Evaluating HIV / AIDS prevention programs. Meeting the challenge.
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Biomedical subjects
Publications and source records attributed to K Henry.
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DNA ploidy of 57 gastric carcinomas with metastases (12 liver, 1 adrenal, 4 ovary and 48 lymph node) were measured by flow cytometry. DNA anueploidy was significantly related to liver metastases: 9 out of 12 gastric carcinomas with liver metastases were anueploid (75%) as compared to 13 out of 45 (28.8%) of cases without liver metastases (P < 0.01); the one gastric carcinoma with adrenal metastasis was also anueploid. DNA ploidy was not related to ovarian or lymph node metastases. Another interesting finding was that all of 3 gastric carcinomas with liver metastases which showed a diploid DNA pattern, expressed p53 protein, while all of 3 carcinomas with liver metastases but no p53 protein expression were anueploid. The expression of p53 protein was not related to ovarian metastases. The results suggested that an anueploid DNA pattern and the expression of p53 protein are both objective markers valuable in predicting high risk potential of metastases to the liver, and that the combined detection of these markers can be a most useful method in the follow-up of patients with gastric carcinoma in detecting those at high risk of developing metastases following surgical resection. Also the poorer prognosis of patients with gastric carcinoma showing an anueploid DNA pattern may be related to the development of distant organ metastases through the blood vascular system. Furthermore, the clone of gastric carcinoma cells which accumulate p53 protein or show an anueploid DNA pattern may have a causative role in the development of liver (& adrenal) metastases.
Peroxisome proliferators include a heterogeneous group of xenobiotic agents capable of inducing peroxisome proliferation and hepatocellular carcinomas in rodent model systems. These chemicals appear to mediate their activity through a family of transcription factors known as peroxisome proliferator-activated receptors (PPAR). Recently it has been shown that DNA binding of PPAR is contingent upon heterodimerization with a member of the retinoic acid X (RXR) family of receptors. In this report transcription parameters of a rat PPAR alpha were analyzed using mammalian and yeast cotransfection assays. PPAR activity was observed to be peroxisome proliferator dependent in the mammalian cotransfection assay, and heterodimer dependent but peroxisome proliferator independent in a yeast version of the same assay. Moreover, when the naturally occurring ligand for RXR, 9-cis-retinoic acid (RA), was tested in the same assays, it was observed to generate an RXR-specific response in the yeast cell assay but host cell-specific response in the mammalian cell assay. Finally, the combination of peroxisome proliferator and 9-cis-RA had very little added effect on the yeast cell assay but again produced a cell-specific synergistic response in the mammalian cell assay. These data demonstrate that PPAR transcriptional activity is strongly influenced by the RXR family of receptors, and that peroxisome proliferators may be regulating PPAR mammalian cell activity through a secondary mechanism.
A pregnant woman with acquired immunodeficiency syndrome had nonprimary cytomegalovirus (CMV) viremia and died of complications from Pneumocystis carinii pneumonia and CMV sinusitis and pneumonitis. A boy was delivered by cesarean section at 34 weeks of gestation as the mother's health deteriorated and fetal distress developed. The infant died soon after delivery of interstitial pneumonitis and hyaline membrane disease with invasive CMV disease that affected the kidneys, adrenal glands, and placenta; the CMV strains from the mother and neonate were identical.
A focus group comprised of persons who use power wheelchairs and professionals working in the field were asked to participate in a brainstorming session to determine priorities for the development and application of power mobility input devices and control concepts. The group consensus was that durability and reliability are the most important criteria. Essentially, the expectation is that a power wheelchair must work everyday in the way a person needs it and wants it. At the same time, there is a desire to enhance and advance the features of input devices and control systems. Many would say these changes constitute designing "smarter" power wheelchairs, such as systems that can independently detect obstacles and can provide users with more feedback. This paper presents the rationale behind forming this focus group and details of the results of a brainstorming session where ideas were generated and prioritized. The five most important issues as determined by the group are discussed in depth.
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Explore the source record for details and available documents.
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Although the challenges of HIV/AIDS care may seem overwhelming, we are better able than ever to positively affect the course of HIV for each individual patient. Treatment goals involve three areas: 1) Antiretroviral drugs aimed at retarding the rate of HIV replication, thus reducing the rate of damage to the immune system; 2) drugs used to treat or prevent opportunistic infections seen in the context of HIV-related immune deficiency; and 3) drugs used to treat symptoms or syndromes commonly seen in these patients (including dementia and wasting syndrome). The multitude of clinical problems seen in advanced HIV disease leads to significant polypharmacy and costs resulting in a very complex and confusing situation. I recommend that physicians with little HIV experience link up with an HIV specialist when caring for HIV-infected patients to optimize access to the best therapies or research studies currently available. With no cure in sight, physicians need to focus on educating the public and patients about how to avoid HIV infection and to identify persons who are infected to minimize spread.
Clinical studies involving HIV therapeutics are becoming ever more challenging because of the changing epidemiology of HIV infection, the rapid evolution of standard clinical practice, and a more difficult economic environment for research. Recent studies relating to HIV pathogenesis have provided novel insights into the interactions between HIV, the immune system, and antiretroviral therapies. Current dogma now suggests that the interaction of HIV and the immune system is an incredibly dynamic process. HIV is an intimidating pathogen capable of replicating quickly and mutating very rapidly in response to antiretroviral therapy. An important question being studied by Minnesota-based investigators is how well plasma analysis reflects HIV-immune system interactions in the lymphoid tissue where most virus and CD4+ (T-helper) cells are located. Most of the HIV clinical studies in Minnesota are conducted under the auspices of the AIDS Clinical Trials Group (ACTG) or the AIDS Research Consortium of the Twin Cities (ARCTiC). Much expertise is available in Minnesota addressing a wide range of topics, from epidemiology, to basic virology, to prevention. To optimize patient access to clinical studies, we recommend that physicians discuss available clinical studies with an HIV investigator soon after first seeing a new HIV-infected patient.
Exposure to HIV in the workplace is a major concern for health care workers. The greatest risk for bloodborne pathogen transmission is associated with percutaneous injuries involving hollow-bore needles contaminated with patient blood. Limited data are available about how many sharps injuries (SIs) and needlesticks (NSs) occur in the United States, with estimates ranging from 100,000 to 1 million injuries per year. We conducted a survey of 100 infection control practitioners located at randomly selected U.S. hospitals to assess the number of SIs or NSs occurring during 1990; 65 (65%) responded. The mean number of NS/SIs reported was 45, with a mean of 1.1 known HIV-related NS/SIs. The underreporting rate was estimated to be 18.5%. Assuming that the hospitals provided exact numbers of injuries and were representative of the approximately 5,100 U.S. hospitals, then about 252,000 NS/SIs were reported in U.S. hospitals in 1990 (95% CI = 193,000-312,000). If the under-reporting rate was 33% to 66%, then the point estimate for the total number of NS/SIs ranges from 378,000 to 756,000. Similar extrapolation involving the reported number of NS/SIs contaminated with blood from an HIV-infected patient yields an estimate of 5,610 exposures in 1990 (95% CI = 1,300-8,300). The number of U.S. hospital workers sustaining NS/SIs with potential exposure to HIV appears to be considerable. Efforts to reduce the risk of bloodborne pathogen transmission from NS/SIs are warranted.
PURPOSE: To examine Department of Corrections (DOC) policies prohibiting prisoner participation in research studies and to assess the variables associated with state policies and practices relating to access by inmates in U.S. prisons to HIV-related clinical studies and experimental therapies. METHODS: A telephone survey conducted in 1994-95 of DOC medical directors from 32 states throughout the United States to obtain information about state DOC policies and practices relating to HIV clinical studies. RESULTS: State policies governing prisoner participation in clinical trials and access to new therapies vary widely. States with high AIDS incidence rates, a large number of AIDS-related deaths in prison, and high concentrations of minorities in the correctional system were more likely to allow prisoners to enroll in clinical studies and to receive experimental medications. Overall, a relatively small number of prisoners in state prisons have enrolled in clinical studies. Participation of a prison representative on the board reviewing a clinical study was identified as an important factor in allowing prisoner participation in studies. CONCLUSIONS: Barriers to prisoner participation in clinical studies are numerous but not insurmountable. Results from this study have led to efforts in Minnesota to revise current policy in order to permit prisoner participation in studies if appropriate guidelines are followed.
It is hoped that this survey conveys a sense of the many positive uses of focal and nonfocal MC stimulation already manifest within a decade of its introduction. As with other techniques of investigating brain function, MC stimulation has its relative advantages and disadvantages. The precision of defining the site of MC effects currently is inferior to that achieved with PET scanning, but the precision of timing of effects is superior, being on the order of milliseconds. Perhaps the special value of MC stimulation is in moving closer to specifying cause-effect relationships, through interference or facilitatory effects, than when techniques yielding more circumstantial evidence are used. However, it is the testing and cross-validation of the conclusions from the different modes of neuroscientific inquiry that we look to in synthesizing explanations of brain function.
BACKGROUND: This report is a study of prognostic factors, including adjuvant chemotherapy, that influence survival of patients with malignant melanoma who have clinical and pathologic involvement of regional lymph nodes. METHODS: A total of 169 evaluable patients with malignant melanoma metastatic to regional lymph nodes were registered consecutively and prospectively between June 1977 and December 1986 in the computerized data base of the melanoma registry at Westminster Hospital. Eighty-seven of these patients received adjuvant chemotherapy with vindesine after resection of palpable metastatic lymph nodes, and 82 had no systemic treatment after surgery. All were followed up for at least 2 years (median, 8 years) after involvement of regional lymph nodes was noted or until death. Statistical analyses included simple life-table comparisons, unadjusted for covariates. In addition, Breslow's thickness, ulceration of the primary lesion, its anatomical location, number of regional lymph nodes histologically involved, dissection site, patient age and sex, and adjuvant vindesine therapy were included as covariates in Cox regression models. RESULTS: The disease-free interval (P = 0.0001), time to dissemination from lymph node metastases (P < 0.0001), survival time after lymph node dissection (P = 0.0227) and overall survival time after initial diagnosis of malignant melanoma (P = 0.0095, log-rank chi-square test) were superior for the 87 patients who received adjuvant chemotherapy with vindesine. Cox regression analysis confirmed adjuvant vindesine as a highly significant variable influencing all of these outcomes, including overall survival time after first diagnosis (P = 0.003). CONCLUSIONS: The apparent effect of adjuvant vindesine on overall survival in this study is large (hazard ratio, 0.52) and highly statistically significant. Adjuvant vindesine therapy merits consideration for malignant melanoma metastatic to regional lymph nodes. However, these results observed in concurrent, but nonrandomized, patients clearly require confirmation.