Single oral doses of amisulpride do not enhance the effects of alcohol on the performance and memory of healthy subjects

Objectives: Amisulpride is a benzamide antipsychotic that binds selectively to dopamine D₂- and D₃-receptors, preferentially in limbic and hippocampal structures. Since other substituted benzamides have a limited or negligible interaction with alcohol on human performance, amisulpride was studied for this potential. Methods: In a randomised double-blind crossover study, 18 young, non-smoking men took single oral doses of placebo and amisulpride 50 mg and 200 mg, without and with ethanol (0.8 g ⋅kg⁻¹) taken 30 min later. Objective performance tests and self-ratings were done at baseline and 1.5, 3.5 and 6.5 h after drug intake. Memory (immediate and delayed recall) was tested 2 h after dosing. Breath ethanol and the plasma concentrations of amisulpride and prolactin were measured. Three-way ANOVA + Newman-Keul tests were used for statistical analyses; interactions were confirmed by factorial contrast ANOVA. Results: Mean blood ethanol was 0.94, 0.62 and 0.26 g ⋅l⁻¹ at the three test times. It produced significant impairment in all performance tests (symbol digit substitution, simulated driving, body sway, flicker fusion, tapping, nystagmus), reduced both immediate and delayed recall in memory tests, and caused subjective clumsiness, muzziness and mental slowness, mainly between 1.5 to 4.5 h after dosing. Amisulpride, 50 and 200 mg elevated plasma prolactin but had minimal or no effect on performance, attention and memory. The decreases in immediate free recall after the 50 mg dose and in delayed free recall after the 200 mg dose were slight. Amisulpride neither modified blood ethanol concentrations nor enhanced the detrimental effect of ethanol on skilled and cognitive performance; it slightly antagonised ethanol in the digit copying test. Ethanol did not modify the effect of amisulpride on plasma prolactin, and the plasma concentrations of amisulpride were little changed by ethanol. Conclusions: Amisulpride in single oral doses of 50 and 200 mg did not interact significantly with the effects of high, moderate or low concentrations of ethanol on human skilled and cognitive performance. The drugs did interact pharmacokinetically. Received: 22 December 1995/Accepted in revised form: 1 April 1996     

Gay men's safer sex behavior: An integration of three models

This cross-sectional study explored gay men's sexual risk behavior from the perspective of three popular conceptual models, the health belief model, the theory of reasoned action, and social cognitive theory. Data were collected from sexually active gay men via anonymous questionnaire containing questions about sexual behavior and items related to the constructs comprising the three models. Using structural equation modeling techniques (LISREL 8), self-reported condom use was examined from the perspective of each theory. The results suggested that a substantial part of the variance in unprotected anal intercourse could be explained by conceptually analogous constructs common to these models. These constructs referred to the cognitive-affective reactions toward condoms and to the social context of using condoms. An additional variable unique to social cognitive theory, self-efficacy, added to the explained variance in the criterion above and beyond the variables that were common to the models. Relevant variables from the three theories were integrated into an expanded self-efficacy model.     

Effects of chronic alcohol consumption or Diazepam administration on item recognition and temporal ordering in a spatial working memory task in mice

This study was aimed at determining the effects of either Diazepam administration or chronic alcohol consumption (CAC) on spatial memory measured by concurrent discriminations in an eight arm radial maze using mice as subjects. Two different protocols involving a non-matching rule were used to evaluate either temporal order (recurrent items) or item recognition (non-recurrent items). Results showed that both Diazepam administration and CAC produced a memory deficit which was primarily observed in the temporal task, whereas item recognition was spared. These data show that Diazepam and CAC produced similar memory impairments. Thus, our study stressed the potential importance of the GABA/BDZ dysfunction in the production of organic amnesia of alcoholic origin. The overall analysis of the data suggests that both CAC and Diazepam injections would impair forms of memory sustained by automatic or incidental learning.     

An integration of cognitive-behavioral therapy and interpersonal psychotherapy for bulimia nervosa: a case study using the case formulation method

OBJECTIVE: The current study provides an illustration of an integration of cognitive-behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for the treatment of bulimia nervosa (BN), based on the case formulation strategy. METHOD: A 25-year-old Hispanic female referred herself for the treatment of eating difficulties and depressed mood. Diagnostic criteria were met for BN, major depressive episode, and alcohol abuse. Components of both CBT and IPT were utilized throughout the course of treatment. RESULTS: CBT techniques appeared to be most effective in eliminating binge eating and binge drinking behavior, whereas IPT techniques seemed to be most effective in reducing purging behavior. Results revealed that the client was no longer experiencing clinically significant symptoms of BN, depression, or alcohol abuse at end of treatment and follow-up (18 months after treatment onset). DISCUSSION: Findings support the integration of CBT and IPT for the treatment of BN and, potentially, other eating disorders.     

Reliability of the clinical teaching effectiveness instrument

INTRODUCTION: The Clinical Teaching Effectiveness Instrument (CTEI) was developed to evaluate the quality of the clinical teaching of educators. Its authors reported evidence supporting content and criterion validity and found favourable reliability findings. We tested the validity and reliability of this instrument in a European context and investigated its reliability as an instrument to evaluate the quality of clinical teaching at group level rather than at the level of the individual teacher. METHODS: Students participating in a surgical clerkship were asked to fill in a questionnaire reflecting a student-teacher encounter with a staff member or a resident. We calculated variance components using the urgenova program. For individual score interpretation of the quality of clinical teaching the standard error of estimate was calculated. For group interpretation we calculated the root mean square error. RESULTS: The results did not differ statistically between staff and residents. The average score was 3.42. The largest variance component was associated with rater variance. For individual score interpretation a reliability of > 0.80 was reached with 7 ratings or more. To reach reliable outcomes at group level, 15 educators or more were needed with a single rater per educator. DISCUSSION: The required sample size for appraisal of individual teaching is easily achievable. Reliable findings can also be obtained at group level with a feasible sample size. The results provide additional evidence of the reliability of the CTEI in undergraduate medical education in a European setting. The results also showed that the instrument can be used to measure the quality of teaching at group level.     

Profound hypothermia protects neurons and astrocytes, and preserves cognitive functions in a Swine model of lethal hemorrhage

BACKGROUND: Lethal injuries can be repaired under asanguineous hypothermic arrest (suspended animation) with excellent survival. This experiment was designed to test the impact of this strategy on neuronal and astroglial damage in a swine model of lethal hemorrhage. Furthermore, our goal was to correlate the histological changes in the brain with neurological outcome, and the levels of circulating brain specific markers. MATERIALS AND METHODS: Uncontrolled hemorrhage was induced in 32 female swine (80-120 lbs) by creating an iliac artery and vein injury, followed 30 min later by laceration of the thoracic aorta. Through a thoracotomy approach, organ preservation fluid was infused into the aorta using a roller pump. Experimental groups included normothermic controls (no cooling, NC), and groups where hypothermia was induced at three different rates: 0.5 degrees C/min (slow, SC), 1 degrees C/min (medium, MC), or 2 degrees C/min (fast, FC). Profound hypothermia (core temperature of 10 degrees C) was maintained for 60 min for repair of vascular injuries, after which the animals were re-warmed (0.5 degrees C/min) and resuscitated on cardiopulmonary bypass (CPB). Circulating levels of neuron specific enolase (NSE) and S-100beta were serially measured as markers of damage to neurons and astrocytes, respectively. Light microscopy and quantitative immunohistochemical techniques were used to evaluate hippocampal CA1 area and caudate putamen for neuronal injury and astrogliosis (astrocyte hyperplasia/hypertrophy). Surviving animals were observed for 6 weeks and neurological status was documented on an objective scale, and cognitive functions were evaluated using a technique based upon the concept of operant conditioning. RESULTS: Normothermic arrest resulted in clinical brain death in all of the animals. None of the surviving hypothermic animals displayed any neurological deficits or cognitive impairment. On histological examination, normothermic animals were found to have ischemic changes in the neurons and astrocytes (hypertrophy). In contrast, all of the hypothermic animals had histologically normal brains. The circulating levels of brain specific proteins did not correlate with the degree of brain damage. The changes in NSE levels were not statistically significant, whereas S-100beta increased in the circulation after CPB, largely independent of the temperature modulation. CONCLUSIONS: Profound hypothermia can preserve viability of neurons and astrocytes during prolonged periods of cerebral hypoxia. This approach is associated with excellent cognitive and neurological outcome following severe shock. Circulating markers of central nervous system injury did not correlate with the actual degree of brain damage in this model.     

Mice lacking dopamine D2 and D3 receptors exhibit differential activation of prefrontal cortical neurons during tasks requiring attention

Mice lacking dopamine D2 and D3 receptors and wildtype littermates were tested in a two-choice perceptual discrimination test that is dependent upon optimal functioning of the prefrontal cortex. Both mutants showed no deficits in attending to the perceptual stimuli or in shifting attention between stimulus dimensions. However, the performance of both mutants differed from the wildtype in different test phases. D2 mutants exhibited significant impairment in the first compound discrimination, indicating deficits in the initial acquisition of the task-governing rules. In contrast, D3 mutants performed significantly better in a set-shifting phase that required reversal learning. The higher response accuracy of D3 mutants was also accompanied by significantly increased response latency. A stereological assessment of test-induced expression of the c-fos gene in neurons of the anterior cingulate and prelimbic/infralimbic cortices revealed highest activation in D3 mutants, intermediate activation in wildtype and lowest activation in D2 mutants, indicating that response accuracy in the cognitive test correlates with the magnitude of prefrontal cortical activation regardless of which test phases revealed different performances. The study illustrates that dopamine differentially modulates prefrontal cortical activity during tasks requiring attention depending upon the type of D2-like receptor that is activated.     

特发性脊柱侧凸患者脊柱畸形段凸侧及凹侧关节突松质骨三维微结构比较

目的比较青少年特发性脊柱侧凸(AIS)患者脊柱畸形顶椎区和端椎区两侧关节突松质骨的三维微结构。方法AIS患者9例,均为女性,年龄12～17岁,平均14.9岁;Cobb角48°～84°,平均56°。患者均接受后路矫形融合内固定手术,术前与患者家长签署同意书,在去皮质手术时取下顶椎区和上下端椎区两侧关节突。标本取材后用中性福尔马林固定,然后用解像度为20μm的微焦点CT扫描,三维图像重组进行骨形态计量学测量对比。结果顶椎区凸侧与凹侧相比有显著差异,分别为:骨量容积比BV/TV为0.268/0.354(P<0.05),骨小梁厚度TbTh为0.20/0.24(P<0.05),骨小梁分离度TbSP为0.66/0.56(P<0.05),骨小梁面积体积比BS/BV为12.7/10.4,P<0.05)。端椎区左右两侧关节突松质骨骨小梁无明显差异,上胸椎和胸腰椎关节突骨小梁微结构比较未见差异。结论由于脊柱侧凸凹侧承受不同应力,凹侧关节突出现更多的骨小梁,骨小梁间的连接更紧密,而且骨小梁更粗,从而可使脊椎楔形变的速度变缓,提示脊柱的骨骼本身并不是AIS脊柱侧凸畸形进展的促进因素。