["Worthy of life and unworthy of life"--not an alternative for the physician].
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Biomedical subjects
Publications and source records attributed to H Berger.
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Evidence is presented for defective pyruvate dehydrogenase (EC 4.1.1.1) in leukocytes and muscle tissue from a 10-year old child with persistent lactic acidosis, suffering from myasthenia and growth retardation. The defect is expressed in vitro by a depressed stimulation of pyruvate dehydrogenase catalytic activity by exogenous phosphoprotein phosphatase, and in vivo by a lack of response to muscle work, in comparison with healthy controls. Pyruvate dehydrogenase activity is in the normal range when measured without addition of phosphoprotein phosphatase in cells obtained from the resting patient. The defect reported here represents a new, hitherto undescribed form of a pyruvate dehydrogenase deficiency. The insufficient catalytic activity explains the observed accumulation of pyruvate, lactate, oxaloacetate and alanine and the decrease of citrate concentration in the blood of this patient. Electron microscope studies of the muscle tissue show an enhanced number of enlarged mitochondria with bizarre shapes and high densities of cristae.
Vitamin C (ascorbic acid) levels in cerebrospinal fluid (CSF) and plasma from 67 children, in whom lumbar puncture had to be performed for medical reasons, are reported in this preliminary paper. 14 children of this group show normal CSF laboratory values and serve as controls. Vitamin C concentrations in CSF of controls are on average 2.5-3-times higher (30.1 +/- 6.3 mg/l) than the pertaining values in their plasma (12.2 +/- 4.9 mg/l). Significant differences are exhibited by premature and term babies, which have up to 16-times higher values of vitamin C in CSF than in plasma. Furthermore CSF vitamin C is 4-5 times higher in premature babies than in schoolchildren of our group (118.2 +/- 65.9 versus 28.3 +/- 3.0 mg/l). Another interesting finding in this study is a significant decrease of CSF vitamin C in cases of acute purulent meningitis (12.3 +/- 4.8 versus 30.1 +/- 6.3 mg/l, p less than 0.05). These results, in connection with reports about high vitamin C concentrations in brain tissue, particularly in prematures, make one suspect important functions of this vitamin in physiological and pathological mechanisms in the central nervous system.
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The catabolism of human tissue plasminogen activator (t-PA) was studied in mice. The clearance of t-PA labeled with iodine 125 was rapid (t1/2). The clearance of phenylmethylsulfonyl-125I-t-PA, which is active site-inhibited, was identical to the active enzyme. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that the vast majority of 125I-t-PA injected into the circulation was present as free enzyme and not in a complex with inhibitors. The clearance of 125I-t-PA was unaltered by large molar excesses of several ligands of known clearance specificities, including macroalbumin, asialoorosomucoid, and diisopropylphosphorylthrombin and was also not altered in the presence of a 1,000-fold molar excess of unlabeled t-PA. Organ distribution studies demonstrated that the early rapid clearance of 125I-t-PA occurred in hepatocytes, followed by a later renal phase of clearance. The clearance of 125I-urokinase (UK) also was studied and was very similar in all aspects to the clearance of 125I-t-PA. These results suggest that both t-PA and UK are cleared from the circulation by unique nonsaturable processes localized in the liver that are independent of the proteinase active site.
Randomized serial tests of their metabolic state over four weeks, without self-testing and during daily urinary glucose-profile testing (4 tests) with the Diabur-Test or blood-glucose levels with the Haemo-Gluco-test 20-800 (5 tests daily) on two days weekly were undertaken on 27 unselected insulin-treated outpatient diabetes. HbA1, blood glucose, serum cholesterol, triglycerides and VLDL, LDL and HDL cholesterol were the target values. The following metabolic values were significantly reduced (P less than 0.05) during blood-glucose self-testing, compared with the results during the non-testing phase: HbA1 on average by 11%, blood-glucose (starving) by 20%, serum cholesterol by 9%, serum triglycerides by 13%. Self-testing of urinary glucose (compared with the test-free phase) brought little improvement in the metabolic state. The results of self-testing were the more impressive the worse the metabolic state during the phase without self-testing. Except for VLDL and HDL cholesterol, changes in HbA1 correlated well during all phases with changes in the other metabolic values (P less than 0.05).
11 different feedstuffs (barley, wheat, rye, oat, wheat bran, soybean meal, peanut meal, cottonseed meal, rapeseed meal, horse bean, fish meal) were tested with adult colostomized broiler hens in digestion experiments; the digestibility of the crude protein and the amino acid (AA) balance of the gastro-intestinal tract were ascertained. The results achieved can be summarised as follows: The AA-composition in faecal protein is relatively independent of the AA-composition of the feedstuffs, it is not constant, however. The NPN-quota in faecal crude protein rises with the increasing crude fibre content in the feed. AA-digestibility calculated from the balance of the gastro-intestinal tract is, with the exception of some AA, in particularly the limiting ones, higher than the digestibility of the crude protein. As the AA-balance of the gastro-intestinal tract does not give a realistic picture of the digestibility of the AA, we recommend to ascertain the AA-balance up to the end of the small intestines in order to gain more profound knowledge with the help of such basic investigations with selected feedstuffs.
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Medical problems occurring during electroconvulsive therapy were studied in a population of 293 psychiatric inpatients who received 2,809 treatments. Geriatric patients (N = 199) developed significantly more medical problems that required medical treatment or temporary discontinuation of electroconvulsive therapy than did younger controls (N = 94). The most important of these were cardiovascular in nature. Despite their increased frequency, the majority of medical problems that occurred were reversible. Electroconvulsive therapy therefore appeared to be a safe procedure for elderly psychiatric patients.
The case of a male child with primary hyperoxaluria type I is reported. In spite of many therapeutic trials, haemodialysis treatment for several years and renal transplantation at the age of 11 years, the patient died after the transplanted kidney had failed.
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Anthelmintic efficacy, safety, and residue studies were conducted in beef calves using a levamisole gel formulation. The effectiveness of levamisole gel and tablet formulations was studied in 30 calves with experimental infection of Ostertagia ostertagi. Removal of 33- to 34-day-old O ostertagi was 99.6% and 97.7%, for the gel and tablet formulation, respectively, when administered orally to supply 8 mg of levamisole HCl equivalent/kg of body weight. A comparative blood concentration study was also used to demonstrate bioequivalence of the levamisole gel to the tablet formulation. In a cross-over-designed test, 5 cattle/treatment group were dosed orally with levamisole 11.5% gel or levamisole tablets at the dosage rate of 8 mg of levamisole HCl/kg. Blood levamisole values were similar with the levamisole gel and tablet formulations. In a safety study, 3 groups of 6 calves each were given levamisole gel orally to provide 8, 24, or 40 mg of levamisole HCl/kg. A 4th group served as controls. Adverse clinical signs were not observed in cattle treated with the recommended dosage level of 8 mg/kg. Transient salivation was noticed in 1 placebo control calf, 2 calves given 24 mg/kg, and 4 calves given 40 mg/kg. Edible tissues from cattle given a single oral dose of levamisole gel (8 mg/kg) were analyzed for drug residues 2 hours and 2, 3, 5, and 7 days after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Analogs of luteinizing hormone-releasing hormone (LHRH) having higher biological activity than LHRH itself are being mainly used to study the biological effects and the mechanism of action of LHRH. In the present study, conditions for the direct 3H-labelling at the histidine residue of analogs of LHRH were worked out, circumventing the synthesis of precursor peptides for labelling. [D-Phe6,desGly10]-LHRH ethylamide and [D-Ser(But)6,desGly10]-LHRH ethylamide were tritiated by tritium gas and a 10% Pd/Al2O3 catalyst to high specific radioactivities. The labelled peptides are sufficiently stable to be used in biochemical studies. The degradability of the analogs by homogenates of various tissues of rats was compared with that of the native LHRH. The analogs were shown to be distinctly degradable, but to a lower extent. The kidney homogenate degrades the analogs [D-Phe6,desGly10]- and [D-Ser(But)6,desGly10]-LHRH ethylamide with 35 and 50%, respectively, of the velocity observed with LHRH, whereas the degradation velocity of the analogs by a homogenate of the hypothalamus and pituitary is only 10% of that of LHRH. It is suggested that the lower degradability of the analogs at peripheral sites and target sites (pituitary, ovary) explains partly their higher biological activity.
Hairless female Ng/-mice were irradiated by UV-light for 16 h daily over a period of 24 weeks. Monooxygenase activities were measured in liver and skin, and an induction of the aryl-hydrocarbon hydroxylase was detected in liver by both fluorometric and radiochemical methods, whereas no induction of this enzyme could be demonstrated in the skin.
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