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Biomedical subjects

B Maher

Publications and source records attributed to B Maher.

15 recordsLinked to original sources

Short-term exercise training improves body composition and hyperlipidaemia in HIV-positive individuals with lipodystrophy.

Exercise/physical activity is increasingly being advocated as a positive addition to the treatment regimen of HIV-positive individuals. We investigated the effects of 10 weeks' aerobic and resistance training on individuals with HIV-related lipodystrophy. These individuals demonstrated an improvement in exercise tolerance, body composition and blood lipid profiles. Potentially, such changes may contribute to an amelioration of some of the adverse metabolic effects associated with highly active antiretroviral therapy.

Adult↗

Expression of P-glycoprotein and multidrug resistance-associated protein in healthy volunteers and HIV-infected patients.

Increased expression of the multidrug efflux transporters P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) has been suggested as a potential mechanism for decreased drug availability at certain intracellular sites that provide sanctuary for HIV. Here we investigate the expression of these transporters in peripheral blood mononuclear cells (PBMCs) of HIV-infected patients and healthy volunteers. Venous blood (30 ml) was taken from healthy volunteers (n = 21) and HIV-infected patients (n = 21; 4 antiretroviral drug naive, 17 antiretroviral drug experienced). PBMCs were isolated and fixed. To assess P-gp expression, PBMCs were incubated with an isotype control antibody or an antibody directed to an external epitope of P-gp (UIC2). To assess MRP expression, cells were permeabilized before incubation with either a control antibody or an antibody directed to an internal epitope of MRP (MRPm5). After washing, a secondary phycoerythrin-bound antibody was incubated. After additional wash steps, samples were fixed and analyzed by flow cytometry. The median fluorescence intensity of 5000 events was recorded. Results are expressed as fold increase between isotype control and UIC2/MRPm5 samples. Expression of P-gp in HIV-infected patients (1.42 +/- 0.36) was significantly lower (p = 0.0021; 95% CI, -0.633 to -0.164) than in healthy volunteers (1.82 +/- 0.55). However, MRP expression was similar in HIV-infected patients (1.37 +/- 0.34) and healthy volunteers (1.37 +/- 0.21; p = 0.91; 95% CI, -0.148941 to 0.165191). We conclude that in HIV infection, P-gp expression in total PBMCs is reduced whereas MRP expression appears to be unaltered.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Effect of alpha1-acid glycoprotein on the intracellular accumulation of the HIV protease inhibitors saquinavir, ritonavir and indinavir in vitro.

AIMS: Since alpha1-acid glycoprotein (AGP) levels may be raised during HIV infection, we have examined in vitro the effect of increasing the concentration of AGP on the intracellular accumulation of the HIV protease inhibitors saquinavir (SQV), ritonavir (RTV) and indinavir (IDV). METHODS: U937 cells (5 x 10(6) cells in 5 ml RPMI growth medium) were incubated at 37 degrees C for 18 h with [14C]-SQV (0.1 microCi), [3H]-RTV and [3H]-IDV (0.135 microCi) to a final concentration of 1 microM in the presence of 0, 0.5 and 2.0 mg x ml(-1) AGP. Following extraction in 60% methanol the intracellular drug concentration was determined by liquid scintillation counting. RESULTS: Binding to AGP (2.0 mg x ml(-1)) reduced the mean intracellular concentration of SQV from 31.5 microM to 7.4 microM (P < 0.0001; 95% CI 19.4-28.8). RTV concentration was also reduced (8.8 microM to 1.6 microM; P < 0.0001; 95% CI 5.4-9.0) as was the concentration of IDV (3.0 microM to 1.5 microM; P < 0.0001; 95% CI 1.1-1.9). CONCLUSIONS: Reduced intracellular protease inhibitor concentrations in the presence of increasing concentrations of AGP will certainly impact on the antiviral activity in vitro. However, since protease inhibitors are high clearance drugs, free drug concentration will likely remain unaffected in the presence of elevated AGP during chronic oral dosing although there will be an increase in total plasma drug concentration.

Cell Line↗

The environmental contaminant DDE fails to influence the outcome of sexual differentiation in the marine turtle Chelonia mydas.

In many turtles, the temperature experienced during the middle of egg incubation determines the sex of the offspring. The implication of steroid sex hormones as the proximate trigger for sex determination opens the possibility that endocrine-disrupting contaminants may also influence the outcome of sexual differentiation. In this study we investigate the potential effects of DDE (a common DDT metabolite) on sexual differentiation of Chelonia mydas (green sea turtle). Four clutches of eggs collected from Heron Island, Queensland, Australia, were treated with DDE at the beginning of the thermosensitive period for sexual determination. An incubation temperature of 28 degrees C or less produces male hatchlings in this species, whereas 30 degrees C or more produces female hatchlings. Dosed eggs were consequently incubated at two temperatures (27.6 degrees C and 30.4 degrees C) on the upper and lower boundaries of the sex determination threshold for this species. DDE, ranging from 3.3 to 66.5 microg, was dissolved in 5, 10, and 25 microl ethanol and applied to eggshells above the embryo. Less than 2.5 ng/g DDE was present in eggs prior to dosing. Approximately 34% of the applied DDE was absorbed in the eggs, but only approximately 8% of applied DDE was found in embryos. Thus, treated eggs, corrected for background DDE, had up to 543 ng/g DDE. The sex ratio at these doses did not differ from what would be expected on consideration of temperature alone. Incubation time, hatching success, incidence of body deformities, hatching size, and weight were also within the limits of healthy developed hatchlings. This indicates that the eggs of C. mydas in the wild with concentrations of DDE less than 543 ng/g should produce hatchlings with relatively high hatching success, survival rate, and normally differentiated gonads.

Animals↗

Isometric muscle strength in alcoholic and nonalcoholic liver-transplantation candidates.

Intensity of isometric muscle contractions was measured in alcoholic subjects with cirrhosis (N = 42), nonalcoholic subjects with cirrhosis (N = 33), and normal controls (N = 31). Muscle strength and endurance were comparable in the alcoholic and nonalcoholic cirrhotic subjects for all variables. Both cirrhotic groups were inferior to normal controls for all variables. The quantity x frequency (Q x F) index reported for the period during peak alcohol consumption correlated with 6 muscle-force variables, accounting for 9-20% of the variance. Alcoholic and nonalcoholic cirrhotic subjects did not differ in Quality of Life Inventory (QOLI) scales. Significant correlations, however, were found for the alcoholic cirrhotic subjects but not for the nonalcoholic cirrhotic subjects between quality-of-life indices and muscle strength and endurance. Muscle weakness is thus differentially associated with quality of life in alcoholic cirrhotic subjects as compared with nonalcoholic subjects with cirrhosis even though level of strength and endurance in the two groups is comparable.

Adult↗

Firearm injury in Orleans parish: a 24-month perspective.

This study is a retrospective review of all gunshot wounds treated at Charity Hospital, the Orleans Parish designated trauma center, for the 24-month period from November 1993 to November 1995. Its purpose was to define the magnitude of firearm injury in the parish and the impact on the health care system. One-thousand-six-hundred-sixty-nine gunshot wounds were analyzed. Most involved African-American males. Twenty percent were fatal. Two-thousand-forty-three emergent operations were performed. Ten percent of surviving patients had some permanent disability, 6% required institutional care. In 760 patients, initial hospital charges totaled $5,153,516. Extrapolation of these figures to the entire group yields an initial hospital cost of $11,317,392. Transport by the "911" system and in-house trauma team activation were required in most patients. In summary, firearm injury poses a serious economic problem and is a substantial drain on health care providers and their resources.

Adolescent↗

Object chaining and thought disorder in schizophrenic speech.

The phenomenon of object chaining was investigated to determine its relationship to thought disorder in schizophrenia. Samples from thought-disordered schizophrenics (N = 12) and controls (10 non-thought-disordered schizophrenics and 10 normals) were analysed. Using the object subject ratio (OSR) to measure object chaining, we found higher OSRs in the speech of thought-disordered subjects than in that of subjects free of thought disorder. Object chaining correlated with low predictability of speech. We conclude that object chaining is associated with reduced speech comprehensibility and probably contributes to the judgement that thought disorder is present.

Adult↗