Lack of response of anal intra-epithelial neoplasia to highly active antiretroviral therapy.
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Biomedical subjects
Publications and source records attributed to Mark Nelson.
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A small proportion of patients with human immunodeficiency virus type 1 (HIV-1) remains asymptomatic for a long period after infection. It is thought that a vigorous immune response may contribute to long-term nonprogression, though studies are confounded by heterogeneity among patients. We studied the levels of HIV-1 receptors, costimulatory T-cell molecules, and dendritic cell (DC) numbers in 18 patients with long-term infection, CD4 counts greater than 400 cells/mm(3), and HIV-1 viral loads lower than 50 copies/mL. These patients were further differentiated through the presence or absence of 2-LTR DNA circles, a possible marker for residual ongoing HIV-1 replication. A statistically significant increase in levels of CD91, the heat-shock protein (HSP) receptor, was observed in therapy-naive patients who had no evidence of ongoing viral replication (P =.01). This difference was most notable on their monocytes. High levels of CD91 may be a host factor that contributes to the maintenance of long-term nonprogression. The ability of CD91 to internalize alpha-defensins and to cross-present exogenous antigen to cytotoxic T lymphocytes through major histocompatibility complex (MHC) class 1 may maintain CD8(+) responses in these patients.
Oral fluid testing is an effective alternative to serum antibody testing for surveillance of human immunodeficiency virus (HIV) and hepatitis B infections, and is being extended to hepatitis C infections. The objective of this study was to determine and compare the sensitivity and specificity of a modified commercial assay for the detection of antibody to hepatitis C virus (anti-HCV) in oral fluids collected by two different oral fluid collection devices (the Epitope OraSure trade mark and Sarstedt Salivette ) and in dried fingerprick blood spots. In this study, 253 anti-HCV seropositive patients and 394 blood donors (all anti-HCV negative) were recruited between August 2000 and January 2001. Each participant provided oral fluid specimens by OraSure and Salivette, and at least one dried blood spot. Serum specimens were collected from the patients whenever possible. For those injecting drug users who did not provide a serum specimen, HCV status was established on the basis of previous testing. All the nonserum samples were tested for the presence of anti-HCV, using a modified Ortho HCV 3.0 SAVe enzyme-linked immunosorbent assay (ELISA) protocol. The recommended preliminary cutoffs for the modified ELISA were suboptimal. Further, the sensitivity, specificity, and positive and negative predictive values could be improved by varying the cutoff and taking into account the likely prevalence of HCV in the population under investigation. For instance, given a population with a 50% prevalence of anti-HCV, the optimal sensitivities of the modified assay on OraSure, Salivette, and dried blood spots were 92%, 83%, and virtually 100%, respectively, in contrast to 83%, 59%, and 99% using the preliminary cutoffs. The respective optimal specificities were 99%, 93%, and 100%. In conclusion, oral fluids collected by the OraSure device provide an extremely useful method to conduct public health surveillance of not only HIV, but also hepatitis C, among injecting drug users. In addition, dried blood spot specimens may be useful for surveillance and could be employed as a first line diagnostic specimen.
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Low-dose aspirin (acetylsalicylic acid) therapy has been shown to reduce the risk of vascular events and there is increasing evidence of its potential to reduce the rate of cognitive decline in the elderly. Adverse effects including gastrointestinal and intracranial haemorrhage may offset these benefits. The balance of risks versus benefits of aspirin for the primary prevention of cardiovascular disease and vascular dementia has not been established in the elderly. There is clearly a need to conduct a study in family practice to investigate whether routine use of low-dose aspirin for the primary prevention of cardiovascular disease and vascular dementia in the elderly is beneficial or harmful. Aspirin in reducing events in the elderly (ASPREE) is a placebo-controlled trial of low-dose aspirin for the primary prevention of major adverse cardiovascular events and vascular dementia. It will follow 15,000 subjects aged 70 years or more for an average of 5 years. This sample size has a power of 87% to detect a 15% reduction in primary events in the aspirin group, with an anticipated combined primary event rate of 20 per 1000 patient years.
OBJECTIVE: To compare the computed tomographic (CT) findings of abdominal Mycobacterium tuberculosis (MTB) infection and Mycobacterium avium intracellulare (MAI) infection in patients with human immunodeficiency virus (HIV) infection. METHODS: A retrospective review of the CT findings of 30 patients with HIV and proven MTB (n = 9) or MAI (n = 21) infection was conducted. Images were reviewed by a radiologist blinded to the diagnosis, and the radiologic findings involving the abdominal viscera, peritoneum and lymph nodes were compared. RESULTS: The following were more frequent in patients with MAI infection: hepatomegaly (MAI 71% v. MTB 44%, p < 0.05), uniform attenuation of lymph nodes (MAI 90% v. MTB 55%, p < 0.05) and clustered pattern of lymph nodes (MAI 57% v. MTB 22%, p < 0.05). In patients with MTB infection, lymph nodes with low attenuation centrally were more common (MAI 10% v. MTB 44%, p < 0.05), and mesenteric lymph nodes were significantly larger (MAI mean = 20 mm v. MTB mean = 40 mm, p < 0.05). CONCLUSION: Although nonspecific, CT may be useful in the early diagnosis of MTB and MAI infection, allowing for presumptive treatment before microbiologic confirmation.
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A combination of highly active antiretroviral therapy (HAART) and liposomal anthracycline chemotherapy is the standard of care for advanced HIV-associated Kaposi's sarcoma, despite concerns that the chemotherapy may adversely affect lymphocyte subsets and HIV viraemia. We showed in 50 patients that liposomal anthracyclines used with HAART did not lead to a significant loss of CD4 or CD8 cells or an increase in HIV-1 viral load during or up to 12 months after chemotherapy.
OBJECTIVE: To measure the effects of combined chemotherapy and highly active antiretroviral therapy (HAART) on immune cell counts and plasma HIV-1 RNA loads in patients with AIDS-related lymphoma (ARL) to determine the implications for opportunistic infection prophylaxis and medium-term immune function. DESIGN AND METHODS: Peripheral blood total lymphocyte count, CD4 T-cell count, CD8 T-cell count, CD19 B-cell count, CD16/CD56 natural killer cell count and plasma HIV-1 RNA load were prospectively measured at ARL diagnosis, at 1 and 3 months during and 1, 3 and 6 months after chemotherapy in twenty patients receiving HAART. RESULTS: Significant declines in T-helper cell (CD4) count, natural killer cell (CD16/CD56) and B lymphocyte count (CD19 cells) occurred during the first 3 months of chemotherapy. There was no significant alteration in the T-cytotoxic cell (CD8) count, CD4 percentage or HIV-1 RNA load during the study period. The T-helper cell and natural killer cell counts recovered to pre-treatment levels within 1 month of finishing chemotherapy. The recovery of B-cells was slower with pre-treatment levels only being achieved after 3 months. The recovery of CD4 T-cell count following completion of chemotherapy was more rapid than described for ARL patients who were not receiving concomitant HAART. CONCLUSIONS: By combining chemotherapy with HAART, immune function is better maintained in the medium term. The CD4 T-cell count falls by 50% during chemotherapy and this will help to identify patients who require opportunistic infection prophylaxis during chemotherapy.
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Human factors are a key component to the success of long-term space missions such as those necessitated by the human exploration of Mars and the development of bioregenerative and eventually self-sufficient life support systems for permanent space outposts. Observations by participants living inside the 1991-1993 Biosphere 2 closed system experiment provide the following insights. (1) Crew members should be involved in the design and construction of their life support systems to gain maximum knowledge about the systems. (2) Individuals living in closed life support systems should expect a process of physiological and psychological adaptation to their new environment. (3) Far from simply being a workplace, the participants in such extended missions will discover the importance of creating a cohesive and satisfying life style. (4) The crew will be dependent on the use of varied crops to create satisfying cuisine, a social life with sufficient outlets of expression such as art and music, and to have down-time from purely task-driven work. (5) The success of the Biosphere 2 first 2-year mission suggests that crews with high cultural diversity, high commitment to task, and work democracy principles for individual responsibility may increase the probability of both mission success and personal satisfaction. (6) Remaining challenges are many, including the need for far more comprehensive real-time modeling and information systems (a "cybersphere") operating to provide real-time data necessary for decision-making in a complex life support system. (7) And, the aim will be to create a noosphere, or sphere of intelligence, where the people and their living systems are in sustainable balance.
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The electrosensory and mechanosensory lateral line systems of fish exhibit many common features in their structural and functional organization, both at the sensory periphery as well as in central processing pathways. These two sensory systems also appear to play similar roles in many behavioral tasks such as prey capture, orientation with respect to external environmental cues, navigation in low-light conditions, and mediation of interactions with nearby animals. In this paper, we briefly review key morphological, physiological, and behavioral aspects of these two closely related sensory systems. We present arguments that the information processing demands associated with spatial processing are likely to be quite similar, due largely to the spatial organization of both systems and the predominantly dipolar nature of many electrosensory and mechanosensory stimulus fields. Demands associated with temporal processing may be quite different, however, due primarily to differences in the physical bases of electrosensory and mechanosensory stimuli (e.g. speed of transmission). With a better sense of the information processing requirements, we turn our attention to an analysis of the functional organization of the associated first-order sensory nuclei in the hindbrain, including the medial octavolateral nucleus (MON), dorsal octavolateral nucleus (DON), and electrosensory lateral line lobe (ELL). One common feature of these systems is a set of neural mechanisms for improving signal-to-noise ratios, including mechanisms for adaptive suppression of reafferent signals. This comparative analysis provides new insights into how the nervous system extracts biologically significant information from dipolar stimulus fields in order to solve a variety of behaviorally relevant problems faced by aquatic animals.
PURPOSE: Intravitreal injection of triamcinolone acetonide has been advocated to treat exudative diabetic macular edema. The purpose of the study was to evaluate the clinical outcome of an intravitreal injection of triamcinolone acetonide as treatment for diffuse diabetic macular edema. METHODS: This study was a retrospective, interventional, clinical case series examining 210 eyes of 174 patients who received an intravitreal injection of 1 or 4 mg of triamcinolone acetonide for treatment of diffuse diabetic macular edema. Inclusion criteria were clinically significant macular edema, visual acuity loss, and leakage shown by fluorescein angiography. Main outcome measures were visual acuity and intraocular pressure. Mean follow-up time +/- SD was 6.6 +/- 3.1 months. RESULTS: In the study group, visual acuity improved significantly (P < 0.001) from a median of 20/200 (mean logMAR, 0.92) at baseline to 20/80 (mean logMAR, 0.82) at 6 months. Mean intraocular pressure +/- SD increased from 15.4 +/- 3.4 mmHg (median, 16 mmHg; range, 6-26 mmHg) to a maximal value of 20.4 +/- 6.2 mmHg (median, 19 mmHg; range, 12-51 mmHg) during the follow-up period. Complications included culture-negative sterile endophthalmitis in six cases and cataract extraction in five eyes. CONCLUSIONS: Intravitreal injection of 1 to 4 mg of triamcinolone acetonide may benefit patients by improving visual acuity in eyes with clinically significant diabetic macular edema. This study did not provide significant evidence to justify its routine use in clinical practice for all patients with diabetic macular edema. A randomized clinical trial on this issue would provide more conclusive evidence and help identify those patients most likely to benefit from intravitreal triamcinolone acetonide.