Clinical Immunology Newsletter最新文献

In conclusion, with improved primary suppression of HIV-1 replication using triple drug combinations including a protease inhibitor, it is likely that HIV-1-infected patients will survive longer, as CDC data have already to some extent demonstrated. Longer patient survival is especially likely given the successes of Pneumocystis carinii pneumonia and Mycobacterium avium complex prophylaxis. However, the current FDA-approved anti-retroviral regimens do not penetrate well into the CSF or brain tissue. Hence, HIV-1 may continue to replicate relatively unencumbered in brain, especially given the relatively muted immunological response therein. As result, a current hypothesis is that a greater prevalence of these disorders is expected in the near future. Moreover, given the improved prophylaxis and treatment of several lethal complications of HIV-1 infection, it might be expected that the complaint of cognitivemotor impairment will be afforded a higher priority for intervention. It is likely that patients with HIV-1 infection will become more and more focused on maintenance of their functional status as opposed to survival alone in the coming years. Further, while indirect mechanisms of cell death may not be of prominent importance in the periphery, evidence accumulated thus far suggests that such mechanisms (e.g., apoptosis) may be more important in the brain. It might be expected, therefore, that future CNS-specific treatment developments will require a focus on adjuvant therapies used in conjunction with primary anti-retroviral combination therapies. The use of cytokines, monoclonal antibody to cytokines, soluble cytokine receptor, and down-modulators of cytokine secretion represent one category of such adjuvant therapies requiring further development. Current data suggest that the development of such therapies will require an investment in additional basic science research aimed at uncovering the relationship of cytokines and chemokines to neuronal cell death in tissue, as it has already been demonstrated that the effects of several cytokines differ with response to the pathogenesis of MCMD and HAD (more closely related to macrophage activation) versus the progression of disease in the periphery (more closely related to CD4+ T lymphocyte depletion). Hence, a CNS-specific pharmacopeia of anti-retroviral and combination therapy is required to deal with the potential onslaught of cognitivemotor dysfunction and disorders that currently looms as a possibility in the next decade of HIV/AIDS.

The medical benefits of leukocyte-reduced blood components have been well documented. Standards for the labeling of these products have been defined. Manufacturers of leukocyte-reduced blood components must demonstrate compliance with the Guidelines and Requirements for these products published by CBER. The implementation of these requirements by a manufacturer could have a significant impact on the quality of product. It is critical that both process control and product quality control be addressed by the strategy established by the manufacturer for these products. An alternative method for the enumeration of residual leukocytes in these blood components has been described. With this method, accurate enumeration of leukocyte concentration can be obtained with simple processing steps and automated analysis.

Is a molecular diagnostic method needed for the laboratory diagnosis of syphilis? The answer is that in several instances a sensitive and specific method for the direct demonstration of T. pallidum would be beneficial. To date, the clearest progress has been made in the area of GUD and congenital diagnosis. The multiplex PCR method promises to be useful in GUD. It may be particularly useful in large scale epidemiological studies of GUD. For diagnostic purposes, its use will likely be limited to larger centers seeing sufficient numbers of patients. Congenital syphilis diagnostics could certainly use a tool that would help distinguish truly infected from noninfected asymptomatic infants born to seropositive mothers. IgM serologies are useful tools in symptomatic infants but their role, and that of PCR, in asymptomatics is not clear at this time. Certainly, prospective studies with adequate follow-up of infants to clearly document infection are needed to resolve this. Finally, neurosyphilis patients would also benefit from a sensitive and specific test to identify the presence of T. pallidum in the CSF and monitor effective therapy. To date, the experience with PCR is not consistent and additional investigations are needed. The use of molecular diagnostics in syphilis is not as well established as it is for other STDs. However, there is a need and it is hoped that work in this area will continue.