Treatment of dyslipidaemia in HIV-infected persons

Accumulating evidence suggests that HIV-infected individuals have an increased risk of cardiovascular events. This risk seems to be at least partially mediated by dyslipidaemia, which is related to the use of highly active antiretroviral therapy (HAART). As HIV-infected individuals live longer due to HAART, their cardiovascular risk will invariably increase. Because HAART is likely to be used indefinitely, HAART-related dyslipidaemia has emerged as a major cardiovascular concern. This article summarises the evaluation of dyslipidaemia and cardiovascular risk in HIV-infected individuals, the potential pathophysiological and genetic mechanisms involved in HAART-related dyslipidaemia and the current treatment approaches. In general, dyslipidaemia is evaluated and treated as in HIV-negative persons. The first step is cardiovascular risk assessment and the determination of target lipid levels. A healthier lifestyle and, in particular, smoking cessation should be promoted. Lowering levels of low-density lipoprotein cholesterol (or, in the setting of significant hypertriglyceridaemia, non-high-density lipoprotein cholesterol) is the primary target of intervention. Switching HAART to a more lipid-favourable regimen should be considered if this does not jeopardise virological control. Many patients will need lipid-lowering drug therapy. Appropriate low-density lipoprotein cholesterol target levels may be more difficult to reach than in the HIV-negative population, and the potential for drug interactions when using lipid-lowering agents together with HAART needs to be considered. The identification of HAART strategies with no or minimal metabolic toxicity, and the identification of the safest and most efficacious lipid-lowering therapies for HIV-infected individuals with dyslipidaemia are important research goals.     

Bringing good teaching cases "to life": a simulator-based medical education service.

Realistic medical simulation has expanded worldwide over the last decade. Such technology is playing an increasing role in medical education not merely because simulator sessions are enjoyable, but because they can provide an enhanced environment for experiential learning and reflective thought. High-fidelity patient simulators allow students of all levels to "practice" medicine without risk, providing a natural framework for the integration of basic and clinical science in a safe environment. Often described as "flight simulation for doctors," the rationale, utility, and range of medical simulations have been described elsewhere, yet the challenges of integrating this technology into the medical school curriculum have received little attention. The authors report how Harvard Medical School established an on-campus simulator program for students in 2001, building on the work of the Center for Medical Simulation in Boston. As an overarching structure for the process, faculty and residents developed a simulator-based "medical education service"-like any other medical teaching service, but designed exclusively to help students learn on the simulator alongside a clinician-mentor, on demand. Initial evaluations among both preclinical and clinical students suggest that simulation is highly accepted and increasingly demanded. For some learners, simulation may allow complex information to be understood and retained more efficiently than can occur with traditional methods. Moreover, the process outlined here suggests that simulation can be integrated into existing curricula of almost any medical school or teaching hospital in an efficient and cost-effective manner.     

Increased expression of the cyclin-dependent kinase inhibitor p27 in cleavage-stage human embryos exhibiting developmental arrest

It is accepted that approximately 50% of embryos obtained after IVF arrest during the first week. Traditionally, chromosome abnormality and suboptimal culture conditions have been proposed as factors commonly associated with embryo arrest. However, even when considering 'ideal' conditions and embryos of only excellent morphology in vitro, there is still a significant incidence of embryonic arrest. There is considerable evidence that the nuclear protein p27, a member of the Cip/Kip family of CDK inhibitors, plays an important role in multiple fundamental cellular processes, including cell proliferation, cell differentiation, and apoptosis. The present investigation, using immunocytochemical techniques coupled with confocal microscopy, was undertaken to determine whether p27 could play a role in the arrest of 4-8-cell human embryos. A total of 28 preimplantation embryos at the 4-8-cell stage were investigated. Of these, 16 were diploid embryos showing cleavage arrest with no further progression, and 12 were normally developing embryos. There was a 2-fold increased expression of the cell-cycle inhibitor p27 in arrested embryos compared with control normally developing embryos. This study represents the first demonstration of an increased expression of p27 in cleavage-stage human arrested embryos.     

Coronary heart disease: acceptance of guideline recommendations irrelevant in Germany?

It is important to conduct research on how guidelines are acceptedand implemented among GPs and to look for barriers to theirimplementation. We believe, however, that a comparison betweencountries must be made with great care; we know that there aredifferences in the organization of primary care between differentEuropean countries. We also know there are differences in theprocess of implementing guidelines between     

In vivo actions of the selective 5-HT1A receptor agonist BAY x 3702 on serotonergic cell firing and release

We investigated the effects of the novel 5-HT1A receptor agonist BAY x 3702 on the serotonergic function in rat brain using single unit recordings in the dorsal raphe nucleus (DR) of anesthetized rats and in vivo microdialysis in freely moving rats. The administration of BAY x 3702 (0.25-4 microg/kg i.v.) suppressed the firing activity of 5-HT neurones. This effect was antagonized by a low dose of the selective 5-HT1A receptor antagonist WAY 100635 (5 microg/kg i.v.). In microdialysis experiments, BAY x 3702 (10-100 microg/ kg s.c.) reduced dose-dependently the 5-HT output in the dorsal and median raphe (MnR) nucleus, dorsal hippocampus (DHPC) and medial prefrontal cortex (mPFC) in a regionally selective manner. Maximal effects were observed in the MnR and mPFC, with reductions to approximately 15% of baseline at a dose of 0.1 mg/kg s.c. The decrease in 5-HT output produced in the DR and DHPC was more moderate, to 45% of baseline at 0.1 mg/kg s.c. BAY x 3702. WAY 100635 (0.3 mg/kg s.c.) completely antagonized the effect of BAY x 3702 (30 microg/kg s.c.). The application of BAY x 3702 in the DR (1-100 microM) reduced the local 5-HT output to 25% of baseline. In rats implanted with two dialysis probes (in DR and mPFC) the application of BAY x 3702 (30 microM) in the DR reduced the 5-HT output in the DR and that in mPFC. These effects were significantly antagonized by the co-perfusion of WAY 100635 (100 microM) in the DR. Overall, these results indicate that the systemic administration of BAY x 3702 reduces the 5-HT release with high potency through the activation of midbrain 5-HT1A receptors.     

Efficiency of endoscopic treatment for vesico‐ureteric reflux in adults

OBJECTIVE

To evaluate the results of our experience with endoscopic management of vesico‐ureteric reflux (VUR) in adults, and to describe factors and complications that might contribute to the failure of the technique.

PATIENTS AND METHODS

Between 1992 and 2006, 21 patients (17 women and four men; mean age 32.1 years, sd 15.6) had endoscopic treatment for VUR (14 unilateral and seven bilateral ureteric units, UU). Patients previously operated for VUR were excluded. The VUR grades were II, III, IV and V in 10, 12, five and one UUs, respectively. The main indication for treatment was a history of repeated episodes of acute pyelonephritis (61%). Complications after surgery were evaluated.

RESULTS

The success rate of the first endoscopic treatment was 69%, and was 81% after the second. Two UUs with grade IV VUR were endoscopically managed for a third time with complete resolution. Only one UU with grade V VUR required open surgery. The success rate for VUR grades II, III and IV after the first treatment was five of eight, 12/12 and one of five, respectively. After the second treatment the success rate increased to seven of eight and two of five for grades II and IV, respectively. There were no complications related to the intervention. Factors related to a failure of technique were duplex ureter and dysfunctional voiding in eight UUs (seven patients).

CONCLUSIONS

The endoscopic management of VUR in previously untreated adult patients is a simple and efficient technique, with low comorbidity.     

Genetics of ABO, H, Lewis, X and Related Antigens

The present knowledge on chemical, enzymatic, serologic and genetic aspects of ABH antigens is reviewed in an effort to produce a simple and coherent genetic model for the biosynthesis of these antigens and chemically related structures. The genetic control of type 1 (Le(a), Le(b), Le(c) and Le(d)), type 2 (X, Y, I, and H), type 3 and type 4 ABH and related antigens in different animal and human tissues is analyzed, taking into account the properties of the glycosyltransferases which are involved in their synthesis and considering possible competition for common acceptor and donor substrates. The phylogeny of ABH determinants shows that they appeared as tissular antigens much earlier than as red cell antigens. The ontogeny of ABH antigens suggests that they behave as differentiation antigens, and an effort is made to correlate their tissular distribution in the adult with the embryological origin of each tissue.