H. Hamelmann

Elevated plasma histamine concentrations in surgery: causes and clinical significance

SummaryHistamine concentrations in plasma, whole blood and various tissues of human subjects, monkeys, pigs and dogs were determined by fluorometric methods before, during and after surgical operations. Following intraabdominal surgery in 6 of 22 patients elevated plasma histamine levels were found several hours after the end of operation. Some of the causes of histamine release in surgery were found to be premedication by atropine, intravenously administered anaesthetics, infusion of plasma substitutes and manipulation on the gut. Acute blood losses were without effect on the plasma histamine levels. Clinical symptoms and pathophysiological reactions, such as tachycardia, hypotension, increased gastric secretion and anaphylactoid reactions could be related to the release of histamine in some circumstances.ZusammenfassungHistaminkonzentrationen in Plasma, Vollblut und verschiedenen Geweben von Mensch. Affe, Schwein und Hund wurden vor, während und nach Operationen mit fluorometrischen Methoden gemessen. nach intraabdominellen eingriffen wurden bei 6 von 22 Patienten erhöhte Plasmahistaminspiegel noch Stunden nach der Operation gefunden.Als Ursachen der Histaminfreisetzung bei Operationen wurden nachgewiesen: Prämedikation durch Atropin, Anästhesieeinleitung mit intravenös verabreichten Kurznarkotika, Infusion von Plasmasubstituten und Manipulationen am Darm. Akuter Blutverlust war ohne Einfluß auf die Plasmahistaminspiegel. Klinische Symptome und pathophysiologische Reaktionen, wie Tachykardie, arterielle Hypotension, erhöhte Magensekretion und anaphylaktoide Reaktionen konnten auf Histaminfreisetzung unter bestimmten Umständen zurückgeführt werden.

Eine prospektive, kontrollierte Studie zur selektiven Vagotomie beim chronischen Duodenalulkus: Frühergebnisse mit einer standardisierten Operationsauswahl und Operationstechnik

SummaryA prospective, controlled study on a standardized selection procedure of patients for the surgical treatment and on a standardized operation technique of selective vagotomy was carried out with 65 patients suffering from chronical uncomplicated or complicated duodenal ulcer. The operation technique, the aim, preparation and performance of the study, the designation of operators and investigators for the follow-up, the selection of patients for surgical treatment as well as the methods for measuring pre- and postoperatively various clinical and clinical chemical parameters are described in detail.The first follow-up was performed 6 to 12 months following surgical treatment in 60 patients. 4 patients died in the meantime, 1 patient could not be controlled because of an unknown new address. The operative mortality was 0%, intraoperative and postoperative complications were observed in 2 and 15% of the patients, whereas recurrent ulcers were found in 2 cases. The overall assessment of the clinical condition according to a modified classification of Visick was good in 85% and satisfactory in 93% of the patients. Mild diarrhoea was observed in 8%, severe diarrhoea in none and mild dumping in 30% of the patients. Positive insulin tests according to the criteria of Hollander were observed in 27% of the cases, but only in 7% were there early positive tests according to Ross and Kay. Depending on the drainage procedure, the basal secretion was reduced by 83–98%, the pentagastrin stimulated maximum secretion by 51–95%.This prospective controlled study was a preliminary investigation completed by another trial, in which two operative techniques for the treatment of chronical duodenal ulcer will be compared. The early results of our study, however, are in favour of the concept of an individually adapted treatment with selective vagotomy in duodenal ulcer.ZusammenfassungEine prospektive, kontrollierte Studie über eine standardisierte Operationsauswahl und Operationstechnik der selektiven Vagotomie wurde an 65 Patienten mit kompliziertem und unkompliziertem chronischem Duodenalulcus durchgeführt. Operationstechnik, Ziel, Vorbereitung und Durchführung der Studie, Operateure und Nachuntersucher, Patientenauswahl und die Methoden der Nachuntersuchung werden im Detail beschrieben.In einem Zeitraum von 6–12 Monaten postoperativ wurden 60 Patienten nachuntersucht, 4 Patienten waren verstorben, 1 Patient nicht auffindbar. Die operative Letalität betrug 0%, intra- und postoperative Komplikationen wurden bei 2 bzw. 15% der Patienten beobachtet, 2 Rezidive wurden festgestellt. Das klinische Allgemeinbefinden war bei 85% der Patienten gut, bei 93% befriedigend. Leichte Diarrhoen wurden bei 8%, schwere in keinem Fall beobachtet. Dumping trat dagegen in 30% der Fälle auf, war aber immer nur geringfügig. Positive Insulinteste nach verschärften Hollander-Kriterien wurden in 27% der Fälle gefunden. Die Basalsekretion wurde um 83–98% reduziert, die mit Pentagastrin maximal stimulierte Sekretion um 51% nach Vagotomie und Pyloroplastik, um 87% nach Vagotomie und distaler Antrektomie (BI) und um 95% nach Vagotomie und Antrektomie (BII).Die vorgelegte prospektive Studie stellt den ersten Teil einer Untersuchung dar, die zur Beurteilung verschiedener Vagotomieformen in der chirurgischen Therapie des chronischen Duodenalulcus herangezogen werden soll. Die Frühergebnisse dieser Studie rechtfertigen aber vorläufig die Empfehlung einer individuellen Anwendung der selektiven Vagotomie in Kombination mit Drainageoperation oder Antrektomie.

Marburg Experiment on Surgical Research: A Five-Years' Experience on the Cooperation between Clinical and Theoretical Surgeons* **

ZusammenfassungDie Organisation der chirurgischen Forschung in Marburg ist ein Experiment, das seit fünf Jahren läuft und versucht, eine Kooperation zwischen klinischen und theoretischen Chirurgen zu installieren. Das Experiment wurde 1970 mit der Gründung einer Abteilung für Experimentelle Chirurgie und pathologische Biochemie an der chirurgischen Universitätsklinik begonnen. Strukturen und Funktionen in dem Experiment waren 6 „kleine Arbeitsgruppen“, spezielle Dienstleistungen für diese Gruppen und die gesamte Klinik und ein Ausbildungsprogramm für theoretische Chirurgen. Die Beurteilung von Erfolgen und Fehlleistungen bei dem Experiment erfolgte nach Kriterien, die drei Grundfunktionen chirurgischer Forschung prüfen sollten: (1) Ausbildung von klinischen und theoretischen Chirurgen in Methoden und Techniken chirurgischer Forschung, (2) Durchführung kontrollierter, klinischer Studien und (3) Grundlagenforschung in der Chirurgie. Die Frühergebnisse des Marburger Experiments erscheinen hoffnungsvoll.SummaryThe organisation of surgical research in Marburg is an experiment which has run for five-years and war carried out in attempt to establish a cooperation between clinical and theoretical surgeons (scientists in basic research). The experiment was started 1970 by creating a Division of Experimental Surgery and Pathological Biochemistry at the Surgery Clinic of the University. Structures and functions in this experiment were 6 small working teams, special services for the teams and for the whole Department of Surgery as well as a training programme in surgical research for theoretical surgeons. Success and failure in the experiment were evaluated by criteria testing three principal functions of surgical research: Training of clinical and theoretical surgeons in methods and techniques of surgical research, performance of controlled clinical trials and basic research in surgery. The early results of the Marburg experiment seem to be promising.

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 antihistaminic drugs on possibly histamine-induced physiological and pathophysiological processes should be interpreted very carefully as far as their specificity is concerned.

Alterations in the circulatory system of anaesthesized dogs following administration of histamine and histamine H1- and H2-receptor antagonists in relation to plasma histamine levels

ConclusionDue to the large number of parameters in this communication only one dose of histamine was investigated. This dose (6 μg/kg) was chosen because it caused short-acting but remarkable effects in the circulatory system and induced plasma histamine levels as high as found after administration of histamine releasers [8]. With this dose of histamine it could be shown that several effects of histamine in the circulatory system of dogs depended on the actual plasma histamine levels. H1- and H2-receptor antagonists applied separately from each other are able to block only few histamine effects in the circulatory system. They influence the circulatory reactions to histamine not only by acting on the receptors, but also by altering the actual plasma histamine levels.

Studies on a mechanism of enhancement of maximum gastric secretory response: Its possible importance in recurrent ulcers after surgical treatment

The determination of maximum gastric secretory response to histamine, histalog and pentagastrin is considered as the clinically most important test of gastric secretion. In man and dogs, Marks et al. [1, 2] examined whether there exists a relationship between the maximum secretory response to histamine and the parietal cell mass of the stomach and found a highly significant correlation between these two parameters. However, in a simplified interpretation of these results [3], the maximum gastric secretory response to various stimuli was set equal to the secretory capacity of the stomach, within small limits. However, in our in vivo studies with amodiaquine, a strong inhibitor of gastric histamine methyltransferase in vitro, we obtained results which are incompatible with such an hypothesis. Methods. In 8 mongrel dogs (both sexes, 14--30 kg) with Heidenhain pouches secretory tests were carried out not prior than 6 weeks after operation, in the same room, at the same time of day and the same day of the week twice a week during 10 months. First, the maximum secretory responses of the pouches to i.m. administered pentagastrin (Merck, Darmstadt) and histamine were determined by doseresponse curves and were considered to be reproducible when at least 3 consecutive stimulations with maximum doses of both substances induced the same volumes of