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Notes: Abstract 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.

Notes: Conclusion Due 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.

Notes: Abstract Histamine concentrations in canine whole blood and plasma were determined under several pharmacological, pathophysiological, and clinical conditions, using fluorometric methods. The specificity of the assay for whole-blood histamine was investigated by comparing 3 purification procedures for the isolation of histamine from whole blood including butanol extraction (Shore), ion-exchange chromatography on Dowex 50 W-X 8, and the combination of these 2 methods (Lorenz). Histamine in whole blood was identified in analytical and preparative samples by fluorescence spectra, thin-layer chromatography, degradation by diamine oxidase from pig kidney and inactivation by histamine methyltransferase from guinea-pig brain as well as by biological tests on the isolated guinea-pig ileum. Since butanol extraction resulted in significantly higher ‘histamine’ values than the other two purification procedures, ion-exchange chromatography on Dowex 50 was recommended as the method of choice for the specific determination of histamine in dog's whole blood. Normal values of histamine concentrations in canine plasma were tentatively estimated. They depended on the time between pretreatment of the animals (anaesthesia, operation) and the collection of blood and showed an approximately logarithmic normal distribution. The median, the lower/upper quartiles and the range of the plasma histamine levels obtained 30 minutes after the end of pretreatment were 0.2, 0–0.4 and 0–1.2 ng/ml, respectively. Nearly 50% of the values were zero (below 0.1 ng according to the sensitivity of the method), only 1% of them exceeded slightly 1 ng/ml. Thus histamine release by drugs or by other medical treatments was only stated, when plasma histamine levels exceeded 1 ng/ml and decreased in a way to give an elimination curve of approximately first-order kinetics (Bateman function). Histamine concentrations in dog's whole blood showed approximately a logarithmic normal distribution. The median, lower/upper quartiles and range were 47, 34/75 and 13–209 ng/ml respectively. The histamine levels in the whole blood of four circulatory regions did not show any significant differences. The plasma histamine concentrations in the portal vein were slightly higher than in the hepatic veins. The injection of exogenous histamine and the concomitant determination of plasma and whole-blood histamine levels in four circulatory regions showed that the plasma histamine determination was the more sensitive method for measuring histamine elimination curves than the whole-blood histamine assay. The elimination of exogenous histamine administered intravenously was influenced by several drugs including inhibitors of histamine inactivation and histamine receptor antagonists. Aminoguanidine and the H2-receptor antagonist burimamide slowed down the disappearance of histamine from the plasma, the H1-receptor antagonist dimethpyrindene enhanced it, but amodiaquine had no significant effects. Dimethpyrindene and burimamide were capable of releasing histamine in dogs, in some cases to a considerable extent. The plasma substitute Haemaccel®, a chemically modified gelatin, released histamine in dogs. Using batch 3000, from 27 animals investigated, 15 animals showed elevated plasma histamine levels and a hypotensive blood pressure response, whereas in 12 of the dogs it did not show an effect on these parameters. The plasma histamine levels at the time of maximum hypotension showed an approximately logarithmic normal distribution. This frequency distribution in combination with the varying incidence of anaphylactoid reactions depending on the batches used seemed very important for the interpretation of clinical reactions to Haemaccel in human test persons and patients. By histamine determinations in plasma and whole blood of several circulatory regions and in various tissues before and after infusion of Haemaccel it could be demonstrated that the sites of histamine release by Haemaccel in dogs were especially the skin of the upper hemisphere of the body and the liver, whereas the gastro-intestinal tract took up histamine from the circulation. These numerous results under various experimental conditions may be considered as an evidence for the high quality and reliability of the method to study histamine release in the whole animal or in human subjects by evaluating histamine elimination curves in plasma.

Notes: Summary Retrospective chart analysis of 88 operated patients with bronchial carcinoma showed grave deficiencies. In 15 % the reason for admission to hospital was not available and the exact smoking habits of 74 % were not known. Retrospective TNM-classification was possible in only 59 %. It was known in 67 % whether a radiotherapy and in 17 % whether a cytostatic therapy was additionally performed. Only 13 of the 20 surviving patients participated in the follow-up. In contrast with these figures, a prospective collection of data (44 patients) has an effectiveness of 95 % or more for all parameters.

Notes: Summary Previous examination methods of the microcirculation did not allow an exact estimation of the tissuePO2. The development of insertable platinum electrodes has made it possible. This suggested the measurement of the tissuePO2 with these platinum electrodes in haemorrhagic shock and in the subsequent haemodilution with various volume replacement agents. Blood gases and regional flow were recorded simultaneously. The following results were obtained. The tissuePO2 on the kidney surface in the initial phase of shock sank more slowly than the flow. Apart from an electrolyte solution, volume replacement with artificial colloids, blood and albumin raised the tissuePO2 on the kidney surface to ca. 90 % of the initial value. There were signs that after blood and albumin the tissuePO2 rose more quickly than after artificial colloids. DuringPO2 estimations on the liver surface, isolated anoxic fields were seen even in the early phase of shock at blood pressure values around 100 mm Hg.

Notes: Summary Analysis of retrospective evaluation of case histories in 88 lung cancer patients showed grave faults in documentation. Quantitative knowledge of parameters of history, diagnostic findings, therapy and follow-up was reduced up to 17% (knowledge of adjuvant cytostatic therapy). Prospective data collection (n=44) had an evaluability of more than 95% in all parameters. The value of a retrospective study is reduced therefore, and should be considered in the conclusions.

Notes: Summary Of 45 patients with bronchial carcinoma, 25 had no trouble preoperatively; 9 complained of expectoration, cough, and fever; and 8 of pain. From 3–6 months after the operation, only 15 reported no trouble. In 14, the main problem was pain, 9 needed medication for pain, and 8 suffered from weakness. In the systematic follow-up of 22 patients, the longer-surviving 8 showed good quality-of-life and subjective well being, while these parameters were reduced continuously in the 14 who had died in the meantime.

Notes: Summary A double-blind, randomized, controlled trial in the treatment of primary chronic fissure-in-ano by digital stretching of the anal canal or by a modified lateral subcutaneous sphincterotomy is reported. Whereas there was no difference in the postoperative course of both groups, by checking 65 of 66 patients 6 months postoperatively, we found significantly more lacks of continence after stretching. There was no difference regarding recurrence rate. Pressure monitoring of the anal canal showed significantly higher values at rest in both groups before operation. No correlation between results of monitoring anal pressure and defects of anal continence has been seen. These results point out that in treatment of primary chronic fissure-in-ano the Lateral subcutaneous sphincterotomy is superior to anal dilatation regarding postoperative defects of anal continence. The recurrence rate in the present study does not force to prefer one of these two methods. Manometric investigations show that the resting pressure in anal canal seems to be elevated in primary chronic fissurein-ano.

Notes: Summary Thioacetamide-fed rats developed cirrhosis with portal hypertension (P portal = 23.0 ± 5.2 cm H2O, controls: 14.4 ± 1.0 cm H2O). The PO2 of liver tissue was markedly reduced in cirrhosis (PO2 = 7.6 ± 3.4 torr, controls 22.3 ± 5.8 torr), and the aortal pH was significantly lower as well. No correlation was found between portal hypertension, development of large—nodular cirrhosis, and ascites.