.I 1
.C
5
.W
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 .           
.I 2
.C
5
.W
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 .                                           
.I 4
.C
5
.W
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 .              
.I 5
.C
5
.W
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 .                   
.I 6
.C
5
.W
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 .              
.I 7
.C
5
.W
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 .                 
.I 8
.C
5
.W
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
.C
5
.W
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 .                                              
.I 10
.C
5
.W
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
.C
5
.W
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
.C
5
.W
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 .                                                  
.I 13
.C
1
.W
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 .                                                           
.I 14
.C
1
.W
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
.C
1
.W
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 .                                      
.I 16
.C
12
.W
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 .                                       
.I 17
.C
12
.W
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 .                                                            
.I 19
.C
12
.W
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 .                
.I 20
.C
12
.W
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 .                                                             
.I 21
.C
13
.W
fine structure of subtilis phage sp-50 .                                
  some structural details and anomalous forms of subtilis phage sp-50   
are described .                                                         
.I 22
.C
13
.W
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 .  
.I 23
.C
14
.W
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 .                                                       
.I 24
.C
14
.W
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 .                   
.I 25
.C
14
.W
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 .                                                    
.I 26
.C
14
.W
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 .                                            
.I 28
.C
14
.W
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 .                                                            
.I 29
.C
14
.W
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 .          
.I 30
.C
9
.W
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 .                                                             
.I 31
.C
9
.W
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 .     
.I 32
.C
11
.W
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 .      
.I 33
.C
15
.W
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/ .                      
.I 34
.C
15
.W
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 .                    
.I 35
.C
16
.W
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 .                                                               
.I 36
.C
16
.W
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 .                        
.I 37
.C
17
.W
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 .                                                        
.I 38
.C
17
.W
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 .            
.I 39
.C
17
.W
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 .          
.I 41
.C
17
.W
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 .                            
.I 42
.C
17
.W
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 .            
.I 43
.C
18
.W
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 .     
.I 52
.C
8
.W
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 .                                                           
.I 53
.C
9
.W
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 .                         
.I 54
.C
10
.W
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 .                                                               
.I 55
.C
10
.W
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 .                                                              
.I 56
.C
9
.W
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 .                        
.I 57
.C
9
.W
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 .            
.I 58
.C
10
.W
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 .                                        
.I 59
.C
3
.W
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 .                                    
.I 60
.C
8
.W
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 .                                                       
.I 61
.C
8
.W
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 .                            
.I 62
.C
3
.W
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 .              
.I 63
.C
11
.W
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 .                  
.I 64
.C
9
.W
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 .                                                           
.I 66
.C
11
.W
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 .                                                         
.I 67
.C
3
.W
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 .                                                     
.I 69
.C
3
.W
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 .                                         
.I 70
.C
3
.W
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 .                                                 
.I 71
.C
3
.W
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 .                                        
.I 72
.C
1
.W
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 .                                    
.I 73
.C
3
.W
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 .                                               
.I 78
.C
3
.W
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
.I 79
.C
1
.W
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 .                                                             
.I 80
.C
2
.W
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 .                                         
.I 81
.C
3
.W
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 .          
.I 83
.C
9
.W
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 .                                             
.I 84
.C
9
.W
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 .                     
.I 89
.C
9
.W
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 .             
.I 90
.C
2
.W
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 .                                
.I 92
.C
7
.W
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 .                                 
.I 93
.C
4
.W
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 .                                      
.I 94
.C
4
.W
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 .   
.I 96
.C
4
.W
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 .                                      
.I 98
.C
16
.W
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 .                            
.I 99
.C
16
.W
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 .                                 
.I 101
.C
15
.W
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 .                                                              
.I 102
.C
15
.W
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 .                                       
.I 104
.C
15
.W
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 .        
.I 105
.C
15
.W
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 .                         
.I 107
.C
15
.W
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 .                             
.I 109
.C
15
.W
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 .     
.I 110
.C
15
.W
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) .                                                      
.I 112
.C
6
.W
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 .                                             
.I 115
.C
6
.W
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 .                    
.I 116
.C
6
.W
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 .                                                         
.I 118
.C
6
.W
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 .    
.I 121
.C
7
.W
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 .     
.I 122
.C
6
.W
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 .                             
.I 123
.C
8
.W
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 .            
.I 124
.C
9
.W
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 .                                                            
.I 125
.C
9
.W
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 .       
.I 126
.C
9
.W
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 .                                                
.I 127
.C
17
.W
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 .                            
.I 129
.C
17
.W
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 .                                                 
.I 130
.C
17
.W
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 .                                         
.I 131
.C
17
.W
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 .                                  
.I 132
.C
17
.W
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 .                                
.I 133
.C
17
.W
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 . 
.I 138
.C
1
.W
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 .                                                      
.I 140
.C
15
.W
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 .         
.I 141
.C
4
.W
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 .                               
.I 142
.C
1
.W
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 .          
.I 143
.C
13
.W
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) .                            
.I 144
.C
13
.W
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 .                                                           
.I 145
.C
13
.W
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 .                      
.I 146
.C
13
.W
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 .            
.I 148
.C
11
.W
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 .   
.I 150
.C
11
.W
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 .                                                            
.I 152
.C
10
.W
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  
.I 153
.C
10
.W
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 .                        
.I 154
.C
10
.W
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 .                                     
.I 155
.C
10
.W
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 .                                                 
.I 158
.C
5
.W
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 .                                          
.I 159
.C
5
.W
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
.C
3
.W
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 162
.C
2
.W
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 .                          
.I 163
.C
3
.W
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 .                                  
.I 164
.C
1
.W
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 .                                                  
.I 165
.C
1
.W
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
.C
1
.W
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
.C
1
.W
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
.C
1
.W
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
.C
1
.W
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
.C
1
.W
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
.C
1
.W
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 .                                
.I 172
.C
1
.W
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 .                       
.I 173
.C
4
.W
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 .                         
.I 174
.C
4
.W
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 .                                                                
.I 175
.C
4
.W
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 .                                    
.I 176
.C
4
.W
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 .                                                  
.I 177
.C
4
.W
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
.C
4
.W
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 180
.C
1
.W
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
.C
1
.W
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
.C
1
.W
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 .                   
.I 183
.C
1
.W
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
.C
1
.W
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 .                                                 
.I 185
.C
1
.W
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
.C
1
.W
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 .                                                                 
.I 187
.C
2
.W
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 .                                           
.I 188
.C
5
.W
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
.C
7
.W
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
.C
8
.W
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 .                                                       
.I 192
.C
9
.W
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
.C
12
.W
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
.C
13
.W
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 .                                          
.I 195
.C
13
.W
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 .                                                
.I 196
.C
13
.W
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 .                                                     
.I 197
.C
13
.W
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 .                                     
.I 198
.C
13
.W
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 .                         
.I 199
.C
13
.W
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                       
.I 202
.C
16
.W
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 .                          
.I 205
.C
16
.W
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 .                                                      
.I 207
.C
4
.W
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 .                                                          
.I 208
.C
4
.W
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 .                                                               
.I 209
.C
4
.W
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 .      
.I 210
.C
4
.W
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 .                                              
.I 211
.C
1
.W
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 .                          
.I 212
.C
1
.W
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 .                                                           
.I 215
.C
15
.W
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 .                                                               
.I 216
.C
15
.W
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 .                            
.I 218
.C
15
.W
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 .                                                             
.I 219
.C
15
.W
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 .                               
.I 220
.C
15
.W
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 .                                                          
.I 222
.C
15
.W
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 .                                                       
.I 225
.C
11
.W
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 .          
.I 226
.C
11
.W
/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 .                                                
.I 228
.C
11
.W
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 .                                                                 
.I 229
.C
11
.W
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 .                                                          
.I 230
.C
3
.W
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 .                     
.I 231
.C
3
.W
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 .                                              
.I 232
.C
3
.W
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 .                         
.I 233
.C
3
.W
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 .
.I 236
.C
2
.W
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 .                                                            
.I 237
.C
2
.W
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 .                                   
.I 238
.C
6
.W
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 .                                       
.I 239
.C
6
.W
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 .                                                
.I 242
.C
6
.W
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 .                                                                
.I 247
.C
7
.W
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 .                                                                
.I 251
.C
8
.W
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 .                      
.I 252
.C
9
.W
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 .                            
.I 253
.C
9
.W
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 .                                   
.I 254
.C
10
.W
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 .      
.I 255
.C
10
.W
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 .                               
.I 256
.C
10
.W
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 .                                                   
.I 257
.C
10
.W
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 .                                       
.I 258
.C
2
.W
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 .            
.I 259
.C
4
.W
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 .                                                               
.I 260
.C
6
.W
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 .                                   
.I 261
.C
7
.W
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 .                                                  
.I 262
.C
8
.W
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 .                     
.I 267
.C
9
.W
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 .                                
.I 268
.C
9
.W
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 .               
.I 269
.C
9
.W
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 .                                                               
.I 270
.C
9
.W
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 .                                     
.I 289
.C
2
.W
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.
.I 290
.C
2
.W
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.
.I 292
.C
2
.W
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.
.I 293
.C
2
.W
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.
.I 304
.C
5
.W
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.
.I 305
.C
5
.W
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
.C
5
.W
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.
.I 307
.C
5
.W
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 334
.C
17
.W
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.
.I 335
.C
17
.W
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 337
.C
17
.W
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.
.I 349
.C
15
.W
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.
.I 350
.C
15
.W
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
.C
15
.W
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
.C
15
.W
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 364
.C
12
.W
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 382
.C
7
.W
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 385
.C
7
.W
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.
.I 386
.C
7
.W
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.
.I 387
.C
7
.W
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
.C
7
.W
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 396
.C
4
.W
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 440
.C
11
.W
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
.C
11
.W
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 444
.C
11
.W
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 454
.C
14
.W
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
.C
14
.W
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
.C
14
.W
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
.C
14
.W
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 459
.C
14
.W
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 470
.C
13
.W
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
.C
13
.W
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 484
.C
16
.W
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 487
.C
16
.W
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
.C
16
.W
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 514
.C
18
.W
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
.C
18
.W
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
.C
18
.W
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
.C
18
.W
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
.C
18
.W
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
.C
18
.W
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 521
.C
18
.W
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
.C
18
.W
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
.C
18
.W
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
.C
10
.W
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 531
.C
10
.W
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
.C
10
.W
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
.C
10
.W
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
.C
10
.W
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 544
.C
19
.W
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
.C
19
.W
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 549
.C
19
.W
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
.C
19
.W
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 555
.C
19
.W
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 560
.C
19
.W
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 562
.C
19
.W
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
.W
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
.W
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
.C
19
.W
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
.C
19
.W
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
.C
20
.W
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 570
.C
20
.W
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
.C
20
.W
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 573
.C
20
.W
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
.C
20
.W
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
.C
20
.W
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
.C
20
.W
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
.C
20
.W
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
.C
20
.W
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 580
.C
20
.W
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
.C
20
.W
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 584
.C
20
.W
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
.C
20
.W
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 588
.C
20
.W
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
.C
20
.W
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
.C
20
.W
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 593
.C
20
.W
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
.C
20
.W
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
.C
20
.W
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
.C
20
.W
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
.C
20
.W
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
.C
20
.W
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
.C
20
.W
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 601
.C
20
.W
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
.C
20
.W
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 604
.C
21
.W
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
.C
21
.W
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 608
.C
21
.W
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 610
.C
21
.W
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 612
.C
21
.W
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
.C
21
.W
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 615
.C
21
.W
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
.C
21
.W
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 618
.C
21
.W
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
.C
21
.W
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
.C
21
.W
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 622
.C
21
.W
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 626
.C
21
.W
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 630
.C
21
.W
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
.C
21
.W
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 633
.C
22
.W
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 635
.C
22
.W
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
.C
22
.W
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 638
.C
22
.W
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 640
.C
22
.W
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
.C
22
.W
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 643
.C
22
.W
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
.C
22
.W
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
.C
22
.W
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 647
.C
22
.W
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
.C
22
.W
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 651
.C
22
.W
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
.C
22
.W
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 654
.C
22
.W
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
.C
22
.W
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
.C
22
.W
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
.C
22
.W
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 663
.C
24
.W
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 666
.C
24
.W
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
.C
24
.W
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
.C
24
.W
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
.C
24
.W
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
.C
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
.C
24
.W
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
.C
24
.W
(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
.C
24
.W
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
.C
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
.C
25
.W
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
.C
25
.W
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
.C
25
.W
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
.C
25
.W
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
.C
25
.W
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
.C
25
.W
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
.C
25
.W
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
.C
25
.W
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
.C
25
.W
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
.C
25
.W
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
.C
25
.W
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
.C
26
.W
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
.C
26
.W
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
.C
26
.W
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
.C
26
.W
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
.C
26
.W
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
.C
26
.W
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
.C
26
.W
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
.C
26
.W
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
.C
26
.W
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
.C
26
.W
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
.C
26
.W
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
.C
26
.W
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
.C
26
.W
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
.C
26
.W
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
.C
27
.W
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
.C
27
.W
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
.C
27
.W
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
.C
27
.W
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
.C
27
.W
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
.C
27
.W
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
.C
27
.W
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
.W
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
.C
27
.W
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
.W
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
.C
27
.W
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
.C
27
.W
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
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
(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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
29
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
28
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
23
.W
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
.C
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
.C
23
.W
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
.C
23
.W
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
.C
30
.W
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
.C
30
.W
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
.C
30
.W
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
.C
30
.W
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
.C
30
.W
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
.C
19
.W
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
.C
19
.W
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
.C
19
.W
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
.C
19
.W
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
.C
20
.W
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
.C
23
.W
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
.C
24
.W
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
.C
24
.W
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
.C
24
.W
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
.C
19
.W
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
.C
19
.W
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
.C
19
.W
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
.C
20
.W
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
.C
21
.W
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
.C
21
.W
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
.C
21
.W
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
.C
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
.C
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
.C
24
.W
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
.C
25
.W
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
.C
25
.W
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
.C
25
.W
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
.C
25
.W
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
.C
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
.C
26
.W
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
.C
26
.W
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
.W
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
.C
26
.W
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
.W
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
.C
28
.W
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
.W
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
.C
30
.W
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
.C
30
.W
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
.C
30
.W
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.
