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.     

Repair of large midline incisional hernias with polypropylene mesh: Comparison of three operative techniques

Polypropylene mesh is widely used for the reconstruction of incisional hernias that cannot be closed primarily. Several techniques have been advocated to implant the mesh. The objective of this study was to evaluate, retrospectively, early and late results of three different techniques, onlay, inlay, and underlay. The records of 53 consecutive patients with a large midline incisional hernia — 25 women and 28 men, mean age 60.4 (range 28–94) — were reviewed. Polypropylene mesh was implanted using the onlay technique in 13 patients, inlay in 23 patients, and underlay in 17 patients. Either the greater omentum or a polyglactin mesh was interponated between the mesh and the viscera. The records of these 53 patients were reviewed with respect to: size and cause of the hernia, pre- and postoperative mortality and morbidity, with special attention to wound complications. Patients were invited to attend the outpatient clinic at least 12 months after implantation of the mesh for physical examination of the abdominal wall. Postoperative complications occurred in 14 (26.4%) patients. The onlay technique had significantly more complications, as compared to both other techniques. Reherniation occurred in 15 (28.3%) patients. The reherniation rate of the inlay technique was significantly higher than after the underlay technique (44% vs 12%, P=0.03) and tended to be higher than the onlay technique (44% vs 23%, P=0.22). Repair of large midline incisional hernias with the use of a polypropylene mesh carries a high risk of complications and has a high reherniation rate. The underlay technique seems to be the better technique.     

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.     

Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation

Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs.     

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.