia.  iii. the
differential response of the
bone marrow to primary and
secondary hypoxia
twenty-five adult male guinea pigs were
placed in a decompression chamber, at a
simulated altitude of 14,000 feet for 5 days,
then kept in ordinary air for 5 days,
and finally returned to the decompression
chamber to be subjected to hypoxia a
second time, for periods ranging from 1
to 5 days.  during this period of secondary
hypoxia quantitative studies were made
of the changes in the blood and bone marrow.
in secondary as in primary hypoxia there
is a significant increase in the nucleated
red cells of the marrow.  in secondary
hypoxia, however, there is a very marked
increase in the marrow lymphocytes,
whereas in primary hypoxia the lymphocytes
fall.  the marrow reticulocytes remain
at a fairly constant level despite marked
fluctuations in erythropoiesis.
.I 433
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31
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1044. an investigation of lymphocyte
production in guinea-pig
bone marrow
evidence from a variety of experiments indicates
that lymphocytes are produced in
guinea-pig bone marrow.  under certain conditions
the numbers produced appear to
be considerable.  during recovery from irradiation
there are numerous telophases
in marrow smears which appear to be forming small
lymphocytes.  moreover, many
lymphocytes are still found in shielded bone marrow
after the rest of the body, in-
cluding the conventional lymphoid tissues, has
received lethal or supra-lethal irra-
diation.  almost 50% of these cells are formed
after the irradiation.  finally, when
bone marrow is cultured in the peritoneal cavity
of a host whose own lymphocyte
production has been suppressed by irradiation,
small percentages of newly-formed
small lymphocytes are found in this marrow.
.I 434
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103. repopulation of bone marrow
in mice  number and type of
cells required for
post-x-irradiation protection
fractionation of cells from mouse bone
marrow and autologous mouse spleen indi-
cates that the cell responsible for bone
marrow repopulation and x-irradiation
protection resembles the small lymphocyte.
experiments with injection of different
numbers of bone marrow and spleen cells
and observations on survival obtained by
fractional irradiation of the entire body and
of extirpation of the shielded spleen
after irradiation indicate that approximately
3 x 10 4 cells of this type are required
to provide 50% survival, and that approximately
this number migrates from the
shielded extremity or spleen of a mouse per hour
(slightly faster for spleen and slower for bone marrow).
.I 435
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104. hyperbasophilic cells as an
indication of proliferation of
bone marrow transplanted to
irradiated dogs
a study was made of hyperbasophilic cells
which appeared following transplantation
of bone marrow to 20 irradiated mongrel
dogs of both sexes.  in the main series of
experiments the animals were irradiated
with a dosage of 600 r., using a four-tube
rum-3 x-ray machine  voltage 200 kv,
current 10 ma, filters 0.5 cu mm + 1.0
mm.al, target distance 60 cm., rate
18-22 r./min.  at 1-2 days after irradiation,
a suspension of bone marrow cells in a
dosage of 10 9 - 5 x 10 9 nuclear cells was
administered i.v.  the marrow was
obtained by aspiration from various skeletal
bones or by compression from the
sternum, ribs and other bones.  a study was made
of the morphological composition
of the blood and bone marrow before irradiation
and at 1-5, 10, 15, 20, 25 and 30
days after irradiation and transfusion of bone mar-
row, and thereafter at 10-15 days
intervals.  smears of blood and marrow were
stained with azure-ii-eosin.  it was
found that distinctive cells with basophilic proto-
plasm and frequent incidence of an
immature nucleus were present in the blood of
dogs following irradiation with 600 r.
and transplantation of bone marrow.  hyper-
basophilic cells appeared in the blood
at 2 - 4 days after transplantation and attained
a maximum 14 - 21 days later; thereafter
their number diminished rapidly.  the
trend of number of hyperbasophilic cells
coincided with that of other donor elements
(leukocytes, erythrocytes).  hyperbasophilic
cells were not found during acute radia-
tion sickness in dogs which were not given
injections of bone marrow.  they were
found 3 mth. after transplantation of bone
marrow to nonirradiated puppies at 2-3
days of age.  when the irradiation dosage
was increased to 800-1,000 r., the number
of hyperbasophilic cells increased and
attained a peak sooner than after the 600 r.
dosage.  such cells were formed from
the donor cells.
.I 436
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172. autoradiographic
studies of lymphoid
cells in blood and
bone marrow of nor-
mal and irradiated
dogs
the migration, fate, and
turnover of lymphoid
cells in blood and bone marrow
of 4 irradiated and 4 non-
irradiated dogs were studied
by serial autoradiography
with clamping of the hind legs
during the plasma clear-
ance time of h3-thymidine
injected into an anterior
vein.  in irradiated dogs, the
h3-thymidine injection pro-
cedure was carried out during
the early recovery phase
after 250 r of whole-body
x-irradiation.  the results on
2 irradiated and 2 normal
dogs were described in de-
tail.  migration of lymphoid
cells from blood to marrow
parenchyma was confirmed
in the irradiated dogs.  con-
clusive evidence of transformation
of these cells into
hemopoietic precursors was not
found.  the relative
number of large lymphoid cells,
the labeling index of
the whole population of lymphoid
cells, and that of small
lymphoid cells were increased
in irradiated marrow;
few initially labeled small
lymphoid cells could also be
observed.  these data indicate
that the pattern of pro-
liferation of lymphoid cells is
changed in irradiated re-
generating bone marrow.
.I 437
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175. lysozyme in bone
marrow and periph-
eral blood cells
by means of an indirect
histochemical technique,
the intracellular lysozyme of
the formed elements of the
peripheral blood and bone marrow
was estimated.  evi-
dence is presented that monocytes,
as well as mature
neutrophils and their precursors
extending back to the
progranulocyte, contain significant
amounts of this en-
zyme.  a rare mature eosinophil
demonstrated a trace
of lysozyme activity.  there was
no evidence of lyso-
zyme activity in basophils,
erythrocytes, megakaryo-
cytes, platelets, plasma
cells, tissue mast cells or
bone marrow
reticuloendothelial cells.
.I 438
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1770. proliferative activity of the
lymphatic tissues of rats as
studied with tritium-labelled
thymidine
cytokinetic data are presented, employing
quantitation of h3dna in the lymphatic
tissues of normal rats serially sacrificed
after h3tdr administration.  a marked
difference in the patterns of initial labeling
and label loss was observed between the
thymus and peripheral lymphatic tissue.
the data are compatible with other indica-
tions of rapid cell renewal in the thymus.
there is suppression of initial uptake of
h3tdr into the dna of each large lymphocytic
progenitor cell in the thymus, appa-
rently because of a feedback of thymidine
containing material from small lympho-
cytes in the thymus.  depletion of the thymus
of small cells, as by operative stress
or whole body x-ray, leads to a marked
increase in the uptake of h3tdr into the
dna of large thymocytes.  this finding,
which is in agreement with the previous
findings of sugino et al. suggesting transfer
of thymine nucleotides from small thy-
mus lymphocytes to precursor cells, may or
may not be related to the apparent
transfer of dna label between thymic cells.
the evidence for the latter consists of
the curvilinear dilution of the dna label in
the thymus proliferating cell population
and the relationship between the rate of dna
label dilution in large cells and the
dna in the small cells in the thymus.  after
the dna label in progenitor cells in
the thymus and lymph nodes has entered the
small cell population, the subsequent
dilution of grains in these dividing cells follows
the same slope as the loss of radio-
activity from the entire lymph node.  there is a
long retention of some h3dna label
in the dividing lymph node cell population.  this
suggests that the loss of radioacti-
vity from the dividing cells and from the small
cell population as a whole occurs e-
qually.  this pattern prevails regardless of
whether the percentage of large and
small cells is altered experimentally.  these
findings can be explained by an inter-
change of the dna nuclear label between small
lymphocytes and large lymphocytes.
this could occur by some process such as
phagocytosis or pinocytosis, or by trans-
formation of the small lymphocyte into a large,
dividing cell.  the data fit best with
the latter possibility.  all or any of these
mechanisms would lead to an equilibration
of the dna label between large and small
cells.  this finding prevents the assign-
ment of a finite life span to lymphocytes on
the basis of dna labeling kinetics.  ne-
vertheless, there appear to be at least two
different types of lymphocytes.  one,
the 'thymus-type' lymphocyte, is found in the
thymus cortex, bone marrow and ger-
minal centers of lymphoid follicles.  the other
type, found abundantly in the wide-
spread peripheral lymphatic tissue, shows a
very prolonged retention of dna la-
bel and is believed to be recirculating,
'immunologically committed' cells described
by others.  these cells do not appear to
enter the thymus cortex.
.I 439
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6674. the free and glucuronic acid-bound
17-hydroxy-corticosteroids in the
plasma of patients with cancer of the
breast on i.v. infusion of acth
seventeen patients with advanced mammary
cancer were given an infusion with
3 u. of acth in 5 hr. and 6 others an infusion
of 25 u.  determinations were made
of the plasma 17-hydroxy-corticosteroids,
free and bound to glucuronic acid both
before and after the infusion.  in rapidly
growing carcinomas, high initial values
were found for the free corticosteroids
(more than 20 ug./100 ml. of plasma).
the ratio of free to bound corticosteroids is
for stage iv patients 1.8 on the average,
and approximately 1 for the mixed
forms stage iv + m.  these ratios are not
altered by acth.  shifts in the ratio
of free to bound corticosteroids with acth
treatment can be seen, depending on
the initial value of the free corticosteroids.
the administration of 3 u. is enough
and the 5 hr. value is some 70%, related to a
maximal stimulation with 25 u.
.I 440
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4179. reduced estriol excretion in patients
with breast cancer prior to endocrine
therapy
the urinary quotient of estriol/estrone +
estradiol-17b(eq) was measured chemically in
women with and without breast cancer, as an in-
dex of the ratio of noncarcinogenic impeded es-
trogens to mammary carcinogenic estrogens.  in
34 controls, the median eq was 1.3 before and 1.2
after menopause, with only 21% of the patients sub-
normal.  in 26 breast cancer patients without endo-
crine treatment or recent surgery, the median eq
was 0.5 and 0.8 respectively, with 62% of the pa-
tients subnormal.  after major surgery or hormo-
nal therapy, only 23% of 53 patients were subnor-
mal, no remissions being observed unless the eq
rose toward normal.  matching of 24 controls and
patients in pairs by age and ovarian status in the
wilcoxon test indicated that the decreased eq ex-
creted in untreated cancer was significant at the
0.2% confidence level.  the marked increase in eq
induced by castration and androgen, estrogen, and
corticosteroid therapy suggests that normaliza-
tion of a precancerous metabolic imbalance be-
tween impeded and active estrogens derived from
ovarian and adrenocortical sources contributed to
arrested growth of estradiol-dependent metastases.
.I 441
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1107. urinary excretion of estrone,
estradiol and estriol by pa-
tients with breast cancer and
benign breast disease
premenopausal patients with breast cancer
and benign breast disease appear to ex-
crete a significantly lower percentage of
the total estrogen as estrone and a signifi-
cantly higher percentage as estriol than
women in the premenopausal control group.
there was no significant difference in the
excretion of total estrogen between cancer
groups and controls in good health.
postmenopausal patients with cancer excreted
higher levels of estriol than postmenopausal
control groups.  the increase in estriol
excretion cannot be explained by debilitation.
.I 442
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5323. systemic effects of androgenic
and estrogenic hormones in advanced
breast cancer
the systemic effects of diethylstilbestrol
(45 patients), testosterone propionate
(48 patients), and both hormones (22 patients)
were studied during the treatment
(six weeks to over three months) of advanced
breast cancer in postmenopausal
women.  serious complications included
induced hypercalcemia and fluid re-
tention.  physiologic effects such as
urinary incontinence (diethylstilbestrol),
virilization (testosterone), or nausea and
vomiting did not necessitate disconti-
nuance of treatment.  androgenic therapy
stimulated erythropoiesis.  observa-
tions on the systemic reactions to these
hormonal agents definitely contribute to
the evaluation of sex steroid therapy.
.I 443
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3478. the effect of dehydroepiandrosterone
on the 17-hydroxycorti-
costeroids in the plasma in various stages
of cancer and other diseases of
the breast
the reducing effect of dehydroepiandrosterone
on the plasma corticosteroids is
on the average shortened in advanced
(stage iv) cases of breast cancer.  in 3
groups of patients, the lowest corticosteroid
levels were found up to 6 hr. after
infusion of dehydroepiandrosterone-phosphate.
in patients with mastopathy the
effect was still detectable 12 hr. later; in patients
with breast cancer in stage iv the
initial levels were reached at that time.  in
cases with stages i and ii lesions, the
findings were intermediate.  the shortening
is attributed to a more intensive
transformation of dehydroepiandrosterone in
advanced cases of breast cancer.
.I 444
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5274. urinary excretion of estrone,
estradiol and estriol by patients with
prostatic cancer and benign prostatic
hypertrophy
and hopkins c.e.
urinary estrone, estradiol, and estriol
fractions excreted by 21 patients with
prostatic cancer, 17 patients with benign
hypertrophy, and 59 clinically well
subjects were assayed to determine whether
differences exist.  absolute levels of
estrone, estradiol, and estriol fractions were
not significantly different.  the
excretion of relatively lower levels of estrone
and estradiol, and relatively higher
levels of estriol by patients with prostatic
cancer compared to clinically well
subjects resulted in significantly lower
proportions of the total estrogen being
excreted as estrone and estradiol.  differences in
the proportions of estrogen frac-
tions between patients with benign hypertrophy
and clinically well subjects were
not significant.  with the exception of a significantly
higher percentage of the total
estrogen being excreted as estrone by the patients
with benign hypertrophy,
differences between that group and the cancer
group were also not significant.
clinical variations between the 3 groups, and
within the cancer and hypertrophy
groups, preclude assignment of significant
differences to prostatic dystrophies
alone.  cancer patients experiencing inanition
due to a loss of appetite excreted
significantly lower levels of estrone than patients
who reported no loss of appetite.
significantly lower levels of estrone were excreted
by patients with benign hyper-
trophy hospitalized 6 days or more compared to
patients hospitalized 5 days or less.
a significantly higher urinary estrone-androsterone
ratio was present in the cancer
group than in the clinically well group.  it is not
believed, however, that an arbi-
trary ratio can be used to suggest an internal
estrogen-androgen imbalance.
.I 449
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414. estimation of the urinary
17-ketosteroids in the diagnosis of car-
cinoma of the prostate
in 33 patients with histologically
confirmed carcinoma and in 37 patients with
confirmed benign hyperplasia of the
prostate the amount of neutral 17-ketosteroids
was estimated in 24-hr. samples of
urine.  the results revealed that, contrary to
reports in the literature, this diagnostic
method is quite unreliable.  raised
17-ketosteroid levels were found also in
a high percentage of control subjects.
moreover, the estimation of 17-ketosteroids
is a very laborious biochemical
method and involves a relatively great
experimental error.
.I 450
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2820. influence of small doses of corticosteroids
on the excretion of pregnanetriol and oestrone
in a series of patients with breast cancer
excretion of oestrone and pregnanetriol
was determined.  with administration of
corticosteroids oestrone excretion in
postmenopausal women diminished   67%.
a decrease of pregnanetriol ex-
cretion values was observed as well.  evidently
a low oestrone excretion in patients
subjected to corticosteroid therapy is due to a
depression of the adrenal function.
.I 453
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5319. urinary porter-silber chromogens
following intravenous metho-
pyrapone and acth in patients with breast cancer
urinary porter-silber chromogens have been
measured in 2 groups of patients
with breast cancer before, during and after
intravenous methopyrapone and
acth administration.  the control group
consisted of females free of disease
5 years or more following mastectomy while
the study group had documented
metastatic disease.  no significant difference in
the urinary porter-silber chromo-
gens was found between the 2 groups on any day
during the course of the study and
were within the range of normal as measured
in this laboratory.  it is concluded
that the functional reserve capacity for both
pituitary acth secretion and adreno-
cortical steroidogenesis in patients with
advanced metastatic breast cancer is rela-
tively normal.
.I 454
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2349. amyloidosis in the autopsy material of the pathology department of
tuberculosis institute, warsaw, in 1945-1962
the autopsy material of the pathology
department of the tuberculosis institute, in
1945-1962, included 1218 postmortem
examinations of patients who died from tuberculo-
sis.  in 111 cases tuberculosis was
complicated by amyloidosis.  in 1945-1957 amy-
loidosis accounted for 8.7% of the cases;
in 1958-1962 this percentage was 10.8.
there was no difference in the incidence
between men and women, the only difference
between the two sexes was that the peak
tuberculosis fatality curve in men was in
the 40-60 years age group, and that of
amyloidosis at the 20-30 age group, while in
women the greatest number of death from
tuberculosis was in the 20-30 age group,
and from amyloidosis in the 30-40 age group.
.I 455
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766. certain features of the haemogram in patients with pulmonary tuberculosis
complicated by amyloidosis (russian)
regression of amyloidosis in the early stages
seems possible and for this reason
russian clinicians are exploring the possibilities
of finding means of early diagnosis
of this complication.  the author studied 300
complete clinical blood analyses made
in 60 patients, viz. 30 with chronic fibrocavernous
and cirrhotic forms of tb com-
plicated by amyloidosis and 30 with the same forms
of tb without amyloidosis.  from
detailed serial study of the haemogram in patients
with pulmonary tb it is possible
to diagnose associated amyloidosis of the internal
organs in its initial stage.  the
presence of amyloidosis of the internal organs can
be inferred from the following
changes in the blood picture  (a) the appearance of
normochromic and hypochromic
anaemia in patients with various forms of tb (with
the exception of tb of the kidneys,
intestinal tract or larynx, and of caseous lymph
nodes), (b) progressive increase
in the leucocyte count with a neutrophil shift to
the left not corresponding with a
phase of quiescence of the main disease, (c) consistently
high esr in the absence
of an active process, (d) thrombocytosis in the phase of
subsidence of a flare-up,
and also changes in the thrombocytic formula tending
towards the appearance of de-
generative forms and old and mature thrombocytes.
.I 456
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1319. diffuse tracheo-bronchial amyloidosis  a rare variant of a protean disease
a patient with diffuse tracheo-bronchial
amyloidosis is described; brief clinical
details supplement those published in a
previous report (prowse,1958) and are
followed by an account of the necropsy
findings and the histological appearances
at the site of amyloid deposition.  the
literature is reviewed and arguments are
advanced in favour of a common aetiology
for amyloidosis in all its forms.  if this
acts through the immunity mechanism, it is
suggested that variations in the site,
strength, duration, and frequency of the
antigen stimulus and the antibody response
may determine the nature and distribution
of the amyloid deposits.
.I 457
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2091. modern methods of treatment of visceral amyloidosis in patients with
pulmonary tuberculosis (russian)
the immediate and long-term results of
treatment during 1945-1962 of 414 patients
with pulmonary tuberculosis complicated
by amyloidosis were studied.  hormonal
(corticosteroid) therapy is the pathogenetic
treatment for visceral amyloidosis and
is indicated in the proteinuric and early
edema-hypotonic phase of amyloidosis when
the functional capacity of the kidneys and
the liver is still adequate.  in the azotemic
phase of amyloidosis, hormonal (corticosteroid)
therapy is not indicated, since it
leads to rapid deterioration in the patient's
condition.  since hypoxemia is one of the
main factors in the pathogenesis of amyloidosis,
oxygen therapy is rational patho-
genetic therapy for patients with pulmonary
tuberculosis complicated by hypoxemia
and with symptoms of the proteinuric or
edema-hypotonic phase of amyloidosis
(without ascites), in the form of
subcutaneous introduction of oxygen or oxy-
geno-peritoneum.  in patients with
pulmonary tuberculosis surgical interven-
tion on account of the main process
is indicated only in the early stages of amyloi-
dosis when pronounced functional
disorders of the kidneys and liver are absent.  co-
joint therapy using protein vitamins
(particularly ascorbic acid), hormonal (corticos-
teroid) preparations, oxygen and
desensitizing agents and elimination of all foci of
infection is indicated in treatment
of pulmonary tuberculosis with even the earliest
signs of amyloidosis.
.I 458
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2317. the use of needle biopsy of the liver in the diagnosis of visceral
amyloidosis in patients with pulmonary tuberculosis (russian)
the results of 86 puncture biopsies of the
liver in 84 patients with pulmonary tuber-
culosis (55 men and 31 women aged from
18 to 73 yr.) for the purpose of diagnosing
amyloidosis are reported.  puncture was
performed when amyloidosis was suspected
on the basis of the case history (destructive
process of more than 2-3 years' duration),
clinical signs in the form of enlargement of
the liver and spleen, edema, changes
in the blood picture and blood protein formula,
and changes in the urine (proteinuria,
cylindruria, isohyposthenuria).  amyloidosis
was diagnosed or its presence surmised
before puncture in 23 patients; the puncture
biopsy confirmed the diagnosis in 14
and refuted it in 9 of them.  in 8 patients without
clinical symptoms, amyloidosis
was diagnosed on the basis of the puncture biopsy
alone.  in 9 cases with fatal out-
come, the post-mortem findings coincided with
the results of the bioptic puncture.
of the 62 patients in whom amyloidosis was not
detected by biopsy, 31 had moderate
dystrophic changes and 9 had marked dystrophic
changes while in 22 cases no patho-
logical changes were found; 6 of these patients
later developed amyloidosis.  these
findings supported the contention that liver
amyloidosis is linked with dystrophic
changes in the epithelial cells.  marked
dystrophic changes can precede amyloidosis
or may occur simultaneously with it.  moderate
dystrophic changes are quite common
in patients with an exacerbating tuberculous
process in the lungs.  the wide applica-
tion of bioptic puncture of the liver in indicated
cases can increase our knowledge
of the morphological changes taking place in the
liver in tb.
.I 459
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2701. the role of certain additional factors in the development of amyloidosis,
and its prophylaxis in patients with pulmonary tuberculosis (russian)
in patients with chronic fibrocavernous
tuberculosis of the lungs, any toxic-aller-
gic side reactions to antibacterial therapy,
chronic foci or infection and diseases
with an allergic component can contribute
to the development of amyloidosis.  the
early detection and clearing of chronic
foci of infection and effective measures
against even mildly pronounced toxic-allergic
side reactions are of prime impor-
tance in the prevention of amyloidosis.  the
unsystematic and prolonged administra-
tion of antibacterial preparations, along with
their toxic side effects, tends to in-
crease the incidence of amyloidosis in patients
with chronic fibrocavernous pulmon-
ary tb.  individual constitutional factors are
of great importance in the development
of side effects.  side reactions to chemopreparations,
in cases of hypofunction of
the liver and kidneys and autonomic
dysfunction promote the development of dys-
trophic processes, as is confirmed
by the high frequency of toxic-allergic reac-
tions in patients with fibrocavernous
pulmonary tb who later develop amyloidosis.
the administration of desensitizing drugs
to patients showing side reactions there-
fore helps to prevent amyloidosis in cases
of chronic fibrocavernous tb, and chemo-
therapy should be automatically combined
with the administration of desensitizing
and stimulatory drugs in this class of case.
.I 460
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1835. the decrease of the steroids in the urine in the course of lung tb.
(the therapeutic value of their increase after calciferol)
quantitative determination of the urinary
steroids in 38 patients with extensive ul-
cero-caseous pulmonary tb confirmed
that the 17-ketosteroids are always decreased
in these cases.  calciferol, in the form
of one ampoule of vit.  d2 of 600,000 u.
every 10 days, in combination with active
tuberculostatic drugs, in the majority of
the cases leads to an increase of the
urinary 17-ketosteroids from 50 to 100% in 2
mth.  it appears that the calciferol
exerts its action through proteolysis; it stimulates
the liquefaction and evacuation of the
caseous material.  this proteolytic effect is
related to that of the mineralocorticoids,
which are phlogistic and proteolytic sub-
stances.  calciferol offers the advantage
over these substances that it does not affect
the electrolytes and is well tolerated by
the organism.  for this reason, good results
may be expected from its administration
in cases of extensive pulmonary tb, in
which the myc. tuberculosis has remained
sensitive to the administered tuberculostic
drugs but nevertheless does not proceed
towards recovery because of the marked caseous
lesions.  in such cases calciferol treatment
leads to a rapid and pronounced decrease
of the radiological shadows, improves the
general condition and also modifies the
steroid metabolism rendered abnormal by the disease.
.I 462
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2216. the relations between lupus erythematosus and diseases of the
lympho-reticular system
a case report of a patient with led
(aged 48 years), who developed secondarily
a lymphoblastic sarcoma.  when the
sarcomatous degeneration of the lympho-
reticular system became apparent,
the serological and immuno-hematological tests,
typical for led, were negative.  to
interpret the observation, 62 further patients
with lymphogranuloma, lymphosarcoma,
leukemias, other malignant tumors, sar-
coidosis, and tuberculosis were investigated
serologically and immunohematolo-
gically.  antinuclear factors were found in
serum of 4 patients with lymphogranulo-
ma, one patient with anaplastic carcinoma,
and one patient with metastasizing
mixed parotid-tumor.  the identity of the
antinuclear antibodies with those found in
led could not be proved by different methods.
the importance of certain diseases
of the lympho-reticular system for the production
of antinuclear factors was dis-
cussed.
.I 464
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564. tumoral amyloidosis of the lung
an incidental finding at necropsy on a woman
aged 95 was a tumor-like mass, 8.5
x 6.5 x 6 cm., in the lower lobe of the left lung.
the detailed structure of this
may suggested angioma of hamartoma; the stroma
and some vessels contained
amyloid.  amyloid is not uncommon in the stroma
of tumors.  a summary of 17
tumoral amyloid cases reported by others is included.
.I 465
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7364. experimental amyloidosis in immunity
much of interest in the mechanism of
experimental amyloidosis as a result of the
parenteral introduction of foreign protein
has been centered around the nature of
the links leading to cytological and biochemical
changes in tissues and body fluids.
some of the authors suggested that such links
may be of immunological nature.
there is however, no clear-cut proof either
in favor of or against the theory of an
immunological origin of amyloid.  since
injection of proteins during the perinatal
period prevents an immune response when
the animal is subsequently challenged
with the same antigen, the authors studied
amyloidosis caused by casein in mice
treated after birth with this protein.  mice
exposed soon after birth to casein ac-
quire an immune tolerance to this antigen.
this was demonstrated by the absence
of circulating antibodies as measured by the
disappearance of i-labeled casein
from the circulation and by means of passive
hemagglutination tests with ascitic
fluids.  both tolerant and control animals
developed amyloidosis to the same extent.
the results imply that the pathogenesis of
amyloidosis does not rest upon a classic
immunological basis; they do not exclude
the possibility, that the disease may be
due to some auto-immune process.
.I 469
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3724. the bacterial induction of homograft sensitivity. ii. effects of
sensitization with staphylococci and other microorganisms
heat-killed strains of staph. aureus and staph.
albus can induce in guinea pigs a
state of altered reactivity to skin homografts
which is indistinguishable from that
which results from sensitization with homologous
tissues or group a streptococci.
challenge of suitably prepared recipients
with 1st-set skin homografts obtained
from unrelated randomly selected donors
elicits white graft reactions or accelera-
ted rejections of such grafts.  other bacteria
tested included lancefield streptococcal
groups b, c, d, e, g, h, l, and o,
pneumococcus types ii, iii, xiv and a rough
strain, c. xerosis, b. subtilis, e. coli,
a. aerogenes, s. typhimurium, pr. vul-
garis, n. catarrhalis, h. influenzae, and
2 human virulent strains of myc. tuber-
culosis.  none of these microorganisms was
active in the induction of homograft
sensitivity in the guinea pig.  pretreatment of
recipients with gram-negative bac-
terial suspensions was associated with a slight
increase in the mean survival time
of 1st-set skin homografts.  results of this study
suggest the presence in staphylo-
cocci, as well as in group a streptococci, of antigens
related in their biologic ef-
fects to tissue transplantation antigens.
.I 470
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6590. structure and function of cross-linked dna. i. reversible denaturation and
bacillus subtilis transformation
reaction of nitrous acid with dna
results in covalent linkage of complementary
polynucleotide strands.  the resulting
material denatures reversibly and retains
biological activity in bacterial transformation.
.I 471
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4958. the mechanism of messenger-rna replication in bacteria
the transformation of bacillus subtilis
sb25 his-tryp-by two linked genetic mar-
kers under the action of hybrid molecules
of dna was investigated.  the molecular
hybrids were obtained by thermal denaturation
and annealing of a mixture of two
dna's, each one extracted from a single
auxotrophic strain (h25 his-and 168 tryp-).
the formation of the heterozygous dna
double helices was proved by special experi-
ments.  the transformation procedure
excluded dna synthesis by recipient cells
prior to the formation of enzymes for
histidine and tryptophane synthesis.  it was
found that heterozygous molecules of
dna are able to transform in these conditions
the double auxotrophic cells to prototrophic
ones.  this means that both strands of
the dna double helix can serve as templates
for the m-rna synthesis.  the possi-
bility of a secondary replication of m-rna
outside the chromosome under the action
of rna-polymerases, using rna as a primer,
is discussed.
.I 472
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2567. the molecular basis of histidase induction in bacillus subtilis
bacillus subtilis growing at 37  on
glutamate, as only carbon source, is induced
to form histidase by l-histidine.  this
enzyme, converting histidine to urocanic
acid, was isolated in a purified form.
a highly sensitive and convenient assay for
the induced enzyme is described and
applied to show that histidase appears in the
cell 5 min. after addition of the inducer.
histidase-synthesizing capacity appears
after 2 min. and decays exponentially after
addition of actinomycin (an inhibitor
of dna-dependent rna synthesis).  the
half-time value of histidase-synthesizing
capacity of 2.4 is high, compared with the
half-time value of messenger rna.
the histidase formation after addition of
actinomycin was not only due to protein
synthesis directed by accumulated m-rna
but also by conversion of an enzymatical-
ly inactive protein, present on the moment
of actinomycin addition and product of
the specific m-rna, to the active enzyme.
the existence of this enzyme pre-
cursor was shown by means of experiments
performed in the presence of chlor-
amphenicof.  finally, numerical values for
the steady state of histidase synthesis,
reached 9 min. after addition of the inducer,
are calculated, on the basis of ki-
netics of histidase synthetic capacity, precursor
and enzyme formation  the cell
contains sufficient precursor to form
approximately 100 molecules of histidase.
the cell produces approximately 50
molecules histidase per min.  the cell ac-
quires and loses, every minute, the
capacity to make 15 molecules of histidase
per minute.  the maximal enzyme
level is 15,000 molecules per cell.
.I 473
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2542. symposium on the fine structure and replication of bacteria and their
parts. ii. bacterial cytoplasm
comparison of the fine structure of the
cytoplasm of the bacterial cell with that of
the 'cell in general' reveals important
differences leading to the conclusion that, in
the bacterial cytoplasm, there is little
differentiation into separate functional en-
tities.  there is no nuclear membrane, and
fine fibrils appear to extend from the nucleo-
plasm into the cytoplasm where they may
expand in all directions.  the cytoplasm is not
necessarily intersected by membranous
profiles of special configuration, as is borne
out by e. coli b and other gram-negative
organisms.  when membranous profiles
of special configuration are present, as
in the gram-positive b. subtilis, these
do not appear differentiated into clearly
definable endoplasmic reticulum, golgi
substance, microbodies, etc., and mitochondria.
as for kinetosomes, the presence
of centrioles is perhaps not very likely.  the
experiments in which tellurite is re-
duced in the cells suggest that there are
structures at the base of the flagella with
reductive capacity.  however, upon application
of the tetranitro-blue tetrazolium
technic to b. subtilis, these are not stained.
they are presumably identical with
basal granules.  the membranous structures
in b. subtilis are called chondrioids
by the author because probably one of their
functions is that they are the sites of
the respiratory enzyme chain.  in the
gram-negative p. vulgaris, the probable site
of the respiratory chain has a structure
very different from that in the bacillus; it
is not clear whether membranes are
involved in their structure.  morphologically,
even in b. subtilis chondrioids differ
fundamentally from the mitochondria in that
they are not built up from composite
membranes, they are extensions of the plasma
membrane, and they may not be completely
closed systems.  regarding this last
point, it was observed that chondrioids may
possibly stand in open connection with
the cell's environment, since its lumen is not
separated from the cell wall by a
plasma membrane.  although as yet nothing is
known about this, it does not seem to
be precluded that these membranous organelles
may function also as intracellular
transport systems.  contrary to porter's ideas
about er, the chondrioids are not
extensions of a nuclear envelope, but of the
plasma membrane.  on the other hand,
they are in the nuclear area, in direct contact
with the nucleoplasm, and therefore,
perhaps, they need not carry in their interior
some dna, as is now becoming known
for ordinary mitochondria.  the chromatophore
vesicle is of a simple structure and
in connection with the plasma membrane.  it is
covered by a single membrane and
thus resembles the granum disc, but it is much
smaller.  in tissue cells, an im-
portant function of the er is the support of protein
synthesis by ribosomes bound
to their surfaces.  evidence is now accumulating
that the active complexes for poly-
peptide synthesis in bacteria are also membrane-bound
and are series of 70s ribo-
somes using the same messenger rna molecule.
it remains a contradictory situ-
ation that the particles obtained here through release
of cytoplasm from protoplasts
in diluted, rather crude fixing media, and identified
as ribosomes, could not be
recognized as such in thin sections of the ryter-kellenberger
fixed protoplasts.
this point is much in need of clarification.  but
even if the cytoplasm in the thin
sections of the protoplasts is in a state of
dispersion brought about artificially, it
is still apparent from the various micrographs
that basically the cytoplasm is a
network of presumably linear arrays, with many
interconnections due to fibrillar
systems.  fibrils from the nucleoplasm penetrate
deeply into the cytoplasm.  the
presence of fine fibrils of various thicknesses,
electron densities, and orientations
makes high-resolution study of the cytoplasmic
details an intriguing prospect from
which much fundamental information can be
gained.  the organizational pattern on
the ultrastructural level in bacteria reveals
fundamental similarities and divergen-
cies from that in the 'cell in general'.
.I 476
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1361. the mechanism of histidase induction and formation in bacillus subtilis
the role of the inducer, l-histidine, in the
synthesis of histidase (l-histidine am-
monia lyase) in b. subtilis was investigated.
it was found that induced cells poisoned
with actinomycin, an inhibitor of rna synthesis,
lose their capacity for the forma-
tion of a protein precursor of histidase at a rate
which is independent of the presence
or absence of the inducer.  these results show
that the inducer does not increase
the intracellular level of histidase-specific
messenger rna by preventing the des-
truction of the major portion of this material,
the fraction that is engaged in pro-
tein synthesis.  the possibility has not been
excluded that the inducer exerts its
effect by bringing about the stabilization of
the messenger rna that is still attached
to dna or has not yet become attached to
ribosomes.  alternatively, the inducer may
actually stimulate the synthesis of
histidase-specific messenger rna.  the conver-
sion of the precursor to active enzyme
appears to involve polymerization of mono-
mers, rather than the release of
ribosome-bound inactive enzyme.
.I 480
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31
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2564. chemical inactivation and reactivation of transforming dna (russian)
the kinetics of the inactivation of linked
and unlinked genetic markers by means
of hno2 or uv light was studied.  closely
linked markers are inactivated simul-
taneously, unlinked markers are inactivated
independently.  it seems that the
chemical attack on dna impairs a large part
of macromolecule, including many
cistrons.  it was shown by genetic experiments
that chemical inactivation prac-
tically does not influence the process of dna
inclusion into competent cells.  by
means of viscosity measurements it was
shown that the molecular weight and
macromolecular properties of dna do not
significantly change during chemical
inactivation by means of hno2.  two explanations
for the inactivation of trans-
forming activity of dna are discussed  (1) structural
deteriorations, preventing
integration of dna molecule into the genome of
recipient cell, or (2) deletion of
a chain unit out of dna chain resulting in wrong
reading of code triplets.  it was
previously described in the literature that extensive
inactivation leads to a state
of dna, apparently more resistant than the initial one.
inactivation does not con-
firm to exponential kinetics.  the authors discuss the
coding mistake hypothesis
as an explanation for this remarkable fact.  extensive
hno2 or uv light action re-
sults in multiple lesions in the dna molecule and
leads to reactivation because
the deletions restore correct reading of the code
in a large part of dna molecule.
on the basis of this explanation reactivation of
chemically injured dna by means
of fusion and annealing with homologous but
genetically inactive dna, or by slight
fragmentation of dna by means of ultrasonic
vibrations may be expected.  attempts
to achieve reactivation by both methods gave
positive results.
.I 482
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2529. repair of damage induced by a monofunctional alkylating agent in a
transformable, ultraviolet-sensitive strain of bacillus subtilis
a uv sensitive, transformable strain of
b. subtilis (uvr-) was unable to carry out
host cell reactivation of the virulent
bacteriophage spo1.  the ratio of the slopes
(kuvr-/kuvr+) of the uv inactivation curves
was 6-8 for cells or for whole phage, and 2
for indole+ transforming dna or for
spo1 phage dna measured in a transforming
system.  whole phage inactivated with
nitrogen mustard showed greater survival on
uvr+ cells than on uvr-; there was no such
difference for whole phage inactivated with
methyl methanesulfonate.  whole uvr+ cells
recovered from uv induced damage, as
determined by an increase in extractable
transforming activity during a period of
incubation in which net dna synthesis did
not occur.  uvr- cells were unable to reco-
ver from uv induced damage but they did
recover from methyl methanesulfonate
induced damage in similar experiments.
density labeled (h2n15) methyl methanesul-
fonate treated uvr+ cells incubated in (h1n14)
medium containing (h3) thymidine show-
ed a 3-fold increase in extractable transforming
activity, with no formation of new
dna molecules as determined by pyknometric
analysis.  the repair of damage in-
duced by uv irradiation differs by at least one
step from the repair of damage in-
duced by methyl methanesulfonate.
.I 484
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5574. death anxiety in children with a fatal illness
the author reports studies of a series
of 50 children hospitalized because of fatal
illness due to leukemia or some other
form of cancer.  it was postulated that the
younger children would experience
separation anxiety while the older children
would be more likely to experience
death anxiety.  in general the hypothesis
was supported by the results of the study.
there was some evidence to indicate that
the younger children perceive death
anxiety but deal with it in more symbolic form.
in older children, it was felt that boys
tended to react to death anxiety by acting out
behavior while girls tended to become depressed.
.I 485
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1209. the theory and practice of the family diagnostic.  ii. theoretical
aspects and resident education
family intervention and observation have proved
useful in 3 areas.  the 1st of these is observation of the
psychosocial context in the patient.  on admission to a
mental hospital the phenomenon of extrusion and separ-
ation from the family is evident, and the need for study
of the interaction between the patient and his family
milieu is vital.  the 2nd area where the family inter-
view has a major role is resident education.  the tra-
ditional medical education of the ill prepares the stu-
dent for consideration of the multifactorial problems of
emotional disorder in which balances between mem-
bers of a group may be the issue rather than external
pathogenes.  the family interview offers a unique point
of observation of factually evident and emotionally con-
vincing group data.  in addition to the observation of
family phenomena, mutual understanding of others'
problems is created.  finally, the family interview
serves as an instrument for data collection and hypo-
thesis seeking in relating individual psychopathology
to family adaptations.  the patient and his family at
the time of admission are dealing with a crisis.  some-
times this is traumatic, such as the unexpected loss
of a young marital partner, an unexpected illness, or
a financial reverse.  more commonly, however, it is
developmental being a natural part of the life cycle.
characteristically, the developmental task involved
in dealing with the crises has been postponed so that
one does not see the family at the age specific and ap-
propriate time for this task.  the crisis emerges dis-
ruptively because of inevitable biological maturation,
personal decision, or social expectation.  a primary
concern of the leader is to determine what life task is
being faced.  families have a mentally ill member not
merely because they are dealing with the vicissitudes
of life.  they are unable to cope with the crisis, be-
cause of the feelings which are aroused.  each life cri-
sis leads to a particular constellation of effects in any
given family.  these include primarily, sadness, anger,
and guilt, but there may well be specific affective con-
stellations appropriate to different developmental tasks.
the patient's inability to cope with a life crisis is due
to his particular adaptation of a style of dealing with
feelings that is employed by other members of the family.
.I 486
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31
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265. studies in personality.  ii. a bio-psychological and experimental
approach to problems of human adaptation in modern society
experimentally determined fixation-ambivalence
measures are related to some anxiety estimates obtain-
ed from a projective test in a group of male adolescents.
it is shown that (1) fixation increases with increase in
corporal injury anxiety when ambivalence is kept con-
stant, (2) ambivalence increases with increase in separa-
tion anxiety when fixation is kept constant, (3) extremely
hetero-fixated subjects show presence of intense guilt
and absence of aggression towards the mother; one ef-
fect of this system of organizers seems to be
suicidal
tendencies, (4) extremely ambivalent subjects have in-
tense separation anxiety; one effect seems to be suicidal
tendencies combined with high ambition and impaired
cognitive capacity.
.I 487
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2837. early indicators of outcome in schizophrenia
the case material of 50 persons who
were seen at a child guidance center in child-
hood or adolescence and were later
hospitalized with schizophrenia were examined
intensively.  the study concentrated
especially on the differences associated with
chronicity vs. hospital release.  the
following 12 factors were significantly related
to chronicity  (1) psychotic or schizoid
pathology in the mothering person, (2) no se-
paration of any kind from the pathogenic
families, (3) pre-illness history of poor so-
cial and sexual adjustment, (4) failure
to continue in treatment (during childhood)
for at least 3 mth., (5) less acting out
in the community, (6) neither disorientation
nor confusion on admission, (7) no
symptoms of depressive psychosis, (8) premor-
bid schizoid personality, (9) no clear
precipitating events, (10) no concern with dying
during the acute phase of the illness,
(11) length of onset over 6 mth., and (12) schi-
zophrenic reaction in patients' heredity.
items 1, 2, and 5 were derived from early
life history data and are thought to be
new to the literature of prognosis in schizo-
phrenia.  the remaining 8 factors can be
scored from hospital data alone, and have
been cited in previous prognostic studies.
.I 488
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4854. on the formation of object-relations and identifications of the
kibbutz child
some of the issues relevant to the early
stages of object relation formation and
identification of kibbutz children are
discussed.  for this purpose the child rearing
milieu of the kibbutz child is described
and some clinical illustrations are given.
the relationship to the mother is seen
as the main object-relation and those to the
educators as transient-interchangeable
need-satisfying relationships.  on the basis
of retrospective analytical material it
appears that in the course of development
the two relations as well as the two
respective, originally distinct, object represen-
tations are synthetised into one.  the
conditions of communal education, character-
ised by double object-relation formation
from birth on, are seen as factors that in-
tensify the 'normative crisis of infancy',
especially the transition from the symbio-
tic to the separation-individuation stage
of object-relation development.
.I 489
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31
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4846. the meaning of crying
the multiple meanings of crying are
reviewed and, in particular, stress is laid
on tears as a response to some type of separation loss.
.I 491
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31
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1848. the child's concept of death
in this translation of a paper, which first
appeared in 1912, it is shown, according
to freud, how far a child's appreciation
of being dead differs from its true signifi-
cance.  death means a reversible decrease
in life functions, that can be interrupted
at any time, like sleep.  at other times it
may mean a temporary separation; but
always it is in man's power to change it.
in this concept, the child's unconscious
finds license for his sadism.  cruelty to
animals and death wishes against persons
close to him appear, in overcompensation, as
exaggerated pity for dead creatures
and the belief in man's power over life and death.
.I 494
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2906. early childhood separations
every child in this long-term study of child
rearing showed significant reactions to
ordinary separations by about 1 yr. of age.
the similar pattern of response in this
group of children suggests a biologically
determined cause.  the clinging reaction
appeared when the child became mobile and
able to move away from his mother re-
gardless of the frequency or duration of his
separations.  the majority of the mothers
did not understand this natural phenomenon
and regarded the clinging and crying of
the 1-year-old as evidence of spoiled or
regressed behavior.  the pediatrician can
be helpful to a mother by anticipating and
explaining separation responses, by indi-
cating their universality, and by giving
specific recommendations for gradual changes
to modify these reactions.
.I 496
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1808. separation anxiety  a factor in the object relations of
schizophrenic patients.
the thesis is advanced that
special vulnerability to separation anxiety is a crucial
factor in the schizophrenic's difficulty in establishing
and maintaining satisfactory interpersonal relationships.
2 major reasons for this are lack of autonomy and lack
of object constancy.  without a stable autonomous
capacity for self-regulation and adaptation, he is inordi-
nately dependent upon others for help, protection, and
direction.  without object constancy, he is unable to
maintain a stable representation of the needed person in
the latter's absence.  evidence is presented from the
intensive psychotherapy of schizophrenic patients.
many of the vicissitudes of the doctor-patient relation-
ship center about the patient's separation anxiety and
his attempted defenses against it.  these include clinging,
perceptual and cognitive distortions designed to deny
separation, and recourse to substitute objects.  promi-
nent in many of these efforts is the attempt to reverse
passive victimization into active mastery.  the practical
implications of this thesis for the treatment of schiz-
ophrenic patients are discussed.
.I 497
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31
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9101. separation experiences and health records in a group of normal adults.
about 25% of 455 ostensibly normal ss
reported a recent "separation experience" as defined
in this study.  the frequency of visits to the dis-
pensary for symptomatic complaints was not signifi-
cantly higher among those who reported separation
than among those who did not.  the data suggest
that an apparent association between relatively high
cornell medical index score and history of separation
experience may be understandable in terms of a cause-
effect relationship between separation experience and illness.
.I 498
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31
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11306. separation and attempted suicide.
of 3 groups of psychiatric patients-at-
tempted suicides, those with suicidal urges, and non-
suicides-there were significantly more attempted
suicides among patients with a history of childhood and
antecedent separation than controls.  in childhood the
significant difference was found primarily in the period
from birth to 7 yr.  there was no significant interaction
between childhood and antecendent separation and
suicide attempt or suicide urge.
.I 505
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31
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773. the effect of radiation on lenticular epithelial enzymes
in young rabbits
the mitochondrial fraction and the soluble
fraction of the epithelial cells of the lens
from 6-week-old new zealand white male
rabbits, exposed to 800 r of whole-head
x-irradiation, were evaluated for glucose
6-phosphate dehydrogenase, isocitrate
dehydrogenase, malate dehydrogenase,
glutathione reductase, glyceraldehydephos-
phate dehydrogenase, purine nucleoside
phosphorylase, nadph2 diaphorase, and
nadh2 cytochrome c reductase activities.
increased enzyme activities were noted
in the irradiated lenticular tissues for
purine nucleoside phosphorylase, nadph2
diaphorase and nadh2 cytochrome c
reductase.  decreased activities for glucose
6-phosphate dehydrogenase, malate
dehydrogenase, glutathione reductase and gly-
ceraldehydephosphate dehydrogenase
were observed in the lenticular tissues of ir-
radiated animals.  the activity of isocitrate
dehydrogenase was the same in the ir-
radiated and in the control animals.
.I 509
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1752. separation of the soluble proteins of bovine lenses on
polyacrylamide gels
the soluble proteins of bovine lenses were
separated by gel filtration on polyacryl-
amide gels.  the presence of ethylenediaminetetra-
acetate in the buffer was found
to be essential for achieving a good separation
of the lens homogenate into four
fractions - a, b, c and d.  ultracentrifugal,
electrophoretic and immunochemical
analyses were used to compare these fractions
with the soluble crystallin fractions
of the lens.  fraction a was compared
with a-crystallin, fractions b and c with
b-crystallin and fraction d with y-crystallin.
the distribution of these four protein
fractions in the nuclear and cortical parts
of calf and cow lenses was determined.
the oxidation-sensitive protein fraction of
the calf lenses was separated from
fraction b on an se-sephadex column.
.I 512
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787. further autoradiographic studies of the lens epithelium.
normal and x-irradiated rat eyes
cell proliferation and migration in
the lens epithelium of normal and x-irradiated
rat eyes were studied by means of
autoradiography after labelling with tritiated
thymidine.  cells of the normal lens
epithelium require 16 hr. to pass from the
beginning of the synthesizing period
to the completion of mitosis.  this interval is
partitioned as follows  s period,
approximately 10 hr.; g2, slightly less than 5 hr;
and mitosis, 72 min.  following division,
labelled daughter cells migrate from the
germinative zone to the postequatorial
rows, and by 2 weeks after tracer injection
many radioactive nuclei are found in the
lens bow.  epithelial cells irradiated while
in the dna synthesis phase undergo
degeneration beginning approximately 8 hr.
after exposure.  the onset of cell death
corresponds to the time at which these cells
would normally be preparing for mitosis
indicating that they die in abortive divisions.
a small percentage of the originally
labelled cells survived until 3 days after irradi-
ation, but by 2 weeks this number fell
almost to zero.  the loss of radioactive cells
occurred most rapidly in the equatorial zone.
.I 514
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1494. selenium content of fish flour in relation to kwashiorkor and dental
caries
the fact that fish flour was shown to be a rich source of
dietary selenium (169 p.p.m. may have important implications (i.e. deleterious
effect on teeth) in the treatment and prevention of protein malnutrition.  it
indicates that some disease syndromes in man may be a manifestation of selenium
deficiency.  it is recommended that the role played by selenium in protein
malnutrition should be given serious consideration by research workers.
.I 515
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2192. selenium content of fresh eggs
during a study of effects of traces of se on dental caries the authors
determined this element in eggs.  whole egg contains appreciable
amounts of se; this is found chiefly in the yolk (mean value 0.324
0.039 p.p.m.) with only 0.051 0.029 p.p.m. in the white.
.I 516
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1541. selenium content of human milk  possible effect on dental caries
selenium appears to be a factor capable of increasing susceptibility to
dental caries in children and rats.  in an area considered to be
nonseleniferous, milk collected from 15 mothers (17-44 yr. old) of low
socio-economic class had a mean selenium content of 0.021 p.p.m.
(standard error  0.003).
.I 517
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1577. mode of action of selenium in relation to biological activity of
tocopherols
dietary selenium at levels below 1 ppm has a partially beneficial effect
upon nutritional muscular dystrophy but is ineffective or detrimental
at higher levels.  the role of selenium in improving the effectiveness of
vitamin e is due at least in part to the fact that dietary selenium increases
the retention of the a-tocopherols, especially d-a-tocopherol.  this has been
shown by chemical determination of plasma tocopherols and also by tracing the
activities of tritiated tocopherols and selenium75 in serum and in various
fractions of serum proteins in chicks receiving these nutrients alone and in
combination.  se75 and h3-a-tocopherol activities followed each other very
closely in the serum proteins.  these studies indicated that vitamin e may be
carried by a selenolipoprotein fraction associated with serum y-globulin.  thus,
one biological role of selenium appears to lie in a selenium-containing
compound which acts as a carrier of vitamin e and which may function in
absorption, retention, prevention of destruction, and perhaps transfer across
cell membranes of d-a-tocopherol, thereby enhancing its biological activity
in the blood and perhaps in cells throughout the body.
.I 518
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3123. effect of sodium selenate on acute poisoning with thallium
experiments were performed on wistar rats weighing 150-200 g.  thallium was ad-
ministered s.c. in doses of 20 mg/kg and 30 mg/kg.  sodium selenate was
given per os in doses of 10 mg/kg 2 hr after poisoning and 5 mg/kg daily
for the next 2 days.  results indicate that sodium selenate protects the
animals from death.  it binds the thallium ions and increases their deposition
in organs.  comparison of the level of thallium in organs of treated rats
shows that selenate increases in liver by 290.6%, in kidneys by 326.8% and in
bones by 210.0%.  no influence of selenate on excretion of thallium in the
urine was found, but fecal excretion of thallium increased by an average of
45% of the treated animals.
.I 519
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2281. inhibition of active transport of sugars through rat intestine in vitro.
ii. action of mepacrine, atractyloside and selenite
it is shown that mepacrine, atractyloside and selenite, which had been regarded
as inhibitors of intestinal absorption of glucose, are inhibitors of active
transport of sugars in sacs of everted jejunum of rat (wilson and wiseman's
method).  mepacrine 5 x 10 -3 m and 10 -2 m inhibit, by 85% and 100%
respectively, the active transport of galactose.  with atractyloside 10 -5 m
and 10 -3 m, the inhibitions were 77% and 100% and, with selenite 10 -4 m and
10 -3 m, about 70%.  in general the inhibitors are effective within orders of
magnitude which are similar in vivo and in vitro.  atractyloside is rather more
effective in vitro than in vivo, and mepacrine rather less.  it is easier to
achieve total inhibitions of the active transport of sugars in vitro than of
intestinal absorption from isotonic solutions in vivo.
.I 520
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31
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2284. analogs parasympathetic neuroeffectors.  ii. comparative pharmacological
studies of acetylcholine, its thio and seleno analogs, and their hydrolysis
products
acetylthiocholine and acetylselenocholine exert acetylcholine-like effects on
the guinea-pig ileum and frog rectus abdominis preparations.  with the
latter preparation, responses to acetylthiocholine and acetylselenocholine,
in contrast to that to acetylcholine, are not enhanced by the addition of an
anticholinesterase.  this is attributable to the relatively high activity of
the hydrolysis products, cholinethiol and cholineselenol; acetylthiocholine
and acetyselenocholine undergo enzymatic hydrolysis at approximately the same
rate as does acetylcholine.  the hydrolysis products of acetylthiocholine and
acetylselenocholine, which have effects on the guinea-pig ileum comparable
to those of the parent esters, are readily oxidized in air to the relatively
inactive choline disulfide and choline diselenide, respectively.  these
observations are helpful in explaining many of the apparently contradictory
statements in the literature regarding the actions of acetylthiocholine.
.I 521
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18
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3604. cytotoxicity of organophosphorus compounds.  comparative activities of
trimethyl derivatives of thiophosphoric and selenophosphoric acids on vegetable
(pisum root) and human (hela) cells
of the 4 compounds studied, the seleno compounds were more cytotoxic for
hela cells than their thio analogues, whereas the activities on pisum
root cells were equal.  the parent phosphoric acid derivatives have a
wider activity range on hela cells than the seleno and thio derivatives.
further studies are in progress.
.I 522
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18
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3640. poisoning with sodium selenite
chronic poisoning with na selenite (in the drinking water) causes hepatic
cirrhosis, usually of atrophic type, in rats.  in rabbits there seems to be a
definite diabetogenic action, while attempts to demonstrate such action in
dogs have so far given inconclusive results.  the difference between these
2 species is perhaps due to the technique used (different spacing of injections
for practical reasons).  the action of selenite on the pancreas is discussed
and it is pointed out that se can replace s in sh groups, thus rendering the
latter ineffective.  both in effects on the liver and in those on the pancreas
se seems to resemble alloxan.
.I 523
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18
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2552. the tissue distribution of se75 -selenouracil and se75 -selenourea
when selenium analogues of thiouracil and thiourea labelled with se75 were
injected into rabbits, high radioactivity appeared in lung, liver and kidney.
the animal's lungs could be visualised by photoscanning, but quality was
poor, and neither compound is recommended for trial for lung or
adrenal scanning in man.
.I 529
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10
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1845. further studies on specific transplantation antigens in rous sarcoma of
mice
mice allografted with different sarcomas, induced by the schmidt-ruppin variant
of rous sarcoma virus (rsv-sr), showed a resistance against subsequent
isografting of 9 different rous sarcomas.  transplantation
resistance could also be induced by
rous mouse tumor cells x-irradiated with 8000 r
or with cell-free tumor extracts,
containing no demonstrable virus.  no
transplantation resistance could be demon-
strated after allograft pretreatment with
various polyoma tumors or non-viral tu-
mors.  allograft pretreatment with rous
tumors induced no demonstrable resistance
against isografting of polyoma tumors.
inoculation of rsv-sr or rous chicken sar-
coma suspension into adult mice gave
no clear cut resistance against isograft-
ing of mouse sarcomas.  neither after
allografting of rous tumors nor after virus
or chicken sarcoma inoculation into adult
mice could virus-neutralizing activity be
demonstrated in the sera.  the results
demonstrate the presence of common, speci-
fic transplantation antigen(s) in different
rous sarcomas in mice and speak against
an identity between the transplantation
antigen(s) and viral antigen(s).
.I 530
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31
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1846. anaphylactic tests in model tumour antigen investigations
the efficacy of anaphylactic tests in detecting
'tumor' antigen in serum was investi-
gated.  a simple model of a tumor-antigen
study was carried out using rat tissue
and rat serum, with bovine y-globulin (byg)
acting as a mock cancer antigen.  it
was found that if byg (absolute dosage 100
ug.) had formed 1/6 of the antigen mix-
ture used for sensitization it was readily
detected when present in a concentration
of 10-3 in the serum used for challenge,
but not invariably detected in a concentra-
tion of 10-4.  if byg (absolute dosage 50
ug.) had formed approximately 1/50 of the
sensitizing mixture, it was infrequently
detected even when present in the challeng-
ing serum in a concentration of 10-2.  it
is concluded that anaphylactic tests used in
this context do not have a very high
sensitivity or discriminatory capacity.
.I 531
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10
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1066. the effect of lymphoid cells from
the lymph of specifically immunised sheep
on the growth of primary sarcomata in
rats
the growth of primary fibrosarcomata induced in
rats with 3:4-benzpyrene was retarded by the injection
of lymphocytes obtained from the efferent duct of a
lymph node in a sheep immunized with a piece of the
tumor to be treated.  the action of the heterologous lym-
phocytes was specific to the particular tumor used for
immunization suggesting that reaction against tumor-
specific antigens is involved.  the cells responsible are
believed to be medium-sized pyroninophilic lymphocytes
which may stimulate the immune system of the host to
react against the autochthonous tumor.
.I 532
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10
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2570. treatment of canine neoplasms with autogenous vaccinial preparations
inbred mice with transplantable sarcoma
and carcinoma were treated with im-
plants of their tumours which had been
grown in strains of mice normally resistant
to the tumours.  complete regression of
transplantable tumours was noted in 22%
of the treated mice and 78% had life
spans double that of untreated controls.
one dog with spontaneous scirrhous
mammary carcinoma and another with
lymphosarcoma were treated with implants
of their own tumours after growth in
cortisone-treated mice.  regression of the
spontaneous neoplasms followed in both
cases.  it is suggested that growth of a
neoplasm in a foreign host alters the mole-
cular structure of the neoplasm, making it
antigenic when returned to the original
host.  antigens produced are also effective
against the original lesions.
.I 533
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10
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744. studies on protein and nucleic acid metabolism in virus-in-
fected mammalian cells.  the formation of a virus-specific
antigen in krebs ii ascites-tumour cells infected with ence-
phalomyocarditis virus
krebs ii mouse ascites-tumor cells infected
with encephalomyocarditis virus were
found to contain, in addition to mature virus,
a virus-specific protein antigen.  an
assay, based on the ability of this antigen
to block the neutralization of purified virus
by its specific antiserum, was developed.
this antigen was present both in the cul-
ture fluid 17 hr. after the infection of cells
with virus and intracellularly, where its
titer increased at a time when viral capsid
protein was being synthesized.  within the
cell, it was mostly localized in the soluble
cell sap.  in contrast with virus, the anti-
gen did not agglutinate sheep erythrocytes,
and its immunological properties were
destroyed by digestion with trypsin.  ribonucleic
acid was not detected in concentrat-
ed preparations of the antigen, nor was the titer
of antigen affected by ribonuclease.
the antigen had a sedimentation coefficient (20 )
of approx. 14s, and its diffusion co-
efficient, determined by the method of allison and
humphrey (1960), was 3.2 x 10-7
sq. cm. sec.-1.  the particle weight of the antigen
was hence 420,000   40,000.  the
capsid protein from purified encephalomyocarditis
virus could be degraded by treat-
ment with ethanolamine into a protein of sedimentation
coefficient (20 ) of approx. 4s.
the 14s antigen, when similarly treated, yielded
a protein of similar size.  however,
no such smaller antigen was detected in virus-infected
cells.  it is concluded that the
non-hemagglutinating antigen represents a polymeric
form of the basic viral capsid-
protein molecule and that it is synthesized in the
cytoplasm of infected cells.  it may
be either an intermediate or a by-product in the
process of viral capsid-protein syn-
thesis.
.I 534
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10
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1368. immunologic competence and induction of neoplasms by
polyoma virus
thymectomy at 3 days of age in several
inbred strains of mice and in an f1 hybrid
resulted in a strikingly increased frequency
of neoplasms following infection with
polyoma virus.  age susceptibility was extended
to at least 30 days of age in highly
resistant c57bl mice.  the usual stigmata
associated with thymectomy at birth were
not found in the 3-day thymectomized mice.
nonetheless the methods used to restore
immunologically deficient thymectomized
neonates were also effective in restoring
the capacity to resist polyoma virus tumor
induction: adult syngeneic spleen cells,
thymus tissue in millipore diffusion chambers
and syngeneic thymus grafts.  growth
curves of polyoma virus in kidney, salivary
glands and liver were quite similar in
thymectomized and intact litter mates.
hemagglutination-inhibition antibodies deter-
mined periodically up to 30 days after
infection were also similar in both groups.
these results are discussed in terms of
a concept involving virus-specific 'tumor'
antigens and the immunologic status of the animal.
.I 536
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31
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2354. isoantigenic properties of tumors transgressing histocompatibility
barriers of the h-2 system
sublines capable of transgressing h-2 histocompatibility
barriers have been derived
from strictly strain-specific tumors by 1) passage
through newborn hosts of a
foreign genotype; 2) passage through adult h-2
incompatible recipients pretreated
with isoantisera directed against the tumor cells.
the nonspecific character induced
by these procedures was usually expressed in a
number of different h-2 incompa-
tible recipients.  the changes responsible for
the conversion to nonspecific growth
appeared to proceed in a stepwise fashion.
expression of the nonspecific character
required exposure to the foreign host environment
for more than 30 days.  at this
stage and during the subsequent 3 transfer
generations, reversion to strain-specific
growth occurred on back-transfer to the
strain of origin; after 4 passages in the
foreign hosts the nonspecific character was
permanently established, however, and
could not be reverted by prolonged passage
in the original host genotype.  the
growth rate of strain-specific tumors and
their nonspecific sublines was compared
in the strain of origin.  no difference was
found with one tumor, while the strain-
specific line grew better than the nonspecific
sublines with another.  this difference
was detected in the homozygous strain of
origin and in different semi-isologous f1
hybrids.  all lines grew better in the
homozygous strain than in the f1 hybrids,
however.  a comparison was made
between the concentration of h-2 isoantigenic
surface determinants in strain-specific
tumors and their nonspecific sublines by a
quantitative absorption technique in
vitro.  all nonspecific sublines had a lower
concentration of h-2 isoantigens than
the strain-specific tumors.  this suggests
that nonspecific tumors develop as a result
of immunoselection of variants resistant
to the homograft reaction and are characterized
by a lowered concentration of
h-2 antigens.
.I 544
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19
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effets de la carence potassique
chez le rat sur le squelette,
le cholesterol plasmatique
l'histologie des surrenales
r. habib, j. lefebvre et p. royer
potassium deficiency in the male rat at the time of weaning,
provokes an increase in the weight of the suprarenals, an
atrophy of the glomerular zone and a lipoid hypertrophy of
the fasciculae.
it causes a rise in the level of the blood cholesterol.  it
reduces the phosphate level in the blood and increases the
phosphate in the urine.
the blood calcium level is not altered but a hypocalciuria is
noted.
it leads to a severe osteopathy which has been investigated
by radiography, microradiography and histological and bio-
chemical study of the skeleton.  the following are the charac-
teristics : arrest of osseous growth, delay of maturation, arrest
of chondrogenesis, formation of dense metaphyseal lines or
lines of arrest, osteoporosis.
these facts are discussed and compared to the analogous
changes found in the syndrome of chronic idiopathic hypo-
kalaemia with hyperkaluria in the infant.
.I 545
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19
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vergleichende renale phosphatelearance-untersuchungen
beim hyperparathyreoidismus und beim sog.  phosphatdiabetes
the analysis of the function of the kidneys give a contribution to
the pathophysiology of two different diseases of general osteopathies
whose pathogenesis or etiology are still not clear in some points.  the
phosphate clearance pre- and postoperative in one patient with hyper-
parathyroidism showed that after the removal of the adenoma of the
parathyroid the renal reabsorption of phosphate improved only tempo-
rary as a secondary form of hyperparathyroidism was already present.
in a patient with a "phosphatdiabetes" the clearance examination showed
that under a high dosage of vitamin d the reabsorption of phosphate did
not increase.  based on these results we have not continued therapy
with vitamin d which is certainly not indifferent.  comparative renal
clearance examinations were carried out in 10 patients which did not
show any disturbances of calcium/phosphate-metabolism.
.I 546
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31
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the unreliability of the titan yellow method
for the determination of magnesium
in patients receiving intravenous
calcium gluconate
gluconate was found to interfere with the determination of magnesium by the
titan yellow method.  with this method, false low results were found in the
serum and urine of patients receiving intravenous calcium gluconate.  the
interference can be prevented by ashing of the specimen.
.I 547
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31
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absorption and excretion of toxogonin, an alkyl-phosphate antidote,
after intramuscular injection in man
tolerance, absorption and urinary excretion stu-
dies of toxogonin (bis-(4-hydroxyiminomethyl-
pyridine-1-methyl) ether dichloride), a specific anti-
dote in poisoning by esterase-blocking organic
phosphates, were made on 11 men by intramuscular
injection of 250 mg. (ca. 3 mg./kg.) of the drug,
given by self-injection ampoules.  injections made
with the automatic ampoule autule caused no local
irritation.  certain facial symptoms reported can for
the time being be regarded as resorptive side-effects
of toxogonin.  maximum blood levels of 6 ug./ml.
were recorded within 20 minutes.  even after four
hours the level was still 1-2 ug./ml., a concentra-
tion amply sufficient to ensure reactivation of blood
esterases.  of the injected dose, 52% was excreted
in the urine after two hours, 87% after eight hours.
toxogonin appears to pass through the body un-
changed.
.I 548
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31
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the study of osteoporosis
and osteomalacia
radiological evidence strongly suggests that
osteoporosis (with the possible exception of acute
immobilization osteoporosis) may be an irrever-
sible condition.  the changes therefore to be
expected in calcium balance when an osteoporotic
is treated are small compared with those often
seen in osteomalacia.  methods of obtaining more
accurate calcium balances are needed to show
these small changes, especially when a high
calcium intake is used.  the method of continuous
marking of stools with chromium sesquioxide
seems to provide just such a method.  using this
method, it has so far proved impossible to obtain
prolonged large positive calcium balances in
osteoporosis on either high calcium intake,
anabolic hormones, or sodium fluoride.
two alternative therapies to vitamin d have
been explored for use in vitamin d-resistant
osteomalacia.  atp has been found to be inneffective.
intravenous phosphate alone has been ineffective
in producing positive calcium balances, but is
effective as a complement to vitamin d under
certain conditions.
.I 549
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19
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the aetiology and treatment of
urinary calculus
investigations in this laboratory have been
based on the hypothesis that calculus formation is
primarily a process of crystallization from super-
saturated solutions rather than one of adsorption
on a specific protein matrix, as has been postulated
by boyce and his colleagues (boyce and king,
1963).  that crystallization is the primary factor
is strongly suggested by the recent studies of
vermeulen, lyon and gill (1964).  these authors
produced artificial concretions which closely
resembled urinary calculi by immersing a rotating
wire loop in normal urine for several days and
slowly adding the appropriate stone-forming
elements.
if the above hypothesis is correct then the
factors of primary interest in urinary stone
formation are those responsible for supersaturation,
nucleation and crystal poisoning.  much remains
to be learnt about these various factors, their
inter-relationships, and their relative importance.
the significance of the urinary colloids (proteins,
muco-proteins and polysaccharides) in calculus
formation is still not clear but it is probable that
they play an important secondary role in binding
crystalline precipitates to form a non-friable
calculus.  since time is an important factor in
crystal growth such non-specific binding by
proteins would increase the chances of stone
growth and retention within the upper urinary
tract.
.I 550
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19
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control of idiopathic hypercalciuria
the paper discusses the causes of hypercalciuria and describes
15 cases of different origins all of which presented similarly
with renal stones.  the diagnosis of idiopathic hypercalciuria
was made by exclusion.  the effects of dietary restriction of
calcium, sodium bicarbonate, cortisone, sodium phosphate,
sodium phytate, and cellulose phosphate were demonstrated by
calcium and phosphorus balance techniques.  all were shown
to have some urinary-calcium-lowering effect.  finally, a
chlorothiazide derivative--namely, bendrofluazide--was also
demonstrated to have a hypocalciuric effect, and the mode of
action is discussed.
.I 551
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31
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effects of parathyroid hormone and other proteins in vitro
on mitochondrial metabolism
it is apparent that in addition to parathyroid hormone, several
non-hormonal basic proteins stimulate mitochondrial respiration, ion
transport, and atpase, but inhibit the 32pi-atp exchange reaction.
thus these effects may not be so uniquely a measure of the biological
actions of parathyroid hormone as the previous reports suggested.
rasmussen et al. (1964) have also isolated from parathyroid
extracts a protein that is inert in vivo but stimulates mitochondrial
transport of phosphate in vitro.  they postulated that this protein
might be yet another biologically important factor produced by para-
thyroid glands.  the latter speculation may not be warranted in view
of the uncertain specificity of protein effects on mitochondria.  all
of our tests completed to date show that the non-hormonal parathyroid
proteins c1 and c2 are unrelated either biologically, immunologically,
or chemically (by amino-acid analysis) to the parathyroid hormone.
further rigorous studies are necessary to precisely determine
whether any effects of parathyroid hormone on mitochondria validly
reflect the mechanism of action of the hormone and whether it is sound
to use the in vitro tests as bioassay tools.
.I 552
.C
31
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the treatment of phosphatic encrusted cystitis
(alkaline cystitis) with nalidixic acid.
phosphatic encrusted cystitis is caused by
persistent infection by b. proteus or ps. pyocyaneus
associated with an alkaline urine.  its incidence
may be increasing and may follow megavoltage
therapy of a bladder tumour.  its incidence in
post-radiation cases is 2 per cent.
mandelamine often fails to relieve this
condition.  in this series of ten patients who had
failed to respond to mandelamine, eight
responded to treatment with nalidixic acid.  no side
effect of treatment was noted in the series.
nalidixic acid is of value in the treatment of b. proteus
infections of the urinary tract, and is the drug
of choice in the treatment of phosphatic encrusted
cystitis.
.I 553
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31
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role of the liver in the glycoprotein mobilizing property of
parathyroid extract
studies were carried out to de-
termine the action of hepatectomy on the
glycoprotein action of pte as well as on
pte-induced renal calcification and deposi-
tion of glycoprotein.  our data showed that
in hepatectomized rats, pte no longer caused
an elevation in serum glycoproteins.  how-
ever, hepatectomy did not alter the forma-
tion of glycoprotein tubular casts produced
by pte administration.  the data suggest
that the liver is the major source of the ele-
vated serum glycoproteins found in rats re-
ceiving pte.  in addition, it is possible that
pte may have a direct stimulating action
on biosynthesis of glycoprotein by the kidney.
.I 554
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31
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distribution and excretion of radioactivity after parenteral
administration of radioactive polydiethylstilbestrol phosphate
to rats and a cow.
polydiethylstilbestrol phosphate
(psp), a water soluble polyester of phos-
phoric acid and diethylstilbestrol, was in-
jected in rats and a cow and the distribution
and excretion of radioactivity were followed
in both species.  after a subcutaneous or
intramuscular injection the bulk of the radio-
activity was accumulated at the site of injec-
tion.  the disappearance of radioactivity from
this depot was very slow.  as late as 90 days
after the injection into rats, 20% of the
administered radioactivity was still accumu-
lated at the site of injection.  the liver was
very effective in removing labeled material
from circulating blood.  twenty-four hours
after intravenous injection in rats, about
50% of the radioactivity was recovered from
this organ.  the distribution of radioactivity
in the cow indicated that the polymer was
preferably accumulated in organs containing
reticuloendothelial cells.
.I 555
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19
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study of phosphate excretion by the stop-flow
technique
m. de myttenaere
the stop-flow technique has been applied to the dog in an attempt to
rule out tubular secretion of phosphate and to locate the site of action of
parathyroid hormone (p.t.h.) on the renal tubule.  under the experimental
conditions used, no significant inward transtubular movement of p32 could be
demonstrated, ruling out tubular secretion of phosphate.  stop-flow
experiments performed in parathyroidectomized dogs before and after p.t.h.
administration demonstrated inhibition of phosphorus reabsorption by the
hormone.  in addition, the stop-flow pattern indicated that this
phenomenon took place mainly in the distal part of the proximal tubules.
.I 556
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31
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stupor, hypercalcemia and carcinoma of the
renal pelvis
since albright suggested that some tumors
"might be producing parathyroid hormone," hy-
percalcemia associated with malignant tumors with-
out bony metastases has been recorded with increas-
ing frequency.  transitional-cell carcinoma of the
renal pelvis is here added to the list of neoplasms
that hypercalcemia may accompany.
.I 557
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31
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anodized aluminium grains labelled with radiophosphorus
for medical purposes
g. b. fasolo, r. malvano, u. rosa and e. zimmer
interstitial b-therapy, by implantation in tissues of
radioactive sources, is widely applied to the treatment
of certain forms of human malignancies.  among the
radio-elements proposed for this therapeutic technique,
yttrium-90 and gold-198 are the most generally used.
radiophosphorus (32p) shows some attractive features
because of its suitable half-life (14.3 days) and its rather
high-energy b-emission (maximum energy 1.71 mev);
but the use of this radionuclide is limited by the diffi-
culties found in the preparation of safe solid sources.  the
only techniques we have found in the literature are those
reported by riechert and mundinger and by rames and
moravek, who used respectively small plastic capsules
filled with phosphomolybdic acid solution, and ca(po4),
grains, labelled with phosphorus-32.  these methods
require a delicate preparative work, and, moreover, a
large b-self-absorption effect can be expected in both
cases.
a new simple method for the preparation of grains
labelled with phosphorus-32 basically consists in ad-
sorbing labelled po4 3- ions on an active aluminium oxide
film produced by anodic oxidation of aluminium wire.
the adsorption capacity of the oxide film for po3 3- ions
is quite high, but the process is reversible: the phos-
phorus-32 activity is partially desorbed, even after
'sealing' in boiling water, when the labelled wire is kept
in isotonic sodium chloride solution.
.I 558
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31
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effect of parathyroidectomy and ferric dextrin
upon calciphylactic sensitization by uremia
experiments on the rat indicate that calciphy-
lactic sensitization can be achieved by bilateral
nephrectomy.  intravenous administration of a
ferric dextrin preparation (fe-din) induces
selective calcification in the buccal mucosa,
esophagus, trachea and mediastinum of the
nephrectomized rat although it produces no such
changes in intact control animals.  conversely,
fe-din prevents the cardiovascular calcification
normally elicited by nephrectomy.  parathy-
roidectomy protects the nephrectomized rat
against the fe-din-induced calciphylaxis.
hence, it may be concluded that: 1) autologous
parathyroid hormone, in amounts secreted by
the glands, can act as a calciphylactic sensitizer
and 2) fe-din is highly effective in protecting the
cardiovascular system against uremic damage.
.I 559
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31
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mediastinal parathyroid adenoma
a case of hyperparathyroidism with hypercalcemic crisis is presented.  the
tumor was a well differentiated and encapsulated parathyroid adenoma, un-
usually located in the anterior mediastinum, lying both within and without
the pericardial sac.  the surgical approach was directly through the sternum
with a mediastinal exploration.  the postoperative course was uneventful and
gratifying, with complete correction of both symptoms and abnormal laboratory
findings.
.I 560
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19
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clinical experience with
primary hyperparathyroidism:
evaluation of treatment
forty-four patients with "operatively proven" hyperparathyroidism were
evaluated to decide 1) whether or not the diagnosis could be substantiated
by some postoperative observations other than the gross anatomic diagnosis
of the operative specimen and 2) what the long term value of operative
treatment would be.  it was found that an immediate and significant fall
in urinary phosphorus excretion best documented the diagnosis of primary
hyperparathyroidism.  over intervals up to 10 years, follow-up of the
patients suggested a favourable response of the disease to operative
treatment.
.I 561
.C
31
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the dilution test as a measure of renal function in niobium-poisoned rats
control, female, albino rats given a water load of 50 ml/kg, excreted
50 per cent of this load as urine within 94  11 minutes (teu50).
the administration of a single intraperitoneal dose ranging from 10
to 30 mg nb/kg resulted in 2- to 4-fold increases in the teu50 value
24 hours after the niobium was injected.
when niobium was complexed with ascorbic acid prior to injection the
teu50 value was within control limits.  however, rats given a single
intraperitoneal dose of niobium and then given 3 doses of ascorbic acid at
intervals of 1, 3, and 6 hours showed teu50 values that were not markedly
different from those observed in rats given niobium only.
increased teu50 values were observed in rats given single intraperitoneal
doses of uranyl nitrate (1.2-2.4 mg u/kg), mercuric chloride (2.0 mg hg/kg)
and sodium tripolyphosphate (480 mg/kg).
.I 562
.C
19
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influence of parathyroid activity on ion
exchange in various tissues
1. balance data from three patients with hypoparathyroidism, who were
given parathyroid extract, are presented.  the metabolic response was
complex.  the data demonstrate losses of phosphate, magnesium, sodium
and potassium which were not accounted for by destruction of either bone
or non-osseous tissues.  preferential depletion of these minerals from bone,
or loss from non-osseous tissues, must be presumed.
2. the exchange of ca45, mg28, and p32 in a spectrum of rat tissues has
been studied in sham operated, parathyroidectomized, and parathyroid
extract treated rats.  the effects of parathyroidectomy on the development
of magnesium deficiency were determined.
3. four hours after parathyroidectomy, increased transport of calcium
into bone, kidney, intestine, liver, brain, and muscle was found.  six days
after parathyroidectomy equilibrium had been reestablished and exchange
rates were identical to those in sham operated animals.
4. the administration of parathyroid extract was associated with de-
creased transport of ca15, mg28, and p32 into bone.  ca15 exchange in kidney
was reduced but in all other tissues exchange of ca15 and mg28 was in-
creased.  p32 exchange in both intestine and kidney was mardedly increased
in animals receiving the extract.
5. parathyroidectomy greatly minimized the manifestations of mag-
nesium deficiency in young rats on magnesium deficient diets.
6. the results suggest that parathyroid hormone may affect the trans-
port and exchange of calcium, magnesium, and phosphate (and perhaps
sodium and potassium) in tissues other than those usually considered to
be target organs.
.I 563
.C
19
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effects of alkalosis on plasma concentration and urinary
excretion of inorganic phosphate in man
acute respiratory and metabolic alkalosis have
been shown to depress plasma phosphorus con-
centration in normal man.  the fall in plasma
phosphorus concentration is greater in respiratory
than in comparable levels of extracellular meta-
bolic alkalosis.  this fall is not attributable to in-
creased renal excretion or to migration into red
blood cells.  the evaluation of low serum phos-
phorus concentrations should always be carried
out with a knowledge of the ph and total co2
content of the plasma.
.I 564
.C
19
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the relationship between vitamin d and parathyroid
hormone
marit von stedingk
the effect of parathyroidectomy and parathy-
roid hormone administration upon the concentra-
tions of plasma calcium and phosphate have been
measured in vitamin d-deficient rats and the re-
sults compared to those observed in d-fed ani-
mals.  also, the influence of dietary calcium and
phosphate content upon these responses has been
investigated.  parathyroidectomy in the d-fed ani-
mal results in a rapid fall in plasma calcium and a
biphasic plasma phosphate response with an initial
fall followed by a striking rise.  in contrast,
parathyroidectomy in the d-deficient rat is fol-
lowed by no significant change in plasma calcium
and an immediate rise in plasma phosphate that
can be prevented by the administration of para-
thyroid hormone.  dietary phosphate restriction
abolished the effect of parathyroidectomy in both
groups of animals.
administration of a dose of 500 u of hormone
to the intact d-deficient rat had little influence
upon plasma calcium; a dose of 2,000 u did in-
crease plasma calcium.  a dose of 25 u was suffi-
cient to increase the plasma calcium of the d-fed
animal.  these results are discussed in relation
to the effects of vitamin d and parathyroid hor-
mone upon mitochondrial metabolism.
.I 565
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decrease in serum and urinary phosphorus in man
in the course of pyrotherapy
during the fever
peak occurring a few hours after the in-
jection, urinary phosphorus (up) dis-
appears entirely.  this fact cannot be
accounted for by the parallel decrease in
gfr, because serum phosphorus level
(sp) does not increase (as it would be
expected to, should retention occur) but
on the contrary, it, too, declines to a
marked degree.
the possibility that changes in sp and
up could have been brought about by an
increased utilization of glucose was also
considered.  an intravenous glucose toler-
ance test (method of macho and licko
(8)) was carried out in another group of
patients on control days and on days of
pyrotherapy five hours after the pyrogen
administration.  an increase in the rate of
"glucose utilization" was observed
(table 2).  however a different opinion is
found in the literature.  in the course of
glucose tolerance tests, conn (3) and
comparini (9) observed a lowered rate of
glucose utilization in febrile subjects.
malizia (10) found an accentuated rate
of decline of serum phosphorus during
glucose tolerance tests in subjects with
high temperatures, but the glycemic
responses did not differ from those ob-
tained when controls without fever were
subjected to the same tests.  whether it
be for utilization purposes or not, the
fact remains that a massive transfer of
phosphorus from the serum into the
tissues takes place in fever.
.I 566
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relationship of maximal tubular phosphate
reabsorption to filtration rate in the dog
a maximal renal tubular rate of reabsorption of phos-
phate (tmp) has been demonstrated in the normal dog.  in
the dog, as in the man, considerable variability in the tmp
often occurs.  while some of this variability remains unex-
plained, a direct relationship between glomerular filtration
rate (gfr) and tmp can be demonstrated when the gfr is
varied over a wide range.  this relationship suggests that
glomerular intermittency may exist in the dog.
.I 567
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20
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human growth hormone
clinical measurement, response to hypoglycemia and suppression by
corticosteroids
a standard test of growth-hormone secretory ca-
pacity, based on radioimmunoassay of plasma growth
hormone after insulin hypoglycemia, is described.  in
normal subjects a standard insulin tolerance test, caus-
ing an average blood glucose drop to 34 per cent of
resting values, produced a mean rise in growth hor-
mone to 45.2 millimicrogm. per milliliter at one hour,
with a total range of 25 to 70 millimicrogm. per mil-
liliter.  no response was observed in 5 hypopituitary
subjects.
under comparable hypoglycemic stimulation glu-
cocorticoid-treated patients showed a marked in-
hibition of the growth-hormone response, which was
related to dose.  subjects receiving more than 60 mg.
of cortisol equivalent per day showed a mean plasma
rise to 6.7 millimicrogm. per milliliter (range, 1.5
to 13 millimicrogm.).  subjects receiving 20 to 60 mg.
of cortisol equivalent per day showed a mean rise to
16.6 millimicrogm. per milliliter (range, 13 to 20
millimicrogm.).
inhibition of human growth hormone was also
affected by duration of glucocorticoid treatment, be-
ing greater with long-term than with short-term ad-
ministration.
.I 568
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31
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obesity and plasma levels of insulin and
growth hormone
studies of serum levels of glucose, free fatty acids, insulin, and growth
hormone during prolonged fasting suggest that insulin and growth hormone are
not responsible for certain metabolic abnormalities accompanying obesity.
.I 569
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31
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hypophysectomy, replacement therapy, and the tolerance of the
euryhaline killifish, fundulus heteroclitus, to hypotonic media
hypophysectomized fundulus heteroclitus, as previously reported, survive only a
few days after transfer from salt to fresh water.  survival time is the same
when fish are tested 2 weeks or 2 months after hypophysectomy.  gradual
dilution of the external medium produces failure at an average salinity of
0.26% (0.67-0.02%).  this salinity is comparable to that causing failure after
abrupt transfer.  although failure is associated with hypochloremia, daily
injections of a balanced salt solution or 0.6% nacl shorten survival.
daily injections of teleostean neurohypophysial peptides, arginine vasotocin
(2.25 and 0.0225 pressor mu per gram) and isotocin (1.32 and 0.026 oxytocic mu
per gram) do not prolong survival.  an extract of caudal neurosecretory tissue
(urophysis) from male tilapia mossambica had no beneficial action at doses of
50 ug per gram every other day.  purified ovine prolactin.  105 mu per gram on
alternate days, maintained survival of 10 of 11 fish for the duration of the
28-day test period in fresh water, irrespective of the period of pretreatment
in salt water.  purified bovine prolactin prolonged survival and 2 of 6 fish
were maintained for 28 days.  purified bovine growth hormone was ineffective.
monkey growth hormone containing 2 u per milligram of prolactin activity,
administered at a dose of 20 ug per gram (equivalent to 40 mu per gram
prolactin activity), prolonged survival.  human growth hormone containing 4 u
per milligram of prolactin activity, at a dose of 20 ug per gram (equivalent to
80 ml per gram prolactin activity) also prolonged survival and 4 of 6 fish
were maintained for 28 days.
the ability of pituitary preparations to protect hypophysectomized
f. heteroclitus from failure in fresh water appears to be related to their
prolactin activity and not to their content of neurohypophysial peptides.
this suggests that an adenohypophysial hormone resembling mammalian prolactin
is essential for survival of this fish in hypotonic external media.  carp
pituitary preparations do not protect hypophysectomized f. heteroclitus
although f. heteroclitus pituitaries are known to be effective.
.I 570
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resistance to human growth hormone in pituitary dwarfism:
clinical and immunologic studies
thirteen pituitary dwarfs have
been treated with human growth hormone
(hgh), and growth acceleration with doses of
5-7 mg/week has been observed in all but one
patient.  on therapy, this 7 1/2-year-old girl grew
at a rate of 1.05 cm/month for 7 months.
thereafter, despite larger doses of growth
hormone (15 mg/week), growth rate fell to
0.27 cm/month.  this rate of growth persisted
after stopping hgh.  on retreatment on 2
occasions, acceleration of growth did not
occur.  antibodies to hgh, absent in her
serum before treatment, were repeatedly
demonstrated in her serum in high concentra-
tion (hgh binding capacity up to 100 mg/1)
during treatment.  comparable titers of anti-
body have not been found in any of the 12
other patients receiving long-term hgh treat-
ment.  the specificity of the human anti-hgh
serum differed from rabbit anti-hgh serum.
whereas both monkey growth hormone
(mgh) and hgh were effective inhibitors of
the binding of hgh-131i by rabbit antiserum,
only hgh was an effective inhibitor with
human antiserum.  in like manner, a crude
placental extract which was an effective in-
hibitor for rabbit antiserum was ineffective
with human anti-hgh serum.
.I 571
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20
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influence of alloxan diabetes on
growth hormone content of the rat hypophysis
homog-
enates of adenophypophysial tissue obtained from alloxan-
injected adult male rats varying in duration and severity of
diabetes, as well as from diabetic rats maintained on an
insulin replacement regimen, were assayed in immature
hypophysectomized female rats.  the ability of these crude
hypophysial extracts to encourage tibial cartilage width ex-
pansion gain in body weight, and to depress hematocrit and
blood area levels was determined.  significant decrements in
ability to increase epiphysial cartilage width and ability to
depress hematocrits were noted 14 to 28 days following injection
of alloxan.  increasing the intensity of the diabetic state was
associated with decreased growth-promoting potency of hypo-
physial preparations as well as with decreased ability to
influence the hematological indices.  hypophysial extracts taken
from insulin-treated diabetic rats contained more growth
hormone than equivalent amounts of tissue obtained from
control rats.  it is concluded that the adenohypophyses of
diabetic rats contain diminished amounts of growth hormone
and the insulin repairs or encourages greater than normal ac-
cumulation of somatotrophin in these animals.
.I 572
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31
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pheochromocytoma
without hypertension
the patient developed symptoms of pheochromo-
cytoma about 15 years after the diagnosis of
eosinophilic adenoma of the pituitary gland.  the
predominating symptoms were profuse sweating
and tachycardia.  hypertension, hyperglycemia, and
glycosuria were absent.  the relation of the quan-
tity and the relative composition of catechol
amines to the symptomatology is discussed.  some
speculation regarding the etiological importance of
hypersecretion of growth hormone in pheochromo-
cytoma seems to be in order.
.I 573
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20
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hypoglycemia, growth retardation, and probable
isolated growth hormone deficiency in a
1-year-old child
a heretofore unreported association of defects, namely hypoglycemia, growth
retardation, and deficiency of serum growth hormonelike activity in a
1-year-old child is described.  human growth hormone (hgh), 3 mg. a day for 7
days, doubled the fasting blood sugar, prevented the postprandial hypoglycemia,
and reversed the sensitivity to tolbutamide and leucine.  treatment with 1 mg.
of hgh 3 times a week produced a growth of 7 inches in 3 months compared to a
growth of 1 inch in the previous 13 months.  since the protein-bound-iodine and
the response to methopyrapone were normal and the blood level of growth hormone
was low, this case is presented as a probable isolated growth hormone
deficiency.
.I 574
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20
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production, secretion, and availability
of insulin
a more precise understanding of the metabolic phase of diabetes mellitus
requires reliable information concerning the synthesis, manner of release and
transport of insulin, as well as of the behavior of agents which interfere with
the actions of the hormone by inhibition or destruction.  we shall deal with a
variety of these problems here and it might be helpful at the outset to outline
first our present understanding of the chemical structure of insulin since
many useful hints flow out of a consideration of the nature of the molecule.
.I 575
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20
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growth and growth retardation
various attempts have been made over the years to define growth.  from
the standpoint of this review, growth is the physiological accretion of new
tissue which is reflected in the acquisition of protein and water.  this
process in almost all instances leads to increase in size (length, weight, and
volume) and actively progresses from the fertilization of the ovum to the
period of sexual maturity where millions of cells are present in a state of
advanced organization.  with further time, growth is less and, indeed, may
become negative insofar as cells are lost.
.I 576
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20
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long-term treatment of hypopituitary and of
achondroplastic dwarfism with human
growth hormone
we have treated an 8 year old hypopi-
tuitary dwarf intermittently with hgh
(wilhelmi) for 4 years.  with 1 mg. 3
times a week the monthly growth rate
was 1/4 inch.  as treatment continued he
became resistant.  increasing the dosage
to 3 mg. 3 times a week at the age of 12
induced a monthly growth rate of 2/5
inch.  this growth-promoting effect is at
least as great as that reported for the
li and raben preparations.  we have
also treated a 15 year old severely de-
formed 'achondroplastic' dwarf for a
year.  with 3 mg. 3 times a week he
grew 1/2 inch in the first month.  the
spurt in growth subsided.  with 5 mg.
3 times a week he grew another 1/2 inch
in a month, but growth was not main-
tained.
.I 577
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20
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acromegaly
the effects of various steroid hormones on the
insulin-induced growth hormone response
and peter h. forsham
the availability of a sensitive assay for human growth hormone has made
it possible to directly measure the effects of various agents purported to
alter growth patterns.  acromegalic patients present a special problem both in
early diagnosis and in therapy.  being able to measure growth hormone in
these patients provides an accurate index of activity and a precise measure
of therapeutic effectiveness.
in an attempt to determine whether a pituitary block of growth hormone
secretion is feasible in this condition, a study was made of the effects of
estrogen, androgen and glucocorticoid administration on growth hormone
response to a standard insulin tolerance test in a patient with active acro-
megaly.  in the dosage schedules used in this study, it was not possible to
suppress either basal growth hormone secretion or blunt its responsiveness
to the normal physiologic stimulus of hypoglycemia.
.I 578
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20
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practical human growth hormone
preparation and clinical use
human growth hormone was prepared from
acetone-dried pituitary powder by hot glacial
acetic acid extraction and subsequent precipita-
tion by sodium chloride and cold acetone.  the
yield was 13 per cent and the preparation was
called practical growth hormone in recognition
of its complement of corticotropin.
treatment of two dwarfs with practical growth
hormone in aqueous solution, 1 or 2 mg intra-
muscularly on alternate days, accelerated the
growth rate and there were no physical signs or
laboratory indications of adrenal stimulation or
other adverse effects.  the preparation is recom-
mended for its safety, simplicity and relatively
good yield.
.I 579
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hypophysectomy and the lipolytic action of epinephrine in vitro
the response of normal adipose
tissue to epinephrine (0.05 ug/ml incubation
medium) is completely abolished by hypo-
physectomy of the donor rats.  treatment of
hypophysectomized rats with crude, whole
rat pituitary extract restored the lipolytic ac-
tion of epinephrine to normal.  posterior pi-
tuitary extract and corticotropin replacement
was without effect.  thyrotropin injections
produced a partial, and growth hormone
treatment a full restoration of the lipolytic
action of epinephrine.  treatment of hypo-
physectomized rats with cortisol or cortico-
sterone reestablished the sensitivity of their
adipose tissue to epinephrine, but only when
relatively large doses of these hormones were
given.  physiological doses of triiodothyronine
(1 ug/rat/day), however, restored the nor-
mal response to epinephrine.  it is concluded
that several endocrine factors can influence
the lipolytic action of epinephrine but that
their physiological importance cannot yet be
quantitated.
.I 580
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20
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c-acetyl bovine growth hormone
a procedure is described for labeling bovine growth hormone
and human albumin with c-acetylation.  the labeled molecule
was biologically and antigenically similar to unlabeled bovine
growth hormone.  following administration of the labeled
hormone to animals, the label appeared to remain attached to
the growth hormone molecule for at least 4 hours.  administra-
tion of the labeled hormone promoted growth in hypophysec-
tomized rats and increased the free fatty acid concentration
in rabbit serum to a degree comparable with that seen following
administration of unlabeled growth hormone.  rabbit anti-
bovine growth hormone serum neutralized the rat growth
response to the acetylated hormone, and immunized rabbits
had altered isotope dilution and no increase in serum free fatty
acids after intravenous injection of the labeled hormone.
.I 581
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20
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growth hormone
growth hormone influences protein, fat,
carbohydrate, and mineral metabolism.  it
promotes nitrogen retention, growth of
cartilage, transportation of amino acids
through the cell wall, and incorporation of
amino acids into protein.  this factor mo-
bilizes free fatty acids from adipose tissue
and increases the serum concentration of
these substances; long-term administration
of this hormone is followed by depletion of
body fat stores and inhibition of fatty acid
synthesis.  in diabetic subjects growth hor-
mone administration is followed by hyper-
glycemia, glycosuria, and ketosis; its effect
on carbohydrate metabolism in normal sub-
jects is more subtle.  sodium, potassium, and
inorganic phosphate are retained following
the administration of growth hormone.
hypercalciuria also accompanies such treat-
ment, an effect mediated through the para-
thyroid glands.
human growth hormone may be detected
in the serum through the use of the radio-
immunoassay.  the hypothalamus is inti-
mately involved with the control of the
secretion and release of growth hormone
from the pituitary.  there is a correlation
between the availability of glucose for me-
tabolism and the plasma concentration of
growth hormone; when glucose is unavail-
able growth hormone is released in order to
provide a substitute source of energy, fatty
acids.
the administration of growth hormone
to the patient with hypopituitarism is fol-
lowed by growth in many instances, but it
has not usually been effective in promoting
growth in individuals with other abnormali-
ties.  acquired resistance to the effect of
growth hormone is accompanied by the de-
velopment of antibodies directed against
this protein.
.I 582
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31
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recent advances in physiology of bone: part i
our introductory textbook summarizes knowledge of the biochemistry and
physiology of bone and calcium metabolism up through 1960.  in this lecture,
we will outline a few important advances appearing since that time.  references
to the original literature need not be repeated here.  the
object is to bring some of the subjects we are investigating up-to-date and
to present new problems for laboratory research.  the hypothetical new hormone,
calcitonin, of copp and cameron will be discussed in detail in dr. mclean's
lecture on the parathyroid glands and bone.
.I 583
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31
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hyperplastic lesions of mouse mammary
glands after treatment with 3-methyl-
cholanthrene
hyperplastic lesions were present in the mammary glands of
mice treated with 3-methylcholanthrene and exogenous hormones.  the
lesions were similar to those found in glands that were exposed to mammary
tumor virus.  it is probable that the production of mammary gland hyper-
plastic lesions could serve as a measure of the effectiveness of a chemical
compound as a carcinogenic agent for the mammary gland.
.I 584
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20
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bone growth and metabolic studies of premature
infants treated with human growth hormone
the influence of exogenous human
growth hormone on growth and metabo-
lism of premature infants was observed.
it was not possible to register any in-
crease of linear bone growth after hormone
administration; concomitantly urinary hy-
droxyproline excretion did not change
significantly.
nitrogen balance studies indicated a
sharp increase of nitrogen retention, due to
a reduced urinary excretion, in all infants.
calcium and phosphorus balances rose in
three out of four premature infants treated
with growth hormone, but the characteris-
tic sth calciuric action of sth was not
observed.  furthermore, sth failed to in-
duce any significant increase in nefa
serum concentration of premature infants.
it may therefore be concluded that the
metabolic response of premature infants to
sth differs consistently from that normally
observed in more mature subjects.
.I 585
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20
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growth hormone action on rat liver rna
polymerase
the effect of growth hormone on the activity of the
rna polymerase measured in this system is shown in
table 2.  it can be seen that hypophysectomy of the rat
results in decreased activity of the rna polymerase and
that the injection of 1 mg of human growth hormone into
the rat 12 h before death increased the enzyme activity
both in hypophysectomized rats and in normal rats.
however, the stimulating effect of growth hormone was
only seen in the absence of high concentrations of ammon-
ium sulphate; raising the ionic strength of the assay
medium abolished the growth hormone effect.  it should be
mentioned that addition of growth hormone in vitro in the
presence or absence of ammonium sulphate has had no
significant effect on the labelling of the rna by the
nuclear preparations.
.I 586
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31
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mammary growth in rats treated with somatotropin during
pregnancy and/or lactation
groups of rats received daily
injections of 2 mg somatotropin (sth) from
either day 3-19 of pregnancy or day 1-13
of lactation.  another group of rats received
graded increments (0.5-3.0 mg) of sth
every 6 days during both pregnancy and
lactation.  other groups of rats served as
pregnancy and lactation controls.  mammary
gland deoxyribonucleic acid (dna) content
was determined in all rats and milk yield
was determined in all rats carried to day
14 postpartum.  significant increases in mam-
mary dna occurred in all rats treated with
sth irrespective of dose or schedule of in-
jections when compared to gestation controls.
a significant elevation in mammary dna
above the lactation control level was also
evident in rats receiving the hormone and
carried to day 14 of lactation.  milk yield
of rats treated with graded increments of
sth was significantly greater than that of
control lactators but milk yield of rats re-
ceiving a constant daily dose of the hormone
did not differ from that of controls.
.I 587
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31
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growth retardation accompanying diabetes insipidus: an additional
mechanism?
from the above considerations, we may divide patients with nephrogenic
diabetes insipidus into at least two categories: (1) those who fail to respond
to currently available therapeutic products as well as to their own presumably
normal secretion of adh; (2) those with similar similar unresponsiveness to
treatment but with presumably reduced secretion of adh.  the adh-growth hormone
theory may well account in part for growth retardation in the later group.
.I 588
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20
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studies on growth hormone secretion
in rats with the hypophysis autotransplanted
to the kidney capsule
the secretory capacity of the pituitary gland, autotransplanted to the
kidney capsule, was studied with special regard to the secretion of growth
hormone (gh).  body weight, body length, tibial epiphyseal width and
the mammary gland development after testosterone stimulation were
studied.
body growth and tibial epiphyseal width were markedly reduced in the
rats with transplanted hypophysis, but not as much as in the hypophys-
ectomized controls.  after injections of 0.25 mg testosterone propionate
daily for 10 days, only a few groups of alveoli were seen in the mam-
mary glands of the transplanted rats.  these observations show that there
is a considerable deficiency of gh in rats with the pituitary gland auto-
transplanted to the kidney capsule.  however, the development of a few
alveoli in the mammary glands is in favour of the theory that a small
amount of gh is secreted from the transplanted pituitary tissue.
injections of a purified vasopressin preparation (pitressin) in the rats
with autotransplanted hypophysis did not influence body growth, tibial
epiphyseal width or mammary gland development.  further, no effect of
pitressin was seen on the tibial epiphyseal cartilage of rats with intact
pituitary gland as has been reported by del vecchio et al. (1958) and
hiroshige & itoh (1960).  these experiments therefore do not support the
view that vasopressin acts as a gh releasing factor.
.I 589
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20
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the effect of human growth hormone in
hypopituitary dwarfism
human growth hormone (hgh) raben has been
used in a dosage of 2 mg./m.2/day or 5 mg./m.2 twice
weekly.  this dosage is probably in or below, but
certainly not above, the range of physiological
replacement therapy.
in a standardized five-day metabolic hgh test
hypopituitary dwarfs retain more n than children
without gh deficiency.  this test is valuable
diagnostic help in hypopituitary dwarfism.
a prolonged treatment with hgh accelerates
growth in hypopituitary dwarfs but not in children
without gh deficiency.  growth rate, induced by
this treatment, is first above average and later average
or below average for age.  this decreasing response
to hgh is typical for the general phenomenon of
catch-up growth and is not caused by the develop-
ment of antibodies.
of 9 hypopituitary dwarfs, treated for at least 9
months, 3 were growth resistant from the beginning
in spite of a high n retention in the preceding hgh
test.  this resistance is caused by the development
of high titres of specific hgh antibodies in the very
first few months of treatment.  these antibodies
suppress the effect of hgh both on metabolism and
on growth.  the unexpected occasional induction in
man of antibodies against a homologous protein
hormone is of great interest.  the possibility that
these antibodies might be active not only against the
homogenous but also against the endogenous hormone
could have a far-reaching biological importance.
.I 590
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20
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effects of short term administration of
hysiological doses of human growth hormone
in three patients with turner's syndrome
h. e. sjoberg
the effect of apparently physiological doses of human growth hormone
was investigated in three patients with turner's syndrome in short term
metabolic balance studies.  the subjects presented an abnormal sex chro-
mosome constitution and an increased level of sulphation factor activity
in serum.
two dose levels of hormone were used, and there appeared an anabolic
response to both.  no correlation with dose was obtained for any of the
parameters used except for urinary magnesium, where the retention was
greater with the higher dose.  the sulphation factor activity of serum in-
creased during hormone administration in the one case studied in this
respect.
the urinary excretion of hydroxyproline was within the normal range in
the two patients studied in this respect, and was not altered by growth
hormone.
all patients had an increased urinary excretion of creatine which at
present cannot be explained.  the creatinuria diminished during growth
hormone treatment.
the mechanism behind the retarded growth is discussed.  it is suggested
that a major factor might be a defect in the center for linear growth,
i.e. the epiphyses that would make these less responsive to all the factors
normally stimulating the growth processes in the epiphyseal zones.
.I 591
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31
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the effect of growth hormone
on kidney transamidinase in the
hypophysectomized mouse
the role of growth hormone and certain other endocrine factors in re-
gulating kidney transamidinase has been investigated in the mouse.  the
kidney transamidinase values are low following hypophysectomy.  growth
hormone administration in doses of 0.5 to 5.0 ug/day (ovine nih) restore
the enzyme activity towards normal.  a bioassay for growth hormone is
suggested based on the determination of the total kidney transamidinase.
intact mice that had been given relatively large doses of triiodothyronin
had low enzyme activities.  enzyme values in alloxan-treated mice were
normal.
.I 592
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31
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influence of hormones on tumor growth and plasma prolactin levels in rats
bearing a pituitary "mammotropic" tumor
the effects of estradiol, cortisol acetate, thyroxine, or thiouracil on
tumor growth, organ weights, and plasma prolactin levels were determined
in rats bearing a furth pituitary "mammotropic" tumor (mtt.f4).  this
tumor is known to secrete large amounts of adrenocorticotropin, somatotropin,
and prolactin, but no follicle-stimulating hormone, luteinizing hormone,
or thyrotropin.  at the dose levels used, estradiol significantly suppressed
tumor growth without influencing body growth, and it partially inhibited
enlargement of the adrenals and atrophy of the thymus.  cortisol acetate
significantly reduced both tumor and body growth.  thyroxine had no significant
effect on tumor growth but enhanced the somatotropic effect as indicated by
increases in body growth and organ weights.  thiouracil had no significant
effect on tumor or body growth, although it significantly increased thyroid
weight.  estradiol, cortisol acetate, and thyroxine each increased the plasma
prolactin levels of the tumor-bearing rats.
.I 593
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20
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studies with human growth hormone
ten dwarfed patients whose short stature was of
varying aetiology were studied by investigation of
some of the metabolic effects of human growth
hormone, 10 mg. being administered daily for a
period of 5 to 9 days.  the patients were maintained
on a constant diet during a preliminary control
period, while receiving hgh, and in 7 patients from
2 to 7 days in the post-hgh period.  hgh produced
a reduction in serum cholesterol, with a
rebound on withdrawal, in 7; a delayed clearance of
fat from the blood after a fat load in 9; and the
appearance of pre-b lipoprotein in the fasting state,
as measured by paper electrophoresis, in all of them.
the fall in serum cholesterol and the rebound on
withdrawal of hgh has some relevance to the
observation that hypercholesterolaemia occurs in
some hypopituitary patients even in the absence of
hypothyroidism.
no change was observed in tests of thyroid and
adrenocortical function during the short-term high
dosage administration of hgh.
hypopituitary patients show a considerable
retention of nitrogen on hgh administration, and
we have confirmed the work of prader and his
colleagues that this provides a valuable diagnostic
test for growth hormone deficiency.  the measurement
of urinary nitrogen excretion after the withdrawal
of hgh also promises to be a useful investigation
in the differential diagnosis of short stature.
nitrogen excretion in the withdrawal phase in
hypopituitary children returns slowly to its pre-hgh
levels; two non-hypopituitary dwarfed
children excreted much more nitrogen in the withdrawal
period than they retained in the hgh
period.  one primordial dwarf showed a negligible
change in urinary nitrogen excretion both in the
hgh and in the post-hgh periods.
.I 594
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hormonal modification of the distribution of 1-amino-
cyclopentanecarboxylic acid-1-c14 in the rat
four hormones have been examined for their ability to alter the distribution
in the rat of the new model amino acid,
1-aminocyclopentanecarboxylic acid-1-c14.  although
the total tissue concentrations of this
amino acid were considerably less than those
found previously for a-aminoisobutyric acid,
the changes produced by the hormones were
much the same for both amino acids.  hydrocortisone
elevated the liver level of 1-aminocyclopentanecarboxylic
acid within 2 hr.
bovine growth hormone accelerated entry of
the amino acid into both skeletal muscle and
liver of hypophysectomized rats within 1 hr.
testosterone propionate elevated its distribution
ratio in the kidney but not in skeletal
muscle, whereas b-estradiol significantly increased
uptake of the model amino acid only
by the immature uterus.  only growth hormone
produced a significant change in the serum
level of 1-aminocyclopentanecarboxylic acid
under the conditions used.
.I 595
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insulin and insulin antagonism
as i said earlier, no simple answer
has yet emerged from the large amount of
research that has been directed toward determining
the nature of the substance or substances
responsible for the diabetes-inducing
and insulin-antagonizing actions of the
anterior lobe of the pituitary gland, and to
ascertaining their mechanism of action.
growth hormone and corticotropin certainly
qualify, but so do any other factors that can increase the mobilization of fats
as plasma albumin-bound free fatty acids.  the idea
that the yet incompletely characterized insulin
antagonist in the pancreas may be
liberated into the blood under the influence
of growth hormone and may play a role in
the process by which growth hormone diminishes
the activity of insulin in promoting
the utilization of glucose is attractive to me,
but still remains to be confirmed.
.I 596
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relationships of growth hormone, steroids and relaxin in the
transformation of pubic joint cartilage to ligament in
hypophysectomized mice
the histological changes occurring
in the pubic joint of hormonally
treated intact or hypophysectomized mice
have been studied.  estrogen treatment resulted
in bone resorption and transformation
of the cartilage caps of the pubic bones to
fibrocartilage in intact mice but not in hypophysectomized
mice.  furthermore, relaxin
failed to influence the appearance of the pubic
joint of estrogen-primed hypophysectomized
mice, whereas it induced the development of
long interpubic ligaments in intact mice.
when growth hormone (sth) was administered
to hypophysectomized mice, the pubic
joints responded to estrogen with bone resorption
and transformation of the cartilage caps
to fibrocartilage.  sth treatment also restored
the ability of the pubic joint of hypophysectomized
mice to proliferate long interpubic ligaments
when estrogen and relaxin were administered.
progesterone specifically inhibited
ligament formation due to relaxin injection
without altering the histological changes
associated with estrogen treatment, both in
intact mice and in sth-maintained, hypophysectomized mice.
.I 597
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effect of testosterone propionate and growth hormone on
growth and chemical composition of muscle and other
tissues in hypophysectomized male rats
the effect of testosterone
propionate and growth hormone on the
growth of muscle, bone, pelt, viscera and
seminal vesicles was studied in hypophysectomized
male rats.  testosterone (0.1 mg/day)
stimulated growth in the levator ani muscle
and seminal vesicles but had no effect on the
other tissues studied.  growth hormone (0.1
mg/day) accelerated growth in all tissues
except the seminal vesicles.  testosterone did
not enhance the growth-promoting effect of
growth hormone in any tissue except the
levator ani muscle.  growth hormone stimulated
deposition of myosin, sarcoplasmic
proteins, collagen and alkali-soluble proteins
in the thigh muscle of hypophysectomized
rats.  the composition of the muscle in treated
and control hypophysectomized rats was the
same as that in normal rats.  growth hormone
also increased the collagen, keratin-clastin
and globular protein content of the pelt.  the
effect of growth hormone on the proteins of
muscle and pelt was not enhanced by testosterone.
testosterone given alone had no effect
on the chemical composition or content of the
muscle and pelt in hypophysectomized rats.
.I 598
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growth hormone and diabetes mellitus
since the advent of insulin the vascular and neurological
lesions have replaced ketoacidosis as the major
problem in diabetes.  although good control of hyperglycemia
and glycosuria with diet and insulin may
influence favorably the development of the ocular angiopathy,
there remains a high incidence of these
lesions with resulting blindness despite such good
control.
growth hormone may be a major factor in the
pathophysiology of diabetes mellitus and its effects
may be a reflection of the genetic disturbance.  its importance
was first realized by the classical experiments
of houssay and those of young which revealed its
diabetogenic effects in experimental animals.  the association
of acromegaly with diabetes has been for a
long time the major argument in support of the hypothesis
of the diabetogenic effect of growth hormone
in man.
.I 599
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experiments on the contribution of somatotrophin to prenatal growth in the rat
hypophyseoprivus in a fetal rat induced by decapitating the fetus in utero
retards fetal growth.  this effect can be prevented by injected somatotrophin.
these observations substantially support the view that in the normal rat
shortly before birth the fetal somatotrophin from the developing hypophysis
governs in part the prenatal growth which occurs at that time.  although
complete hypophysectomy of a pregnant rat retards
the growth of fetuses, the manner
of its action is obscure.  in an individual litter, combined hypophysectomy
of the mother and hypophyseoprivus in a fetus retards fetal growth but not
to any greater extent than hypophysectomy of the mother without
hypophyseoprivus in the fetus.  in the intact fetus injections of somatotrophin
(armour) do not accelerate fetal growth, presumably because ample fetal
somatotrophin from the developing hypophysis is present.
.I 600
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insulin and protein metabolism
the present status of protein synthesis within cells has
been outlined.  protein is formed in the absence of insulin;
the net formation of protein is accelerated by insulin.  the
effects of insulin on protein metabolism take place independently
of the transport of glucose or amino acids into the
cell; of glycogen synthesis; and of the stimulation of high
energy phosphate formation.  in the case of protein metabolism,
as in certain studies on the pathways of glucose and
fat metabolism, these observations reveal striking intracellular
effects of insulin in many tissues.  within most
tissues the effect of insulin appears to find expression predominantly
at the microsomal level.  incidentally, other
hormones which affect protein metabolism such as growth
or sex hormones appear to act at the microsomes.  the fact
that insulin exerts effects on protein metabolism at other
intracellular sites as well as the above independent effects
leads one to agree that its action consists of a stimulation
of multiple, seemingly unrelated, metabolic events.
the fact that an immediate effect of insulin on protein
synthesis is independent of the immediate need for extracellular
glucose or amino acids does not mean that the
sustained functioning of cells is likewise independent.  the
biochemist is fully aware of metabolic defects in diabetes
which are not altered by insulin in vitro, but which demand
varying periods of pretreatment of the animal.  it is
also known that in diabetes some proteins (enzymes) may
be deficient while others may be produced in excess in the
absence of insulin.
it is suggested that the physician desires at least two
kinds of relation between these fundamental studies and his
patients.  one is the possible relation of a deficiency of insulin
action to pathological processes in tissues which have
not as yet been examined by the methods described.  the
other is the need for more accurate measurements of the
metabolic disorder and its control than such things as
urinary and blood glucose.  in developing such future improvements,
the place of insulin in protein biosynthesis
must be kept in mind.
.I 601
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the influence of blood glucose on the plasma
concentration of growth hormone
a. berson, m.d.
a sensitive and specific assay method has been used to
demonstrate acute changes in plasma hgh in normal and diabetic subjects.
hgh secretion is suppressed by glucose administration
and markedly stimulated by hypoglycemia, by interference
with intracellular glucose utilization.  high levels of hgh
were also observed during prolonged fasting, after exercise,
and four to six hours following oral glucose administration.
abnormalities in hgh secretion were found in association
with acromegaly and obesity, and following section of the
hypophyseal stalk.
the half time for disappearance of endogenous plasma
hgh is twenty to thirty minutes.
.I 602
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failure to thrive: the diencephalic syndrome of infancy and childhood
we have presented a case of a patient with an
astrocytoma of the optic chiasm who demonstrated
the features of the "diencephalic" or
"failure-to-thrive" syndrome.  overactivity, overalertness
and emaciation were significant symptoms
in this patient.  roentgenograms characteristically
demonstrate normal bone growth,
good muscular outline, and absent subcutaneous
fat.  increased growth hormone was found and
may be a factor in the disturbed lipid metabolism.
.I 603
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increased stature
the fact that some patients respond to growth-hormone
administration with linear growth does not indicate growth-hormone
deficiency or hypopituitarism.  yet this appears to
be the main factor that led these authors to assume that
their patients were suffering from hypopituitarism.  the
conclusion that children with growth retardation should be
subjected to a short trial period of treatment with growth
hormone to single out those who are deficient in growth hormone
is therefore of questionable validity.
rather, because of the limited supply of human growth
hormone, it appears that much more stringent criteria for
administration of human growth hormone should be advocated.
every effort should be made to uncover the patients
who might benefit from growth hormone by utilizing reliable
tests of pituitary function and perfecting a suitable growth-hormone
assay.  those who have more than suggestive evidence
of hypopituitarism and growth-hormone deficiency
should then be treated and carefully evaluated for response
after long-term treatment.
.I 604
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on language disorders in young children: a reorganization of thinking
current questions and confusions about
the use of the term aphasia with reference
to young children seem often to
reflect semantic problems accruing
from professional habits of thinking in
terms of etiologic and pathologic labels.
it is argued that if the term aphasia is
generalized simply to refer to inabilities
or interferences in the development of
language comprehension and use, then
it is the task of an evaluating group to
describe as well as possible, and in detail,
the specific impairments of function
in each child.  this task commonly
requires the use of an extensive period
of "diagnostic teaching," wherein care
is taken to explore which sensory and
motor modalities are working and
which are not, and whether integration
of various stimuli is taking place.
some current ideas are discussed with
reference to descriptions of impairment,
causal factors that are fairly unique in
childhood, some thoughts about the
neurophysiology of the human "language
system," and some psychosocial
factors important for language-learning.
special attention is given to various relations,
in terms of temporal resolving
power, between sensation and sensory
integration.  a scheme, or model, is suggested
which may prove fruitful for
experimental design in attacking some
of these problems at a prelanguage or
premeaning level.  it is argued that the
proportion of "unknowns" can be reduced
by careful study based on information
about impaired functions within the sensory-integrative-motor complex,
without particular regard for "site and
extent of lesion."
.I 605
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therapy for hearing-impaired children
in comparison with the u.s.a. and
europe, canada is still in the early
stages of developing rehabilitative services
for speech and hearing-impaired
children and adults.  they are available
in some large canadian cities, but in
the opinion of the authors, these services
and more should be made available
to the hearing impaired of every canadian community.
specialists in the rehabilitation of
communication problems, along with
members of other medical, paramedical and social services, recognize
the vast variety of communication
problems that can occur in persons
of all ages, the tremendous handicap
that such problems represent to the
individual, the loss that such handicapped
persons represent to our society
and the pressing need for efficient and
effective rehabilitation.  more practically,
it is hoped that this article has
made its readers more aware of the
vast variety of rehabilitative procedures
available today for the hearing
impaired.  with a better understanding
of the problems of defective hearing,
it is hoped that all readers, professional
and non-professional, will join
in mutual support for the establishment
of these vitally needed services
in their respective communities.
.I 606
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baby habits, genesis and ontogenesis
for adam may be looked upon
as the personification of paleolithic
man-100,000 generations of primitive
human animal-whose evolution
can be of vast importance to
the understanding of the ontogenesis
of the behavior of babies.  not
for nothing did the deuteronomist
reiterate "remember the days of
old, consider the years of many generations"
.I 607
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speech therapy with selected patients with
congenital velopharyngeal inadequacy
this paper has described the clinical speech problems of three patients
without cleft palates but with velopharyngeal inadequacy.  pharyngeal
flap surgery was performed on each patient after speech therapy was
found to be ineffective following systematic trial.  therapy continued
following the surgery.  the youngest child, a first grader, realized normal
speech following the surgery and therapy.  the two other children continue
to have aberrant but improved speech.
.I 608
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stimulus overload, action cycles, and the completion gradient
systematic inquiries into the origin of certain emotional disturbances
of infants show that consistent maternal care is vital for the
child's normal physical, psychic, and social development, indeed,
for his survival.  the most elementary precondition for consistent
maternal care is the physical presence of the mother or her substitute.
it has, however, become increasingly apparent that children's
development can also be stunted, and that they suffer damage of
varying extent by the attention of, and close contact with, a mother
who dispenses what seems to be the "wrong kind of mothering".
a model of the mother-baby interaction is proposed to explicate
the dynamics of the "wrong kind of mothering" and its
consequences: my proposition is that the mutual exchanges between
mother and baby consist in a give and take of action and
reaction between the two partners, which requires from each
of them both active and passive responses.  these responses form
series and chains, the single links of which consist in what i call
"action cycles," each completed in itself and at the same time
anticipating the next link.  i designated these seriated response
exchanges as the "precursor of dialogue," as a primal dialogue.
the dialogue acts as a vector of the baby's development,
influencing its direction and stimulating it to adaptive efforts and
psychic growth.  it follows that inappropriate mothering (quantitatively
as well as qualitatively) results in what is referred to at
this time as the "derailment" of the primal dialogue.
controlled experiments with animals, findings of experimental
psychology, and, lastly, clinical findings illustrate the
mechanics of the derailed dialogue and its sequelae.
in the cases under review a surfeit of stimulation, a psychic
overloading, resulted in the derailment of dialogue.  overloading
prevents its subject from completing actions or responses initiated
by him.  long-lasting overload results in the cumulation of "incompleted
action cycles".  the sequelae of this cumulation are
profound changes in the behavior of the individual.  these changes
are manifested in a departure from the norms of individual and
social behavior patterns that are maladaptive for the individual
and asyntonic with his society, that is, asocial.
the derailment of the dialogue is triggered, perhaps even
caused,
by the nature of the social setting.  one setting, over-population,
is extensively discussed in connection with an animal
experiment, and the implications for the human community are
examined.
.I 609
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children at kelbourne
kelbourne school, glasgow, which educates both
spastic and aphasic children, is the first school of its
kind to be administered by a local education authority.
its aphasic department, largely experimental in nature,
contains children aged three to eight.  in the spastics
department there are 45 children with severe physical
handicaps and their ages range from 3 to 16.
the school, which celebrated its golden jubilee last year,
has its origins in the maryhill hall public school for
defective and epileptic children which opened in 1907
with 12 pupils in premises of which, as an h.m.i. reported
four years later, 'it was impossible to speak favourably'.
the report continued, 'a public hall, used frequently in
the evenings for public entertainments, lacking proper
cloakrooms, bare in appearance, and generally comfortless,
should not be used for this purpose'.  the inspector's
words did not go unheeded and seven years later the
children were transferred with others to the new buildings
of percy street special school.  in the 1950s the name was
changed to kelbourne school.
between and through two world wars the school
provided education for physically and mentally handicapped
children but in 1955 a new unit was added and
spastic children were admitted for the first time.
gradually the emphasis shifted from children with other
physical and mental handicaps to the cerebrally palsied
and finally the entire building became available for
spastics.  two years ago the aphasic children joined the
school.  miss e.f. hamilton is the headmistress.
.I 610
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deafness
methods of detection, diagnosis, and management of deafness
in children depend so entirely on a knowledge of the processes
involved in communication by speech and in the acquisition of
this skill that i propose to consider them first.  it will be found
that the practical steps to be taken in dealing with patients flow
naturally from this knowledge.
.I 611
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pharyngoplasty in speech
where adequate palate repair is undertaken at 1 year there is no indication
for pharyngoplasty as well at that age.
pharyngoplasty is indicated as a "supportive" operation only when the
result of the palate repair can be assessed (5 years plus), and where the
speech result proves disappointing.
the figure of 171 pharyngoplastics in 944 cases applies to the known speech
results up to april 1963.  it follows that with follow-up of the more recent
primary cases pharyngoplasty may well be necessary in some.
the hynes pharyngoplasty has proved to be the most satisfactory.
.I 612
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verbal effects in the intermediate-size transportation problem
preschool children were given an intermediate-size discrimination problem,
told before each response that the reward was under the "medium" stimulus:
and 1- and 3-step transposition tests.  during training, group i was
group ii was told that it was "not under the big or little one"; and group
iii was not told anything.  the verbalizations were not given during the
tests.  groups i and ii learned the initial discrimination faster than group
iii, and transposed more than group iii, but there was a distance effect
in all three groups.  these results, and other data, suggest that the
deficiency in the verbal control over motor behavior in young children arises
from deficiencies in both the decoding and encoding processes.
.I 613
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the acquisition of formal features of language
children from different groups do not learn the same uses and functions for
language.  but every child must learn the formal features, or the "code" for
his language, thus creating a constant in every language acquisition situation.
.I 614
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mongolism-some clinical aspects
this is a review of 86 mongoloids seen over 5 years at the nebraska psychiatric
institute.  one-half of the sample were evaluated before their second
birthday.  eighteen per cent of the cases for whom birth weight data were
available weighed less than 5 1/2 lbs., double the national rate for
prematurity.  there was a bi-modal distribution of mother's age at the birth of
the mongoloid child.  pregnancy, labor and delivery complications were
reported in almost one-half of the cases.  seven per cent were breech
deliveries.  all cases were mr.  the most frequent type was moderate.  most
frequently mentioned characteristics were: generalized hypotonia (all but 2
cases); psychiatric disorders, 11 cases; abnormal eeg, 8 cases; hearing loss,
5 cases.
.I 615
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learning problems in children: ii. emotional aspects
at the last meeting we tried to deal with a general over-all approach
to the problem of learning, considering it not merely as a problem in
reading, but learning in general which begins at birth.
we hope to deal with this problem at a relatively high level and we
want to have the emotional problems dealt with in this manner rather
than in terms of diagnostic criteria.  the child with learning problems
should not be compartmentalized in terms of "organicity" and "nonorganicity".
the subject of this talk, then, is emotional issues in learning.
.I 616
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management of communication problems in infants and children
early detection and referral of a
child with a hearing or speech-language problem
is feasible and in most cases, very critical.  further
consultation can then be obtained and the child
placed on a training program geared to his needs.
.I 617
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the formation of a cleft palate unit- a preliminary report
with cleft palates, as in other surgical fields, changing
techniques and better management of the patient as a whole
render inexcusable the operative procedures that merely
drag together the edges of the defect and then leave a
cosmetically and functionally crippled child, to adapt itself
as best it may to the harsh competition of the outside
world.
ironically the problem of congenital defects increases as
our competence to deal with them advances.  in the past
these cases struggled to take their place on the marriage
market but the more skilled our rehabilitative procedures
become, the more likely are they to perpetuate their disability,
since a significant number show a hereditary tendency.
.I 618
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acquisition of language
although the work of bullowa, jones, and bever has some of its greatest
promise in the light it may shed on the development of functions of language
in children, the promise cannot be realized unless the authors give
a great deal of explicit attention to the framework of such analysis, for there
is not, as may be the case for phonological and grammatical development,
anything like a satisfactory body of linguistic theory and method as to the
terminal state.  while a good deal may be learned without such a theory, and
necessarily must be so learned, since the work in progress cannot be suspended
until such an unpredictable millenium, it still would be a pity if the
chance were lost for the interaction of the acquisition of data and the
improvement of theoretical notions.
let me complete my discussion by developing my argument in two
ways: (a) by briefly stating the nature of the problem with regard to the
terminal state of verbal development, (b) and by indicating what present
and future contribution such fields as anthropology, sociology, and social
psychology may be able to make to the solution of the problem.
.I 619
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the speech production and spoken language of the deaf
the distinction was made between speech production and spoken language in
analysing the oral output of those with hearing impairment.  a brief review of
studies in both areas was undertaken, including the report of a new electronic
visual monitoring device, the glossal transducer.  it was postulated that the
deaf utilise a unique visual-to-motor conversion within the brain when speaking
and monitor conscously by tactile-kinaesthetic control.  the more recent
studies relate to the syntactical features of the speech of the deaf.  these
show that deafness creates telegraphic speech with reduced sentence length and
omissions of essential words such as functors.  the speech of the deaf seems to
contain mostly nouns and verbs, with a limited number of words used to expand
verb forms.
.I 620
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cognitive functioning in early infantile autism: an examination of four cases
by means of the wechsler intelligence scale for children
the results are communicated which were obtained from an examination,
by means of the wechsler intelligence scale for children, of four cases of
early infantile autism.  these cases had developed in such a way that a
reliable investigation by means of a mental test had become possible.
according to their full scale iq's the four cases fell within the category of
dull normal intelligence or less.  all of them showed a considerable
discrepancy between the verbal and the performance iq, the performance iq being
of much higher value.  the composition of the autistic test profiles was
characterized by a large variability in the subtest scores, discriminating the
autistic group significantly from non-autistic control groups.  the subtest
score divergencies, responsible for the large variability, showed a distinct
pattern, being specific for the autistic group as a whole.  this group could
be considered as a distinct group particularly by a marked tendency to achieve
poorly and far below the subject's average level in the subtests comprehension
and vocabulary, and to achieve superiorly and far above that level in the
subtests block design and object assembly.  by specifying the mental functions,
conditional for success in these four subtests that occupy extreme positions
within the autistic test profiles, it was concluded that the autistic patients
apparently were able to achieve well, or even superiorly, only if the task
could be performed on a purely perceptual level.  but they failed as soon as
an appeal was made to thinking proper.  this was thought to be due to a
disability in dealing with imaginary things and imaginary situations, or,
in other words, to an incapability to objectify what is not actually present
in the subject's concrete situation.  it is proposed that this impairment
could be reduced to a lack of symbolic means, being the correlate of a
defective or insufficiently developed language in the patients.  it is further
proposed that children suffering from early
infantile autism might not be able,
or at a later stage only, to reach that level of language development in which
words can be used as symbols,
representing absent things and absent situations.
.I 621
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otologic care of cleft palate cases
the purpose of this study was to review the ear pathology
in 480 patients whose cleft palates had previously been repaired.
despite concern over speech regression, tonsil and
adenoid surgery was carried out on 66 of these patients.  when
carefully done, this was accomplished with considerable overall
improvement, particularly for the benefit of the conductive
hearing loss.
sixteen cases had exact documentation of these results by
virtue of speech recording and accurate audiometric records.
.I 622
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congenital heart disease, deaf-mutism and associated somatic malformations
occurring in several members of one family
m.d. and patrick h. lehan, m.d.
a unique family is described in which the
mother and four of her eight children have pulmonary
stenosis.  two of the four affected children
are deaf-mutes; one of these has, in addition
to the pulmonary valvular stenosis, idiopathic
hypertrophic subaortic stenosis.  all the affected
children had several associated somatic malformations.
genetic and nongenetic factors and
their role in the development of the malformations
are discussed.  it is suggested that the cardiac
defect is transmitted by a single non-sex-linked
genetic factor (dominant autosomal
inheritance).  in the presence of a normal karyotype
it appears that a single dose of either a
point mutation, or a small deletion or translocation
is the most likely cause.
.I 623
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histidinemia
a review of published reports of
histidinemia indicates that this condition
has a variability of clinical and biochemical
expression.  three children with histidinemia,
born of a consanguineous marriage
are reported here.  they had blond hair,
blue eyes, speech defects, mental retardation,
and a peculiar eeg abnormality.  they
also exhibited characteristic biochemical
findings of the disease: elevated blood and
urine histidine, increased urine imidazolepyruvic
acid, and a sustained high rise in
plasma histidine following an oral histidine
tolerance test.  they did not, however, have
the reduction of skin histidine a-deaminase
activity which has been observed in some
children with this condition.  tests for determination
of heterozygotes in the family
were not successful.
parental consanguinity and normal skin
a-deaminase activity set these children apart
from other reported cases.  the first lends
support to the hypothesis that histidinemia
is inherited as an autosomal recessive trait;
the second supports the idea that the genic
fault which results in reduced histidine a-
deaminase activity can be expressed to a
different degree in different tissues.  these
children seem to represent a variant of
histidinemia where liver histidase activity is
reduced while skin histidase activity is
present.
.I 624
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interpretation within the metaphor
analytic investigation of the use of the metaphor was first given impetus
by ella freeman sharpe (1950), who explored the symbolic
meaning of particular metaphoric phrases with reference to the body
and libidinal needs.  currently, interest has become focused upon the
use of the metaphor as a self-conscious, rational therapeutic technique
of communication, of particular value with those patients who have
reached "the borderline of sanity".  ekstein (1961) and ekstein and
wallerstein (1957) have emphasized that the use of the metaphor
should be regarded as an essential technique for gradually establishing
communication and initial insight with borderline and schizophrenic
patients but that it must not be regarded as a treatment technique
in itself.  it is but a preliminary approximation to the final therapeutic
act, which ultimately will consist of a classical interpretation
at the level of the secondary process.  the use of the metaphor derives
its primary value from maintaining contact with patients who are
constantly in danger of being inundated by a break-through of primary-
process material.
.I 625
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evolution of a characteristic speech disorder in
juvenile cerebral lipidosis
juvenile cerebral lipidosis is being diagnosed with increasing frequency in
this country, especially in schools for the visually handicapped.  the
manifestations of rapidly developing loss of vision, seizures, muscular
rigidity, ataxia, retinitis pigmentosa and eeg abnormalities are well known in
this disorder.  a speech disorder described as a "lolling, stammering speech"
was mentioned by sjogren (1931) in his comprehensive description
of juvenile amaurotic idiocy, but this has not been emphasized in
recent descriptions.  this report, based upon an analysis of 5 cases,
describes the evolution of a characteristic form of speech pathology that
is invariably present in juvenile cerebral lipidosis.
the initial speech abnormality seen early in the disorder is a hesitancy of
speech and occasional repetition of words.  in time, dysarthria becomes
evident with slurring, nasality and impairment of phonation similar to that
seen in pseudobulbar palsy.  in addition to the dysarthria, a highly
characteristic perseverative speech appears which often has a close resemblance
to true stuttering.  this stuttering-like speech has been observed in 4 of the
5 cases at some time during the course of their illnesses.  as the speech
patterns deteriorate, the patient becomes less communicative and finally lapses
into mutism.  the speech disorder is often the most disabling aspect of this
syndrome.
.I 626
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relation of crying activity in early infancy to speech and intellectual
development at age three years
rosenfeld
cries of 38 infants, age 4 to 10 days, were measured for outburst
frequency during the most active 20-sec. period of crying.  crying
scores showed a significant correlation (.45) with stanford-binet iq
at 3 years, a borderline correlation (.32) with cattell iq at 15 to 20
months, and a nonsignificant trend with speech ratings at 3 years.
although no correlations were adequate for individual prediction,
infant crying is deemed worthy of further investigation as a possible
indicator of intellectual potential.
.I 627
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31
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labial supportive appliance
the patient with a repaired cleft lip and palate and an associated
displacement and deficiency of the premaxilla presents problems which
may be of concern to the plastic surgeon, speech pathologist, orthodontist,
and prosthodontist.
the upper lip may appear flat or retruded in relation to the lower lip.
when maxillary anterior teeth are missing, either congenitally, naturally
(as in the mixed dentition period), or because of neglect, the upper lip
may appear to be rolled under the premaxilla.  the lower lip usually
assumes a characteristic 'pouty' appearance.
this complex of tissue deformities also may be important in the articulation
of speech sounds.  fricatives and plosives are difficult to produce
correctly because of the malposition of the lip.  there may be interference
with direction of air current, contact of tongue to alveolar ridge, and
normal contact of lips.
corrective procedures are designed to improve the labial profile and to
establish more normal relationships of intraoral structures.  these
procedures, employed individually or in combination, may include othodontic
movement of maxillary segments, dental prosthesis, and cheiloplasty.
another more recently developed adjunct involves autogenous
osscous implantation in the cleft areas.
.I 628
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heterogeneity of the 'cleft palate population' and research designs
the primary point made in this paper is that we must reject the notion
that there is some inherent, universal commonality among individuals
who are born with a cleft lip and/or cleft palate.  we must recognize the
various pertinent subgroups within this population.  this does not mean,
however, that one must always recognize the smallest subgroup in doing a
given study.  on the contrary, we would defend the use of fewest possible
subgroups consistent with the specific research purpose.  nevertheless, we
feel that time spent considering the purposes of a study and the subgroups
which need to be identified will tend to minimize the number of
contradictory results, and will assist us in the interpretation of the
observations that our insight and technology make possible.
.I 629
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31
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cineradiographic comparison of normal to noncleft subjects with velopharyngeal
inadequacy
cineradiographic studies of the normal subjects were compared with
studies of noncleft subjects who demonstrated velopharyngeal inadequacy.
the following conclusions were made: a) there was a significant difference
between soft palate length in normals and the velopharyngeal inadequacy
group.  b) there was not a significant difference between depth of nasopharynx
in normal and the velopharyngeal inadequacy group.  c) the
difference of the means of the soft palate length and depth of nasopharynx
between the normals and velopharyngeal inadequacy group was significant.
d) the thickness of the soft palate was greater in the normal than the
abnormal group.  e) in 70% of the normal and velopharyngeal inadequacy
groups the height of soft palate elevation was above the palatal plane.   f)
in 80% of the normal group the height of velopharyngeal closure took
place below the palatal plane.  none of the subjects in the velopharyngeal
inadequacy group obtained velopharyngeal closure.  g) there was no significant
correlation between amount of gap and voice quality.  h) there was
no significant correlation between amount of gap and intelligibility of
speech.  i) there was a difference between vital capacity readings for the
velopharyngeal inadequacy group with nose occluded and unoccluded.  j)
the correlation coefficient between quality judgment and intelligibility
judgment was highly significant.
.I 630
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spontaneous verbal rehearsal in a memory task as a function of age
a distinction is made between 2 alternative hypotheses for explaining an
often-reported deficiency in verbally mediated performance during early
childhood: (1) the verbal response is made, but tends not to mediate
performance ("mediational-deficiency hypothesis"); (2) the verbal response
tends not to be made ("production-deficiency hypothesis").  a study is
described which attempts to meet the ideal criteria for a test of the
production-deficiency hypothesis.  the method used was that of direct
observation of s's spontaneous verbalizations, and the hypothesis was confirmed
by the finding that kindergarteners are less likely than older children to
rehearse stimulus names in a nonverbal serial recall task.
.I 631
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early experience and the socialization of cognitive modes in children
this paper deals with the question: what is cultural deprivation and how
does it act to shape and depress the resources of the human mind?  the
arguments presented are: first, that the behavior which leads to social,
educational, and economic poverty is socialized in early childhood; second,
that the central quality involved in the effects of cultural deprivation is a
lack of cognitive meaning in the mother-child communication system; and, third,
that the growth of cognitive processes is fostered in family control systems
which offer and permit a wide range of alternatives of action and thought and
that such growth is constricted by systems of control which offer predetermined
solutions and few alternatives for consideration and choice.
the research group was composed of 160 negro mothers and their
4-year-old children selected from four different social status levels.
the data are presented to show social status differences among the
four groups with respect to cognitive functioning and linguistic codes and
to offer examples of relations between maternal and child behavior that are
congruent with the general lines of argument laid out.
.I 632
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recovery of mycoplasmas in the study of
human leukaemia and other malignancies
numerous reports have been published concerning the
necessity of testing for the presence of mycoplasmas before
the interpretation of experiments performed in cell
cultures.  such tests are especially important when
the presence of viruses is suspected, since recent evidence
indicates that some mycoplasmas are capable of eliciting
a transmissible cytopathic effect.
in addition, some mycoplasmas and viruses share
properties, such as size, filterability, morphology in
electron microscopy, sensitivity to ether, ability to
haemagglutinate and cause haemadsorption, interference
with virus replication in vitro, lack of inhibition by certain
commonly used antibiotics and inhibition of growth by
homologous antiserum.  thus, the absence of ordinary
bacteria and moulds in preparations eliciting a cytopathic
effect in cell cultures is an unreliable criterion for viral
identification.  great caution should be exercised in
classifying new agents as viruses, especially as myxo-
viruses, without adequate testing to exclude their identity
as mycoplasmas.
.I 633
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pneumonia due to mycoplasma pneumoniae
its incidence in the membership of a co-operative medical group
ruth mcmahan, edmund r. clarke, william a. maccoll, and j. thomas grayston
a total of 1051 cases of pneumonia occurred in
72,992 persons who were members of a medical
co-operative in the period december 1, 1963, to
december 31, 1964.  the annual rate of pneumonia
was 12.9 per 1000.  isolation of mycoplasma pneumoniae
from throat swabs was attempted in over
half the cases reported, and paired blood specimens
were obtained in one third.  on the basis of laboratory
examination of these specimens, the incidence
of clinically recognized pneumonia due to m. pneumoniae
was between 1 and 1.5 persons per 1000
per year.
although peak rates of pneumonia occurred under
five years of age (45 per 1000) pneumonia due to m.
pneumoniae was uncommon in this age group.  it
was most common in children five to nine years old,
and was frequently the cause of pneumonia in adolescents
(ten to nineteen years of age).  the rates in
children in primary school was twice the average
incidence.  m. pneumoniae pneumonia also differed
from the pneumonias of other etiology in that it
occurred throughout the year, with no seasonal excess
whereas total pneumonia showed a predominance
in winter.
the typical clinical syndrome of the pneumonias
in which m. pneumoniae was isolated was one of
prominent systemic manifestations of headache and
fever, but few respiratory symptoms occurred except
cough.  upper-respiratory-tract complaints and an
elevated white-cell count were much more frequent
in the other pneumonias.  the patients with m.
pneumoniae pneumonia were almost never hospitalized
but suffered significant absenteeism.  they
came from larger families, usually with children of
school age.  reporting physicians were usually correct
in diagnosing these pneumonias as "atypical" or "viral."
.I 634
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31
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establishment of a turkey flock free of 'n' strain mycoplasma
mycoplasma of the 'n' strain are frequently isolated from
turkey poults affected with airsacculitis but free of
mycoplasma gallisepticum.  research on the 'n' strain has
been impeded by the presence of a high proportion of
turkey poults with airsacculitis in all breeding flocks
examined, by the difficulty of culturing and identifying
the mycoplasma strains, and by the lack of a practical
serologic test.  this communication describes the establishment
of a small nucleus of 'n'-free turkeys from a commercial
breeding flock known to carry 'n' mycoplasma.
hens and toms for the production of 'n'-free poults were
selected from the parent flock by serology and culture.
.I 635
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22
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septicemia due to mycoplasma hominis type 1
viola m. young, ph.d., and sheldon m. wolff, m.d.
a febrile illness that followed therapeutic abortion
and was accompanied by the presence of
mycoplasma hominis type 1 in the blood is described.
the patient upon recovery exhibited a specific
antibody response to the mycoplasma isolated
from the blood, as well as to another strain of the
same serotype.  these findings are regarded as additional
evidence for the pathogenicity of m. hominis
type 1 organisms, particularly in situations favoring
their dissemination from the female genital
tract.
.I 636
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infectie door mycoplasma hominis bij een pasgeborene
mycoplasma hominis infection in a newborn child.  --in a baby
born by a difficult forceps delivery, abscesses began to form
in the neck a few days after birth.  mycoplasma hominis was
recovered from the pus.
.I 637
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31
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some intraspecies differences in antigens on
the surface of certain living human cells
surface antigens of several types of living cells of human
origin were partially characterized with hyperimmune antisera prepared in
the rabbit against living hela cells and living, uncultured, full-term, human
amnion cells.  hemagglutination, mixed-agglutination, and direct and
indirect immunofluorescence (fab) techniques were employed.  with
these techniques and fractional absorption procedures, common and specific
cell antigens were detected on the surface of several human living cells:
uncultured and primary amnion, two established human cell lines (rp am 1
and u amnion) of presumed normal origin and two (hela and hep-2) of
presumed malignant origin, and human erythrocytes.  none of the antigens
were found on nctc 2555 mouse cells.  the human cells possessed species-
related antigens demonstrable by hemagglutination.  after removal of
the hemagglutinins by absorption with human erythrocytes, antibody in high
titer for the homologous cells was detected by fab methods.  in addition,
some changes in antigens on the surface of amnion cells during primary
culture were observed.  finally, an antigen was found on hela and hep-2
cells, by use of anti-hela serum absorbed with human erythrocytes and rp
am 1 cells, that was not found on either human erythrocytes, uncultured
amnion cells, or on the cells of the two established amnion cell lines.  at
the dilutions used in the tests, antibodies to the abo blood group isoanti-
gens, forssman hapten, or adsorbed serum proteins could not account for
the antigens detected.  the possibility that mycoplasma sp. antigens
were responsible for the reactions was inconsistent with the results.  the
specificity of the fab methods on living cells was confirmed.
.I 638
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22
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coombs-positive hemolytic anemia and generalized amyloidosis in
mice following transmission of subcellular leukemic material
following transmission with
cell-free supernatant fluid or with virus ex-
tract of leukemic tissue or plasma from vari-
ous types of murine plasma cell leukemias
a disease developed, characterized by hyper-
gammaglobulinemia, weight loss, anemia,
marked splenic, renal and hepatic amyloido-
sis and plasma cell infiltrations in the lungs.
the disease was also transmissible through
the placenta or with the milk of infected
mice.  in dba/2 males the incidence of the
disease was much higher (100%), the sur-
vival shorter and the anemia much more
severe than was the case in dba/2 females
and in (dba/2 x cba) f1 mice of both
sexes.  it is proposed that the development
of the lesions is mediated through an auto-
immune mechanism created by the antigenic
effect of the virus-transformed host cells.
.I 639
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the ph 6 antigen in strains of pasteurella pseudotuberculosis
and its relation to biological activities
it may be concluded that only part of the p.
pseudotuberculosis strains can synthesize the ph
6 antigen, whereas this property seems to be
shared by all the strains of p. pestis.  as in the
case of p. pestis, three kinds of biological activi-
ties were related to the presence of the ph 6
antigen isolated from a strain of p. pseudotubercu-
losis.
.I 640
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22
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serological relationships among human mycoplasmas as shown
by complement-fixation and gel diffusion
and robert m. chanock
antigenic relationships among human
mycoplasmas were studied by complement-
fixation and agar gel diffusion techniques.  four
recognized human species.  mycoplasma hominis
type 1, m. hominis type 2, m. salivarium, and
m. fermentans were antigenically distinct in
these tests.  in addition, m. pneumoniae (eaton
agent, the etiological agent of cold agglutinin-
positive atypical pneumonia) was different from
these four species.  although these species were
distinct, evidence of shared antigenic components
was obtained in complement-fixation and agar
gel diffusion tests.  since rabbits were immunized
with mycoplasmas grown in rabbit muscle infu-
sion broth supplemented with rabbit serum or,
in the case of m. pneumoniae, with infected chick
embryo lung suspension, the possibility that the
heterologous reactions resulted from antibody
to growth medium components could be excluded.
four recent mycoplasma isolates from the oro-
pharynx were analyzed, and three were shown to
be closely related to m. hominis type 1, and the
fourth was closely related to m. salivarium.
although the recent isolates could not be dis-
tinguished from the related "prototype" human
species by complement-fixation, differences could
be detected by the agar gel diffusion technique.
.I 641
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mammalian cell cultures contaminated with
pleuropneumonia-like organisms
ii. effect of pplo on cell morphology in established
monolayer cultures
the occurrence of cytopathogenic changes in monolayer cultures of
pplo-contaminated mammalian cells has been shown to be related to
deficiency of arginine in the medium.  the same effects were seen when the
cell culture medium was depleted by pplo prior to application to pplo-free
cell cultures even though viable pplo were no longer present.  the fact that
the same picture resulted in the absence of pplo when either arginine or
glucose were omitted from the medium would indicate that, while the defi-
ciency created under the conditions described was specific, the cellular
changes could as well be the result of omission or depletion of other mam-
malian cell growth requirements.  the importance of surveillance of cell
lines for the presence of pplo to avoid misinterpretation of cytopathogenic
effects was stressed.
.I 642
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suppression of rous sarcoma virus growth in tissue
cultures by mycoplasma orale
an agent
which produced cell destruction in human diploid and chick-embryo fibroblasts
was isolated from wi-26 strain of human diploid fibroblasts and shown to be a
mycoplasma.  the multiplication of rous sarcoma virus (rsv) and rous associated
virus (rav) was inhibited in wi-26, wi-38, and chick-embryo fibroblasts
infected with this mycoplasma.  the mycoplasma isolate, designated strain 941,
reacted strongly in the complement-fixation test with antiserum to mycoplasma
orale ch19299, an isolate obtained from the human oral cavity.  the cytopathic
effect of mycoplasma strain 941 could be eliminated by growing the mycoplasma
on an artificial agar medium before inoculation into chick-embryo fibroblasts.
serial passage in chick-embryo fibroblasts restored the cytopathogenicity of
the agar-grown mycoplasma.  however, growth of rsv and rav was inhibited by
both the tissue culture-grown and the agar-grown 941 strain, and also by the
ch19299 strain which did not produce any cytopathic effect.
.I 643
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22
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a method for direct demonstration of pleuropneumonia-like
organisms in cultured cells.
direct microscopic observation
of pleuropneumonia-like organisms (pplo)
in cell cultures is easily accomplished follow-
ing hypotonic treatment, air-drying and
staining with orcein.  a rapid technique using
fl human amnion cells, inoculated with su-
pernatant from suspected cultures, is de-
scribed.  the demonstration of pplo con-
tamination of 30 cell lines by this rapid
method was in complete agreement with re-
sults of pplo-agar techniques.
.I 644
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22
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a fatal septicemic disease of infant puppies caused by
cytopathogenic organisms with characteristics of mycoplasma.
pathogenic organisms were iso-
lated from 2 outbreaks of a fatal septicemic
disease of infant puppies and from dog kidney
cells that degenerated spontaneously.  the iso-
lates were indistinguishable serologically and
possessed characteristics of mycoplasma.  the
pathogenic organisms were cytopathogenic for
dog kidney cell cultures, and in inoculated
puppies, produced pathological changes that
resembled those seen in natural cases.  le-
sions consisted principally of necrosis and
hemorrhage.  the isolates were culturally and
serologically distinct from recognized canine
mycoplasma species.
.I 645
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chromosome changes in pplo-infected fl human amnion cells.
characteristic chromosome
changes were observed in pplo-infected fl
human amnion cells.  these changes included
a gradual reduction in chromosome numbers,
increase in chromosome aberrations, and the
appearance of 3 new varieties.  although some
of the aberrations appeared early after infec-
tion, most changes developed slowly, over a
period of several months.
.I 646
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31
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studies on mycoplasma pneumoniae
infection in sweden
sera from 107 cases of pneumonia and 132 cases of milder respiratory
infection were examined by the cf test against m. pneumoniae antigen.
thirty-five patients with pneumonia and 2 patients with bronchitis had
serologic evidence of m. pneumoniae infection.  all cases which had a
significant antibody rise with the cf test also showed a corresponding
rise with the fluorescent antibody test.  m. pneumoniae was isolated
from 10 of 18 serologically positive cases.  cold agglutinins were demon-
strated in 17 of 37 cases (46 per cent) with m. pneumoniae infection.
m. pneumoniae infections occurred during all seasons of the year and
were most common in older children and young adults.  the clinical
features of the cases with m. pneumoniae infection in this study re-
semble those described in similar investigations in other countries.
.I 647
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spontane genetische veranderungen am zellstamm l (earle)
the chromosomal constitution of a clone of the cell strain ,,l'' was studied by
repeated chromosomal analyses within 2 years.  there resulted the stability of
the cellular clone with regard to the tested feature for the duration of about
one year.
the maximal number of chromosomes amounted to 60-64.  in later tests a spon-
taneous doubling of the chromosomal number (maximum 120 chromosomes) was
ascertained.  the cause of this phenomenon could not yet be cleared up.  this
new chromosomal pattern remained unchanged in the subsequent examination period
of 6 months.
as was proved by these observations, under the present cultivation-conditions
cell populations can be retained stabile in vitro for a certain period.  the
defined substances, however, still imply unknown factors which may have a
mutagenous effect, so that sudden changes of cell populations may result.  the
respective physiological features are hardly known as yet.
.I 648
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22
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chromosome changes in human diploid-cell cultures infected
with mycoplasma
this communication shows that mycoplasma may also
change cell chromosomes, and therefore emphasizes the
need for caution in interpreting experimental results
without adequately testing for the presence
of mycoplasma.  chromosome damage similar
to that described here has been induced by
viruses in cell cultures and in blood cul-
tures.  chromosomal abnormalities have
also been reported in blood cultures and bone
marrow from leukaemic patients.
.I 649
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31
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evaluation of tylosin in
preventing egg transmission of
mycoplasma gallisepticum in
chickens
the inoculation of mycoplasma gallisepticum infective
yolk into the left posterior thoracic air sac of laying chickens
resulted in an infection which produced a rate of egg infection
satisfactory for experimental purposes.  culturing of all live
embryonating eggs as well as all dead and infertile eggs was
necessary to determine the rate of egg infection.  tylosin,
either injected subcutaneously, administered in the drinking
water, or employed in an egg-dipping solution, greatly reduced
but did not completely eliminate egg infection.  in the 3 egg
dipping trials, only 11 isolates of m. gallisepticum were ob-
tained from 2329 tylosin-dipped eggs, compared to 400 isolates
from 2984 control eggs.
.I 650
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31
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epidemiology of mycoplasma pneumoniae
infection in families
and ruth mcmahan
the transmission and clinical manifestations of in-
fection with mycoplasma pneumoniae were studied in 114
families in which there was a case of atypical pneumonia.
m pneumoniae was isolated from a throat culture of the
index pneumonia patient in 36 of these families.  trans-
mission to other family members occurred in 23 of the
36 families.  in these 23 families, 84% of the children
and 41% of the adults were infected.  the index cases
are included.  of the total 59 patients with family-contact
infections, 42 had lower-respiratory-tract symptoms, 6
had pharyngitis alone, 9 (all children) were asympto-
matic, and 2 had probably unrelated symptoms.  the
time intervals between cases within a family suggested
a median incubation period of 23 days.  treatment with
tetracycline seemed neither to cure the symptoms com-
pletely nor to abolish the carrier state that often lasted
one to three months.
.I 651
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case of salpingitis due to pleuro-pneumonalike
organisms
a case of acute salpingitis following a diagnostic curettage and
aspiration of the pouch of douglas is described.  this case was resistant
to penicillin and streptomycin therapy.  a pure culture of pleuropneu-
monia like organisms (pplo) grew from pus removed from the secon-
dary pyosalpinx by aspiration.  these organisms were sensitive to tetra-
cycline which cured the adnexal infection.  no pplo were found in the
vaginal discharge.
pplo have frequently been isolated from the vaginae of healthy
and infected women.  however, only 9 cases of pelvic inflammatory
disease with a pure culture of pplo have been reported.  the possibi-
lity that these growths of pplo in the internal genitalia followed the
use of antibiotic therapy is discussed.
infection with pplo should be considered when pelvic inflam-
matory disease proves resistant to the common antibiotics.
.I 652
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the serological differentiation of mycoplasma strains (pleuro-
pneumonia-like organisms) from various sources
a complement fixation test with rabbit antisera was used to differentiate 82
cultures of mycoplasma from man, mammalian cell cultures, laboratory rats and
mice, cattle, goats, poultry, embryonated eggs and sewage.
seventeen serotypes were distinguished, 5 from man, 1 from mammalian cell
cultures, 4 from rats and mice, 4 from cattle and goats, 2 from poultry and one
saprophytic.  most of these corresponded to recognized species of mycoplasma,
but 1 of human origin (represented by 1 strain, navel), and 1 from tissue
cultures (5 strains), may represent new species.  r38, one of the serotypes
from rats, could be distinguished from the species m. arthritidis, but is
probably an antigenic variant rather than a distinct species.  two species
hitherto recognized as distinct m. arthritidis and m. hominis type 2, could not
be distinguished and appear to constitute a single species.  these findings
illustrate the necessity, from the viewpoint of taxonomy, of comparing
mycoplasma strains by serological methods.
the serotypes of human and animal origin were largely host-specific.
exceptions were the inclusion of m. arthritidis from rats and m. hominis type 2
from man in a single serotype, the finding of a bovine organism among the
strains isolated from goats and of a saprophytic strain in a rat.
in relation to the aetiology of disease in man and animals, the isolation of
an endogenous mycoplasma from embryonated eggs used to passage infective
material illustrates the importance of identifying these organisms
serologically.  the demonstration of mixed mycoplasma infections in lesions
in two rats shows the necessity of adequately purifying all cultures of
mycoplasma before examination.
.I 653
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31
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spiramycin in the treatment of experimental
mycoplasmosis in day-old chicks and turkey
poults
day-old chicks and turkey poults experimentally infected with
m. gallisepticum have been treated at the time of infection, with
spiramycin administered by subcutaneous injection or drinking water
medication.
a dose of 100 mg/kg. bodyweight by subcutaneous injection or an
0.04 per cent. concentration in the drinking water continuously for
three days eliminated the infection in most of the birds, which
remained free of air-sac lesions and did not react to the slide agg-
lutination or haemagglutination inhibition tests.
.I 654
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22
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further studies of agents isolated from tissue cultures inoculated
with human leukaemic bone-marrow
d. a. woods
mycoplasmas were isolated from tissue cultures inoculated
with bone-marrow from leukaemic patients.
all cultures which showed a cytopathic effect contained
mycoplasmas.
there was no evidence of mycoplasmas in control cultures.
the mycoplasmas isolated seemed biologically and serologic-
ally to be of one strain which was different from any previously
reported as being isolated from human sources although there
was some relationship to a rodent mycoplasma, m. pulmonis.
mycoplasmas cannot readily be distinguished from viruses
electron-microscopically.
the relationship of mycoplasmas to leukaemia is not yet
clear.
.I 655
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22
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microbiological studies of reiter's disease
attempts were made to demonstrate viruses and
pplo in body fluids and synovial tissues of patients
with various rheumatic diseases.  all attempts to
demonstrate viruses were negative.  pplo were
looked for in 499 specimens from 114 patients with
rheumatic and non-rheumatic diseases.  whereas
these organisms were readily isolated from genito-
urinary specimens, they were found in none of 31
synovial fluid specimens.  they could not be grown
from synovial tissue biopsies of patients with
rheumatoid arthritis, ankylosing spondylitis, gout,
gonococcal arthritis, psoriatic arthritis, traumatic
arthritis, or arthritis accompanying ulcerative colitis,
but they were present in one and possibly in two of
eight synovial tissue specimens from patients with
reiter's disease.  complement-fixation tests were
negative in nine patients with reiter's disease,
including the two from whose synovial tissues
pplo were thought to have been isolated.
.I 656
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22
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recovery of a pleuropneumonia-like organism
(p.p.l.o.) from the genitalia of the female
albino rat
the genital organs of seventy-seven nonproductive breeder female rats
were examined grossly and histologically and bacteriological cultures of the
uterus and ovaries were made.  three of the seventy-seven animals showed a
purulent salpingitis and oophoritis.  a pleuropneumonia-like organism was
isolated from the uterus and ovaries of 29% of the animals examined.  the
cultures obtained from the genitalia were compared with the p.p.l.o. isolated
from the middle ears of some of these same animals and the two appeared to be
identical.  intraperitoneal injection of the p.p.l.o. cultures into young
rats and mice produced oophoritis and salpingitis in the mice but not in the
rats.
.I 657
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22
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chronic respiratory disease in mice and rats
chronic respiratory disease (crd) in both mice and rats embraces two
separate entities, namely: infectious catarrh caused by mycoplasmas
(pleuropneumonia-like organisms) and enzootic bronchiectasis by a virus.
the two syndromes are discussed in regard to their etiology, pathologic
manifestations, and transmission.  particular attention is paid to the relation
of mycoplasmas to infectious catarrh.  the morphologic and cultural
characteristics of the catarrhal types of these organisms are considered
from the standpoint of differential diagnosis.  the importance of crd in the
maintenance of breeding colonies and in the use of animals for experimental
purposes is stressed.  methods for the establishment of specific pathogen-free
colonies, as a means of control, are briefly outlined together with
observations on a cesarean-derived line of swiss mice.
.I 661
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31
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problems of disease of
parathyroid glands
if biochemical tests indicate unequivocally
that there is a functioning parathyroid tumour,
usually an adenoma, its removal will relieve
symptoms and prevent any further damage to
organs such as the kidneys.  in 80 per cent,
of such cases the operation is not particularly
difficult to anyone with experience of thyroid
surgery.  the tumour is seldom of great size,
usually less than half an inch in diameter, but
a careful search in the expected position, in
close apposition to the posterior surface of the
thyroid lobes, will usually reveal it.  such
adenomata are usually more brown in colour
than the normal yellow gland; but in some 20
per cent, of cases one or more of the glands
may be aberrant, or possibly absent, and super-
numerary glands may be present.  it is usually
one of the lower pair of glands which occupies
an ectopic position and, as i explained in the
outline of the embryological development, it
may accompany the thymus into the mediasti-
num, rather a vast area in which to seek a small
tumour.  such an exploration cannot be lightly
undertaken, but if the evidence is indisputable
the burden must be shouldered.  it is correct
policy, i believe, first to carry out a thorough
exploration of the neck, and if this proves un-
availing, to inspect the mediastinum through a
sternum-splitting incision some two weeks later,
rather than completing this major undertaking
at one session.
.I 662
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31
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the age factor in experimental hypertension
of the dca type in rats
rats aged 25 and 86 days were sensibilised by unilateral nephrectomy and a week
later were given 1.1 mg/100 g dca every third day for 6 weeks and a 1% nacl
solution to drink.  the younger rats reacted with a greater increase in blood
pressure, more so male rats.  hypertrophy of the heart and kidneys and
mortality and supression of growth were also all more evident in the younger
age group.  only male rats given the steroid hormone starting from day 25
showed permanent suppression of growth.
.I 663
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24
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response of a serum glycoprotein to tissue injury
and necrosis
1. the response to necrosis, hyperplasia and tumour growth
a serum glycoprotein of the rat underwent a 20-fold increase during 15 days
growth of the walker tumour and this increase was not affected when the rats
were treated with terramycin.  the protein increased at the same or a greater
rate when rats were subjected to ischaemic necrosis of one kidney or of two-
thirds of the liver.  boiled kidney tissue, on the other hand, had little
effect upon the protein response, and kidney hyperplasia had none.  it is
suggested that this protein increase is a response to substances liberated from
damaged or necrotic cells.
.I 664
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31
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the natural history of autoimmune
disease in nzb mice
a comparison with the pattern of human
autoimmune manifestations
all mice of the nzb/bl strain spon-
taneously develop serological and
pathological evidence of autoimmune dis-
ease during adult life.  the nzb/bl strain
was developed by dr. marianne bielschow-
sky in dunedin, new zealand, by inbreed-
ing from an outbred colony of mixed coat
color.  several inbred strains--nzb, nzc,
nzo, nzw, nzy, and others, have been
evolved in dunedin from the original col-
ony.  evidence for autoimmune disease in
the nzb strain was first reported by
bielschowsky, helyer, and howie who
found evidence of an autoimmune hemo-
lytic anemia.  the dunedin group used the
presence of agglutinins for ficin-treated red
cells as the index of the disease.
.I 665
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31
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the remaining kidney in irradiated
survivors of wilms's tumor
the intravenous urograms of 10 patients
who had survived 5 years after irradiation
for wilms's tumor were studied for kidney
size and configuration.  the diseased kidney
had been removed by nephrectomy.
the remaining kidneys had been sub-
jected to varying doses of ionizing radia-
tion at the time the area of the diseased
kidney was irradiated.  in none was there
evidence of atrophy.  all were within the
range of expected normal size and most of
them were enlarged.
.I 666
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24
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cellular proliferation and deoxyribonucleic acid
synthesis in compensating kidneys of mice
and the effect of food and water
restriction
compensatory enlargement of the kid-
ney occurred after unilateral nephrectomy
in mice.  fourteen days after the removal of
one kidney the surviving renal tissue                                  6
weighed 23 per cent more than single kid-
neys from sham-operated animals.  the
hyperplastic response of the cortex on the
second postoperative day was 8 times
greater than that seen in the same zone of
kidneys from sham-operated animals.  by
10 days after surgery the mitotic index of
the cortex returned to control values.  the
outer medulla also underwent hyperplasia
but only on the second day following
unilateral nephrectomy was the increase
significant.  an increase in mitotic activity
was found in the inner medulla of surviving
kidneys, but it was not statistically signifi-
cant.
both starvation for 48 hours and water
restriction for 60 hours prevented the hyper-
plastic responses in the remaining kidneys
2 days after unilateral nephrectomy.  when
water was given 48 hours after unilateral
nephrectomy (after 60 hours of water
restriction) significant increases in mitotic
activity were noted in the cortex of remain-
ing kidneys on the fourth and fifth post-
operative days.  however, even after free
access to food was allowed (after 48 hours
without food) no significant increase in
mitotic frequency of the remaining kidney
was found.
deoxyribonucleic acid synthesis in con-
trol kidneys of mice was highest in the cor-
tex and lowest in the inner medulla as
revealed by radioautographic studies fol-
lowing the injection of tritiated thymidine.
two days following removal of one kidney
the labeling index of the cortex of remaining
kidneys increased 3-fold.  no statistically
significant increases of deoxyribonucleic
acid synthesis were noted in either the outer
or inner medullary regions of the remaining
kidneys.
.I 667
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24
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compensatory renal enlargement
hypertrophy versus hyperplasia
after unilateral nephrectomy in the mouse, the compensatory growth
of the remaining kidney is characterized by an increase in rna and
protein synthesis within the first hour.  dna synthesis remains un-
changed for about 18 hours and then rises to a maximum at 48 hours.  by
the end of the fifth day, when dna synthesis has passed its peak and is
in decline, cellular hyperplasia has accounted for only one-fourth of the
increase in kidney weight.  thus it is shown that cell hypertrophy is both
the primary and the predominant response in the early phase of compen-
satory renal enlargement.
.I 668
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24
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cell proliferation
in experimental hydronephrosis
and compensatory renal hyperplasia
mitosis counts and autoradiographic counts of nuclei labeled with
tritiated thymidine were made in the renal cortex of male rats in which
the left ureter was ligated.  these were compared with corresponding
counts in the remaining kidney after left nephrectomy, and in sham-
operated controls 24, 48 and 72 hours after operation.  the cortex of
the kidney on the obstructed side showed a greater number of tritium-
labeled nuclei and mitotic figures than in the kidney undergoing com-
pensatory hyperplasia.  epithelial and interstitial cells responded simul-
taneously on the obstructed side, whereas in the remaining kidney after
nephrectomy, the epithelial response preceded a slight interstitial re-
sponse by 48 hours.  the contralateral kidney in rats subjected to
ureteral ligation showed no response.
we concluded that the early response of increased dna synthesis
and cell division in the obstructed kidney was not mediated by humoral
factors; it was localized and probably had a different mechanism than
the proliferative response occurring in compensatory renal hyperplasia.
.I 670
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cell proliferation in compensatory renal growth
rats with one kidney removed showed a progressive increase in weight of the
remaining kidney over a six-week period.
autoradiographic and radiochemical studies with 3h-thymidine indicated that the
increase in new kidney cell formation was maximal forty-eight to seventy-two
hours after unilateral nephrectomy.  this early response was chiefly due to the
production of new cells by the renal cortical tubules.  normal rates of tubule
cell turnover were achieved two weeks after operation.  the glomerular tufts
contained fewer new cells and their peak production was delayed to the
one-week period with a slow decline thereafter.
rats forty-eight hours after unilateral nephrectomy were chosen as a model to
study the effect of various substances on the magnitude of new cell formation.
the number of dna-synthesising cells in the stimulated kidney was reduced by
treatment with hydrocortisone, acth, 9,10-dimethyl-1,2-benzanthracene, and
1,2-benzanthracene; the numbers were increased by the administration of
deoxycorticosterone and aldosterone.
.I 674
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24
.W
experimentelle nierenvergroberung nach unilateraler
nephrektomie bei ratten
untersuchungen mit 3h-thymidin
in this paper it is attempted to clarify certain questions as to the mechanism
of compensatory renal hypertrophy by means of histological, cytological, and
autoradiographical examinations in nephrectomy experiments on young and grown
rats.  based on the results of this investigation the process of compensatory
renal hypertrophy must be imagined as follows:
as early as two hours after unilateral nephrectomy, a distinct increase of the
mitosis index without a simultaneous increase in dna-synthesizing cells was
observed in the remaining kidney.  it is assumed that a cell division of
polyploid cells is involved, which were in a prolonged premitotic rest phase.
after a latent period of 48 hours, the dna-synthesizing cells and dividing
cells start to increase.  the maximum of the regenerative processes is reached
between the 3rd and 4th day after nephrectomy.  twenty days after unilateral
nephrectomy, the regenerative processes are largely concluded.
all tubule sections participate in the compensatory renal hypertrophy.
although the regenerative processes are most marked in the central section,
one cannot speak of the development of an actual indifference zone in the
regenerating kidney.
in young test animals, compensatory renal hypertrophy is determined more
by mitotic cell division, in older test animals more by polyploidization
processes.
the results of these investigations provide no certain indications for the
assumption that amitotic nuclear divisions play a major part in compensatory
renal hypertrophy.
proliferation processes which in extent and localization run parallel to the
regeneration of the parenchyma, are also observed in the cells of the
connective tissue of the renal vessels.
.I 682
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24
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age differences in cellular
proliferation in rat kidneys
the hyperplastic response to unilateral ne-
phrectomy after 48 hours in the cortex and
medulla of the remaining kidneys of weanling
and young adult rats was studied by means of
autoradiography.  tritiated-thymidine, which
is destined exclusively for nucleoprotein synthe-
sis, was administered to 11 control and 11 ex-
perimental rats 4 hours prior to sacrifice.
labeled tubular cells were rare in control
tissues, especially in medulla, where the per-
centages did not differ greatly for the two age
groups.  in the cortex of controls such cells were
three times more frequent for weanling rats
than for adults.  significant increases in per-
centages of labeled cells over control levels
were found in both regions of the remaining
kidneys for both age groups.  the percentage of
increase was greater in medulla than in cortex
and most pronounced in medulla of the young
adult rats.
.I 684
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24
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(on the erythropoietic effect of different
tissue suspensions)
the stimulating effect on erythropoiesis of regenerated liver and hyper-
trophic kidney tissue after partial hepatectomy and unilateral nephrectomy
respectively was studied in the rat by means of the erythrocyte count, haemo-
globin determination, reticulocyte count and 59fe utilization.  the
reticulocyte count and 59fe utilization increased significantly after treatment
with normal liver and renal tissue and more strongly after regenerated liver
and hypertrophic kidney tissue.  the same effect was seen after treatment
with the sera of rats which had undergone partial hepatectomy or unilateral
nephrectomy.
.I 686
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24
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chemical aspects of compensatory renal hypertrophy
the effect of unilateral nephrectomy on the size and composition of the
remaining kidney has been investigated in rats.  in normal rats the right
kidney is, on the average, significantly heavier than the left and has a
higher total content of dna and rna.  the 2 kidneys have almost identical
ratios of rna/dna and protein/dna.  after unilateral nephrectomy the surviving
kidney increases steadily in wet and dry weight for the 1st 4 days after the
operation.  this is accompanied by a much slower increase in total dna
content and by a dramatic increase in rna/dna ratio.
the rna/dna ratio in kidney is also affected by diet, being higher on a
high-protein than on a low-protein intake.  moreover, the rise in rna/dna
ratio that follows unilateral nephrectomy is greater in animals fed a
high-protein diet.  the changes in kidney weight and in total contents of dna,
rna, protein, and lipid phosphorus resulting from the feeding of a high-protein
diet were found to be of approximately the same magnitude as those in the
remaining kidney 4 days after unilateral nephrectomy.  the rna/dna and
protein/dna ratios are also greater in rats fed a diet containing 10% urea,
but the increase is much less than that in the remaining kidney after
unilateral nephrectomy.
.I 687
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25
.W
the antidiuretic mechanism of hydrochlorothia-
zide in the treatment of diabetes insipidus
the changes in water and electro-
lyte balance during hydrochlorothiazide
therapy in 2 patients with vasopressin-
deficient diabetes insipidus were studi-
ed.  in 1 case, under fixed daily so-
dium intake, the urinary sodium excre-
tion markedly increased on the first day
of treatment, but the urinary volume
began to fall on the second day and per-
sisted low for 3 days after discontinua-
tion of the drug.  in the other case the
urinary volume markedly decreased
when the daily sodium intake was strict-
ly limited.  it further decreased on
hydrochlorothiazide therapy but after
sodium intake was restored it returned
to the pretreatment level despite con-
tinued use of the drug.
the antidiuretic action of hydro-
chlorothiazide in the treatment of dia-
betes insipidus is believed to be related
to the sodium depletion state of the body
brought about by increased output or
decreased intake of sodium.  sodium
and water reabsorption in the proximal
convoluted tubules in the kidney in-
creases and the amount of glomerular
filtrate reaching the distal convoluted
tubules decreases.  thus the final
urinary volume falls.
.I 688
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25
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the action of oral diuretics
in diabetes insipidus
chronic administration of chlorothiazide and
other thiazide analogues in diabetes insipidus
results in a striking reduction in urinary volume
with increase in urinary osmolality.  this curious
antidiuretic action was first described by
crawford & kennedy (1959), and though it has
since been widely confirmed in both the pituitary
and nephrogenic forms of the disease, its precise
mechanism remains obscure.  a number of
investigators have sought to explain the phenom-
enon entirely on the basis of the renal actions of
these drugs (earley & orloff 1962, goodman &
carter 1962), whilst others have contended that
abatement of polyuria may be secondary to a
central effect of the thiazides in decreasing thirst
(robson & lambie 1962, skadhauge 1963).
over the past two years, we have conducted
detailed in-patient studies of the action of
various diuretic drugs of the thiazide and other
series in a group of 7 patients with pituitary
diabetes insipidus.
.I 689
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25
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investigations into the thiazide-induced antidiuresis in
patients with diabetes insipidus
plasma sodium, osmolality and serum
chloride, together with creatinine clear-
ance, were studied before and during
thiazide treatment of 7 patients with
diabetes insipidus.
the diuresis was reduced by 28-39%.
the urine osmolality was increased by
7-128%.  an average decrease in plasma
sodium of 4 meq/i, in plasma osmolality
of 21 mosm/kg, and in serum chloride of
8 meq/i was observed.  only in one pa-
tient was the creatinine clearance re-
duced significantly.  the thirst-feeling was
reduced even from the first day of treat-
ment.  the diuresis was not minimal until
the third to fourth day.  if the diuresis was
corrected for the extra electrolyte ex-
cretion initiated by the thiazide, the
antidiuresis was found to be operating to
the full extent even on the first day of
treatment.
it is concluded that the antidiuresis is
mainly secondary to the natriuresis and to
a certain degree due to a decreased thirst-
feeling; but there seems also to be a direct
renal action, involving at least a reduc-
tion of the glomerular filtration rate.  a
pronounced antidiuresis was found by a
water deprivation test after thiazide
treatment in one patient.
.I 690
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25
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salt and water
the antidiuretic effect of thiazides is thus the
result of the induced sodium deficit.  the fall in
serum osmolality may be contributory by
reducing thirst.  as depletion of body sodium will
be self-limiting the major hazard to the use of
thiazides is potassium depletion.  treatment of
patients with vasopressin insufficiency type of
diabetes insipidus with thiazides is only indicated
for those who are intolerant of hormone replace-
ment.  in nephrogenic diabetes insipidus thiazides
have a more important therapeutic application.
.I 691
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25
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nephrogenic diabetes insipidus
chlorothiazide has been found of value in
establishing and maintaining adequate hydra-
tion in some patients; its exact mechanism of
action is not known.  the antidiuretic effects
of chlorothiazide and its analogues have been
studied in six patients with ndi, two of
whom were infants less than six months of
age.  dehydrated infants showed a dramatic
response to treatment.  with those unable to
achieve an optimal fluid intake prior to treat-
ment, the initial beneficial response was asso-
ciated with an increased fluid intake.  follow-
ing this initial antidiuretic response, a vari-
able degree of "escape" or resistance to the
action of the drug commonly occurred.  de-
spite the unpredictability of a prolonged anti-
diuretic response, a therapeutic trial of chloro-
thiazide in ndi seems warranted if diet alone
is not sufficient to maintain hydration.  it must
be remembered, however, that this drug is po-
tentially toxic.
.I 692
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25
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fluid and electrolyte metabolism in nephrogenic diabetes insipidus
the body fluid volumes have been fol-
lowed in two infants with nephrogenic
diabetes insipidus.  without treatment both
patients had a low extracellular fluid
volume (ecv) and a normal to low-
normal total body water (tbw).  following
thiazide therapy (case 1) and during a
fluid deprivation test (case 2) a further
reduction of ecv and tbw was found.
untreated both patients revealed a se-
vere hypernatriemia without any increase
in the urinary aldosterone excretion.
the first patient had a cerebral atro-
phy and a rightsided hydronephrosis, a
higher diuresis and a lower concentration
capacity was found on this side.  the
patient was treated continuously with
thiazide.  when an ordinary house diet
was given this drug could only maintain
normal electrolytemia in combination
with spirolactone.  a considerable increase
in height and psychic development took
place during this combined treatment.
it is noted, that nephrogenic diabetes
insipidus may be present in infants with
unexplained fever and vomiting in the
absence of polydipsia and polyuria.  the
urine may even be hypertonic.
.I 693
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25
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diuretics in pediatric practice
clinical notes and comments
with the development of more and more
potent oral diuretics in recent years, these
drugs which were once looked upon as being
of only limited usefulness in pediatrics are
now receiving clinical application.  they per-
mit a new approach to the management of
edematous states.  that most of them can be
given orally is a significant advantage, par-
ticularly when coupled with their relative lack
of toxicity.  although the number of patients
in the pediatric age range who require these
agents is relatively small, they are valuable
adjuncts in the management of chronic renal
disease, refractory heart failure, and hyper-
tension.  this discussion reviews their pharma-
cology and clinical indications.
.I 694
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25
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the role of aldosterone and vasopressin in the postural
changes in renal excretion in normal subjects
and patients with idiopathic edema
the effects of the upright posture
(leisurely walking for 2 hours) on half-
hourly urine volume, and excretion of
sodium and creatinine were studied in
13 normal subjects and 13 patients with
idiopathic edema, while they drank 150
or 300 ml. of 0.14 per cent sodium
chloride solution every half hour.  when
the 2 hours of walking were compared
with a preceding recumbent period of
4 hours, both groups were found to show
a significant antidiuresis upright.  the
administration of ethanol during the last
half hour of recumbency abolished the
fall in urine flow and in free water clear-
ance during the first hour of walking in
the normal subjects and significantly re-
duced this fall in the patients with
edema.  sodium excretion in the normal
subjects was slightly but not significantly
lower when upright than when recum-
bent, but in the edematous patients was
significantly lower when upright and fell
progressively over the 2 hour period.  ad-
ministration of spironolactone or d-
amphetamine increased sodium excretion
during recumbency in both groups but
increased sodium excretion upright only
in the edematous patients to equal that
of the normal subjects.  creatinine excre-
tion was not changed in either group by
posture or drug therapy.  similar studies
were performed on 5 patients with un-
treated diabetes insipidus and on 6 pa-
tients with adrenal insufficiency treated
with hydrocortisone alone.  lack of al-
dosterone (in adrenal insufficiency) did
not increase the amount of sodium ex-
creted above that of normal subjects in
recumbency and did not prevent the oc-
currence of significant sodium retention
in the upright posture.  however, lack
of adh (in diabetes insipidus) delayed
the antidiuresis upright for 30 minutes.
the results indicate that adh release
is probably responsible for the reduction
in urine volume during the first 30 min-
utes after assuming the upright posture,
but not thereafter.  the excessive magni-
tude of the orthostatic antidiuresis in
idiopathic edema probably results from
a cause other than adh release, since it
is not completely overcome by ethanol.
reduced na excretion during 2 hours in
the upright posture can occur in the
absence of circulating aldosterone, but
the abnormal magnitude of the na re-
tention in the patients with idiopathic
edema probably results from hyperal-
dosteronism.
.I 695
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25
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the use and mode of action of ethacrynic acid
in nephrogenic diabetes insipidus
the use of diuretic agents in the treatment
of nephrogenic diabetes insipidus had been re-
ported to result in decreased urine volume
and decreased clearance of free water.  a
study of the use of ethacrynic acid, a potent
saluretic agent, was instituted in patients
with nephrogenic diabetes insipidus in an
attempt to achieve a significant antidiuretic
response while allowing a liberal sodium diet.
intravenous ethacrynic acid resulted in de-
creased urine volume, decreased clearance of
free water and decreased rpf and gfr.
prolonged oral administration of ethacrynic
acid promoted a significant antidiuretic re-
sponse when the daily sodium intake was
limited to 60 meq.  the effect of ethacrynic
acid on renal function, potassium and chlo-
ride excretion, and uric acid metabolism are
discussed.
.I 697
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25
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antidiuretic effect of hydrochlorothiazide
in diabetes insipidus
and ch'iuan-lu
12 cases of diabetes insipidus
were studied during hydrochlorothia-
zide therapy under a fixed diet.  the
symptoms, blood pressure, urinary
volume, blood and urinary electrolytes,
plasma volume, electrocardiogram and
hypertonic saline intravenous drip test
were compared before and after treat-
ment.
a daily dose of 100-150 mg
brought down the urinary volume to
about 50% of the pretreatment value.
the initial antidiuretic effect was noted
8 hours after medication and the
maximal effect after the fourth or fifth
day.  owing to the kaluretic action of
the drug, 2-4 gm of potassium salt was
also given each day.  satisfactory re-
sults were obtained with dietary sodium
ion at not more than 200 meq daily, but
ingestion of excessive table salt fre-
quently diminished or even destroyed
the therapeutic effect.
the physical signs, blood pres-
sure and ecg were essentially un-
changed and the plasma volumes were
altered after treatment.  the hyper-
tonic saline test was improved in some
of the patients.
low salt syndrome was fre-
quently encountered as the therapy
continued over 1 month.  but this and
even secondary failure could be pre-
vented by timely use of intermittent or
alternative regimen.
the therapeutic mechanism,
indications and side effects of the drug
were briefly discussed.  the drug might
possibly act through the mechanism of
salt depletion, contraction of extracel-
lular fluid volume and decrease of renal
glomerular filtrate, and in consequence
urinary volume decreases and thirst is
alleviated.
.I 698
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25
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the effect of hydrochlorothiazide on water intake
and plasma osmolality in diabetes insipidus in
the rat
a fall in plasma osmolality accompanied the reduction of urine volume in
rats with hypothalamic diabetes insipidus, given hydrochlorothiazide and an
otherwise normal diet.  the plasma concentration was not reduced with a
high sodium intake, although urine volume still fell.  normal rats and hypo-
thalamic obese rats increased their water turnover after hydrochlorothiazide,
yet their plasma concentration fell.  moreover the antidiuretic response to
vasopressin, which is purely renal, was also accompanied by plasma dilution;
although it is self-evident that rats which drink less are less thirsty, the
reduction in thirst after hydrochlorothiazide may not be a direct result of the
change in plasma osmolality.
as previously shown in patients (kennedy and hill, 1963) a high sodium
intake increased free water clearance in diabetes insipidus but did not
interfere with the reduction of polyuria by hydrochlorothiazide, whereas a high
potassium intake reduced free water clearance and prevented any effect of the
drug on urine volume.
.I 699
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25
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antidiuretic properties of chlorothiazide
in diabetes insipidus dogs
chlorothiazide was found to decrease
urine volume and increase urine con-
centration in diabetes insipidus dogs.
there was no change in gfr, rpf,
tmpah, plasma volume, extracellular
fluid or total body water.  the one con-
sistent altered function was a decrease
in "free water" clearance.  diazoxide and
mercuhydrin were not antidiuretic.  it is
believed that the antidiuretic action is
dependent on the chlorothiazide-induced
saluresis.  although the mechanism of
this antidiuresis has not been clearly de-
fined, it seems best explained by postu-
lating a decrease in filtrate reaching the
distal nephron (giving a decreased final
urine volume) coupled with inhibition of
solute reabsorption in the distal tubule
(preventing the selective reabsorption of
solute in the distal tubule that is nor-
mally seen, accounting for the increase
in urine concentration).  the possible
role of the mineralocorticoids in the
antidiuretic response to chlorothiazide
therapy was investigated in diabetes in-
sipidus and adrenalectomized dogs.  ad-
ministration of sodium-retaining steroids
to diabetes insipidus dogs did not re-
produce the urinary changes associated
with chlorothiazide therapy.  in addition,
the antidiuretic response to chlorothia-
zide was not altered by adrenalectomy
or spironolactone administration.  there-
fore, the presence of the sodium-retain-
ing steroids are not essential for the anti-
diuretic response of chlorothiazide in
diabetes insipidus.
.I 708
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26
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experimental studies on cerebrospinal
fluid flow
a mixed suspension of kaolin and lyco-
podium was injected into the cisterna magna
of dogs.  blockade of csf space was produced
successfully in 63 of 75 dogs; in 48 of the 63,
ventricular dilatation of more than interme-
diate degree was observed.
in these hydrocephalic dogs experimental
shunting was performed either between the
lateral ventricle and the lumbar cistern or be-
tween the unilateral lateral ventricle and the
contralateral cerebral subarachnoid space.  uni-
directional, steady csf flow averaged 0.15 ml. per
hour in the cases of the former shunting,
and the flow averaged 0.25 ml. per hour in the
cases of the latter shunting.
csf flow rate from the ventricle toward the
cerebral subarachnoid space was larger when
intraventricular pressure was higher.  this in-
crease in flow rate parallel to increasing pres-
sure probably results from an increase in csf
absorption.  there seems to be an upper limit
of the flow rate as the pressure is raised.
transient reflux of csf flow was induced by
jugular or abdominal compression.
following intravenous administration of hy-
pertonic solutions, csf flow rate decreased
parallel to the fall of csf pressure and re-
gained the original value as the pressure was
recovered.  when the pressure fell as low as
50 mm. of water the flow almost stopped.
.I 712
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26
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hydrocephalus: changes in formation and absorption
of cerebrospinal fluid within the
cerebral ventricles
formation, flow and absorption of
cerebrospinal fluid were measured in normal
and progressively hydrocephalic dogs by
steady-state studies during ventricular per-
fusion.  the formation of cerebrospinal fluid
was found to be constant, independent of
hydrostatic pressure, and unaffected by the
development of hydrocephalus.  the normal
dog produced 0.016 ml. cerebrospinal fluid
/min. in the lateral ventricles, 0.011 ml. cere-
brospinal fluid/min. in the 4th ventricle and
0.20 ml. cerebrospinal fluid/min. in the sub-
arachnoid space.  the intraventricular forma-
tion of fluid was calculated to be 0.24 ml.
cerebrospinal fluid/min./gm. of choroid
plexus, and 0.3x10-3 ml. cerebrospinal fluid
/min./cm.2 of ependymal surface.
absorption of cerebrospinal fluid was
found to take place within the ventricles as
well as in the subarachnoid spaces.  the re-
sistance to absorption of cerebrospinal fluid
in the normal ventricle was much higher than
in the hydrocephalic ventricle.  the decrease
in resistance occurred as the ventricular
volume increased and the ependyma became
flattened so that in chronic hydrocephalus
the resistance was not significantly different
than in the normal dog.  the theory of re-
stricted diffusion was applied to the data to
calculate the diffusive permeabilities of crea-
tinine and urea, and from this the mean pore
radius within the ventricle.
using formation of cerebrospinal fluid
and data on absorption, the hydrocephalic
animals could not be distinguished from the
normal with sufficient accuracy to suggest
using this as a clinical test.  the reason for
this is that intraventricular pressure has
always been considered as if it were constant
when, in fact, it is changing constantly.  the
problem of ventricular enlargement concerns
the ability of the craniospinal contents to
adjust to and absorb the small but very rapid
changes in intracranial contents that occur
with each beat of the pulse.
.I 713
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26
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dural sinus pressure
in normal and hydrocephalic dogs
simultaneous measurement of cerebro-
spinal fluid pressure (csfp) and venous
pressure in the anterior (ssvp) and poste-
rior sagittal sinus (tvp) has demonstrated
that in the normal dog the mean pressures are
related as follows: csfp>ssvp>tvp.
the statistical relationship between the pres-
sures has shown a poor correlation of ssvp
and tvp with changes in csfp.  on the
other hand, in the hydrocephalic dog, ssvp
rises to meet csfp and is related to fluid
pressure in a 1:1 fashion.  this could be ex-
pected to cause a "non venting" of acute
changes of csfp and a decrease in fluid ab-
sorption.  it is postulated that the mechanism
of ssvp elevation is a partial occlusion of
the sinus.
.I 714
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26
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intraventricular papilloma
a case of intraventricular papilloma of the left
lateral ventricle is reported.  craniotomy was
performed and removal of the tumor was ac-
complished without incident.
the literature is reviewed.
an unusual although perhaps relatively unim-
portant observation in the reported case was that
for four or five days postoperatively the patient,
a 17-month-old female, kept her head tilted to
the right but at the time she left the hospital she
was holding it erect and unsupported and was
sustaining weight satisfactorily on both feet.
.I 715
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26
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five-year comparative study of hydrocephalus in
children with and without operation (113 cases)
on the basis of a 5-year study of 113 hy-
drocephalic children of whom 65 were oper-
ated on early with ventriculo-atrial shunting
and 48 were not operated on, all of them hav-
ing been studied periodically in a similar
manner to determine mortality, morbidity,
intelligence, and related factors, the follow-
ing conclusions are justified:
the program in which shunting opera-
tions were done apparently gives significant
advantages to the children over the program
in which no shunting operations were done
(based on life-table data projected from birth
to 10 years)
survival: 61.8 per cent as compared to
22.2 per cent;
number of competent children (i.q. of
75 or better): 33.8 per cent vs. 5.5 per
cent;
number of noncompetitive children
(i.q. below 75): 27.6 per cent vs. 16.7
per cent.
the major cause of death and morbid-
ity in both groups is infection.
in the operative group, morbidity
associated with the shunting procedure is
related to obstruction of the shunt and
septicemia.  the early occlusions show a
correlation with abnormal, inflammatory
type of spinal fluid being shunted into the
blood stream.  the late obstructions are
associated with mechanical breakage of the
shunt or factors of growth causing retraction
of the cardiac end from the atrium.  prompt
re-establishment of a functioning shunt has
been possible in all instances.  periodic follow-
up examinations, irrespective of symptoms,
have proved invaluable in early recognition
of malfunctioning shunts.  septicemia usually
required removal of the shunt.
from the program of periodic evalua-
tions, including "bubble" ventriculograms,
studies of clearance of risa, and psycho-
logical testings, correlations showed:
intellectual ability seemed associated
with width of cerebral mantle;
width of cerebral mantle in hydrocepha-
lus decreases with ventricular pressures
of 120 or over; it increases with pres-
sures less than this;
prolonged shunting of cerebrospinal
fluid can give dramatic increase in
width of cerebral mantle, apparently
irrespective of basic etiology of the
hydrocephalus;
intellectual capacity could not be cor-
related with the basic etiology of the
hydrocephalus, but did correlate in-
versely with duration of increased in-
tracranial pressure.
the many etiologies of hydrocephalus
require large numbers of patients in each
group for thorough evaluation.  factors
favoring such studies should be carried out in
medical centers where appropriate disciplines
can study in depth.  prevention should be the
ultimate goal.
in the operative group, only 1 patient
compensated his hydrocephalic process and
no single patient demonstrated "arrest" of or
recovery from the basic hydrocephalus-pro-
ducing process in spite of numerous attempts
to demonstrate this.  this might imply a
necessity for life-long shunting of cerebro-
spinal fluid in these cases.
.I 716
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26
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hydrocephalus
any present day definition of
hydrocephalus is very loose.  the
authors would rather adopt the
concept that hydrocephalus is an
abnormal condition characterized
by excessive amount of cerebrospi-
nal fluid with or without enlarge-
ment of the head.
the most common cause of
hydrocephalus is arachnoiditis fol-
lowed by congenital anomalies.  a
neoplasm is a rare cause.
the ideal surgical procedure
is the placement of a ventriculo-
atrial shunt, using either pudenz
or halter valves.  where these
valves cannot be availed of the
choice is between a conservative
waiting with medical support and
ventricular tapping from the older
surgical shunting procedures, like,
ventriculo-peritoneal, choroidoplex-
ectomy, thecal-fimbia, subarach-
noid-ureteral, and others.
.I 717
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26
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recognition and treatment of hydrocephalus following
spontaneous subarachnoid hemorrhage
eight adult patients with hydrocephalus
secondary to spontaneous subarachnoid hem-
orrhage have been presented with a discus-
sion of diagnosis and treatment.  a number of
possible mechanisms for the development of
ventricular dilatation in this condition have
been advanced and pathological data have
been presented in 2 cases.
.I 719
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26
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the family history of spina bifida cystica
the family histories of 722 infants who
were born with spina bifida cystica were
studied.
the index cases were referred for sur-
gical treatment and were not selected in any
way from the genetic point of view.
intensive inquiries were made to ob-
tain a complete family pedigree, including
a prospective follow-up of siblings born after
the index case.
of 1,256 siblings 85 or 6.8% had gross
malformation of the central nervous system:
spina bifida cystica in 54, anencephaly in 22,
and uncomplicated hydrocephalus in 9.
of 306 children born after the index
case 25 (8%) or 1 in 12 were affected.
there was a progressive increase in
multiple cases in the family with increasing
family size.  in sibships of five or more, mul-
tiple cases occurred in 24.1%.
in 118 families cases of gross malfor-
mation of the central nervous system were
known to have occurred among members of
the family other than siblings.  cases oc-
curred in three generations.
it is possible that spina bifida cystica
might be a recessively inherited condition.
.I 721
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26
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etiology of trypan blue induced antenatal
hydrocephalus in the albino rat
wistar strain albino rats were injected with 1 cm3 of a 1% solution
of trypan blue.  three types of dye were used: matheson, coleman and bell,
chroma-gesellschaft and a highly purified sample.  the dyes were injected on
days 6, 7, and 8 of gestation.  fetuses were excised from days 16 through 20,
fixed, decalcified where necessary, embedded in paraffin, serially sectioned
and stained.  newborn young were treated similarly.  chroma-gesellschaft
trypan blue was without reproductive or teratogenic effect at the above doses.
increasing the dose did not increase the teratogenicity but did yield a
decrease in litter size.  both matheson, coleman and bell trypan blue and the
purified sample were teratogenic.  the most frequent neural defect observed
was hydrocephalus.  serial sections of the newborn hydrocephalics showed an
occluded or extremely tenotic aqueduct of sylvius in 31 of 33 sectioned
animals.  the fetuses collected from days 18 through 20 also had occluded or
stenotic aqueducts if hydrocephalic.  aqueductal stenosis or occlusion was
present in 17-day-old fetuses, but hydrocephalus was not conclusively
demonstrated at this age.  sixteen-day-old fetuses did not have aqueductal
occlusion in any of those examined, but stenosis was evident.  it is concluded
that the defect predisposing to hydrocephalus in the young of trypan blue
treated rats of this strain is aqueductal stenosis or occlusion.
.I 722
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26
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bilateral papilloma of the choroid plexus
a rare case of bilateral papilloma of the choroid plexus
in a five-and-a-half-year old hydrocephalic girl is pre-
sented.
the tumor encountered at autopsy was not suspected
during life, the existing hydrocephalus being attributed
to either cytomegalic inclusion disease or toxoplasmosis.
after post mortem examination, it was evident that
the hydrocephalus was due to two factors; hypersecretion
from the tumor itself, and obstruction at the level of the
sylvian aqueduct by a delicate, tense, translucent mem-
brane.
an interesting and uncommon additional feature of
this case was the presence, within the choroidal papillo-
ma, of well-formed haversian bone.
a plea is made for regularly considering papilloma of
the choroid plexus in the differential diagnosis of hydro-
cephalus in children, for here, early diagnosis and treat-
ment might conceivably result in total cure.
.I 723
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26
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the diagnosis of hydrocephalus
the early diagnosis of hydrocephalus
is imperative if definitive steps for
its correction are to be effective.
transillumination is a fairly accurate
procedure that may offer the earliest
means of determining whether or not
the infant's head is enlarging.
however, serial head measurements
constitute the easiest and most
accurate method for early detection
of hydrocephalus.  charts of normal
head size of full-term and premature
infants are available to aid the
physician in evaluating any deviation
from normal.  once the condition has
been detected, it is up to the
neurosurgeon to determine the
treatment plan.  the operative procedure
most widely used for shunting the
excessive cerebrospinal fluid is
insertion of a spitz-holter valve.
early detection and improved treatment
methods will help prevent irreversible
intellectual damage likely to develop
if hydrocephalus continues unchecked.
.I 724
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26
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infantile hydrocephalus and hematoma in the posterior fossa
we have presented a case of hydrocephalus in
an infant, the basic cause being intracranial
hemorrhage in the perinatal period.  surgical re-
moval of a hematoma in the posterior fossa did not
give permanent relief of the raised intracranial
pressure.  a lumbar air study at this stage dis-
closed information that the passage through the
intracerebral cerebrospinal-fluid pathways was
normalized whereas the extracerebral ones still
were occluded by arachnoiditis.  the condition
necessitated a ventriculo-atrial shunt.
.I 725
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26
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urinary excretion of i131-diodrast injected intraventricularly
in communicating hydrocephalus and aqueduct stenosis
nine cases of expansive infantile hydro-
cephalus were investigated by injecting
small amounts of i131-diodrast intra-
ventricularly.  urinary excretion of the
tracer was determined during the first
4-5 hours after injection.  the cumulative
excretion of diodrast from the c.s.f. dif-
fers in cases with communicating hydro-
cephalus from those with stenosis of the
aqueduct.  the investigation is rapid and
easily performed and has not produced any
side effects.
.I 726
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26
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gastrointestinal
ulceration and central
nervous system lesions
there is both a real and an apparent in-
crease in the incidence of severe gastroin-
testinal ulceration due to central nervous
lesions.  some of this increased incidence
reflects recently devised iatrogenic measures
including new drugs and surgical therapy.
in adults, cerebrovascular lesions are the
commonest single cause of acute peptic ul-
ceration found at autopsy.  in children, we
found 25 instances of upper gastrointestinal
ulceration due to central nervous system le-
sions in 1,750 autopsies.  two general ana-
tomical categories could be recognized: acute
ulceration and malacias.
a variety of causative central nervous sys-
tem lesions was responsible in these 25 cases,
the commonest being bacterial meningitis.
other causes were poliomyelitis, brain tu-
mor, hydrocephalus, etc.
theories of pathogenesis are presented.
more experience with both drug and surgical
therapy is needed.  the recent development
of local freezing techniques offers promise
for reduction of mortality.
.I 727
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27
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mansonia crassipes as the natural vector of filarioids, plasmodium gallinaceum
and other plasmodia of fowls in ceylon
it would appear from these
observations that m.
crassipes is the natural vector of
p. gallinaceum of fowls
in ceylon and possibly of other
species of plasmodium of
fowls or of related avian hosts.
if one of the other
plasmodia from m. crassipes is
in fact p. lophurae
then this will be the first record
of p. lophurae from
this part of the world.  we are,
however, not certain
whether the fowl is the natural
vertebrate host of
p. lophurae in ceylon.
we have seen crithidial forms in
the midgut of engorged
wild-caught m. crassipes.  this
mosquito may, therefore,
prove to be the vector of the
trypanosome as well.  the
trypanosome differs from
trypanosoma gallinarum and
t. calmettei which have previously
been reported from
fowls.
.I 728
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27
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filariasis in portuguese timor, with observations on a new microfilaria
found in man
the results are described of an
investigation into filariasis in portuguese timor.
two types of microfilariae were
found in blood films: one was wuchereria bancrofti
and the other, referred to as the timor
microfilaria, is probably a new species.
blood surveys showed that w.
bancrofti and the timor microfilaria were widely
distributed in the territory but that infection
rates were usually low.
clinical lesions were few and mild;
elephantiasis was confined to oedema of the
lower limbs below the knee.
the timor microfilaria resembles
that of brugia malayi in general staining
reaction and appearance and in the possession
of two nuclei in the terminal thread, but
differs in over-all length, in cephalic-space ratio,
and in failure of the sheath to stain with
giemsa.  it is nocturnally periodic.  it was
rapidly removed from the peripheral blood
by treatment with diethylcarbamazine citrate
in daily doses of 9.3-13.3 mgm. per kgm. body
weight or 3.3-5.0 mgm. per kgm. body weight
for seven days.  only damaged fragments of
adult female worms were recovered.
the timor microfilaria was not
found in cats, dogs or monkeys.
the vectors of filariasis in timor
are still unknown.
.I 729
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27
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dipetalonema obtusa (mccoy,1936) comb. n. (filarioidea:
onchocercidae) in colombian primates, with a description of the adult
microfilaria obtusa mccoy, 1936, was identified in
the blood of 29 (31%) of 93 cebus
capucinus and c. albifrons from northern colombia, but was not
found in an additional 42 c. apella and
99 saimiri sciurea from other areas in colombia.  the adult male
and female, recovered from the peri-
esophageal connective tissue of the infected animals, are described
in detail.  dipetalonema obtusa (mc-
coy, 1936) comb. n. resembles tetrapetalonema marmosetae faust,
1935, but is smaller and the right
spicule is complex, not simple.
.I 730
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27
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experimental onchocercal ocular lesions in the chimpanzee
this is the first attempt to produce
onchocercal eye lesions with microfilariae of
o. volvulus in the chimpanzee.
live microfilariae, once in the anterior
chamber of the eye, could penetrate the an-
gle of the anterior chamber, the iris, the
ciliary body, the choroid and the vitreous.
most of the microfilariae injected alive
into the anterior chamber of the eyes of the
chimpanzee died within a short time.  com-
parison, therefore, could not be made be-
tween the effects of live and dead micro-
filariae.
microfilariae debris was demonstrated
within giant cells for the first time.
subconjunctival and limbal infiltration
with incipient pannus, inflammation within
the trabecular meshwork of the angle of the
anterior chamber and extensive active iri-
docyclitis were demonstrated in histologic
sections, although the conditions were clini-
cally quiescent.
the posterior segment lesion of oncho-
cercal chorioretinal degeneration could not
be reproduced.
subcutaneous and intravenous injec-
tions of worm extracts, derived from human
onchocercomas, may have contributed to the
onset of active choroiditis.  this sensitization
alone, without the intraocular injection of
microfilariae, had no effects on the eye.
various aspects of the pathogenesis of
human onchocerciasis are discussed on the
basis of present experimentation.
.I 731
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27
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the occurence of dirofilaria magnilarvatum price
and brugia sp. in philippine monkeys
of 356 macaca philippinensis examined, three were
found infected with dirofilaria magnilarvatum price, 1959.
one of these was infected also with a species of brugla.
both species showed a sub-periodic type of microfilarial
periodicity.  these observations suggest that philippine
macaques may serve as reservoirs for sub-periodic
b. malayi on palawan, where high rates of infection have
been found in people living in small villages in the
forests.  mansonia bonneae was found naturally infected
with third stage larvae of d. magnilarvatum.  it is sug-
gested that monkeys may serve as reservoirs for sub-
periodic b. malayi on the island of palawan, where high
rates of infection with this species have been observed
in people living in small villages in the forest.
.I 732
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27
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the filarial parasites of the eastern gorilla in the congo
a survey for parasites has been undertaken in 20 mountain
gorillas (gorilla gorilla beringei) from the eastern congo kivu
province.
six full-grown (two males and four females),
three adolescents
(one male and two females), and eleven
young gorillas were
examined, some of them during several
consecutive months.  nine
autopsies were performed.
no protozoa were discovered in the blood.
plasmodium parasites
which are common in gorillas and chimpanzees
from west africa
were never found in the eastern congo primates,
including ten
other gorillas examined previously and some fifty chimpanzees.
severe diarrhoea with a balantidiasis picture developed in two
young gorillas.  autopsy revealed however an intensive infection
with oesophagostomum stephanostomum and resulting fatty degenera-
tion of the liver.  oligotrichida belonging to the genus troglodytella
were commonly found in the intestinal tract.  oesophagostomum
stephanostomum eggs were consistently present in the stools of
the gorillas and autoinfection caused the death of several young
gorillas 4 to 6 weeks after their capture.
many microfilariae were found in the blood and the skin.  pre-
liminary communications were published mentioning the existence
of four different microfilariae in the blood of gorillas and of three
others in the dermal layers of the skin.  after a detailed study seven
species have been identified and described:  dipetalonema leopoldi,
d. gorillae, d. vanhoofi, d. streptocercum, microfilaria binucleata,
loa loa gorillae n.subsp. and onchocerca volvulus.  three of the
worms described have so far been discovered only in gorilla gorilla,
namely dipetalonema leopoldi, d. gorillae and loa loa gorillae.  two
of them were previously known from the chimpanzee, namely
d. vanhoofi and microfilaria binucleata.  one species, d. strepto-
cercum, first discovered in man and later described from the chimpan-
zee, is now also known from gorilla gorilla.  onchocerca volvulus has
been found in only one of the 20 gorillas examined.  gorilla gorilla
beringei in eastern congo might become through close contact
with man and his filarial vectors an abnormal or accidental host of
d. streptocercum and onchocerca volvulus or else might be considered
as an original reservoir of these filarial parasites of man.
.I 733
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27
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a pilot project for the control of filariasis
in thailand
in a village in kanjanadit district of surat-thani province, south thailand,
where a field station for filariasis studies had been established by the
bangkok school of tropical medicine, blood films were examined from 977 persons
(95.5 per cent. of the total population of 1,023).  two thick films (each of
20 c.mm.) were prepared from each person and stained with giemsa.  it was found
that 21.1 per cent. of the people harboured microfilariae (all brugia malayi).
elephantiasis was found in 5.3 per cent. of the population.
microfilarial periodicity was studied in 25 persons; in every case it was
found to be markedly nocturnal.
the blood of 98 cats, 52 dogs and two monkeys was also examined.  no b. malayi
larvae were recovered.
mosquitoes were caught and identified.  in an initial survey, 4,557 mosquitoes
were examined, of which 568 were mansonia spp.  in 4,136 dissections, b. malayi
larvae in stage ii were found in one m. uniformis and in stage iii in another;
the infection rate for m. uniformis was 0.6 per cent.
spraying with ddt was carried out in all the houses during the last phase of
the investigation.  it resulted in a slight decline in the numbers and
percentage of mansonia mosquitoes caught.
diethylcarbamazine was administered to as many of the villagers as possible,
in a dose of 5 mgm. of the citrate salt per kgm. body weight once weekly for
six weeks.  eight hundred and eighty-eight persons received the drug (86.8
per cent. of the population).  considerable side-effects were observed in
nearly all microfilaria-carriers.  blood examinations were repeated one month
and again one year after cessation of the drug.  it was found that the
proportion of microfilaria-carriers had decreased from 21.1 per cent. to 2.2
and 2.2 per cent. respectively, the filariasis infection rate from 26.1 per
cent. to 8.6 and 8.5 per cent., and the mean microfilarial density of all films
from 4.8 per 20 c.mm. blood to 0.48 and 0.12.  larvae of b. malayi were not
found in mosquitoes dissected one month and one year after the mass therapy.
.I 734
.C
27
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studies on loiasis in monkeys.
iv.--experimental hybridization of the human and
simian strains of loa
in the cameroons rain-forest there exist two strains of loa, each apparently
evolving in its own host-vector complex (duke and wijers, 1958).  the natural
simian parasite which is found most abundantly in the drill (mandrillus
leucophaeus), is characterized by the large somatic size of the adult worms
and microfilariae and by its nocturnal microfilariae periodicity.  it is
transmitted among the monkey population by the crepuscular canopy-dwelling
chrysops langi and c. centurionis.  the natural human parasite has diurnally
periodic microfilariae and is transmitted by the day-biting anthropophilic
c. silacea and c. dimidiata (bombe form).  it can also be transmitted
experimentally to the drill, in which host the parasites are of small somatic
size and maintain their diurnal periodicity.
as the two strains of contrasting periodicity can be maintained in drills, it
was decided to try cross-mating them to produce hybrids.  the present paper
describes the methods by which this was done, records the characteristics of
the hybrid parasites, and suggests that, when interbreeding, the two strains
segregate according to a simple mendelian pattern as regards periodicity and
somatic size.
.I 735
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27
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development of dirofilaria immitis in anopheles quadri-
maculatus after exposure of the microfilariae to a
freezing temperature
blood samples containing dirofilaria
immitis microfilariae were stored frozen for
periods ranging from 24 hr to 4 months,
thawed at 38 1c and
fed through an animal-derived bandrode membrane to laboratory-reared anopheles
quadrimaculatus.  the microfilariae were capable of developing to the third or
infective larval stage and migrating to the head and labium of the mosquito.
.I 736
.C
27
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advances in filariasis
especially concerning periodicity of microfilariae
a review is given of some advances in our knowledge about filariasis during the
past ten years.
it is urged that investigations should be continued on methods to facilitate
the control of filariasis in large populations, by means of
diethylcarbamazine--e.g. incorporation of the compound in cooking salt, as
was done with chloroquine against malaria.  furthermore, steps should be taken
to protect young people against filariasis by systematic treatment in the
schools.
in order to understand the cyclical disappearance of microfilariae from the
peripheral blood and their accumulation in the lungs, the movements of
microfilariae in the pulmonary capillaries has been studied by cinematography.
apparently their accumulation in the lungs is not due to mechanical retention,
but perhaps they migrate round and round in the pre-capillary network of
arterioles.
the periodicity of microfilariae is best considered as a biological rhythm.
apparently the microfilariae have a circadian rhythm of their own which is
entrained and synchronized by stimuli from the circadian rhythm of the host.
judging by experiments with monkeys containing microfilariae of edesonfilaria
malayensis, the most effective of these stimuli from the host seems to be the
rhythmic variation of body temperature which occurs every 24 hours.
.I 737
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27
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attempts to transmit wuchereria bancrofti to cats and to a toque monkey
there are no records of the larval development of wuchereria bancrofti in
experimental animals.  in attempts to transmit periodic w. bancrofti to
domestic cats and to a toque monkey we recovered from one of the cats an
infective larva that had undergone some development.  this finding was
reported in a preliminary note (dissanaike and niles, 1963); the present paper
gives the experimental details and describes the larva.
.I 738
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27
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the periodicity of microfilariae.
x. the relation between the circadian temperature cycle
of monkeys and the microfilarial cycle.
monkeys were used whose blood contained the microfilariae of edesonfilaria
malayensis, which has a nocturnal periodicity.
artificial lowering of the body temperature during the daytime caused the
microfilaria count in the blood to rise; and artificial raising of the body
temperature during the night caused it to fall almost to zero, i.e. inversion
of the normal circadian temperature rhythm of the body was followed by
inversion of the microfilarial rhythm.
the hypothesis is put forward that the circadian rhythm of the microfilariae
of e. malayensis (but probably not of the microfilariae of some other species)
is entrained by the circadian rhythm of body temperature, which thus provides
the "effective stimuli" to which these microfilariae respond.
.I 740
.C
29
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biliary tract morphology and prognosis
of biliary atresia
in 86 infants who did not have extrahepatic "hepatic" ducts, present
observation after use of artificial
bile ducts suggests that the presence of the
gallbladder may be of good prognostic significance in biliary atresia.
there are 11 long-term survivors (as of october 1965) up to 8 1/4 years of
age (100 months) after use of artificial bile ducts in 86 babies.  a
gallbladder was identified in 10 of the 11 infants.
other specific factors for this prolonged survival pattern in these infants
with biliary atresia have not yet been identified, although suggestive
correlations among minimal hepatic fibrosis, maximal bile ductule
proliferations and the presence of the gallbladder were noted.
it is suspected that if any opportunity for long-term survivals exists for
infants to overcome the tragic occurrence of biliary atresia that the
surgeon should avoid trauma to the hepatic pedicle.
we may be able to provide a "guarded" rather than a "pessimistic" prog-
nosis when the gallbladder is found in the babies with biliary atresia.
.I 741
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29
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current concepts in the management
of congenital biliary atresia
the current management of congenital
biliary atresia at the university of cali-
fornia, los angeles is reviewed.
biliary enteric decompression was
performed on 18 of the 27 patients, eight
of whom are presently alive (29.6%).
these figures are higher than the cure rate
of 8% previously reported.
described recently.  five additional patients
with extrahepatic atresia underwent biliary
decompression by means of a hepatic
lymphaticojejunostomy.
early diagnosis of biliary atresia is im-
perative in order that any corrective sur-
gery may be performed before advanced
biliary cirrhosis develops.
.I 742
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29
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congenital atresia of
the extrahepatic bile ducts
because congenital atresia of the extra-
hepatic biliary tract is almost always fatal,
exception to this course becomes of interest.
the remarkable history of one such infant
was reported in 1960 when he had attained
the age of 2 1/2 years and, after three opera-
tions, he was in good health developing nor-
mally and free of jaundice.  since he is now
8 1/2 years of age, has had two more opera-
tions, is still free of jaundice, and is again
in good health, his further course since 1960
should be of interest.
.I 743
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29
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neuroaxonal dystrophy in congenital
biliary atresia
neuroaxonal dystrophy has been described in 8 patients with congenital
biliary atresia.  the characteristic changes include axonal dystrophy, a mild
loss of nerve cells and a variable degree of astrocytic reaction, mainly in the
gracile, cuneate and trigeminal nerve nuclei in the medulla, and rarely in
other parts of the central nervous system.
the neuroaxonal dystrophy in these patients is remarkably similar to that
in patients with prolonged mucoviscidosis and in experimental vitamin
e-deficient rats.
it is strongly suggested that the neuroaxonal dystrophy in these patients
with congenital biliary atresia is a manifestation of prolonged vitamin e
deficiency.
the neuroaxonal dystrophy in these patients is also similar to that seen
in aging and bears resemblance to the axonal change encountered in a group
of heredo-degenerative diseases, the various forms of "hallervorden-spatz
disease".  the pathological similarity between these diverse conditions
warrants further investigation as to the possible metabolic
relationship between them.
.I 744
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29
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extrahepatic biliary atresia: comments on the
frequency of potentially operable cases
in a 10 year period, 35 infants with extrahepatic biliary atresia were
encountered.  twenty-eight babies, who were subjected to surgery and operative
liver biopsy, are discussed.  although an operable lesion was detected at
laparotomy in only one baby, 5 further potentially correctable lesions were
discovered in the 14 necropsies performed.  review of the literature revealed
that few authors have discussed necropsy findings and that confirmation of the
diagnosis by liver biopsy has been neglected in many cases, including some
of those claimed as surgical cures.  it is concluded that the frequency of
potentially operable forms of biliary atresia is not really known.
.I 745
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29
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metabolism and excretion of c14-labeled bilirubin in children
with biliary atresia
and judson g. randolph
radioactive bilirubin was injected intravenously
into 3 children with biliary atresia.  the isotope
over a period of ten to fourteen days was recovered
principally in the urine.  sixty per cent of the label
in the urine was found to be in the form of bili-
rubin.  distribution of the radioisotope was observed
to be principally extravascular but not, as in other
forms of jaundice, in the same distribution as albumin.
daily turnover of bilirubin was several times greater
than the calculated normal daily production of bili-
rubin.  this was assumed to be due to increased
hemoglobin breakdown, confirmed by survival studies
of cr51-tagged red cells.  the serum half-life of intra-
venously administered radioactive bilirubin may have
useful prognostic value in children with biliary atresia.
.I 746
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29
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central regulation of enzyme activity and synthesis
in embryonal and adult mammalian tissues
activity of non-specific hexokinase (hk) in soluble fraction and,
particularly, in mitochondria of embryonal liver is much higher than
in the adult rabbit; it decreases in the prenatal period, gradually
approaching adulthood values postnatally (fig.1).  embryonal liver
lacks specific glucokinase (gk) (1,2), although during the second half
of embryonic development there occurs incretion of insulin, known
to induce gk synthesis in the liver of alloxan diabetic animals (3,4).
activity of glucose-6-phosphate dehydrogenase (g6p dh) in
soluble liver fraction is subject to quite similar changes during
embryonic development.
.I 747
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29
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ribonuclease activity in hepatic nuclei during development
mammalian liver undergoes marked qualitative and quantitative changes
during the development from the embryonic to the adult stage.  many of these
events are associated with the derepression or repression of certain enzymes
which may be related to specialized subcellular activity.  the involvement
of ribonucleic acid in the transcription of the information from the genome
into the construction of a finished protein molecule has prompted a study of
biosynthesis of the rna during differentiation.  although considerable effort
in this regard has been expended in amphibian1-5 and avian6,7 systems, as well
as in the sea urchin8-11, a paucity of literature exists with mammalian liver.
accordingly, an investigation of the alterations in rna metabolism which
occur during the development of the rat embryonic liver has been undertaken.
this report concerns the fluctuations in nuclear ribonuclease during hepatic
development and some of the properties of the enzyme.
.I 748
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29
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an electron microscopic study of developing gall
bladder epithelium in the rabbit
the gall bladder epithelium of the
adult rabbit consists of two types of cells.
the first and more common type shows features associated with absorption,
notably microvilli, limited pinocytosis, some lysosomes and an elaboration of
the lateral cell membrane and intercellular spaces.  the mitochondria are
concentrated in a subapical band.
the second and more infrequent type is a dark rod-shaped cell of unknown
function but which may be a dehydrated epithelial cell.
foetal epithelial cells lack the functional adult characteristics; the mito-
chondria are uniformly distributed.  in addition they display basal granules
and apical apocrine bullae.
epithelial cell damage and white cell infiltration occurs between 24 days
after birth or just after.
just before birth some epithelial cells are very large and pale with smooth
outlines, others are more dense and display vigorous pinocytosis.
adult characteristics are acquired at or immediately after birth and pino-
cytosis subsides.  it is believed that water resorption occurs before the
functional changes which allow continuous passage of water into the
circulation.
.I 749
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29
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congenital anomalies of the cystic duct
and phineas rabinovitch
anomalies of the cystic duct, of four differ-
ent types, are reported.  the characteris-
tic anatomic appearance and embryonic
development of each of these anomalies
are described and the clinical and surgical
significance discussed.
.I 750
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29
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lesions of the liver in hereditary
metabolic diseases
whether the various cells of the liver, both parenchymal and stromal,
receive genetic misinformation in all hereditary diseases caused by gene
mutation is unknown, but the metabolic capabilities of these several cell
types are so diverse that it is not surprising that their involvement in
many such diseases can be demonstrated by clinical, pathological, or bio-
chemical methods.  repetitive abnormality of the liver has apparently not
been defined for any disease caused by quantitative (i.e., chromosomal)
gene anomaly, whether produced by nondisjunction, translocation, or
major deletion, perhaps because relatively few such diseases have been
described.  as a result, the genetically determined disorders of the liver
surveyed in this paper appear to be the result of conventional "single
gene" abnormalities, and to be transmitted in affected families by men-
delian mechanisms.
.I 751
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29
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acid catabolic enzyme activity in relation
to accessory limb and cancer initiation in amphibia
cathepsin and acid phosphatase were determined in livers and kidneys
of adult rana pipiens and triturus viridescens.  organ-specific and species-
specific differences in distribution of these enzymes were found, as well as
considerable differences in the effect triton x-100 on the two enzymes.
a heterogeneous population of lysosomes in respect to enzyme content and
stability is deduced.
we have found positive correlations between catheptic activity of the
implant and host tissue dissociation, and between acid phosphatase and
inducibility, as features of the phenomenon of implant-induced accessory
limb formation in urodeles.  further, we have found a positive correlation
between catheptic activity and resistance to virus-induced renal adenocar-
cinoma development in rana pipiens.
.I 752
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29
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neonatology
considerable progress has been made in the
knowledge of bilirubin metabolism since the char-
acterization of "direct" (conjugated) bilirubin as an
ester glucuronide.  the metabolic pathway involved
in this hepatic conjugation is now well established
and has been the subject of excellent reviews by
sherlock and billing.
sherlock's diagrammatic representations of biliru-
bin metabolism (fig. 1) and of the possible mecha-
nisms of jaundice (fig. 2) are reproduced here
because they furnish a clear picture to serve as a
reference point for the discussion to follow.
it is interesting to re-examine current concepts of
the etiology of physiologic jaundice with this dia-
gram in mind.  jaundice may occur for a number of
reasons, described below.
.I 754
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29
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trisomy 17-18 syndrome with congenital
extrahepatic biliary atresia and congenital
amputation of the left foot
the phenotypic characteristics of
the 17-18 trisomy syndrome have been well
described.  among the most recently docu-
mented cases of this syndrome are those
with findings of agenesis or aplasia of various
bones of the forearm and hand, in addition
to the more classical symptoms.
we have recently studied a case of trisomy
17-18 syndrome with congenital absence of
the left foot, and congenital extrahepatic
biliary atresia.
.I 757
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29
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les icteres du nouveau-ne en dehors
de l'incompatibilite foeto-maternelle
statistical data pulled off a study of 30 haemolytic neonatal icteri
not linked to a foeto-maternal incompatibility, and of 200 non haemo-
lytic neonatal icteri.  among this latter, the two most important groups
are the malformative icteri (69 cases) and the neonatal hepatitis
(109 cases).  the difficulties of the diagnosis frequently rencountered
between these two groups clearly appear in the comparative statistical
analysis of the clinical, histological and evolutive data.
.I 759
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29
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galactosemie congenitale
this observation of a case of congenital galactosemia with
a particular familial incidence gives the opportunity of a
brief review on the subject.
of a certain point of view we must consider that galac-
tosemia is much more frequent than we suppose, that there
are many severe cases with a reserved prognosis, that even
with very slight degree of galactosemia, the disease must
receive the most careful attention from the pediatrician.
.I 760
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29
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postnatal changes in the portal circulation
during foetal development a large portion of the
oxygenated umbilical blood flows through the
umbilical recess directly into both main portal
branches.  accordingly, these are exposed to the
umbilical blood pressure and have a wide
by contrast, the trunk of the portal vein is narrow
and there is probably only a small blood flow through
it from the inactive digestive tract, though the
pressure in it is approximately the same as in the
umbilical vein or perhaps somewhat higher.
immediately after birth the liver is deprived of the
substantial umbilical blood flow.  the portal
venous pressure falls to about one-quarter of the
umbilical venous pressure at birth.  however the
pressure gradient between the portal veins and
inferior vena cava remains constant.
.I 761
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29
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pattern of serum transaminase activity
in neonatal jaundice due to cytomegalic inclusion
disease and toxoplasmosis with hepatic involvement
the pattern of serum transaminase ac-
tivity that evolved in a newborn infant with
congenital toxoplasmosis and in another new-
born infant with congenital cytomegalic in-
clusion disease is described.  this enzymatic
pattern was unlike that found in infants with
any other cause of neonatal jaundice studied
to date.
.I 762
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29
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impaired development of rat liver enzyme activities at
birth after irradiation in utero
development of activity of three liver enzymes at birth was studied in rats re-
ceiving 180 rads of x-rays on day 15 of gestation.  at 20 days of gestation,
activities of lactic and glycerophosphate dehydrogenases and
glucose-6-phosphatase were not altered.  the subsequent increases in enzyme
activities in the 3 days between 20 days of gestation and 1 day of age were
only 30 to 60% of those observed in controls.  this finding suggests that
irradiation in utero may alter later development of enzyme activity in the
perinatal period.
.I 763
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29
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(cytological and cytochemical study of
hepatic cells in the human embryo)
changes in golgi apparatus and mitochondria as well as in the contents of
nucleic acids, proteins, polysaccharides, lipids and iron in the hepatic cells
of developing human embryo were studied; the data obtained in human embryos and
adults were compared.  it was found that during the developmental process some
changes in localisations of golgi apparatus and iron salts were taking place.
the contents of rna and polysaccharides in the cytoplasm increased:
mitochondria in the form of granules were revealed throughout the embryonic
period and in adults.  no essential alterations in the contents of dna,
proteins, and lipids were noted.
.I 764
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29
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risk of severe jaundice in
glucose-6-phosphate-dehydrogenase
deficiency of the newborn
the incidence of g.-6-p.d. deficiency and neonatal
jaundice in all male infants born in one year in an area of
the island of lesbos was studied.
of 634 infants tested, 29 (4.6%) were found to be
g.-6-p.d. deficient.  hyperbilirubinaemia of 16 mg. per
100 ml. or over was observed in 34% of g.-6-p.d.-
deficient newborn males and in 9.1% of those with normal
enzyme activity--in more than half of them in the absence
of incompatibility or prematurity.
this is the first time that such a high incidence of
severe neonatal jaundice has been reported in both a
g.-6-p.d.-deficient and a g.-6-p.d.-normal group.  it is
postulated that in the population of lesbos a second
factor increases the incidence of neonatal jaundice,
especially when this factor is combined with g.-6-p.d.
deficiency.
.I 765
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29
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studies of b-glucuronidase acti-
vity in bile and liver of devel-
oping chick embryos and chicks
in search for the reason of the occur-
rence of unconjugated bilirubin and
biliverdin in chick-embryo and in chick
bile the possibility of a b-glucuronidase
function must be taken into serious con-
sideration.
.I 766
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29
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jaundice in infancy
most causes of jaundice in infancy are discussed.  the empha-
sis has been on those syndromes solely or usually encountered
in the neonate and infant.
.I 767
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29
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absence of the cystic duct
a case of congenital absence of the cystic
duct is described, the 18th reported case in
the literature.  the embryogenetic basis of
anomalies of the extrahepatic biliary tree
is discussed.  methods of early operative
recognition and surgical management of
the anomaly are suggested.
.I 768
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29
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familial extrahepatic biliary atresia
a fifth family with familial congenital
extrahepatic biliary is described.
clinically and pathologically familial
and nonfamilial biliary atresia are similar
except for a predominance of males in the
familial condition.
the sex incidence and association of
other congenital anomalies is discussed in
relation to a possible etiology.  further in-
formation must be correlated and new facts
uncovered before the nature of this syn-
drome will be known.
.I 770
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28
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adjuvant chemotherapy in cancer of the
large bowel
the completeness of reporting, the avail-
ability of continuous statistical analysis to
warn of adverse effects, and the accumulation
of 300 cases a year have demonstrated that this
cooperative study group can provide a rela-
tively quick assessment of a new approach to
treatment of cancer of the large bowel.  it is
hoped that a study begun in january, 1962, on
the use of 5-fluorodeoxyuridine as an adjuvant
to adequate excisional surgery may demon-
strate that, with a drug known to produce
objective remissions in 20 per cent of a group
of unresectable cases of colon carcinoma
the five year survival rate in curative resections
may be improved.
.I 771
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28
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cancer chemotherapy by prolonged arterial
infusion
our current experience is reported with
136 patients treated by prolonged arterial
infusion chemotherapy.  the patients pre-
sented a variety of far advanced cancers un-
suitable for conventional surgical or roent-
gen therapy.  antimetabolite solution, either
methotrexate or a fluorinated pyrimidine,
was injected continuously through a small
plastic catheter into the unobstructed artery
to provide a high regional drug concentration
for days to weeks.  the patients have received
drug infusion for up to 45 days.  their course
has been followed for up to 37 months after
treatment.
methotrexate with antidote therapy by
systemic administration of citrovorum fac-
tor was used preferentially in most patients.
a fluorinated pyrimidine, most commonly,
5-fluoro-2'-deoxyuridine, was preferred for
hepatic artery infusion of liver metastases.
.I 772
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28
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the montgomery tube to palliate
hypopharyngeal cancer
three cases of advanced, incurable cancer of the hypopharynx
have been presented.  in each instance, the simple procedure of insert-
ing an available prothesis served as an effective palliation for an
otherwise difficult or hopeless situation.
.I 773
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28
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adjuvant cancer chemotherapy
development of a dosage schedule for adjuvant cancer chemotherapy
in surgical cases
an account is given of the development
of a dosage schedule for adjuvant can-
cer chemotherapy for surgical patients.
this treatment was administered for
two purposes:
as an adjuvant to radical surgery
to reduce the risk of blood-borne
metastases.
as a palliative measure for non-ra-
dically operated and inoperable pa-
tients.
for these purposes 3 dosage levels
were fixed:
a maximum tolerated dose for ad-
juvant therapy.
a maximum tolerated dose for pa-
renteral palliative therapy.
a maximum tolerated dose for oral
palliative therapy.
for this treatment the authors used
2 antimitotics, sp-i and sp-g, both of
which are podophyllin derivatives.
.I 774
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28
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surgical palliation for lung cancer
the results of resecting incurable lung cancer
in an effort to improve the terminal course of a
small number of patients are briefly presented.
this is not a comparative study and no in-
ferences or conclusions are justified regarding
the choice of this form of therapy as palliation
in preference to other forms of palliative ther-
apy; however we do believe that the terminal
course of the patient with lung cancer is bene-
ficially effected by removal of the primary
tumor whenever this is technically feasible.
.I 775
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28
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management of advanced endometrial
adenocarcinoma with medroxyprogesterone
acetate
a basis for progestin therapy for patients
with advanced endometrial adenocarcinoma
is presented.  the criteria for selection of
patients for hormone therapy and the sched-
ule of administration of medroxyprogester-
one (provera) is discussed.  evaluation of
patients for objective changes only, i.e., by
visual, palpable, histologic, or roentgeno-
logic means, revealed complete or partial
remission with significant palliation in 8 of
20 patients (40 per cent).  response to me-
droxyprogesterone therapy is apparently re-
lated to degree of differentiation of the pri-
mary neoplasm, the well-differentiated le-
sions being more responsive.  documentation
of tumor effect by serial biopsies during
treatment provides an index to the histologic
changes this progestin produces in suscep-
tible cases.  the effects of therapy upon
serial urinary hormone excretion rates is
documented in several patients.
on the basis of our experience, the treat-
ment of patients with advanced endometrial
adenocarcinoma with the potent progestin
medroxyprogesterone seems justified.
.I 776
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28
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chemotherapy of breast cancer
the majority of cancer patients who are
referred for chemotherapy are in far advanced
stages of the disease.  the difficulty in deliver-
ing an effective dose of an oncolytic agent
to the involved areas may limit the results of
treatment unless the patient's tumor is an un-
usually responsive one.  the variability in re-
sponse between apparently similar cases of
cancer of the same cell type has become in-
creasingly evident, and is as puzzling as the
fact that 20 per cent of patients with breast
cancer will live 5 years with no treatment.  the
decisions as to the choice between chemother-
apy and hormone therapy, as well as to the
choice of the chemotherapeutic agent to be
employed, may be difficult.
as experience increases, the usefulness of
chemotherapy in the treatment of cancer is
becoming increasingly apparent.  it also has be-
come apparent that chemotherapy cannot be
regarded as a curative procedure in advanced
cancer even though an occasional patient ap-
pears to have been cured.  however, the value
of the oncolytic agents in prolonging useful
survival time, ameliorating many of the dis-
tressing symptoms associated with cancer, and
providing the physician with an extra tool for
a positive program in the care of the cancer
patient is now established.
.I 777
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28
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clinical experience with palliation
of metastatic adenocarcinoma with
5-fluorouracil chemotherapy
chemotherapy of solid tumors is becoming a
more and more helpful therapeutic tool.  it
is probable that within a few years chemother-
apy will become firmly established as an ad-
junct to the primary treatment of solid tumors.
perhaps someday a cancerocidal chemical will
be devised that can actually act as antibiotics
do on bacteria.  for this reason it is important
for all surgeons interested in the treatment of
cancer to try to keep abreast of the recent ad-
vances in the field of chemotherapy.  surgeons
should also begin to use some of the technics for
palliation of incurable patients so that when
these drugs are added to the armamentarium of
primary treatment of cancer, they will be
familiar with the various technics and the mode
of actions of the drugs.
5-fluorouracil (5-fu) has had extensive clin-
ical use and has produced significant palliation
in breast and colon cancers with about a third
of these patients receiving palliation for five to
six months.
.I 778
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28
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pelvic perfusion and carcinoma
of the rectum
a method of regional chemotherapy through
isolation of the pelvis has been presented.
all of the subjects were near the terminal
stage at the time of perfusion.  the survival
time and degree of palliation have been en-
couraging.
.I 779
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28
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carcinoma of the esophagus
a survey of fifty-seven patients with cancer
of the esophagus occurring over a twenty year
period is presented.  the presenting complaints
of the disease, methods of diagnosis, and char-
acteristics of the disease are discussed.  three
equal treatment groups consisting of no treat-
ment, x-ray treatment, and surgical resection
were compared and the results were extremely
poor.  only one patient in all three groups sur-
vived longer than two years.  it was our con-
clusion, supported by the opinion of others,
that x-ray therapy gave the best palliation in
most cases and that surgical resection for cure
should be used in only the most suitable pa-
tients.
.I 780
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28
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carcinoma of bladder: cobalt therapy
from 1959 to 1962, 202 patients have received
radiotherapy for carcinoma of the bladder.  radi-
cal therapy with cobalt-60 has been done in 121
of these cases.  these patients received tumor
doses in excess of 5000 rad in 3 weeks.  of 49 pa-
tients followed for 2 years after radical treatment,
28 are alive.  sixteen out of 32 patients with
stage b2, c or d tumors are alive; while 15 pa-
tients survived out of 30 with tumors of grades
3 and 4 (broders').  four of the 28 survivors had
cystectomy performed and none showed residual
disease in the bladder or lymph nodes.  the com-
plications of radiotherapy presented were not
considered to be excessive.
we believe that radiotherapy should be the
initial treatment for patients with infiltrative
carcinoma of the bladder.  the survivals pre-
sented at 2 years are better than those quoted for
radical cystectomy (whitmore and marshall)
and useful bladder function is preserved for the
majority of survivors.  we reserve cystectomy for
specific indications.
.I 782
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28
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systemic chemotherapy
for cns metastases
of solid tumors
of the 13 cases studied, remissions were ob-
tained in eight.  this 62% remission rate is not
significant because of the number of variables
present.  however, we believe that chemother-
apy for this type of patient is indicated, as sup-
ported by the reported data.  the results suggest
that the blood supply to solid tumors is different
from that of tumors associated with hematopoi-
etic disorders.  the latter respond very poorly,
if at all, to systemic therapy.  although we were
not able to measure the central nervous system
(cns) lesions exactly, the regression of the
cns symptomatology was significant.  in pa-
tients who had other demonstrable metastatic
disease, those lesions also regressed.  with this
evidence we feel that patients with metastatic
cns lesions, even when these have recently
resulted in paralysis or seizures, should be con-
sidered for systemic chemotherapy.
.I 783
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28
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combined 5-fluorouracil and supervoltage
radiation therapy in the palliative manage-
ment of advanced gastrointestinal cancer:
a pilot study
malcolm y. colby, margaret a. holbrook
5-fluorouracil in combination with supervoltage radiation
therapy was employed in the palliative treatment of 44 pa-
tients with advanced gastrointestinal carcinoma.
a total dose of from 40 to 50 mg. per kilogram of body
weight of 5-fluorouracil given by rapid intravenous injection
at the onset of radiation therapy was found to be relatively
safe and tolerable.  larger doses were associated with excessive
toxicity and mortality.
a sufficient number of patients achieved objective and
subjective palliation to justify controlled study of the possible
additive or synergistic role that 5-fluorouracil may have when
combined with radiation therapy.
.I 784
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28
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palliation by radiotherapy
the purpose of radiotherapy in the management
of cancer of the lung is first to cure the disease;
second, to prolong useful and comfortable exist-
ence; and third, to provide comfort and relief of
suffering to those who are symptomatic and in-
curable.
cancers of the lung vary quite widely in their
response to radiation.  those of glandular origin,
the adenocarcinoma, are more often than not of
modest susceptibility and sometimes quite resis-
tant.  the very undifferentiated, the so-called oat-
cell cancers, are often of exquisite sensitivity, re-
sponding to irradiation almost like lymphomas.
most cancer of the lung, however, is squamous-cell
carcinoma and as such may be considered to be
moderately radiosensitive in much the same order
of magnitude as squamous-cell carcinoma of the
skin, cervix or larynx, and should, in theory, be
curable by this means in the same degree.  unfor-
tunately, this has to date not been found to be
true.  the reasons are principally two: first and
foremost, by the time a diagnosis is made, cancer
of the lung has more often than not, estimated at
80% and more, spread beyond the site of origin,
thus making cure by any effective means presently
available unlikely.  second, the substrate in which
the cancer grows, the lung, tolerates radiation less
well than do the tissues which surround the highly
radiocurable epithelial cancers such as carcinoma of
the skin, cervix, and larynx, thus making an un-
favorable therapeutic ratio.
.I 785
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28
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chlorambucil-prednisolone therapy
for disseminated breast carcinoma
over a 7 1/2-year period, 71 patients with
disseminated breast cancer were treated
with combined alkylating-agent-cortico-
steroid therapy.  chlorambucil and pred-
nisolone were the drugs of choice.  these
agents, administered orally, produced no
serious or disagreeable toxic effects.  twen-
ty-four patients (33.8%) had objective
regression of six months' duration or long-
er; average survival time after therapy
was 23.9 months.  results are statistically
similar to those obtained with sex-steroid
and endocrine-ablation therapy, presum-
ably because the three modalities have a
similar mechanism of action, ie. suppres-
sion and/or eradication of endogenous
estrogen.
.I 786
.C
28
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recent advances in the treatment of
cancer of the esophagus
whether combining surgery and supervoltage radiation therapy will
noticeably improve the 5-year survival rate for carcinoma of the esopha-
gus remains to be seen.  it is encouraging, however, to observe at the time
of operation that the previously irradiated esophagus is firmly encased in
fibrous tissue, which gives the impression that the danger of disseminating
tumor at the time of resection is diminished.  in addition, the fibrosis sug-
gests that the tumor that had spread locally, beyond the limits of surgical
excision, may have been destroyed.
.I 787
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28
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cyclophosphamide in the management of
advanced bronchial carcinoma
forty patients suffering from advanced bronchial
carcinoma who were treated with cyclophospha-
mide are reviewed.  the selective effect of the drug
in tumours of the oat-cell type is noted.  it is
suggested that relapses which occur while the
patient is on oral maintenance therapy may be
controlled by a further intravenous course of
cyclophosphamide.
full clinical and statistical details of all the
patients referred to in this paper are available on
application to the author.
.I 788
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28
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esophageal obstruction
the use of an endoscopically inserted tube in the
care of esophageal carcinoma
our experience suggests that the en-
doscopic insertion of intraluminal tubes
provides a relatively simple and reason-
ably safe method of dealing with some
of the problems which arise in the man-
agement of patients with esophageal car-
cinoma.  such tubes would appear to be
of particular use in handling the prob-
lems of obstruction and regurgitation in
patients with incurable tumors, but may
also be helpful in preparing severely
debilitated patients with esophageal car-
cinoma to withstand the rigors of opera-
tion and radiation therapy.
.I 789
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28
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palliative radiation therapy
the care of the patient with "incurable" cancer may be
directed by physicians of various backgrounds and per-
suasions.  if this physician has little experience in such
care, he is prone to be influenced by still prevalent atti-
tudes of therapeutic futility or by equally unjustified
premature claims for widely publicized methods recent on
the scene.  surgery and radiation therapy remain the
dominant treatment forces for the patient with cancer.  it
is unfortunate that lack of demonstration of good radiation
therapy has led to unjustified condemnation of the method
rather than the user, with resultant loss to the patient's
welfare.  to obtain maximal benefit, radiation therapy
must be allowed indications and contraindications like any
therapeutic modality.  these must be the responsibility of
the therapeutic radiologist.  application of realistically
stringent indications and contraindications does not lessen
useful accomplishment, but avoids unnecessary morbidity,
waste of time, money and effort, and delay in seeking
suitable treatment.
.I 790
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28
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carcinoma of the middle ear
the results of radiotherapy in a relatively large
number of cases of carcinoma of the middle ear
are reported.  the crude 5 year survival rate of 100
cases is 29%.  there is no difference in survival
between those cases who had a preliminary
mastoidectomy and those who did not.  the use of
megavoltage x-rays probably increases the survival
rate.
.I 791
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28
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sustained palliation in
ovarian carcinoma
management of 64 cases of advanced
ovarian carcinoma has been analyzed.
an attempt is made to compare the
value of radiation and the value of chloram-
bucil, using salvage time and sustained pal-
liation as end points.
chlorambucil, an outpatient oral medi-
cation, appears to be as efficacious as ra-
diation in advanced ovarian carcinoma.
chlorambucil may be used before or
after irradiation therapy.
pleural and peritoneal effusion respond
favorably to chlorambucil 80% of the time.
the possibility of using a different
dosage schedule is discussed.
.I 792
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28
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clues in dealing with
cancer patients
it is clear that the patient with cancer changed
his pattern of communication at different stages of
the disease.  these patterns in communication were
the basis or clues for the doctor and paramedical
personnel to consider in making total care more
effective.  the bedside clinician of past days knew
these clues instinctively in his wise ministrations.
thanks to a gifted social worker these have been
now made manifest to help all of us in dealing
with cancer and perhaps other chronic relentless
diseases.
.I 793
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28
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radon and radioactive seed volume implants
for extensive recurrent vaginal-pelvic cancer
radioactive seed volume implants for
extensive recurrent vaginal-pelvic cancer
result in extended control of otherwise
untreatable disease.  immediate and early
reactions are practically nonexistent.  late
complications are also rare, the most
serious being severe hemorrhagic cystitis
in 2 of the author's 13 patients.
.I 795
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28
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advanced cancer of the breast
treated primarily with irradiation
the five-year results in 109 patients
treated primarily with irradiation for
cancer of the breast, mostly in the late
stages, have been analyzed.
in all cases, the initial intent was to
control with x radiation alone the primary
tumor involving the breast and its entire
lymphatic drainage.  irradiation remained
essentially the sole method of treatment in
84 cases.  postirradiation mastectomy was
performed in the 25 other patients, who
initially had been considered inoperable.
the plan of treatment has consisted of a
single continuous course of radiation ther-
apy, protracted over a period of seventy-
five to one hundred days and administered
in 3 closely integrated phases.  tissue
doses, superficial and deep, must be
brought to the highest levels required for
maximum biological effects within the
tolerance of the structures involved.
the immediate effects of irradiation
alone have been remarkable.  the re-
gression of neoplastic manifestations in the
breast and palpable nodes, the degree of
healing of ulcerated carcinoma, and the
incidence of recurrence have been re-
corded and assessed to determine the
efficacy of treatment.
.I 796
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28
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the management of disseminated
cancer of the breast
when mammary cancer has spread to tissues beyond
the breast and axilla, the disease is incurable by present
day methods.  however the patient may be greatly helped
and tumor growth retarded by skillful and sympathetic
application of irradiation, surgical ablation, hormone ad-
ministration, and chemotherapy.  given in conjunction
with analgesics, sedatives, and ataractic drugs, these
measures can frequently reduce disability and pain and
prolong the period of useful comfortable life.
.I 797
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23
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toilet training of an autistic eight-year-old through
conditioning therapy: a case report
operant conditioning techniques have been successfully
used in the treatment of a wide variety of be-
havioral problems including hysterical blindness (brady
and lind, 1961), tics (barrett, 1962), psychotic
symptoms (lindsley, 1956; 1960, 1961), reading disabilities
(rachman, 1962) stuttering (flanagan et. al.,
1958) enuresis (mowrer and mowrer, 1938; lovibond,
1961, 1963a, b) and encopresis (neale, 1963;
madsen, 1965).  neale (1963) successfully treated three
out of four encopretic children using operant
training techniques.  in the case of one 9-yr-old boy, with
an 18 month history of encopresis, going to the
toilet was rewarded by a candy, praise and recording the
event in a special book in the boy's presence.
soiling was not inadvertently rewarded (e.g. attention) or
punished; the boy would be given a clean pair
of pants without comment.  neale reports that response to
treatment was rapid and complete and 6 months
after toilet training there had been no relapse in bowel habits.
procedures similar to those used by neale were used in
the case reported here.  positive and, in a
small number of instances, negative reinforcement were used
to toilet train an 8-yr-old boy diagnosed by
a child psychiatrist/neurologist as having infantile autism.
.I 798
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incidence of symptoms of early infantile autism in
subsequently hospitalized psychiatric patients
this study was concerned with the
relationship between the occurrence dur-
ing the first two years of life of symptoms
of early infantile autism, as retrospective-
ly reported by the mothers of s's and
subsequent adjustment.  the mothers of
69 unmarried young hospitalized psychia-
tric patients were interviewed to deter-
mine the presence or absence of each of
28 different signs contained in a check
list.  the signs represent characteristic
features that are reportedly often found
in conjunction with early infantile autism.
as a control, 50 mothers of high school
students residing in the community and
presenting no significant adjustment prob-
lems were questioned in regard to the
very same items.
the results indicated that there were
significantly more symptoms reported for
patients than for normals, and that this
finding applied to the overall number of
symptoms as well as to several subcate-
gories of symptoms.  the items classified
under the heading of "social withdrawal"
appeared to be the most sensitive in dif-
ferentiating the groups.  it was also found
that 11 of the 28 signs distinguished be-
tween the patients and normals, with all
except one occurring more frequently in
the former group.  it was concluded that
a significant relationship existed between
the reported presence of symptoms that
are often associated with severe and early
ego impairment and subsequent status as
a mental hospital patient.  this study does
not provide any direct answer to the ques-
tion of what proportion of children with
infantile autism are later able to make an
adequate adjustment outside of a mental
hospital.
.I 799
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23
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eeg abnormalities in early childhood schizophrenia:
a double-blind study of psychiatrically distrubed
and normal children during promazine sedation
eeg tracings during promazine sedation
were obtained on 58 children who had
autistic or symbiotic childhood psychosis.
for comparison eeg's were done under
identical conditions on 4 other groups of
children: 44 with chronic undifferentiated
schizophrenia; 37 non-psychotic children
with severe, acting-out behavior disorders;
10 with neuroses; and 13 psychiatrically
normal children.  final clinical diagnoses
were made without knowledge of the eeg
readings as determined for this study, and
the eeg's were all placed in random order
and read without any knowledge of the
clinical diagnosis.  eeg abnormalities ac-
cepted were focal slowing, focal spikes,
paroxysmal spikes and waves, and par-
oxysmal spikes and waves with independent
spikes.
among the 149 patients 51% had abnormal
records.  none of the psychiatrically normal
children had eeg abnormalities.  except
for the neurotics, the eeg abnormalities
were qualitatively and quantitatively sim-
ilar in the psychiatric patients.  the
most frequent abnormalities were ir-
regular paroxysmal spike and wave com-
plexes, often best seen during the
transition from wake to sleep.  of the 149
patients, 33% had this complex, either alone
or with independent spikes.  although these
complexes were most frequent in the au-
tistic-symbiotic group, the incidence was
not statistically significantly different from
the higher performing, chronic undiffer-
entiated schizophrenics who had communi-
cative speech or the non-psychotic children
with acting-out behavior disorders.
of the 58 autistic-symbiotic children, 19%
had seizures, which is similar to the 13%
seizure incidence in the remaining 91 psy-
chiatric patients.
whether the cerebral dysfunction im-
plied by this study is a primary disorder
or is secondary to some factor such as the
effect of prolonged anxiety on body chem-
istry cannot be decided at this time.  never-
theless, an organic concomitant has been
demonstrated in 51% of the psychiatrically
disturbed children.  by increasing the
amount of time included in the eeg sam-
ple, the incidence of electrical abnormalities
might be even higher.
.I 800
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23
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on early infantile psychosis.
the symbiotic and autistic syndromes
in conclusion, i wish to state that the
core of child psychosis must
be sought in one or the other of the
described distortions of the sym-
biotic phase.  in the first case, what lay
at the heart of the psychotic dis-
turbance was the marked emotional
unavailability of the mother,
which alternated with a purely physical
extreme closeness during the
breast-feeding situations, and particularly
with the destructiveness of
the mother's unpredictable rage attacks.
the contrasting experiences
drove the child to the autistic warding
off of any human contact and
the de-animation of the world of reality.
constitutional factors could
not, in this case, be evaluated with any
degree of accuracy.
in the second case, it was, by contrast,
the mother's ever-presence
that created an unendurable instrusion
upon and interference with
the structuralization of the budding ego,
which constitutionally and
perhaps predispositionally may have been
very vulnerable.  this made
it impossible for the infant to experience
the normal alternation of
the gratification-frustration sequences at
his own pace; it also made
the process of individuation in the
separation-individuation period
one which was beset with abysmal panic.
in both instances, we can see that it was
primarily in the severe dis-
tortions of the normal symbiosis that the
child psychosis had its roots.
.I 801
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23
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autopathy:follow-up of cases
the publication of two papers
recently in the acta paedopsychiatrica by
d. arn. van krevelen on the subject of "autistic
psychopathy", has stimulated the author
to present 5 cases which appear to conform to
his description.  the only value of this brief
contribution lies in the fact that they have all
been followed up for at least 10 years, and
this may give some idea of the eventual results
in this type of cases.
.I 802
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23
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sensory dominance
in autistic imbecile children and controls
in a previous experiment (hermelin and
o'connor, 1964) it was found that autistic
and control imbecile children responded most
frequently to a light stimulus in conditions of
bimodal, simultaneous stimulation.  however,
the role of the relative intensity level of the
stimuli remained to be determined.  in the
present experiment a light and a sound, or a
light and a verbal command were presented
simultaneously in various intensity combina-
tions.  all responses, irrespective of the stim-
ulus to which they were made, were
rewarded.  autistic, mongol, and nonmongol
imbecile children were tested.  in addition to
a tendency for visual dominance results
showed that independent of modality, high
intensities affected all groups.  nonmongol
imbecile children also responded significantly
more frequently to the verbal than to the
sound stimulus, while the other two groups
did not.
.I 803
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23
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dreaming sleep in autistic twins
each of 5-year-old identical autistic twins
was observed during one spontaneous all
night sleep session during which their
electroencephalogram, eye movement, heart
rate, and chin muscle potential were recorded.
these autistic twins showed a similar
patterning and amount of dreaming sleep to
each other and to that reported for normal
children of the same age.
.I 804
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23
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twins discordant
for early infantile autism
a pair of heterozygous twins discordant
for early infantile autism is reported and the
relevant literature reviewed.  although mani-
fest organic factors were ruled out, the twins'
physical development was different.  a spe-
cific emotional etiology was not demon-
strated.  the few available twin studies offer
findings consistent with the hypothesis that
genetic factors are relevant to the develop-
ment of childhood autism.  evidence is also
presented that impaired acquisition of lan-
guage may have hereditary determinants.
a second set of probably homozygous
twins are reported who were also discordant
for autism.  this second case suggests that,
although genetic factors may play a part, in
some cases the syndrome of infantile autism
appears to be a reversible one.  in view of
this set of twins and of kanner's sibling data,
the role of genetic factors remains obscure,
and more twin studies properly documented
with blood typing are needed.
.I 805
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23
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evaluation and treatment planning
for autistic children
infantile autism is considered to be a re-
action on the part of an immature organism
at a primitive and undifferentiated stage of
ego development.  little choice of defensive
reactions is available; the possibility of sub-
limation does not exist and, even though
other object relationships are gradually
developing, the mother is still the child's
primary object.  at this vulnerable develop-
mental stage, a wide range of pathological
circumstances, ranging from the most severe
family psychopathology to the most adventi-
tious physiological traumata or the most un-
fortunately malignant circumstances, may
constitute an acute or cumulative cata-
strophic stress.  the primitive organism
tends to respond to this overwhelming stress
with a paranoid reaction which is directed at
the mother (regardless of the actual etiologi-
cal variables) because the mother is still the
child's primary object.  we believe that the
child then responds with an autistic reaction
and shows varying degrees of simple with-
drawal, obsessional behavior, magical or de-
lusional thought processes, and consequent
disruption of developmental skills, speech,
and relationships with others.
many families can and do make every
effort to counter the paranoid reaction of the
child and do not respond to his rejection with
counterrejection and counterwithdrawal.
some of the child's autistic symptoms may
abate without formal treatment.  yet, since
the mother (and family) are the primary
objects of the child's paranoid attitude, it is
felt that formal therapeutic intervention is
necessary to modify the paranoid core of
the autistic reaction.
.I 806
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a twenty-five year view of
therapeutic results
thus this group of ten patients shows a complete range of
chronic schizophrenia from a bright pseudoneurotic never hospitalized,
to an inaccessible patient chronically hospitalized for 20 years.
physiological therapy in the form of metrazol-induced convulsions
given in the course of a puberty schizophrenic psychosis, has been
helpful to some by making them more accessible for the total treat-
ment program in the hospital or by raising their margin of tolerance
sufficiently so that they could live at home and attend public schools
at least for a time and at best, indefinitely.
several of the most regressed, deteriorated patients in state hospitals
for many years, have been brought back to some level of meaningful
living again by the current drug therapy program, and are still im-
proving.
now we have not determined who the sinner may be.  there are
many who will believe that the mother is always the sinner; is she
not schizophrenogenic?  there are others who will believe that the
individual himself is the sinner since, after all, is he not the one
whose behavior and fantasies are schizophrenic?  however, there will
be many of you attending this fifty-second annual meeting of the
american psychopathological association, who will judge the speaker
to be the sinner, for have i not given you this wealth of clinical ma-
terial without charts, graphs, or statistical evaluation?
.I 807
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group psychotherapy with preschool
psychotic children and collateral
group therapy of their parents:
a preliminary report of the first two years
a group approach in the treatment of preschool-aged psychotic children is
reported.  autism is a defense against loss of the symbiotic partner.  the
group of children penetrates this defense and forms a "group ego," which
constitutes one pole of a new therapeutic symbiosis from which
separation-individuation can occur.
.I 808
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23
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autistic reactions in early childhood:
differential diagnostic considerations
the term "autism" is frequently used today
in the differential diagnosis of the severe
emotional disturbances of early childhood.
however, to label a child as "autistic"
presents some formidable problems with
regard to definition of the term, the specific
etiological-diagnostic implications, and
treatment considerations for any given
child so designated.  the purpose of this
paper is to briefly review some of the
historical psychiatric background of the term
"autism", its more recent ramifications,
and our clinical experiences in this field.
.I 809
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infantile autism: a family approach
the autistic child appears to be unable to integrate or to respond to
stimuli, both from an internal source, the body, as well as from external
sources, such as human contact.  we have noted in the children at our
residential treatment center how in their preliminary period with us they
appear to be unaware of their body; they give the impression of being
insensitive to pain, display little autoerotic behavior, inflict injury on
themselves, such as hitting their heads against objects and biting their own
bodies, with little outward display of distress.  in working with these
children in therapy, one of the guideposts for change and for growth is a
display on the child's part of an increased body awareness and autoerotic
behavior.  for example, one child who developed polio during his early stay
at the clinic residence did not communicate this to anyone and it was only
made known by observing the child's dragging one leg (memorial guid-
ance clinic, 1959).  later, he was able to point to his body and to indicate
pain.  another child, who at first seemed to be quite unaware of both himself
and others, concurrent with his growing display of affective expression
toward the therapist also manifested pleasure through genital stimulation,
was quite ticklish, and when injured would display the area of pain quite
readily.
.I 810
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23
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an analysis of the language of fourteen
schizophrenic children
fourteen schizophrenic (autistic) children were studied by means of detailed
behavioural histories and observations.
the language recorded in history and observation protocols was analysed and
compared with available data on normal children.
all schizophrenic children were grossly retarded in their language development
and all measures of this correlated highly with a previous overall clinical
assessment of the severity of illness.
the most striking abnormalities in the language of the children studied were
stereotyped repetition of utterances appropriate to an earlier developmental
level or to a previous environmental context, accompanied by a lack of normal
expressions of curiosity and of responsiveness to changing environmental cues.
.I 811
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a behavioural and electroencephalographic
study of autistic children
short biographies are given of 10 children,
age 3 to 6 years, diagnosed as suffering from
kanner's syndrome (early infantile autism).
an analysis was made of the free-field acti-
vities of these children compared with a group
of normal children of similar age.  electro-
encephalographic studies were also carried out
on all 10 children, and in two it was possible
to carry out simultaneous behavioural and
eeg observations by means of telemetry.
the children were observed for three minute
periods in four environments of varying
complexity: a. an empty room; b. the same
room with toy wooden blocks present; c.
blocks plus passive adult; d. blocks plus active
adult.  except in a the visual fixations and
manipulatory activities were of significantly
shorter duration in the autistic children than
in the normals, lacked clear 'cut-off' points
and showed relatively little variability between
environments.  the autistic children as a
whole showed virtually no constructive play in
contrast with the normals, though more
time was spent in contact with play materials in
the social environments.  changes in the
time spent in locomotion, gesturing, block-play
and manipulation of other objects in the
environment showed that the autistic children
were acutely responsive to changes in their
environment, including the presence of the social
stimulus.  if the autistic children were
subdivided into those who characteristically showed
stereotypies and those who did not, the
latter sub-group showed a behaviour structure which
was very similar to that of the normals,
whereas the stereotypy sub-group was clearly
differentiated from both the normal children
and the non-stereotypy sub-group.
eight autistic children had waking eeg
records characterized by low voltage irregular
activity without any established rhythms;
one child, a record containing irregular alpha
and another unstable theta activity.  two of
the children with 'flat' laboratory eegs showed
more rhythmic, higher voltage records when
their eegs were telemetred in environment a.
they also showed less stereotyped behaviour.
in environments b and d they showed pro-
gressively more irregular eeg activity and
more stereotypy.
the hypothesis is advanced that autistic
children are in a chronically high state of physio-
logical arousal.  the findings of the present
study and those of other workers are discussed
with respect to this hypothesis.
.I 812
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23
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the autistic child in the school and the
school-nurse teacher responsibility
autistic children demonstrate a more persistent pattern of retreating
from reality than is apparent in those children categorized as normal.
some psychologists have established the cause of symptoms in the autistic
child as extreme anxiety which forces withdrawal from social contact.
such anxiety is reported to have its initial occurrance during the age
range of one to five years.  a sense of security which is considered es-
sential for a child is gained through overt manifestations of love, care and
approval of those adults most closely associated with him.  when this
need is not satisfied, the child's attempts at self-realization and esteem
are deterred or thwarted, and a state of anxiety may result.  the severity
of the anxiety may be the forerunner of a schizophrenic disorder.  such
a condition can develop in a child, an adolescent or an adult.  schizo-
phrenia, a serious mental illness, is considered to be a major cause for
admitting patients to mental institutions.
another school of thought has placed infantile autism in the category
of a disturbance resulting from abnormalities of development during the
intrauterine period.  such a congenital condition is not categorized as
mental retardation.
yet another concept of autism conceives of the problem as the absence
of an innate ability or capacity for developing meaningful contacts with
other people.  a detachment of varying degrees persists where human
contacts are concerned.
.I 813
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the autistic child
the conditions most frequently mistaken
for autism are speech disorder, brain damage
and mental deficiency, each a prominent
symptom of the psychotic child.  careful his-
tory and close observation to disclose symp-
toms of withdrawal, lack of ego, compulsion
for sameness, and displays of intelligence
give incomplete clues to the diagnosis.
the etiology of autism is uncertain.  sev-
eral factors seem significant.  the important
role of organic damage of the brain is under-
scored by the coincidence of epilepsy, eeg
and neurological abnormalities in these chil-
dren.  in our series seizures of various types
occurred in 25%, eeg abnormalities in 58%,
and minor neurological deficits in 70% of
the cases.  environmental factors are quite
obviously important in many instances.  the
emotional and behavioral pattern of the par-
ents toward the infant is often incriminated.
separation, inattention, coldness, rejection,
etc. have been found in many situations.  fa-
milial incidence of psychoses is low; so is
that of autism in siblings.
.I 814
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23
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shadow therapy
shadow therapy was developed at sunland
training center in gainesville, florida, because of communica-
tion difficulties with disturbed, psychotic children.  it was con-
jectured that subjects would reveal their anxieties and conflicts
more readily in a simulated night situation.
the therapy was conducted in a darkroom with projector
light used to produce silhouettes and their accompanying
shadows as additional stimuli.  twelve subjects attended.  in
this article, the reaction of a child who was autistic and severely
disturbed is used as an illustration of subject reactions.  in the
playroom, he exhibited static behavior; in the darkroom, re-
gressive-transcendential behavior.  he also transcended his usual
level of vocalizing and socializing.
.I 815
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23
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language training in the treatment
of the autistic child
functioning on a retarded level
a preliminary study to
determine the effect of language and
speech therapy on the development of
communication and the lessening of un-
relatedness in a group of non-verbal,
autistic children functioning on a retarded
level is reported.  on the basis of the re-
sults of the study, it is suggested that the
inclusion of language and speech therapy
techniques be considered in developing a
treatment program for such children.
.I 816
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23
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the convergence and interaction of visual,
auditory, and tactile responses in human
nonspecific cortex
the relation between the electrical responses in the human brain and
mental processes of integration and association is perhaps the most chal-
lenging of all the problems facing neurophysiologists today.  until quite
recently the prospect of unifying physiological and psychological concepts
by electro-encephalographic (eeg) techniques seemed to be receding
because of the baffling complexity of the intrinsic electrical rhythms, and
this difficulty has still not been overcome.  the most intriguing, and at
the same time most elusive, of the properties of these rhythms is that,
although often remarkably constant in their variations with respect to
time, they fluctuate also, in a much less regular manner, within the three
dimensional space of the brain.  the continuous analysis and display of
such a phenomenon presents serious difficulties, and no method has yet
given entirely satisfactory results.
the incentive to construct adequate equipment and to design and per-
form crucial experiments is undoubtedly limited by the uncertainty as
to whether the information likely to be obtained in this way is essential
to understanding brain mechanisms; few experimenters imagine that it
would be sufficient.
.I 817
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23
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infantile autism and the schizophrenias
in a paper published in 1943, entitled "au-
tistic disturbances of affective con-
tact," i reported from the children's psychi-
atric service of the johns hopkins hospital
observations of 11 children (8 boys and 3
girls) who had in common a pattern of be-
havior not previously considered in its
striking uniqueness.  the symptoms were
viewed as a combination of extreme alone-
ness from the beginning of life and an anx-
iously obsessive desire for the preservation
of sameness.  i concluded the discussion by
saying: "we must assume that these chil-
dren have come into the world with an
innate inability to form the usual, biologi-
cally provided affective contact with people,
just as other children come into the world
with innate physical and intellectual handi-
caps.  if this assumption is correct, a further
study of our children may help to furnish
concrete criteria regarding the still diffuse
notions about the constitutional components
of emotional reactivity.  for here we seem to
have pure-culture examples of inborn au-
tistic disturbances of affective contact."
in my search for an appropriate designa-
tion, i decided in 1944, after much groping,
on the term early infantile autism, thus
accentuating the time of the first manifesta-
tions and the children's limited accessibility.
.I 818
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23
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autistic children
autism is a form of childhood schizophrenia.  a sudden
separation from his mother or traumatic shock in
early life causes the child to reject the world of nor-
mal relationships.  leading him back to the original
traumatic situation is part of the treatment described
in this article.
.I 819
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23
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gilles de la tourette syndrome in an autistic child
a case of gilles de la tourette syndrome
presenting an early infantile autism is
described.  the treatment applied is outlined.
.I 820
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23
.W
psychodrama for disturbed children
psychodrama is especially adaptable to the treat-
ment of mentally ill children.  it evokes a degree
of spontaneity and involvement that is difficult to
attain with many group therapies, and it offers situa-
tions in which the children can participate as actors
or as observers.  competition and restriction are
minimal: the child can do what comes naturally.  in-
deed, much of children's natural play is in the form
of dramatic activity.  their make-believe is, how-
ever, more intense than acting, for a child becomes
the person or thing he pretends to be: a fireman,
an indian, a horse, a tiger.
.I 821
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23
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the speech and language abilities of
emotionally disturbed children
the speech and language disorders of
these severely disturbed children can be
divided into two categories which relate
to the type of psychiatric disturbance.
the autistic-schizophrenic children used
bizarre forms of language or did not use
communicative language at all.  the non-
autistic-schizophrenic, the neurotic, the
primary behaviour disorder, and the
minimally brain-damaged children as a
group, had similar speech and language
problems to normal children but of a
more severe and frequent nature.  their
problems were predominantly in the
areas of speech and language develop-
ment, articulation, rate of speech and
fluency.  the children with primary be-
haviour disorders had the more severe
speech and language problems.
.I 822
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23
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a study of childhood schizophrenia
and early infantile autism
(part i--description of the sample)
following a period of observation of
three months' duration, a group of twelve
autistic schizophrenic children were se-
lected for a treatment program.  the
group was selected on criteria which
would allow a reasonable chance of suc-
cessful treatment in a group homo-
geneous enough to allow statistical con-
siderations to be valid.
younger age, average intellectual func-
tioning, presence of an intact family in
or near to metropolitan toronto and a
firm diagnosis of autistic schizophrenia
were the limiting factors.
rather distinct differences were noted
in this treatment group as opposed to the
larger observation group.  the dis-
tinguishing characteristic was undoubted-
ly the speech abnormalities present.
.I 823
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30
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discussion sur les pseudo-tumeurs osseuses
des hemophiles
doctors queneau and josso each described one
case of pseudo-tumour of the calcaneum analagous
to that described by trillat and favre-gilly; they
demonstrated x-rays; dr. alagille referred to a
haemophilic cyst of the maxilla and dr. favre-gilly
to a cyst of the perineum; dr. kugler had seen a
case where an erroneous diagnosis of osteosarcoma
had been made.
.I 825
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30
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haemophilic blood cyst
a mongol boy of ten, a known haemophiliac, was seen in the orthopaedic
department of southmead hospital in may 1962 with a swelling of the left foot.
the parents were aware of a steady increase in size since the swelling was
first noticed two months before.  on examination, a cystic swelling was seen to
occupy the forefoot, the skin on the dorsum being stretched over it and a
dusky red in colour (fig. 1).  radiographs showed destruction of the proximal
two-thirds of the third metatarsal bone, an appearance consistent, it was
thought with destruction from within by an expanding lesion (fig. 2).  the
diagnosis of a haemophilic blood cyst was made.
.I 827
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30
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osteopatia in emofilia
the aa. present the case material of the literature and one
personal remark of extrarticular osteopathy in
hemophilia.  they examine the anatomic and clinical picture of
the illness in its most important and less known
peculiarities and they dwell upon the curative medico-surgical
problems of the affection.
.I 831
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30
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haemophilia in sweden
vii. incidence, treatment and prophylaxis of
arthropathy and other musculo-skeletal
manifestations of haemophilia a and b
the clinical material consisted of 242 of the 308 known haemophiliacs
(a and b) in sweden.  the investigation included clinical examination of
all major joints in 95 of 116 patients with severe haemophilia, in 38 of
65 patients with moderate haemophilia, and in 24 of 127 patients with
mild haemophilia, and roentgen examination of practically all joints
found to be abnormal at the clinical examination.  in addition information
about 7 patients with severe haemophilia, 21 with moderate haemophilia,
and 57 with mild haemophilia was obtained by questionnaire only.
the degree of arthropathy (grades 2, 3 and 4) was classified largely
according to depalma and cotler (1956).  evaluation of general disability
was made with regard to ability to manage (walk, dress, eat, toilet) with-
out help.  this latter evaluation comprised also extra-articular manifesta-
tions of haemophilia.
.I 843
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30
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the haemophilic pseudotumour
or haemophilic subperiosteal haematoma
the case history of a haemophiliac in whom a large haematoma of the thigh was
treated by amputation of the limb is described.
examination of the available radiographs and of the histology led to the
conclusion that the cyst was subperiosteal in origin.
evidence is presented to support the hypothesis that haemophilic pseudotumours
are always associated with subperiosteal haemorrhage, and that those
haemophilic cysts which are confined to muscle have little or no effect on the
adjacent bone.
.I 844
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19
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actinomycin d and the response to parathyroid hormone
actinomycin d inhibits the effect of
parathyroid hormone upon bone, as measured
by ca mobilization, without altering
its effects upon the renal excretion of
phosphate and ca in rats.
.I 845
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19
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aspects of circadian periodic changes in
phosphorus metabolism in mice
kinetic studies on the p32 content of
mouse brain phosphorus fractions following
the intraperitoneal injection of p32-labeled
orthophosphate were performed during
two selected segments of the 24-hour time scale.
the results of these studies suggest
that the circadian periodicity in relative
specific activity of brain phospholipids
is probably a consequence of a variation in the extent
of p32 incorporation into brain
inorganic phosphate and is not indicative
of a periodicity in the rate of intermediary
phospholipid metabolism.  data on the postinjection
time course of the specific activities
of plasma inorganic phosphate, liver inorganic phosphate,
and liver phospholipid
suggest a similar explanation for
the circadian periodic changes in relative
specific activity of liver phospholipids.
a circadian rhythm of inorganic phosphate
concentration in mouse plasma is demonstrated.
consideration of a mathematical
model suggests that the observed within-day
variation in p32 distribution and the
circadian periodicity of phospholipid relative
specific activity in liver and brain
are a consequence of this periodicity in
plasma phosphate content.  a significant
within-day variation in total phosphorus
content of liver was observed.  the disturbance
of mice incident to p32 injection
has a marked effect on the plasma content
of inorganic phosphate and corticosterone.
.I 846
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19
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specificity of the inhibition of tubular
phosphate reabsorption by certain amino-acids
the inhibition of tubular phosphate
reabsorption by certain amino-acids is a highly
specific one in which differentiation between
such closely related compunds as the
d and l isomer is clearly possible.
.I 847
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19
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localization of phosphaturic effect of
parathyroid hormone in nephron of the dog
the renal mechanism and tubular site of the phosphaturic action of
parathyroid hormone were investigated by clearance and stop-flow
techniques in one intact and seven thyroparathyroidectomized
dogs.  administration of hormone caused a significant increase
in the excretion of phosphate without increasing the filtered
load.  stop-flow analysis indicated that in the absence of parathyroid
hormone most of the filtered phosphate was reabsorbed
in the proximal tubule, and that the hormone increased the
rate of phosphate excretion by inhibiting this reabsorptive
mechanism.  p32 injected during stopped flow showed no significant
transport across the renal tubule despite the presence of
excess parathyroid hormone.  significant p32 activity appeared
in the stop-flow collections simultaneously with the appearance
of new filtrate.  there was no evidence that parathyroid hormone
mediated a secretory process for phosphate excretion.
.I 848
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20
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the regulation of growth hormone secretion
in the present communication we summarize
our investigations on the control
of secretion of hgh using radioimmunoassay
for the measurement of plasma
gh. the assumption, implied throughout this
presentation, that changes in
secretory rate are responsible for acute
changes in plasma concentration of
hgh appears reasonable since the
fluctuations in plasma hgh concentration
are often too rapid to be caused solely by
alterations in hormonal
degradation or excretion.  for slower changes
in plasma hgh concentration,
however, alterations in the rate of removal
of hormone from the body fluids
might play a contributory role.  however,
there is no evidence that important
changes occur in the rate of removal of
hgh from the circulation except in
patients who have developed antibodies
to hgh following treatment with hgh.
.I 849
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23
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early infantile autism and receptor processes
the syndrome of early infantile autism is examined
as a function of deviation in
near-distance receptor usage.  these receptor
deviations are compared with normal
receptor hierarchies developing from near
to distance receptor dominance.  the
available information is consistent with the
view that early infantile autism involves
early sensory deprivation.  this sensory
deprivation results from an interaction
between a constitutional deficiency inhibiting
certain reticular arousal functions
and mothering tending to understimulation.
treatment of the young autistic child is suggested
including stimulation and communication
via the available near receptor
systems.  in the framework of sensory development,
directions for the study of early
diagnosis and treatment are indicated.
.I 850
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24
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studies on compensatory renal hypertrophy.  i.  effect of
unilateral ureteral ligation and transection
data are presented comparing the relative rate
of compensatory renal hypertrophy
and hyperplasia of the control kidney of rats
following either unilateral ureteral
transection, ligation, or nephrectomy.  the growth
of the control kidney on the unoperated
side was strikingly slower after ureteral
transection and ligation when
compared with that resulting from the removal
of one kidney.  progressive hydronephrosis
was observed on the operated side following
ureteral transection and
ligation and was more pronounced in the latter.
degree of hypertrophy of the control
kidney showed a close correlation with degree and
duration of the hydronephrosis of
the kidney on the operated side.  these observations
have been interpreted as indicating
the operation of a control system regulating
kidney growth in response to
changes in some way related to kidney size.
.I 851
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24
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studies of the changes in growth
and dna synthesis in the rat kidney
during experimentally induced
renal hypertrophy
there is a high rate of accumulation of
newly synthesized dna in the kidney after folic
acid injection, compared with the small increase
during the first few days after unilateral nephrectomy.
there is a large increase in the water content
of the kidney after folic acid which does not
occur after unilateral nephrectomy.  the changes
in the wet and dry weight and the rna and dna
content of the kidney have been compared after
administration of folic acid, unilateral nephrectomy
and unilateral nephrectomy followed by folic
acid 24 hr later in an attempt to study the nature
of these differences.  after unilateral nephrectomy
there was a steady increase in wet weight, dry
weight and rna content of the kidney, each parameter
reaching about 35 to 40% above normal by
14 days, by which time the dna content had increased
by only about 25%.  an increased rate of
dna synthesis was found between 2 and 4 days,
returning almost to normal by 7 days.  after folic
acid injection there were very large increases in
wet weight (60%), rna content (100%) and dna content
(70%) during the first 4 days accompanied by
a smaller increase in dry weight (30%).  thereafter
these parameters declined, relative to body weight,
returning almost to normal by 14 days.  the rate
of dna synthesis was greatly increased as early
as 24 hr after injection and reached a much higher
level than that found after unilateral nephrectomy,
before returning to the normal level by 7 days.
when unilateral nephrectomy was followed 24 hr
later by folic acid injection, the increases in
weight, nucleic acid content and rate of dna synthesis
were greater than at the corresponding
times after either treatment alone.  marked differences
were found in the labeling indices of kidney
cells after either unilateral nephrectomy or folic
acid injection.  the latter treatment resulted in very
large increases in all three zones of the kidney,
whereas after unilateral nephrectomy the responses
of the cortex and outer medulla were much lower,
with no significant increase in the inner medulla.
when both treatments were combined, the response
of the remaining kidney was similar to, though
more exaggerated than, that of the normal kidney
after folic acid injection.
.I 852
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24
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renal and adrenal relationships
in compensatory hyperplasia
the compensatory renal hyperplasia that
normally follows unilateral nephrectomy
is abolished by bilateral adrenalectomy if
rats are maintained on fresh drinking
water, but is restored when saline drinking
water is provided or if such animals are
injected with doca.  the adrenals are also
important for the increased proliferation
caused by unilateral hydronephrosis.  these
experiments suggest that the role of the
adrenal cortex in renal hyperplasia may be to
secrete mineralocorticoids, which
promote the retention of sodium and thereby
stimulate cell division in the kidneys.
.I 854
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19
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parathyroid extract-induced changes in the oxidation of citrate,
succinate and other organic acids by liver.
parathyroid extract (pte) or partially
purified parathyroid hormone administered in
vivo markedly altered the oxidation
in vitro by rabbit liver minces of citrate, -keto
glutarate-c, succinate-c, fumarate-c
and lactate.  with ca ++ present in the
incubation medium, minces from pte
treated animals produced more co and had
a greater o consumption than did control
minces.  this stimulation was due, in part
at least, to a more rapid decline in metabolic
activity of the control tissues.  when
ca++ was absent, total metabolism was
increased and the tissue derived from pte
treated animals was less active than the
control tissue.  the effect was detected as
early as 4 hr after injection (750 u/kg)
and could be elicited with as little as 200 u
(at 14 hr).  the action of pte could not
be duplicated by the injection of cacl into
the animal.  the data suggest that one effect
of treatment was a general inhibition of
oxidation.  the stimulation of metabolism
could be a consequence of this inhibition
or a separate unrelated alteration.
.I 856
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19
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the ultrastructure, histopathology, and
histochemistry of the parathyroid glands of pregnant
and nonpregnant cows fed a high level of vitamin d.
the parathyroid glands of pregnant and
nonpregnant cows were studied by light and
electron microscopy following the daily
feeding of 30 million units of vit d for 30
days and compared to untreated controls.
in both the pregnant and nonpregnant cows
the parathyroid glands became markedly
atrophic with a diminution in the amount of
parenchyma compared to the untreated controls.
after vit d feeding the number of
actively secreting dark and intermediate
chief cells was reduced and the percentage
of inactive (light) and atrophic chief cells
was increased.  the parathyroid glands
of the vit d-fed, nonpregnant cows were
dominated by severely atrophic chief cells.
these cells were characterized by their
highly irregular shape, shrunken nucleus
and cytoplasm, widened intercellular spaces
traversed by numerous cytoplasmic
processes, increased electron density, few
secretory granules, inactive ergastoplasm
and golgi complexes.  atrophic chief
cells were not present in the untreated
controls.  the predominating cell type in
the parathyroids of the vit d-fed pregnant
cows were the inactive chief cells.  in contrast
to the atrophic chief cells, they were
larger and more regular in shape with
relatively straight cell membranes.  they
were comparatively electron-transparent,
containing more glycogen and fewer
secretory granules.  organelles concerned
with protein synthesis and packaging into
secretory units were poorly developed.
inactive chief cells were observed only
occasionally in the parathyroid glands of
untreated pregnant cows where the actively
secreting dark and intermediate chief cells
predominated.
.I 857
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19
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effect of heparin and parathyroid extract an acid phosphatase in bone.
   to test the theory that heparin
might stimulate acid
phosphatase in the bone of
young rats, heparin, pte,
or a combination of both were
injected.  after an appropriate
time interval acid phosphatase
activity of bone of
treated animals was compared
with controls.  it was
found that heparin enhanced
the pte-stimulated acid
phosphatase activity of both
calvaria and metaphysis but
not diaphysis.  the possible
relation of these facts to
the presence of lysosomes in
osteoclasts was discussed.
.I 869
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20
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studies on hydroxyproline excretion and corticosteroid-induced
dwarfism: treatment with human growth hormone.
   two children who had been receiving large doses
of corticosteroids for years and were growing at a retarded
rate were treated with human growth hormone.
growth rate increased 2.5 to 3-fold and urinary hydroxyproline
excretion which was initially low increased
to the normal level.  when treatment was stopped, growth
rate and hydroxyproline excretion decreased promptly.
.I 884
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21
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clinical features of the alalies (russian).
the term 'alalies' is applied to the various
states of absence or insufficient development
of speech in children, resulting
from defective development or affections
of the speech centers before the development
of speech.  from the clinical
study it is possible to distinguish between several
forms: motor, sensory, and
semantic alaly with signs of amnesia.  the
causes are multiple: trauma, perinatal
cerebral hemorrhage, inflammatory processes,
metabolic disorders before the
development of speech, and alimentary and
trophic disorders.  the alalies show
varying degrees of severity.  in most children
suffering from alaly, neurological
signs can be demonstrated on the right side,
an indication of the organic nature of
the condition.  the presence of local symptoms
in the various forms of alaly is
often associated with signs indicating involvement
of adjacent regions of the cerebral
hemispheres in the pathological process
which would explain why the alalies
are often complex.  the character of the alalies
depends on functional disorders
resulting from the lesion in the frontal, anterior,
motor, temporal or parietal
region of the dominant cerebral hemisphere.
patients with alaly often show neurotic
reactions, resulting from the disorders
of the processes of inhibition and excitation
of the cerebral cortex and the subcortical
formations.  early treatment of
the alalies with drugs combined with logopedic
and pedagogic measures gives good results.
.I 885
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21
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an unusual form of acquired aphasia in children.
an unusual form of acquired aphasia-both
receptive and executive is described
as occurring in 10 children, 6 girls and 4 boys.
the onset occurred between 5 and
6 yr. of age with one or more epileptiform
attacks-which were not repeated-but
were followed by some degree of hearing
loss (later improving), failure to
comprehend spoken language and finally loss
or impairment of executive speech.
examination of csf and peg yielded normal
results.  eeg's were abnormal mainly
in the temporal leads.  the disorder appeared
self-limiting and throughout non-verbal
intelligence was not imparied.
.I 886
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21
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childhood echolalia in delayed, psychotic and neuropathologic
speech patterns.
some linguistic analytical procedures and
preliminary findings from controlled tape-recorded
samples of a group of echolalic
children are reported together with the
clinical and experimental rationale for the
investigation.  the subjects are echolalic
3-yr. olds and a group of young clinical referrals
representing a variety of pathological
conditions.  variables selected for
study include the proportion of echo to
non-echo and silence, the quality and appropriateness
of the non-echoed speech, the
amount of the stimulus echoed, the nature
of the triggering stimulus, the deviation of
echo pattern from stimulus pattern, pitch-loudness-time
variations, and the child's
chronological and mental ages.  early quantitative
results yielded very similar echo:
non-echo:silence percentages with echolalia
representing a mean of about 40% of the
conversation of each experimental group.
.I 929
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24
.W
the effect of folic acid on growth and deoxyribonucleic acid synthesis
in the rat kidney.
   the effect of a single injection of folic acid (250
mg/kg of body wt) on growth of the rat kidney was studied.
the patterns of the response were found to be essentially
similar in animals aged between 3 wk and 12 mth.
maximum values of kidney weight and nucleic acid content,
relative to body weight, were found at 4 days at
folate administration.  the increases in wet and dry
weights at this time were approx. 80% and 30% resp.
above the control weights, and the percentage dry matter
of the kidney was significantly lower than normal during
this period.  at 4 days the rna content of the kidney was
also maximal, being about 90% greater than the control
value, and the dna content after 4 days was increased
by about 60%.  whereas the dna values in 6-wk-old rats
were slightly lower at 7 and 10 days than at 4 days, in
12-mth-old animals a further small increase was observed
at 7 days, suggesting a prolongation of dna synthesis
in the older animals.  autoradiographic studies of
dna synthesis with thymidine-h have shown a greatly
increased labeling index in all zones of the kidney following
folate injection.  maximum values were observed
at 48 hr in the cortical zone, but the patterns of the
changes in the medulla were less well defined.  the labelling
indices in the kidneys of 12-mth-old rats remained
above normal for a longer period than in 6-wk-old rats.
these results concur with the evidence of an increased
dna contents of the kidneys of older rats between 4 and
7 days after folate.
.I 930
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24
.W
renal renin in unilaterally nephrectomized hypertensive rats.
juxtaglomerular index, renal pressor
activity and width of the zona glomerulosa
were normal in unilaterally nephrectomized
hypertensive rats maintained on a normal
sodium intake, increased in those
subjected to sodium depletion and decreased
in those receiving 1% saline.  this indicates
that renin formation and secretion are
most likely the result of the sodium state
of the animal rather than loss of a renin-stimulating
agent in the contralateral or
unclipped kidney.  failure of sodium to influence
the degree of hypertension in
unilaterally nephrectomized hypertensive rats
militates against a direct quantitative
relationship between blood pressure and the
renin-angiotensin-aldosterone system.
.I 932
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24
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effects of hypophysectomy and growth hormone on renal compensatory
hypertrophy in rats.
   the effect of hypophysectomy on renal compensatory
hypertrophy (rch) was observed in unilaterally
nephrectomized rats receiving no therapy and those
receiving replacement therapy and was compared to the
rch attained by non-hypophysectomized unilaterally
nephrectomized rats at 2, 5, and 10 days.  in the latter
group there was an initial rapid rch seen at day 2
which continued, but at a slower rate, through day 10.
in the hypophysectomized group without replacement
therapy there was also an initial rch in the first 48 hrs.
however, instead of the rch continuing there was a
regression in kidney size at 5 days and with no subsequent
change at 10 days.  in the hypophysectomized group
receiving hormone replacement there was an initial
rch comparable to the other 2 groups, but the further
renal enlargement at 10 days was much less than that
of the non-hypophysectomized animals.  the results of
this experiment and of other reported studies imply
existence of a renotropic factor which is not produced
in the pituitary, but which requires an intact pituitary
for full effectiveness.
.I 944
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25
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two brothers with nephrogenic diabetes insipidus.
the patients, a 5-year-old and a 13-year-old
boy, had suffered from polydypsia
and polyuria since the age of 1 yr.  physical
and mental retardation, hyperchloremia,
and lowering of kidney concentrating power
were observed.  the patients were resistant
to pitressin.  they were considered
to be suffering from nephrogenic diabetes
insipidus caused by a recessive heredity factor.
.I 945
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25
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studies on the sweat in renal diabetes insipidus during
treatment with saluretics.
description of a 5-month-old boy suffering
from familial diabetes insipidus.  his
sweat as well as that of his mother had an
increased nacl content.  chlorthalidone
and fursemide had a different effect both
on the quantity and on the nacl content of
the sweat.  a single dose of chlorthalidone
decreased the nacl content for a short
time, but increased the quantity of sweat
during 3 days.  fursemide given intermittently
produced a decrease of the sweat nacl
also during the intervals and an increase
of the quantity of sweat; however, as a
contraregulation during the intervals, the
quantity of sweat decreased and at the same
time the urea content increased.  from
the isotonic serum filtrate in the sweat
glands ho and nacl were reabsorbed in
the ducts and the urea concentration
increased but the reabsorption of ho and nacl
did not go parallel, therefore the sweat is
hypotonic.  this regulation is altered in
diabetes insipidus, therefore the high values
of nacl.  without changing the osmolarity,
na is exchanged with k.  this mechanism
is accentuated if the na-concentration
is high.
.I 947
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25
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the action of vasopressin in renal diabetes insipidus.
as the water-retaining action of antidiuretic
hormone is eliminated in renal diabetes
insipidus, the steps in na transport can
be separately determined.  vasopressin
induced a prompt increase in freewater
clearance and urinary volume, as well
as a delayed increase in sodium clearance.
it is suggested that vasopressin brings
about stimulation of sodium reabsorption in
the ascending limb of henle's loop.  it
is supposed that both physiological actions
of antidiuretic hormone - the antidiuretic
and the sodium-active effect - become operative
in two different places in the nephron
and synergistically produce a maximum
concentration of urine.
.I 948
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25
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pituitary diabetes insipidus associated with progressive urinary
tract dilatation.
a case of pituitary diabetes insipidus with
associated obstructive urinary tract
changes is described.  the patient was treated
both by surgical correction of lower
tract obstruction as well as by control of
the diabetes.  reversal of anatomic changes
over a 1-year followup period is demonstrated.
.I 959
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26
.W
evaluation of 20 years' experience with the treatment of hydrocephalus
in infants.
a total of 394 infants were examined between
1943 and 1962.  till 1961, 369 infants
were examined and 246 were operated on (66.7%);
this group is analyzed.  laurence's
opinion on the favorable spontaneous
evolution is not agreed to and the
merits of surgical treatment are proved.  a
dynamic form of hydrocephalus in
operated infants is shown; the patients who
were not operated on suffered from other
diseases combined with macrocephaly which
must be distinguished from hydrocephalus.
a spontaneous arrest of the process
was observed in only 14 children, e.g.
3.8%, as compared with laurence's 42.6%.
the cause and pathological findings are
analyzed in 102 infants operated on between
1957 and 1962.  a great discrepancy
between the time of the onset of first symptoms
and the time of operation was found.
this disease manifests itself in 50% of infants
in the first month of life, but the average
age of infants at the time of operation is
6.1 mth.  only 3% of infants are operated
on in the first month.  thirteen operating
procedures were used in the 20 yr. under
review.  until the introduction of deviation of
the csf into the jugular vein or into
the cardiac atrium, 15.33% of the infants
survived 1 yr. after operation.  since the
introduction of this procedure the survival
rate of infants was 67.8%.  in spite of
the late operation about 27% of surviving
children showed an average mental
development.  surgical treatment of dynamic
hydrocephalus is advocated.  they
consider this method as the only means of helping
the infant at present.
.I 960
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26
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cerebrospinal fluid dynamics in the arnold-chiari malformation.
a method using radio-iodinated serum albumin
to measure the volume of the ventricular
system, and the rate of disappearance
of csf from the lateral ventricles, has
been described.  newborn infants with a rate
of flow less than 70 ml. /24 hr. after
surgical repair of the myclomeningocele
will develop progressive hydrocephalus
requiring a ventriculo-atrial shunt.  the
test can be used to detect the patency of a
ventriculo-atrial shunt, and may allow safe
removal of the shunt in selected patients.
.I 961
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coexistent cranial and spinal defects with hydrocephalus in five
infants.  the etiology and significance of craniolacunia in these
defects.
the clinical, roentgenographic and etiologic
factors in 5 infants with varying cranial
defects (craniolacunia and craniofenestra
or cranial meningocele), hydrocephalus,
and spinal defects (meningocele or myelomeningocele)
are described.  all of the
infants expired of bacterial complications.
the etiologic factors and significance
of cranial defects in these coexistent
malformations of the central nervous system
are reviewed.
.I 962
.C
26
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hydrocephalus and myelomeningocele.  central nervous system infection.
a series of 38 incidents of cns infection
in 34 patients with hydrocephalus,
myelomeningocele, or both have been summarized.
gram-positive organisms occurred
more frequently and caused infections
resulting in a mortality of 33%.  the gram-negative
organism induced infections
resulted in a mortality of 60%.  nearly 50% of
the infections occurred in patients before
any shunting procedure was done.  the
staphylococcus caused two-thirds of the
infections in patients with a shunt in situ.
no obvious portal of entry could be
demonstrated in a majority of patients.  of 5
patients who received nonspecific prophylactic
therapy because of an oozing
myelomeningocele 4 survived.  of the 5 given
no prophylactic therapy, one survived.  a
combination of kanamycin, sodium
methicillin, and chloramphenicol appeared in
vitro to be effective against most of the
gram-positive cocci.  the combination of
chloramphenicol, kanamycin, and
polymixin b appeared in vitro to be an effective
combination against most of the gram-negative bacilli.
.I 963
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26
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myelomeningocele and hydrocephalus.  the first year of 50 patients.
fifty infants with hydrocephalus and
myelomeningocele were treated comprehensively
by a team of specialists.  patients
were evaluated at death or the first birthday,
whichever occurred first.  twenty
patients died, 13 from bacterial infection.
thirteen of the survivors were classified
as noncompetitive, that is, were thought
to have a poor prognosis based on a
developmental quotient of less than 80.  seventeen
patients were judged competitive; in
each case the latest developmental quotient
was more than 79 and the urinary tract
was not irreversibly decompensated.
developmental quotient was based on motor
development, adaptive behavior, language
development, and personal-social development.
this report is a progress report
in a longitudinal study.  in comparison
with a previously surveyed group the results
seem encouraging: current data from 39
older patients followed 6 to 13 yr. show
2 competitive survivors, 11 noncompetitive
survivors, and 26 deaths.
.I 989
.C
28
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chemotherapy of metastatic gastro-intestinal cancer.
   cancer of the digestive tract is the commonest
cause of death from neoplastic disease in the united
states.  a large number of patients with these forms of
incurable cancer may be candidates for specific anti-tumor
drug therapy.  the criteria employed for the selection
of patients for systemic or regional chemotherapy
are reviewed and methods of treatment are outlined.
systemic chemotherapy, using fluorinated pyrimidines,
the antifol, methotrexate, and the alkylating agent, cytoxan,
has been found to be of significant practical value
in 10 to 30% of the patients receiving these anticancer
drugs.  protracted hepatic artery infusion chemotherapy
in patients with primary and secondary hepatic neoplasms
and tumors of the biliary system has resulted in
objective tumor response and associated clinical benefit
in 60% of the patients treated.  length of survival has
been prolonged in patients with advanced metastatic liver
cancer from primary tumors of the colorectum.  it is
concluded that systemic and regional cancer chemotherapy,
in selected cases, has contributed to the practical
management of patients with incurable cancer of the
gastrointestinal tract.
.I 990
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28
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palliative treatment of osseous metastases from carcinoma of the breast
and carcinoma of the prostate with radio-active phosphorus and
testosterone.
fifty-three patients suffering from pain arising
in bony metastases from carcinoma
of the breast and prostate are discussed.
a method of palliative treatment is outlined
and the results reported.
.I 1019
.C
30
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major surgery on the severe hemophiliac, lessons in management.
three cases of pseudotumor of the thigh which
required surgical amputation and one
case of open pericardial drainage for cardiac
tamponade are briefly reported in severe
hemophiliacs.  in the first case hemostasis, following
amputation, was produced, but the
patient died of septicemia secondary to proximally
infected tissues; the level of amputation
should, therefore, be proximal to all grossly
infected tissues.  in the second case, with
infected massive pseudotumor of the left thigh,
5 separate operative procedures were
performed.  the last procedure was elective revision
of skin flaps at the hip disarticulation
site.  here application of the knowledge gained
from previous experience resulted in a completely
uncomplicated postoperative course by
dint of timing of the surgical procedure
in relation to control of infection, loss of plasma
fastness, and the judicious use of antibiotic
and direct-current electrocoagulation therapy.
a plea is made to avoid the use
of plasma and ahg therapy in hemophilias
for trivial reasons and to consider patients
for surgical procedures early in the course of their
complications, which demand surgery,
at a time when the patient is still responsive
to hematologic therapy and prior to the
onset of infection in areas of hematoma.  it is
felt that a second significant hemorrhage
in any particular site constitutes a bona fide
indication for surgical intervention, long
before the time when surgery is considered as
the last resort by the physician, patient and
family.  although the authors believe that surgery
in the hemophiliac is not to be taken
lightly, they do not endorse the prevailing nihilistic
attitude that has resulted in temporizing
delays which can only guarantee a fatal outcome.
.I 1020
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30
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immunological demonstration of factor viii protein in the plasma of
hemophiliacs and its value for an insight into hemophilia a.
by immunization of rabbits one obtains antisera
against human factor viii, the action
of the immunsera has been determined using
a modification of the thromboplastingenerations
test (the factor viii neutralization
test).  the antibodies against factor viii
are equally absorbed by either normal or hemophilia
a plasma.  this observation shows
that hemophilia a plasma contains as much factor
viii protein as normal plasma does.
in normal and hemophilia a serum one finds
at a lower level similar concentrations of
factor viii.  in analogy with cross-reacting substances
(crm) in bacteria mutants an
hypothesis has been made according to which
the authors are dealing with the product
of a genetically altered synthesis of factor viii.
this product is functionally less active
but possesses the same antigenic determinants
as the normal factor viii.  some inhibitor
properties of the hemophilia plasma can be
explained by competitive inhibition made
possible by the similarity of structure.  the fact
that the inhibitor discovered by mammen
and factor viii have similar properties support
the hypothesis.  the theory of some
authors according to which the plasma of an
hemophiliac a contains normal amounts
of a normal factor viii blocked by a specific
inhibitor, the pathogenetic agent of hemophilia a
is rejected because of genetic considerations
and because the accelerator appearing
after ether treatment of hemophilia a plasma is
not identical with factor viii.
.I 1021
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30
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haemophilic pseudotumours (3 cases).
the 2 first cases of haemophilic pseudo-tumours
in 2 adults affected with haemophilia
a reported are remarkable on account of their
clinical latency and their intertrochanteric
localization.  the third, in a haemophiliac b, is
very extensive and is accompanied by very
marked clinical symptoms of tumour.  there is
an extensive femoral gap with a subjacent
image of osseous infarction and a progressive
turgid tumour of the iliac wing of the
same side.  the literature data stress the discrepancy
between the progressive character
of this veritable tumour and the absence of
any sign of histological malignancy.
.I 1022
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30
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protein-losing enteropathy complicating prolonged bleeding in
hemophilia.
gastrointestinal bleeding in a severe hemophiliac
continued for 110 days, and 263
pints of fresh blood were replaced.  treatment
with eaca, steroids, and factor
viii, rich fibrinogen did not control bleeding.
marked hypoproteinemia developed
by the 94th day of bleeding.  a protein-losing
enteropathy was suspected on the basis
of x-ray findings of mucosal thickening and
altered motility.  discontinuance of
steroids and protein replacement resulted
in the appearance of a more normal
small bowel mucosal pattern and coincided
with the cessation of bleeding.
