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     

Prospective study of antigenemia,plasma viremia and lymphocytic viremia in HIV-infected hemophiliacs

A total of 186 blood samples from 24 HIV-1 seropositive hemophiliac patients, monitored every four months for 29 months, were investigated for the presence of viral antigen in plasma. In addition, peripheral blood mononuclear cells (PBMC) were cultured for HIV-1, using normal PBMC as a target for replication. Antigenemia was detected in 51 % of the patients and from PBMC in 87.5 % of the patients. The incidence of HIV isolation in asymptomatic patients (42.8 %) was similar to that found in symptomatic patients (51.4 %). Patients with opportunistic infections had a higher incidence of lymphocytic viremia (p<0.05). Plasma viremia was closely associated (p<0.05) with low CD4+ counts and infection progression. The persistence of antigenemia was also a marker of a poor clinical course. In treated patients, plasma viremia was the marker that better correlated with the clinical course, and it did not appear during the first nine months of therapy. Zidovudine doses of >500 mg/day significantly lowered the appearance of antigenemia and lymphocytic viremia (p<0.05).     

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.     

Variations in peroxisomal catalase of neonatal rat hepatocyte subpopulations

Alcohol consumption during pregnancy is teratogenic and induces severe alterations in hepatocytes. In the hepatocyte peroxisomal system, ethanol is converted in the presence of H₂O₂ to acetaldehyde and water. Therefore, peroxisomal catalase also acts as an antioxidant defence mechanism by removing H₂O₂ and preventing the formation of hydroxyl radicals in the cell. Alterations in peroxisomal catalase after pre- and pre+postnatal alcohol exposure were investigated in the rat. The effect of pre- and postnatal exposure to ethanol on hepatocyte subpopulations was analysed in isolated hepatocytes originating from periportal, intermediate and perivenous zones. Analysis of catalase revealed that the total activity and content of this enzyme were higher in 12-day-old cells than in cells from newborns and that this increment was more pronounced in treated cells. In controls, the amount of peroxisomal catalase increased mainly in periportal cells, whereas alcohol exposure induced a significant increase in the catalase of perivenous hepatocytes. We conclude that pre- and postnatal alcohol exposure mainly affects the perivenous hepatocyte peroxisomes and that the increase in peroxisomal catalase could constitute a defence mechanism against free radical generation induced by alcohol exposure during the perinatal period.     

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%.