Zaleplon and triazolam in humans: acute behavioral effects and abuse potential

Zaleplon, a pyrazolopyrimidine that is under development as a hypnotic, produces its pharmacological effects at the benzodiazepine-recognition site on the GABA_A benzodiazepine-receptor complex. Unlike most benzodiazepines, zaleplon binds selectively to the BZ₁ (ω₁) subtype of the benzodiazepine receptor. The present study compared the acute subject-rated effects, performance-impairing effects, and abuse potential of zaleplon and triazolam, a triazolobenzodiazepine hypnotic, in 14 healthy volunteers with histories of drug abuse. Zaleplon (25, 50, and 75 mg), triazolam (0.25, 0.5, and 0.75 mg) and placebo were administered orally in this double-blind, crossover study. Zaleplon and triazolam produced comparable dose-related effects on several subject-rated drug-effect questionnaires. Zaleplon and triazolam also produced comparable dose-dependent decrements on several performance tasks including balance, circular lights, digit-enter and recall, DSST, picture recall/recognition and repeated acquisition. Same-day and next-day subject-rated measures reflecting abuse potential (e.g., drug liking, good effects, and monetary street value) also suggest that zaleplon and triazolam were comparable. The only notable between-drug difference observed in the present study was that the time-action function of zaleplon differed from that of triazolam. The onset time, time to maximum drug effect, and duration of action were shorter with zaleplon than triazolam. Thus, despite its non-benzodiazepine structure and unique benzodiazepine-receptor binding profile, the behavioral pharmacological profile of zaleplon is similar to that of triazolam. Received: 14 April 1998/Final version: 13 January 1999     

Communication practices in the social construction of health in an AIDS kesidence

Physical illness and well-being, while grounded in bodily and psychological experiences, are also constructed socially through communication practices. Significant symbols, rituals and myths, among other forms, converge to create shared meanings that help define the health/illness experience. This article first provides a conceptual framework for understanding how communication intertwines physical, psychological and collective worlds. This perspective is then contextualized by illustrating some communication practices within a residential facility for people with AIDS that help residents cope with the 'depression bind' created by the need to 'grieve efficiently' over the loss of fellow residents. In- depth interviews with residents uncover metaphors that describe this bind, the military and journey myths embedded in the language of 'fighting AIDS' and 'passing', and the remembering and 're membering' rituals of bereavement. These communication practices help residents grasp elusive meanings, discharge deep and contradictory feelings and manage the tensions of everyday life.     

Allergen tachyphylaxis of guinea pigs in vivo: A prostaglandin E mediated phenomenon?

Ovalbumin (OA) sensitized guinea pigs were repeatedly challenged with 1% OA in saline nebulized ultrasonically at the 0, 10, 20, 60 and 70th min. The intensity of bronchial obstruction was measured by body plethysmography. The first three challenges (0, 10, 20 min) caused strong asthmatic reactions in all animals, the last two (60, 70 min) only mild ones in 10 out of 15 animals. The development of this tachyphylaxis was markedly reduced by pretreatment of the animals with cyclooxygenase inhibitors (indomethacin 10 mg/kg intraperitoneally resp. acetylsalicylic acid 10 mg/kg orally 2h before test). The effect of both inhibitors (i.e. inhibition of tachyphylaxis) was abolished by supplementing prostaglandin E₂ as aerosol simultaneously to the allergen (100–200 ng per inhalation). The results suggest that allergen tachyphylaxis we have observed in vivo might be due to synthesis of cyclooxygenase products, e.g. prostaglandin E.Supported by Deutsche Forschungsgemeinschaft (grant Do 240) in part presented at the 17th workshop on pediatric research [Göttingen 1981, Eur. J. Pediatr. 135: 336 (1981)]     

Radon daughter plateout--II. Prediction model

By a linear programming procedure, we have optimized the Jacobi room model to fit our data on the partitioning of radon daughters between air and wall surfaces (plateout), obtained at high radon concentrations in a small chamber. Subsequently, the optimized model yielded estimates that compared well with plateout data obtained at lower concentrations in a room-sized chamber. (The experimental work is described separately.) The major change made in the Jacobi model was to reduce the deposition velocity of free airborne radon daughters from 1 to 0.05 cm/sec. This value was obtained by using a fast algorithm to solve the linear programming to arrive at the "best fit". Lesser changes were made in other parameters.     

Parametric in vivo imaging of benzodiazepine receptor distribution in human brain.

Emission computed tomographic methods for the in vivo quantification of radioligand-binding sites in human brain have previously been limited either by a lack of correction for possible effects of altered ligand transport or by highly complicated physiological models that preclude display of binding data in a detailed anatomical format. We investigated the application of a simplified compartmental model to the kinetic analysis of in vivo ligand binding to central benzodiazepine receptors. The human brain distribution of [11C]flumazenil, as determined by dynamic positron emission tomography, combined with metabolite-corrected arterial blood samples, permitted estimations of local cerebral ligand transport and of receptor binding. This approach allows calculation of transport and binding "maps" on a pixel-by-pixel basis, resulting in the display of binding data in a familiar tomographic format while maintaining much of the physiological accuracy inherent in more complex methods. The results obtained in a study of 6 normal volunteers revealed good interindividual precision, with coefficients of variation between 10 and 15% of mean regional values, suggesting the utility of this approach in future clinical studies of benzodiazepine receptor binding.     

Mechanism of the cardioprotective effect of triamterene in the rat heart. Myocardial protection via elevation of extracellular K+ and Mg++ concentrations

1. 2,4,7-Triamino-6-phenyl-pteridine (triamterene) protects the rat heart against isoproterenol-induced myocardial lesions: Whilst cardiotoxic doses of isoproterenol produce deleterious myocardial Ca overload, simultaneous admistration of triamterene diminishes myocardial Ca incorporation considerably. 2. As to the mechanism of action, triamterene increases the plasma contents of K and Mg by inhibiting renal excretion. Accordingly, oral administration of K and Mg salts, leading to a similar rise in the K and Mg concentrations of the plasma, also prevents abundant myocardial Ca incorporation. 3. Cardioprotection by triamterene can, in fact, be simply explained by its action on the plasma K and (particularly) Mg levels. This conclusion is drawn from a quantitative comparison of the inhibitory effects of triamterene (40 mg/kg s.c.) with those of KCl or MgCl2 (10 mMol/kg p.o.) on the isoproterenol-induced increase in myocardial 45Ca uptake and absolute Ca concentration. 4. Isoproterenol induced cardiomyopathy of the rat, an experimental model of non-coronarogenic myocardial lesions, has hitherto been successfully prevented with the use of Ca-antagonists (verapamil, D 600, prenylamine, fendiline). These compounds reduce Ca influx by restricting the Ca conductivity of the myocardial sarcolemma membrane ("slow channel"). The action of triamterene, on the other hand, is based on a totally different cardioprotective principle, namely competitive inhibition of intracellular myocardial Ca accumulation via an increase in K and Mg supply. In the future treatment of cardiomyopathy it seems rather promising to try a combination of both a Ca-antagonist and triamterene, thus applying two different therapeutic principles simultaneously.     

Intermittent atrial level right-to-left shunt with temporary hypoxemia in a patient during support with a left ventricular assist device

We report a 56-year-old male patient developing hypoxemia after surgical replacement of infected valves of a left ventricular assist device (LVAD, Novacor) which had supported him during the previous 15 months. Contrast transesophageal echocardiography (TEE) revealed an atrial septal defect with intermittent right-to-left shunt across a patent foramen ovale. We postulate that the shunt detected in this patient occurred as a consequence of reduced pulmonary vascular compliance due to positive end-expiratory pressure (PEEP) and an increase of mean intrathoracic pressure. Furthermore, we hypothesize that synchronized LVAD operation exacerbates any potential right-to-left shunt due to the profound left ventricular unloading which occurs during LVAD support. In this first report of a right-to-left shunt from a previously unrecognized patent foramen ovale in a Novacor patient, the subsequent transient hypoxemia could be managed by avoiding PEEP of more than 3 mmHg, and mean airway pressure of more than 11 mmHg and by careful volume replacement in order to prevent the pump from completely emptying the left ventricle (LV) and the left atrium (LA). Thus, prior to every LVAD implantation a transesophageal contrast echocardiography with Valsalva maneuver should be performed to identify intracardiac right-to-left shunt.     

Pulmonary and systemic bacterial co-infections in severe RSV bronchiolitis.

In 127 infants admitted to intensive care for RSV bronchiolitis, concomitant bacterial sepsis was a rare event. However, in the subgroup of intubated patients the incidence of bacterial pneumonia was 43.9% (95% CI 31.0-56.8%), half community acquired and half nosocomial. As clinical signs are not helpful in identifying these patients, tracheal aspirates have to be investigated microbiologically on a routine basis in order to start antibiotics in time.     

What is the difference between squamous cell carcinoma and adenocarcinoma of the cervix? A matched case–control study

The objective of this study was to investigate the efficacy of treatment strategies in patients with adenocarcinoma (AC) of the cervix and compare it with those with squamous cell carcinoma (SCC) of the cervix. Women with FIGO (1994) stage IB1 AC, especially pathologic tumor size of 2-4 cm, treated with class III hysterectomy, were compared with those with SCC treated with comparable strategy in a case-controlled study. Eighty patients (20 cases, 60 controls) were analyzed. Lymphvascular space invasion (P = 0.01) and lymph node metastasis (P = 0.07) were more frequent in patients with SCC than in those with AC. However, there was no significant difference in depth of stromal invasion (P = 0.51) and invasion of the parametrium (P = 0.44) between two groups. And there was also no statistically significant difference in disease-free survival (P = 0.86) and overall survival (P = 0.89) between two groups. Primary radical surgery followed by adjuvant therapy, same as for SCC, would be acceptable for AC with pathologic tumor size of 2-4 cm. Although it was difficult to determine whether AC recurred more systemically, more effective treatment strategies than those currently available for AC should be considered to reduce the systemic recurrence.