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E Neugebauer

Publications and source records attributed to E Neugebauer.

142 records · Page 8Linked to original sources
PubMed1987

[Mediators in septic shock: strategies of securing them and assessment of their causal significance].

More than 100 different mediators are discussed as being responsible for the progression of the septic shock syndrome. A new concept is described to establish the causal role of a single mediator by using a decision tree which excludes different non-causal associations (different kinds of bias and chance). By definition of several criteria and methodological standards, the published studies on mediator release/formation could be analysed and evaluated (meta-analysis). Furthermore, the classical concept of one cause--one disease (Koch-Dale) is extended to a concept of multiple determining factors. The role of a single mediator can be assessed quantitatively by notation of conditional probabilities in the presence of other causal factors. A mediator can be classified as a necessary, sufficient or contributory determinant in septic shock. Improved therapeutic concepts can be expected from this approach.

Biogenic Amines↗
PubMed1986

Induced histidine decarboxylase in endotoxic shock: identification of the enzyme in rat liver and influence of its inhibitors on survival parameters.

The hypothesis of a causal relationship between a progressive and unrestrained increase of tissue histamine formation by activation of an inducible histidine decarboxylase (HDC) and lethality in endotoxic shock (Schayer's 'induced histamine concept') was tested in a standardized rat endotoxic shock model. Initial enzyme identification studies in the rat shock liver (8 hrs after endotoxin challenge) clearly demonstrate that the 'induced' histidine decarboxylase is an acid (specific) HDC. The succeeding randomized, controlled study with appropriate inhibitors of the enzyme, alpha-methyl-histidine (competitive inhibitor) and alpha-fluoromethyl-histidine (irreversible inhibitor) using doses of 2, 20 or 100 mg/kg showed no significant effect on the survival rate of rats in endotoxin shock. The survival rate of the non-treated endotoxin control group (NaCl) was 25%; all methylprednisolone treated rats (50 mg/kg) survived. Thus, the 'induced' histamine is not a predominant factor (necessary or sufficient determinant) for the lethal outcome in rat endotoxic shock. The protective effect of MP is not predominantly due to the inhibition of the 'induced' histidine decarboxylase. The use of HDC-inhibitors as the appropriate instruments for evaluation of the significance of this mechanism is discussed.

Animals↗
PubMed1985

Identification and measurement of acid (specific) histidine decarboxylase activity in rabbit gastric mucosa: ending an old controversy?

One of the main obstacles in assigning any distinct function to histamine in health and disease was the longlasting controversy on the existence of any physiological, endogenous histamine formation in man and most of the other mammals except the rat. Using a modification of Schayer's isotope dilution method, a renewed attempt was made to identify the very low activities of an acid (specific) histidine decarboxylase in rabbit gastric mucosa capable of producing endogenous histamine in physiological conditions, to develop tests for its identification in crude enzyme extracts and to demonstrate the specificity of the enzymatic assay by excluding any relevant Dopa decarboxylase activity and also nonenzymatic decarboxylation interfering with the determination of acid (specific) histidine decarboxylase. To achieve this aim five tests were developed: In the pH profile (test 1), a pH optimum was found at 7.0 in the presence of a low substrate concentration (1.6 X 10(-6)M L-[ring-2-14C]-histidine). The apparent Michaelis concentration at the pH optimum (test 2) was 1.8 X 10(-4)M, the maximum rate 12.5pmol [14C]histamine formed X min-1. To increase the specificity of inhibition experiments with alpha-methylhistidine and alpha-methyl-L-Dopa a pH profile was determined in the presence of these two enzymatic inhibitors (test 3 and 4). alpha-Methylhistidine was used for a reliable diagnostic confirmation test, alpha-methyl-L-Dopa for a reliable exclusion test. Benzene showed no influence on either blanks or recovery rates, but inhibited the enzymic activity at pH 7.0, not however that of unspecific histidine decarboxylase and hence was very valuable as an additional diagnostic exclusion test (test 5). Although these new tests identifying acid (specific) histidine decarboxylase and demonstrating the specificity of its determination were tedious, despite the use of the modified isotope dilution method, they excluded the presence of any Dopa decarboxylase activity in mixtures with crude enzyme preparations as well as of any kind of nonspecific and nonenzymatic histidine decarboxylation. An endogenous histidine decarboxylase in rabbit gastric mucosa is postulated, capable of forming histamine in vivo.

Animals↗
PubMed1983

Metabolism and function of gastric histamine in health and disease.

Histamine is not uniformly distributed in the human and animal organisms, but occurs in high concentrations in the gastric mucosa. The enzymes responsible for its metabolism--histidine decarboxylase, histamine N-methyltransferase and diamine oxidase--seem to be less predominantly localized in the stomach. Considerable effort was necessary to detect and measure histamine formation in the gastric mucosa. This was a controversial subject that only was solved recently. Histamine inactivation by histamine methyltransferase occurs in man in the fundic gastric mucosa that has reasonable enzymic activity. However, liver, spleen and intestine show much higher activities indicating less specificity of histamine catabolism in the gastric mucosa. Finally, diamine oxidase activity was once thought to be absent in the corpus mucosa, but more recently, moderate activities of this enzyme were found in several species, including man. Thus, histamine metabolism in the gastric mucosa is by no means unique in mammalian tissues, but the presence of these enzymes may be regarded as an indicator of its physiological function. To some extent enzymic activities involved in histamine formation and inactivation are regulated in the process of acid secretion. Histidine decarboxylase and histamine N-methyltransferase activities are enhanced by gastrin, but are not influenced by vagal stimulation. Hitherto, only histamine methylation was found to be diminished in duodenal ulcer disease. Vagotomy and histamine H2-receptor antagonists modulate histamine catabolism by histamine methyltransferase. The implication of these findings for treatment of duodenal ulcer are discussed.

Amine Oxidase (Copper-Containing)↗
PubMed1982

A modified Schayer procedure for the estimation of histidine decarboxylase activity: its application on tissue extracts from gastric mucosa of various mammals.

The question of whether the gastric mucosa of mammals other than rats, mice and hamsters contains an acid (specific) histidine decarboxylase was re-investigated by using a modification of the classical isotope dilution method of Schayer. Its reliability was tested regarding sensitivity, specificity, precision and accuracy, applying criteria recommended by the International Federation of Clinical Chemistry. The assay is now suitable for measuring rather large series of samples. The suitability of several blanks for detecting histidine decarboxylase activity was investigated as a special problem of accuracy. The semicarbazide blank was found to be as reliable as the heating blank, the blank with tissue extract pretreated with perchloric acid or an incubation mixture without radio-labelled histidine. Reaction kinetics of histamine formation were linear over an incubation period of at least 3 h. Histidine decarboxylase activity as a rather low pH and substrate concentration, which is characteristic for the acid (specific) histidine decarboxylase, was demonstrated inthe gastric mucosa of human subjects, dogs, rabbits and guinea-pigs, always using the same incubation conditions for all species investigated. The highest enzymic activity was present in the oxyntic mucosa, but could be measured also in other parts of the stomach.

Animals↗
PubMed1982

[Plasma histamine assay in anaphylactoid reactions of the anesthetized subject. Effects of collection methods and plasma preparation on measured histamine].

Plasma histamine assay in man is indicated for the diagnosis of histamine release, as well as the elucidation of the mechanisms of adverse drug reactions, and the identification of clinical situations in anaesthesia and surgery where a pathological plasma histamine level may occur. Normal and pathological plasma histamine levels vary considerably in the literature. Data from various studies, especially one involving 300 patients in Heidelberg (G.F.R.), allow us to define the normal range for human plasma histamine as 0-1.0 ng . ml-1 . Values greater than 1 ng . ml-1 have to be considered as pathological. The problems related to blood collection and plasma preparation are considered here. Any judgement concerning the method described in the test must take into consideration our long experience of 15 years with it, its reliability in clinical conditions, its practicability, its relatively low cost, and finally, the absence of radioisotopes.

Adult↗
PubMed1980

H1 + H2-receptor antagonists for premedication in anaesthesia and surgery: a critical view based on randomized clinical trials with Haemaccel and various antiallergic drugs.

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.

Adolescent↗
PubMed1978

[Coagulation inhibition caused by selective thrombin blockade with hirudin].

Hirudin causes a rapid inhibition of blood coagulation as shown by in vitro and in vivo experiments in the dog. The substance appears to be a rather specific antithrombin. Its inhibitory action is linearly dose related and therefore easy to control and reproduce. Side effects can be expected to be abolished after further purification of the substance.

Animals↗
PubMed1978

[Plasma histamine level during and following kidney allotransplantation in man].

In human kidney allotransplantation, elevated plasma histamine levels were measured before surgery, following revascularization, and in single cases also several days after surgery. The maximum extent of this histamine release must be tested with respect to time and to localization. Its significance must be established. The intermittently increasing plasma histamine levels (greater than 1 ng/ml) must be considered as a possible risk regarding stress ulcer pathogenesis.

Adult↗
PubMed1977

Histamine release in dogs by Cremophor E1 and its derivatives: oxethylated oleic acid is the most effective constituent.

Several preparations of Cremophor E1, several of other non-ionic detergents and several components of Cremophor E1 were tested for their histamine-releasing capacity in dogs. Lutensol AP 10 and a derivative of 1,2-propylenglycol were ineffective, but showed excellent properties as detergents. Thus the histamine-releasing capacity was not necessarily combined with the tenside effect of the surfactants. Oleic acid found in Tween 80 as well as in Cremophor E1 seems to be the most effective constituent, but the alcohol seems also to be important for the histamine-releasing capacity. The development of a non-toxic solubilizer for lipophilic drugs seems of considerable clinical interest.

Animals↗
PubMedDate not supplied

Preincisional local anesthesia with bupivacaine and pain after laparoscopic cholecystectomy. A double-blind randomized clinical trial.

The aim of this study was to investigate whether local anesthesia of abdominal wall wounds prior to laparoscopic cholecystectomy leads to decreased pain beyond the immediate postoperative period and thus improves the comfort of the patient. In a randomized, double-blind study 50 patients scheduled for laparoscopic cholecystectomy were divided into two groups. In one group (n = 25) the skin, subcutis, fascia, muscle, and preperitoneal space were infiltrated with 8 ml of bupivacaine 0.5% 5 min before each abdominal wall incision. The control group (n = 25) received normal saline. The intensity of pain was assessed by a 100-point visual analogue scale (VAS) at rest and during movement and by the consumption of analgesics. Analgesic therapy was provided by on-demand analgesia with piritramide intravenously for 24 h and continued by ibuprofen orally on request. The mean intensity of pain at rest and during movement was lower but not statistically significant in patients who received bupivacaine compared to the control group up to the second postoperative day. The difference was between 4 and 9 VAS points and therefore of doubtful clinical relevance. Similar statistically nonsignificant results were found for the mean consumption of piritramide up to 16 h after the operation. Three patients (12%) in the bupivacaine group localized the most severe pain up to the second postoperative day to the right lower abdominal wall wound where the gallbladder had been extracted compared to 11 patients (44%) of the control group (P = 0.012). These results indicate that bupivacaine was effective at the site where it was administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Significance of histamine formation and release in the development of endotoxic shock: proof of current concepts by randomized controlled studies in rats.

The significance of histamine in the initiation and progression of septic (endotoxic) shock is still uncertain. Increased new formation and increased release of histamine are the two hypotheses currently considered as the basis for a causal relationship. Both hypotheses were tested in a standardized rat model of endotoxic shock. Several randomized controlled studies were performed with inhibitors of histamine formation (histidine decarboxylase inhibitors) and of its action via receptors (H1 and H2 receptor antagonists). Two inhibitors of histamine formation (alpha-methylhistidine and alpha-fluoromethylhistidine) in a wide range of doses exerted no significant effects on survival curves for rats in endotoxic shock, despite enzyme inhibition in vitro and in homogenates of liver obtained from rats immediately after death. In addition, three H1 and three H2 receptor antagonists, which were selected on the basis of markedly different antihistaminic efficacies and of defined non-antihistaminic (nonspecific) efficacies, gave no indications of specific histamine-mediated effects on survival parameters in these studies when tested either singly or in various combinations. Thus, histamine cannot be shown to be a predominant factor in the lethal outcome of endotoxic shock in rats.

Animals↗