Synthesis, configuration, and calcium modulatory properties of enantiomerically pure 5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylates.

Enantiomerically pure hexahydroquinolinones of the structural type 9 were prepared by a variation of the Hantzsch synthesis in which an optically active acetoacetate served as a chiral auxiliary reagent. Determinations of the de and ee values are described. The absolute configurations of the optically pure products were characterized by single-crystal X-ray analysis. The antipodes 9a and 9b exhibited calcium antagonistic activities on smooth musculature; the (S)-(-)-enantiomer 9b was the more potent compound with regard to the EC50 values which differed by a factor of 100; the intrinsic activity of 9b was 1.2, compared with a value of 0.54 for 9a. On the other hand, R-(+)-9a exerted positive inotropic effects on electrically stimulated atria. The cause of these effects is discussed.     

Prediction of phenotype for acetylation and for debrisoquine hydroxylation by DNA-tests in healthy human volunteers

Summary The debrisoquine/sparteine-type polymorphism of drug oxidation and the polymorphism for acetylation are two common inherited variations in human drug metabolism. The phenotypes for hydroxylation and acetylation can be predicted be newly developed methods based on mutation-specific amplification of DNA by the polymerase chain reaction (PCR), which also allow for identification of heterozygous carriers of one mutant allele.In the present study, the results of genotyping of 81 healthy European volunteers were compared with the phenotype obtained by the classical biochemical approach using debrisoquine and caffeine as probe drugs.Genotyping correctly predicted all 73 extensive metabolisers (EMs) and 6 out of 8 poor metabolisers (PMs) of debrisoquine. All 48 rapid acetylators and 33 of 35 slow acetylators were predicted.Overall, the DNA analysis result matched the in vivo phenotype in 97.5 % of individuals.     

Arthroscopic synovectomy of rheumatoid shoulder and elbow

Surgical Principles Radical arthroscopic synovectomy of rheumatoid shoulder and elbow. Revised Version from: Operat. Orthop. Traumatol. 4 (1992), 112–129 (German Edition).     

Die sofort operierte sprunggelenksbandruptur

Die Operation bei Ruptur des talofibularen Bandapparates innerhalb der ersten zwölf Stunden post trauma ergab eine deutliche Verbesserung des Operationsergebnisses im Hinblick auf die Aufklappbarkeit, Gebrauchsfähigkeit und die Dauer des Krankenhausaufenthaltes,     

Surgical Management of Marfan Syndrome in Children

Between August 1983 and January 1991, seven patients with Marfan syndrome underwent surgery for severe cardiovascular complications. The mean age at presentation was 5.7 months (range 4 to 9 months) in the infant group (n = 3), and 13.3 years (range 10 to 16 years) in a group of older children (n = 4). The primary indications for surgery in the infant group (performed at a mean of 3 years after diagnosis) were ascending aortic aneurysm with valvar regurgitation in one patient, and severe mitral valve prolapse with regurgitation in two. In the older group, surgical indications (performed at a mean of 2.8 years after diagnosis) were ascending aortic aneurysm with valvar regurgitation in three patients and acute aortic dissection in one. For aortic surgery, a composite valved conduit was used in four patients, and an aortic homograft in one. For mitral valve surgery, mechanical prostheses were used. Ail patients survived the primary operation. Over a mean follow-up of 17.5 patient-years (range 1 to 9 years), two patients in the infant Marfan group went on to further successful surgery (prosthetic mitral valve replacement and aortic root repair with aortic homograft) at a mean interval of 4.3 years after the Initial surgery. Our results suggest that the major cardiovascular risk factors of Marfan syndrome in the young, even in those diagnosed during infancy, have been favorably changed by surgery with an encouraging medium-term outlook. The correct timing of surgery is aided by echocardiography. (J Card Surg 1994;9:50–54)     

Parity and bone mineral density in middle-aged women

A retrospective study was carried out to determine the relationship between parity and bone mineral density (BMD) in middle-aged women. Eight hundred and twenty-five woman aged 41–76 years were recruited from four general practice registers in Cambridge. Subjects were unselected as to their health status. Each subject completed a detailed health questionnaire. Participation rate was 50%. The main outcome measure was BMD measured at the spine (L2–4,n=825) and hip (neck, intertrochanter and Ward's triangle;n=817) by dual-energy X-ray absorptiometry (DXA) using the Hologic QDR-1000 densitometer. It was found that the unadjusted mean BMD was significantly higher at all sites among the parous women (p=0.031 to <0.00001), and remained significantly higher at the femoral neck (p=0.025), intertrochanter (p=0.001) and Ward's triangle (p=0.045) after adjusting for age and body mass index (BMI). Similar findings were seen after stratifying for potential confounding variables. There was a consistent upward trend of BMD with increasing parity at all sites. Parity remained a significant independent predictor of BMD at all sites after controlling for age, BMI, menopausal status, oral contraceptive and hormone replacement therapy use, smoking status and breast-feeding status in multiple linear regression analyses. There was, on average, a 1.0% increase in BMD per live birth. Our findings therefore suggest a positive relationship between parity and bone mass.