Vitamin D receptor (VDR) gene polymorphisms and expression profile influence upon the immunological imbalance in Turner syndrome.

PURPOSE: Turner syndrome (TS) patients display considerable immune misregulation, and it is hypothesized that Vitamin D (VTD) activity may fluctuate according to Vitamin D receptor (VDR) polymorphisms and/or expression profile. To uncover a possible relationship between VDR genotype and clinical conditions in TS patients, we investigated two functional VDR variants (Cdx-2 and FokI) for allele and genotype frequencies, as well as expression profile in TS individuals versus healthy controls (HC). METHODS: We performed a genetic association study including 100 TS patients and 116 HC. Genotyping for VDR Cdx-2 G > A (rs11568820) and FokI C > T (rs2228570) was performed using Taqman Genotyping Assays. VDR gene expression was also evaluated in 15 TS and 15 HC, using fluorogenic probes by qPCR. Statistical analyses were performed using nonparametric Mann-Whitney test, with a 5% significance level (p < 0.05) to uncover differences between groups. In addition, we investigated whether shifted VDR mRNA levels were associated with Cdx-2 and FokI variants in TS patients. RESULTS: We detected a significantly higher frequency of T allele (p = 0.006) as well as T/T genotype (p = 0.01) for FokI in TS patients when compared to HC. When assessing VDR expression, we identified a downregulation in TS woman (- 2.84 FC) versus HC (p < 0.001). Furthermore, C/T (11.24 FC; p = 0.01) and T/T (9.20 FC; p = 0.01) FokI genotypes were upregulated when compared to C/C reference genotype. CONCLUSION: TS patients show different distribution of FokI polymorphism. Downregulation of VDR gene expression may contribute to immunological imbalance in TS.

Tobacco use among the elderly: The first Brazilian National Survey (BNAS).

OBJECTIVE: This study describes the prevalence and pattern of tobacco use among the elderly in Brazil and establishes its association with socio-demographic characteristics, other substance use and depression. METHOD: The analyses were performed in 400 individuals aged 60 years and over who participated in the first Brazilian national alcohol survey (BNAS) in 2000. RESULTS: Nearly 60% of the sample had ever smoked, of them one in three were still smoking at the time of the interview. Most (94.3%) of the tobacco users were smoking everyday and 34.3% consuming more than 20 cigarettes a day. Only 1% of the former smokers had received support to quit. Over half of the current users (65%) would use free treatment to quit if it existed in Brazil, and just under half of them (47.4%) would consider quitting if cigarettes' price were higher. Currently, tobacco users were more likely to be men and alcohol abusers. Prevalence of depression was high regardless participant smoking status (33.0% among non-smokers, 34.7% among current smokers and 39.3% among former smokers). There was no significant association between smoking and depression. CONCLUSION: This study found a disturbingly high proportion of tobacco users among the elderly in Brazil. According to the Global Burden of Disease project, tobacco has the highest mortality risk of all substance use categories, especially for the elderly. This study shows there is an urgent need to develop smoking cessation interventions targeted specifically to the elderly.

Motivation for change in alcohol dependent outpatients from Brazil.

The general aim of this study was to investigate the reliability and factor structure of the stages of change readiness and treatment eagerness scale (SOCRATES) in 326 outpatients with alcohol dependence. The questionnaire was translated and cross-culturally adapted into Portuguese and back-translated to English. The confirmatory factor analysis showed that two correlated factors provided the best fit for the data.

Reversal of abnormal dexamethasone suppression test in alcoholics abstinent for four weeks.

Fourteen of 64 alcoholic inpatients (22%) showed a nonsuppression postdexamethasone response when tested between the second and fifth days of admission. No association with alterations of hepatic enzymes (GGT, SGOT, SGPT) was observed. At retest (in the fourth week of abstinence), no abnormal response to the Dexamethasone Suppression Test (DST) was detected. The nonsuppressor alcoholics did not meet the criteria for major depression according to the Research Diagnostic Criteria (RDC). The data indicate a lack of specificity of the DST for the diagnosis of depression in alcoholics during the first days of withdrawal.

Transitions in the route of cocaine administration--characteristics, direction and associated variables.

AIMS: To examine transitions in the route of administration of cocaine and the variables associated with them. DESIGN: A cross-sectional study undertaken between January 1996 and October 1997. SETTING: Fifteen different services that offer treatment, counselling or assistance to drug users or HIV-positive patients in the State of São Paulo, Brazil. PARTICIPANTS: Two hundred and ninety-four current or ex-cocaine and crack cocaine users. MEASUREMENTS: A structured interview schedule was developed consisting of 246 questions covering socio-demographic details, drug history, cocaine transitions and HIV-risk behaviours. FINDINGS: Eighty-seven per cent of patients began using cocaine by snorting and 74% subsequently underwent a transition of route--68% towards smoking and 20% to injecting. Half of all transitions occurred in the first 3 years following initiation into cocaine use. Factors associated with transitions were: younger age at cocaine initiation, more frequent use at peak usage, initial use of cocaine by snorting or injecting, a lower level of scholastic attainment and experience with a wider range of drug classes. A cohort effect was apparent with younger cocaine users and those who had begun using after 1990 being more likely to undergo a transition to smoking crack and less likely to start injecting. CONCLUSIONS: Cocaine transitions are very common and are usually towards routes associated with a higher dependency potential and increased HIV-risk behaviour. Further research is needed to see if transitions can be prevented by early identification of potential cases.

Does multisite sampling improve patient heterogeneity in drug misuse research?

The aim of this study was to investigate whether multisite sampling increased heterogeneity among a sample of cocaine users from São Paulo, Brazil. Six hundred and fourteen cocaine users were interviewed at 23 fixed sites plus an out-of-treatment sample. The sites were then regrouped into six main types: university outpatient clinics, public outpatient clinics, public inpatient units, private inpatient units, HIV services and non-treatment. Marked differences were found between users recruited at these sites, especially in relation to age, gender, employment status, criminal history, history of prostitution, previous drug misuse treatment, duration of cocaine use and lifetime use of intravenous cocaine. These results suggest that multisite sampling is a valid method for increasing patient heterogeneity, but whether it improves representativeness and thus the generalisability of drug misuse research is debatable.

Drinking and driving: pre-driving attitudes and perceptions among Brazilian youth.

The aim of this study was to investigate driving under the influence of alcohol (DUI) risk profiles and predictors in a sample of pre-driving Brazilian youth, in the context of Brazil's new Traffic Code. Data were obtained in the Traffic Department in São Paulo from a sample of 2166 individuals. Subjects displayed a low level of knowledge about the laws and few believed the penalties would actually be enforced for those engaging in DUI. Findings suggest that changes in DUI laws in Brazil and elsewhere should be accompanied by enforcement and education in order to enhance levels of knowledge and credibility of the sanctions.

Crack cocaine--a two-year follow-up of treated patients.

OBJECTIVES: To investigate the 2-year outcome of the first 131 crack cocaine users who had been admitted for a period of inpatient treatment. DESIGN: Follow-up study of consecutive patients admitted between 1992 and 1994. SETTING: Inpatient detoxification unit of a public general hospital in São Paulo City, Brazil. PARTICIPANTS: 131 consecutive crack cocaine users. MEASURES: Reported crack use during last 12 months, incarceration and death. FINDINGS: After 2 years, 50 patients reported crack use in the last 12 months, 29 said that they had not used it during this period, 9 were in prison, 13 had died, 2 had disappeared and no information was available on 28. CONCLUSIONS: Crack cocaine use seems to be associated with a high mortality rate and criminal involvement but about one-third of patients give up using the drug within 2 years of inpatient treatment.

Environmental tobacco smoke exposure among non-smoking waiters: measurement of expired carbon monoxide levels.

CONTEXT: Exposure to environmental tobacco smoke is a health risk that is of concern to patrons and of particular concern to employees of restaurants and bars. OBJECTIVE: To assess environmental tobacco smoke exposure (using expired carbon monoxide levels) in non-smoking waiters before and after a normal day's shift and to compare pre-exposure levels with non-smoking medical students. DESIGN: An observational study. SETTING: Restaurants with more than 50 tables or 100 places in São Paulo. SUBJECTS: 100 non-smoking restaurant waiters and 100 non-smoking medical students in São Paulo, Brazil. MAIN MEASUREMENTS: Levels of expired carbon monoxide, measured with a Smokerlyser (Bedfont EC 50 Scientific), before and after a normal day's work. RESULTS: Waiters' pre-exposure expired carbon monoxide levels were similar to those of medical students, but after a mean of 9 hours exposure in the workplace, median levels more than doubled (2.0 ppm vs. 5.0 ppm, P <0.001). Post-exposure carbon monoxide levels were correlated with the number of tables available for smokers (Kendall's tau = 0.2, P <0.0001). CONCLUSIONS: Exposure to environmental tobacco smoke is the most likely explanation for the increase in carbon monoxide levels among these non-smoking waiters. These findings can be used to inform the ongoing public health debate on passive smoking.

Nurses' attitudes towards alcoholism: factor analysis of three commonly used scales.

OBJECTIVE: To investigate the psychometric properties of three scales commonly used to measure attitudes and beliefs about alcoholism. DESIGN: Cross-sectional study using a systematic sample. SETTING: Hospital São Paulo (a public general tertiary hospital) and the adjoining Federal University of São Paulo, Brazil. PARTICIPANTS: 310 nurses and nursing teachers. INSTRUMENTS: The Marcus Alcoholism Questionnaire, The Seaman Mannello Nurses' Attitudes Towards Alcohol and Alcoholism Scale and The Tolor-Tamarin Attitudes Towards Alcoholism Scale, which were combined into one self-administered questionnaire. ANALYSIS: The scales were re-grouped into their original formats and each underwent a principal components analysis with orthogonal rotation of factors. RESULTS: Each scale was found to consist of three main factors. There was some degree of overlap in the nature of the factors that the scales measured but each scale also measured something unique. CONCLUSION: The results of this comparative analysis could be used as a basis for developing a new scale covering all the important attitudinal groups identified by this study.

Psychoactive drug use by medical students: a review of the national and international literature.

Non-medical drug use among medical students is a major concern among researchers and policy makers in several countries, not only because of the personal harmful consequences that may arise from this behavior, but also for the social consequences. This article aims to evaluate national and international data available on non-medical drug-use among medical students and risk factors associated with these problems, as well as social and institutional implications. Prevalence rates, in Brazilian and international samples, of alcohol and drug use, abuse and dependence, reasons for onset, methodological issues, and the role of medical education are presented, compared and discussed. The authors suggest some issues that should be a addressed in order to deal with this complex situation.

The frequency of smoking and problem drinking among general hospital inpatients in Brazil - using the AUDIT and Fagerström questionnaires.

CONTEXT: Although the CAGE questionnaire is one of the most widely used alcohol screening instruments, it has been criticized for not identifying people who are drinking heavily or who have alcohol related problems but do not as yet show symptoms of alcohol dependence. The AUDIT (Alcohol Use Disorder Identification Test) questionnaire was developed by WHO as a screening instrument specifically designed to identify problem drinkers, as well as those who were already dependent on alcohol. OBJECTIVE: The aim of this study was to use the AUDIT and Fagerström questionnaires in a general hospital inpatient population to measure the frequency of problem drinking and nicotine dependence, and to see if levels varied between medical speciality. DESIGN: Retrospective cross-sectional study. SETTING: Federally funded public teaching hospital. SAMPLE: 275 inpatients from both genders. MAIN MEASUREMENTS: Socio-demographic data, AUDIT (Alcohol Use Disorders Identification Test) and Fagerström Test for Nicotine Dependence. RESULTS: We interviewed 275 inpatients, 49% of whom were men and 51% women. Thirty-four patients were identified as "cases" by the Audit questionnaire; 22% of the male patients and 3% of the females. Just over 21% of inpatients were current smokers. The gastroenterology (26%) and general medicine (16%) inpatient units had the largest number of individual cases. CONCLUSIONS: Only by knowing the prevalence of alcohol abuse/dependence and nicotine dependence in a general hospital can we evaluate the need for a specialized liaison service to identify and treat these patients.

[Increase in the search for treatment by crack users in 2 outpatient clinics at the city of Sao Paulo from 1990 to 1993]. / Aumento da procura de tratamento por usuários de crack em dois ambulatórios na cidade de São Paulo, nos anos de 1990 a 1993.

UNLABELLED: An increase in crack use epidemiological research and police data. Currently, in Brazil, no data are available linking the route of administration and attendance to treatment for cocaine dependence. OBJECTIVE: The purpose of this paper was to analyze the changes in cocaine routes of administration in a cocaine dependent population treatment in two outpatient public services (PROAD and UDED). METHOD: Standardized interview data, collected at admission to treatment were compared from 1990 to 1993. The prevalence rates of smoked ("crack"), injected and snorted cocaine were compared. RESULTS: The percentage of patients who reported "crack" cocaine use increased from 17% in 1990 to 64% in 1993 (p < 0.01) The prevalence of snorted cocaine remained stable in the period of time analyzed, being the most frequent route reported. The intravenous route tended to decrease from 40% in 1990 to 28% in 1993. CONCLUSION: The implications of the increase of "crack" cocaine users who sought treatment are discussed. These data are important in planning prevention and treatment strategies, mainly in AIDS prevention.

[Smoking prevalence at the Federal University of São Paulo, 1996--preliminary data of an institutional program]. / Prevalência de tabagismo na Universidade Federal de São Paulo, 1996--dados preliminares de um programa institucional.

PURPOSE: To evaluate the prevalence of tobacco smoking among health workers, professores, nurses and students of Federal University of São Paulo and the acceptance of an institutional program for quitting smoking. METHODS: We analized the answers of a questionnairy with 51 questions, distributed to people from different categories. RESULTS: The total percentage of answered questionnaires was 48.6% (2613). The answers obtained from health workers were 37.3%, professors 49.0%, nurses 52.7% and students 76.5% The total percentage of smokers at UNIFESP was 15.5%:23.7% for health workers, 18% for professors, 16% for nurses and 8.6% for students. There was no significant statistical difference between the prevalence of smoking among females (17.3%) and males (16.3%). The age of major prevalence of smoking was between 31 to 40 years (26.6%). For all ages, people who have university level smoked less, independent of sex. Eighty three percent (83%) of the UNIFESP workers and students are worried of being passive smokers. Between the smokers, 55% were thinking of quiting and 42% declared that need some help to quit. CONCLUSION: We concluded that educational programs and help for cessation at institutional level are necessary and well accepted at UNIFESP, and the completion of these programs will contribute to the obeying of the prohibitive laws of no smoking within the community.

αCaMKII controls the establishment of cocaine's reinforcing effects in mice and humans.

Although addiction develops in a considerable number of regular cocaine users, molecular risk factors for cocaine dependence are still unknown. It was proposed that establishing drug use and memory formation might share molecular and anatomical pathways. Alpha-Ca(2+)/calmodulin-dependent protein kinase-II (αCaMKII) is a key mediator of learning and memory also involved in drug-related plasticity. The autophosphorylation of αCaMKII was shown to accelerate learning. Thus, we investigated the role of αCaMKII autophosphorylation in the time course of establishing cocaine use-related behavior in mice. We found that αCaMKII autophosphorylation-deficient αCaMKII(T286A) mice show delayed establishment of conditioned place preference, but no changes in acute behavioral activation, sensitization or conditioned hyperlocomotion to cocaine (20 mg kg(-1), intraperitoneal). In vivo microdialysis revealed that αCaMKII(T286A) mice have blunted dopamine (DA) and blocked serotonin (5-HT) responses in the nucleus accumbens (NAcc) and prefrontal cortex after acute cocaine administration (20 mg kg(-1), intraperitoneal), whereas noradrenaline responses were preserved. Under cocaine, the attenuated DA and 5-HT activation in αCaMKII(T286A) mice was followed by impaired c-Fos activation in the NAcc. To translate the rodent findings to human conditions, several CAMK2A gene polymorphisms were tested regarding their risk for a fast establishment of cocaine dependence in two independent samples of regular cocaine users from Brazil (n=688) and Switzerland (n=141). A meta-analysis across both samples confirmed that CAMK2A rs3776823 TT-allele carriers display a faster transition to severe cocaine use than C-allele carriers. Together, these data suggest that αCaMKII controls the speed for the establishment of cocaine's reinforcing effects.