Danazol administration after gonadotrophin-releasing hormone analogue reduces rebound of uterine myomas [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

We report the results of administration of danazol after suspension of gonadotrophin-releasing hormone analogue (GnRHa) therapy for uterine myomas. A total of 21 women with uterine myomas was treated with 100 mg danazol for 6 months after GnRHa therapy. Uterine volume and endocrine status were monitored monthly by ultrasound and assay of plasma gonadotrophins, oestradiol and progesterone. The results show a rebound of uterine volume about 30% less than in controls at the end of danazol therapy. Menstrual cyclicity returned after 65 +/- 3 days in 16 subjects and five patients remained amenorrhoeic. Hormone assays confirmed renewed ovarian function in the women whose menstrual periods returned. Bone mineral content was substantially reduced during GnRHa treatment but improved significantly during danazol therapy even in the women who remained amenorrhoeic. These results show the utility of danazol in prolonging the therapeutic effects of GnRHa. The mechanism by which danazol inhibits rebound of uterine volume may be due to its antiprogesterone effects on uterine myomas.      

Pharmacological interactions between serotonin and dopamine on behavior in the squirrel monkey

 The behavioral effects of GBR 12909, a selective dopamine uptake inhibitor, were determined in squirrel monkeys trained to respond under a fixed-interval (FI) schedule of stimulus termination and a second-order schedule of IV drug self-administration. Intermediate doses of GBR 12909 increased FI response rate markedly, and the highest dose decreased response rate below control values. The 5HT uptake inhibitors, alaproclate and fluoxetine, and the 5HT agonist, quipazine, attenuated the behavioral-stimulant effects of GBR 12909, whereas the 5HT_2A/2C antagonist, ritanserin, enhanced the behavioral-stimulant effects of the lowest dose. GBR 12909 reliably maintained self-administration, and ritanserin increased response rate maintained by the highest dose. The dopamine agonist, quinpirole, increased FI response rate in only one of three subjects, and ritanserin enhanced the behavioral-stimulant effects of quinpirole in that subject. The dopamine agonist, apomorphine, only decreased FI response rate, and ritanserin did not alter its behavioral effects. The pharmacological profile of GBR 12909 administered alone and in combination with selective 5HT drugs in the present study was similar to that obtained previously with cocaine, further demonstrating that 5HT can reliably modulate the behavioral effects of psychomotor stimulants with prominent dopaminergic actions. Received: 9 July 1996 / Final version: 22 November 1996     

Start Talking About Risks: Development of a Motivational Interviewing-Based Safer Sex Program for People Living with HIV

The epidemiology of HIV infection in the US in general, and in the southeast, in particular, has shifted dramatically over the past two decades, increasingly affecting women and minorities. The site for our intervention was an infectious diseases clinic based at a university hospital serving over 1,300 HIV-infected patients in North Carolina. Our patient population is diverse and reflects the trends seen more broadly in the epidemic in the southeast and in North Carolina. Practicing safer sex is a complex behavior with multiple determinants that vary by individual and social context. A comprehensive intervention that is client-centered and can be tailored to each individual’s circumstances is more likely to be effective at reducing risky behaviors among clients such as ours than are more confrontational or standardized prevention messages. One potential approach to improving safer sex practices among people living with HIV/AIDS (PLWHA) is Motivational Interviewing (MI), a non-judgmental, client-centered but directive counseling style. Below, we describe: (1) the development of the Start Talking About Risks (STAR) MI-based safer sex counseling program for PLWHA at our clinic site; (2) the intervention itself; and (3) lessons learned from implementing the intervention.     

Spermatozoal characteristics from fresh and frozen donor semen and their correlation with fertility outcome after intrauterine insemination.

OBJECTIVE: To determine if conventional sperm parameters, specific characteristics of sperm motion determined by computer-aided semen analysis (CASA), sperm penetration assay (SPA), and/or spontaneous acrosome reaction assay could best predict fertility outcome after intrauterine insemination (IUI) from frozen donor sperm. DESIGN: A retrospective analysis of 2,245 cycles of therapeutic donor IUIs were initially studied; 1,147 cycles that met selection criteria were used in this report. SETTING: A university-based assisted reproductive technology center. PATIENTS, PARTICIPANTS: All IUIs were performed on women with documented patency of at least one fallopian tube, ovulatory cycles, and who did not receive human menopausal gonadotropins. Sperm donors had to be used for at least four different recipients (mean of 15) and at least 14 different cycles of insemination (mean of 41). INTERVENTIONS: None. MAIN OUTCOME MEASURE: Pregnancy. RESULTS: Statistical comparisons were made between donors of different relative fertility by using the Mann-Whitney test, Spearman's rank correlation, and multiple regression analysis. These analyses demonstrated that the most significant predictors of the fertility of frozen-thawed donor sperm were curvilinear velocity, straight line velocity, and the total number of motile sperm inseminated. The number of sperm with spontaneous acrosome reactions negatively correlated with fertility outcome, and SPA provided no predictive value. CONCLUSIONS: Our study supports the hypothesis that the study of sperm motion characteristics using CASA after thawing and washing of cryopreserved sperm is a better predictor of fertile outcome after IUI than analysis of fresh semen.     

Flexible protocol for administration of human follicle-stimulating hormone with gonadotropin-releasing hormone antagonist.

OBJECTIVE: To test, using a primate model, a new approach for achieving individualized pituitary-ovarian responses to controlled ovarian hyperstimulation. DESIGN: Normal ovulatory adult monkeys were selected and randomly assigned to one of the three groups according to onset of spontaneous menses. They had no prior exposure to gonadotropin-releasing hormone (GnRH) antagonist or exogenous gonadotropin therapies. SETTING: The laboratories of The Jones Institute for Reproductive Medicine were used. PATIENTS, PARTICIPANTS: Normal adult macaque females were studied. INTERVENTIONS: Monkeys received hormonal therapies of gonadotropins in combination with GnRH antagonist. MAIN OUTCOME MEASURE(S): Pituitary luteinizing hormone (LH) secretion and ovarian estrogen and progesterone production were monitored. RESULTS: Adding GnRH antagonist to ongoing human follicle-stimulating hormone (hFSH) stimulation can prevent unwanted LH surges, whether begun at early, mid, or late points in the stimulation protocol. CONCLUSIONS: The flexible protocol for administration of hFSH with GnRH antagonist yielded satisfactory results, with apparent advantages of economy, convenience, and individuality of treatment compared with GnRH agonist plus gonadotropin regimens used currently.     

Myocardial injury during standard treatment of an adult with status asthmaticus.

Asthma affects 5%-10% of adults in the United States. Older adults (> 65 years) with asthma have higher rates of fatal asthma than younger adults. The occurrence of a respiratory emergency, such as status asthmaticus, would seem likely to create a situation of cardiopulmonary dysfunction conducive to myocardial ischemia. However, multiple studies of fatal or near-fatal asthma have failed to incriminate myocardial infarction as a contributing factor. We report a patient without underlying coronary artery disease who sustained myocardial injury consistent with myocardial ischemia and infarction during status asthmaticus while receiving recommended treatment without intravenous sympathomimetics or theophylline.