Nevirapine plasma concentrations and concomitant use of rifampin in patients coinfected with HIV-1 and tuberculosis

OBJECTIVES: In countries with high numbers of HIV/tuberculosis coinfection nevirapine and rifampin are used extensively. However, limited data are available about whether or not nevirapine and rifampin can be safely coadministered without the plasma concentration of nevirapine falling below therapeutic levels. METHODS: Blood samples for determination of nevirapine plasma concentrations were collected from patients using nevirapine 200 mg twice daily with or without concomitant rifampin. Bivariate and multivariate linear regression models were used to investigate factors possibly related to nevirapine concentrations. RESULTS: We received 74 blood samples from patients using nevirapine plus rifampin, and collected blood samples from an equal number of controls using nevirapine only. Groups were similar for age, gender, weight, height and body mass index (BMI). In the rifampin group the mean nevirapine concentration was 5.47 +/- 2.66 mg/l, whereas in the control group the mean nevirapine concentration was 8.72 +/- 3.98 mg/l. In the rifampin group seven nevirapine trough concentrations were low (< 3.1 mg/l), while in the control group two patients had low nevirapine trough concentrations (P = 0.164). In the multivariate linear regression analysis, corrected for time after drug intake, the use of rifampin was significantly (P < 0.001) associated with lower nevirapine plasma concentrations, whereas higher BMI reached borderline significance (P = 0.065). CONCLUSION: Although nevirapine plasma concentrations were 3.3 mg/l lower when co-administered with rifampin, still more than 86% of these patients had nevirapine plasma concentrations > 3.1 mg/l. Our results suggest that from a pharmacological point of view the majority of Thai coinfected patients, who have low BMIs, reach nevirapine plasma concentrations that are adequate for treatment of HIV. However this can only be undertaken if nevirapine plasma concentration monitoring is available and can be closely followed.     

Vasoprotective endothelial effects of a standardized grape product in humans

The pathogenesis of coronary lesion development is a multi-factorial process involving a number of different cell types and covariates, and injury and dysfunction of the vascular endothelium is an important marker and likely participant in the initiation and/or progression of most forms of heart disease. In addition to chronic dysfunction of endothelial responses in patients with established heart disease, there is evidence that 'acute insults' can cause measurable dysfunction in vascular response in humans (drug toxicities, hypoxia, high fat meal). Such repeated acute insults may contribute to disease risk in otherwise healthy individuals or promote disease progression in established patients. Consumption of grape products, especially wine, has been linked to lower cardiovascular risk but the vascular endothelial effects of grape products in healthy normal subjects, in the absence of ethanol, have not been evaluated. We therefore tested the hypotheses that 1) a standardized product derived from fresh grapes (GP, acute and chronic consumption) improves endothelial performance in healthy normal young subjects, and 2) that concomitant grape consumption affects the 'acute endothelial insult' caused by a single standardized high fat meal (HF). Acute consumption of GP equivalent to 1.25 cups of fresh grapes caused significant improvement in brachial artery flow mediated dilation (FMD) within 3 h of consumption, when compared to control consumption of sugar solution (p<0.05). No acute changes in heart rate, hemodynamics, or lipid profiles were observed. When this 'dose' was then consumed twice daily for 3 weeks FMD was further improved and total antioxidant capacity in plasma was slightly increased (p<0.05), with no change in heart rate, hemodynamics, or lipid profiles. A single HF meal (900 cal, 49 g total fat) caused a 50% reduction in FMD response when consumed alone, and this effect coincided with increased blood triglyceride levels within 3 h post-consumption. In contrast the concomitant consumption of GP with the HF meal completely prevented this HF-induced vascular endothelial dysfunction (p<0.05), but had no effect on rising triglycerides. These data demonstrate that a modest intake of fresh grapes can have acute favorable effects on vascular endothelial function in normal healthy subjects, that chronic intake can further improve performance and concomitant intake can blunt the 'acute insult' to endothelium caused by a typical western HF meal. This effect is likely to be related to antioxidant effects at the endothelium, rather than changes in blood lipids. These data support epidemiological data of the health benefits of grapes, and demonstrate that 'favorable' food consumption can apparently reduce some toxicities induced by 'unfavorable' food consumption.     

Cytogenetic and molecular characterization of a hepatosplenic T-cell lymphoma: report of a novel chromosomal aberration

Hepatosplenic T-cell lymphomas (HSTCL) are rare cancers and comprise 5% of peripheral T-cell lymphomas. These well-characterized extranodal lymphomas have a disguised onset, secondary to intrasinusoidal infiltration of the spleen, liver, and bone marrow, with a rapidly progressive course that is poorly responsive to chemotherapy and often ensues in the setting of immune system suppression. We describe the clinical, immunophenotypic, cytogenetic, fluorescence in situ hybridization, and molecular analyses for T cell receptor gene rearrangement in a 21-year-old man diagnosed with HSTCL. Immunophenotypic analysis revealed negativity for CD5 as well as double negativity for CD4/CD8 mature T-cell immunophenotype, which suggested the diagnosis of hepatosplenic T-cell lymphoma. Molecular analysis confirmed a TCR gene rearrangement, thereby verifying the common T-cell origin of the present HSTCL case. Furthermore, cytogenetic analysis revealed a novel chromosomal rearrangement, t(7;15)(p22;q21). Metaphase fluorescence in situ hybridization analysis confirmed the translocation of a chromosomal segment from 15q21 to 7p22.     

Respiratory motion of the heart and positional reproducibility under active breathing control

PURPOSE: To reduce cardiotoxicity from breast radiotherapy (RT), innovative techniques are under investigation. Information about cardiac motion with respiration and positional reproducibility under active breathing control (ABC) is necessary to evaluate these techniques. METHODS AND MATERIALS: Patients requiring loco-regional RT for breast cancer were scanned by computed tomography using an ABC device at various breath-hold states, before and during treatment. Ten patients were studied. For each patient, 12 datasets were analyzed. Mutual information-based regional rigid alignment was used to determine the magnitude and reproducibility of cardiac motion as a function of breathing state. For each scan session, motion was quantified by evaluating the displacement of a point along the left anterior descending artery (LAD) with respect to its position at end expiration. Long-term positional reproducibility was also assessed. RESULTS: Displacement of the LAD was greatest in the inferior direction, moderate in the anterior direction, and lowest in the left-right direction. At shallow breathing states, the average displacement of LAD position was up to 6 mm in the inferior direction. The maximum displacement in any patient was 2.8 cm in the inferior direction, between expiration and deep-inspiration breath hold. At end expiration, the long-term reproducibility (SD) of the LAD position was 3 mm in the A-P, 6 mm in the S-I, and 4 mm in the L-R directions. At deep-inspiration breath hold, long-term reproducibility was 3 mm in the A-P, 7 mm in the S-I, and 3 mm in the L-R directions. CONCLUSIONS: These data demonstrate the extent of LAD displacement that occurs with shallow breathing and with deep-inspiration breath hold. This information may guide optimization studies considering the effects of respiratory motion and reproducibility of cardiac position on cardiac dose, both with and without ABC.