[Effect of perioperative antibiotic prophylaxis on hemodynamic stability during surgery: detection of complex interaction in a simulated clinical randomized animal study]. / Einfluss der perioperativen Antibiotikaprophylaxe auf die hämodynamische Stabilität während der Operation: Nachweis einer komplexen Interaktion in einer die Klinik modellierenden, randomisierten Tierstudie.

In a clinic modelling randomised trial (CMRT) in three groups of 10 land-race pietren pigs each it could be shown that the influence of prophylactic antibiotic administration on intraoperative hemodynamic stability and histamine release is only evident, if by stepwise addition of complicating factors the overall complexity of the experimental setting is increased. Different antibiotic regimen for prophylaxis significantly affected the incidence of cardiovascular instabilities only after relevant blood loss, restoration of circulation and subsequent submaximal induction of anaphylactoid reactions by the histamine liberator Polymyxin B. In conclusion, preclinical testing of therapeutic agents in complex clinic modelling randomised trials should be mandatory to avoid the possible hazards of misconducted clinical trials.

[Reduction of cardiovascular disorders by preventive perioperative antihistamine administration in general surgery: are the drugs interchangeable?]. / Verminderung kardiovaskulärer Störungen durch perioperative Antihistaminikaprophylaxe in der Allgemeinchirurgie: Sind die Medikamente austauschbar?

In clinical reality the drugs used for H1/H2-prophylaxis are not restricted to the combination of dimetinden/cimetidine, also only for this combination the effectiveness for preventing severe cardiorespiratory disturbances is proven in a randomised controlled clinical trial. However, it is almost impossible to conduct such an extended clinical trial in order to check all possible combinations. Instead of this, we developed a complex animal model featuring clinical variability and the principles of a well conducted randomised controlled clinical trial (CMRT = clinic modelling randomised trials), to evaluate different H1/H2 combinations. In this CMRT in pigs (four groups of 15 animals), the H1/H2 combination of dimetinden/cimetidine and dimetinden/famotidine showed an effectiveness similar to the randomised clinical trial. With dimetinden/ranitidine no significant prophylactic effect was observed. Two conclusions can be drawn: (1) CMRTs in animals are able to answer relevant clinical and research questions that otherwise only could be solved by clinical studies and may be a successful intermediate between basic research and clinical trials. (2) Drugs, even of the same substance class, may not be simply exchangeable. Hence, before changing a proven medication, trials in an adequate complex animal model (CMRT) should be mandatory.

Cardiovascular adverse effects of antimicrobials in complex surgical cases.

Previously undescribed adverse effects of antibiotics on the cardiovascular system were described in complex surgical cases. Hypotension, bradycardia and tachycardia were seen in a randomised clinical trial, and confirmed in a randomised experiment with piglets, and in a study with isolated vascular tissue that was exposed simultaneously to antibiotics, endotoxin, and later on histamine at histamine H1-receptors. These findings may influence indications and duration for antimicrobial therapy, and support the concept of "minimal" postoperative antibiotic therapy in emergency abdominal operations.

[The value of double contrast colon imaging in inadequate colposcopic diagnosis]. / Die Wertigkeit der Kolondoppelkontrastuntersuchung bei unzureichender koloskopischer Diagnostik.

PURPOSE: Prospective evaluation of colon double-contrast enemas in patients with incomplete colonoscopy during routine examination. MATERIALS AND METHODS: From 1. February 1993 through 31. January 1994 we prospectively evaluated all patients undergoing a double-contrast barium enema following incomplete colonoscopy in the endoscopy unit of the Department of Surgery of the University Hospital Marburg. The examination was carried out using the typical double-contrast technique at least 24 h after colonoscopy. The results of the barium enema were correlated with the findings at colonoscopy with regard to completion of the diagnostic procedure and additional pathological findings. RESULTS: Of 448 colonoscopies 168 remained incomplete. Sixty patients underwent an additional double-contrast study of the colon. In 43 patients this study was sufficient to complete the diagnostic procedure. Unknown pathological diagnoses were found in 11 patients. In 2 patients an adenocarcinoma and in 9 patients polypoid lesions were detected. CONCLUSION: After incomplete colonoscopy a double-contrast barium enema should be performed to complete the diagnostic examination of the whole colon and to reveal unknown additional pathological findings.

The cardioplegic solution HTK: effects on membrane potential, intracellular K+ and Na+ activities in sheep cardiac Purkinje fibres.

The effects of the cardioplegic solution HTK on membrane potential (EM) and intracellular K and Na activities (aiK, aiNa) were studied in sheep cardiac Purkinje fibres by means of conventional and ion-selective microelectrodes. HTK contains (mM): Na 15, K 10, Ca 0, Mg 4, histidine 180. (1) In control conditions EM was -74.3 +/- 3.3 mV (n = 25), aiK was 116.4 +/- 4.1 mM (n = 7) and aiNa was 8.2 +/- 1.4 mM (n = 15). (2) Exposure to HTK led to a depolarization to -59.7 +/- 3.6 mV (n = 25) which exceeded by about 5-7 mV that induced in a Tyrode solution of 10 mM K and in a modified HTK solution supplemented by 2 mM Ca (n = 6). (3) Addition of 0.5 mM barium eliminated the difference in the steady-state depolarization. (4) HTK superfusion increased aiK to 120.1 +/- 4.4 mM (n = 7) and decreased aiNa to 3.9 +/- 0.9 mM (n = 15). (5) The decrease in aiNa was insensitive to amiloride (1 mM) and to external alkalization but was slightly increased by addition of 2 mM calcium. (6) When the calcium in Tyrode solution was lowered from 2.0 mM to 0.05 mM, aiNa hardly decreased during subsequent exposure to unmodified HTK and it increased in the presence of 0.1 mM dihydroouabain. We propose the hypothesis (1) that the difference in membrane depolarization between HTK and a 10 mM K-Tyrode is caused by a decrease in K conductance by the HTK solution and (2) that the aiNa decline mainly results from a coupled Ca influx via Na-Ca exchange due to a delayed washout of external calcium.