Effect of ritonavir/saquinavir on stereoselective pharmacokinetics of methadone: results of AIDS Clinical Trials Group (ACTG) 401

The effect of ritonavir 400 mg/saquinavir 400 mg twice daily on the stereoselective pharmacokinetics of methadone was examined in 12 HIV-infected, methadone-using study subjects. DESIGN: A 24-hour methadone pharmacokinetic study was performed before antiretroviral therapy was begun and after 15 days of therapy. Methadone concentration was measured by a chiral plasma assay because the drug is administered as a racemic mixture of R- and S-methadone, but only the R-isomer is active. Both changes in plasma protein binding and changes in objective and subjective opioid effect were monitored. RESULTS: Ritonavir/saquinavir administration was associated with 40% decrease in total S-methadone AUC0-24hr and 32% decrease in R-methadone area under the curve (AUC)0-24hr, and both changes were statistically significant (p =.001 for both). When AUC was corrected for the changes in protein binding induced by ritonavir/saquinavir, R-methadone free AUC0-24hr decreased 19.6% whereas the S-methadone decreased 24.6%, neither of these changes was statistically significant (p =.129 and p =.0537, respectively). This change in methadone exposure was not associated with any evidence of withdrawal from narcotics and no modification of methadone dose was required. CONCLUSIONS: Our data indicate that ritonavir/saquinavir administration is associated with induction of metabolism of methadone but this is greater for the inactive S-methadone. However, approximately 37% of the decrease in the total R-methadone exposure can be explained by protein binding displacement. Ritonavir/saquinavir can be used in HIV-infected people taking methadone without routine dose adjustments.     

Repetitive conundrums of centromere structure and function

In the last few years, a paradox has emerged regarding the relationship of centromere structure and its function. Most centromeric DNAs analyzed to date are composed of a remarkably complex array of repeat structures. In contrast, recent analyses of neocentromeric DNA reveal that repetitive DNA is not a prerequisite for centromere activity. The ubiquity of repetitive sequences among diverse species at sites of primary constriction argues that there is a strong evolutionary link between centromere structure and function. Dynamic mutational processes resulting in amplification, deletion and transposition of repetitive sequences appear to occur frequently in such regions, resulting in considerable interspecific diversity in structure and sequence. One possible solution to this conundrum may be that the rapid accumulation of repetitive sequences within centromeric and pericentromeric DNA is a consequence of functionally active centromeres. Emerging repetitive structures at centromeric sites may be an important byproduct of a functional centromere which ensures that site as an evolutionarily favored position in subsequent meiotic and mitotic lineages. The recent identification of large gene duplications in the vicinity of centromeres may be another example of the enhanced mutational lability of such regions of the genome.      

Socio—cultural factors influencing insecticide treated bed net utilization in a malaria endemic city in north—central Nigeria

ObjectiveTo ascertain the socio-cultural factors influencing the rate of utilization of insecticide treated bed nets (ITNs) in a malaria endemic city of Makurdi, north central Nigeria.MethodsThe study was cross-sectional in nature using systematic sampling method to identify households. Both quantitative and qualitative data was generated from adult women using structured and semi structured questionnaires, and focused group discussions (FGDs) to obtain information on rate and patterns of utilization of ITNs. Information such as age, educational level, marital status, awareness or otherwise of the existence of malaria, and factors influencing rate of ownership and utilization of ITNs were obtained. FGDs were used to obtain qualitative information on rate of utilization of ITNs not captured in the questionnaires. Data obtained was analysed using Epi Info 6 statistical software.ResultsAmong the respondents interviewed, 97.0% (2 013/2 075) were aware of existence of malaria and 87.0% of these (1 751/2 013) would associate it with mosquitoes. The rate of ownership of any bed net, ITNs and untreated bed nets (UTNs) was 25.1%, 17.0% and 8.3%, respectively. Utilization of ITNs among children was 30.0% (112/373) and UTNs 12.9% (48/373). Positive contributors to ITNs utilization were literacy, enhanced economy, experience of marriage, and being gainfully employed (P<0.05); while negative contributors were ignorance, poverty and some cultural beliefs and values.ConclusionsA more synchronized advocacy should be carried out on the potential benefits of ITNs utilization and sustained. Also ITNs should be made available to the people of the community at minimal or no cost.     

A study of anemia in women with asymptomatic malaria parasitaemia at their first antenatal care visit at the General Hospital,Ikot Ekpene,Akwa Ibom State,Nigeria

ObjectiveTo assess the prevalence of anemia and asymptomatia malaria parasitemia and the effect of prior antimalarials therapy on the parasite density in pregnant women at their first antenatal visit at the secondary level health care facility in Nigeria.MethodsThis cross sectional observational study was carried out in the antenatal clinic of General Hospital, Ikot Ekpene, Akwa Ibom State, Nigeria for 3 months period (1^st June to 31^st August, 2009). Five hundred and fourteen women attending their first antenatal registration visits in the hospital were recruited in the study. Socio-demographic information was obtained using pre-tested questionnaires. The malaria parasite was obtained by examining thick and thin blood films prepared on 2 glass slides while the hematocrit was obtained through 2 capillary tubes read by a Hawksleys microhematocrit reader.ResultsA total of 514 pregnant women participated in the study with a mean maternal age of 21.4 years and a mean gestational age at booking of 18.3 weeks. The primigravid women booked at significantly lower gestational age than multigravidae (16.2 weeks vs 21.6 weeks). Most of the women (59.3%) were anemic, out of which 60.4% were primigravida. More than half of the women had moderate to high parasite density and only 6.8% had no malaria parasitemia. All patients with severe anemia were parasitemic. Out of the 479 (93.2%) women with parasitemia, a third had taken antimalarial drugs. A majority (60.3%) of those without prior antimalarial drugs had moderate to high density parasitemia.ConclusionsThis study shows high prevalence of anemia in women with asymptomatic malarial parasitemia, particularly the primigravida. The severity of anemia is directly related to the density of malaria parasitemia. Those with effective antimalarial therapy appear to have low density parasitemia and therefore mild anemia. Routine screening for anemia and malaria parasites at booking, prompt parasite clearance and correction of anemia would reduce the associated maternal and perinatal complications.     

Objective and subjective evaluation of adaptive speech enhancement methods for functional MRI

Purpose:

To recover speech corrupted by functional magnetic resonance imaging (fMRI) acoustic noise using two‐channel adaptive speech enhancement techniques.

Materials and Methods:

Speech corrupted by noise generated from a 3 T MRI scanner was recorded using diffuse‐field microphones and a data acquisition board. Multiband and subband adaptive speech enhancement methods are used to recover the speech signal from the recordings. Normalized least mean squares (NLMS) algorithm was used for updating the filter coefficients in each band.

Results:

The methods are successful in enhancing the speech quality. They are successful in improving the convergence rate of the adaptive filter. Multiband and subband methods have a similar performance in terms of noise reduction and in the subjective tests. The subband method introduces less speech distortion compared to the multiband method. The subband method requires a lower number of computations per sample.

Conclusion:

Adaptive speech enhancement techniques are effective in reducing fMRI background noise in the recordings. Based on the analysis, we conclude that subband‐based methods are more suited for enhancing speech corrupted by fMRI noise. J. Magn. Reson. Imaging 2010;31:46–55. © 2009 Wiley‐Liss, Inc.     

9The TANTALUSTM System for obesity: effect on gastric emptying of solids

Background: Gastric electrical stimulation (GES) is currently investigated for the treatment of obesity. The TANTALUS System delivers gastric contractility modulation (GCM) signals in synchrony with gastric slow waves, resulting in significant augmentation of gastric contractions during food intake. We hypothesized that such modulation of contractile activity may affect gastric emptying and plasma ghrelin levels. Aim: To test the effect of GCM of the gastric antrum on gastric emptying of solids and ghrelin levels. Methods: 12 obese subjects were implanted with 2 pairs of antral electrodes and an implantable pulse generator (IPG, TANTALUS ^TM) Gastric emptying test (GE) for solids was performed twice, on separate days, in each subject, starting few weeks after implantation: 1) control, before the start of stimulation, and 2) with stimulation, after device was turned on. Blood samples for ghrelin, were taken at baseline, and at 15, 30, 60 and 120 min after the test meal. Results as mean + SD, analysis by t‐test and p < 0.05. Results: 11 females, 1 male, age: 39.1 ± 8.9 years, BMI: 41.6 ± 3.4, 3 subjects with type 2 diabetes. One diabetic patient did not complete GE test because of technical issues. GCM significantly accelerated gastric emptying: retention at 2 hours 18.7 ± 12.2% vs. 31.9 ± 16.4%, stimulation vs. control respectively, p = 0.008. T ^1/2 78.3 ± 23.5 vs. 95 ± 31.7 min, stimulation vs. control respectively, p = 0.04. Mean results for gastric emptying were within normal at both baseline and stimulation. Meal ingestion induced only minimal, insignificant reduction in ghrelin levels. There was no significant difference in AUC of ghrelin between control and stimulation. Conclusions: After GCM stimulation, there is significant acceleration of gastric emptying of solids in obese patients, without affect on ghrelin levels. The obese subjects did not exhibit the significant, meal‐induced reduction in ghrelin.      

Reliability and validity of the Sexual Pressure Scale for Women-Revised

Sexual pressure among young urban women represents adherence to gender stereotypical expectations to engage in sex. Revision of the original five-factor Sexual Pressure Scale was undertaken in two studies to improve reliabilities in two of the five factors. In Study 1 the reliability of the Sexual Pressure Scale for Women-Revised (SPSW-R) was tested, and principal components analysis was performed in a sample of 325 young, urban women. A parsimonious 18-item, four-factor model explained 61% of the variance. In Study 2 the theory underlying sexual pressure was supported by confirmatory factor analysis using structural equation modeling in a sample of 181 women. Reliabilities of the SPSW-R total and subscales were very satisfactory, suggesting it may be used in intervention research.