[Progress in diagnosis and treatment of pregnancies with low birthweight infants (author's transl)]. In order to prove the progress in diagnosis and treatment of pregnancies with low birthweight we performed a retrospective computer-analysis of three groups of patients including newborns below 2750 g delivered dumping the last 10 years. The first group contains the years 1967/68; the deliveries of low birthweight infants were monitored without cardiotocogram. The second group of patients from the years 1971/72 was monitored continuously during delivery by cardiotocogram. The endocrinologic diagnostic methods for detection of a possible placental insufficiency in low weight fetus were applied regularly (DHEA-S-loading test, oestriol, HPL). The treatment of premature newborns with respiratory distress syndrome was facilitated by CPAP. A thorough ultrasound diagnosis was available additionally for the third group of patients. Long term treatment with Partusisten was applied in cases of premature labour in this group and betamethasone-therapy was used for accelleration of fetal lung maturation. With a nearly constant number of preterm eutrophic newborns, preterm infants with retarded growth and mature infants with retarded growth over a period of ten years the unpurified mortality rate decreased from 14.3% to 6.7% when the pregnancies and deliveries had intensive (obstetrical medical) care. With the help of Shirodkar procedure and tocolytic treatment the birthweight could be shifted significantly into the favourable group over 2000 g. The prenatal prophylactical treatment of the respiratory distress syndrome with beta-methasone and the postnatal CPAP-therapy decrease the mortality rate caused by respiratory deficiency from 13.7% to 6.4%. The preventive caesarean section in cases of low birthweight infants with abnormal positions in utero helped to reduce the mortality rate from 21% to 10.6% in these cases. The accuracy of prenatal diagnosis of intrauterine retarded fetal growth by hormone analysis and ultrasonic measurement of the fetus was improved from 24% to 66%.


[The fluoroscopic detection of micro-calcifications of the breast during the operation in the excisional biopsy material (author's transl)]. In 101 excisional biopsies of the breast the biopsy material was examined fluoroscopically in the operating room for micro-calcifications with a specially constructed X-ray machine. This method of operation and control has the advantage of shortening the operative time and avoiding additional radiation to the breast. The surgeon becomes independent of a radiologist for control. Very accurate excisional biopsies of clinical obscure lesions in the breast become possible.


[Determination of microelements in human placenta II. Commun.: Spectrophotometric determination of zinc content in human placenta (author's transl)]. The zinc content of human placenta is determinaed by means of an improved combined dithizone-zincon-method. The results obtained are given as follows: 11.13 +/- 0.62 ppm in the fresh and 64.98 +/- 3.34 ppm in the dried material.


[Compression of the spinal cord secondary to an intradural metastasis from a primary carcinoma of the breast (author's transl)]. The intradural spinal spread from operated primary carcinomas of the breast is discussed considering our own case and the literature. The identical localization of the intradural spinal metastases at the junction of the cervical to the thoracic spine in all three known cases is striking.


[Description of a new modified clamp for the parametrium in abdominal hysterectomies (author's transl)]. A new modified clamp for the parametrium is presented which facilitates abdominal hysterectomy in large myomatous uteri. The curbed clamp has a blunt angle of 160 degrees to its handle and permits clamping of the parametrium parallel to the longitudinal axis of the cervix. The clamp appears to be an enrichment of the available instruments for abdominal hysterectomies.


[Clinical experimental studies in the treatment of ovarian dysfunction with bromo-ergocryptin (pravidel) (author's transl)]. Among 62 patients with galactorrhoea a corpus luteum deficiency or anovulatory cycles were found in 35 cases by serum progesterone determination, endometrial biopsy or basal body temperature records. 27 patients had a hyperpro-lactenemic amenorrhoea-galactorrhoea syndrome. During treatment with 2.5-5 mg. of Pravidel daily the basal body temperature was recorded, the concentrations of serum FSH, LH, Prolactin and progesterone were determined by radioimmunoassay. Other possible reasons for infertility were investigated. 10 of the 19 patients with normal serum prolactins in the group with deficient corpus luteum or anovulation became pregnant after a short duration of treatment, whereas only 2 of the 16 patients with hyperprolactenemia became pregnant. Among 27 patients with secondary amenorrhoea 11 became pregnant. All these patients had increased serum prolactins. During treatment with Pravidel all patients showed a significant increase of FSH and LH concentrations and a decrease of the prolactin concentrations. The outcome of the pregnancy of the 58 patients who became pregnant during treatment with Pravidel was also reported. 14 of the 58 pregnancies occured following additional treatment with Dyneric or HMG/HCG. Up to now there were 18 term deliveries following uneventful pregnancies. There were no fetal anomalies. The abortion rate was not higher than in the general population. All results show that euprolactinemia is not alone characterized by normal prolactin concentration. The clinical signs and symptoms of galactorrhoea without increase of prolactin over 20 ng/ml. in conjunction with ovarian dysfunction must be classified as dysprolactinemia.


[A subglutaeal abscess as a possible result of pudendal anaesthesia (author's transl)]. Described is the subglutaeal abscess of a 17-year old primigravida that may have been the result of pudendal anaesthesia. This has to be looked upon as an extremely rare and unavoidable complication of obstetric regional anaesthesia. On the basis of known cases of subglutaeal abscess, it cannot be concluded that pudendal anaesthesia should be relinquished.


[Development of a method of screening for hemoglobin S for the purpose of genetic consultation in Cuba. Results of an analysis of 24,000 blood samples]. Electrophoretic screening system is worked out, which combines a high resolving power in polyacrylamide gel and a principle of simultaneous treatment of a large number of examples. 24,000 blood examples from inhabitants of Havana province (Cuba) are analysed in order to check the efficiency of the method described, to find the hemoglobin S frequency and to use these results in further genetic consulting. The frequency of hemoglobin S carriers is found to be 3.0%, that of hemoglobin C--0.7%. 15 rare hemoglobin variants are detected, 9 variants of alpha-chain and 3 variants of beta-chain are detected. One case was a result of hemoglobin S and a variant of alpha-chain interaction. Frequencies of S, C and A alleles were 0.016, 0.0038 and 0.98 respectively.


[Sister chromatid exchanges in human lymphocytes detected by using 5-bromdeoxyuridine]. Sister chromatid exchanges (SCE) were studied in chromosomes of peripheral blood lymphocytes taken from 19 normal individuals of both sexes and cultured in the presence of 5-bromodeoxyuridine (BUdR). BUdR was added to the culture in final concentration of 15 or 30 microgram/ml for the last 28 hours of cultivation. The chromosome preparations were stained with the fluorescent dye Hoechst-33258, followed by Giemsa staining. At BUdR concentration of 15 microgram/ml the mean number of SCE was significantly less (8.9 per metaphase), that at the concentration of 30 microgram/ml (12.3 per metaphase). The incidence of SCE among 19 individuals varied from 6.5 to 13.7. The mean numbers of SCE in five individuals were significantly different from the mean number calculated for the whole group of 19 subjects. There were no differences between the sexes in the incidence of SCE. The distribution of SCE between chromosomes was found to be proportional to the chromosome length and to the amount of DNA. However, the chromosomes of groups E, F and G were highly significantly under-represented in the number of exchanges.


[Effective use of rapid tests to evaluate the mutagenicity of environmental chemicals]. Efficiency of short-term tests for mutagenicity with the use of various Salmonella strains is conditioned by a high sensitivity and a prompt answer. Besides, these tests are valuable because they permit to evaluate quickly a probable cancerogenic activity of the tested chemicals, as there is a high degree of correlation between the mutagenic and cancerogenic response for a great number of chemicals. However, whatever results are obtained with the use of short-term tests, questions arise about the relative force of a mutagenic activity, the spectrum of induced genetic damage, relative frequency of each type of damages, the danger of such a damage for an individual, probability of a successful transmission of each type of damage to the following generation. And the main problem which investigators are facing in this field is the prognostic value of information on the mutagenic activity which is obtained from these tests for the evaluation of risk from the effects of chemicals on human population. The answers to these questions may be got only by means of tests on eukaryotes, as they might give more complete data concerning both quantitative and qualitative effects.


[Photosensitizing effect of 8-methoxypsoralen on bacteriophage cd]. Mutagenesis in extracellular phage sd by 8-metoxypsoralen (8-MOP) and longwave (lambda greater than 310 nm) UV-irradiation has been established. The kinetics of lethal and mutagenic effects of 8-MOP+light was studied. The efficiency of mutagenesis on the first linear part of mutation curve was 0.3% per the lethal hit which is 2 times lower than that of shortwave (lambda=254 nm) UV-irradiation. The maximum yield of mutants makes up 1%, after which the mutation curve is maintained. It has been established that the main (may be the only) contribution into mutagenesis is made by monoadducts, whereas the lethal effect is conditioned by diadducts (cross-links). The comparison of the efficiency of mutagenic effects of 8-MOP+light with mutagenic effects of other kinds of irradiations was carried out. The possibility of repair of damaged 8-MOP+light phage sd DNA by transfection of Escherichia coli C (uvr+) and Cs (uvr-) lysozyme spheroplasts has been established. The repair mechanism of photodamage in intact phage sd induced with 8-MOP+light was also investigated using the method of two-step irradiation. It has been shown that 65% of photodamages are repaired in E. coli SK cells in the M9 medium, i. e. under cellular metabolism. The recovery of phage sd is completely inhibited in phosphate buffer. Unlike chloramphenicol (150 microgram/ml), 1% caffeine blocks the phage recovery only by 30%. The participation of phage sd determining enzymes in its intracellular recovery from 8-MOP+light damages is assumed.


Guidelines for diagnosing and treating urinary tract infections. Urinary tract infections are problems in both men and women in the geriatric age group, although causative factors in each sex differ widely. Diagnostic evaluation is directed at determining obstructive disease in men and underlying anatomic abnormalities in both men and women. Bacteriologic diagnosis is important, and localization studies are often helpful. Antibiotic therapy is guided by the usual standards, with special awareness of the greater incidence of chronic or degenerative disease in older patients.


Intradaily variation of the human ulnar length and short term growth--a longitudinal study in eleven boys. In order to detect the intradaily variation of the clinical ulnar length in eleven boys the right ulnar length was determined using a condylograph at seven set times of each day during a study period of three weeks. The mean standard error of the determinations amounted 0.09 mm. In 86% of the days concerned the ulnar length changed significantly (one way analysis of variance p less than 0.05). As far as the whole group concerned the ulnar length decreased significantly during the time interval from 8.00 h to 12.00 h (Friedman's related samples test, p less than 0.01). The decrement amounted 0.4 mm. During the rest of the day the changes in the ulnar length were not significant. A consistent decrement of the ulnar length during the day in combination with total growth of 0.99 mm during the three week study period suggested that growth in length of the human ulna occurs during the night.


The linear regression of body weight and age in intact, ovariecotomised, and estrogen treated rats: some applications and implications. Many variables, including rat body weight (BWt), are sequentially measured in individuals yet the information obtained is often poorly utilised. Many advantages result if a linear relationship is established, on the original or transformed scales, between the variable and time. For individual rats log BWt, which is normally distributed, is linearly related to the reciprocal of age. Slopes (rates of BWt gain) and constants (ultimate BWts) then serve as data. Linearity extended from 4 weeks onwards in ovariectomised (OvX) and intact rats, implying that puberty does not affect BWt and that BWt increases before puberty following pre-pubertal OvX; the ovary inhibiting growth before puberty. For individual rats weaning BWt was correlated with rate of BWt gain but not with ultimate BWt, indicating postweaning compensatory growth which continues to maturity. Pre-treatment and post-treatment measurements were made on individuals, allowing within-animal comparisons and regression. Thus the BWt response to OvX or estrogen treatment depended on the pre-treatment rate of BWt gain and ultimate BWt, implying that the BWt response entails a form of compensatory growth. OvX at three ages (day 2, week 4, and week 7) produced different rates of BWt gain but similar ultimate BWts. These results support the hypothesis that ultimate BWt is predetermined, but can be modified by treatment.


Growth curve changes associated with long-term selection for body weight in Japanese quail. Four quail lines were utilized to investigate growth patterns in quail. Three of these lines (P, T and S) had previously undergone long-term selection for high 4-week body weight, while line C was maintained as a nonselected control. Quail progeny from generation 37 and 38 breeders were fed diets containing 28% and 20% protein. Within each trial, the diet/line treatments were replicated 3 times with 12 quail per subclass. Body weight measurements suggested that the growth of all lines was best approximated by the logistic growth curve model. When fed a 28% protein diet the age at maximum growth (point of inflection) of selected lines was 4 to 6 days earlier than the corresponding age of controls. Similar rates of gain after 4 weeks of age between selected and control lines suggested that mechanisms influenced by selection for 4-week body weight in quail operate only during the period prior to the age at selection with little or no residual effect.


The effects of lead nitrate on the central nervous system of the chick embryo I. Observations of light and electron microscopy. The effects of lead on the developing central nervous system were studied for the first time by light and electron microscopy in the chick embryo after injecting lead nitrate into the air space of the egg at 10 days of incubation. Lead-treated embryos showed curled toes as a sign of neurological injury, weighed less and were smaller in size than controls of the same incubation age. Light microscope studies of brain and spinal cord revealed the presence of numerous accumulations of blood cells which appeared to accompany the extensive injury found in those tissues. Ultrastructure of spinal cord suggests that neuroglial astrocytes in the vicinity of blood vessels are altered in leaded embryos. Prominent morphological changes were extensive vacuolation and disorganization of the endoplasmic reticulum of the cell. The evidence indicates that the spinal cord like the developing brain is subject to the biological effects of lead. The results encourage further experimentation using the chick embryo for studies of lead neuropathies.


Marginal congenital malnutrition on skeletal muscle composition. Experiments were performed on well fed and marginally malnourished rats from a black and white hooded strain bred for 11 generations. The colony on high protein diet was fed a well balanced cubed diet of net dietary protein energy ratio 10% (Diet F1). The other colony was fed a cubed diet of net dietary protein energy ratio 6.8% (Diet F2). This latter diet is inadequate to maintain normal growth of young rats but adequate for the maintenance of adult life. The animals were killed at various ages from weaning until they aged 330 days. At various time points, the gastrocnemius muscle was excised quantitatively and analysed for RNA. Analyses were also made for DNA and protein and the results were discussed in terms of RNA/DNA, protein/DNA and RNA/protein ratios. During normal growth and development, there was pronounced reduction in the RNA/protein ratio in both colonies similar to reported developmental changes on the rate of protein synthesis. The cause of failure of the "catch up" growth of the marginally malnourished rats was not reduction in RNA concentration but reduction in nuclear proliferation and protein accumulation leading to hyperplastic and hypertrophic growth failures at most stages.


Regulation of skeletal muscle development by the central nervous system in the fetal pig. The effect of upper motor neuron regulation on skeletal muscle development was studied in the fetal pig. A region of the spinal cord at the level of the upper cervical vertebrae was destroyed by cauterization at 45 days of gestation in four pig fetuses. Five fetuses with intact spinal cords served as controls. Innervation and enzyme activities in the longissimus muscle, the ultrastructure and quantitation of satellite cells in the sartorius muscle, and plasma composition were evaluated at 110 days of gestation. The terminal innervation ratios were similar (P greater than 0.05) for muscles from control and cauterized fetuses. Endplate morphology was also similar. Therefore, innervation of newly formed primary fibers is not controlled by upper motor neurons after 45 days of gestation. Mean values for body weight, percentage of muscle dry weight, percentage of myofibers with myonuclei and plasma levels of protein, glucose, triglycerides, lactate, and creatine phosphokinase activity were similar (P greater than 0.05) between the two groups of fetuses. All but one muscle fiber examined was of the secondary fiber type. These observations suggest that the physiological maturity of the muscle was not appreciably altered even though glucose-6-phosphate dehydrogenase activity was higher (P greater than 0.05) and total phosphorylase activity was lower (P greater than 0.05) in the spinal cauterized fetuses than in the control group. The percentage of satellite cells was lower when based on the number of myofibers observed (P greater than 0.005) or on the number of nuclei contained within the basal lamina (P greater than 0.001) in the muscle of the spinal cauterized fetuses than in the control fetuses. The cytoplasm of satellite cells from the muscles of control fetuses was rich in organelles indicative of metabolic and mitotic activity whereas a paucity of such organelles was observed in the satellite cells of cauterized fetuses. Since the percentage of myofibers that had myonuclei was similar (P greater than 0.05) for the control and cauterized fetuses, it appeared that the myonuclear population was maintained by direct incorporation of the parent satellite cell.


Molar polymorphisms and body growth.

Molar polymorphisms and body growth. Body growth at adolescence was later in children of the serial experimental sample of the Burlington Growth Centre who had agenesis of third molars of 4-cusped mandibular permanent first molars. These groups of children tended to have later maximum increment of growth, later completion of the growth spurt, less adolescent prepeak gain and greater postpeak gain in height and weight than the children with four third molars and 5-cusped first molars. Growth of the boys differed significantly (P less than 0.05) according to absence or presence of third molars, whereas in girls it differed significantly (P less than 0.05) by the number of cusps of the mandibular first molars. In skeletal age, the children with the molar reductions were slightly advanced before adolescence, fell behind during prepeak adolescent growth, and caught up to the other children by the end of their growth spurt. Later maturation in association with dental reduction may be an evolutionary trend in man.


Body composition, in vitro lipid metabolism and skeletal muscle characteristics in fast-growing, lean and in slow-growing, obese pigs at equal age and weight. Eight slow-growing feral, obese (Ossabaw) pigs were sacrificed at 45 kg live weight and an average age of 170 days and were compared with a group of fast-growing, lean (Yorkshire) pigs fed the same ration and sacrificed at either 45 kg (average age 130 days) or at 170 days (average live weight 90 kg). Body composition and various carcass measurements, in vitro adipose tissue metabolism and muscle composition were measured. At equal weight, the obese pig had a greater percent body fat (40 vs. 23%) and backfat thickness (3.3 vs. 2.0 cm) than the lean. At equal age, the difference in percent body fat was not as great (40 vs. 31%) while backfat thickness was equal. Percent body protein was greater in the lean pigs at either equal weight or equal age. In vitro lipolysis, per 100 mg adipose tissue, was lower in obese pigs than in lean pigs at equal weight. However, obese tissue exhibited a greater lipolytic reaponse to DBcAMP stimulation than adipose tissue from lean pigs at equal weight; basal lipolysis per total fat mass was similar. At equal age, no differences in lipolysis between lean and obese pigs were observed. When compared at either equal age or equal weight, weight of semitendinosus muscle, and measurements of muscle RNA and DNA were greater in lean compared to obese pigs. RNA/DNA ratios were similar at equal weight and age whereas the protein/DNA ratio was lower in lean muscle compared to obese at equal weight. The decreased protein deposition in the obese, slow-growing pigs appeared due to fewer muscle nuclei rather than a decreased cellular capacity for protein synthesis.


Reabsorption of sodium in the proximal renal tubule in cirrhosis of the liver. Proximal tubular reabsorption was examined in patients with liver cirrhosis and ascites by a variety of indirect methods. Maximal diluting ability, urine flow rate, and free water clearance were reduced. During frusemide administration V/GFR was lower than in normal control subjects, indicating that proximal fractional reabsorption is enhanced in liver cirrhosis. This, by reducing Na delivery to the loop of Henle, impairs maximal urine osmolality. Mannitol, by reducing proximal reabsorption, restores availability of Na to the loop and urine concentrating ability during osmotic diuresis, whereas volume expansion with dextran was ineffective. This could be due to a persistent increase in renal vascular resistance preventing the rise in interstitial pressure responsible for driving fluid back into the proximal tubular lumen.


Long-term follow-up of chronic active hepatitis of moderate severity. A group of patients with only moderately active chronic hepatitis has been studied. The follow-up was long (mean 87 months). All patients except one were treated with prednisone and/or azathioprine. Of the hepatitis B virus positive patients two-thirds developed cirrhosis between the second and fifth year of evolution, while in the hepatitis B negative group this occurred in less than one-third. The transition to cirrhosis was clinically silent. The patients were all allowed to do their normal work except in the terminal stages of cirrhosis. Five patients died of causes related to the disease: three patients with cirrhosis and hepatocellular carcinoma, one with gallbladder carcinoma, and one from bleeding varices. The high incidence of tumour, especially liver-cell carcinoma, may be due to a cumulative effect of the presence of hepatitis B virus, cirrhotic transformation, and immuno-suppression. The other patients are currently in apparently good health.


Congenital hepatic fibrosis: the long-term prognosis. The long-term prognosis in congenital hepatic fibrosis has been assessed in 30 patients, 13 treated at Newcastle and 17 from other British centres. Twenty-four patients had been followed-up for more than five years from diagnosis. Shunt operations, performed in 18 patients, were successful in controlling haemorrhage with a low mortality (1/18), low incidence of recurrent haemorrhage (3/18) and portal-systemic encephalopathy (3/18) but with a higher incidence of postoperative jaundice (7/18). About a third of the survivors had some evidence of hepatic dysfunction but none had chronic portal systemic encephalopathy. Intelligence quotient was close to normal but educational achievement and job status were low. Serum albumin fell after shunt surgery and a few patients developed ascites: anaemia and hypersplenism however, were corrected by surgery. Blood ammonia is raised in survivors with congenital hepatic fibrosis and rises further after a normal meal; further observations are needed on cerebral function after several decades of survival.


Relationship between serum ferritin and total body iron stores in idiopathic haemochromatosis. The relationship between the serum ferritin concentration and total body iron stores was investigated in 41 patients with idiopathic haemochromatosis and 199 first or second degree relatives. Thirty-two relatives (16.1%) had increased iron stores and serum ferritin levels were increased in all but one of them. The false-positive rate in the relatives with normal iron stores was 1.8% compared with 10% for the serum iron concentration and 33% for the transferrin saturation. There was a significant correlation between the serum ferritin concentration and both the chelatable body iron and the hepatic iron concentration. We conclude that in the natural history of classical idiopathic haemochromatosis the serum ferritin concentration is usually raised when hepatic iron stores are increased and before there is architectural damage to the liver.


Advantages of treatment of ascites without sodium restriction and without complete removal of excess fluid. Two modifications of the standard method of treatment of ascites in chronic liver disease were investigated in three separate randomised trials involving a total of 201 patients. These modifications were (1) an unrestricted sodium intake and (2) limitation of diuresis to partial removal of ascites, to the point of relief of abdominal tension. Mean serum sodium fell significantly in all patient groups receiving the low sodium diet and did not fall in the groups given an unrestricted diet. Mean serum urea nitrogen rose significantly in the patient groups undergoing complete diuresis and did not change in the groups undergoing partial diuresis. Mean serum uric acid rose only in the groups undergoing complete diuresis. We concluded that the advantages of these two modifications of therapy of ascites were increased dietary palatability and decreased likelihood of hyponatraemia and of rise in serum urea nitrogen and uric acid. Disadvantages included dissatisfaction of patients over incomplete clearing of ascites, occasional difficulty in performing diagnostic studies because of prolonged ascites, and unsuitability of a high sodium intake in patients whose ascites is highly refractory to treatment.


Epithelial cell proliferation in diverse models of experimental cholelithiasis. Proliferation of the epithelial cells of the gall bladder during the initial stages of experimental cholelithiasis has been studied by autoradiography. Rabbits taking a diet with 1% dihydrocholesterol added showed a rise in labelling index from 1.5%-19% by three days. Mice taking a 1% cholesterol 0.5% cholic acid diet showed a similar rise from less than 1% to 15-21% at two and five days. Guinea-pigs receiving lincomycin showed a rise from less than 1% to 6% after 24 hours. These changes, which appear well before the appearance of gall stones, together with previous reports of enhanced mucous secretion during lithogenesis, make it clear that in these laboratory models of cholelithiasis the gall bladder is abnormal well before stones form.


Intracellular electrolyte depletion in patients with ileostomies. Fourteen apparently healthy patients with ileostomies were found to be depleted of total exchangeable sodium and potassium, but had normal serum electrolyte concentrations and normal extracellular fluid and total body water volumes. The low exchangeable sodium and potassiums were thus primarily due to depletion of the intracellular compartment. There was no evidence of renal or intestinal conservation of these ions and plasma aldosterone, renin activity, and prolactin concentrations were normal in most and only moderately raised in a few. This apparent lack of any hormonal compensatory change to the electrolyte depletion may be due to the normality of the extracellular fluid volume and electrolyte concentrations. These patients seem to have adapted to a stable but depleted intracellular sodium and potassium state.


Clinical and pathological study of asymptomatic HBsAg carriers in Chile. A clinical, biochemical, and pathological study was performed in 38 chronic HBsAg carriers. The study group is a part of 393 carriers found among 117 705 voluntary blood donors at the National Blood Bank, Hospital del Salvador, Santiago, Chile. None of the 38 carriers had a past history of illicit drug abuse, hepatitis, or work involving a high risk of hepatitis B virus infection. Ten individuals had a normal liver biopsy, 17 reactive non-specific hepatitis, one fatty changes, four chr onic persistent hepatitis, one aggressive hepatitis, two post-necrotic cirrhosis, and three alcoholic cirrhosis. There was not a close correlation between liver function test and liver histology. The most significant laboratory finding was the postivity of alpha fetoprotein in two cases. During the follow-up the two alpha fetoprotein patients presented a hepatocarcinoma 12 and 14 months after admission to the study.


Sialic acids of human large bowel mucosa: o-acylated variants in normal and malignant states. Five sialic acid variants have been demonstrated in normal, 'transitional', and tumour extracts of human large bowel mucosa by thin-layer chromatography. Two-dimensional thin-layer chromatography, with intermediate alkaline hydrolysis, confirmed that the variants were N-acetyl neuraminic acids with additional O-acylation. Cases studied so far show changes in the proportions of these variants in malignancy.


Quantitative comparison of the effects of cholecystokinin, secretin, and pentagastrin on gastrointestinal myoelectric activity in the conscious fasted dog. The effects on gastrointestinal myoelectric activity of infused pentagastrin, cholecystokinin (CCK), and secretin at physiological doses were studied in live dogs with implanted serosal electrodes during 56 six-hour studies. Pentagastrin dose-dependently increased gastric and duodenal slow-wave frequencies; secretin and CCK did not. Pentagastrin and CCK diminished the incidence of fasting migrating myoelectric complexes (MMCs), but MMCs were abolished only in the proximal small intestine. Pentagastrin infusion was not reflected in an increased number of spikes, whereas CCK induced a dose-dependent increase in jejunal spike activity. Secretin dose-dependently decreased duodenal and jejunal spike incidence without a marked effect on MMC incidence. Analysis of patterns of spike activity showed significant dose-dependent changes with all three peptides. The different effects of pentagastrin and CCK on spike activity in these studies may have been a consequence of pentagastrin-stimulated gastric acid secretion. None of the three peptides produced a pattern of myoelectric activity which closely resembled that seen on feeding; since, unlike food, all three peptides had little or no effect on the distal small intestine, it seems unlikely that combinations of these peptides are responsible for the change induced by food. The failure of these peptides to abolish fasting patterns in the distal intestine suggests a possible mechanism for some types of post-vagotomy dysfunction.


Alterations of the colonic flora and their effect on the hydrogen breath test. The hydrogen breath test was performed by ingestion of 20 g lactulose and analysis of end-expiratory air. Eighteen patients undergoing colonoscopy, 17 receiving antibiotics, 12 prepared for colon surgery, and 15 controls were examined. The test was repeated under control conditions in the treated patients. Eleven of 55 subjects failed to produce significant amounts of hydrogen under control conditions. This 20% proportion of non-hydrogen producers is much higher than that reported by other investigators. The hydrogen production was very markedly depressed after preparation for colonscopy and antibiotic therapy. The effect of neomycin and enemata as used in preparation for colon surgery was less marked. Hydrogen production by the colonic flora is thus subject to individual variations and may be affected by various therapeutic regimens. All these may cause false negative results when using the hydrogen breath test to evaluate carbohydrate absorption. The test should therefore not be performed for a considerable time after therapeutic manipulation of the colonic flora.


Role of neural influences in the release of gastrin, glucagon, and secretin during hypoglycaemia in man. Both vagal and sympathetic innervation been have described as influencing hormone release from the gastrointestinal tract and pancreas. The role of neural influences on the release of gastrin, glucagon, and secretin has been studied using the potent autonomic nerve stimulus of hypoglycaemia. Healthy subjects were each rendered hypoglycaemic by insulin 0.2 units/kg on three occasions: after atropine 20 microgram/kg: after propranolol 160 mg orally, and without prior drug administration. Adequate beta-blockade was confirmed by observation of the pusle rate response to a standard exercise at the end of the experiment, and by measurements of plasma propranolol levels. Hypoglycaemia failed to produce a rise in plasma gastrin under either propranolol or control conditions but a significant rise was noted with prior atropinisation. The glucagon response to hypoglycaemia, when measured with either the C- or N-terminal reactive antibodies, was found not to be influenced to any significant extent by either beta-blockade or atropinisation. No alteration in plasma secretin levels was noted during hypoglycaemia. It therefore appears that neural influences are relatively unimportant in the release of gastrin, glucagon, and secretin in man.


Changes in the electrolyte content of leucocytes at different clinical stages of cirrhosis. The intracellular sodium, potassium, and water content of isolated leucocytes was estimated in 47 patients with cirrhosis. The values for sodium showed a wide scatter. In patients without ascites the mean value was significantly increased but in those accumulating ascites it was normal, although often reduced in individual subjects. Reduced values were found in patients with hyponatraemia associated with end-stage cirrhosis and diuretic treatment. Changes in leucocyte water content closely followed those in sodium content. Leucocyte potassium content was normal except in patients accumulating ascites in whom it was significantly reduced, indicating whole body depletion, and this could be corrected by administration of spironolactone.


Twenty-four hour gastric acidity after vagotomy. Twenty-four hour intragastric pH during normal daily activity has been studied by nasogastric intubation and aspiration of gastric samples in seven patients four years after vagotomy (four truncal, three selective). Two of these patients also had pre- and early postoperative studies. Mean pH was inversely correlated with basal, insulin- and pentagastrin-stimulated acid outputs. However, one of four patients after truncal vagotomy with drainage, and two of three after selective vagotomy and drainage had most of their hourly intragastric pH values more acidic than pH 3.5 despite more than 70% reductions in preoperative stimulated-acid outputs.


Gastrointestinal somatostatin: extraction and radioimmunoassay in different species. A radioimmunoassay capable of detecting 300 fg somatostatin has been developed and levels of the polypeptide in gastrointestinal tissues from man, dog, and rat have been measured. Rapid freezing of collected samples and careful control of extraction is necessary. Concentrations in different regions of dog antrum (425 +/- 50 to 773 +/- 254 ng/g tissue) are similar to those in antrum from duodenal ulcer patients and control subjects: 614 +/- 125 and 465 +/- 104 ng/g tissue respectively. Levels in histologically normal human pancreas (253 +/- 43 ng/g tissue) are comparable with those in dog pancreas (333 +/- 66 ng/g tissue), whereas in two cases of neonatal hypoglycaemia the concentration exceeded 3000 ng/g tissue. On gel chromatography the majority of immunoreactive somatostatin elutes as the synthetic tetradecapeptide and a small fraction as a larger species.


Comparative clinical impact of endoscopic pancreatography, grey-scale ultrasonography, and computed tomography (EMI scanning) in pancreatic disease: preliminary report. Grey-scale ultrasound scanning (US), computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) were performed in a series of 50 patients with known or suspected pancreatic disease. The impact of the individual tests were assessed in the relevant clinical context. With a maximum of 100, the overall clinical impact score of ERCP (75) exceeded that of CT(63) and US (36). In patients with obscure pain, and in those with relapsing pancreatitis, a combination of US and ERCP provides good clinical guidance. Computed tomography scanning can currently be reserved for documentation of patients with a major mass lesion. None of the techniques can detect early pancreatic cancer, except of the papilla of Vater, where ERCP is diagnostic. Recommendations for future diagnostic strategies may alter as grey-scale ultrasonography and computed tomography develop, and, in any case, depend on many factors including local expertise, availability, and cost.


Computed tomography, ultrasound, and cholestatic jaundice. Computed tomography detected the presence of dilated ducts in 15 of 18 cases with extrahepatic obstructive jaundice and demonstrated the obstructing lesion in 18 out of 25. The cause of the obstruction was detected in the absence of duct dilatation, and calculi which were radiolucent on conventional radiographs were demonstrated. Ulstrasound detected dilated ducts in eight of 10 cases, but demonstrated the cause of the obstruction in only one of 13 cases. Both techniques are capable of demonstrating dilated ducts in the majority of cases, but computed tomography is better at detecting the cause of the obstruction.


G cell population of the gastric antrum, plasma gastrin, and gastric acid secretion in patients with and without duodenal ulcer. Estimates of the G cell population were made in 24 resected human pyloric antra from counts of cells in multiple samples and from measurements of antral size. Measurements had been made previously in 20 subjects of acid output (basal and after pentagastrin) and in 10 subjects of plasma gastrin (basal and after insulin + bicarbonate). G cells were most dense near the pylorus, but their circumferential distribution was even. The G cell populations ranged from 8 to 15 (mean 10) million in four control patients and from 3 to 43 (mean 18) million in 15 patients with duodenal ulcer. Those with recurrent ulcer after vagotomy had either a low G cell count and incomplete vagotomy, or a high G cell count and apparently complete denervation. Two patients with hypergastrinaemia and duodenal ulcer had moderate (29 X 10(6)) or marked (56 X 10(6)) excesses of G cells. 'G cell hyperplasia' may represent the extreme end of the normal range of G cell numbers in the antrum, and can be assessed by semi-quantitative grading of G cell hyperplasia in antral biopsies. There were significant direct correlations between antral area and G cell density, between peak acid output and G cell population, and between basal plasma gastrin and G cell density (but not population). We suggest that, in patients with duodenal ulcer, acid and gastrin secretion are interrelated and that both are related to the masses of parietal cells and of G cells.


Analysis of the effects of food and of digestive secretions on the small intestine of the rat: III. Mucosal mass, activity of brush border enzymes, and in vivo absorption of galactose, sodium, and potassium. A modified Roux-en-y repositioning of rat proximal small intestine resulted in a gut segment (A) exposed only to digestive secretions, but not to food and a gut segment (B) exposed to food, stomach juice and by reflux only to digestive secretions, and a third segment (C) exposed to both, food and digestive secretions. The changes in segment A were qualitatively very similar to those occurring after removal of luminal nutrition (intravenous feeding, self-emptying blind loop, and Thiry Vella loop). These findings support the hypothesis that the presence of luminal nutrition is a major factor regulating mucosal mass and enzyme activity in rat proximal small intestine. The changes in the luminal environment in segment B caused an increase in mucosal mass (in the proximal half only), an increase in sucrase activity which paralleled the increase in mucosal mass, and no change in activity of alkaline phosphatase which in fact was a decrease in activity ;at the cellular level'. Later on the net absorption of sodium and potassium was improved and the disappearance of galactose was unchanged when referred to unit length of small intestine.In segment C there was a small increase in mucosal mass, an increase in activity only for alkaline phosphatase, and an improvement of the net absorption of sodium without changes in the disappearance of galactose. These changes were compatible with a more proximal promotion of a distal gut segment.


Transport of large breakdown products of dietary protein through the gut wall. Ferritin or tritium labelled immunoglobulin G may, by electron microscopy, be demonstrated entering, within, and leaving the epithelial cells. Quantitative studies using various proteins labelled with radioiodine show that large amounts of protein bound radioactivity may be demonstrated in the tissues after feeding the labelled protein to adult rats by stomach tube. The molecular size of this material as determined by sugar gradient ultracentrifugation of tissue extracts ranges when IgG is fed from 50,000-20,000 Daltons. The material retains its ability to react as antigen with antisera specific to the original molecule: precipitation reactions may be obtained in gels and quantitative studies show that cnosiderable amounts of the protein-bound radioactivity are still specifically precipitable. Such studies have been carried out with alpha-gliadin as well as bovine IgG. At 100 days old rats may absorb as much as 40% of a dose of bovine IgG in the form of these large molecular breakdown products.


Effect of dopamine infusion on gastric and pancreatic secretion and on gastrin release in man. The effect of dopamine infusion on basal and pentagastrin-stimulated gastric secretion, on basal and secretin-CCK-PZ-stimulated pancreatic secretion, and on basal and meal-induced gastrin release has been evaluated in healthy volunteers. Both basal and stimulated gastric acid secretion were significantly inhibited during dopamine infusion with a significant rebound to pre-infusion values after discontinuing dopamine. These effects were prevented by pretreatment with the antidopaminergic drug, metoclopramide. A slight but now significant decrease in amylase and bicarbonate outputs was also observed during dopamine infusion, while gastrin release did not change. These data suggest the existence of dopaminergic mechanisms in the regulation of gastric acid secretion in man.


Factors which influenced postoperative complications in patients with ulcerative colitis or Crohn's disease of the colon on corticosteroids. A retrospective analysis was undertaken of the records of 107 patients with Crohn's disease of the colon or with ulcerative colitis who underwent 162 operations under steroid cover. The study revealed no correlation between steroid dosage and postoperative morbidity or mortality. The incidence of wound dehiscence and incisional hernia compared favourably with the reports of other unselected series of similar patients. Contamination did significantly influence results. Septic complications were more frequent when the operative field was contaminated and both delayed wound healing and mortality were related to this sepsis. A ;clean and dirty' technique was effective in controlling contamination during elective bowel division but preoperative bowel perforation and accidental entry into the lumen of the bowel during dissection were potentially avoidable sources of contamination. Primary healing of the perineal wound after proctocolectomy was seldom achieved in contaminated patients where a drain tube was brought out through the main perineal incision. When perineal sinuses or fistulae followed a proctocolectomy, patients with Crohn's disease had a significantly slower rate of healing than did patients with ulcerative colitis. However, there was no difference in the healing of abdominal wounds in relation to the primary pathology. Even abdominal incisions which were used on more than one occasion healed as well as those which were used for the first time. A prophylactic antibiotic regime of either ampicillin or tetracycline offered little protection against postoperative sepsis. The organisms which caused such infections were often insensitive to the two antibiotics.


Response of the skin in dermatitis herpetiformis to a gluten free diet, with reference to jejunal morphology. Twenty-one patients with dermatitis herpetiformis have been on a gluten free diet regularly followed up for at least one year (mean four years). Eighteen patients had a 'flat' mucosal appearance (grade III), one patient had moderately severe mucosal abnormality (grade II), one patient had mild mucosal abnormality (grade I), and one patient had a normal mucosal appearance (grade O). On the diet, 10 patients had no skin rash and took no dapsone, seven patients controlled the skin rash on a lower dose of dapsone, and four noticed no improvement. There was no correlation between pre-diet jejunal morphology and response of the skin. A repeat jejunal biopsy, on the gluten free diet, was possible in 15 patients. While all those with skin improvement showed some improvement in jejunal morphology, there was no association between the degree of skin improvement and the degree of recovery of the jejunal mucosa.


Enteral bacterial infection as a possible cause of cot death. At post mortems performed in cases of cot death, the cause of death has been established as due to a variety of pathological changes. In connection with the anamnesis data, inflammation in the region of the respiratory system, especially of the lungs, infections of the gastrointestinal tract, otitis media and electrolyte shifts can in many cases be traced back to a common origin, if we assume a bacterioenterotoxin poisoning (which takes a different course in infants than in older children or adults). Extensive inquiries prior to the post mortem, autopsies performed always by the same method, as well as all the ensuing examinations, are indispensable in order to explain the cause of the sudden death and to make sure that the results of the post mortem are not influenced by the importance the pathologist attributes to a certain method of examination.


[Long-term treatment with psychoverlan in children and adolescents with behavior disorders]. Numerous pharmacological and clinical long-term studies on mono-magnesium-L-glutamate-hydrobromide. H2O were reason to undertake another trial in adolescents with reactive behavioral abnormalities. The aim of the study was to assess the effecacy of Psychoverlan in abolishing or improving these symptoms and to reveal any possible drug-induced side effects. In a long-term study 19 young females were treated with Psychoverlan capsules or syrup for an average of 11.4 months. Intolerance phenomena and side-effects were not seen. It was even decided to increase the standard dose. None of the patients developed brominism or bromine intoxication. The general state of health of 13 of the 19 subjects was improved by the harmonizing effect of the drug on psychic and vegetative functions. Tiredness and somnolence were not observed.


Problems in brain death determination.

Problems in brain death determination. During the last decade there has been philosophical acceptance of the concept that the state of brain death is equivalent to total patient death. The application of this concept to clinical medicine has been associated with major problems in both the diagnosis of brain death and the medical management of the brain dead patient. In our experience with 176 consecutive cases of suspected brain death over a seven-year period, we have found that a standardized protocol applied by experienced clinicians will minimize these problems.


The value of succinate dehydrogenase stain in the post-mortem diagnosis of early acute myocardial infarction. A forensic study. In consecutive medicolegal material comprising 79 persons, the formazan test revealed recent myocardial infarction in 16 cases (20%). Only 4 of these cases (25%) were demonstrated by macroscopic examination. By means of microscopic examination, the 4 infarctions recognized macroscopically and 5 other cases which were demonstrated by the formazan test could be confirmed. If the formazan test is employed as an independent demonstration of myocardial infarction, a total of 16 cases could be demonstrated (as mentioned above), or four times as many as at macroscopic examination at autopsy.


Comparison of GLC-EMIT analysis for the assay of methadone and its major metabolite in urine. The enzyme-multiplied immunoassay technique (EMIT) was compared with the gas-liquid chromatographic (GLC) method in the analysis of 130 urine samples from subjects receiving methadone treatment and non-methadone controls. The GC method allowed the quantitation of 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, and major metabolite of methadone. A good correlation was found between the two methods. The advantages of using the EMIT system are discussed.


[Critical disorders of circulatory regulation. The vago-vasal syncope]. Disturbances in regulation of circulation dependent vagovasal syncope in combination with fright-shock-syncope or psychasthenic faint can easily be controlled. General treatment like lying down and elevation of the legs is required. The use of medicaments is rarely indicated. Precise recognition of the symptoms is necessary to differentiate against more serious causes of a sudden faint.


Interfering basic materials in urine from racing greyhounds. Three quinoline amines, 2-aminomethylquinoline, 2-hydroxymethylquinoline and quinaldine (2-methylquinoline), are identified in greyhound urine. These amines can interfere in the analysis of greyhound material for basic drugs. This is a special problem in ultraviolet spectrometry since their extinction coefficients are high. Reference analytical data for these quinoline amines and for six related compounds are given. The techniques used are infrared spectrometry, ultraviolet spectrometry, fluorometry, thin-layer chromatography, gas chromatography and mass spectrometry.


[Frequent anal and perianal disorders and their treatment]. Anal fissures, internal hemorrhoids and perianal thromboses are very common and frequent diseases. Diagnosis is simple even with limited experience in endoscopy. Treatment of the anal fissure consists in slow dilatation with a bougie in cases of acute fissues if the sphincter internus muscle is not highly spastic, in cases of chronic or very painful acute fissures a posterior or lateral sphincterotomy should be performed. Hemorrhoids can be treated with different methods, the optimal conservative treatment is by injection of phenol. In cases of prolapsing hemorrhoids an operation should be performed. Perianal thromboses should be opened by incision. The different methods of treatment are described.


[The virostatic effect of adenine-arabinoside monophosphate. Experimental findings and preliminary clinical experiences]. Adenine arabinoside (Ara-A), a synthetic nucleoside, is an antiviral agent, which is effective against poxviruses and viruses of the herpes group. The monophosphate (Ara-AMP) has the great advantage of better solubility, compared to the parent compound. Experimental studies show the outstanding effect of Ara-AMP on the encephalitis by vaccinia-virus in white mice. Even after immunesuppression by total body irradiation, the survival rate of the Ara-AMP treated animals was significantly higher compared to the untreated controls. In experimental vaccinia-virus infections in rabbits, who had undergone total body irradiation. Ara-AMP has a favourable influence upon the course of the disease and the prognosis. Some clinical observations in children with immunesuppression, who suffered from generalized zoster of varicella-infections, are reported. Furthermore in cases of viral encephalitis Ara-AMP was successful. Controlled studies of a greater number of patients on the therapeutic value of Ara-AMP in infections with DNS-viruses are needed.


[Pseudomembranous colitis after antibiotics therapy]. Pseudomembranous colitis may arise as a severe complication of chemotherapy with antibiotics. Lincomycin and clindamycin are especially incriminated, but the condition has also been reported after treatment with other broad-spectrum antibiotics. The endoscopic findings are suggestive, though not specific. Overall mortality is estimated to be 10--20%. There is an increased risk in patients with a previous history and pseudomembranous colitis in relatives of these patients.


[Isolation of soluble tumor-associated antigens of human malignant melanoma]. Experiments were started with an animal model: Tumor antigens could be solubilized from fibrosarcomas of inbred guinea pigs by extraction with physiological saline. Extracts were fractionated by ammoniumsulfate precipitation, gel filtration, ion exchange chromatography, and polyacrylamide electrophoresis. Skin tests and leucocyte migration assays could detect antigenic activity in a number of fractions different with respect to size and charge. A less heterogeneous antigen could be extracted with phenol-water from guinea pig fibrosarcomas. Tumor associated antigens could be demonstrated in phenol-water extracts of human melanoma by leucocyte migration tests. Weak migration reactions were found with leucocytes from melanoma patients, not with leucocytes from controls. The frequency of positive results was similar in patients with and without metastases. No antibodies against antigens of phenol-water extracts could be detected in sera from melanoma patients. No antibodies against tumor associated substances could be demonstrated after immunization of rabbits with phenol-water extracts. Antigens extracted by phenol-water seem to be weak immunogens. Radioactive antigens were extracted from membranes of labelled cell cultures of human melanoma. Antigenic activity was assayed by double immune precipitation followed by sodium-dodecylsulfate-polyacrylamide-electrophoresis. Yields from available cell quantities were too small for further purification and clinical studies.


[Effects and side effects of benzbromaron in the initial treatment of hyperuricemia and gout. Results of a field study on 3899 patients]. In a collective of 3899 out-patients, the effect of uric acid reduction of benzbromarone was tested. Ten days after beginning of treatment, a uric acid concentration of 5.1 to 5.7 mg/100 ml had been obtained. Three months after beginning of therapy, uric acid values were at 4.9 mg/100 ml, independently of age and sex. As side-effects were observed:diarrhoea in 1% (n = 41) of the treated patients, furthermore, 0,8% (n = 31) complained of gastro-intestinal trouble such as pressure over the stomach, nausea, sensation of fullness and epigastric pain. Only in 2 of the 3899 patients (0.05%) the appearance of a renal colic was observed.


Muscle metabolism during exercise in diabetics and in obese during starvation. The influence of exercise on forearm muscle metabolism was examined in 9 healthy subjects, in 16 diabetics and in 4 obese subjects during complete starvation. During exercise glucose uptake rose 7-8 fold in the controls. However, no increase of glucose uptake was observed in the other groups studied. Moreover, a glucose production from the working muscle took place in about 40 percent of both the diabetic patients and the starved obese subjects. The nonutilization of glucose during physical work in the diabetic like states was accompanied by a significantly diminished lactate output. The arterial concentration of FFA, glycerol beta-HOB and Acac was markedly elevated in the starved obese patients. The FFA-uptake at rest and during exercise, however, was not different from results of controls. Whereas an effux of beta-HOB has been observed during exercise, Acac uptake was increased in these patients. It is suggested that in maturity onset and starvation diabetes glycolysis is inhibited.


Non-glucoregulatory hormones (T4, T3, rT3, TSH, testosterone) during physical exercise in juvenile type diabetics. Non-glucoregulatory hormones (T4, T3, rT3, TSH and testosterone) were studied by radioimmunoassay in juvenile-type diabetics in moderate control and in ketosis due to insulin withdrawal and in age matched "normals" during a mild prolonged exercise test. The basal serum hormone levels revealed the following findings: Serum testosterone was markedly lower in diabetics than in normals ( 177 +/- 24 resp. 618 +/- 52 ng/dl). This is in contrast to other studies, but it may reflect decreased testicular function due to an early, clinically not apparent atherosclerotic disease. Serum T3 was significantly lower in diabetics than in normals (110 +/- 16 resp. 145 +/- 19), suggesting an early "low T3-syndrome" in juvenile-type diabetics. However, increased serum rT3 levels were not observed, and serum T4 and TSH were normal. Mild prolonged exercise had no major effects on these nonglucoregulatory hormones. In juvenile-type diabetics the degree of metabolic control had no influence on the response of the mentioned hormones. However, an increased cortisol/testosterone ratio in ketotic diabetics in the basal state with a further increase during exercise was demonstrated, indicating an aggravation of the catabolic state in these patients during exercise.


The effect of altered autonomic tone on alanine induced insulin secretion. The effect of pharmacologically induced altered autonomic tone upon alanine stimulated insulin release was examined in adult norgrel dogs. In control studies, intravenous administration of alanine, 1 gm/kg body weight resulted in a mean rise in plasma insulin concentration from basal levels of 7.4 (+/- 2) MUU/ml to a maximum of 24.5 (+/- 6) muU/ml by 10 minutes after injection. In paired studies, epinephrine infusion or atropine administration had no significant effect on the insulin rise in response to the alanine stimulus. This data indicates that in contrast to a glucose stimulus, the insulin response to the amino acid alanine is not influenced by epinephrine or cholinergic blockade. These studies provide further evidence that alanine acts through alternate pathways, different from those utilized by glucose to effect insulin secretion.


Early effects of feeding upon hormonal and metabolic alterations in adult rats with ventromedial (VMH) lesions. The importance of the nutritional state for the development of metabolic alterations after ventromedial hypothalamic (VMH) destructions has been investigated. In the first experiment, groups of fed and 12 hours fasted animals were operated, given an intraperitoneal injection of 3H2O (1 mCi), and left without food until sacrificed 12 hours postoperatively. The lipogenesis in liver and adipose tissue, and the plasma levels of insulin, glucose, urea, free fatty acids (FFA) and triglycerides (TG) were measured. Animals operated in the fed state had increased lipogenesis in parametrial adipose tissue and hypoglycemia compared to their controls, whereas we found no differences between the groups which had been fasted 12 hours before surgery. In the second experiment, animals were deprived of food for 12 hours before being lesioned or sham-operated, and for 12 more hours postoperatively. They were then given one meal by stomach tube, and groups were killed 2, 4, 8 and 12 hours later. The following differences between groups were observed: 2 hours after feeding, the lesioned animals had increased plasma TG levels, but decreased liver lipogenesis. 4 hours after feeding, animals with lesions were hypoglycemic, and had lower plasma levels of FFA and TG than the controls. Hypoglycemia in lesioned animals was found also 8 hours after feeding, together with increased plasma TG levels. 12 hours after feeding, increased liver lipogenesis in lesioned animals was the only difference observed between the groups. The third and last experiment investigated the effect of three meals given 12, 18 and 24 hours postoperatively. Lesioned animals sacrificed 4 hours after the third meal had hypoglycemia, increased plasma TG levels, and increased lipogenesis, both in liver and adipose tissue. The metabolic differences between lesioned and sham-operated animals persisted also 8 hours after the last meal, except for the lipogenesis in adipose tissue. No differences in plasma insulin levels between animals with lesions or sham-operations were observed in these experiments.


Thyroid function in acute intermittent porphyria: a neurogenic cause of hyperthyroidism? Thyroid function was investigated in 17 patients with acute intermittent porphyria (AIP). In 13 patients in remission and latent for the disease, thyroid function was normal. In contrast, transient hyperthyoridism with elevated total T4, T3 free T4 and T3, and FTI levels occurred in one pregnant patient with severe attacks of AIP, and similar, though less pronounced, alterations in thyroid function were found in three other symptomatic female patients. It is suggested that increased thyroidal sympathetic neural stimulation is responsible for these changes in thyroid function.


Effect of hormone on human mammary duct in vitro. Human mammary ducts were maintained in median-term organ culture. DNA synthesis was assessed by the uptake of 3H-thymidine in epithelial cells; labeling indices were counted on autoradiographies. DNA synthesis grossly remained between starting values in the basic conditions without hormones. Insulin (5 microgram/ml) did not stimulate the uptake of the isotope as compared with the controls. Estradiol (0.001 microgram/ml) and progesterone (1 microgram/ml) highly significantly enhanced DNA synthesis; subsequent waves did occur.


Calcitonin diuretic effect in the rabbit. In an attempt to study the renal effects of Calcitonin (porcine CT) in the rabbit, the excreted fractions of filtered water, osmolality, sodium, potassium and chloride, and the calcium and phosphorus urinary excretions were studied during isotonic (ISD) and hypertonic (HSD) saline diuresis. Four doses (0.1, 0.8, 4 and 20 IU MRC/kg were perfused during one hour in I.S.D.; 4 and 20 IU MRC/kg in HSD. During ISD, Calcitonin at doses of 4 and 20 IU MRC/kg/hr significantly increased the diuresis and the Na+, Cl-, K+, PO4 3-, Ca2+ excreted fractions. This effect was also observed, to a lesser extent, at a dose of 0.8 IU MRC/kg/hr, whereas 0.1 IU MRC/kg/hr produced no significant effect. During ISD, a log dose related effect of CT appeared to exist with all studied parameters. Moreover, a biphasic pattern of free-water clearance was observed during ISD: this parameter increased during the first half hour of CT perfusion, and then decreased dramatically. During HSD, CT perfusion induced a decrease of free-water reabsorption and urinary osmolality/plasma osmolality ratio. These results suggest that the diuretic effect and saliuretic effect of CT (in the rabbit) are mainly the consequence of the decrease of the proximal reabsorption of sodium. The possibility of a second site of action is discussed. The diuretic effects of CT are compared to data observed with the well-known diuretic drugs.


Amniotic fluid, maternal and fetal blood insulin in overweight pregnant women. The effect of excessive maternal weight gain on insulin levels during pregnancy (15 cases) was compared with the insulin levels in a control group (20 normal pregnancies) by radioimmunologic determination of insulin in the amniotic fluid and in maternal and fetal blood. The mean values of insulin in the control group were as follows: mother 24.9 +/- 0.51, fetus 10.86 +/- 0.48 and amniotif fluid 6.08 +/- 0.42 muU/ml, and in patients with excessive weight gain during pregnancy, maternal insulin mean values were 39.45 +/- 1.86, fetal 20.99 +/- 3.39 and amniotic fluid 12.25 +/- 1.15 muU/ml. Insulin concentrations in maternal blood (P less than 0.001), fetal blood (P less than 0.001) and amniotic fluid (P less than 0.001) were higher in excessive weight gain pregnancies as compared to the control group.


The metabolism in man of (3H)-5alpha-16-androsten-3alpha-ol and of (3H)-5alpha-16-androsten-3-one. The in vitro metabolism in man of two 16-androstene steroids, 5alpha-16-androsten-3-one and 5alpha-16-androsten-3alpha-ol, has been studied using 3H-labelled tracers. 4 healthy subjects (2 of each sex) were chosen, and each labelled steroid was administered, by a single injection, to 1 man and 1 woman. Disappearance of (3H)-3alpha-androstenol in the subjects receiving this compound followed a curve which indicated a two-pool distribution in both cases; metabolic clearance rates for these subjects were found to be 3,790 1/24 h in the man and 3,120 1/24 h in the woman. Blood production rates calculated for the 3alpha-androstenol-treated subjects were 875 microgram/24 h in the man and 1,780 microgram/24 h in the woman. Recovery of 3H in the urine of all 4 subjects was very low, between 28 and 42%. Conversion of the injected precursors to urinary 3alpha-androstenol was 13.5 and 12.7% in the 2 men and 6.1 and 5.9% in the 2 women. The male subjects were found to have a lower 24-hour urinary 3alpha-androstenol output (570 and 387 microgram/24 h) than the average for men of their age. The urinary 3alpha-androstenol output in the women was 225 and 276 microgram/24 h, and was within the normal range for women. The urine production rates of 3alpha-androstenol were 2,470 and 4,090 microgram/24 h in the male and female subjects, respectively; the difference between the blood and urine production rates of this compound are thought to indicate the direct secretion of conjugates. Urine production rates of 5alpha-androstenone (measured as 3alpha-androstenol) were 2,370 and 4,340 microgram/24 h in the male and female subjects, respectively.


[Hemoglobin XXIII: note on the sequence of the delta-chains of human hemoglobin (author's transl)]. The minor component of the human adult hemoglobin Hb A2 (alpha2/delta2) was isolated. The peptide chains were separated by counter current distribution, the delta-chains digested with trypsin and all hydrolysis splitting products separated and quantitatively characterized. With the film technique the different peptides were sequenced with hydrophilic phenylisothiocyanates I and IV or by the propyne programme. The complete sequence of the delta-chains is given and compared with the sequence reported in former investigations, in which the delta-chain sequence was only partly elucidated. Having completely sequenced the delta-chains of the human hemoglobin, we found the 10 previously reported exchanges and no additional exchanges with respect to the beta-chains.


Distribution of metabolites between the cytosolic and mitochondrial compartments of hepatocytes isolated from fed rats. In isolated hepatocytes from normal fed rats, the subcellular distribution of malate, citrate, 2-oxoglutarate, glutamate, aspartate, oxaloacetate, acetyl-CoA and CoASH has been determined by a modified digitonin method. Incubation with various substrates (lactate, pyruvate, alanine, oleate, oleate plus lactate, ethanol and aspartate) markedly changed the total cellular amounts of metabolites, but their distribution between the cytosolic and mitochondrial compartments was kept fairly constant. In the presence of lactate, pyruvate or alanine, about 90% of cellular aspartate, malate and oxaloacetate, and 50% of citrate was located in the cytosol. The changes in acetyl-CoA in the cytosol were opposite to those in the mitochondrial space, the sum of both remaining nearly constant. The mitochondrial acetyl-CoA/CoASH ratio ranged from 0.3-0.9 and was positively correlated with the rate of ketone body formation. The mitochondrial/cytosolic (m/c) concentration gradients for malate, citrate, 2-oxoglutarate, glutamate, aspartate, oxaloacetate, acetyl-CoA and CoASH averaged from hepatocytes under different substrate conditions were determined to be 1.0, 8.8, 1.6, 2.2, 0.5, 0.7, 13 and 40, respectively. From the distribution of citrate, a pH difference of 0.3 across the inner mitochondrial membrane was calculated, yet lower values resulted from the m/c gradients of 2-oxoglutarate, glutamate and malate. The mass action ratios for citrate synthase and mitochondrial aspartate aminotransferase have been calculated from the metabolite concentrations measured in the mitochondrial pellet fraction. A comparison with the respective equilibrium constants indicates that in intact hepatocytes, neither enzyme maintains its reactants at equilibrium. On the assumption that mitochondrial malate dehydrogenase and 3-hydroxybutyrate dehydrogenase operate near equilibrium, the concentration of free oxaloacetate appears to be 0.3-2 micron, depending on the substrate used. Plotting the calculated free mitochondrial oxaloacetate concentration against the citrate concentration measured in the mitochondrial pellet yielded a hyperbolic saturation curve, from which an apparent Km of citrate synthase for oxaloacetate in the intact cells of 2 micron can be derived, which is comparable to the value determined with purified rat liver citrate synthase. The results are discussed with respect to the supply of substrates and effectors of anion carriers and of key enzymes of the tricarboxylic acid cycle and fatty acid biosynthesis.


[Improved preparation of des-alanylB30-insulin (author's transl)]. Des-AlaB30-insulin was prepared by incubation of insulin with carboxypeptidase A. The C-terminal alanineB30 of the B-chain was quantitatively liberated without liberating asparagineA21 of the A-chain in ammonium hydrogencarbonate buffer.


Subcellular distribution of [14C]5-hydroxytryptamine in the blood platelets of rabbits: effects of imipramine and and haloperidol. Long-term (10 days) administration of imipramine [20 mg/(kg X d)] to rabbits significantly increases the Km value (4.0 micron) of 5-hydroxytryptamine uptake in their platelets compared to those of saline- (0.7 micron) or haloperidol- (0.4 micron) treated rabbits. Administration of haloperidol inhibits the 5-hydroxytryptamine uptake non-competitively, and in vitro it had an ID50 value of 22 micron. Intravenous injections of [14C]5-hydroxytryptamine were given to the animals 1 h before blood collection. After isolation of platelets, their sonicates were subjected to 30-60% continuous sucrose gradient centrifugation. The subcellular distribution of [14C]5-hydroxytryptamine indicates that imipramine treatment, in contrast to the control and haloperidol treatment, led to a shift in the exogenous 5-hydroxytryptamine peak from within the granular zone (d 1.18) to the extragranular cytoplasm (d 1.15). Compared to control values, the imipramine treatment caused 63% inhibition in the platelet Na-K-ATPase activity.


Structure-function studies on red pigment-concentrating hormone; the significance of the terminal residues. The significance of the terminal residues of the red pigment-concentrating hormone (RPCH: Glu-Leu-Asn-Phe-Ser-Pro-Gly-Trp-NH2) for its blanching effect on crustacean chromatophores has been investigated. The chemical synthesis of the following small analogues, starting from the C-terminal amino acid are described: Ac-Trp-NH2, Boc-Gly-Trp-NH2, Ac-Gly-Trp-NH2, Gly-Trp-NH2, Ac-Pro-Gly-Trp-NH2, Glu-Trp-NH2, Glu-Pro-Gly-Trp-NH2, Ac-Pro-Gly and Glu-Pro-Gly-NH2. Assay of the biological activity of the various synthetic compounds in the shrimp Leander adspersus has established that only the C-terminal tryptophan residue is indispensable for the blanching effect of the hormone, although elongation of the chain length improves its potency.


Fructose, a substrate for energy-yielding metabolism in the heart? Effects of fructose and glucose on cardiac function and 14CO2 production from radioactive hexoses were studied in isolated working guinea pig hearts perfused at constant filling pressure via the left atrium. When hearts were perfused without exogenous substrates external work declined, indicating exhaustion of endogenous energy sources. It was possible to restore left ventricular function with concentrations of glucose in the physiological range; in order to achieve a similar restoration with fructose as the only exogenous substrate concentrations higher than 40mM were necessary. 14CO2 necessary. 14CO2 production from [U-14C]glucose was half-maximal at about 2mM glucose. On the other hand, 14CO2 production from [U-14C]fructose did not show saturation kinetics and, at concentrations around 2mM, was less than 5% of the rates observed with [U-14C]glucose. Moreover, fructose oxidation was suppressed in the presence of 5mM glucose. The data suggest that fructose cannot serve as a major substrate in the heart under in vivo conditions.


Uptake of thymidine into isolated rat hepatocytes. Evidence for two transport systems. Thymidine transport was studied in isolated rat hepatocytes. In these cells no phosphorylation of the substrate by thymidine kinase occurred subsequent to transport. Results from studies of the concentration-dependent uptake of thymidine indicated two transport systems with about 80-fold differences in their kinetic constants. These systems were denoted as high affinity [Km = 5.3 micron, V = 0.47 pmol/(10(6) cells X s)] and low affinity systems [Km = 480 micron, V = 37.6 pmol/(10(6) cells X s)]. From intracellular to extracellular distribution ratios of [3H]thymidine it could be concluded that the uptake by the high affinity system was a concentrative process while the transport by the low affinity system was non-concentrative. The uptake of [3H]-thymidine by the high affinity system could only be inhibited by unlabeled thymidine. In contrast, all other nucleosides tested (uridine, 2'-deoxycytidine, and 2'-deoxyguanosine) were equally effective in inhibiting the low affinity system competitively. The results would suggest that in hepatocytes lacking phosphorylation by thymidine kinase, thymidine is taken up by a high and a low affinity system working in tandem. The high affinity system seems to be an active transport process with narrow substrate specificity. Thymidine uptake by the low affinity system is a facilitated diffusion process. This system is considered to be a common transport route for nucleosides of different structures.


Subunit structure of Micrococcus luteus catalase. Dissociation of M. luteus catalase induced by dodecylsulfate, citraconic and 2,3-dimethylmaleic anhydrides and urea. M. luteus catalase dissociates upon treatment with urea, dodecylsulfate and anhydrides into monomers, the molecular weight of which appears to be 1/4 of that of the native enzyme. The urea-induced dissociation depends upon the incubation time, the urea concentration and the pH of the incubation mixture. Reassociation of the subunits proved to be unsuccessful. Native M. luteus catalase only contains 30% alpha-helix. When fully dissociated in presence of urea, it still retains 15% alpha-helix. Catalase from M. luteus was found to lack cysteine residues.


Ultrastructural features of the colonic epithelium in familial polyposis coli. Colectomy specimens from 6 cases of familial polyposis coli (FPC) were examined. Macroscopically normal mucosa between polyps was taken at intervals along the ascending, transverse and descending colons and studied at EM level. All three regions show the same cell populations varying only in their ratio and height of the epithelium. The same cell types seen in the normal crypt epithelium are present in the mucosa from FPC. As in the normal, 'intermediate' cells are present in FPC but they are less conspicuous than in the mucosa adjacent to colonic carcinoma. However, there are ultrastructural features which distinguish the "normal" mucosa in FPC from the true normal: (a) the presence of "clear columnar" cells; (b) increased vesiculation in the absorptive cells; (c) large number of lysosomes; and (d) the presence of small electron-dense bodies. The ultrastructure of the "clear columnar" cells suggests their being incompletely differentiated cells, thus raising the possibility that their presence in the upper crypt and surface epithelium may represent an early stage in the process of polyp and cancer formation.


Detection of neoplastic and preneoplastic urothelia by combined scanning and transmission electron microscopy of urinary surface of human and rat bladders. Scanning and transmission electron microscopy reveal distinct differences between the appearance of the luminal surface membrane of normal urothelium and those of transitional cell tumours of both human and rat bladder. The luminal surface membrane of the preneoplastic rat urothelium shows features similar to those seen in the fully developed tumour. In human tumour-bearing bladders the urothelium away from the transitional cell tumour is not recognizable as being preneoplastic by light microscopy. However, by scanning or transmission electron microscopy, the luminal membrane in some areas shows changes identical to those in the preneoplastic rat bladder. These observations are in accordance with the clinical behaviour of the urothelium in patients with vesical transitional cell tumours which tend to recur in disparate site. We suggest that scanning electron microscopy of the bladder urothelium away from the tumour may be of prognostic value for indicating the subsequent biological behaviour of the urothelium.


Morphology and staining patterns of endocrine cell tumours in the gut, pancreas and bronchus and their possible significance. We have studied 109 endocrine cell tumours of the gastrointestinal tract, pancreas and bronchus in terms of histological pattern and histochemical staining with immunocytochemical studies on seven tumours. As a result we believe that previous histological classifications need modification. 5-Hydroxytryptamine secreting tumours have a carcinoid (A1) pattern with, in some cases, an additional tubuloacinar element (A1A2) and definable histochemical reactions; well differentiated gastrinomas, insulinomas and glucagonomas are associated commonly, but not exclusively, with particular histological patterns and argyrophilia, but no such association exists for less differentiated tumours. This may be related to the synthesis of precursor hormones by less differentiated tumours. Mixed patterns are common, particularly in tumours of foregut derivation. Prospective studies planned to correlate histology, histochemistry, immunocytochemistry and ultrastructure are needed on all endocrine cell tumours.


Standardization and the histopathology of tumours. Standardization of tumor classifications is a prerequisite in facilitating international communication in cancer research. Standardized classifications are not meant to replace, or compete with, conceptual classifications. The World Health Organization's efforts in this field give consideration to definitions of tumour types, terminology, formats of categorization, and codes.


Localization of glomerular "deposits" in Henoch--Schönlein nephritis. Twenty-five renal biopsies from patients with Henoch--Schönlein nephritis were examined using light microscopy, immunofluorescence, 1 micrometer plastic-embedded sections and electron microscopy. The 1 micrometer plastic-embedded sections and electron microscopy showed deposits in mesangial, subendothelial and subepithelial sites. Some of the latter were very large and similar to those which have been described as "humps" in acute proliferative glomerulonephritis. Immunofluorescence showed the mesangial deposition of IgG, IgA and C3 with extension into a peripheral position in some cases. Fibrin was frequently found associated with crescents. The case for Henoch--Schönlein disease being mediated, in part at least, by immune complex deposition, is presented.


A hospital for all seasons.

A hospital for all seasons. Seasonal variations in occupancy, cash flow, staffing patterns, and emergency department activity are familiar to any hospital, but institutions located in seasonal resort areas must cope with more extreme variations than do most hospitals. Mount Desert Island Hospital, Bar Harbor, ME, has developed several innovative means of handling slack periods in wintertime and intense activity in the summer.


Energy management: total program considers all building's systems. Managing energy consumption, containing fuel usage, and preparing for alternate fuel sources are immediate areas for concern and action for all health care providers. The authors describe how they are meeting the challenge of increased energy costs and reduced availability while maintaining high-quality care by applying the concept of total energy management.


Housekeeping: customized training program keyed to hospital's procedures, staff. Thoughtfully developed, conscientiously applied housekeeping employee training programs are all too scarce. The program described was customized to fit an individual hospital's standard procedures, and it used volunteer models from among the workers to illustrate the video portion of the program. Recognition of employee merit and effective supervision and follow-up were two other key elements.


Joint planning--how a hospital and a city carried it off. Methodist Hospital of Indiana, Inc., and the City of Indianapolis, both having a strong commitment to redevelopment, designed a long-range project in which the hospital, as the dominant permanent institution of its inner-city neighborhood, played an important part in solving the problems faced by the entire community.


Patients and staff favor night ministry program. Patients often are more receptive to pastoral care during the night hours than during the day. When a chaplain remains in the hospital through the night, he is able to translate his religious calling into concern and love where it is most needed.


Understanding trustees' concerns promotes board development. A hospital's CEO has a major responsibility to promote development of the board into an effective, competent, functioning body. To do so, he must understand the special problems, fears, and risks that trustees confront in the health care setting; allow and expect the board to fulfill its own role; and provide a supportive environment in which the board can function and develop.


Nursing aide training by community saves hospital time, space, money. A hospital's staff development department and the community's public school adult education division jointly established an out-of-hospital training program for nursing aides and orderlies. This arrangement has enabled the hospital to devote more resources to other high educational priorities. It also has ensured effective training for the students and excellent employment opportunities for the graduates.


Mobile critical care unit safeguards lives during transfers. Providing access to high-quality critical care services for patients in small or remote hospitals is an important problem faced by many hospitals in this country. In an effort to meet the needs of critically ill patients who might be saved if they could be safely transported from their community hospitals to a large medical center with more specialized care capabilities, the University of Wisconsin Hospitals, Madison, designed a Mobile Critical Care Unit. The details of the unit's construction and of the program's operation are presented herein.


Offering continuity of care for the elderly. St. Benedict Hospital and Nursing Home provides a continuum of patient care services for the elderly ranging from home health service to acute hospital care. The many levels of care provided result in the advantages of economy of scale for the organization and continuity of care for the patients.


The Christian administrator in a secular society. While government involvement with hospitals complicates an administrator's operating environment, much of what government and consumer advocates want is at least philosophically good. In the midst of conflicts between a secular society and the goals of church-related hospitals, Christian administrators must demonstrate integrity and would do well to see adversity as a challenge promoting greater strenghts for themselves and for their hospitals.


Planning for "the technology factor".

Planning for "the technology factor". Modern medical care technology impacts on decision making in the industry as never before. Whether this impact is more positive than negative is debatable; but the dialogue is of vital interest to hospitals, as technology is the central issue in the current furor over cost control.


Distribution of blood groups, serum markers and red cell enzymes in two human populations from Northern Siberia. 555 individuals were examined in relation to the ABO (with A1 and A2 subtypes), MNSs, P, Rh, Lutheran, Kell and Duffy systems. Less individuals were studied for the Kidd and Diego systems as well as for transferrins, haptoglobins and red cell enzymes, i.e. PGM1, 6-PGD, AK, and AcP. Besides, several Gm and Km (1) factors were also studied.


Relationship between Hp1S and Hp2 gene frequencies among human populations. In this work, we present new data on the Hp1alpha- and Hp2alpha-chains polymorphism in different populations. We confirm the singularity of the geographical distribution of the Hp2 alleles in our samples. The analysis of the results shows that a significant correlation exists in the population between the Hp1S and Hp2 gene frequencies. An additional Hp1alpha-chain variant is described in a Pyrenean sample.


Problems in estimating non-disjunction rate from the F-bodies of two-headed human spermatozoa. The F-bodies of two-headed human spermatozoa offer a unique potential for estimating non-disjunction rate of the Y chromosome. But there is an unexplained quantitative discrepancy: a gross deficiency of two-headed spermatozoa with no F-bodies, relative to the numbers with one F-body in each head. Any estimation of non-disjunction rate would be overshadowed by this and other major factors. Two-headed spermatozoa cannot be regarded as a random aggregation of haploid heads in pairs. DNA measurements confirmed that each head of 25 normal-sized two-headed spermatozoa was haploid. The distribution of F-body classes is independent of whether sperm tails are single or double. Donors with an exceptionally high incidence of two-headed spermatozoa exist.


Consanguinity in multifactorial inheritance. Application to data on congenital glaucoma. The increase of parental consanguinity in multifactorial inheritance is evaluated by calculating the expected incidence of affected children whose parents are first cousins, using several values, namely for condition frequency and heritability of liability. This increase is compared to the expected increase in recessive inheritance, when one or more loci are involved. The method is illustrated by examples of recessive and multifactorial conditions and applied, as a test of discrimination between different modes of inheritance, to data on congenital glaucoma.


Serum genetic markers in a Newfoundland isolate with a familial aggregate of Hodgkin's disease. Inherited genetic markers on the immunoglobulins and three other serum proteins were investigated in members of an isolated Newfoundland community. The frequencies found were compared with those from Europe. Whilst the incidence of the commonest variant forms were typically 'European', the occurrence of rare phenotypes pointed towards specific admixture from American Indians and Scandinavia. A possible contribution of these rare alleles, and of others, to pathogenesis in a familial aggregate of Hodgkin's disease within this community is discussed.


Genetic distance between the American Indians and the three major races of man. The genetic distances between the American Indians and the three major races of man, Caucasoids, Negroids and Mongoloids, were determined by using gene frequency data on 14 blood group and 12 protein loci. The results support the general view that the ancestry of the American Indian is predominantly Mongoloid. Using 30,000 years as the separation time between the American Indian and Mongoloid, the divergence time between the three major races of man was estimated to be 33,000-92,000 years.


Linkage of glyoxalase I and HLA in two Newfoundland communities. Family studies in Newfoundland confirm linkage between the glyoxalase I locus and HLA. The combined data gives a map distance of 4.54 centimorgans between the HLA B locus and glyoxalase I.


Genetic investigations in a Northern Brazilian island. II. Random drift. 18 albinos were born on Lençóis island. Since 3 of them died and 5 emigrated, the prevalence of albinism is about 3% in the island. 2 inbred brothers with brachydactyly of the index fingers and 1 case of 'achondroplasia' were also found. The analysis of the population structure of the island suggests that its high frequency of albinism may have been produced by random drift. The index of isolation of its present population is roughly 17--27. Genealogical, clinical and histological data are presented and anslyzed. Natural selection is not acting against the albinism gene at a measurable rate. Cytogenetic investigations among albinos and normals did not reveal any difference as regards frequency of aneuploidy, association of acrocentrics and chromatid gaps. The role of random processes in evolution is mentioned and the possibility that they may be more important than it is sometimes assumed is stressed.


Further data on mitochondrial malic enzyme in man. Mitochondrial malic enzyme was examined by starch-gel electrophoresis in human brain samples from 291 adults and 118 fetuses, all of European origin. Gene frequencies were estimated as MEM10.65 and MEM20.35. There was no significant difference in phenotype distribution between the sexes nor between adults and fetuses. No deviation from Hardy-Weinberg equilibrium was found. Malic enzyme was examined in various other tissues and although strongest in brain, it was also frequently active in adult testis, heart and kidney. An additional isozyme migrating less anodally than mitochondrial malic enzyme and especially prominent in heart muscle was found to be attributable to a combination of aconitase and isocitrate dehydrogenase acting on citrate in the gel buffer.


GLO I and Bf phenotype distribution in a West German population sample. GLO I phenotypes were determined in 1,075 unrelated West German individuals by starch gel electrophoresis. Gene frequencies were 0.4512 for GLO1 and 0.5488 for GLO2.  Association studies between GLO I and Bf in 985 individuals of which Bf phenotypes were known from previous reports gave no significant evidence for close association between the two systems.


Immunoglobulin Gm and Km genetic markers in Vietnamese. The distribution of the G1m (1,2,3,17), G2m(23), G3m(5,10,11,13,14,15,21,28) and Km (1,2) allotypic markers has been examined in 122 unrelated Vietnamese subjects originating from all regions of Vietnam. The 13 observed phenotypes have been explained by means of 8 haplotypes: 5 'major' ones (which are also known to be usual in all other reported Mongoloid populations) and 3 'minor' ones. Consideration of gene frequencies allows easy integration of Vietnamese within the south-north cline of Gm haplotype distribution in East Asia, where they insert between Southern Chinese, on one hand, and Singapore as well as South Central Chinese on the other hand. The observed Km10.290 frequency value revealed to be of the same order of magnitude as the values reported for most other non-Thai Mongoloids.


Genetical distance and dermatoglyphic characters. II. Intrapopulation distance coefficients. This paper attempts to evaluate the dermatoglyphic (genetical) distance between two Polish population samples in relation to the intrapopulation distance coefficients estimated within each sample. All the coefficients have been based, in turn, on frequencies of fingertip, palmar and sole pattern elements, separately and for all characters combined. The results of a comparison of various combinations of dermatoglyphic characters with one another in respect of all successive values of a distance coefficient indicate that, if populations of mostly related individuals were compared, sole patterns have been the most efficient ones in differentiating between the two normal population samples. The values of inter- and intrapopulation distance coefficients obtained from samples consisting mostly of family units have been compared with those estimated in samples of non-related individuals. The limitations and difficulties in the interpretation of the values of a distance coefficient related both to the material used and statistical procedures are discussed.


Chemical models for possible nitrosamine artifact formation in environmental analysis. Preliminary data concerning two different phenomena of potential importance to those studying the analysis and formation of environmental N-nitroso compounds are presented. First of all, we report that inorganic nitrite in the solid phase can serve as an effective nitrosating agent for solutions of amines in certain nonaqueous media. Secondly, we describe evidence suggesting that the appearance of nitrosamines as contaminants in deionized water (Cohen, 1977; Gough et al., 1977; Fiddler et al., 1977) might result at least partly from simple, acid-catalyzed nitrosation of the amine/ammonium functional groups on the anion exchange resins used in the demineralization process. Possible implications of both phenomena are discussed and potentially useful measures for their control are suggested.


Studies related to nitrosamide formation: nitrosation in solvent: water and solvent systems, nitrosomethylurea formation in the rat stomach and analysis of a fish product for ureas. Nitrous acid (HNO2) was partly extracted from water by organic solvents, especially polar ones. Carbaryl was nitrosated in solvent: water mixtures most rapidly when nonpolar solvents, e.g. methylene chloride, carbon tetrachloride and hexane, were used. Under given conditions, carbaryl was nitrosated in methylene chloride:water mixtures 20 times faster than in water alone, mainly because of its insolubility in water. For ethylurea, hexylurea, ethyl N-ethyl-carbamate and aminopyrine, nitrosation by sodium sulfate-dried methylene chloride extracts of nitrous acid ('dried HNO2') was at least 88% complete after reaction for 5 seconds at 6 degrees C. Nitrosation of N-butylacetamide by the same extract proceeded more slowly, with a second-order rate constant 31,000 times greater than for nitrosation in water at pH 2. Butylacetamide was nitrosated in methylene chloride by equivalent concentrations of 'dried HNO2', dinitrogen trioxide and dinitrogen tetroxide at similar rates. Nitrosomethylurea (NMU) formation was measured radioactively in the stomach contents of rats fed [3H]methylurea (MU) and sodium nitrite. When both compounds were given in the food (100 mg MU and 4 g NaNO2/kg) and the rats were killed 3 hours later, the NMU yield was 0.46% of the MU. When the food also contained 11.5 g sodium ascorbate/kg, NMU production was completely inhibited. With 2-4 g/1 sodium nitrite in the drinking water and MU in the food, no NMU was detected. Ureas were determined in dried, salted bonito fish from Japan, by a method involving ion-exchange and paper chromatography. The fish sample contained 80 mg urea/kg, but no MU. When the fish was nitrosated at pH 1 and then denitrosated at pH 0, 25 mg MU/kg was detected. Mu identity was confirmed by mass spectrometry.


Characteristics of the TEA detector in use with high pressure liquid chromatography. It was found that the response of the TEA detector was highly dependent on the operating temperature of the furnace and on the flow rate of gas that is used to purge the furnace. It was also found that the response of the detector was very highly dependent on the volatility of the nitroso compound and the optimum operating conditions were also very different for low and high volatility compounds. When samples containing equal quantities of NDMA, NPYR, NPRO and NPIC were chromatographed at low furnace temperatures, only the peaks for NPRO and NPIC (low volatility) were observed. When a high furnace temperature was used, only NDMA and NPYR (high volatility) were routinely observed. At intermediate temperatures, all four compounds could usually be observed. Under optimum conditions, the sensitivity was 3 microgram/ml for NPRO and 5 microgram/ml for NPIC.