海洛因依赖者戒毒前后肝肾功能的变化

目的:探讨海洛因依赖者在戒毒前后肝、肾功能的变化.方法:收集武汉市戒毒中心60例住院患者戒毒前后的丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、血尿素氮(BUN)、血肌酐(Cr)及尿液α1 MG、清蛋白(ALB)的检测结果,将之与湖北省新华医院70例健康体检者的肝、肾功能检测结果相比较.结果:海洛因依赖者戒毒前血清ALT、AST、尿液α1 MG、ALB含量均显著高于对照组,而血清BUN、Cr则变化不明显;戒毒后,血清ALT、AST较戒毒前有所降低,但仍明显高于对照组,尿液α1 MG、ALB则趋于正常.结论:海洛因依赖者存在肝肾功能损害,其中肾功能损害较轻,宜用早期诊断指标如尿液α1 MG、ALB监测;肝功能损害有一定的持续性,不能完全随戒毒治疗而恢复.提示在进行戒毒治疗的同时,要密切监测肝、肾功能,并了解其变化规律,以利综合治疗.     

Blockade of nitric oxide synthesis reduces responding for cocaine self-administration during extinction and reinstatement

The dementia in Alzheimer disease (AD) is usually attributed to widespread neuronal loss in conjunction with the pathologic hallmarks of intracellular neurofibrillary tangles and extracellular plaques containing amyloid (A beta) in fibrillar form. Recently it has been demonstrated that non-fibrillar assemblies of A beta possess electrophysiologic activity, with the corollary that they may produce dementia by disrupting neuronal signaling prior to cell death. We therefore examined the effects of soluble oligomers of A beta(1-42) on long-term potentiation (LTP) and long-term depression (LTD), two cellular models of memory, in the dentate gyrus of rat hippocampal slices. Compared with vehicle controls, slices pre-incubated 60 min in the presence of A beta-derived diffusible ligands (ADDLs) showed no differences in threshold intensity to evoke a synaptic response, slope of field excitatory post-synaptic potentials (EPSPs), or the input/output function. Tetanus-induced LTP and reversal of LTD were strongly inhibited in ADDLs-treated slices whereas LTD was unaffected. These data suggest that soluble non-fibrillar amyloid may contribute to the pathogenesis of AD both by impairing LTP/memory formation at the cellular level and by creating 'neuroplasticity imbalance' manifested by unopposed LTD in the setting of impaired capacity for neural repair via reversal of LTD or LTP.     

吸食海洛因致海绵状白质脑病的CT及MRI诊断

目的评价海洛因中毒所致的海绵状白质脑病的CT、MRI表现及诊断价值.方法搜集6例海洛因海绵状白质脑病的CT及MRI资料,全部患者均进行MRI检查,检查序列包括T1WI、T2WI、FLAIR序列,其中2例同时行颅脑CT扫描. 结果全部患者MRI显示对称性双侧小脑半球、大脑半球后部、内囊后肢、胼胝体压部、脑干等皮质下白质为主的多发性大片状长T1、长T2信号,加强后病灶无强化;2例行头颅CT检查显示两大脑半球皮质下白质、基底节及两侧小脑呈对称性广泛低密度灶,无占位效应.结论海洛因中毒所致的海绵状白质脑病具有特征性的MRI表现,MRI对本病的诊断具有重要价值.     

Exposure to Family Violence and Temperament Factors as Predictors of Adult Psychopathology and Substance Use Outcomes

This study examines the potential for a negative psychological impact as a result of childhood exposure to family violence. Psychopathological outcomes in adulthood, such as alcohol problems and depression, are examined in light of reports of childhood physical abuse and exposure to parental violence. A national household probability sample of over 3,000 respondents were asked whether they had, as children, observed violence or threats of violence between their parents or whether they had directly experienced violence from one or both parents. Observed threats of violence was the most potent predictor of depression and current heavy drinking in women. Among men, observed threats of violence predicted current heavy drinking, and alcohol dependence symptoms; personal experience of violence predicted depression. Impulsivity was a main effect predictor of virtually all outcome variables for men and women, but typically did not interact with experience or observation of violence. Findings suggest that individuals who remember childhood experiences of indirect violence from parental conflicts have higher rates of pathological adult outcomes. Impulsivity and sensation seeking are highly related to these outcomes over and above violence history. Family conflict variables and temperament variables are highly correlated with one another but make independent contributions.     

长期危险饮酒对酒精依赖者心血管功能的影响

目的探讨长期危险饮酒与心血管功能变化的关系,并分析长期危险饮酒对酒精依赖患者心血管意外发生的影响。方法纳入酒精依赖患者72例,按WHO饮酒分类标准将危险饮酒且超过10年的患者分为长期危险饮酒组(52例),其他患者为非长期危险饮酒组(20例);并纳入无习惯性饮酒嗜好的健康体检者75名为对照组。采用全自动生化分析仪检测被试血脂水平,彩色多普勒超声测量心脏功能以及颈、肱动脉内皮功能,并于患者出院后1年内电话随访其心血管意外发生情况。结果三组血脂各指标差异均无统计学意义(P0.05)。长期危险饮酒组患者左心射血分数低于对照组(P0.01),左房主动排空分数高于非长期危险饮酒组及对照组(P0.05),肱动脉内皮舒张功能、颈动脉内膜中层厚度低于对照组(P0.05)。所有患者饮酒年限与左房被动排空分数(r=-0.246,P=0.014)、左房主动排空分数(r=-0.239,P=0.016)呈负相关,平均每日饮酒量与左心射血分数呈正相关(r=0.256,P=0.010),与肱动脉内皮舒张功能呈负相关(r=-0.256,P=0.010)。多因素logistic回归分析示,酒精依赖患者发生心血管意外与年龄(OR=1.102,95%CI:1.020~1.191)、长期危险饮酒(OR=1.334,95%CI:1.060~1.678)有关联(P0.05)。结论长期危险饮酒可致酒精依赖患者的左室舒张功能及血管内皮功能受损,是导致酒精依赖患者发生心血管意外的独立危险因素。     

Fluoxetine Treatment Seems to Reduce the Beneficial Effects of Cognitive-Behavioral Therapy in Type B Alcoholics

Objective : The aim of this study was to test the hypothesis that, because of abnormalities in serotonergic neurotransmission that may underlie craving and impulsive behavior, fluoxetine treatment differentially affects drinking among type B alcoholics, who are characterized by high levels of both premorbid vulnerability and alcohol-related problems. Methods : Using a k -means clustering procedure, alcohol-dependent subjects from a placebo-controlled trial of fluoxetine were grouped into low-risk/severity (type A n = 60) and highrisk/severity (type B: n = 35) groups. Multivariate analysis of covariance (with pretreatment measures as covariates) evaluated the effects of Alcoholic Subtype, Medication Group, Treatment Completion, and their interactions on measures of drinking, both during the 12-week treatment period and a 6-month follow-up period. Results : Although there were no main effects of Alcoholic Subtype or Medication Group, subjects who completed the treatment trial showed significantly better drinking-related outcomes. There was also an interaction of Alcoholic Subtype by Medication Group during treatment. Among type B subjects, fluoxetine treatment resulted in poorer drinking-related outcomes than placebo treatment. Among type A subjects, there was no effect of Medication Group. This interactive effect did not persist during the 6-month follow-up period. Conclusions : Alcoholic subtypes identified by cluster analysis seem to be differentially responsive to the effects of fluoxetine treatment on drinking-related outcomes. Serotonergic abnormalities previously identified among a subgroup of alcoholics who are also characterized by impulsivity and severity of alcohol dependence may help to explain the differential medication effect. Based on these findings, it is recommended that, in the absence of a comorbid mood or anxiety disorder, fluoxetine not be used to maintain abstinence or reduce drinking in high-risk/severity alcoholics.     

Linkage Analysis of Alcohol Dependence Symptoms in the Community

Background:  We have previously identified suggestive linkage for alcohol consumption in a community-based sample of Australian adults. In this companion paper, we explore the strength of genetic linkage signals for alcohol dependence symptoms.
Methods:  An alcohol dependence symptom score, based on DSM-IIIR and DSM-IV criteria, was examined. Twins and their nontwin siblings (1,654 males, 2,518 females), aged 21 to 81 years, were interviewed, with 803 individuals interviewed on 2 occasions, approximately 10 years apart. Linkage analyses were conducted on datasets compiled to maximize data collected at either the younger or the older age. In addition, linkage was compared between full samples and truncated samples that excluded the lightest drinkers (approximately 10% of the sample).
Results:  Suggestive peaks on chromosome 5p (LODs >2.2) were found in a region previously identified in alcohol linkage studies using clinical populations. Linkage signal strength was found to vary between full and truncated samples and when samples differed only on the collection age for a sample subset.
Conclusions:  The results support the finding that large community samples can be informative in the study of alcohol-related traits .     

Common Genetic Contributions to Alcohol and Cannabis Use and Dependence Symptomatology

Background: Despite mounting evidence that use of and dependence on alcohol and cannabis are influenced by heritable factors, the extent to which heritable influences on these phenotypes overlap across the 2 substances has only rarely been explored. In the current study, we quantified cross‐substance overlap in sources of variance and estimated the degree to which within‐substance associations between use and dependence measures are attributable to common genetic and environmental factors for alcohol and cannabis. Methods: The sample was comprised of 6,257 individuals (2,761 complete twin pairs and 735 singletons) from the Australian Twin Registry, aged 24 to 36 years. Alcohol and cannabis use histories were collected via telephone diagnostic interviews and used to derive an alcohol consumption factor, a frequency measure for cannabis use, and DSM‐IV alcohol and cannabis dependence symptom counts. Standard genetic analyses were conducted to produce a quadrivariate model that provided estimates of overlap in genetic and environmental influences across the 4 phenotypes. Results: Over 60% of variance in alcohol consumption, cannabis use, and cannabis dependence symptoms, and just under 50% of variance in alcohol dependence (AD) symptoms were attributable to genetic sources. Shared environmental factors did not contribute significantly to the 4 phenotypes. Nearly complete overlap in heritable influences was observed for within‐substance measures of use and dependence symptoms. Genetic correlations across substances were 0.68 and 0.62 for use and dependence symptoms, respectively. Conclusions: Common heritable influences were evident for alcohol and cannabis use and for AD and cannabis dependence symptomatology, but findings indicate that substance‐specific influences account for the majority of the genetic variance in the cannabis use and dependence phenotypes. By contrast, the substantial correlations between alcohol use and AD symptoms and between cannabis use and cannabis dependence symptoms suggest that measures of heaviness of use capture much of the same genetic liability to alcohol‐ and cannabis‐related problems as dependence symptomatology.     

Increased Acid Sphingomyelinase Activity in Peripheral Blood Cells of Acutely Intoxicated Patients With Alcohol Dependence

Background:  Acid sphingomyelinase (ASM; EC 3.1.4.12) hydrolyses membrane sphingomyelin into the bioactive lipid ceramide and is thus involved in different cellular processes such as differentiation, immunity, or cell death. Activation of ASM has been reported in particular in conjunction with the cellular stress response to several external stimuli, and increased ASM activity was observed in a variety of human diseases. Ethanol-induced activation of ASM has been observed in different cell culture systems, thus raising the question about the effect of alcohol intoxication in human subjects on ASM activity in vivo.
Methods:  We determined ASM activity in peripheral blood mononucleated cells of 27 patients suffering from alcohol dependence. Patients were classified according to their blood alcohol concentration at admission, and ASM activity was determined repeatedly from all patients during alcohol withdrawal.
Results:  Acutely intoxicated patients displayed significantly higher ASM activity than patients in early abstinence (Mann–Whitney U test: Z  = − 2.6, p  = 0.009). ASM activity declined in acutely intoxicated patients to normal values with the transition from the intoxicated state to early abstinence (Wilcoxon test: Z  = −2.7, p  = 0.007). At the end of withdrawal, ASM activity was significantly increased again compared to the early phase of abstinence in both patient groups (Wilcoxon test: Z  = −2.691, p  = 0.007 and Z  = −2.275, p  = 0.023, respectively).
Conclusions:  Alcohol-induced activation of ASM occurs in human subjects and might be responsible for deleterious effects of ethanol intoxication. Chronic alcohol abuse may induce deregulation of sphingomyelin metabolism in general, and this impairment may cause side effects during withdrawal from alcohol.     

Psychometric properties of the CAST and SDS scales in young adult cannabis users

Aim

To assess the validity of two cannabis use severity scales among young cannabis users and to evaluate their ability to detect Substance Use Disorders (SUD).

Participants

241 volunteers (18–25 years), with a wide spectrum of cannabis use in the last 12 months.

Measurements

The Cannabis Abuse Screening Test (CAST) and Severity of Dependence Scale (SDS) were self-administered. The Psychiatric Interview for Substance and Mental Disorders (PRISM) was used as gold standard for cannabis use disorders according to DSM-IV. Reliability and validity were assessed for two different CAST coding algorithms (b—binary and f—full) and for the SDS. In addition, the cannabis use diagnostic criteria contained in the PRISM were grouped to approximate forthcoming proposed DSM-V criteria to further evaluate these scales.

Findings

26.6% (95% CI: 21.0–32.2) of the subjects met criteria for cannabis dependence, and 49.0% (95% CI: 42.7–55.3) for cannabis use disorders. For both scales internal consistency (Cronbach's alpha > 0.71) and test–retest intraclass correlation coefficients (> 0.80) were good. The score 12 in the CAST-full discriminated better than others between presence and absence of dependence (27.0%; 95% CI: 21.4–32.6) while the score for discrimination of SUD was 9 (51.5%; 95% CI: 45.1–57.8). For the SDS the values were 7 (22.0%; 95% CI: 16.8–27.2) and 3 (64.7%; 95% CI: 58.7–70.8), respectively. According to proposed DSM-V criteria, for moderate and severe addiction the values for the CAST-f were 7 (68.5%; 95% CI: 62.5–74.3) and 12 (27%; 95% CI: 21.3–32.6) and for the SDS, 3 (65.0%; 95% CI: 58.7–70.8) and 7 (22%; 95% CI: 17.0–34.3), respectively.

Conclusions

The CAST and SDS applied to young cannabis users are reliable and valid measures to detect cannabis use disorders when compared to both DSM-IV and proposed DSM-V criteria.