[Company approaches concerning workers with performance alterations or disablement: interview findings on the perspectives of the various parties involved]. / Betrieblicher Umgang mit der Gruppe leistungsgewandelter und behinderter Mitarbeiter/innen: Befragungsergebnisse aus der Sicht unterschiedlicher Funktionsträger.

This paper provides information about the research programme "In-plant interventions in the German car industry to increase job opportunities for employees with (severe) disabilities". The research was done in 2000 by the University of Trier and the International Research Unit for Work and Social Integration (IFASI). The purpose of the study was to capture, document, and analyse internal practices of occupational rehabilitation in five German car factories. Taking a qualitative approach, 23 persons of different company areas were interviewed, and numerous documents were analysed. The article reflects applied disability management strategies and points out success factors and barriers of inclusion.

Histamine release and pseudoallergic reactions induced by radiographic contrast media: comparison of Angiographin, Hexabrix and Telebrix using an in vivo canine model.

Radiographic contrast media (RCM) in clinical use cause unwanted allergic/pseudoallergic reactions of all grades of severity. They also induce histamine release from a variety of mast cell populations, the extent of the histamine release reaction depending on both the organ and species. In this study 3 RCM, which had been previously shown to be effective histamine releasing agents with canine liver cells, were investigated using an in vivo canine model based on the clinical situation. The dogs (n = 36) were randomly allocated to one of 3 treatment groups and received a bolus injection (2 ml/kg body weight) of either Angiographin, Hexabrix or Telebrix. Blood pressure was monitored continuously and blood sampling, for plasma histamine measurements, was performed before and 1, 5, 10, 20 and 30 min after RCM injection. All 3 RCM caused elevated plasma histamine levels in some animals: Angiographin 9 of 12 dogs, 0.40 ng/ml, (0-1.9 ng/ml) median (range); Hexabrix 11/12, 0.5 ng/ml (0-3.8 ng/ml); Telebrix 7/12, 0.4 ng/ml (0-2.0 ng/ml). Cardiovascular reactions were observed in most animals. The hypotensive reactions occurred with a maximum 30 sec after RCM application and recovery was normally observed after 1-1.5 min. The response after Angiographin or Telebrix was significantly greater than after Hexabrix. Hypertensive reactions occurred later (15 min (5-25 min)) and did not differ between the groups. All 3 agents tested were able to elicit histamine release and cardiovascular reactions. In comparison to histamine release occurring after intravenous administration of other agents, such as hypnotics, the degree of histamine release was small.(ABSTRACT TRUNCATED AT 250 WORDS)

Food-induced histaminosis under diamine oxidase (DAO) blockade in pigs: further evidence of the key role of elevated plasma histamine levels as demonstrated by successful prophylaxis with antihistamines.

Using a recently established porcine model, it was clearly shown that oral histamine administration is extremely dangerous in the presence of diamine oxidase (DAO) blockade. Due to the severity of the symptoms (20% death) and the clinical relevance, further interest has been focussed on strategies to prevent or alleviate food induced histaminosis. In a randomized controlled trial, 10 pigs under DAO blockade were challenged with oral histamine (60 mg). Half of these animals received a prophylactic premedication with a combination of H1- and H2-receptor antagonists. As expected, all animals developed a massive increase in plasma histamine levels, with significantly higher values in the control group (median: 123 ng/ml) compared to the antihistamine group (median: 32 ng/ml). In contrast, clinical symptoms were only observed in the control group. The maximum fall in mean arterial pressure (hypotension) was 60 mmHg (median for control group) but only 15 mmHg (median) under antihistamine pretreatment. These results firstly provide further evidence for the causal role of histamine in the new disease concept and secondly enable us to investigate appropriate therapeutic measures for patients at risk.

Reliability and practicability of the fluorometric-fluoroenzymatic histamine determination in pathogenetic studies on peptic ulcer: detection limits and problems with specificity.

Histamine, among various "biologic-physiologic" abnormalities, is considered as a pathogenetic factor in chronic duodenal ulcer disease. The 10-30 per cent difference between its concentration in gastric and duodenal mucosa of patients compared to healthy controls, however, has to be demonstrated to be specific for the disease. It has to be shown to be neither a methodological artefact nor a common effect, concomitant factor or consequence. This study, after a series of pathogenetic trials examines systematic errors (biases) in the fluorometric-fluoroenzymatic histamine assay under the conditions of field studies including tests on specificity over a time period of 10 years. It concentrates on sensitivity (detection limits) and specificity of a standard technique described herein. A modified Shore procedure for large scale assays in human biopsies was developed including reference luminescence values for all reagents, cleaning material and glassware, reduction of OPD concentration to 0.05%, purification of n-heptan, omission of centrifugation steps in the extraction procedure and use of 2 ml 1 M HClO4 in the homogenization step to prevent losses of histamine due to adherence to the mechanical homogenizer. This assay was sensitive enough to measure histamine without difficulty in any biopsy taken. The detection limit was 3 ng/biopsy, but the smallest quantities of the amine ever obtained were 10.6 and 18.3 ng/biopsy (depending on both histamine content and biopsy weight). A series of problems had to be solved both in achieving and demonstrating specificity. It had to be defined not only for the assay in general, but also for assessing the difference in histamine content between ulcer patients and healthy controls. Exogenous more than endogenous fluorescing material interfering with the determination had to be excluded. A series of pitfalls were detected which had to be overcome in demonstrating the specificity of the assay by physicochemical and enzymatic tests. The specificity of the identification tests was more often impaired than the histamine assay itself. Fluorescing material interfering with the assay occurred in the homogenization, extraction and condensation steps, was found in water, OPD, the organic solvents, the cleaning material and in all kinds of plastic vessels. Plasticizers were shown by physicochemical characteristics including fluorescence spectra to be most likely responsible for this interfering material. Rules were developed to exclude such hazards in specificity in longterm pathobiochemical studies. Enzymatic identification test were applied to exclude endogenous fluorecing substances interfering with the standard technique. Simil

Anaphylactoid reactions and histamine release do not occur after application of the opioid tramadol.

After an i.v. application of 100 mg tramadol in 13 healthy volunteers no change in plasma histamine concentration could be detected,( systemic anaphylactoid reactions did not occur, cutaneous reactions were not rated as anaphylactoid since itching and erythema were seen only once after tramadol whereas erythema was also observed twice after saline, blood pressure and heart rate were only very slightly and transiently elevated without any abnormalities in ECG-readings and only side effects typical for opioid therapy were observed.

Comparison of the histamine-releasing activity of cremophor E1 and some of its derivatives in two experimental models: the in vivo anaesthetized dog and in vitro rat peritoneal mast cells.

Histamine release caused by drugs and/or their solvents in clinical conditions is a well documented observation but the mechanism of this reaction is poorly understood. Hence in this study, the histamine releasing ability of cremophor E1 and six derivatives of 12-hydroxystearic acid (12-HSA) were compared in two models: the in vivo anaesthetized dog and the in vitro isolated rat peritoneal mast cells. The results obtained in both systems differed markedly. Only one compound DH (the diester of 12-HSA with polyethylene glycol) released histamine in both systems. The two substances, which exhibited the weakest histamine releasing ability in the dog model (almost inactive at the doses given) were powerful releasers of histamine from rat peritoneal mast cells (TN, 12-HSA polymerized with ethylene oxide; and ME, the monoester of 12-HSA esterified with polyethylene glycol). The release of histamine from rat peritoneal mast cells was potentiated as the temperature was elevated above 37 degrees C. Due to the heterogeneity of mast cells from both different species and different tissues in the same animal, it is important to choose the appropriate predictive model for clinically important adverse reactions to drugs and/or their solvents. Agents which release histamine by non-specific mechanisms are not uninteresting for the clinical situation.

Histamine release and hypotensive reactions in dogs by solubilizing agents and fatty acids: analysis of various components in cremophor El and development of a compound with reduced toxicity.

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.

[Plasma histamine assay in anaphylactoid reactions of the anesthetized subject. Effects of collection methods and plasma preparation on measured histamine]. / Le dosage de l'histamine plasmatique lors de réactions anaphylactoïdes chez le sujet anesthésié. Infuence des méthodes de prélèvement et de la préparation du plasma sur l'histaminémie mesurée.

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.

Intestinal diamine oxidase and histamine release in rabbit mesenteric ischemia.

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.

Incidence and mechanisms of adverse reactions to polypeptides in man and dog.

Adverse reactions (pseudoallergic = anaphylactoid (severe) and allergoid (slight)) to polygeline (Haemaccel) are caused by histamine release. The mechanism by which other polypeptides produce these reactions is unfortunately hitherto unknown. "Purification" of Haemaccel led to a drug which was free from anaphylactoid reactions in a controlled clinical trial. Clinically insignificant allergoid reactions to polygeline (restricted to the skin) could be prevented by premedication with H1 + H2-receptor antagonists.

[Experimental occlusion of the superior mesenteric artery: further evidence of the influence of histamine and diamine oxidase in the development of shock (author's transl)]. / Experimenteller Verschluss der A. Mesenterica superior: Weitere Beweise für den Einfluss von Histamin und Diaminoxidase auf die Schockentwicklung.

In shock produced by temporary superior mesenteric artery occlusion the plasma histamine concentration was enhanced following release of the mesenteric blockade. Furthermore, an inhibition of the diamine oxidase catalysed histamine inactivation resulted in an aggravation of the shock development. These processes, already shown in dogs and mini pigs, were also observed in rabbits. Histamine receptor antagonists abolished the effect of the enhanced histamine concentration appearing in the circulation following inhibition of diamine oxidase. In human intestinal tract a fairly similar distribution of histamine and diamine oxidase was found as in the mammals studied. Thus the indicated pathobiochemical processes should be reckoned with in patients suffering from circulatory disorders of the intestinal tract.

Histamine and acute haemorrhagic lesions in rat gastric mucosa: prevention of stress ulcer formation by (+)-catechin, an inhibitor of specific histidine decarboxylase in vitro.

Acute haemorrhagic lesions in the oesophagus, stomach and duodenum ('stress ulcers') occur relatively often under clinical conditions and are always dangerous to the patient (lethality rate about 70%). Since conservative and surgical treatment are without significant success up to now, prevention by adaptation to stressors or by administration of drugs seems mandatory. An improved technique for producing acute gastric lesions in rats by immobilization and a new method for assessing this disease in the animals is presented in this communication. High precision is obtained within a single experimental series especially from day to day. Since histamine was suggested to be involved in the pathogenesis of stress ulcer disease, (+)-catechin, a rather specific inhibitor of specific histidine decarboxylase from rat stomach, was tested in immobilized rats. It prevented the formation of acute gastric lesions by 80% in seven series of experiments lasting for half a year. Since the drug has low toxicity in man, it is recommended for clinical trials.

Influence of H1- and H2-receptor antagonists on the circulatory system and on the endogenous plasma histamine concentrations in dogs.

The effects of the H1-receptor antagonist dimethpyrindene and the H2-receptor antagonist burimamide on circulatory and respiratory parameters and on plasma histamine levels were tested in 21 mongrel dogs. Both drugs released histamine. The incidence for this effect was 10/11 in the case of dimethpyrindene and 5/10 in the case of burimamide. Following dimethpyrindene all animals showed arterial hypotension, pulmonal hypertension, decrease in peripheral resistance and hyperventilation. The portal venous pressure was increased in dogs reacting by a histamine release. Following burimamide both an initial arterial hypertension and a subsequent hypotension were observed the latter being more pronounced in the group with histamine release. In this group the portal venous pressure raised considerably. In the non-reacting animals cardiac output was elevated, probably due to a release of catecholamines. It seemed remarkable that the effect of exogenous histamine on portal venous pressure was completely blocked by dimethpyrindene, but not the action of histamine released by the drug itself. It is concluded that the effects of anti-histaminic drugs on possibly histamine-induced physiological and pathophysiological processes should be interpreted very carefully as far as their specificity is concerned.

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.

Histamine release in human subjects by modified gelatin (Haemaccel) and dextran: an explanation for anaphylactoid reactions observed under clinical conditions?

Histamine release by modified gelatin (Haemaccel) and dextran (Macrodex) has been demonstrated in volunteers by direct and indirect methods. In a pilot study of Haemaccel, histamine release was observed in six of seven volunteers. The highest plasma histamine concentration was 4.8 ng/ml, the lowest 1.7 ng/ml: two of the subjects showed slight allergic reactions. Using Haemaccel batch 2551, 10 out of 12 subjects reacted to the rapid infusion of Haemaccel with increased plasma histamine concentrations, whereas none reacted to Ringer's solution. None of the 10 subjects had an allergic reaction, but an increase in gastric secretion was observed in eight. Changes in the venous basophil granulocyte count were found in both those who reacted and those who did not react to Haemaccel. After the rapid infusion of dextran the highest plasma histamine concentration was 5.0 ng/ml, the lowest 1.3 ng/ml. The withdrawal of blood had no influence on plasma histamine concentration. The incidences of histamine release produced by Haemaccel varied with different batches. Thus, it seems unlikely that immunological mechanisms are principally responsible. Nine instances of allergic and anaphylactoid reactions to plasma substitutes have been reported, seven after Haemaccel infusion, and two after dextran administration. One of the patients who received dextran died. Histamine release was always associated with Haemaccel infusion and corresponded in extent to the clinical symptoms observed, but there was no significant histamine release associated with the reactions to dextran.