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Biomedical subjects

Robert Nelson

Publications and source records attributed to Robert Nelson.

11 recordsLinked to original sources
PubMed2004

Frequent human leukocyte antigen class I alleles are associated with higher viral load among HIV type 1 seroconverters in Thailand.

The loss of viral control by the host may be due to the evolution of viruses with mutations that limit presentation by human leukocyte antigen (HLA) to cytotoxic T cells. The authors hypothesized that the consequence of such evolution might be that persons with common HLA class I alleles would be less able to control viremia, on average, than would those with rare alleles. HLA class I typing was completed for 128 injection drug users who seroconverted in a prospective cohort study in Bangkok, Thailand. Logistic regression was used to model viral load (greater than or equal to the median) at 9 and 12 months after seroconversion with an HLA score that profiled the relative prevalence of each individual's alleles. At 12 months after seroconversion, injection drug users with the most common HLA alleles (highest quartile HLA score) had an almost 4-fold increased risk for higher viral load (> or = 32,055 copies/mL) than injection drug users with less common HLA alleles (adjusted odds ratio, 3.92; 95% confidence interval, 1.3-11.8). These findings support the importance of frequency-dependent effects of host genes on HIV type 1 evolution in different populations and suggest that HLA-driven viral evolution critically influences control of viremia in early HIV type 1 infection.

Alleles↗
PubMed2004

The European Union Directive and the protection of incapacitated subjects in research: an ethical analysis.

OBJECTIVE: We perform an ethical analysis of European Union Directive 2001/20/EC on the simplification and harmonization of guidelines regarding good clinical practice in the conduct of clinical trials involving drugs. BACKGROUND: The Directive provides guidance on protecting incapacitated subjects who participate in drug clinical trials. Such guidance promotes society's obligations of beneficence because the participation of incapacitated subjects in research is crucial in advancing the understanding and treatment of serious diseases. The Directive requires proxy consent for incapacitated subjects which adheres to the principle of respect for persons. The Directive also recommends additional safeguards to further protect subjects against exploitation and harm. These include respect for the assent and dissent of incapacitated subjects and the "necessity" and "subject-condition" requirements. RESULTS: While these essential protection mechanisms are commendable, the Directive fails to endorse other safeguards that have been recommended by other research ethics guidelines, especially for riskier research. The Directive's silence regarding research in the emergency setting frustrates the principle of beneficence because the lack of guidance might prove to be a barrier for the conduct of such potentially beneficial research. CONCLUSIONS: We conclude that the European Directive fails in many respects to promote several important ethical principles in research involving incapacitated subjects.

Critical Care↗
PubMed2003

Human immunodeficiency virus type 1 subtype and other factors associated with extrapulmonary Cryptococcosis among patients in Thailand with AIDS.

Delineating factors associated with extrapulmonary cryptococcosis (EPC), a major disease burden among Thailand's AIDS patients, can clarify its pathogenesis and guide preventive interventions. From November 1993 through June 1996, enhanced surveillance of 2261 human immunodeficiency virus (HIV)-seropositive patients in a hospital near Bangkok showed EPC among 561 of 1553 AIDS patients (36.1%). Univariate analysis results were confirmed by multivariate analyses of data on 1259 patients. Logistic regression models identified factors significantly associated with EPC to be male sex (adjusted odds ratio [aOR], 2.0; 95% confidence interval [CI], 1.3-2.9), age <33 years (aOR, 1.5; 95% CI, 1.2-1.9), severe immunosuppression (aOR, 1.8; 95% CI, 1.3-2.6), not injecting drugs (aOR, 3.0; 95% CI, 1.7-5.5), and infection with HIV-1 circulating from CRF01_AE (formerly subtype E) versus subtype B (aOR, 2.3; 95% CI, 1.2-4.5). The association with CRF01_AE may result from undetermined markers of exposure or viral subtype effects on host immune responses. Better understanding of the epidemiology of EPC may reduce EPC incidence through targeted primary prevention and treatment.

AIDS-Related Opportunistic Infections↗
PubMed2003

Evaluation of a sensitive/less sensitive testing algorithm using the bioMérieux Vironostika-LS assay for detecting recent HIV-1 subtype B' or E infection in Thailand.

The performance of the bioMérieux Vironostika-LS EIA (less sensitive enzyme immunoassay) was assessed to detect recent seroconversion among injecting drug users (IDUs) in Bangkok, Thailand who were infected with either HIV-1 subtypes B' or E (also known as circulating recombinant form CRF01_AE). To evaluate the Vironostika-LS EIA in non-B subtypes, we collected longitudinal specimens (n = 796) from 115 IDUs (subtype B' infection, n = 24; subtype E infection, n = 91). After testing HIV-positive specimens with the Vironostika-LS EIA, standardized optical densities (SODs) were calculated using median values to determine the window period, which is the time from seroconversion on a standard EIA to seroconversion on the Vironostika-LS EIA for a given SOD, for either subtype. For an SOD cutoff of 1.0, Vironostika-LS EIA results showed a mean window period of 239 days (95% confidence interval [95% CI], 208-287 days) for subtype B' and 356 days (95% CI, 318-402 days) for subtype E in Thailand. This outcome demonstrates that the Vironostika-LS EIA has significantly different performance characteristics in detecting recent seroconversion between different HIV-1 subtypes. Accurate identification of recent infection and estimation of incidence for HIV-1 strains other than North American subtype B, using the Vironostika-LS EIA, requires knowledge of specimen subtype and use of appropriate cutoffs and mean window periods.

AIDS Serodiagnosis↗
PubMed2002

Higher viral loads and other risk factors associated with HIV-1 seroconversion during a period of high incidence among injection drug users in Bangkok.

We analyzed data from a prospective cohort study of injection drug users (IDUs) attending methadone treatment clinics in Bangkok, Thailand, during 1995-1998 to characterize factors associated with a period of high incidence (PHI) from July 1996 through January 1997 compared with periods of lower incidence. Sociobehavioral characteristics were similar for all participants during and outside the PHI except for the following: there was more reported drug injection while IDUs were incarcerated during the PHI (odds ratio, 1.67; p =.02) and significantly higher proportions of persons reported heroin injection (91% vs. 75%, respectively; p =.02) and higher frequencies of daily injection and sharing of injection equipment (40% vs. 25%, respectively; p =.05) during the PHI than outside the PHI. Through most of the first year after seroconversion, plasma HIV-1 loads were significantly higher in persons who seroconverted during the PHI than in those who seroconverted outside the PHI. Higher viral loads may potentially contribute to faster disease progression and increased infectiousness or transmissibility to subsequent contacts. Our findings suggest that prevention efforts to reduce the effective size and turnover within IDU sharing networks may have a significant impact on the epidemic by disrupting the rapid transmission of HIV-1 from recently infected, highly infectious individuals.

Adult↗
PubMed2002

A headache diagnosis project.

BACKGROUND: Despite the availability of objective criteria, the diagnosis of migraine is thought to be missed frequently in primary practice. OBJECTIVE: To determine the most important questions assisting in the clinical diagnosis of migraine headache. METHODS: A cohort of 461 patients referred to headache specialists in Canada was assessed using a pro-forma questionnaire that was completed by the patients alone or administered by the physicians themselves. A final clinical diagnosis was recorded after a complete clinical evaluation. In a subsequent validation study, three questions derived from the results of the first phase of the study were administered to a new cohort of 128 patients, and diagnoses of "migraine" or "not migraine" were recorded according to the decision generated in the first part of the study. The final clinical diagnosis was taken as the "gold standard" for diagnosis, and the results from the two independently derived diagnostic methods were compared. RESULTS: Statistical analysis of the responses from part 1 of the study yielded three questions (related to daily occurrence, unilaterally, and functional impairment) that distinguished between pure migraine and other headache diagnoses with high reliability and validity. The sensitivity and selectivity of the three-question protocol exceeded 91%. CONCLUSIONS: The use of three questions related to headache frequency, laterality, and impact on functioning may represent an attractive screening instrument in primary care practice, alerting physicians to the diagnosis of migraine in patients or to the possibility of a second or alternative headache diagnosis in patients in whom their diagnosis of migraine previously has been made. The presence of multiple headache syndromes in individual patients, as is common in tertiary referral practice, may reduce the discriminating power of the three-question protocol.

Adult↗
PubMed2002

Mouse ovarian follicles secrete factors affecting the growth and development of like-sized ovarian follicles in vitro.

A series of experiments have been carried out to determine whether follicles secrete factors able to affect the growth and development of other, like-sized follicles. Late preantral mouse ovarian follicles were either cocultured or cultured in media conditioned by previously cultured follicles. In particular, the experiments examined whether follicles do secrete such factors, whether the level of FSH in the culture media can affect that process, and what the nature of such secretory factor(s) might be. First, pairs of follicles were cocultured across a polycarbonate membrane containing pores. This showed that communication between the follicles resulted in the stimulation of growth and that the stimulation was due, at least in part, to the production of secretory factor(s). In subsequent experiments, follicles were cultured in media that had been preconditioned by previously cultured follicles. The concentration of FSH in the cultures determined the effect of the conditioned media: conditioned media was stimulatory to follicle growth when levels of FSH remained high throughout the culture, but inhibitory when FSH levels were dropped midway through the cultures. Heat inactivation removed this inhibitory effect, showing that the factor was likely to be a protein; addition of follistatin to the conditioned media did not alter its effect, indicating that the factor was unlikely to be activin. We have shown through a series of culture experiments that mouse follicles secrete factor(s) that can affect the development of other like-sized follicles when cultured from the late preantral to Graafian stages. Furthermore, we have shown that the effect (or production) of such factors is dependent on the FSH environment of the follicles.

Animals↗