[Preservation of porcine livers by retrograde oxygen persufflation].
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Biomedical subjects
Publications and source records attributed to D Weber.
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Changes in histamine storage in the oxyntic mucosa of duodenal ulcer patients and their reversal by vagotomy and the histamine H2-antagonist cimetidine supported the hypothesis that histamine could be a causal factor in peptic ulcer pathogenesis. The specificity of these findings was impaired by problems in biopsy taking, however, and in the preparative steps before measuring the actual histamine contents in all parts of the gastric mucosa and in the duodenum. A prospective trial was carried out in 190 patients to identify these sources of bias and to overcome them by appropriate study designs. Usually a direct correlation was found between weight of biopsy and mucosal histamine content. This problem was solved by selecting a biopsy forceps producing smaller variations in sample size, by limiting the time of cold ischaemia to four to five minutes only and by taking three biopsy specimens for each single histamine value. The actual histamine content of mucosal biopsies remained constant for about four to five minutes only. The 'disappearance' rate was faster in control subjects than in duodenal ulcer patients. Hence by variation of the cold ischaemia time any artefacts of differences between mucosal histamine levels in controls and duodenal ulcer patients could be produced. Using the optimised sample taking procedure mucosal histamine contents of several gastric regions and the duodenal bulb were measured in 24 patients with duodenal ulcer, after selective proximal vagotomy without drainage and in control subjects without any stomach disease (randomised controlled trial). The histamine content was lower in all parts of the upper gastrointestinal tract in duodenal ulcer patients than in controls and was raised again in all regions after selective proximal vagotomy. As the most likely hypothesis it is suggested that vagal reflexes with afferent fibres coming from the oxyntic mucosa stimulate histamine release in duodenal ulcer patients by efferent peptidergic neurones to all parts of the stomach and the duodenum where the ulcer lesion is situated.
To understand the role of histamine in the aetiology and pathogenesis of human diseases reliable data are urgently needed for the histamine content and for the activities of histamine-forming and -inactivating enzymes in human tissues. In order to make a substantial progress toward this aim a tissue-sampling programme during surgical interventions was carefully conceived and conducted. From March 1982 until January 1983 106 tissue specimens were taken from 56 patients who underwent surgery. Only healthy tissues, not injured or oedematous, and without adherent structures were taken by only one surgeon who was interested in this research and experienced in tissue preparation procedures in biochemistry. The times of 'warm' ischaemia during the operative procedures were visually estimated, the times between resection of the organs or specimens and deep-freezing of the tissues were precisely recorded. Compared to previous work in the literature and especially to our own work using the same assays for determination higher histamine contents were found in this study in most of the tissues, in particular in the gastrointestinal tract. Also the diamine oxidase activities were considerably higher in many organs, e.g. 3-4 times higher in the gastrointestinal tract when compared with those in publications of our group who used always the same analytical test. However, the histamine methyltransferase activities in this study were not at variance to those determined in previous investigations. Many of them were reported in this communication for the first time. Since the methods for histamine determination and those for measuring enzymic activities were not different in this study and in previous communications of our group we are convinced that the optimized tissue-sampling and -preparation techniques were responsible for the higher values in this communication. But the problem of the 'warm' ischaemia period could not be solved by sample-taking procedures of this type during operations. There are good reasons to prefer biopsy specimens for the analysis of histamine storage and metabolism in human tissues in health and disease, but - unfortunately - they are not always available.
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630 outpatients and inpatients under rest as well as under conditions of physical loads and psychic stress were examined with the help of a radiobiotelemetry device of own construction, which corresponds to a combination of traditional radiotelemetry and tape storage. In 81.4% of the patients with hitherto unclarified disturbances of the cardiac rhythm telemetry obtained their qualitative clarification. In 50% of all cases with classical angina pectoris symptomatology the ischaemic heart disease was verified by determination of the usual criterias of ECG at the telemetry stripe. Of these 50% only 7 patients had no arrhythmia. In 57.5% of all examined patients with pacemakers of permanent frequency we could prove a considerable parasystoly in load by telemetry. 9 patients with R-demand-pacemakers became evident by triggering defects in load. During the psychoanalytic examination we registered extrasystoles in 25%, apart from this once developed a pancardiac asystolism. The radiobiotelemetry is a valuable completion of the well-known methods of load.
Histamine assays can be unreliable in individual subjects or samples even though the particular method is in general working very well. Therefore the specificity and accuracy of histamine determination in the gastric aspirate of individual duodenal ulcer patients was thoroughly examined and shown to be satisfactory. Pitfalls of the fluorometric assay were investigated. A native (non-histamine) fluorescence in gastric aspirate which occurs before the addition of OPT was not removed by the original Shore procedure. In the combined assay (Dowex 50 + butanol extraction) this fluorescence no longer interferes with the assay. For the identification of histamine in a single gastric aspirate of an individual duodenal ulcer patient, the reversed blank (3 M HCl added to the reaction mixture before OPT instead after OPT), excitation and fluorescence spectra, the heating test with spectra recorded and the HMT test were found to be reliable. The formaldehyde test and the heating test without recording the spectra were useless since they gave false negative results. Since the HMT test was regarded as a reference method it was thoroughly investigated both by theoretical considerations (enzyme kinetics) and by a series of measurements in a single patient as well as in a group of nine subjects. Samples from the period of peak acid output in response to pentagastrin showed an average histamine concentration of about 8 ng/ml and a histamine output of 1.5 microgram/30 min.
Anaphylactoid reactions in man following administration of drugs solubilized with cremophor El (polyethylenglycolglycerol riconoleate) are a considerable clinical problem. Since these reactions occur in dogs on first exposure and in pigs on second exposure, the 'dog model' was used in this communication to analyse components and chemical modifications of cremophor El and its components for their clinical effects, their hypotensive actions and their histamine-releasing capacity. Two series of experiments in 1978 and 1980 were performed in 144 adult mongrel dogs of both sexes. In these studies histamine release was not related to the effect of the solubilizing agents as tensides and was elicited by rather low doses (about 10--100 mg/kg i.v.). The effect of these substances on blood pressure and on blood histamine levels was connected with distinct chemical features: the most potent compounds were oxethylated and additionally esterified unsaturated or hydroxylated fatty acids. Several phases in hypotensive reactions were observed, including an immediate response, a delayed blood pressure response and a late response about 15--20 min after injection. Only the delayed response was associated with histamine release. The combination of cardiovascular effects and histamine release was fatal on some occasions indicating that histamine release can be dangerous. Compared to cremophor El, the tenside effect was equal, but the toxicity was reduced in oxethylated 12-hydroxystearic acid. It is recommended that this solubilizer should be used in further extended studies in animals and - if these are successful - in clinical trials.
In different habitats around Saarbrücken, all fox dens were searched systematically and their use by foxes checked regularly. Most of the dens used were not dug by the foxes themselves. In the wooded sandstone areas, den sites are plentiful, allowing the foxes a wide choice. In the agricultural limestone area, dens are restricted to a few suitable places. During the breeding season, foxes spent their inactive periods mainly inside the dens. At other times, dens seemed to have mainly social functions. The distribution of foxes can be heavily influenced by the distribution of suitable dens. The influence of reducing foxes in dens by gassing and shooting on population dynamics is discussed. It is suggested that it can be a density-limiting mortality factor in areas with restricted den availability.
Postoperative care of patients with a portacaval shunt is identical with the perioperative care performed to avoid the dangerous complications of cirrhosis of the liver. Clinical symptoms (edema, ascites, skin changes) and clinical chemistry (prothrombin time, bilirubin, albumin) will allow, to survey liver function appropriately. Neurological examination and simple psychosomatic tests (test of writing, trail making test) will allow to recognize early the occurrence of hepatoportal encephalopathy. EEG examinations done every 4 to 6 months are helpful in diagnosis. X-ray or endoscopic examinations should be done, if gastric ulcers are suspected. A definite warning must be pronounced against using high ceiling diuretics of unnecessarily; diuretics should be given only for short periods of time and in low dosage. Regular measurements of serum electrolytes are mandatory. The patient must be informed about the rationale of the diet restricted in proteins and abstinence from alcohol.
The ability of moderately mentally retarded children to set self-performance standards was investigated. We hypothesized that (a) subjects who received training based on the relational concept of "between" would be able to acquire and retain superior standard-setting performance compared to nontrained control subjects, and (b) those receiving this training would be able to generalize their superior standard-setting performance to a task involving more variable feedback as well as to a conceptually more abstract task. Results indicated that the subjects learned and retained concepts that allowed them to set appropriate or realistic self-performance standards. Further, retarded subjects were able to set appropriate standards when given less restricted feedback than was given during the initial training. On a more abstract picture-matching task, no significant differences were found between the two groups.
Ventricular flutter evokes quick, haemodynamically little effective ventricular contractions. The still existing minimal circulation does not maintain the vital functions. Ventricular fibrillation is tantamount to the acute standstill of the cardiac circulation. If they are not treated, these malignant disturbances of the rhythm nearly always lead to death. Reentry processes or foci with rapid formation of impulses are discussed as responsible electrophysiological mechanisms. Warning arrhythmias are significant for the evocation of ventricular flutter and fibrillation. But the concept of the warning arrhythmias has no unrestricted validity. Thus also late involving ventricular extrasystoles can evoke ventricular fibrillation. Disturbances of intraventricular conduction are also significant for the development of ventricular fibrillation. In our own patients there were no disturbances of conduction only in 13.1% of the cases with ventricular fibrillation. Etiologically are of concern: acute myocardial infarction, chronic myocarditis, chronic ischaemic heart disease, current accidents, advanced stages of vitia and cardiomyopathies. Frequently ventricular fibrillation appears as paroxysmal form (paroxysmal uncoordinated ventricular tachycardia, "torsades de pointe") due to inhomogeneous repolarisation (prolongation of the QTU-time). Therapeutically only the immediate electro-shock therapy has a chance of success in ventricular flutter or fibrillation. Among our patients out of 61 patients with ventricular flutter and fibrillation 26 could be dismissed.
Within a research program on the functional approach of the handicap we have realized a psychological survey in order to test the relationship between the functional approach and the desires of the disabled. 72 handicapped persons, fairly representative of the general population of our area, were included into the study. A coded interview, a projection test and a connotation test were carried out and their result computerized and statistically analyzed. The results show clearly that the handicap, if it modifies the daily life of the subjects, has no repercussion on personality tendencies. The emotional repercussion of experienced situations is independent of the characteristics of the handicap. The perception of his body is, for the handicapped, in reference to the others. Confrontation favors the integration of handicapped people. The experience of being handicapped in daily life exists only in situations where the others are involved.
It has been suggested that histamine contributes to lethal circulatory collapse after acute superior mesenteric artery occlusion. The activity of the histamine inactivating enzyme diamine oxidase, the release of the amine, and the effect of histamine receptor antagonists was therefore studied in rabbits. The main results were: (a) Diamine oxidase activity decreased by 60% after intestinal ischemia and reperfusion. A monoexponential dose-response relationship was found between the specific diamine oxidase inhibitor aminoguanidine and reduced survival time. (b) Plasma histamine levels in the right atrium rose only slightly after ischemia, but considerably during reperfusion of the gut, and remained high for at least 20 min. In sham-operated animals the plasma histamine concentration was unchanged throughout the experiment. The histamine content in the intestinal wall did not fall significantly at any time after mesenteric artery occlusion and reperfusion. (c) The aminoguanidine-induced reduction in survival time was completely reversed by pre-treatment of the animals with the H1-receptor antagonist dimethylpyridine and the H2-receptor antagonist cimetidine. This study provides strong evidence for the protective role of intestinal diamine oxidase in intestinal ischemia.
Doxycycline levels in various organs of mice after i.v. and p.o. administration were measured by a high-performance liquid chromatography method. When given as a single dose (50 mg/kg) i.v. doxycycline accumulated in the lung. High concentrations were also measured in liver and kidneys. When 50 mg/kg doxycycline were administered by stomach tube to fed mice the antibiotic accumulated to a lesser degree in the lung. On the other hand, the antibiotic levels in the liver and the kidneys were higher as after i.v. injection. The absorption of doxycycline administered p.o. was about 92% and seemed not to be influenced by food in the stomach. The elimination half-life in mice was 170 min independent of the route of administration.
The effects of tetracycline and doxycycline (10-100 mg/g i.v.) on the triglyceride and cholesterol contents of liver and blood were studied comparatively in male and female mice. Only tetracycline increased the triglyceride content of the liver. The cholesterol content of the liver was raised by both tetracycline and doxycycline. Tetracycline and doxycycline increased the concentration of unesterified cholesterol and decreased esterified and total cholesterol in the serum. Most effects were more consistent or more pronounced in females than in males.
The creation of a secure venous access is the basis of the infusion therapy and the parenteral nutrition. As ways of access are suited above all the subclavian vein, the internal jugular vein and the basilic vein. Taking into consideration the contraindications and the exact performance of the various methods early complications such as punctures of the arteries, pneumothorax, rupture of the catheter and extended haematomata may be reduced to a minimum. Abnormal positions are avoided by control of the position by means of endo-ECG via steel mandrin. As late complications are observed infections at the place of puncture, unclear, partly septic temperatures and clinically manifest thromboses. Own experiences with 3,282 central venous catheters (2,057 subclavian catheters, 63 catheter into the internal jugular vein and 1,162 central catheters with access via arm veins) are taken into consideration.
Histamine release by drugs used in anaesthesia and surgery has been often demonstrated in human volunteers, but only occassionally in patients. Three questions arose from these studies. (1) Is the incidence of histamine release high in patients during routine anaesthesia and surgery? (2) Can the clinical effects of histamine release in man be prevented by H1 + H2-receptor antagonists? (3) Are there any side-effects of such a premedication? These problems were investigated in patients and volunteers by randomized controlled clinical trials using only one of the histamine-liberating drugs in man, the plasma substitute Haemaccel. This drug was chosen because it causes a reproducible histamine release in man and because its mechanism of action in man is largely known. (1) Out of 600 orthopaedic patients 30 (5%) showed anaphylactoid reactions following Haemaccel infusion. 26 of these had a histamine release of more than 1 ng histamine/ml plasma. Using predictive values this gives an efficiency of the test by nearly 98%. (2) In volunteers the combination of an H1-plus H2-receptor antagonist (dimethypyrindene and cimetidine) completely prevented the clinical effects of histamine release by Haemaccel (9 allergoid and anaphylactoid reactions in the control group, none in the H1 + H2-group). The incidence of histamine release, however, remained unchanged. (3) The premedication was found to release histamine itself. Cimetidine was effective when given alone but especially in combination with chlorpheniramine (4 events out of 7 applications). The clinical side-effects of these premedication were mild since apparently the free histamine was largely blocked at the receptor sites. It is concluded that premedication with a combination of H1- and H2-receptor antagonists is indicated due to the high incidence of histamine release during anaesthesia and surgery induced by various drugs and treatments. Such premedication is effective but associated with mild side-effects. For this reason more extended clinical trials with dimethpyrindene plus cimetidine in patients are necessary before this premedication can be generally recommended.
From a methodological point of view the relevance of clinical-biochemical trials depends on the answers to mainly four complexes of questions: (1) the reliability of the assays in the clinical situation to be tested, (2) the precision and accuracy of sample-taking, (3) the qualification of the design and the protocols in the clinical part of the trial and (4) the usefulness of the time concepts in the trial concerning biorhythms, seasonal influences, psychological trauma of diagnostic procedures and treatment. In this study mainly the second complex of questions was studied intensely. The precision of the fluorometric histamine assay in biopsy specimens from human gastric mucosa depended on several conditions: Biochemical technique, sample preparation and removal of biopsies from gastric mucosa via endoscopy. The CV% of the whole procedure was about 8-times higher than that of the biochemical technique. In clinical-biochemical studies on the significance of histamine or any other hormone (such as gastrin) in any disease (uch as duodenal ulcer) it seems therefore useless to describe the precision of an assay only by the variance of the biochemical technique. Calculation of the histamine content as mean of 3 samples reduced the CV% from 27.2 to 14.9% and should therefore be recommended.