Bupropion for weight loss: an investigation of efficacy and tolerability in overweight and obese women

OBJECTIVE: On the basis of the clinical observations that bupropion facilitated weight loss, we investigated the efficacy and tolerability of this drug in overweight and obese adult women. RESEARCH METHODS AND PROCEDURES: A total of 50 overweight and obese (body mass index: 28.0 to 52.6 kg/m(2)) women were included. The core component of the study was a randomized, double-blind, placebo-controlled comparison for 8 weeks. Bupropion or placebo was started at 100 mg/d with gradual dose increase to a maximum of 200 mg twice daily. All subjects were prescribed a 1600 kcal/d balanced diet and compliance was monitored with food diaries. Responders continued the same treatment in a double-blind manner for an additional 16 weeks to a total of 24 weeks. There was additional single-blind follow-up treatment for a total of 2 years. RESULTS: Subjects receiving bupropion achieved greater mean weight loss (last-observation-carried-forward analysis) over the first 8 weeks of the study (p = 0.0001): 4.9% +/- 3.4% (n = 25) for bupropion treatment compared with 1.3% +/- 2.4% (n = 25) for placebo treatment. For those who completed the 8 weeks, the comparison was 6.2% +/- 3.1% (n = 18) vs. 1.6% +/- 2.9% (n = 13), respectively(p = 0.0002), with 12 of 18 of the bupropion subjects (67%) losing over 5% of baseline body weight compared with 2 of 13 in the placebo group (15%; p = 0.0094). In the continuation phase, 14 bupropion responders who completed 24 weeks achieved weight loss of 12.9% +/- 5.6% with fat accounting for 73.5% +/- 3.7% of the weight lost and no change in bone mineral density as assessed by DXA. Bupropion was generally well-tolerated in this sample. DISCUSSION: Bupropion was more effective than placebo in achieving weight loss at 8 weeks in overweight and obese adult women in this preliminary study. Initial responders to bupropion benefited further in the continuation phase.     

Preimplantation genetic diagnosis using combined strategies on a breast cancer patient with a novel genomic deletion in BRCA2

Purpose

To perform Preimplantation Genetic Diagnosis (PGD) on a paternal Brca2 unknown mutation carrier with early-onset breast cancer, whose paternal grandmother and mother had breast cancer at 60s.

Method

Elucidating the linkage via single sperm haplotyping on patient''s carrier brother, and identifying the genomic deletion via BLAST followed by PCR screening. PGD was subsequently conducted.

Result

The mutant allele was found by using 4 microsatellite and 2 intragenic SNP markers. Recombination was detected in 8 % of sperms. BLAST was utilized to locate putative hairpin structure(s), followed by PCR screening with seven sets of primers. A novel 2,596 bp deletion containing exon 15 ~ 16 was identified. Due to the severity of phenotype and the integrity of exon 11 encoding RAD51 binding domain, and the fact that the patient''s mother also had breast cancer at her 60s, we speculate a possible coexistence of maternal breast cancer risk allele(s). Embryo biopsy was performed on day 3. Unaffected morula and blastocyst were replaced on day 5, resulting in a singleton livebirth. A breast lump appeared in the patient after delivery without the presence of malignant cells.

Conclusion

Concerning the assisted reproductive option for breast cancer patients, the possibility of coexistence of multiple familial risk alleles and the significance of each mutation to the phenotype should be evaluated. To eliminate misdiagnosis resulting from recombination and/or allelic drop-out, both direct mutation detection and linkage analysis approaches may be necessary. BLAST is a very useful and cost-effective tool for identifying large genomic deletion.     

Effect of fenoprofen on thyroid function tests

We observed that a few patients taking the anti-inflammatory drug fenoprofen showed increases in total and free T3 serum levels without convincing evidence of an associated thyrotoxicosis. To confirm these findings, two volunteers were given fenoprofen for two weeks. Within this time total T3 levels almost doubled and free T3 levels increased threefold. Administration of fenoprofen did not have any measurable effect on T4 or TSH estimations. Cross-reactivities of fenoprofen and 4'-hydroxyfenoprofen were studied with antisera from various total and free T3 assays. Results show that the metabolite cross-reacts with the antisera from Amerlex total and free T3 assay kits. A lesser degree of interference was observed with the Corning total and free T3 assays. 4'-hydroxyfenoprofen had no effect on an 'in house' total T3 assay. Laboratories should therefore be aware of the possibility that their assay may be subject to interference by fenoprofen or its metabolites while clinicians should be aware of this interference in order that they may avoid unnecessary and harmful treatment.     

Occupational exposure to non-ionizing radiation and an association with heart disease: an exploratory study

Exploratory analyses for dose-related exposure to non-ionizing radiation and adverse health effects among male physical therapists were done from a mail questionnaire survey. The cohort consisted of 3004 respondents who were stratified into subgroups according to exposure across and within the various types of non-ionizing radiation energy emitted from diathermy equipment. The radiation modalities considered were ultrasound, microwave, shortwave, and infrared. An association between heart disease and exposure to shortwave radiation was the only consistently significant finding when high and low exposure groups were compared.     

Assessing cumulative acute toxicity of chemoradiotherapy in head and neck cancer with or without induction chemotherapy

Background

To compare cumulative acute toxicity in head and neck cancer patients treated with concurrent chemoradiotherapy alone (CCRT) versus induction chemotherapy (IC) followed by CCRT (I/CCRT).

Tau Phosphorylation is Impacted by Rare <Emphasis Type="Italic">AKAP9</Emphasis> Mutations Associated with Alzheimer Disease in African Americans

We studied the effect of two rare mutations (rs144662445 and rs149979685) in the A-kinase anchoring protein 9 (AKAP9) gene, previously associated with Alzheimer disease (AD) in African Americans (AA), on post-translational modifications of AD-related pathogenic molecules, amyloid precursor protein (APP) and microtubule-associated protein Tau using lymphoblastoid cell lines (LCLs) from 11 AA subjects with at least one AKAP9 mutation and 17 AA subjects lacking these mutations. LCLs were transduced by viral vectors expressing causative AD mutations in APP or human full-length wild type Tau. Cell lysates were analyzed for total APP, Aβ₄₀, and total and T181 phospho-Tau (pTau). AKAP9 mutations had no effect on Aβ₄₀/APP, but significantly increased pTau/Tau ratio in LCLs treated with phosphodiesterase-4 inhibitor rolipram, which activates protein kinase A. Proteomic analysis of Tau interactome revealed enrichment of RNA binding proteins and decrease of proteasomal molecules in rolipram-treated cells with AKAP9 mutations. This study shows the impact of rare functional AKAP9 mutations on Tau, a central mechanism of AD pathogenesis, in LCLs derived from AD and control subjects.     

Athletes’ and Coaches’ Perceptions of Nutritional Advice: Eating More Food for Health and Performance

Background: Low energy availability results in physiological adaptations which contribute to unfavourable health outcomes. Little information exists on perceptions of nutritional advice to eat more food to maintain health and enhance performance. The aim of this study was to explore athletes’ and coaches’ perceptions towards advice to athletes to eat larger than their current quantities of food and to explore how nutritionists could deliver this advice. Methods: Semi-structured interviews (~20 min in length) were conducted using online communication technology, audio-recorded, and transcribed verbatim. The interview explored perceptions of the nutritional advice provided, its role in health and performance, and the challenges to eating larger amounts of food. Data were analysed using NVIVO 1.2 using an inductive thematic approach. Results: Nine elite athletes (female = 6; males = 3) and nine high-performance coaches (female = 3; male = 6) completed the semi-structured interviews. Athletes reported improved training consistency, fewer injuries and illnesses, and improved resilience when consuming adequate energy and nutrients to meet their needs. Lack of time and meal preparation difficulties were the main challenges faced to fuelling. Conclusions: Although education about under-fuelling is important, motivating, enabling, and supporting athletes to change behaviour is pivotal to increasing athlete self-awareness and to make long-term nutritional changes.