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.     

Schwannoma of the lateral ventricle: eight-year follow-up and literature review.

Intracerebral and intramedullary schwannomas are uncommon; but, in general, spinal intramedullary schwannomas are more frequent than intracerebral schwanomas. We present a case of right lateral ventricle schwannoma in a 21-year-old man and review the associated literature. The 21-year-old right-handed man presented with loss of the left-eye vision approximately 8 months before referral to an ophthalmologist. The patient was immediately subjected to computed tomography (CT) scan, which showed an enhanced lesion with cystic component in the right occipital horn of the lateral ventricle. And consecutively, he was admitted to our department. The tumor was evacuated via craniotomy with marked improvement in his clinical state. The postoperative course was uneventful and postoperative CT control showed no residue. On MRI control no recurrence was noted after a follow-up period of 8 years. Intracerebral schwannoma is a rare, benign neoplasm. It is usually located superficially or adjacent to a ventricle. Characteristic imaging features include cyst formation, calcification, and evidence of peritumoral edema or gliosis. The recognition of this benign and potentially curable neoplasm and its differentiation from other neoplasms, some of which have less favourable outcomes, is of obvious importance.     

Three-dimensional biomechanical properties of the human rectum evaluated with magnetic resonance imaging

A method to evaluate the three-dimensional (3-D) geometry of the human gastrointestinal wall may be valuable for understanding tissue biomechanics, mechano-sensation and function. In this paper we present a magnetic resonance imaging (MRI) based method to determine rectal geometry and validation of data obtained in three volunteers. A specially designed rectal bag was filled in a stepwise manner while MRI and bag pressure were recorded. 3-D models of curvatures, radii of curvature, tension and stress were generated and the circumferential and longitudinal strains were calculated. The computed bag volumes corresponded to the infused volumes. A pronounced bag elongation and decrease in wall thickness was observed during the bag filling. The spatial distributions of the biomechanical parameters were distinctly different between individuals and non-homogeneous throughout the rectal wall due to its complex geometry. The average tension and stress increased as a function of infused volume and circumferential strain. The present study provides a method for characterizing the complex in vivo 3-D geometry of the human rectum. The non-homogenous spatial curvature distribution suggests that simple estimates of tension based on pressure and volume do not reflect the true 3-D biomechanical properties of the rectum.