Biomedical subjects
Publications and source records attributed to H Kummer.
A 93 year old man with a severe anaemia with possible origin in the gastrointestinal tract refused any clarifying examinations except palliative blood transfusions. Within half a year, he received 48 red blood cell transfusions without any diagnostic or other therapeutically steps. To further decide on treatment strategies, we discussed this problematic case with our local ethic committee and found a reasonable treatment solution
Seven long-tailed macaques (Macaca fascicularis) were trained by threats not to drink from a juice nipple as long as an experimenter was facing them. However, they were allowed to drink when the experimenter was standing with his or her back turned. During transfer tests, the monkeys had a choice between 2 juice nipples, one uncovered and the other hidden from the experimenter by a wooden screen, while the experimenter was facing them. We tested whether the monkeys would then prefer to drink behind the screen, thus demonstrating that they transferred knowledge acquired during training. Results did not yield a significant outcome, suggesting that the macaques did not transfer the observable "experimenter's visible open eyes" and that they did not take the experimenter's perspective.
Idiopathic hypereosinophilic syndrome (IHES) is a multi-system disorder of unknown origin with eosinophilic infiltration of bone marrow and various organs, including the gastrointestinal tract. Involvement of the heart has a poor prognosis. The etiology of eosinophilic gastroenteritis (EGE) also is unclear. In this disease there is exclusive involvement of the gastrointestinal tract (including liver/bile ducts) and prognosis usually is good. Transition from one disease to the other has not yet been described. We report the 20 years' history of a male patient with an initial IHES without gastrointestinal symptoms and transition to a clinically pure EGE with resolution of any other involvement. At the age of 45 years the patient developed IHES with fever and constitutional symptoms. Fluctuating eosinophilia and symptoms necessitated continuous steroid therapy. After a 10 years' disease course watery diarrhea and malabsorption syndrome became more and more prominent. On the other hand, bone marrow eosinophilia regressed completely and blood eosinophilia partially. Biopsies showed a severe EGE of the mucosal type with involvement of the whole gastrointestinal tract. Besides the prominent eosinophilia there was a dense infiltration of the intestinal mucosa with T-lymphocytes invading the epithelium. We postulate that the destructive eosinophilic/lymphocytic inflammation is caused by a pathologic proliferation of T-lymphocytes with liberation of type 2 helper cell cytokines and consecutive stimulation of eosinophils.
In a Swiss multicenter study with determination of lipid and lipoprotein parameters in a central laboratory, the efficacy of simvastatin, MSD, was evaluated in patients with primary hypercholesterolemia. Lipid and lipoprotein values were determined in 109 patients before and after 6 weeks' therapy with 10 mg simvastatin per day. A significant decrease in total cholesterol, LDL-cholesterol and apo B, of 21.1, 25.8 and 24.1% respectively, was observed. No influence of simvastatin on apo A-II was found, but HDL-cholesterol and apo A-I were slightly increased (+6.1 and 4.4% respectively). The data show that HMG-CoA reductase inhibitors constitute a new class of effective drugs for the treatment of hypercholesterolemia.
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We report on the clinical signs, diagnosis and 8-year course in a 54-year-old female patient with myeloma and gastrinoma with liver metastasis and associated Cushing syndrome treated for the last 3 years with the new H+/K+-ATPase inhibitor omeprazole which has successfully suppressed the massive gastric acid hypersecretion.
From the storage proteins of the pea (Pisum sativum), the fraction which interacts with the pea lectin by the sugar-binding site was studied. By electrophoretical subunit patterns and other criteria, this fraction resembles the group of the 7S storage proteins (vicilins). The fraction was resolved into subunits by micropreparative SDS PAGE. The N-terminal sequences of the individual subunits were determined. Most of these are identical with published vivilin subunit sequences; therefore this lectin-binding fraction belongs to the vicilins. Selected subunits and tryptic fragments were analysed for amino-acid compositions. Though unequivocal assignments to vicilin segments were possible, significant differences could be recognized, in particular in the tryptic fragments.
The alpha-mannosidase from Canavalia ensiformis is devoid of cysteine and cystine. Nevertheless, its cleavage into subunits is facilitated by the presence of mercaptoethanol in the denaturing buffer.
Human purin metabolism is summarized briefly and the terms primary and secondary gout are defined. Asymptomatic hyperuricemia as a risk factor for gout, urate nephropathy and ischemic heart disease is discussed. Treatment modalities of hyperuricemia are presented.
Previous work from this laboratory had shown that Leguminosa seed extracts contain lectin-bound proteins. In the present paper, the isolation of protein bodies from the seeds of 7 Leguminosa species (Canavalia ensiformis, Lens culinaris, Pisum sativum, Glycine max, Sophora japonica, Wisteria floribunda and Phaseolus vulgaris) is described. Protein bodies were characterized microscopically and by their constituents, storage proteins, lectins and some glycosidases. From the protein bodies, lectin-bound proteins were isolated and were shown to be identical with those from whole seed extracts. This indicates a common localization of lectin-bound proteins and of lectins. Lectin-bound proteins belong to the storage proteins and to the proteins with glycosidase activity. The common localization of these proteins and interactions between them suggest a biological role of seed lectins: during maturation they may act as a packaging aid for storage proteins and enzymes into developing protein bodies. Lectins thus may contribute to an ordered construction and degradation of protein bodies.
When humans are primarily impaired or overtaxed in their more elaborate abilities of coping with the social environment they seem to fall back on more primitive coping behaviours known from other mammals in severe conflict situations. This seems true for some behaviours in early childhood autism. Ethology has specialized in analyzing such non-verbal behaviour. Ethological motivation analysis, the study of context dependence and of the development of such behaviours in the individual patient should be exploited for their interpretation. Mere description of behaviour is not likely to contribute much. Psychiatric thinking on the interaction of genetic and environmental factors does not fully agree with ethological and biological views.
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Four patients are described who developed granulomatous hepatitis 4-6 weeks after treatment with nomifensin. The granulomas were located both in the portal tract and the liver parenchyma, and contained eosinophils and a few polynuclear giant cells. Serum alkaline phosphatase, alanine aminotransferase and bilirubin were raised in three, two and one patient respectively. After medication was discontinued all abnormalities disappeared within 6-10 weeks. After oral intake of 25-50 mg nomifensin all patients experienced paroxysms of high body temperature for several hours. Reexposure in one patient resulted in another fever spike 6 hours after ingestion. No other cause of the fever or the granulomatous hepatitis was identifiable. The clinical data, especially the simultanous occurrence of drug fever and the histologic pattern, are compatible with an allergic mechanism of the liver granulomas. In the presence of high fever and abnormal liver tests in relation to nomifensin treatment, an allergic drug reaction should be considered.
In 4 women patients aged over 60 years under anticoagulation, abdominal pain, which was in part clearly localizable, and signs of acute bleeding suddenly occurred. All were under treatment with marcoumar, while one was also in the transitional phase from parenteral to oral therapy with heparin. Initially, apart from pain on pressure, there were no local signs of bleeding. In the acute stage it was impossible to distinguish clinically between abdominal wall bleeding and intraperitoneal bleeding. Ultrasound provided the diagnosis of abdominal wall bleeding in all cases. All of them were successfully treated by conservative means.
A 53-year-old, previously healthy man developed persistent diarrhea 4 days after ingestion of smoked but uncooked pork sausages in the Southern Tyrol. On his return to Switzerland he ate the same sausages and was admitted to hospital with migrating muscle pain, fever and chills. While fever and diarrhea soon regressed, the patient exhibited neurologic symptoms and change of character. The leukocyte count was 14 000/mm3 with 39% eosinophils. 40 days after hospitalization a second muscle biopsy established the diagnosis of Trichinella spiralis infection. At the same time, serologic tests were positive for Trichinella spiralis. Epidemiology, parasitology, symptomatology, diagnosis, therapy, prophylaxis and prognosis of trichinellosis are briefly discussed.
Using 14C-labelled 4-amino-6-methoxy-1-phenyl-pyridazinium methyl sulfate (ameziniummetilsulfate, LU 1631, Regulton), briefly called amezinium, the time course of plasma level in the rat and of blood level and renal excretion rate in the dog has been followed. The distribution of radioactivity in the organism was investigated by autoradiography of whole-animal sections and by quantitative radioactivity determinations in rat tissue as well as by in vitro experiments. From the results we draw the following conclusions: 1. In the two species investigated here, amezinium is almost completely absorbed after enteral administration. In the rat the absorption proceeds with a half-life of 11 min, after a lag phase of 6 min. In the dog, the lag phase is 30-40 min, after which the compound is absorbed with a half-life of 30 min or less. The small intestine appears to be the site of absorption. 2. Amezinium has a high affinity for tissues. Its transport through the cell membrane, in the case of sympathetic neurons and probably also in the case of other chromaffin cells, is mediated by the noradrenaline carrier; in other tissues, for example the liver, a different active transport mechanism, as yet not elucidated, is operating. The placenta and blood-brain barrier are passed only slightly, if at all. In rat blood amezinium distributes between erythrocytes and plasma with a ratio of 2.7:1; the proportion bound to plasma proteins is about 20%. 3. In the rat amezinium is eliminated from the circulation to the extent of about 3/4 by biotransformation; on enteral administration, about 80% is trapped by first-pass metabolism. In the dog biotransformation accounting for about 40% of the elimination is relatively unimportant; the first-pass metabolism is virtually negligible. 4. Amezinium is eliminated by rats about equally with urine and bile, whilst in the dog the predominant proportion is excreted renally. From plasma level curves the terminal half-life t 1/2 (beta) in the rat was found to be 17 h and 21 h after i.v. and p.o. administration, respectively; blood level data and urinary excretion data in the case of the dog gave 5 1/2 (beta) values between 11 h and 20 h. 5. Renal clearance of amezinium in the dog is not constant: initially it is several times greater than the glomerular filtration rate (GFR) decreasing subsequently to about the same magnitude or even below the GFR.
The metabolism of 14C-labelled 4-amino-6-methoxy-1-phenyl-pyridazinium methyl sulfate (ameziniummetilsulfate, LU 1631, Regulton), in the following briefly called amezinium, was studied in 6 animal species (dog, cat, rabbit, guinea-pig, rat, and mouse) and in humans. Two-dimensional thin-layer radiochromatography revealed qualitative and quantitative differences between species. In man, dog, cat, guinea-pig, and mouse unchanged amezinium is the principal excretion product, accounting for 56-89% of the radioactivity in the urine whilst metabolites predominate in the rabbit and particularly in the rat. Since besides unchanged amezinium (I) no radioactive substance from the urine is adsorbed on cation exchanger, the first step of biotransformation is assumed to be the formation of uncharged, pharmacologically inactive 5-amino-2-phenyl-3(2H)-pyridazinone (II). The metabolites excreted by man and dog have largely been identified; apart from small quantities of II, hydroxylated pyridazinones and/or their sulfuric acid conjugates were isolated. The formation of the metabolites is discussed.
During 1979 4 patients were observed who developed short episodes of fever as high as 104 degrees F after oral intake of 25--100 mg nomifensine (Alival). In all four cases a clear fever spike was produced by reexposure to the drug. The reaction time was 4--6 hours. this drug-induced fever appeared initially 2--4 weeks after the commencement of Alival therapy. No other cause for the fever was identifiable. In one patient an allergic alveolitis was suspected to be a further reaction. In another patient a concomitant granulomatous hepatitis was possibly also due to this drug. It is probable that the febrile reactions have an allergic mechanism. Allergologic investigations have not yet been completed.