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Biomedical subjects

R Fox

Publications and source records attributed to R Fox.

At least 145 records · Page 8Linked to original sources
PubMed1996

Anti-malarial drugs: possible mechanisms of action in autoimmune disease and prospects for drug development.

A wide variety of mechanisms of anti-rheumatic action have been proposed for anti-malarial agents. The molecular actions of chloroquine have been most thoroughly studied in vitro and in vivo, but it is likely that hydroxychloroquine works by a similar mechanism. Both agents are weak diprotic bases that can pass through the lipid cell membrane and preferentially concentrate in acidic cyto-plasmic vesicles. The resulting slight elevation of pH within these vesicles in macrophages or other antigen-presenting cells may influence the immune response to autoantigens. We hypothesize that anti-malarial agents influence the association of autoantigenic peptides with class II MHC molecules in the compartment for peptide loading and/or the subsequent processing and transport of the peptide-MHC complex to the cell membrane. This model of anti-malarial action provides a method to test additional drugs for their ability to modulate the immune response.

Antigen Presentation↗
PubMed1995

Dedicated short-stay spinal unit.

Prolonged waiting periods for patients with benign spinal surgical lesions led to the creation of a Dedicated Short Stay Spinal Surgical Unit. This unit was implemented in November, 1992, on a 29 bed Neuroscience Unit in a 1200 bed Acute Care Teaching Hospital. Considerations for implementation were many, including psychological impact of chronic pain for patients on prolonged waiting lists, the increased probability of permanent waiting lists, the increased probability of permanent neurological deficits, and the economic impact to patient, societal and hospital budgets. This paper will focus on explanation of the design of the unit, define the benefits and provide study results of the first 85 patients admitted to the unit.

Adult↗
PubMed1994

Thermodynamic characterization of an equilibrium folding intermediate of staphylococcal nuclease.

High-sensitivity differential scanning calorimetry and CD spectroscopy have been used to probe the structural stability and measure the folding/unfolding thermodynamics of a Pro117-->Gly variant of staphylococcal nuclease. It is shown that at neutral pH the thermal denaturation of this protein is well accounted for by a 2-state mechanism and that the thermally denatured state is a fully hydrated unfolded polypeptide. At pH 3.5, thermal denaturation results in a compact denatured state in which most, if not all, of the helical structure is missing and the beta subdomain apparently remains largely intact. At pH 3.0, no thermal transition is observed and the molecule exists in the compact denatured state within the 0-100 degrees C temperature interval. At high salt concentration and pH 3.5, the thermal unfolding transition exhibits 2 cooperative peaks in the heat capacity function, the first one corresponding to the transition from the native to the intermediate state and the second one to the transition from the intermediate to the unfolded state. As is the case with other proteins, the enthalpy of the intermediate is higher than that of the unfolded state at low temperatures, indicating that, under those conditions, its stabilization must be of an entropic origin. The folding intermediate has been modeled by structural thermodynamic calculations. Structure-based thermodynamic calculations also predict that the most probable intermediate is one in which the beta subdomain is essentially intact and the rest of the molecule unfolded, in agreement with the experimental data. The structural features of the equilibrium intermediate are similar to those of a kinetic intermediate previously characterized by hydrogen exchange and NMR spectroscopy.

Calorimetry, Differential Scanning↗
PubMed1994

Outcome of inadvertent administration of a gonadotrophin-releasing hormone agonist (buserelin) in early pregnancy.

All women undergoing pituitary down-regulation before planned in-vitro fertilization (IVF) treatment in two IVF units were studied to assess the risks of and to pregnancies occurring inadvertently when gonadotropin-releasing hormone agonists (GnRHa) were used to achieve pituitary desensitization during the luteal phase prior to planned IVF treatment. In 2670 cycles, 25 women conceived (0.9% of cycles). Of these, three resulted in pre-clinical abortions (12%) but there were no clinical abortions, and 22 have ended with live births at term of apparently normal infants. Collation of these and other published data suggest that pregnancy outcome is not adversely affected by GnRHa administration in the luteal phase of the conception cycle.

Abortion, Spontaneous↗
PubMed1994

Multiple follicular development associated with herbal medicine.

After three endocrinologically normal cycles while undergoing unstimulated in-vitro fertilization treatment, a woman took a herbal medicine (Vitex agnus castus) at the beginning of a fourth unstimulated IVF treatment cycle. In this fourth cycle, her serum gonadotrophin and ovarian hormone measurements were disordered. One embryo resulted from the three eggs collected but a pregnancy did not ensue. She had symptoms suggestive of mild ovarian hyperstimulation syndrome in the luteal phase. Two subsequent cycles were endocrinologically normal. We do not advocate the use of this herbal medicine to promote normal ovarian function.

Adult↗
PubMed1994

Seroconversion in patients attending sexually transmitted disease clinics.

OBJECTIVES: To characterize recent HIV seroconverters in a sexually transmitted disease (STD) clinic population, and examine changing transmission patterns. METHODS: We conducted a case-control study nested within a retrospectively defined cohort of individuals attending Baltimore STD clinics between January 1988 and July 1990. Seroconverters, who tested HIV-positive after having a negative test, were compared to both HIV-negative controls, who were also tested twice, and a second, prevalent HIV-positive control group. Controls were matched 2:1 by sex, clinic, and month of HIV test. RESULTS: Forty-nine out of 6175 (0.79%) patients tested at least twice had documented HIV-1 seroconversion. On multivariate analysis, seroconversion was significantly associated with self-reported injecting drug use [odds ratio (OR), 7.3; 95% confidence interval (CI), 2.3-23)], with being a man who has had sex with other men (OR, 3.5%; 95% CI, 1.2-10), or with having sex with a known HIV-infected person (OR, 11; 95% CI, 1.3-96). Thirty-five per cent of seroconverters did not report a risk for HIV infection, and a higher proportion of recent seroconverters also reported no risk. Compared to the prevalent positive control group, more seroconverters reported no risk and a lower proportion reported recognized risks. A diagnosis of gonorrhea was also significantly associated with seroconversion (OR, 2.5; 95% CI, 1.1-5.7). CONCLUSIONS: These data suggest increasing heterosexual transmission of HIV in this inner-city STD clinic population. Incident STD, in particular gonorrhea, may increase a patient's risk for HIV infection, suggesting that patients with STD should be targeted aggressively for HIV prevention activities.

Adult↗
PubMed1994

Zidovudine phosphorylation in HIV-infected patients and seronegative volunteers.

OBJECTIVES AND DESIGN: Measurement of phosphorylated zidovudine (ZDV) inside infected cells is more likely to provide satisfactory dose response relationships than serum concentrations. This study provides information on ZDV phosphorylation in HIV-seronegative volunteers (n = 5) and in patients with HIV infection (n = 12). METHODS: Intracellular ZDV phosphate metabolites were measured in peripheral blood mononuclear cells isolated from whole blood by density cushion centrifugation. Cells were washed and extracted overnight with 60% methanol prior to analysis by high performance liquid chromatography. Fractions eluted from the column corresponding to ZDV, ZDV monophosphate (ZDV-MP), ZDV diphosphate (ZDV-DP) and ZDV triphosphate (ZDV-TP) were collected, hydrolysed by acid phosphatase and ZDV levels quantified by radioimmunoassay. RESULTS: The area under the plasma ZDV concentration-time curve (AUC0-6 h) was similar in seronegative volunteers and patients [mean +/- SD, 4.64 +/- 2.50 versus 5.56 +/- 2.67 mumoles/l h; 95% confidence interval (CI), -4.39-2.23; P = 0.646, Mann-Whitney U test]. However, ZDV phosphorylation was greater in patients, with the AUC0-6 h for total phosphate metabolites being 5.91 +/- 3.42 pmoles/10(6) cells h compared with seronegative volunteers (0.66 +/- 0.48 pmoles/10(6) cells h; 95% CI, -8.35 to -2.32; P = 0.0003). The concentration of ZDV-TP was similar in both groups, the increase in total phosphates in patients being due primarily to ZDV-MP. ZDV-MP AUC0-6 h and total ZDV phosphate AUC0-6 h were closely correlated (r2 = 0.94). The relationship between total ZDV phosphate AUC0-6 h and the CD4 count demonstrates that patients with a count < 100 x 10(6)/l have much higher ZDV phosphate levels, predominantly ZDV-MP. CONCLUSION: ZDV is phosphorylated to a greater extent in patients than in healthy volunteers. The increased ZDV-MP in patients with low CD4 counts may explain the well known occurrence of increased ZDV toxicity in patients with more advanced disease. The ability to measure ZDV phosphorylated metabolites (without the administration of radiolabelled nucleoside) represents a significant advance in our understanding of the clinical pharmacology of the drug.

Acquired Immunodeficiency Syndrome↗