Therapeutic studies in NZB/W mice. I. Synergy of azathioprine,cyclophosphamide and methylprednisolone in combination

This study compares different immunosuppressive regimens in the treatment of the lupus-like nephritis of NZB/W mice. Groups of 5-month-old female NZB/W mice were given azathioprine, cyclophosphamide and methylprednisolone in all one-, two- and three-drug regimens, each drug in the relatively low dose of 1.5 mg/kg/day. Treatment for 3 months with one or two drugs resulted in modest suppression of NZB/W disease. Mice receiving all three drugs had significantly less proteinuria, lower titers of anti-DNA antibody and less severe, histologically evident renal involvement than mice treated with one or two drugs. Survival at 1 year was 10% for untreated controls, 44% for one-drug-treated, 37% for two-drug-treated and 86% for the three-drug-treated mice. The survival for the three-drug regimen was significantly longer than any other group (P < 0.01). The three-drug regimen was synergistic, since mice treated with each drug at three times the dose had significantly more proteinuria after 3 months of treatment and lowered 1 year survival (33%). The beneficial effects of triple-drug therapy were attained without increased toxicity. This study represents the first controlled evaluation of single versus combination therapy in a model of autoimmune disease. Based on these results, a controlled evaluation of triple-drug therapy in human systemic lupus erythematosus appears warranted.     

Long-term complications and risk of other serious infections following invasive Haemophilus influenzae serotype b disease in vaccinated children

This study describes the long-term complications in children with Haemophilus influenzae serotype b (Hib) vaccine failure and to determine their risk of other serious infections. The families of 323 children with invasive Hib disease after appropriate vaccination (i.e. vaccine failure) were contacted to complete a questionnaire relating to their health and 260 (80.5%) completed the questionnaire. Of the 124 children with meningitis, 18.5% reported serious long-term sequelae and a further 12.1% of parents attributed other problems to Hib meningitis. Overall, 14% (32/231 cases) of otherwise healthy children and 59% (17/29 cases) of children with an underlying condition developed at least one other serious infection requiring hospital admission. In a Poisson regression model, the risk of another serious infection was independently associated with the presence of an underlying medical condition (incidence risk ratio (IRR) 7.6, 95% CI 4.8–12.1; p < 0.0001), both parents having had a serious infection (IRR 4.1, 95% CI 1.6–10.3; p = 0.003), requirement of more than two antibiotic courses per year (IRR 2.3, 95% CI 1.4–3.6; p = 0.001) and the presence of a long-term complication after Hib infection (IRR 1.8, 95% CI 1.1–3.1; p = 0.03). Thus, rates of long-term sequelae in children with vaccine failure who developed Hib meningitis are similar to those in unvaccinated children in the pre-vaccine era. One in seven otherwise healthy children (14%) with Hib vaccine failure will go on to suffer another serious infection requiring hospital admission in childhood, which is higher than would be expected for the UK paediatric population.     

Laparoscopy and laparoscopic surgery

Today, laparoscopy is an alternative technique for carrying out many operations that have traditionally required an open approach. The benefits of minimal access surgery have been well recorded, including lower post-operative morbidity, shorter duration of hospital stay and a shorter return to work. Advances in technology, specifically in fibre optics and video imaging, have made the relatively recent rapid progress in laparoscopic surgery possible. Operative laparoscopy, however, requires a high degree of technical skill and training. The use of small instruments and imaging systems that provide magnification allow for the high degree of precision that can be achieved with laparoscopic surgery. This is often difficult to obtain by a conventional laparotomy, as magnification is not available and the surgeon's hands and large instruments often obscure the operative field. It is this precision that has lead to advances in the treatment of conditions such as endometriosis, adhesions and in the field of reproductive surgery. It is unfortunate however that in reality very few major gynaecological procedures are performed laparoscopically. They are technically difficult and require the surgeon to master a whole new set of surgical skills and in effect to return to the bottom of the surgical learning curve. A wide range of simple laparoscopic procedures needs to be mastered to develop the hand eye coordination required to perform complex tasks. These procedures need to be performed on a regular basis to maintain skills and only when these skills can be regularly performed accurately can complex surgical tasks be carried out. As a result of this, most established gynaecologists have very little time and resources to be able to retrain in what is essentially a new surgical field, although most experts throughout the country agree that the vast majority of gynaecological surgery could safely and efficiently be performed laparoscopically.     

Changes in fibrinogen adsorbed to segmented polyurethanes and hydroxyethylmethacrylate-ethylmethacrylate copolymers.

Fibrinogen adsorption from blood to biomaterials may regulate platelet adhesion and thrombus formation because of fibrinogen's central role in the coagulation cascade and its ability to bind specifically to the platelet membrane glycoprotein (GP) IIb-IIIa. Adsorption of fibrinogen from blood plasma to many materials exhibits a maximum with respect to plasma dilution and exposure time (the Vroman effect). In this study fibrinogen adsorption to several polymers was examined to ascertain the influence of controlled changes in surface chemistry on the Vroman effect. The materials included hydroxyethylmethacrylate-ethylmethacrylate (HEMA/EMA) copolymers, Biomer, and a series of segmented polyurethanes (PEUs), two of which contained fluorinated chain extenders. Each material exhibited maximal adsorption of fibrinogen at intermediate plasma concentrations. Little effect of soft-segment type or molecular weight was observed and no significant differences in fibrinogen adsorption to the fluorinated PEUs were seen. Changes in the strength of fibrinogen attachment to these materials with time after adsorption were also assessed. Fibrinogen adsorbed for 1 min was displaced more readily by blood plasma than that adsorbed for 1 h, regardless of the material. The more hydrophobic polymers exhibited greater retention of adsorbed fibrinogen. In addition, the fraction of fibrinogen retained by polyethylene depended on the amount of fibrinogen adsorbed to the surface, being greatest when the surface loading was the least. These studies indicate that spreading or transition of adsorbed fibrinogen molecules from a weakly to tightly bound state is a general consequence of protein adsorption to solid surfaces.     

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.