Steady-state pharmacokinetics of bupropion SR in juvenile patients

OBJECTIVE: To examine the steady-state pharmacokinetic properties of bupropion sustained release (SR) and their potential developmental differences in youths. METHOD: Eleven boys and eight girls aged 11 to 17 years old were prescribed bupropion SR monotherapy for attention-deficit/hyperactivity disorder (n = 16) and/or depressive disorders (n = 16). Bupropion SR was given in morning doses of 100 mg/day (n = 11) or 200 mg/day (n = 8) for 14 days or less, with five subjects studied on both doses. All subjects had blood draws from an intravenous port every 1 to 3 hours for 24 hours after their usual morning doses. Pharmacokinetic variables were determined by noncompartmental and compartmental analyses for bupropion and metabolites, respectively. RESULTS: Bupropion and its metabolites exhibited linear pharmacokinetics. Areas under the concentration curves for the hydroxybupropion, threohydrobupropion, and erythrohydrobupropion were 20, 12, and 2.7 times higher, respectively, than for bupropion. Relative to adults, the mean half-lives of bupropion (12.1 hours) and threohydrobupropion (26.3 hours) were significantly shorter, and areas under the concentration curve ratios of metabolites to bupropion were 19% to 80% higher. CONCLUSIONS: Youths metabolize bupropion SR faster to hydroxybupropion and other active metabolites than adults. Until the clinical importance of bupropion's metabolites is clarified, bupropion SR should be given in divided doses to youths, as the manufacturer recommends for adults taking higher doses.     

Learning places from views: variation in scene processing as a function of experience and navigational ability

Humans and animals use information obtained from different viewpoints to form representations of the spatial structure of the world. We used functional magnetic resonance imaging (fMRI) adaptation to investigate the neural basis of this learning process and to show how the concomitant representations vary across individuals as a function of navigational ability. In particular, we examined the effect of repeating viewpoint and/ or place information over both short (within-trial) and long (across-scan) intervals on the neural response in scene processing regions. Short-term fMRI adaptation effects in the parahippocampal cortex were initially highly viewpoint-specific but became less so over time. Long-term fMRI repetition effects included a significant viewpoint-invariant component. When individual differences in navigational ability were considered, a significant correlation between the strength of these effects and self-reported navigational competence was observed. In particular, good navigators encoded representations that differed between new and old views and new and old places, whereas bad navigators did not. These results suggest that cortical scene representations evolve over time to become more viewpoint-invariant and that the quality of these representations directly impacts navigational ability.     

Endometrial plasma cells: do they indicate subclinical pelvic inflammatory disease?

BACKGROUND: Subclinical pelvic inflammatory disease (PID) is a common condition among women with lower genital tract infection and is believed to be responsible for a greater proportion of PID-related sequelae than acute PID. Subclinical PID is diagnosed histologically after endometrial biopsy. In the literature, many different histologic criteria have been used to define subclinical PID. GOAL: To determine if endometrial plasma cells are commonly found in women at low likelihood of PID. STUDY: A cross-sectional study of 33 women undergoing tubal ligation and at low likelihood of PID was performed. At the time of tubal ligation, study participants underwent visualization of pelvic organs and an endometrial biopsy, which was analyzed for the presence of neutrophils and plasma cells. Demographic, clinical, and microbiologic data were compared among women with and without endometrial plasma cells. RESULTS: Endometrial plasma cells were identified in one third (33%) of the asymptomatic, fertile, healthy women in our cohort. The presence of plasma cells was not associated with lower genital tract infection, including bacterial vaginosis. Laparoscopic evidence of fallopian tube damage was similar in patients with and without endometrial plasma cells (22% in each group). CONCLUSION: Plasma cells are commonly found in the endometria of healthy women and may not represent upper genital tract inflammation.     

A pilot study of the effects of behavioral weight loss treatment on fibromyalgia symptoms

OBJECTIVE: Previous studies have found a relation between weight loss and pain severity in various chronic pain populations. However, there has been little research examining the relation between body mass index (BMI) and fibromyalgia syndrome (FMS). The purpose of this pilot study was to investigate the relationship between BMI and FMS symptoms and to determine if FMS symptoms would decrease following weight loss. METHODS: Overweight and obese women participated in a 20-week behavioral weight loss treatment. RESULTS: Participants, on average, lost 9.2 lbs (4.4% of their initial weight), and there were significant pre-postimprovements on several outcome measures. Although weight was not significantly related to pain at baseline, weight loss significantly predicted a reduction in FMS, pain interference, body satisfaction, and quality of life (QOL). CONCLUSION: Findings suggest that behavioral weight loss treatment could be included in the treatment for overweight/obese women with FMS.     

Ondansetron treatment in Tourette's disorder: a 3-week, randomized, double-blind, placebo-controlled study

OBJECTIVE: The aim of the present study was to evaluate the efficacy of ondansetron, a selective 5-HT(3) antagonist, in the treatment of Tourette's disorder. METHOD: Participants (N = 30) aged 12 to 46 years, diagnosed with DSM-IV Tourette's disorder and resistant to previous haloperidol treatment, were enrolled in a 3-week, randomized, double-blind, placebo-controlled outpatient study. Assessments were conducted at baseline and once a week during the study period. Scales used included the Tourette's Syndrome Global Scale (TSGS), the Yale Global Tic Severity Scale (YGTSS), and the Yale-Brown Obsessive Compulsive Scale. Ondansetron dose was 8, 16, and 24 mg/day in the first, second, and third weeks, respectively. RESULTS: A significant positive effect of ondansetron on tic severity, as assessed by the TSGS, was noted (baseline vs. endpoint: mean +/-SD = 29.62 +/-20.33 vs. 20.58 +/-12.82, p = .002 vs. placebo). However, no significant effect was detected upon assessing ondansetron/ placebo effect on tic severity with the YGTSS (baseline vs. endpoint: mean +/-SD = 24.04 +/-9.44 vs. 17.50 +/-9.48, p = .15 vs. placebo). No change in obsessive-compulsive symptoms was noted in either group. Adverse effects included mild and transient abdominal pain. CONCLUSIONS: Ondansetron may have antitic effects in patients with Tourette's disorder. Large-scale, double-blind studies should further assess the antitic efficacy of ondansetron.     

Gender-specific 5-HT1A receptor changes in BrdU nuclear labeling patterns in neonatal dentate gyrus

The actions of 5-HT1A receptors on cell proliferation in the rat neonatal dentate gyrus are unknown. We injected a 5-HT1A receptor agonist (ipsapirone) or antagonist (Way 100635) 1 h before injections of BrdU in neonates of both genders between days 2-4, a peak time of dentate gyrus granule cell proliferation. The BrdU immunoreactive (IR) nuclei in the granule cell layer and subgranular zone were examined after 2 weeks. The BrdU-IR nuclear staining patterns were classified as being either diffuse (homogenous dark BrdU-staining throughout the nucleus) or punctate (multiple distinct small stained spots within the nucleus). Most BrdU-labeled nuclei with a diffuse pattern were seen in the subgranular zone while the punctate pattern nuclei were seen within the granular cell layer of the dentate gyrus. 5-HT1A antagonist showed no overall change in absolute number or pattern of labeled nuclei compared to control animals. After a 5-HT1A agonist, there was also no differences in the total number of BrdU-IR nuclei (punctate and diffuse pattern). However, in both genders, the proportion of the BrdU-labeled nuclei showing a punctate compared to diffuse pattern increased: 33% in females and 18% in males. In females, the 5-HT1A receptor agonist increased the number of nuclei showing a punctate pattern by 41%, while in males the 5-HT1A receptor agonist decreased the number of nuclei showing a diffuse pattern by 29%. These results indicate gender-specific 5-HT1A receptor action on the state of nuclear DNA in the cells of the dentate gyrus, without increasing the total number of BrdU-labeled nuclei.     

Do older adults use the Internet for information on heart attacks? Results from a survey of seniors in King County, Washington

BACKGROUND: Early treatment can reduce mortality from heart attacks. However, patient delay, especially among the elderly, has slowed progress in this area. One of the reasons for delay may be because of a lack of knowledge about symptoms of acute myocardial infarction (AMI) and treatment benefits. The Internet is a new and promising source of heart health information, but we know little about how elderly people use this medium. METHODS: This study investigates the demographic and psychosocial variables that are related to Internet access, health information seeking, and information seeking about heart attacks from the Internet among seniors. We interviewed seniors (N = 323) aged more than 65 years and asked them questions about Internet access, health information seeking, and information seeking on heart attacks, as well as demographic information, risk perceptions for AMI, and personal experience with AMI. RESULTS: The results showed that several demographic variables were related to access to the Internet. Only 7% of the seniors who reported access to the Internet had sought information on heart attacks from the Internet. Age, history of AMI, and family history of AMI were significant predictors of information seeking on heart attacks. This suggests that to date only a very small, high-risk group of seniors actually seeks information on heart attack emergencies from the Internet.     

Generic antiretroviral efficacy in AIDS-associated Kaposi's sarcoma in sub-Saharan Africa

Generic antiretroviral drugs are pivotal in the implementation of WHO's '3 by 5' programme. However, clinical experience with generics in sub-Saharan Africa is insufficiently documented. We report on 50 patients with HIV-associated Kaposi's sarcoma treated with generic fixed-dose highly active antiretroviral therapy. At 52 weeks, 74% achieved an undetectable viral load of < 50 copies/ml, 86% achieved < 400 copies/ml, and a 3.1 log10 decline from baseline. Side-effects were minimal. The outcomes support the use of generic antiretroviral therapy.