Changes in hepatic blood flow in jaundice due to hilar carcinomas, the so-called Klatskin tumours

The hepatic circulation of patients with hilar carcinoma and icterus was studied by isotope technique. A marked alternation in blood flow was observed, that is that the ratio of the circulation of the hepatic artery and the portal vein became balanced. By elimination of the icterus, the hepatic circulation normalized. This allowed the conclusion that the change in blood flow must have rather been due to the mechanical icterus and the increased pressure of the bile duct than to the tumorous infiltration and therefore the earliest possible elimination of the icterus is urgently indicated.     

Incidence of femoral and tibial shaft fractures. Epidemiology 1950-1983 in Malm?, Sweden

We studied 362 fractures of the femur that had occurred during the years 1950-57 and 1973-83, and 849 fractures of the tibia that occurred during the the years 1950-55 and 1980-83. There was an increase in age-specific incidence over aged 60 years. The risk of low-energy femoral shaft fractures also had increased in elderly women. Both fracture types shifted their age- and sex-specific incidence in the direction of a fragility pattern. There was no increase in the incidence of tibial shaft fractures. Fracture type, site, and degree of displacement of the tibial fractures remained unchanged during the 30 years, i.e, they were predominantly distal, longitudinal fractures with moderate displacement.     

MAO-A inhibition in brain after dosing with esuprone, moclobemide and placebo in healthy volunteers: in vivo studies with positron emission tomography

Objective: The aim of the study was to investigate whether or not esuprone binds substantially to MAO-A in the human brain. Methods: In a randomised double-blind placebo-controlled study 16 male healthy volunteers were examined␣with positron emission tomography (PET) with [¹¹C]harmine. Eight of the volunteers were given daily doses of 800 mg esuprone, four were given bi-daily doses of 300 mg moclobemide, and four volunteers were given placebo tablets. PET was performed before initiation of a 7-day treatment period. On day 7, one investigation was made immediately before administration of the drug, representing 23 h after the previous day's treatment for esuprone and 11 h after the last tablets of moclobemide. Further investigations were made 4 h and 8 h after the morning dose on day 7. Results: PET showed a high degree of binding of [¹¹C]harmine, a high-affinity ligand for MAO-A, before the start of treatment, and a marked and similar reduction after treatment with esuprone and moclobemide. A slight tendency for normalisation of enzyme binding was observed at the last time point. In the placebo group no change was observed. Plasma kinetics of esuprone showed a rapid elimination with a half-life of about 4 h. Conclusion: The study demonstrates that esuprone was comparable to moclobemide in its effect on MAO-A inhibition in the brain at the doses given. This is an illustration of the potential of PET to monitor drug effects directly on target biochemical systems in the brain in human volunteers, and the possibility of using these data, rather than pharmacokinetic data, for the determination of dosing intervals. Received: 21 August 1996 / Accepted in revised form: 22 November 1996     

Epidemiology of Inhibitors in Haemophilia A

One of the most serious complications of the treatment of haemophilia A is the development of inhibitors. Former studies mostly considered the prevalence of inhibitor development, thus underestimating its true risk. Prevalences ranged widely (7–18%) probably due to the populations studied and the study design. Recent prospective previously untreated patients (PUP) studies were more comparable because of similar study designs. Eight PUP studies regarding the incidence of factor VIII inhibitors were analyzed: The inhibitor incidences (Independent of severity of haemophilia) ranged from 18.4 to 28%. Evaluating only severe haemophiliacs (factor VIII<2%) significantly higher incidences were found. After 9–36 exposure days (as medians inhibitor development occurred at 0.8-3.3 years of age (as medians).     

Synthesis of N-(phosphonoacetyl)-dipeptide derivatives and evaluation of their antihypertensive activity

A series of N-(phosphonoacetyl)-dipeptide derivatives was synthesized for pharmacological testing as antihypertensive compounds. Several of these compounds demonstrated a moderate antihypertensive effect in Wistar spontaneous hypertensive rats (SHR) with p.o. dosing. ACE inhibition by the compounds was studied using ACE from rat plasma and lung. Inhibitors containing esterified C-termini are pro-drugs and showed activity only for plasma ACE.     

Organization of gallbladder lithotripsy with the MPL-9000 at the Zurich university hospital. Initial results

Gallstone shock wave therapy at the University Hospital of Zurich is a joint venture between the Medical Clinic, Medical Policlinic and Surgical Clinic. Patients with symptomatic cholecystolithiasis willing to submit themselves to a long period of treatment, were accepted for ESWL, should no contraindications be present. From October 1988 through May 1989 we treated 48 patients. In approximately two thirds of our patients we were successful with one ESWL alone, in one third 2 sessions and in two patients even 3 sessions were needed. In 42 patients course after therapy was as planned. Six had to be cholecystectomized later on. Best results were achieved in patients with single gallstones. In 2 of 5 cases there was disagreement between the number of gallstones found sonographically and the intraoperative findings. Histologic examination of gallbladders after ESWL showed no pathologic changes.     

Adverse drug reactions: physicians' opinions versus a causality assessment method

Since spontaneous reporting of adverse drug reactions depends on the physician's opinion of the relationship between the drug and the adverse event, we compared physicians' opinions with the scores obtained by the causality assessment method used in France. During a 2 month period, all physicians who reported adverse drug reactions (ADRs) to our pharmacovigilance centre expressed their opinions on the causal link by means of visual analogue scales. ADR reports were then assessed with the French causality assessment method by a clinical pharmacologist who was blind to physicians' opinions.The assessment by both physicians and the standardized method was performed for 75 ADR cases involving 120 drugs. Physicians used a wide range of assessments, with a preponderance of extreme scores, resulting in a U-shaped distribution, while the standardized method gave generally low scores. Scores given by physicians were very high (causality considered very likely or likely) in 60% of cases and very low (causality considered unlikely or dubious/possible) in 32% of cases. Scores obtained using the causality assessment method were low (causality dubious/possible) in 89% of cases and causality considered likely in only 11 cases, essentially in cases with positive rechallenge. Complete agreement occurred in only 6% of cases. Adding complete agreement and minor discrepancies raised the percentage to 49%.     

On the effects of Fusarium toxin contaminated wheat and wheat chaff on nutrient utilisation and turnover of deoxynivalenol and zearalenone in vitro (Rusitec).

The objective of the present study was to investigate the effects of Fusarium toxin contaminated wheat and wheat chaff (mycotoxin diet) on nutrient degradability and the metabolism of the mycotoxins deoxynivalenol (DON) and zearalenone (ZON) using the rumen simulations technique (Rusitec). A 6 day application period with control wheat and wheat chaff (control diet) was followed by an 8 day sampling phase. During this time three fermenters received the mycotoxin diet (64.9 mg DON/kg dry matter (DM) and 500 microg ZON/kg DM) and the remaining fermenters served as the controls (1.0mg DON/kg DM and 6 microg ZON/kg DM). Feed residues of the bags and samples of the effluent liquids were pooled per fermenter during the last 8 days of the experiment. Additionally, effluents of the mycotoxin fermenters were taken 6, 12 and 24h after the morning feeding on the first day of the sampling phase. The degradation of organic matter (OM; P<0.05), neutral detergent fibre (NDF; P<0.01) and protein (P<0.001) were increased by administration the Fusarium contaminated diet which was accompanied by an increased ammonia concentration (P<0.01) and increased butyrate (P<0.01), isobutyrate (P<0.01) and isovalerate (P<0.05) values of the mycotoxin effluents in relation to the controls. High proportions of ingested DON of 90% (85-93%) and ingested ZON of 93% (80-104%) were recovered at the pooled feed residues and effluents in form of DON and de-epoxy DON, and ZON and alpha-ZOL after administering the Fusarium toxin contaminated feed. While adsorption of DON as DON and de-epoxy DON in the feed particles was only minor (5%), a higher amount of 38% of ingested ZON was recovered as ZON and alpha-ZOL at the feed residues. The total recovery of DON plus de-epoxy DON in effluents as a percentage of DON intake reached 8%, 9% and 22% of ingested DON at 6, 12 and 24h after application of the contaminated diet the first time, whereby the recovery of de-epoxy DON as percentage of DON intake was only 5% at 24h. Concentrations of ZON and metabolites were lower than detection limits in the time dependent effluent samples.