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Summary report: workshop on the potential risks of antibody-dependent enhancement in human HIV vaccine trials.

Concern that ADE of HIV infection could occur in vivo, as a result of HIV immunization, has arisen for several reasons. Immune-mediated disease enhancement occurs in several human and animal viral diseases, including lentiviral diseases. Tropism for host M/M cells is a common characteristic in these diseases. Sera from naturally infected, and possibly HIV-immunized, individuals have been shown to contain infection enhancing antibodies in vitro. Finally, there is considerable genetic, and potentially antigenic, diversity among HIV-1 isolates. This workshop was convened to evaluate these concerns regarding ADE of HIV infection in human HIV vaccine trials and to propose studies that would address this potential risk. Although there is currently no evidence that immune-mediated enhancement of disease occurs in HIV, there is clearly a need for carefully designed experiments to further evaluate this issue. As there are several notable diseases for which in vitro ADE does not correlate with ADE in vivo, in vitro data are insufficient to deter development of current HIV-1 vaccine candidates. In vivo correlates of protection/enhancement are necessary to evaluate the ADE risk accurately. The development of an HIV animal model that would allow testing of vaccine candidates is of primary importance.

AIDS Vaccines↗

Importance of dose intensity in neuro-oncology clinical trials: summary report of the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium.

Therapeutic options for the treatment of malignant brain tumors have been limited, in part, because of the presence of the blood-brain barrier. For this reason, the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium, the focus of which was the "Importance of Dose Intensity in Neuro-Oncology Clinical Trials," was convened in April 2000, at Government Camp, Mount Hood, Oregon. This meeting, which was supported by the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, and the National Institute of Deafness and Other Communication Disorders, brought together clinicians and basic scientists from across the U.S. to discuss the role of dose intensity and enhanced chemotherapy delivery in the treatment of malignant brain tumors and to design multicenter clinical trials. Optimizing chemotherapy delivery to the CNS is crucial, particularly in view of recent progress identifying certain brain tumors as chemosensitive. The discovery that specific constellations of genetic alterations can predict which tumors are chemoresponsive, and can therefore more accurately predict prognosis, has important implications for delivery of intensive, effective chemotherapy regimens with acceptable toxicities. This report summarizes the discussions, future directions, and key questions regarding dose-intensive treatment of primary CNS lymphoma, CNS relapse of systemic non-Hodgkin's lymphoma, anaplastic oligodendroglioma, high-grade glioma, and metastatic cancer of the brain. The promising role of cytoenhancers and chemoprotectants as part of dose-intensive regimens for chemosensitive brain tumors and development of improved gene therapies for malignant gliomas are discussed.

Adult↗

Summary report: evidence for the effectiveness of rehabilitation for persons with traumatic brain injury.

We evaluated the evidence for effectiveness of rehabilitation methods throughout the phases of recovery from traumatic brain injury (TBI) in adults. MEDLINE, HealthSTAR, CINAHL, PsycINFO, and the Cochrane Library were searched, and a total of 3,098 abstracts were reviewed. The strongest studies were critically appraised and their data placed in evidence tables. Results showed that to determine the effectiveness of rehabilitation interventions for persons with TBI, a commitment must be made to population-based studies, strong controlled research design, standardization of measures, adequate statistical analysis, and specification of health outcomes of importance to persons with TBI and their families.

Adult↗

The Canadian whole body counting intercomparison program: a summary report for 1989-1993.

The Human Monitoring Laboratory, which is the Canadian National Calibration Reference Centre for In-Vivo Measurements, has been conducting an annual intercomparison program for whole body counting facilities since 1989. Each year a number of phantoms are prepared for participants to measure the accuracy, precision, size dependency, and identification capabilities of their whole body counters. Other tests are designed to measure the sensitivity of the whole body counter to geometry factors. Some phantoms are prepared with the same radionuclide from year to year so that time dependent data can be acquired, whereas other phantoms are prepared as unknowns. This article describes the tests that were performed, gives the results for Canadian participants, and compares the results to interim performance criteria. Measurement results from a human volunteer who ingested 137Cs contaminated caribou meat and was counted at a number of facilities in 1990 are also presented.

Canada↗