ZK 91296, a partial agonist at benzodiazepine receptors

ZK 91296 (ethyl 5-benzyloxy-4-methoxymethyl--carboline-3-carboxylate) is a potent and selective ligand for benzodiazepine (BZ) receptors. Biochemical investigations indicate that ZK 91296 may be a partial agonist at BZ receptors. Such partial agonism may explain to some extent why ZK 91296 needs higher BZ receptor occupancy than diazepam for the same effect against chemical convulsants and for behavioural effects. The lack of sedatiye effects, and the very potent inhibition of reflex epilepsy, spontaneous epilepsy and DMCM-induced seizures suggest, furthermore, that ZK 91296 may possess pharmacological selectivity for a particular type of BZ receptor interaction, perhaps including topographic as well as receptor subtype differentiation.     

Sex Differences in Voyeuristic and Exhibitionistic Interests: Exploring the Mediating Roles of Sociosexuality and Sexual Compulsivity from an Evolutionary Perspective

Sociosexuality and sexual compulsivity predict sex differences in voyeuristic interest in the population. In this study, we used a sample of 1113 participants from the UK (46% men) to consider whether sociosexuality and sexual compulsivity interacted to explain these sex differences and whether this relationship extended to the related domain of exhibitionism. In doing so, we tested novel predictions derived from an evolutionary perspective which views voyeuristic and exhibitionistic interest as manifestations of a short-term mating strategy. Participants reported their levels of repulsion toward voyeurism and exhibitionism and their interest in performing such acts under different levels of risk. There were clear sex differences in voyeuristic and exhibitionistic repulsion that were partially mediated by the serial combination of sociosexuality and sexual compulsivity. Examining the sexes separately revealed qualitatively different relationships between sociosexuality and sexual compulsivity when predicting exhibitionistic, but not voyeuristic, repulsion. Combined, sociosexuality and sexual compulsivity also mediated the sex difference in willingness to commit acts of voyeurism, but not exhibitionism, which was equally low for both sexes. The results highlight the role sociosexuality plays in voyeuristic and exhibitionistic interest, which coupled with an evolutionary perspective, may have implications for how we view courtship disorders.

     

Continuous blockade of the lumbar plexus after knee surgery: a comparison of the plasma concentrations and analgesic effect of bupivacaine 0.250% and 0.125%

In 20 patients a continuous block of the lumbar plexus was administered after knee-joint surgery, and the analgesic effect of two different concentrations of bupivacaine was compared. The same volume of bupivacaine was given to both groups of patients: a bolus dose of 0.4 ml/kg, 0.5% or 0.25%, followed by infusion of 0.14 ml/kg/h, 0.25% or 0.125%, respectively, via a catheter placed in the neurovascular fascial sheath of the femoral nerve according to the "3-in-1 block" technique. The median morphine consumption during the first 16 h postoperatively was 6.0 mg when bupivacaine 0.5/0.25% was used and 9.5 mg when 0.25/0.125% was used. This difference is not significant. The visual analogue pain scores were also similar in the two groups (P greater than 0.05). All plasma concentrations were below 4 micrograms/ml, the highest concentration measured being 3.6 micrograms/ml. It is concluded that when used for a continuous block of the lumbar plexus after knee-joint surgery, bupivacaine in a concentration of 0.125% offers the same pain relief as a concentration of 0.25%, and the risk of toxic reactions is reduced.     

Does the level of stapled ileoanal anastomosis influence physiologic and functional outcome?

PURPOSE: The aim of this investigation was to ascertain how the length of anal canal preserved above the dentate line in stapled end-to-end ileoanal anastomosis influenced late outcome. METHODS: Two groups, high cuff group and low cuff group of nine subjects with stapled anastomosis, matched for sex, age, pouch configuration, and mean follow-up, representing the highest (median, 2.5 cm) and lowest (median, 0.7 cm) anal cuff lengths in our series, were selected. Physiologic and functional parameters were appraised preoperatively, at the time of ileostomy closure, and at 1, 3, 6, and 12 months after reestablishment of intestinal continuity. RESULTS: At one year, the drop in mean anal canal resting pressure was 13 percent in the high cuff group (not signficant) and 31 percent in the low cuff group (P <0.05); mean maximum squeezing pressure did not differ significantly from preoperative values in both groups. The mean volume of the ileal pouch was higher in the low cuff group at all insufflation pressures. The rectoanal inhibition reflex reappeared in four high cuff group patients and in none of the low cuff group patients. Mean distention pressure (cm H ₂ O) and volume (ml) eliciting urge sensation were 80 and 360 in the low cuff group compared with 40 and 240 in the high cuff group (P ?0.05). Daytime bowel movements and night incontinence were significantly better in the low cuff group. No statistical differences were observed for night stool frequency, daytime incontinence, pad use (day and night), discrimination between gas and feces, ability to defer evacuation, and difficulty in emptying the pouch. CONCLUSION: Patients with stapled anastomoses and a low rectal cuff length, despite presenting lower anal resting pressure and absence of rectoanal inhibition reflex, had a better functional outcome in terms of continence than those with a high cuff length.     

The role of national quality registers in the Swedish health service

This article reports on a quality movement in Sweden that has gone largely unnoticed, namely the national quality control registers. These registers represent a potentially important primary data source for comparative studies and can play an important role in a national strategy for control and improvement of health care quality. First, we review the recent health care quality initiatives in Sweden and the background of national quality control registers. Secondly, we discuss our findings from a study on the purpose, content, value and problems associated with the registers. Our findings are based on (a) interviews with physician managers of the registers, (b) questionnaires to selected hospital departments participating in the registers and (c) questionnaires to elected officials and administrators representing the local health care providers. Finally, we discuss several crucial issues related to the registers. Although some have existed for several years, the registers are still defining their roles. Traditionally, this activity has been managed by the medical profession. However, interest in register information is increasing among health care policy makers and administrators at all levels in the system. Two key issues concern register ownership and finance, but the most sensitive issue concerns the right of policy makers and the public to access register information. The registers and the information they contain illustrate the ongoing conflict between openness and consumer sovereignty in health care on the one hand and professional autonomy on the other.     

Genotoxic activity of chlorohydroxyfuranones in the microscale micronucleus test on mouse lymphoma cells and the unscheduled DNA synthesis assay in rat hepatocytes

Chlorohydroxyfuranones (CHFs) are mutagenic disinfection by-productsfound in chlorine-treated drinking water. In the current study,the genotoxicity of four CHFs, 3,4-dichloro-5-hydroxy-2(5H)-furanone(MCA), 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF), 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone(CMCF) and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone(MX), was determined. Two in vitro assays, the microscale micronucleusassay on L5178Y mouse lymphoma cells and the unscheduled DNAsynthesis assay on a hepatocyte primary culture from FisherF344 rats, were carried out. All four CHFs demonstrated genotoxiceffects in both assays. In the two systems used, CMCF was themost genotoxic compound, followed by MCA, MX and MCF, respectively.This work was the first study of the DNA damaging propertiesof all four CHFs in two in vitro genotoxicity tests. These newdata expand the range of genetic damages induced by this groupof compounds. ² To whom correspondence should be addressed. Tel: +33 3 20 8779 14; Fax: +33 3 20 87 73 10; Email: daniel.marzin{at}pasteur-lille.fr     

Pharmacokinetic and pharmacodynamic responses to chronic administration of the selective serotonin reuptake inhibitor citalopram in rats

The number of drugs used to treat affective disorders such as depression is rapidly increasing. Citalopram (CIT), an antidepressant, is a selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI). In the present study, rats were treated with 10 mg/kg/d racemic CIT for two weeks with use of osmotic pumps, and the following were monitored: open-field behavior, racemic and enantioselective concentrations of CIT and metabolites in blood, brain parenchyma, and extracellular space, and the brain extracellular monoamine levels. The racemic CIT concentration in serum was estimated about tenfold lower than in brain parenchyma but much higher than in brain extracellular fluid. The major CIT metabolites, demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) were 20% and 30%, respectively, of the amounts of CIT in serum and even lower in the brain parenchyma. The S-enantiomer/R-enantiomer ratios for CIT and DCIT were about 1.01 and 0.31, respectively, in blood and brain. There was a clear correlation between the different drug components within and between blood and brain compartments. Citalopram had no measured effect on open-field behavior, but it elevated extracellular 5-HT and decreased 5-HIAA levels. No correlations between any of the drug components and the brain monoamines were found. In summary, the drug components after chronic dosing correlated well between the periphery and the brain, but not with the brain monoamine concentrations. Further studies investigating the combined pharmacokinetic/dynamic effects could take advantage of blood drug monitoring for the commonly used novel antidepressant drugs.