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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 Histamine 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.

Notes: Zusammenfassung Die Früherkennung und Prävention von zerebralen Schäden, die im Zusammenhang mit den herzchirurgischen Korrekturoperationen angeborener Herzfehler mit Hilfe des kardiopulmonalen Bypasses (CPB) im Neugeborenen- und Kleinkindesalter auftreten, ist von besonderer prognostischer und therapeutischer Bedeutung. Wir untersuchen daher prospektiv die Kinetik der Serumkonzentration von S-100, einem glia- und schwannzellspezifischen Protein, bei Kindern vor und nach Korreturoperationen mit Hilfe des CPB. Methoden: Es wurden bei 42 Kindern (16 Neugeborene und 26 Kleinkinder) intra- und postoperativ Blutproben entnommen und mit Hilfe eines kommerziell erhältlichen Radioimmunassays (Sangtec Mediacal AB, Bromma, Schweden) die S-100-Konzentration im Serum bestimmt. Bei allen Kindern wurde die Korrekturoperation mit Hilfe des full-flow-CPB in tiefer bis moderater Hypothermie durchgeführt. Ergebnisse: Bei allen Patienten fanden sich signifikant erhöhte Werte (p = 0,001) während der ersten 24 postoperativen Stunden, die sich jedoch innerhalb 72 Stunden den präopertiv bestimmten Werten anglichen. Bei den Neugeborenen wurden höhere Maximalwerte bestimmt (3,6μg/l) als bei den Kleinkindern (0,95 μg/l), sie wiesen auch höhere präoperative Werte auf. Es zeigte sich eine negative Korrelation zwischen dem maximalen S-100-Wert und dem Alter (r =–0,74; p 〈0,0001), dem Gewicht (r =–0,72; p = 0,002) und der minimalen rektalen Temperatur (r =–0,67; P = 0,0004) der Kinder während CPB. Schlußfolgerung: Der Nachweis von S-100-Serum und somit das Übertreten von S-100 aus dem Zytoplasma der Astrozyten im Blut kann möglicherweise ein Zeichen für auftretende zerebrale Schäden sein. S-100 könnte daher als ein früh-biochemischer Marker genutzt werden. Beeinflussende Faktoren der S-100-Serum-Konzentration sind Alter, Körpergewicht, Länge des kardiopulmonalen Bypasses und Grad der Hypothermie.

Notes: Summary Introduction: The aim of this study was to investigate the kinetic patterns of the protein S-100, a specific cerebral astroglial cell protein, and the relationship to changes of cerebral oxygenation before, during, and after corrective cardiac surgery in infants and children.¶   Methods: 63 neonates, infants and children (age range 0.2–216 months) were included. Cardiac surgery was performed using full-flow cardiopulmonary bypass with moderate hypothermia and alpha-stat strategy. Regional cerebral hemoglobin saturation was continuously determined by near infrared spectroscopy (INVOS 3100A, Somanetics®, USA). The protein S-100 serum concentrations were analyzed using a commercially available two-site immunradiometric assay kit (Sangtec® IRMA, Bromma, Schweden).¶   Results: A significant increase in serum levels of S-100 was found immediately after termination of cardiopulmonary bypass (p〈0.001). The post-bypass S-100 serum levels significantly correlated with age ¶(r=–0.75, p〈0.0001), weight (–0.72, p〈0.005), bypass time (r=0.44, p=0.005), minimal rectal temperature (r=–0.67, p=0.004) and the decrease of regional cerebral hemoglobin saturation during reperfusion (r=–0.37, p=0.02) and at the end of cardiopulmonary bypass (r=–0.37, p=0.008).¶   Conclusion: The release patterns of S-100 in association with CPB may indicate increased cell membrane permeability of the astrocytic-endothelial cell complex forming the blood-brain barrier. The increased post-bypass serum levels of S-100 were related to younger age, longer duration of bypass, deep hypothermia and decreased regional intravascular cerebral oxygenation during reperfusion and at the termination of cardiopulmonary bypass.

Notes: Zusammenfassung An einem Biopsiematerial von 546 menschlichen Carcinomen beider Geschlechter und verschiedener Organe wurde das Kerngeschlecht untersucht. Dabei sind die Kriterien, wie sie für das normale Körpergewebe Gültigkeit haben, nicht anwendbar. Mit fortschreitender Entdifferenzierung der Carcinomzellen sinkt der Prozentsatz der geschlechtschromatinhaltigen Zellkerne ab, so daß — mit statistischer Signifikanz — der Grad der Kernatypie und die Zahl der Geschlechtschromatinkörper sich umgekehrt proportional verhalten. Somit sind Carcinome für eine genaue Bestimmung des Kerngeschlechts ungeeignet. Der Prozentsatz der Kerne mit Geschlechtschromatin kennzeichnet höchstens den Malignitätsgrad eines Carcinoms, über den aber die gewöhnliche Histo- und Cytomorphologie ebenso gut Auskunft gibt.

Notes: Abstract Haptoglobin (HP), transferrin (TF), group specific component (GC) and protease inhibitor (PI) polymorphisms were studied in three population samples from Thuringia: Jena, n=204; Erfurt, n=213; Suhl, n=180. GC and in particular TF allele frequencies show some statistically significant distribution heterogeneity, whereas HP and PI allele frequencies do not show any remarkable distribution differences. The results are discussed and compared with those obtained previously on other population samples from the eastern parts of Germany.