Investigation of hormonal male contraception in African men: suppression of spermatogenesis by oral desogestrel with depot testosterone

BACKGROUND: Suppression of spermatogenesis to azoospermia is required for effective hormonal male contraception, but the degree of suppression varies between ethnic groups. We here report the first study of hormonal suppression of spermatogenesis in two African centres using a regimen of oral progestogen with depot testosterone. METHODS A total of 31 healthy men (21 black) were recruited in Cape Town and 21 men in Sagamu, Nigeria. Subjects were randomized to take either 150 or 300 micro g desogestrel daily p.o. with testosterone pellets. In Cape Town, desogestrel was administered for 24 weeks with 400 mg testosterone re-administered 12 weekly. In Sagamu, desogestrel was administered for 52 weeks with 200 mg testosterone (later increased to 400 mg) re-administered 12-weekly. RESULTS: In Cape Town, 22 men completed at least 20 weeks treatment. Azoospermia was achieved in 8/10 and 8/12 men in the 150 micro g and 300 micro g desogestrel groups. Four men in Sagamu withdrew. Azoospermia was achieved in all 17 men in the two groups. There were no significant changes in lipoprotein or haemoglobin concentrations in any group. CONCLUSION: These data demonstrate that the combination of oral desogestrel with depot testosterone is an effective regimen for suppression of spermatogenesis in African as in Caucasian and Chinese men, with azoospermia achieved in a total of 83/98 (85%) men.     

A multi-biomarker approach to study the effects of smoking on oxidative DNA damage and repair and antioxidative defense mechanisms

Carcinogenesis,      

Pharmacosimulation of delays and interruptions during administration of tirofiban: a systematic comparison between EU and US dosage regimens

Journal of Thrombosis and Thrombolysis - Tirofiban is a glycoproteine (GP) IIb/IIIa receptor antagonist, which inhibits platelet-platelet aggregation and is a potential adjunctive antithrombotic...     

Neurobehavioral Profiles in Individuals with Hyperimmunoglobulin E Syndrome (HIES) and Brain White Matter Hyperintensities

Purpose

Individuals with hyperimmunoglobulin E Syndrome (HIES) have central nervous system abnormalities, including focal white matter hyperintensities (WMH), or unidentified bright objects. This cross-sectional study aimed to describe the cognitive and emotional functioning and quality of life of people with HIES. We also sought to explore the relationship between cognitive functioning and WMHs in this population.

Methods

Twenty-nine individuals (13 males) with autosomal-dominant HIES (mean age?=?35.1 years, range 16–55) were administered a comprehensive psychological assessment as part of a natural history protocol. The assessment included measures of global cognitive functioning (Wechsler Adult Intelligence Scale-III), memory (California Verbal Learning Test-II, Wechsler Memory Scale-III), executive skills (Delis Kaplan Executive Function System), and attention (Test of Everyday Attention). Emotional symptoms and quality of life also were assessed.

Results

All mean cognitive scores were within normal limits. Mean scores on memory and executive functioning measures were significantly lower than Full Scale IQ scores (ps?<?.05). Substantial percentages of patients self-reported executive skills to be in the clinical range. Patients with fewer (1–20) versus more (21+) WMHs scored significantly better on measures of global cognitive skills, visual-perceptual skills, and working memory. Mean scores on emotional symptom and quality of life measures were in the average range and unrelated to WMHs.

Conclusions

Global cognitive functioning was average to high average in our sample of individuals with HIES. However, focal brain lesions were associated with lower scores in specific domains. Emotional functioning and quality of life are within normal limits in this sample.     

Durability of the Diagnosis of Irritable Bowel Syndrome Based on Clinical Criteria

Our purpose was to evaluate the durability of the diagnosis of irritable bowel syndrome (IBS) based on clinical criteria. The study population consisted of a cohort of previously published study patients evaluated for IBS between 1989 and 1992, who met the International Congress of Gastroenterology criteria for IBS. Patients were reinterviewed for cardinal features of IBS, Rome I, Rome II, and Manning criteria 10-13 years after the initial diagnosis. During the observational follow-up period, there were 75 patients, 14 males and 61 females, with a mean age of 47.5 +/- 11.3 years (SD; range, 20 to 75 years). Mean time of reinterview after initial diagnosis was 11.8 +/- 0.9 years (range, 10 to 13 years). None of the 75 patients had an abdominal condition which could have been mistaken for IBS. Other abdominal conditions diagnosed during this period included diverticulitis (five), uterine fibromyoma (three), and gallbladder disease (three). Sixty-nine patients (92%) did not consider their symptoms as resolved. Thirty-five (46.7%) had repeat structural evaluation of the colon for similar symptoms without any new diagnoses made. Twenty-six (34.7%) and 32 (42.7%) presently meet the Rome II and Rome I criteria for IBS, respectively. Clinicians are advised to use clinical criteria for a specific and durable diagnosis of IBS.     

Effect of Steady-State Faldaprevir on the Pharmacokinetics of Steady-State Methadone and Buprenorphine-Naloxone in Subjects Receiving Stable Addiction Management Therapy

The effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC_0–24,ss), the steady-state maximum concentration of the drug in plasma (C_max,ss), and the steady-state concentration of the drug in plasma at 24 h (C_24,ss) of 0.92 to 1.18 for (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01637922","term_id":"NCT01637922"}}NCT01637922.)