Early learning and retention of a conditioned taste aversion. Weanling rats were trained on a taste aversion task and tested 60 days later using the single bottle and preference methods for assessing the retention of a taste aversion, and a competitive situation in which the CS was eventually substituted for plain water. Only the competitive situation showed the effects of the early taste aversion training. The results are discussed in terms of the conditioning and reactivation of adrenocortical steroid elevations and how these might affect subsequent retrieval.


The ontogeny of plasma osmolality and intravascular volume maintenance during short-term starvation in rats. Body fluid deviations were examined in albino rats of both genders between 30 and 100 days of age during food deprivation. Plasma volume declined with age in free-feeding control groups. Hypovolemia induced by starvation (4 days) was more intense in 30- to 60-day-old animals than in 80- and 100-day groups. Plasma ismolality concentration of control groups indicated increases with age leveling off after 60 days. The initiation of drinking during fasting was accompanied by physiologically significant elevations in plasma osmolality over ad libitum concentrations at each age tested. In a second experiment, repeated exposure to short periods of food deprivation (2 days) during development resulted in the maintenance of intravascular fluid at control volumes. Longer periods (4 days) of deprivation did not result in savings of intravascular volume loss evidenced during starvation. These results suggest that rats compensate for hypovolemia induced by short-term starvation when provided experience with food restriction during development.


Alterations in the maternal behavior of rats rearing malnourished offspring. Investigations of maternal behavior of mothers fed a low-protein diet indicated deficits in retrieval and in the rate of nest-building. In addition, they indicated a concomitant increase in time spent with young when assessed during periods not associated with the retrieval/nest-building test session. The adrenalectomized mother, another case that produces growth-stunted progeny, was compared with both low-protein and control mothers for maternal behavior. Unlike the low-protein mother, the adrenalectomized mother did not exhibit retrieval or nest-building deficits; however, the adrenalectomized mother did display an increase in time spent with young. These data suggest that although deficits in retrieval and nest-building can be attributed to the nutritional condition of the mother, the stimulus characteristics of the malnourished pup are important in eliciting the increased time spent with the litter.


Response to auditory stimuli in 6- and 9-week-old human infants. Response to 5-sec, 75-dB complex sounds was studied in groups of 24 infants each at 6 and 9 weeks of age. Under conditions appropriate for eliciting orienting, no significant cardiac response appeared at 6 weeks, but a significantly decelerative response did appear at 9weeks. Measurement of noncardiac responses suggested that sucking suppression is also a component of orienting to sound, that the status of eye-opening is equivocal, and that previously reported eye-movement responses are probably a component of startle. We concluded that age changes in orienting may occur in young infants, even when state is controlled, and that the probability of orienting varies with the kind of stimuli employed.


Ontogeny of observational learning in the dog (Canis familiaris). A split-litter technique was used to test observational learning in 4 litters of Miniature Dachshund puppies, 21, 28, 38, and 60 days old at the beginning of the experiment. In one side of a duplicate cage, one puppy of a litter, the demonstrator, learned to pull in a food cart on a runner by means of a ribbon, while another puppy, the observer, watched from an adjacent compartment, separated by a wire screen. Observational learning was demonstrated by the saving in time for the 1st trial when the observer was given the same problem to solve. Maturation, particularly the development of visual function and motor coordination, set a lower age limit for the emergence of observational learning.


Interaction-induced reduction in differential maternal responsiveness: an effect of cue-reduction or behavior? Litters from donor mothers received differential treatments (handling or shocking) and were then placed in wire-mesh baskets affixed to the cage tops of test mothers. Pup-produced cues from donor litters elicited different patterns of maternal behavior from test mothers that interacted with their own litters. In addition to these differences in maternal behavior, cues from the donor litters elicited a differential pattern of pituitary-adrenal activity. Shocked pups elicited larger corticosterone elevations than handled pups. These data suggest that the elimination of differential pituitary-adrenal responsiveness evidenced when mothers interact directly with pups subseuqent to pup treatment resllts from the termination of pup-produced cues that normally accompany active mother-infant interactions.


Peripheral and autonomic nerve function in newly diagnosed diabetes mellitus. Peripheral and autonomic nerve function was assessed in 10 newly diagnosed male diabetics (six insulin-treated and four sulfonylurea-treated) with repeated observations over the subsequent six months. There was significant impairment of motor-conduction velocity in the common peroneal nerve at diagnosis in both treatment groups, with improvement following treatment in only the insulin-treated patients. In contrast, although the blood glucose level fell in both groups, the mean level was significantly lower in the sulfonylurea-treated patients at two months and at each subsequent visit. In the autonomic function tests significant abnormality was found in the electrocardiographic R-R-interval (beat-to-beat) variation in resting heart rate in two of the insulin-treated patients and all of the sulfonylurea-treated group, with improvement in only one of the latter. One patient in the sulfonylurea-treated group also showed an abnormal response to the Valsalva maneuver (expressed as the Valsalva ratio), and this remained abnormal throughout the period of study. All other patients had normal responses to the Valsalva maneuver and sustained handgrip test. None of the patients had postural hypotension. Abnormalities in autonomic nerve function in diabetics at diagnosis have not been previously reported.


Glucagon response to arginine stimulation in obese and diabetic children. The effect of arginine infusion on blood sugar and plasma levels of growth hormone and glucagon has been studied in children with clinical diabetes mellitus and in obese children with normal carbohydrate tolerance. Basal levels of plasma GH are significantly lower in obese children than in diabetics and controls; in obese subjects the increment of GH is significantly lower than in diabetics and controls. Basal plasma glucagon levels are comparable in all three groups despite the high sugar levels in diabetic patients. After arginine infusion there is a significant rise in glucagon levels without significant differences between the three groups.


Control of hyperglycemia in adult diabetics by pulsed insulin delivery. Nine adult diabetic subjects were treated for two weeks by an intravenous insulin-delivery system that provided preprogramed five-hour pulses of insulin with each meal such that a normal diurnal pattern of plasma insulin was attained. Plasma insulin peaked at 800 per cent of basal and at approximately 45 minutes after the onset of each pulse. On day 14, mean plasma glucose (hourly sampling X 22) was 94 mg./100 ml., with a range of 66 to 125 mg./100 ml. Eighty-eight per cent of all values were between 50 and 150 mg./100 ml. The dose of insulin required correlated significantly with the degree of obesity. On the first posttreatment day, hourly plasma glucose remained significantly below pretreatment levels while the endogenous plasma insulin area increased 46 per cent above pretreatment values (p less than 0.01). Six of the patients still exhibited slight improvement in glucose tolerance for seven days while on diet but not on insulin treatment. It is concluded that insulin replacement, coordinated with meals in a physiologic manner, can virtually normalize plasma glucose even without feedback control of delivery rates. Definite but transient remission of beta-cell dysfunction may follow.


HLA system in Japnaese patients with diabetes mellitus. Seventy-eight Japanese diabetics were HLA-typed, with special reference to age at onset, insulin dependency, and family history. HLA-A9, B5, and BW40 were increased, but A1, A3, and B8, which are found frequently among Caucasians, were almost absent among Japanese healthy controls as well as diabetics. J-1, a Japanese specific subclass of BW22, was significantly increased in juvenile-onset diabetics as compared with controls or diabetics with late onset. J-1 was also increased in the diabetics with insulin dependency and/or positive family history. But the association of J-1 with juvenile-onset diabetes mellitus was found to be the strongest. A tendency to a decrease in B5 was also observed in Japanese diabetics with juvenile onset, but this did not reach statistical significance as far as corrected P was concerned. These results showed that genetic markers for diabetes mellitus, especially that with juvenile onset, were different among Japanese from those found among Caucasians. There is ample evidence to indicate a race specificity in HLA phenotypes in diabetics as well as in controls. These findings also strongly suggest that juvenile-onset diabetes mellitus is a disease entity in itself and different from late-onset diabetes mellitus in origin and pathogenesis.


HLA and chronic active hepatitis (CAH).

HLA and chronic active hepatitis (CAH). A family study of 2 parents and 5 SD identical (HLA-A1, A3, B7, B8) siblings, one of whom has 'classic CAH' has been used to demonstrate that in this family the maternally ingerited HLA-B8 antigen is not solely serving to mark genetic predisposition to this disease. The patient's lymphocytes both responded to, and stimulated those of her 4 siblings in MLR indicating the possible involvement of an HLA-D antigen in CAH. This HLA-D antigen could have been of paternal orgin, or could have been a result of a recombination event involving an HLA-D antigen liked to the maternal HLA-A2, B12 haplotype. The lymphocytes of the four helthy siblings were mutually unresponsive in MLR.


HLA in different forms of chronic active hepatitis. A comparison between adult patients and children. 108 adult patients and 34 children with chronic active hepatitis (CAH) are divided in four groups on the basis of presence and absence of hepatitis B surface antigen (HBsAg) and autoantibodies (AutoAb). There are significant differences in the numeric distribution among the four groups and the sex distribution between adult patients and children, but no differences in the frequencies of the HLA antigens tested. An increased frequency of HLA-B8 (and HLA-A1) compared with normal controls and the other groups is only found in autoimmune types of CAH, characterized as HBsAg-negative, AutoAb-positive CAH. HBsAg-negative, AutoAb-negative forms of CAH are called cyptogenic CAH and these are most likely non-hepatitis B virus induced types of CAH. In these and hepatitis B virus induced forms of CAH no significant deviation of any HLA antigen tested could be found.


HLA and chronic active hepatitis.

HLA and chronic active hepatitis. 42 patients (33 males and 9 females) with chromic active hepatitis (CAH) mostly HBsAg+, were typed for 24 alleles of the A and B loci. Diagnosis was performed according to the criteria outlined by the European Association for the Study of the Liver. The increased frequency of HLA-A3 (47.6% instead of 19.1% in 266 healthy controls) is significant after correction. The relative risk is 3.83. The phenotypic association A3/Bw35 is also increased (28.5% instead of 6.0 in the control group). The risk of the A3/Bw35 association is 6.25. The risk of A3 calculated in patients lacking Bw35 is 1.6. A family study in 5 patients over 5 showed an haplotype A3/Bw35.


Effect of local circulatory arrest on the structure of the enterocytes of the isolated intestinal loop. Fusion of the microvilli of the enterocytes, breakdown of the microvillous structure, vacuolization of the cytoplasm, and separation of the cells from one another, were observed in the early period of anoxia in the isolated small intestinal loop of dog. Filling the intestinal lumen with isotonic glucose solution inhibited the occurrence of the morphological changes observed. These observations furnish new data to the understanding of the very initial stage of small intestinal cell destruction due to anoxia.


Feedback regulation of pancreatic enzyme secretion by intestinal trypsin in man. In a patient a papilla Vateri tumor completely prevented the bile-pancreatic flow into the intestine although the pancreatic juice was secreted into the bile duct via a common channel. Consequently, the bile-pancreatic juice was possible to sample via a percutaneous transhepatic cholangiography (PTC) catheter. This made it possible to study the effect of duodenal infusion of different substances on the bile-pancreatic secretion. In repeated experiments a suppression of the secretion was observed by intraduodenal trypsin as well as the patient's own bile-pancreatic juice. In the presence the bile-pancreatic juice intraduodenal trypsin inhibitor infusion caused a marked stimulation of the secretion. The results are in accordance with the hypothesis that trypsin in the upper part of the intestine exerts a negative feedback regulation of the pancreatic secretion in man.


Relationship of the gastrin response to the amount of food ingested in normal subjects. The serum gastrin response to three different amounts of a same meal was studied in 8 normal subjects. The peak gastrin response was similar for the three meals, but the integarated gastrin response was larger with the largest meals. Comparison of the response to the two largest meals indicates that in a given subject the gastrin response is similar when test on different occasions. A good correlation was found between individual fasting concentrations of gastrin and peak gastrin levels after feeding but not between basal gastrin and integrated gastrin response. This could indicate that in normal subjects the first two parameters are primarily related to the same control mechanisms (possibly the G cell mass), while the integrated gastrin response reflects the effectiveness of the feedback mechanisms controlling gastrin release.


In-situ-isolated perfused rat pancreas: a new method for pharmacological studies of the exocrine pancreas. A method of in-situ-isolated perfused rat pancreas is described. In situ perfusion of the isolated rat pancreas allows a faster set-up, thanks to a simpler operating procedure. The sensitivity of the isolated rat pancreas has been tested with secretin and cholecystokinin. The pancreas responds to doses of secretin as low as 0.005 CU/kg-h. Such a highly sensitive model might prove to be useful for the bioassay of secretin and the study of the effects of pancreatic secretagogues.


The effects of cholecystectomy on the bile salt pool of the syrian hamster. The half-life, distribution, size and composition of the bile salt pool were determined in intact and cholecystectomized Syrian hamsters. Cholecystectomy had no effect on the half-life of either the cholate or chenodeoxycholate pool. Fasting in intact hamsters resulted, as expected, in a shift of bile salts from the small intestine, cecum and liver to the gallbladder. In cholecystectomized hamsters there was a moderate shift of salts from the liver and small intestine to the cecum. Cholecystectomy had no significant effect on the size of the total bile salt pool. The total bile salt pool size of fed and fasted intact hamsters was the same; fasting in cholecystectomized hamsters resulted in a large decrease in the pool. There was no significant difference in the bile salt pool composition of intact and cholecystectomized hamsters, and hamsters were shown to efficiently convert deoxycholate to cholate.


Determination of protein synthesis elongation factor activity in liver biopsy specimens from normal and cirrhotic rats. In liver biopsy specimens (between 8.5 and 22 mg wet weight) obtained from normal and thioacetamide-induced cirrhotic rat liver the polypeptide-chain-elongationpromoting activity (elongation factors 1 and 2) was determined. In liver cirrhosis the activity is reduced by about 50%.


A biopsy study of gallstones in Nigerian igbos. Within 6 years, approximately 7,500 surgical specimens were collected at a central laboratory serving the Igbos of Nigeria. Only 28 specimens were gallbladders. Gallstones were found in 5 females and 2 males. As in other developing communities in which the diet consists largely of traditional foods, pigment stones outnumbered cholesterol stones, the ratio being 6:1. The know complications were single instances of carcinoma and rupture of the gallbladder.


Vitamin B12 and bile acid metabolism in patients with partial iieal resection. The vitamin B12 and bile acid metabolism was studied in 20 patients in whom a standardized Bricker procedure without irradiation was performed. No significant vitamin B12 malabsorption, steatorrhea, fecal bile acid loss or bile acid deconjugation was found. Therefore, no long-term adverse metabolic consequences of segmental preterminal ileal resection are to be expected in these patients.


[Junctional reciprocating tachycardia with second degree A-V block (author's transl)]. Two cases of paroxysmal supraventricular tachycardia sustained by an atrioventricular junctional reentry mechanism are presented. During the electrophysiological study it was possible to induce paroxysms of tachycardia showing 3:2 Lucianai-Wenckebach type and 2:1 atrioventricular block. The site of the block, its functional nature and the possible involvement of an anterogradely blocked atrio-nodal or atrio-His accessory pathway in the reentry circuit are discussed.


[Clinical and echo-phonomechanocardiographic study of the mitral valve prolapse (author's transl)]. The results of a study of 32 patients with the clinical and auscultatory suspect of M.V.P., confirmed echo-cardiographically, are reported. Part of the pathogenetic cause of the symptomatology and ECgraphic alterations are attributed to the hypomagnesiemia. The relation between exercise test positivity and gravity of the symptomatology is confirmed. The phonomechanocardiographic tracings were studied and the morphological features from C.P. and apexcardiogram are described and shown, with particular attention given to the clicks and systolic murmurs. The authors describe three types of prolapse, early, "U"-and "double U"--shaped pansystolic, and, relating echo-to-phonomechanocardiographic results, point out features which seem typical of the M.V.P. Echo-phono mechanocardiography is confirmed as a technique which is useful and sufficiently safe and reliable in diagnosing, detecting and following the disease in its not yet perfectly acknowledged evolution. It avoids the use of invasive tools which could become extremely dangerous.


[Left ventricular microcatheterization during acute myocardial infarction (author's transl)]. Left ventricular microcatheterization at the bedside was accomplished in 20 acutely ill patients with myocardial infarction. Direct measure of the left ventricular end-diastolic pressure shows that its values can substantially differ from those of the pulmonary artery end-diastolic pressure. The authors observed that left ventricular microcatheterization is indicated, in the course of acute myocardial infarction, in the following circumstances: --when either the pulmonary artery end-diastolic or the pulmonary capillary pressure is beyond normal limits; --in the presence of tachyarrhythmias which, for alteration of the dynamics of atrial contraction, increase the difference between the left ventricular and pulmonary artery end-diastolic pressures; --when a mitralic defect is associated with the acute myocardial infarction.


[Kinetocardiographic surveys in coronary heart disease patients during infusion of isoproterenol and dopamine. A contribution to the diagnosis of coronary insufficiency (author's transl)]. 80 patients affected by coronary heart disease, with or without infarction, were studied by kinetocardiographic technique before and after infusion of isoproterenol (ISP) (40 patients) or dopamine (DOP) (40 patients). 40 healthy subjects served as controls (20 for ISP and 20 for DOP). Whereas the infusion of ISP or DOP caused no abnormalities in the healthy subjects, pathological changes of the kinetocardiogram (KCG) were often induced in patients with coronary heart disease. In particular, these changes demonstrated the appearance of paradoxical outward systolic movements, reduction or disappearance of the volume effect during the ejection phase, an increase of atrial waves expressed in per cent of the total amplitude of the KCG. The abnormalities observed during the intravenous infusion of ISP or DOP were interpreted as signs of ventricular dysfunction consequent to the myocardial ischaemia induced by these amines. The use of ISP or DOP together with KCG is recommended as a diagnostic method for coronary insufficiency.


[Electrode surface areas, pulse duration and stimulation threshold. Acute and chronic study with endocardial unipolar electrodes (author's transl)]. Acute and chronic voltage-threshold of cardiac stimulation was studied in patients with complete A-V block. Endocardial unipolar electrode with three different cathodial surface areas were used (54, 22 and 12 sqmm), and tested with rectangular stimulus of variable duration (from 0.2 to 3.5 msec.). The results show that the threshold values, at first implantation and at pulse-generator replacements, are low when short-duration stimulus and smaller electrode surface area are used. The practical advantages of this study are evident.


[Rupture of the posterior wall of the left ventricule after replacement of the mitral valve: a description of 8 cases (author's transl)]. Eight cases of left ventricular rupture at the atrio-ventricular groove among 693 mitral valve replacements, isolated or associated with  other surgical procedures, are reported. In the authors' opinion, the surgical technique of the mitral valve's removal, especially if calcific or with subvalvular disease, as well as the method and the site of implantation of the prosthesis, are the main factors in determining this severe complication. In order to avoid the rupture of the posterior wall of the left ventricle, a simple modification of the surgical technique which reinforces the valvular annulus is suggested.


[Precordial ST segment elevation mapping: a new method for a technically easier recording (author's transl)]. Precordial ST segment maps are currently recorded using a 35 electrode blanket connected to an electrocardiograph through a switch box. Problems in adjustment to patients' chests and artifacts are frequently encountered. Other techniques using a single suction electrode placed on different reference points are time wasting. The authors suggest the use of 35 self-adhesive electrodes (3M "Red Dot" chloride free gel pediatric electrodes--cat N. 2243) connected by a press button to a multichannel EKG recorder. This technique prevents artifacts, assures constant arrangement of the electrodes, is suitable for different thoracic structures and does not need any additional device. The authors consider that such a practical method should make precordial ST mapping a more widespread clinical procedure.


Analysis of DNA from adenovirus 12-transformed cells for virus-specific DNA sequence with viral DNA fragments cleaved with restriction endonuclease. 32P-Labeled adenovirus-12 (Ad-12) DNA was treated with restriction enzyme (EndoR-Hin dIII) isolated from Haemphilus influenzae (Rd strain) and the resulting 16 specific fragments were separated through gel electrophoresis. This kinetics of renaturation of each of the fragments was measured in the presence of unlabeled Ad-12-transformed hamster embryo cell, clone 9 (Ad-12HE-C19). more than 77% of the viral genome nucleotide sequence was present in Ad-12he-c19 cell DNA with 5 to 10 copies per haploid quantity of cell DNA of each of the sequences of 11 fragments examined; A, C, D, E, F, G, H, I, J (J1+J2), K, and L. However, it is suggested that only a part of the nucleotide sequence in B fragment may b present in the cell DNA.


Combined treatment with anaerobic Corynebacterium liquefaciens and chemotherapeutics against solid tumor in mice. The combined effect of anticancer agents (Mitomycin-C, cyclophosphamide, or 5-fluorouracil) and anaerobic Corynebacterium liquefaciens on subcutaneously induced solid Ehrlich carcinoma in mice was examined. Mitomycin-C and cyclophosphamide were given intraperitoneally on day 7 after inoculation of tumor cells. 5-Fluorouracil was administered intraperitoneally for 7 consecutive days from day 9 to 15. C. liquefaciens was given in two ways, intraperitoneally and intratumorally. Its injections were made on days (--7, --5), (--4, --2) (+2, +4), or (+5, +7) in the intraperitoneal groups and in every way varying from (+9, +10) to (+19, +20) days in the intratumoral groups. The best result was observed in combination of C. liquefaciens and 5-fluorouracil in the intraperitoneal groups and that of C. liqlefaciens and cyclophosphamide in the intratumoral groups. Although the results were not necessarily good, probably due to the poor design on time schedule of C. liquefaciens, they partly confirm the hypothesis that the activity of conventional anticancer drugs can be potentiated by a non-specific immunostimulation by anaerobic C. liquefaciens in the solid tumor of mice same as in the ascitic tumor reported previously.


Frozen preservation of human malignant tumors transplanted into nude mice. Five transplantable tumors, which originated from human maligant neoplasms and had been maintained in nude mice, were frozen at--70 degrees preserved for 1226 days. Tumor tissue was minced in a mixture of tissue culture medium, 10% dimethyl sulfoxide, and 10% calf serum before freezing. The transplantability of frozen tumors was examined after thawing. Morphological and functional characteristic of each tumor were compared before and after the frozen storage. The results suggest that low-temperature preservation technique can be applied satisfactorily for the maintenance of human malignant tumors which have been maintained by using nude mice.


Glycosaminoglycans in human lung carcinoma. The glycosaminoglycans were prepared by exhaustive Pronase digestion and alkaline treatment of squamous cell carcinoma and adenocarcinoma tissues of human lung, and of tissues taken at a site distant from the tumor as a control. The glycosaminoglycan classes were characterized by chemical enzymic, and electrophoretic methods. The presence of oversulfated chondroitin-and/or dermatan-sulfates which have not up till now been found in lung tissues was also demonstrated in carcinoma and control tissues, their contents being higher in the carcinoma tissues. The levels of whole glycosaminoglycans were markedly increased in carcinoma tissue. The classes of glycosaminoglycans which increased in lung carcinoma tissue were predominatly chondroitin-4-and/or-6-sulfates and hyauronic acid.


Transplacental carcinogenesis and chemical determination of 1-butyl-1-nitrosourea in stomach content after simultaneous oral administration of 1-butylurea and sodium nitrite to ACI/N rats. Solutions of 100 mg/kg 1-butylurea and 50 mg/kg sodium nitrite were administered daily by a stomach tube to pregnant ACI/N rats from the 13th to 21st day of gestation. Neurogenous tumors were induced in their offspring. The incidence of tumours and mean survival time of rats with nervous tumours were 64% (23/36) and 309 (189672) days respectively. Localization and histological findings of the nervous tumors were similar to those observed previously in rats whose mothers received 1-butyl-1-nitrosourea (BNU) during pregnancy. Neurogenous tumors did not develop in the offspring of the mothers that received 100 mg/kg of 1-butylurea alone in the same manner. In several rats of both group, a few spontaneous tumors of the testis, pituitary gland, urinary bladder, uterus, and colon were detected. In vivo formation BNU in stomach content after intubation of 1-butylurea and sodium nitrite was determined. BNU was detected in the stomach content at levels of 25 ppm at 30 min and 23 ppm at 60 min after administration. The concentration of BNU in the stomach content corresponded to 48.3 and 29.2 microng/rat, respectively.


Ultrastructural investigation of the effect of mitomycin C on the rat exocrine pancreas. In order to clarify the pathophysiology of digestive disorders which are caused with anticancer agents, Mitomycin C was intravenously administrated to rats and the ultrastructure of the pancreas was studied. The alteration of acinar cells after under 4 daily administrations of 1.0 mg/Kg of Mitomycin C was not remarkable and in an early stage returned to normal structure. In above 8 daily administrations of 1.0 mg/Kg of Mitomycin C, however, pronounced degeneration of acinar cells was induced and acinar cells did not recover to the previous level, but die within one month. The ultrastructural changes induced by Mitomycin C were mainly aggregation of chromatin in the nuclei, tubularly dilatation of the rough endoplasmic reticulum, and swelling of the mitochondria. It was surmised that the biosynthesis and supply of protein such as digestive enzymes were not amply carried on; hence, the ehcmotherapy could give rise to severe digestion disorders. It appeared necessary to further study the dosage and dosage schedule of the anticancer agents, along with the necessity for taking ample care of patients presenting such disorders.


Acute terminal ileitis and Yersinia enterocolitica infection. Diarrhea, moderate to high fever and pain in the RLQ associated with a tender mass or swelling of the terminal ileum arouse suspicion of acute terminal ileitis. Will diagnostic of the disease be laboratory data compatible with acute inflammatory disease and radiological findings of the terminal ileum, i.e., thickening of mucosal folds, round filling defects on the mucosa indicative of swelling of lymphoid tissue and fine irregularities of the margin without narrowing of the lumen. Yersinia infection was demonstrated in 7 of 10 patients whose stool and/or serum were examined. Yersinia enterocolitica was found to be an important causative agent of acute terminal ileitis. Its detection will be useful for differentiating the disease from acute stage of Crohn's disease.


Assessment of endoscopic aspiration cytology and endoscopic retrograde cholangi-pancreatography (ERCP) in patients with cancer of the pancreas. Part I. This report is concerned with studies on duodenofiberscopic examinations with aspiration cytology endoscopic retrograde cholangio-pancreatography (ERCP) in 44 patients with cancer of the pancreas. Aspiration cytology alone was diagnostic in 91% of cancer of the head of the pancreas, 55% of cancer the body and tail of the pancreas and 100% of cancer of the whole pancreas. ERCP alone was diagnostic in 59% of cancer of the head of the pancreas, 75% of cancer of the body and tail of the pancreas and 100% of cancer of the whole pancreas. By combining these two approach a diagnostic result was obtained in 95% of cancer of the head of the pancreas and 90% of cancer of body and tail of the pancreas. It is concluded that the combined diagnostic approach has enhanced diagnostic accuracy of malignant lesions of the pancreas and that it has not yet led to an improvement resectability and mortality.


Assessment of endoscopic aspiration cytology and endoscopic retrograde cholangio-pancreatography in patients with cancer of the hepato-biliary tract. Part II. Aspiration cytology and ERCP were evaluated in 66 patients with cancer of the hepato-biliary tract. Cytology was diagnostic in 100% of ampullary cancer, 83% of cancer of extrahepatic bile duct, 0% of cancer of intrahepatic bile duct, 25% of cancer of gall bladder and 0% of cancer of liver. ERCP was diagnostic in 65% of ampullary cancer, 90% of cancer of extrahepatic bile duct, 100% of cancer of intrahepatic bile duct, 25% of cancer of gall bladder and 25% of cancer of liver. Endoscopic findings was diagnostic in 77% of cancer of ampullary region. By combining these approaches, a diagnostic result was obtained in 100% of ampullary cancer, 96.5% of cancer of extrahepatic bile duct, 100% of cancer of intrahepatic bile duct, 50% of cancer of gall bladder and 25% of cancer of liver. It is concluded that the combined diagnostic approach has enhanced the diagnostic accuracy of malignant lesions of the hepato-biliary tract and that it has not yet led to an improvement in resectability and mortality.


On a therapeutic target point for the non-operative treatment of intestinal obstruction. The period necessary to obtain a 95% improvement level through non-operative treatment of simple obstruction of the small bowel was found to be about six days, based on a study of 29 patients selected from approximately 1,000 clinical cases of verified or suspected intestinal obstruction. An additional experimental study confirmed the case-screening criteria.


Circadian study of immunoreactive prolactin in patients with cirrhosis of the liver. The pattern of immunoreactive prolactin secretion over 24 hr in a group of patients suffering from cirrhosis of the liver has been studied and compared to that of healthy controls. The results were analyzed by use of chronograms and by mean cosinor. Although the daily mean average secretion of serum prolactin by the cirrhotics is not different from that of the control subjects utilizing the standard t-test, cosinor analysis of the data fails to demonstrate a circadian rhythm for prolactin secretion in the cirrhotics. These results are discussed in view of the apparent clinical hyperestrogenization and known changes in electrolyte balance which are commonly found in persons with advanced liver disease.


Role of acetaldehyde in the ethanol-induced impairment of glycoprotein metabolism in rat liver slices. The mechanism responsible for ethanol-induced changes in the glycosylation of proteins was investigated in rat liver slices. Ethanol (5 to 50 mM) decreased [1-14C]glucosamine and [14C]leucine incorporation into total liver and microsomal proteins and greatly inhibited incorporation into medium (secretory) proteins. Pyrazole prevented the inhibition of glycoprotein synthesis by ethanol. Additions of methylene blue or pyruvate, which corrected the disordered redox state caused by ethanol oxidation, did not reverse the inhibitory effects of ethanol on glycosylation. Sorbitol, which mimics ethanol in generating reducing equivalents in the hepatocyte, also inhibited glycosylation; however, fructose, the immediate oxidation product of sorbitol, similarly inhibited glycoprotein synthesis without altering the redox state. When low levels of acetaldehyde (0.12 to 0.70 mM) were maintained in the medium by means of infusion, a significant inhibition of glycoprotein synthesis was observed. Acetate did not impair glycosylation. These data suggest that the ethanol-induced impairment of glycoprotein synthesis and secretion is a consequence of ethanol metabolism and further suggest that this inhibition is attributable to acetaldehyde formation rather than to the altered redox state resulting from ethanol oxidation.


Nonoperative management of biliary ductal stenosis. Report of a most unusual case. A patient with documented iatrogenic stricture of the common duct is reported. Certain very unusual characteristics of this lesion suggested that it was not precisely similar to ordinary biliary strictures and that nonoperative care was worthy of trial. No reconstructive operation has been done. The strictured segment has resolved so that the patient is completely asymptomatic and has no direct or indirect laboratory or radiographic evidence of biliary obstruction.


Segmental obstructing acute jejunitis in a child. Acute localized enteritis is a disease of the terminal ileum in adults and children. We have observed acute enteritis confined to the jejunum in a 3 1/2 year-old girl presenting with partial upper intestinal obstruction. Surgical biopsy of the involved region of jejunum revealed acute inflammatory changes in the mucosa and severe edema of the submucosa. Resection of the edematous segment was followed by prompt and apparently permanent recovery.


Stimulation of gastric inhibitory polypeptide in normal and duodenal ulcer patients. To investigate the role of gastric inhibitory polypeptide (GIP), a potent inhibitor of gastric acid secretion, in the hypersecretion associated with duodenal ulcer, we compared the serum GIP concentrations in 11 healthy subjects and 16 duodenal ulcer patients after the stimulation of GIP release by a mixed meal. Fasting and postprandial serum gastrin and GIP concentrations were measured by radioimmunoassay at frequent intervals after the ingestion of a test meal. The duodenal ulcer patients showed an augmented and significantly greater release of GIP as well as of gastrin compared to normal subjects. These results indicate that a defective GIP release cannot account for the gastric hypersecretion seen in patients with duodenal ulcer. The mechanism of the increased GIP response in patients with duodenal ulcer is not clear from these studies.


Nonparallel secretion of enzymes in human duodenal juice and pure pancreatic juice collected by endoscopic retrograde catheterization of the papilla. Duodenal juice was collected from 50 healthy patients in the basal state, and after intravenous injection of 1 clinical unit of secretin kg-1 + 3 Crick-Harper-Raper units of cholecystokinin-pancreozymin (CCK-PZ) kg-1. Amylase to chymotrypsin and amylase to lipase ratios were significantly decreased by stimulation. Pure pancreatic juice was collected from 7 healthy subjects by endoscopic retrograde catheterization of the papilla. Secretin (1 clinical unit kg-1 hr-1) was infused intravenously during 30 min, and a single intravenous injection of CCK-PZ (3 Crick-Harper-Raper units kg-1) was done at the 15th min of the secretin infusion. Chymotrypsinogen and lipase secretions did not parallel that of amylase during CCK-PZ stimulation. As in the first set of experiments, amylase secretion was proportionally less stimulated by CCK-PZ injection than were chymotrypsinogen and lipase secretions. However, in approximately 20% of subjects the secretion of the enzymes was parallel in both duodenal and pancreatic juice.


A study on the nature of macroamylase complex. Dissociation of macroamylase by substrates. Characteristics of a macroamylase that was considered not to be formed by the binding of normal amylase to immunoglobulins were studied. The macroamylase was reversibly dissociated into apparently normal amylase by treating the macroamylasemic serum with guanidine hydrochloride. Concanavalin A precipitated a large portion of the macroamylase. When the macroamylase was purified by affinity chromatography using an insoluble starch polymer at neutral pH, a considerable dissociation of the enzyme into apparently normal amylase was observed with the purified preparation. Such dissociation of the macroamylase was demonstrated by briefly incubating the patient's serum with a low-molecular weight starch, a substrate of the enzyme. This dissociated enzyme showed upon electrophoresis essentially the same isozymic pattern as that of normal serum amylase. When the patient's serum was incubated with the low molecular weight starch for a prolonged period to hydrolyze the starch completely and was dialyzed, reconstitution of macroamylase resulted. The amylase-binding substance(s) that is supposed to be involved in the formation of macroamylase was found to release when the enzyme was adsorbed on the insoluble starch polymer at 0 degrees C. The present results strongly suggest that the amylase-binding substance(s), probably polysaccharide(s) or glycoprotein(s), binds to the substrate-binding site of normal amylase to form a macroamylase complex.


Effect of cholecystokinin-octapeptide on lower esophageal sphincter. The effect of cholecystokinin-octapeptide (CCK-OP) on the lower esophageal sphincter (LES) was studied in 50 cats in vivo. CCK-OP caused a dose-dependent fall in LES pressures in all but 4 animals. Maximal sphincter relaxation was obtained with 200 to 400 ng of CCK-OP per kg of body weight. Atropine sulfate and/or hexamethonium, or adrenergic blocking agents (phentolamine or propranolol), in doses that completely inhibit the action of maximal doses of their respective agonists, failed to block the CCK-OP effect. Tetrodotoxin, however, in doses that denervates the LES, antagonized the CCK-OP-induced sphincter relaxation. In these tetrodotoxin-treated animals, CCK-OP produced LES contraction similar to that observed after pentagastrin. These results suggest that CCK-OP stimulates the postganglionic nonadrenergic, noncholinergic inhibitory neurons responsible for sphincter relaxation. CCK-OP also stimulates the circular muscle by direct action causing LES contraction. The latter becomes apparent when the innervation of the LES is abolished by tetrodoxtin.


Influence of isoproterenol and cholestyramine on acute gastric mucosal ulcerogenesis. One thesis concerning the pathogenesis of "stress ulcer" states that the combination of (1) bile acid-induced H+ "back diffusion" and (2) gastric mucosal ischemia is acutely Hg) to induce ischemia, this thesis was further tested by selectively mitigating either the ischemic or the back diffusion components of the model. Vascularized wedges of proximal canine gastric wall mounted on Lucite chambers were studied. With the mucosa directly visualized, control group A (6 dogs) was subjected sequentially to (1) topical acid test solution alone (ATS), (2) ATS + S, and (3) ATS + S + topical 5 mM Na taurocholate (TC). Study group B (6 dogs): (1) ATS, (2) ATS + S + the beta adrenergic agonist, isoproterenol, 1.5 microng per kg-min infused into the splenic artery, and (3) ATS + S + TC + isoproterenol. Study group C (6 dogs): (1) ATS, (2) ATS + S + the bile acid binding resin, cholestyramine (C), 4 g per liter, and (3) ATS + S + TC + C. During each period the net flux of H+, the electrical potential difference, and the aminopyrine clearance (AC) were determined. Mucosal damage (intramucosal hemorrhage, erosions, and ulcers, graded 0 to 5) was assessed blindly by an independent observer using photographs. The results indicate (1) that, despite H+ back diffusion comparable to ATS + S + TC, intraarterial isoproterenol significantly protects against lesion formation by increasing AC, and (2) that, despite a reduction in AC comparable to ATS + S + TC, topical C significantly protects against lesion formation by preventing excessive back diffusion of H+.


Effect of graded mechanical ischemia on oxygen tension and electrical potential in the canine gastric mucosa. A new experimental model. Oxygen tension and potential difference were measured in the gastric mucosa of anesthetized dogs with an ultramicroelectrode technqiue while total blood flow and arteriovenous oxygen content difference were measured. In the control period, measurements were: gastric  blood flow, 102.4 +/- 3.0 ml per min per 100 g of tissue; calculated oxygen consumption, 2.4 +/- 0.1 ml per min per 100 g of tissue; intracellular oxygen tension, 15.0 +/- 0.6 mm Hg; and intracellular potential difference, -50.8 +/- 1.5 mv. When gastric blood flow was reduced 50% by tourniquet ischemia, oxygen tension decreased 20% (P less than 0.05) but electrical potential and oxygen consumption did not change. When blood flow was reduced 75%, oxygen tension and potential difference decreased significantly, 60% and 35%, respectively, but oxygen consumption was unchanged. Zero blood flow reduced oxygen tension, electrical potential, and total oxygen consumption to zero; release of the arterial tourniquet allowed them to return to control levels. The critical oxygen tension at which the electromotive force generated by the gastric mucosal cells was reduced averaged 9 mm Hg. This suggests that safety factors exist in the gastric circulation which permit a 60% reduction in total gastric blood flow to occur before an insufficiency of intracellular oxygen begins to limit cellular metabolism within the mucosa.


Perfusion of rabbit colon with ricinoleic acid: dose-related mucosal injury, fluid secretion, and increased permeability. Morphology of the rabbit colon was examined by light and scanning electron microscopy after perfusion of the organ with 2.5, 5.0, 7.5, and 10 mM sodium ricinoleate. Colons perfused with control buffer showed the expected normal appearances, whereas ricinoleate produced desquamation of surface epithelial cells. Surface changes in the colon were comparable with those reported after similar treatment of the rabbit ileum. Concomitant with these histological changes was loss of DNA into the lumen of the colon. Dose-related changes in net fluid transport and mucosal permeability (as assessed by lumen to plasma flux of low molecular weight polyethylene glycols and plasma to lumen flux of urea and creatinine) were also associated with ricinoleate perfusion. These structural and functional alterations may contribute to intraluminal accumulation of fluid and catharsis that can result from administration of ricinoleic acid (castor oil). The findings might also pertain to the pathophysiology of steatorrheal diseases, because dietary fatty acids of similar chemical structure are known to have comparable effects on the intestinal mucosa.


Genetic analysis of phototactic behavior in Drosophila simulans. Phototaxis mazes have been employed to select photopositive and photonegative strains of Drosophila simulans. The results suggest that phototactic behavior in D. simulans, as in other Drosophila species, is a polygenic trait. Hybridization using divergent strains revealed that the genes controlling negative phototactic behavior in D. simulans are autosomal, as opposed to D. melanogaster in which negative phototactic behavior is known to be very strongly sex-linked.


A morphogenetic fate map constructed from Habrobracon juglandis gynandromorphs. A morphogenetic fate map is presented for the parasitic wasp, Habrobracon juglandis. Twenty adult cuticular structures of 1211 haploid-diploid gynandromorphs were placed on the fate map using the sturtoid calculation. The overall shape and organization of the Habrobracon fate map are similar to those of the Drosophila fate mape, both of which approximate the shape of an insect embryo but show structures arranged in a manner resembling the adult body plan. Independent samples of gynandromorphs yield similar maps.


Cortisone-induced cleft palate in the mouse. A search for the genetic control of the embryonic response trait. The cause of the difference in the mean tolerance (ED50) to cortisone-induced cleft palate between the embryos of the A/J and C57BL/6J strains appears to be due to a small number of genes. A single major gene effect and a polygenic model, in the sense of many equal and additive genes, have been ruled out. The embryonic tolerance of C57BL/6J  is greater than and dominant to that of A/J; two or three loci, possibly with independent effects, appear to explain the variability. A component of the variation in embryonic response may be associated with or linked to the major histocompatibility locus (H-2). No evidence was found to support the hypothesis of X-chromosome linked susceptibility to cortisone-induced cleft palate.


Effects on sperm morphology by alleles at the pink-eyed dilution locus in mice. Sperm head morphology was analyzed in all genotypic combinations for alleles dark pink-eye (pd) and p-sterile alleles, p6H, pbs (p-black-eyed sterile) and p25H. Three of these, p6H, pbs and p25H, were radiation induced; homozygotes and heterozygotes of these three alleles are male sterile, whereas pd/--genotypes are fertile. Sperm heads were examined by light microscopy and assigned to one of five classes: A. normal and near-normal, B. triangulate and oblate, C. spatulate, D. elongate, and E. filamentous. Males of each sterile genotype had grossly abnormal sperm and each sterile genotype differed from all other sterile genotypes and from fertile genotypes in at least one class, except p6H/p6H compared to pbs/pbs. Frequency distribution profiles (1) revealed a complex pattern of allelic interaction and do not support a deletion-complementation hypothesis, (2) do not show simple bimodality, which might suggest post-meiotic (haploid) gene expression, and (3) together with unpublished breeding data, show that p25H is not a remutation of p6H.


Genetic effects of acute spermatogonial X-irradiation of the laboratory rat. The genetic effects of one generation of spermatogonial X-irradiation in rats, by a single dose of 600r in one experiment and by a fractionated dose of 450r in another, were measured in three generations of their descendants. Estimates of dominant lethal mutation rates--(2 to 3) X 10-4/gamete/r--from litter size differences between irradiated and nonirradiated stock were consistent with previous estimates from rats and mice. Similar consistency was found for estimates of sex-linked recessive mutation rates--(1 to 2) X 10-4 chromosome/r--from male proportions within strains; however, when measured in crossbreds the proportion of males was higher in the irradiated than in the nonirradiated lines. This inconsistency in results is in keeping with the contradictory results reported for recessive sex-linked lethal mutation rates in mice. The effects used to estimate recessive lethal mutation rates which were unusually high--(2 to 14) X 10-4/gamete/r--were not significant. Other factors that could have contributed to the observed effects are postulated.


Distribution of nucleotide differences between two randomly chosen cistrons in a finite population. Watterson's (1975) formula for the steady-state distribution of the number of nucleotide differences between two randomly chosen cistrons in a finite population has been extended to transient states. The rate for the mean of this distribution to approach its equilibrium value is 1/2N and independent of mutation rate, but that for the variance is dependent on mutation rate, where N denotes the effective population size. Numerical computations show that if the heterozygosity (i.e., the probability that two cistrons are different) is low, say of the order of 0.1 or less, the probability that two cistrons differ at two or more nucleotide sites is less than 10 percent of the heterozygosity, whereas this probability may be as high as 50 percent of the heterozygosity if the heterozygosity is 0.5. A simple estimate for the mean number (-d) of site differences between cistrons is d = h/(1 - h) where h is the heterozygosity. At equilibrium, the probability that two cistrons differ by more than one site is equal to h2, the square of heterozygosity.


Variance of gene frequencies from recurrent selection in finite populations. An equation was derived for estimation of the variance of gene frequencies due to drift in the presence of recurrent selection. The equation assumes knowledge of gene frequencies in successive generations. These can be approximated in at least three ways. Simulation data demonstrated that when satisfactory approximations are used, the variances supplied by the derived formula agree well with observed variances.


The evolution of one- and two-locus systems. II. Weak selection in a monoecious population is studied in two multiallelic panmictic models. In the first, a single locus is considered with continuous time and age-independent fertilities and mortalities. If the fertilities of the various matings and the genotypic mortalities may be expressed with an error at most of the second order in s (i.e., O(s2)), where  s is the intensity of selection, as sums of terms corresponding to the different genotypes and alleles, respectively, then after several generations the deviations from Hardy-Weinberg proportions are of O(s2). In the second model, two loci are treated with discrete nonover-lapping generations. It is shown that if the epistatic parameters are of O(s2), then after several generations the linkage disequilibria are reduced to O(s2). Assuming only weak selection, it is proved that in both models, after several generations, the total change is mean fitness is generally positive. It is likely that the exclusion of the initial period is usually unnecessary in natural populations. Exceptions are discussed.


Inbreeding estimation from population data: models, procedures and implications. Four different estimation procedures for models of population structure are compared. The parameters of the models are shown to be equivalent and, in most cases, easily expressed in terms of the parameters WRIGHT calls "F-statistics." We have estimated the parameters of each of these models with data on nine codominant allele pairs in 47 Yanomama villages, and we find that the different estimators for a given parameter all yield more or less equivalent results. F-statistics are often equated to inbreeding coefficients that are definid as the probability of identity by descent from alleles taken to be unique in some founding population. However, we are led to infer from computer simulation and general historical considerations that all estimates from genotype frequencies greatly underestimate the inbreeding coefficient for alleles in the founding population of American Indians in the western hemisphere. We surmise that in the highly subdivided tribal populations which prevailed until the recent advent of civilization, the probability of identity by descent for homologous alleles was roughly 0.5. We consider some consequences of working with the customary, much lower, estimates--0.005 to 0.01--if, on the time scale of human evolution, these represent only a very recent departure from the inbreeding intensity that prevailed before civilization.


The effect of combining alleles into electrophoretic classes on detecting linkage disequilibrium. When alleles are combined into few detectable classes, linkage correlations are underestimated most of the time. The probability that the linkage correlation will be underestimated is a function of the actual degree of correlation and the evenness of the allelic distribution, but is mainly determined by the distribution of alleles into distinguishable classes. With only two alleles per class this probability will usually be higher than 0.7. Also, the consistency in the sign of the linkage disequilibrium over many populations may escape detection. An increase of sample size by one order of magnitude or more may be required to compensate for the loss in detection power. It follows that the available electrophoretic studies of linkage correlations, although negative in their majority, do not suggest that epistatic interactions and linkage disequilibria are rare in natural populations.


Simulation of quantitative characters by genes with biochemically definable action. VI. Modifications of a simple model. Investigations on metric characters of defined genotypes of Matthiola incana, and application of different linear models for the estimation of genetic parameters, indicate that the use of midparental value as a reference point results in parameter estimates that do not correspond to the actual biological situation. Use of the most recessive genotype as a reference point causes all of the contributions of single loci to be undirectional and positive, and all the allelic and nonallelic interactions to be unidirectional and negative, in accord with our Model 2.2. The results indicate that the phenotypic response to allelic substitutions follows the characteristics of a saturation curve. The possibility is discussed that the saturation character results from regulating processes, whereas deviations of single measurements from the response curve, or response surface, reflect real interactions between allelic and nonallelic genes.


Influence of gene duplication and X-inactivation on mouse mitochondrial malic enzyme activity and electrophoretic patterns. We have investigated, with and without the influence of X-inactivation, the relationship between autosomal gene-dosage and gene-product in a mammalian system, the mouse. The gene was mitochondrial malic enzyme (Mod-2), shown to lie on Chromosome 7 between the albino (c) and shaker-1 (sh-1) loci, and the enzyme was its product, mitochondrial malic enzyme (MOD-2). Gene duplication, with and without the influence of X-inactivation, was achieved using a translocation that involves the insertion of a portion of Chr 7, including Mod-2, into the X, T(X;7)1Ct. A 1:1 relationship for Mod-2 dosage and MOD-2 activity was found in heart mitochondria. Evidence of X-inactivation of Mod-2 was noted in heart and kidney preparations from females carrying a Mod-2 duplication (one copy of Mod-2 in the X and two copies of Mod-2 on Chr 7). We conclude that the expression of an autosomal locus attached to X-chromatin depends upon whether the translocation is in a balanced or unbalanced state.


Genetic parameters of serum cholesterol levels, activity and growth in mice. Heritabilities (h2) of, and phenotypic and genetic correlations among, serum cholesterol (SC), levels of physical activity, growth, and body moisture content were estimated from data on 466 sire-son pairs of random-bred, ICR albino mice. Heritability estimates of SC and body moisture content were 0.31 +/- 0.07 and 0.29 +/- 0.11, respectively. Estimates of h2 for activity measured by standard exercise wheels at 28, 49 and 70 days of age were 0.31 +/- 0.17, 0.50 +/- 0.11 and 0.27 +/- 0.14 and for weight at 21, 44 and 67 days of age, were 0.11 +/- 0.09, 0.33 +/- 0.09 and 0.42 +/- 0.08, respectively. The estimates of h2 for weight gain ranged from 0.22 +/- 0.07 to 0.27 +/- 0.08. Significant negative phenotypic correlations occurred between activity and rate of body weight gain. A negative genetic correlation of -0.70 +/- 0.11 between SC and body moisture implied that SC and percent body fat are positively correlated. Genetic correlations among SC values and activity scores and between SC values and body weight gains were near zero.


Identification of a major locus contributing to erythrocyte 2,3-diphosphoglycerate variability in hooded (Long-Evans) rats. The erythrocyte glycolytic intermediate 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP) play an important role in oxygen transport and delivery by binding to hemoglobin (Hb) and reducing its affinity for oxygen. Considerable quantitative variability in the levels of DPG and ATP exists in human populations and in a population of hooded (Long-Evans) rats we have studied. This paper presents the results of studies on the genetic component of DPG-level variation in an outbred population of hooded rats. Beginning with about 100 rats, a two-way selection experiment was initiated. Pairs of rats with the highest DPG levels were mated to produce a High-DPG rat strain and animals with the lowest DPG levels were mated to produce a Low-DPG strain. Mean DPG levels responded rapidly to selection and, from generation 3 on, the differences between strain means were highly significant. Ten High-DPG strain rats were intercrossed with 10 Low-DPG strain rats of generation 10 to produce an F1 generation in which the DPG levels were almost as high as those of High-DPG animals. This indicates partial dominance of High-DPG alleles. The F2 DPG-level distribution showed two distinct subpopulations. The high DPG subpopulation contained three times as many animals as the low DPG subpopulation. From these results and the statistical analyses performed, it was concluded that the DPG differences between strains were due to an allelic difference at one major locus, the allele carried by the High-DPG strain showing partial dominance over the allele carried by the Low-DPG strain. It appears that this locus may also effect ATP levels to a large extent and is polymorphic in hooded rat populations. Identification of this locus gives us a useful tool for studies of the physiological effects of DPG variability, as well as providing an example of a major gene effect in a quantitatively varying trait.


Microgeographic differentiation of chromosomal and enzyme polymorphisms in Drosophila persimilis. We studied microgeographic and temporal genetic differentiation in natural populations of Drosophila persimilis with respect to chromosome inversion and enzyme polymorphisms. Both inversion frequencies and allozyme frequencies varied significantly over short distances. Neither differed significantly between morning and evening collections. Because several studies of the dispersal behavior of this species have been performed, we attempt to fit the observed data to mathematical models which relate dispersion to random genetic drift and to spatially varying selection coefficients. We conclude that the observations are due at least partly to behavioral differences among genotypes. i.e., habitat preferences. These results have implications for genetic load theory and models of selection in heterogeneous environments.


A comparative study of the esterase-5 locus in Drosophila pseudoobscura, D. persimilis and D. miranda. Electrophoretic phenotypes of the esterase-5 locus were examined in the sibling species D. pseudoobscura, D. persimilis and D. miranda. D. persimilis alleles were found to have uniformly higher charge on monomers than corresponding alleles of either D. pseudoobscura or D. miranda. Consequently, D. persimilis shares no alleles in common with either D. pseudoobscura or D. miranda, while the latter two species share a number of alleles. It was discovered that by increasing the concentration of acrylamide gel and increasing the length of migration, more allelic differences could be distinguished. Also more alleles were discovered by examining monomer mobility in addition to dimer mobility. In D. persimilis and D. miranda it was found that the previously known high frequency allelic classes broke down into several allelic classes. A test of goodness-of-fit to the infinite alleles model was done and a rough agreement with the model was found.


Further studies on gene polymorphism in the mainbody and geographically isolated populations of Drosophila pseudoobscura. We have examined polymorphism at 22 additional loci in the populations from the mainbody of Drosophila pseudoobscura and an isolated population from Bogotá, Columbia, which also shows partial reproductive isolation from mainbody populations. These studies extend our previous observations of reduced gene polymorphism and apparent lack of unique allele in the Bogotá population.


Multivariate analysis of gametic disequilibrium in the Yanomama. The gametic disequilibria between all possible pairs of loci were examined for a set of eight codominant loci in each of fifty Yanomama villages, using a multivariate correlation analysis which reduces the results to a single measure of departure from multiple-locus-gametic equilibrium. Thirty-two of the fifty villages departed significantly from multiple-locus gametic equilibrium. The largest contributions to the departure from multiple-locus equilibrium were due to the disequilibria between MN and Ss and between Rh(Cc) and Rh(Ee), indicating the effects of tight linkage. After removing the effects of these obvious sources of disequilibrium, sixteen of the fifty villages still remained significantly out of equilibrium. The disequilibrium between any particular pair of loci was highly erratic from village to village, and (with the exception of the MN-Ss and Cc-Ee disequilibria) averaged out very close to zero overall, suggesting a lack of systematic forces (epistatic selection). The departure from equilibrium in any one village is in excess of that expected from random sampling alone, and is attributed primarily to the fission-fusion mode of village formation operative in the Yanomama and the fact that a single village consists of a few extended lineages. Village allele frequencies are highly correlated across loci, and most of the non-independence is accounted for by large correlations in the average allelic frequencies of different loci for related villages. It is suggested that these correlations also are due to territorial expansion and population growth. For the tribe as a whole, all but the tightly linked markers of the MNSs and Rh complexes are approximately uncorrelated, and large departures from multiple-locus Hardy-Weinberg expectation are primarily due to substantial Wahlund variance within the tribe. There is no need to postulate a role for selection in these disequilibria.


The effect of a selected locus on linked neutral loci. The effects produced on linked neutral loci as a selected locus evolves towards its equilibrium value are considered. Significant effects on the neutral loci arise if the recombination fraction between the neutral and selected loci is smaller than the order of magnitude of the selective differences at the selected locus. The effect on gene frequencies at the neutral loci, that is, the hitchhiking effect, is determined, as well as the linkage disequilibrium generated by this hitchhiking effect. One of the more important findings is that significant disequilibrium can be generated between two neutral loci by the evolution of a linked selected locus. Consideration is given to the problem of determining how the effect of selection operating in natural populations can be detected, the question of the establishment of inversions in populations, and also to the nonequilibrium properties of populations.


Heterosis or neutrality?

Heterosis or neutrality? Various statistics have been proposed on an ad hoc basis to test whether alleles at a locus are selectively neutral. By considering population models in which selection operates, this paper shows that the population homozygosity is a powerful test statistic for testing departures from neutrality, in the direction of heterozygote advantage or disadvantage. The sample homozygosity plays a similar role when only sample data are available. Some numerical examples are included, showing the application of the test.--An analysis is made of the effect of heterosis on such quantities as the expected number of alleles in the population or sample, the effective number of alleles, the expected homozygosity, and on the population and sample allele frequency distributions generally.


How aging affects the ear.

How aging affects the ear. With aging, a different variety of ear diseases becomes more common. External ear disease is often a local reflection of generalized skin problems aggravated by retained water or local manipulation. Hearing loss may be the result of long-standing middle ear disease rather than aging. In this situation, the inconveniences and possible dangers of a chronically infected ear may be resolved with surgical intervention. Nasopharyngeal or lymphomatous disease must be suspected in any geriatric patient manifesting middle ear disease for the first time. Like presbyopia, presbycusis is a normal consequence of aging. It may be severe, but it does not lead to total deafness and equally involves both ears. Early discovery of the condition and institution of hearing rehabilitation methods will minimize the individual's communicative handicap and tendency to withdraw from society. Unilateral or asymmetric sensorineural hearing loss should be thoroughly evaluated for the purpose of identifying a curable and potentially life-threatening disease.


Ischaemic strictures of the small intestine in Nigeria. Eleven specimens of small intestinal strictures were seen at the Pathology Department of the University of Benin Teaching Hospital, Benin City, Nigeria, during a period of two and a half years. Eight of them were ischaemic in origin and the clinical and pathological features of these eight cases are described. In five of the cases, the ischaemia could be related to inguinal hernia, with herniorrhaphy a few weeks before surgery for stricture in four cases. The most important factor in making a clinical or pathological diagnosis of ischaemic stricture of the small intestine appears to be awareness of the condition. The importance is emphasised of studying the mesentery, with particular attention to lymph nodes and blood vessels, before making a final diagnosis on intestinal lesions.


Intestinal alkaline phosphatase in the diagnosis of liver disease. Alkaline phosphatase isoenzymes have been studied by acrylamide gel disc electrophoresis in 76 patients with liver disorders comprising 15 with an extrahepatic lesion, 53 with an intrahepatic lesion, and eight patients who had features of both intra- and extrahepatic disease. No intestinal band was found in the 15 cases of extrahepatic liver disease, in marked contrast to the patients with intrahepatic lesions in whom an intestinal band was found in 45% of cases. The intrahepatic group was heterogeneous, a high incidence of intestinal bands being found in patients with cirrhosis of the liver. It is concluded that where a raised serum alkaline phosphatase is found in a patient with jaundice, and a gut band is present on electrophoresis, the lesion is likely to be intrahepatic.


Activation and release of proteolytic kinin-forming enzymes from rat jejunal loops perfused with hyperosmolar glucose solutions. Loops of rat jejunum were perfused in vivo for one hour with de Jalon solutions of increasing glucose concentration. The esterolytic activity of the perfusate and of the extracted loop was measured using benzoyl arginine ethyl ester (BAEe) as substrate. The enzymes lactate dehydrogenase, isocitrate dehydrogenase, and acid phosphatase were measured in the perfusate to estimate the degree of cellular damage. There was a significant depletion of kallikrein from the intestine and a raised level in the perfusate during the hyperosmolar perfusions. No significant difference in the kallikrein levels was observed between the normal jejunum and the iso-osmolar perfused jejunum. Prolonged contact with hyperosmolar solutions caused some cellular damage but this effect appeared to be distinct from the release of kallikrein, which occurred very rapidly during the first 20 minutes. These results confirm that hyperosmolar intestinal contents result in the release of kinin-forming proteolytic enzymes into the circulation and suggest that this mechanism is involved in the syndrome of vasomotor dumping after gastric surgery.


Rectal potential difference and histology in Crohn's disease. The rectal potential difference (PD) was measured in 27 patients with Crohn's disease, and in 16 subjects without gastrointestinal disease to establish a normal range. Sigmoidoscopic assessment and rectal biopsy were performed in all patients with Crohn's disease, and the mean resting rectal PD was significantly reduced in patients with sigmoidoscopically active disease and in those with abnormalities of the superficial epithelium on rectal biopsy. Patients with diarrhoea had a significantly lower mean resting PD than those with normal bowel habit, suggesting that an abnormality of rectal sodium transport may be contributing to the diarrhoea in these patients. The response of rectal PD to mineralocorticoid stimulation with oral fludrocortisone was measured in 13 patients. The PD failed to rise only with patients with sigmoidoscopically active disease, and the test proved to be a less sensitive indication of minor mucosal abnormalities than sigmoidoscopy of biopsy.


Symptomatic significance of gastric mucosal changes after surgery for peptic ulcer. Eighty-four patients who had undergone different types of operation for duodenal ulcer have been studied by endoscopy and gastric biopsy. Half suffered from dyspepsia and vomiting but the other half had no symptoms and acted as controls. Endoscopic and histological abnormalities were found in both groups of patients. However, certain findings occurred more commonly in those with symptoms; severe and extensive hyperaemia, bile staining of the gastric mucus, and bile reflux seen on endoscopy were all significantly more common in those with symptoms than in those without. Active gastritis in the proximal stomach was also more common in those with symptoms. Gastritis of the stoma and antrum was found in 89% of all patients; as it was unconnected with symptoms it can be regarded as a "normal" finding. The incidences of contact bleeding, erosions, and oedema were not significantly different in the two groups.


A search for volatile nitrosamines in East African spirit. Spirits from areas of high and low incidence of cancer of the oesophagus were examined for volatile nitrosamines using a chemiluminescent detector. No nitrosamines were found, the detection limit being 0.001 microng/ml.


Effect of atropine and proximal gastric vagotomy on the acid response to fundic distension in man. In four healthy subjects and in 12 patients with duodenal ulcer (DU), graded balloon distension of the gastric fundus and body caused increments in acid output related to the distension volumes. The mean peak distension response amounted to about 50% of the mean peak acid output (PAOpg) evoked by intravenous infusion of pentagastrin in a dose of 300 microng/h, eliciting maximum observed secretory response. During distension with the largest balloon volume, 1-0 mg atropine injected intravenously significantly depressed the acid secretory rate, the median inhibition amounting to about 80%. In two patients with DU, 2-5 mg atropine completely abolished acid secretion during fundic distension. In nine subjects with DU, complete proximal gastric vagotomy profoundly depressed the secretory responses to graded fundic distension, eliminating the acid response to the smallest balloon volume used. A slight, but significant, response to the largest distension volume persisted after complete vagotomy. Incomplete proxomal gastric vagotomy was found to reduce only moderately the distension responses in five patients, and the peak acid response to fundic distension as related to PAOpg remained unchanged. In conclusion, distension of the gastric fundus and body in man stimulates acid secretion by means of an atropine-sensitive, presumably cholinergic, reflex mechanism and the findings after vagotomy are in agreement with the concept that this reflex mechanism is conveyed by both short intramural and long vagovagal pathways.


Alteration of rat bone marrow megakaryocytes following administration of cytosine arabinoside, daunomycin and hydroxyurea. The in vivo effects of three cytotoxic agents--cytosine arabinoside, daunomycin and hydroxyurea on rat bone marrow megakaryocytes were studied, specifically the relative count, the type percentage and the morphology. All three agents caused thrombo-cytopenia, a decrease in the number of megakaryocytes relative to the nucleated bone marrow cells, and a decrease in the percentage of megakaryoblasts, associated with an increase in the percentage of granular megakaryocytes. A decreased lobulation of the megakaryocytes was observed following the administration of cytosine arabinoside and of daunomycin. Thrombosthenin, examined immunologically, remained detectable in the bone marrow smears throughout the various stages of megakaryocyte alteration.


Comparable inhibition of aggregation of PRP of neonates and adults by aspirin. We have determined the minimal concentrations of 4 aggregating agents that were required to cause a 65-75% increase in light transmission without disaggregation during the 5-min recording period in PRP samples of 14 neonates and 10 adults. We found, for example, that this degree of aggregation could be elicited in adult PRP by a mean value of 2.09 micronM ADP, whereas similar aggregation of neonatal PRP required 5.16 micronM ADP. Based on these figures, we observed that adult PRP was about 2.5 times more sensitive to ADP, at least 10 times to epinephrine and 2.3 times to collagen than neonatal PRP. However, neonatal PRP was approximately 20% more sensitive to ristocetin than adult PRP. By using concentrations of aggregating agents that caused comparable aggregation of neonatal and adult PRP, we noted comparable inhibition of aggregation in these samples by aspirin. While neonatal PRP was less sensitive than adult PRP to physiological aggregating agents, there was no evidence that the former was more susceptible to in vitro aspirin inhibition.


Impaired fibrin formation in advanced cirrhosis. The process of fibrin formation was systematically in 25 patients with severe alcoholic cirrhosis. Results of functional tests are reported. A significant lengthening of the thrombin time was found which could not be completely attributed either to hypofibrinogenaemia or to an increase in physiological anticoagulants or to the presence of pathological antithrombins. A defect in fibrin polymerization was seen in the absence of significant levels of antipolymerizing agents. Indirect evidence pointed to an abnormal fibrinogen function. This was mainly suggested by the "polymerization curves" of mixtures of normal and pathological plasmas and the changes in physico-chemical properties of the clot (optical and elastic properties; tensile strength). Altered synthesis in hepatocytes may lead to an "acquired dysfibrinogenaemia" in the late stages of liver cirrhosis, although alteration of a normal fibrinogen molecule after secretion cannot be definitely excluded.


Cytoenzymatic investigations of parathyroid glands in acute anaphylactic shock of guinea pig. 50 guinea pigs were allergized three times in 3 days intervals by subcutaneous injection of 25% solution of egg-white in physiological saline in a dose of 0-1 ml/100 g of body weight. On the 21 day after the last injection the animals were exposed to aerosol of antigen of egg-white. 11 animals died in acute anaphylactic shock. The control group consisted of 12 guinea pigs which received subcutaneously a solution of physiological sodium chloride of the same dosis--0-1 ml/100 g of body weight and were also exposed to the allergen, together with the experimental group. The removed parathyroids together with the thyroid gland were studied with histologic and cytoenzymatic methods. The activity of alkaline and acid phosphomonoesterase, nonspecific AS-naphtol acetate esterase, succinic (SDH), lactic (LDH) and D-L-alfaglicerophosphate dehydrogenase (alpha-GPD) were tested. No morphological changes in the parathyroids of guinea pigs in anaphylactic shock were found. Instead a decrease of the enzymatic activity of dehydrogenases was found, what might be connected with the decrease of metabolic activity of the cells. The decrease of alkaline phosphatase activity in the endothelial cells of the capillaries was another finding. It is likely that in an acute anaphylactic shock in guinea pigs only functional changes develop which have not counterparts in histology visible under the light microscope.


Seasonal changes in the histoenzymatic distribution of acid and alkaline phosphatases activity in the B cells of the thoracic ganglion of fresh-water crab, Potamon magnum magnum (Pretzman). The present study deals with acid and alkaline phosphatases activity determination in B cells of the thoracie ganglion of Potamon magnum magnum. Intense alkaline and acid phosphatases activity is seen in the neurosecretory granules as well as in the neural sheath. Acid phosphatase activity unlike alkaline phosphatase distribution, is seen in form of positive stained spherules showing different pattern of distribution. Alkaline phosphatase activity is linked with the metabolic process. The significance of these results is discussed.


Some remarks on oxidation of aryl- and alkylamines in fibers of the central nervous system. A histochemcial study. Experiments were performed on brains of white Wistar rats, of both sexes, weighing 180-200g and 24 cats from various sources. Frontal sections were fixed in Backer's formalin and thereafter cut in a cryostat on 10 microns thick slices, dried on air. The slices were: a) either preincubated 1 hr in room temperature in solutions of the following amines: adrenaline, noradrenaline dopamine and L-dopa, para amino-diphenylamine and its derivatives, thereafter incubated in an incubation medium which conatained nitro-BT, phenazine-methosulfate (PMS), and glycine-buffer pH 9-5 b) or simultaneously incubated with the above mentioned standard medium. It has been found that all compounds tested, enhanced the reaction significantly in the fibers of the central nervous system except L-dopa. The last compound underwents very intensive autooxidation so that its influence on the reaction could not be taken into account. The observed reaction results allow us to suggest that the oxidation-reduction reaction in the nerve fibers might be of significance in the catabolism of biogenic amines.


Morphology and histochemistry of the "C" cells of guinea pig thyroid gland after treatment with STH preparation: Part II--young animals. Investigations were carried out on 32 male guinea pigs 2 to 3 months of age. The STH (produced by BIOMED, Warszawa, Poland) was administered intramuscularly every other day, in 7 injections of 20 Evans's units (E. U.) or 100 E. U./kg body weight each. Thyroid gland sections were stained with heamatoxylin and eosin and with the Azan method. The C cells were detected with the modified silver method of Grimelius and with the HCl-toluidine blue and HCl-lead haemotoxylin techniques. Moreover, reactions were performed for succinate and alpha-glycerophosphate dehydrogenases and also for non-specific esterases and non-specific acetylcholinesterase. STH evoked proliferation of the C cells, changed their morphology and activity pattern of the enzymes present therein, probably testifying to an enhanced secretory activity of these cells.


Chronic tellurium intoxication in rats.

Chronic tellurium intoxication in rats. (1) Accumulation of neuronal lipofuscin was clearly demonstrated in the chronic tellurium intoxication in young rats with histological, fluorescent and electron-microscopical methods; (2) The needle-shaped crystal in the neuronal lysosomes were demostrated to contain the tellurium with electron dispersive spectrophotometry analysis. (3) The vacuolation of the cytoplasm of Schwann cells was the initial pathological change noted in the tellurium peripheral neuropathy.


Effect of neonatal thyroidectomy on nucleic acids and protein contents of the developing rat brain. (1) Thyroidectomy at birth caused a temporal reduction of the DNA content only in the cerebellum during the periods from 7 to 21 days after birth, but not in the cerebrum and brain stem. (2) The ratio of RNA to DNA in cerebrum from the thyroidectomized rats was underwent a marked decrease from 14 to 56 days as compared with those of the normal controls. On the other hand, the effect of thyroid deficiency on the ratios of cerebellum and brain stem as a whole was very small. (3) The ratios of protein to DNA generally declined in the three brain regions during the periods from 14 to 56 days as a result of throid deprivation.


Some methodological considerations for the clinical evaluation of neuroleptics--comparative effects of clozapine and haloperidol on schizophrenics. For the purpose of evaluating objectively the characteristics of clinical effects of clozapine and haloperidol, a double-blind comparative trial was conducted on 91 schizophrenic in-patients. The changes of symptoms were assessed by means of several psychiatric and behavioral rating scales. The results were analyzed by means of nonparametric statistical methods. Furthermore, application of multivariate analysis was considered. After 12 weeks of treatment, though no significant difference in general improvement rate was noted between the two groups, a marked different spectrum of clinical effects was observed according to the rating scales. Clozapine is superior in anti-delusional, contact-promoting and sedative anxiolytic effect, while haloperidol is superior in anti-autistic effect. Among the side-effects, extrapyramidal symptoms appeared significatly more severe in the haloperidol group. The frequency of appearance of fever, was significantly greater in the clozapine group than the other. The four dropout cases of the clozapine group were all caused by fever. Through this clinical trial, clinical availability and validity of various statistical analytical methods were reconsidered.


Monoamine oxidase activity in blood platelets from manic and depressed patients. To evaluate the possible abnormality in MAO activity in affective disorders, blood platelet samples were obtained from 80 patients with mania and depression. Blood-platelet MAO activity was measured by a newly developed assay procedures using serotonin as substrate. MAO activities in 121 normal adult subjects were in a range of 2.49-12.05 nM/mg protein/hour, with the mean values of 4.91 +/- 1.72 (+/-S.D.) for men and 6.88 +/- 1.99 for women. (p less than 0.001) MAO activities in the manic and depressed patients were in a range of 0.65-13.40 nM/mg protein/hour, and both manic and depressed patients showed the mean value very familiar to that in the normal subjects. Bipolar depressed patients did not exhibited lower MAO activity in the blood platelets than other clinical subtypes of depressive illness, including unipolar, involutional, neurotic and chronic characterological, and first-episode depression. No significant differences were established between these five subcategories of depression, while significant higher values were evident in female than male patients (p less than 0.001). No correlation was found between the MAO activity and serotonin levels in the blood platelets either in the normal subjects or in the depressed patients.


[Religious experiences in schizophrenics]. Two cases of the schizophrenia are reported with phenomenological discussion of their religious experiences of Christian nature that appeared in the course of the illness. These experiences are so similar to the conversion and continue in the subsequent spiritual life of these patients and exert influences deeply upon the healing process of the illness. Their experiences of Christian nature didn't appear suddenly, but arose as consequence of a concentration of conflicts that had been accumulated up to that time similar to the phenomena of the conversion. The problem of the insight into the illness was also refered; the attitude toward the illness changed after the religious experiences into an "affirmative attitude with positive acceptance of one's own illness.".


Dissociation of sleep stages between the two hemispheres in a case with unilateral thalamic tumor. A case with an astrocytoma in the right basal ganglia, suspected of having originated from the posterior ventro-lateral part of the thalamus, without any clinical findings indicating severe internal hydrocephalus and cortical damaged, showed dissociation of sleep stages between the two hemispheres, i.e., the affected side always fell earlier into deeper stages of sleep and was more difficult to arouse by sonic stimulations than the other side. It is assumed that this bilateral dissociation with ipsilateral deactivation is due to the severe unilateral reduction of EEG activating influences from the brain stem and a possible functional damage to the interthalamic commissures. This finding can be explained sufficiently by recent theories based on experimental results in animals. The clinical value of this findings is also discussed in this paper.


Serum creatine phosphokinase activity in newly admitted chronic alcoholics. Serum CPK activity was measured for a total of 33 cases of chronic alcoholics who were admitted to the mental hospital from April, 1975 to January, 1976. The result was examined in relation to the manifestation of the psychotic symptoms in the patients: (1) Twenty six (78.8%) out of 33 cases showed increased serum CPK activity within 48 hours of admission. (2) In most cases that showed abnormal CPK activity, CPK value was the highest at the moment of admission, and then began to fall rapidly, and after one or two weeks settled to the normal CPK level. (3) There was a positive correlation between abnormal CPK activity and the manifestation of the psychotic symptoms in the month before and after entering hospital. In this cases of those having more than 101 IU in serum CPK value, the rate of presenting the psychotic symptoms in a month before or after admission was 90.5% and 71.4%, respectively. The author has given here a report on the above-mentioned results and made some considerations as to pathogenesis of abnormal CPK activity in chronic alcoholism.


Threats to the president revisited.

Threats to the president revisited. Ten prisoners charged with "threatening the President of the United States" were evaluated in an effort to seek out psychiatric and sociological factors involved in this offence. Comparisons were made with known presidential assassins. A history of abandonment as a child, single or divorced state, and a diagnosis of paranoid schizophrenia were prominent in both the study group and the group of know assassins. Additionally, the apparent psychological need behind both the threats and the actual assassinations appeared remarkably similar in both groups. The primary differentiating variable related to lethality was "opportunity and happenstance". It is proposed that those threatening the President by letter are at high risk for carrying out their threat if intervention does not take place.


The detection, identification and measurement of indole, tryptamine and 2-phenethylamine in putrefying human tissue. Indole, tryptamine and 2-phenethylamine are putrefactive products which may be found in decaying human tissue. They may be identified by the data given found in decaying human tissue. They may be identified by the data given for infrared and ultraviolet spectrometry, fluorometry, thin layer and gas chromatography and mass spectrometry. Quantitative studies may be made using the gas chromatography method described. The rate of formation is affected by temperature and preservatives and may be prevented if necessary by the use of sodium fluoride. No relationship between the production of these materials (and alcohol) and time since the post-mortem examination could be established. The post-mortem examinations took place within 24 hours of death.


[Communicating hydrocephalus. Clinical aspects, diagnosis, pathogenesis]. A description of the clinical symptoms of the communicating hydrocephalus (normal-pressure hydrocephalus = NPH) is given: progressive psycho-organic alterations, ataxia, tetraspastic signs, urinary incontinence, without increased intracranial pressure. Diagnosis can be confirmed by use of pneumencephalography, isotope-cisternography and tomography of the brain by use of a water-solubile contrast fluid. Skull radiographs. EEG, testing of liquor and psychological examinations are of less diagnostic value. The illness is the result of a disturbance of liquor resorption and circulation. In this context there is to differentiate between cases of known (Hydrocephalus communicans obstructivus = HCO) and unknown etiology (Hydrocephalus communicans non obstructivus = HCNO). The group of cases with unknown etiology represents the central part of cases of normal-pressure hydrocephalus (NPH). The prognosis after a ventricular shunt-procedure is here worse than in the group of cases with known etiology. For differential diagnosis presenil dementia, cerebrovascular insufficiency, intracranial tumors and reactive and psychotic depressions are to be considered.


A suicide by thiopentone injection.

A suicide by thiopentone injection. Post-mortem tissues from a thiopentone suicide were analysed by ultraviolet spectrometry and gas chromatography. The thiopentone concentrations found (0.6 mg/100 ml of blood and 2 6 mg/100 g of tissue) are consistent with those reported for 'anaesthetic' deaths where only thiopentone and other anaesthetic agents were present. The gas chromatographic method gave more accurate result with the tissues.


Family murder followed by suicide.

Family murder followed by suicide. Four examples of family murder followed by suicide are presented with relevant clinical data from the coroners' reports. In retrospect it would appear that three of the offenders were suffering from severe depression, and the fourth showed features of morbid jealousy. In each case there were factors suggestive of mental illness apparent before the tragedy. This is consistent with recent studies of murder followed by suicide and of suicide alone, and raises the possibility that psychiatric intervention may have altered the course of events. Though such tragedies may never be totally eliminated it is considered that close co-operation between coroner, forensic pathologist and psychiatrist may promote greater professional understanding of these tragedies, and provide the impetus for the detection and treatment of potentially remediable psychiatric illness.


Ethnic/racial misidentification in death: a problem which may distort suicide statistics. Since the majority of suicide studies are ex post facto studies of demographic data collected by pathologists anc coroner's investigators, the role of the forensic scientist in determining the accuracy of statistical analyses of death is extremely important. This paper discusses how two salient features of a decedent, surname and residence location, can be misleading in determining the ethnic/racial classification of the decreased. Because many Southern California Indians have Spanish Surnames and most do not reside on an Indian reservation it is shown that the suicide statistics may represent an over-estimation of actual Mexican-American suicidal deaths while simultaneously representing an under-estimation of the suicides among American Indians of the region.


The effect of ethanol on the ability of guinea-pigs to survive severe cold. Some parameters related to withstanding severe cold (-20 degrees C) after administration of increasing doses of ethanol were investigated using guinea-pigs. The animals had been reared either at 22-23 degrees C or at 17-18 degrees C. They received ethanol in doses of 0.8 g, 1.2 g, 1.4 g or 1.6 g per kg of body weight. The fall of rectal temperature and its level at death were registered. The survival time, ethanol concentration in the blood and the brain, serum glucose and serum FFA at death were determined. In the animals reared at 22-23 degrees C the ethanol doses of 1.2-1.6 g/kg caused a significant shortening of the survival time and accelerated the fall of the rectal temperature. In addition the rectal temperature at death after ethanol was lower than in the controls. In the animals reared at 17-18 degrees C the ethanol doses used did not have any significant effect on the survival time and the rectal temperature. In both groups, ethanol concentration in the brain was lower (about 20-40%) than in the blood, the difference being greater in the group reared at 22-23 degrees C. Ethanol had no effect on the glucose concentrations. Serum FFA levels were slightly lower in animals reared at 22-23 degrees C than in those grown in the cooler temperature. It became evident that ethanol has a dose dependent deleterious effect on the thermoregulation of animals reared in warm (22-23 degrees C). The effect was seen at and above the dose of 1.2 g/kg. The results indicate further even a slight acclimation to cold was able to abolish the effect of these rather great doses of ethanol in severe cold exposure.


[Anesthesia in pacemaker implantation. Experiences in 935 cases of anesthesia for the implantation or revision of a cardiac pacemaker]. Observations during 935 anesthesias for implantation or revision of permanent pacemakers are presented. Using different methods of anesthesia we found the light halothane anesthesia introduced by inhalation to be best, provided that only atropine was used for premedication. Applying this method we saw asystolies or ventricular fibrillation in 3% of all cases--3 patients (i.e. 0.4%) died in tabula. Tachycardia (2.4%) occuring mostly during the introduction period were successfully treated by verapamil or practolol. Hypotension (5.4%) mostly took place in the course of anesthesia after implantation of the pacemaker. This depression may be due to a normalisation of the enhanced stroke volume whedication with pethidine or induction with propanidid was followed by comparatively more complications such as exitus letalis (2% resp. 1.5%), cardiac arrest (6.5% resp. 9%) and hypotension (24% resp. 10.5%). Regional anesthesia did not bring specific advantages. The good experiences with soft halothane anesthesia for implantations or revisions of pacemakers include 125 high risk patients (ASA classification IV to VII).


[Diagnosis of the bronchitic syndrome in the aged]. The cumulation of exogenic factors on the basis of an endogenic disposition and the addition of physiologic aging processes cause an increase of the "bronchitic syndrome" in old age. Heart insufficiency, tuberculosis, lung embolism and bronchial carcinoma are the important differential diagnostic aspects in these patients. The structural and functional changes of the lung in old people and the polypathy, resp. multimorbidity of the whole organism cause the complications and disadvantageous interferences. The prognostic important disturbances of the ventilation mechanics are early recognizable with new diagnostic tools, particularly with the whole body plethysmography.