Inhibition of synovial fluid lysosomal glycosidases by anti-Arthritic gold preparations

The ability of currently available anti-arthritic gold preparations to inhibit lysosomal glycosidases from rheumatoid synovial fluid and normal human serum was studied in vitro.It was shown that these preparations differ markedly in their ability to inhibit the enzymes. Gold thioglucose (Solganal) did not inhibit -glucuronidase (-GLUC), -N-acetylglucosaminidase (-NAG) or hyaluronidase (HASE). Chloro(triethylphosphine)gold (SK&F 36914) was a potent inhibitor of -NAG only. Sodium aurothiomalate (Myochrysine and sodium 3-aurothio-2-propanol-1-sulphonate (Allyochrisine) were inhibitors of all three enzymes, notably -GLUC.Kinetic analysis of inhibition by aurothiomalate demonstrated apparent competitive inhibition with -GLUC, but non-competitive inhibition with HASE and -NAG -GLUC was also strongly inhibited by silver and copper thiomalates.The concentrations of these drugs required for effective inhibition of lysosomal glycosidases probably exceed those attained in serum and therefore preclude this action extracellularly. It is suggested that durg sequestration and retention within phagocytic cells facilitates inhibition of glycosaminoglycan catabolism that mediates cleavage of glucuronidic linkages of hyaluronic acid and chondroitin sulphates.The hypothesis that gold dompounds act in vivo by attenuating the activity of lysosomal enzymes is discussed in relation to these and previous findings.     

Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.      

An allergic reaction following intrauterine insemination

Intrauterine insemination is a common procedure used for the treatment of different causes of infertility. Adverse reactions associated with this procedure are very rare and usually the procedure is well tolerated by the patient. We report a case of an allergic reaction after intrauterine insemination. The patient developed fever, difficulty breathing and wheezing in both lung fields. Although a low concentration of penicillin in the medium was used, it caused a significant allergic reaction. When intrauterine insemination was performed in subsequent cycles with an antibiotic-free medium, no allergic reaction occurred, and the procedure was well tolerated by the patient. A careful allergy history is essential in patients pursuing infertility treatment where antibiotics are utilized. Patients who are known to be allergic to penicillin should have semen prepared by an antibiotic-free medium.      

The newer unconventional indications of permanent pacemakers

In recent years, the indications for permanent pacemakers have expanded. The interest has focussed on hypertrophic cardiomyopathy, dilated cardiomyopathy and a new entity called hypertensive hypertrophy with cavity obliteration (HHCO). Pacemaker therapy is establishing itself for the prevention of atrial fibrillation. Pacing for neurocardiogenic syncope with newer pacing mode has encouraging datas. Pacemaker for long QT syndrome, after cardiac transplant and for haemodynamic improvement in occasional cases of first degree atrio-ventricular block is getting attention. The AHA and ACC guidelines updated in 1998 for implantation of cardiac pacemakers, now include several of these newer indications.     

A 3 year retrospective review of intrauterine insemination, using cryopreserved donor spermatozoa and cycle monitoring by urinary or serum luteinizing hormone measurements

Insemination with donor spermatozoa is an integral part of infertility treatment. For the last 3 years in our unit, intrauterine insemination with donor spermatozoa (IUID) has been used in preference to vaginal insemination. In this retrospective study, patients were offered an initial course of five single intrauterine inseminations with cryopreserved donor spermatozoa and treatment was then reviewed. A total of 389 patients received 1465 inseminations. In all, 1119 cycles were monitored using luteinizing hormone serum analyses and 346 cycles using the urine home test kits. The clinical pregnancy rate per insemination for the cycles monitored by the serum assay was 18.0% (202/1119) compared with the urine cycles (13.7%, 46/346) (P <05). The pregnancy loss rate was not significantly different (14.4%, 29/202 and 21.7%, 10/46) (serum and urine cycles respectively). The viable clinical pregnancy rate was significantly higher (P <03) for the serum cycles than for the cycles using the urinary monitoring (15.5%, 173/1119 and 10.4%, 36/346 respectively). The cycles monitored by serum assay had a significantly higher cumulative viable clinical pregnancy rate (P <0001) of 70.2% after nine inseminations compared with the urine monitored cycles of 54.8%. The majority of patients opted for the serum cycles, with a minority self-selecting the urine cycles mainly for travelling convenience. The explanation for the significant differences between the viable clinical pregnancy rates per insemination and the cumulative viable clinical pregnancy rates may be due to the sensitivity of the urine home test kit or the patients' interpretation of the result.      

MR imaging of posteromedial and posterolateral stabilisers of the knee: anatomic basis and patterns of lesions in knee injuries

Summary The angular points are the ligamentous and tendinous structures that reinforce the posteromedial and posterolateral capsule of the knee and share in fixation of the posterior horns of the menisci. They are often damaged in acute injuries and this is usually associated with ruptures of the cruciate and collateral ligaments and may add to the degree of laxity. We describe the normal appearance of these structures in terms of the sectional anatomy, correlated with the lesional appearances of complete and incomplete ruptures and associated meniscal detachments as shown by clinical testing and arthrotomy findings.

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IRM des points d'angle du genou : bases anatomiques et applications aux genoux traumatiques

Résumé Les points d'angle sont des structures ligamentaires et tendineuses qui renforcent la capsule postéro-médiale et postéro-latérale et participent à la fixation des cornes postérieures des ménisques. Leurs lésions, fréquentes au cours des traumatismes aigus, sont généralement associées à des ruptures des ligaments croisés et des ligaments collatéraux et peuvent être source d'une aggravation de la laxité. Nous rapportons, en corrélation avec l'anatomie en coupe, l'aspect normal de ces structures, et en corrélation avec les données de l'arthrotomie et du testing les aspects lésionnels observés au cours des traumatismes : ruptures complètes, incomplètes et désinsertions méniscales associées.