bluuebunny/crossref_metadata_2025 huggingface dataset:
Society for Research on Nicotine and Tobacco
Authors: HEISHMAN STEPHEN J. , BALFOUR DAVID J. K. , BENOWITZ NEAL L. , HATSUKAMI DOROTHY K. , LINDSTROM JON M. , OCKENE JUDITH K.
Published: January 2006

The proceedings of the second annual scientific conference of the Society for Research on Nicotine and Tobacco are summarized. The goal of the annual conference was to disseminate information about ongoing nicotine research from biological, behavioral and social perspectives. Data were presented describing our current understanding of the structure and function of neuronal nicotinic acetycholine receptors, by which nicotine exerts most, if not all, of its effects in the brain. The conformational complexity of receptor subunits expressed in different brain areas contributes significantly to the complexity of responses observed to nicotinic agonists. Nicotine is being developed as a medication that might be used to maintain smoking cessation and to treat various medical diseases. The potential toxicity of nicotine, apart from cigarette smoking, is an important variable in assessing the benefits and risks of such therapeutic applications. The risks of nicotine‐containing medications appear to be far less than those associated with tobacco use. Recent data indicate that cigarette smoking is increasing among youth in the United States. Adolescent smokers are interested in quitting and make frequent quit attempts, but are usually not successful. Effective methods are needed to manage adolescent smokers before they become heavily addicted. Nicotine replacement as a pharmacological treatment for smoking cessation has made a significant contribution in improving quit rates. New medications have been developed that target specific populations of smokers.
Assessment of cocaine use with quantitative urinalysis and estimation of new uses
Authors: PRESTON KENZIE L. , SILVERMAN KENNETH , SCHUSTER CHARLES R. , CONE EDWARD J.
Published: January 2006

Qualitative urinalysis methods of monitoring cocaine use may over‐detect frequency of use, possibly decreasing the ability of clinical trials to detect effective treatments. Quantitative urinalysis and newly developed criteria for identifying new cocaine use were evaluated as alternative measures of cocaine use. Urine specimens collected in a cocaine dosing study in non‐treatment‐seeking subjects (n = 5) and a cocaine treatment trial (n = 37) were analyzed for the cocaine metabolite, benzoylecgonine, with qualitative and quantitative methods. Pharmacokinetic criteria (‘New Use’ rules) were applied to quantitative data to identify occasions of new cocaine use. Results were compared to known cocaine administrations in the laboratory study and to self‐reported drug use and qualitative urinalysis for subjects in the clinical trial. New Use criteria correctly identified cocaine administrations in the cocaine dosing study in all but a small number of specimens. In the clinical trial, quantitative urinalysis and estimated New Uses provided more information about patterns and frequency of use than qualitative urinalysis in the different treatment conditions in the clinical trial. Interpretation of quantitative urinalysis with New Use rules appears to be a useful method for monitoring treatment outcome and may be more accurate than traditional qualitative urinalysis in estimating frequency of cocaine use.
Access to alcohol from licensed premises during adolescence: a longitudinal study
Authors: CASSWELL SALLY , ZHANG JIA‐FANG
Published: January 2006

Control of young people's access to alcohol via licensed premises has been shown to be an effective alcohol harm reduction strategy in the United States. In a longitudinal study of young New Zealanders their access to alcohol at the ages of 15 and 18 years was shown to be significantly predictive of the quantities of alcohol they consumed during a drinking occasion both then and in subsequent years. In turn the quantities of alcohol consumed were predictive of the respondents' experience of intoxication related adverse consequences. The impact of access via licensed premises on drinking and related problems was greater in this cohort of young people than the impact of peer or parental influences.
Prescribing amphetamines to drug misusers: data from the 1995 national survey of community pharmacies in England and Wales
Authors: STRANG JOHN , SHERIDAN JANIE
Published: January 2006

Results from the 1995 survey of community pharmacy services for drug misusers provide data on 177 amphetamine prescriptions dispensed by pharmacists; this extrapolates to an estimated 900‐1000 patients receiving amphetamine for the treatment of addiction in England and Wales, at any one time. Seventy‐three per cent and 24% of prescriptions were for dexamphetamine tablets and oral liquid, respectively, and 3% for injectables amphetamines. Fifty‐seven per cent of prescriptions were from doctors working in hospital/clinics and 92% in NHS practice. Hospital/clinic‐based prescribes tended to prescribe lower daily doses and were more likely to instruct daily pickups than general practitioners, as did those in NHS compared with private practice. Major regional variations were noted in the overall distribution of prescriptions and for the different dosage forms. In conclusion, we find that there is a disturbing lack of consistency nationally and a lack of safeguards against diversion into the black market.
The Self‐Rating of the Effects of Alcohol (SRE) form as a retrospective measure of the risk for alcoholism
Authors: SCHUCKIT MARC A. , SMITH TOM L. , TIPP JAYSON E.
Published: January 2006

Aims. A low level of response (LR) to alcohol is a characteristic of sons of alcoholics and predicts an elevated future alcoholism risk. A 12‐question Self‐Rating of the Effects (SRE) of alcohol form has been shown to correlate cross‐sectionally with a designation of a low LR determined by alcohol challenges. Design. his study evaluates the potential usefulness of the SRE as a retrospective measure of both the response to alcohol and of subsequent alcoholism in two samples. Setting. All subjects were studied in the United States, most in California. Participants. First, 94 sons of alcoholics and controls completed the SRE 15 years after an alcohol challenge, and SRE values were compared to their prior LR results and their alcoholic outcomes. Secondly, the relationship between SRE results and alcoholic status was determined in 551 men and women alcoholics, their relatives, and controls. Measurements. Subjects were evaluated with face‐to‐face interviews. Findings. Despite the interval of 15 years, the correlation between the SRE and the subjective high feelings on the alcohol challenge was between ‐0.3 and ‐0.4. For those 94 subjects the full SRE correlated with a diagnosis of alcohol dependence at 0.5, a figure that remained at 0.3 even when only the estimates related to the earliest drinking experiences were considered. For the 551 men and women, the correlation between the SRE and alcohol dependence diagnoses was 0.6, including 0.3 for the estimates of the first five times of drinking. All major findings in both samples remained robust when the recent drinking history or the number of items endorsed was considered, or when the most severe alcohol problem, passing out, was deleted from the analysis. Conclusions. When alcohol challenges are not possible, these retrospective reports indicate that the SRE is a potentially useful surrogate for determining a subgroup of people who might carry a low level of response to alcohol and a subsequent elevated risk for alcoholism.
An evaluation of the effectiveness of alcohol treatment, driver license actions and jail terms in reducing drunk driving recidivism in California
Authors: DEYOUNG DAVID J.
Published: January 2006

Aim. There has been long‐standing interest in determining which sanctions work best to reduce drunk driving. This study examines the effectiveness of alcohol treatment, driver license actions and jail terms in reducing drunk‐driving recidivism. Design. This quasi‐experimental study examines the relationships between the sanctions that drivers convicted of driving‐under‐the‐influence (GUI) receive and their subsequent reconviction of DUI, while statistically controlling for pre‐existing differences among groups receiving different sanctums. Separate analyses were conducted for subjects having 0, 1 or 2 or more prior DUI convictions on their driving record. Setting. The study analyzes drunk driving reacidivism throughout the state of California. Participants. All drivers holding a California driver license who were convicted of DUI by a California court during 1990 and 1991 were selected for inclusion in the study. Measurements. A number of demographic, prior personal driving history and surrogate traffic environment measures were collected and used as covariates in the analyses. Data were also gathered on subsequent DUI reconvictions, and the number of days to first subsequent DUI reconviction, and used as outcome variables in the study. Findings. Results of the analyses showed that for all levels of prior DUI convictions, combining alcohol treatment with either driver license restriction or suspension is associated with the lowest DUI recidivism rates. Conclusions. Based on this research, and the results of prior studies, it can be persuasively argued that combining license actions with alcohol treatment represents the most effective sanction combination for combating DUI recidivism.
Methadone maintenance and hepatitis C virus infection among injecting drug users
Authors: CROFTS NICK , NIGRO LUCIANO , OMAN KIMBERLEY , STEVENSON ELAINE , SHERMAN JOHN
Published: January 2006

Harm reduction strategies for the prevention of transmission of human immunodeficiency virus (HIV) transmission among injecting drug users (IDUs) have been widely implemented in Australia and are seen to have been effective in preventing the spread of HIV. A major strategy has been increasing the availability of and accessibility to methadone maintenance therapy (MMT) programmes. We have reviewed the experience of a major MMT general practice with hepatitis C virus (HCV) infection from 1991 to 1995. Of 1741 individuals tested for HCV antibodies at least once 66.7% were positive. Of 73 IDUs who were initially seronegative and were retested at least once, 19 were subsequently seropositive. Seroconverters to HCV were younger than non‐seroconverters, and were more likely to have evidence of previous hepatitis B infection. The overall HCV incidence rate was 22 cases per 100 person‐years, and this did not differ between those on MMT programs (continuous or interrupted) between HCV tests and those not on MMT. These findings suggest that the role of MMT in the control of the spread of HCV infection among IDUs needs further assessment, and that control of the current epidemic of HCV infection among IDUs in Australia will be very difficult.
The effect of drinking and driving interventions on alcohol‐involved traffic crashes within a comprehensive community trial
Authors: VOAS ROBERT B. , HOLDER HAROLD D. , GRUENEWALD PAUL J.
Published: January 2006

The Drinking and Driving Component, one of five elements of the Community Trials Project, involved the implementation of a special drink driving countermeasure in the three experimental communities, one in Northern California, one in Southern California and another in South Carolina. This intensified enforcement of driving under the influence (DUI) was designed to deter potential drinking drivers by increasing their perception of the risk of being arrested leading to a reduction in the consumption of alcohol before driving. See component detailed description in Voas (1997, this issue). The evaluation found that media advocacy training and technical assistance resulted in increased DUI news coverage and that additional police officer hours for DUI enforcement, greater use of breathalyzer equipment, increased officer training and more checkpoints produced increased DUI enforcement. The combined effects of increased DUI news coverage and DUI enforcement yielded increased public perceived risk of arrest and subsequently less drinking and driving. Overall the evaluation found that alcohol‐involved traffic crashes were reduced as a result of this component in the experimental communities as contrasted with the matched comparison communities.
Summing up: lessons from a comprehensive community prevention trial
Authors: HOLDER HAROLD D. , SALTZ ROBERT F. , GRUBE JOEL W. , TRENO ANDREW J. , REYNOLDS ROBERT I. , VOAS ROBERT B. , GRUENEWALD PAUL J.
Published: January 2006

This paper presents the findings and lessons from a community prevention trial involving three experimental communities in the United States to reduce alcohol‐involved trauma. The paper provides recommendations for other community prevention efforts. Effectiveness was demonstrated by: (a) 78 fewer alcohol‐involved traffic crashes as a result of the Drinking and Driving Component alone (approximately a 10% reduction); (b) a significant reduction in underage sales of alcohol, i.e. off‐premise outlets sold to minors about one‐half as often as in comparison communities; (c) increased implementation of responsible beverage service policies by bars and restaurants; and (d) increased adoption of local ordinances and regulations to reduce concentrations of alcohol outlets.
End‐of‐treatment self‐efficacy: a predictor of abstinence
Authors: GOLDBECK RAINER , MYATT PAUL , AITCHISON TOM
Published: January 2006

Results of previous studies suggest that end‐of‐treatment self‐efficacy in problem drinkers has limited predictive validity. One explanation for this finding has been the postulated existence of a ceiling effect, i.e. the possibility that subjects who rate themselves highly in terms of self‐efficacy form a heterogeneous group with some subjects making inflated self‐efficacy judgements based on an over‐optimistic perception of their coping abilities. In the present study, end‐of‐treatment self‐efficacy in 63 problem drinkers, as measured by the Situational Confidence Questionnaire and a newly designed Self‐Efficacy Questionnaire (SEQ), was predictive of abstinence status at 3 month follow‐up. In those patients who on the SEQ had expressed great confidence in their ability to remain abstinent over the follow‐up period, the additional consideration of keyworkers' confidence in their patients' ability to remain abstinent as well as patients' anticipated need for future help improved the prediction of abstinence status. These results are discussed with respect to the postulated ceiling effect. A prognostic tree using just three baseline variables predicted abstinence status correctly in 88% of all cases.
The efficacy of disulfiram: a review of outcome studies
Authors: HUGHES JULIAN C. , COOK CHRISTOPHER C. H.
Published: January 2006

Twenty‐four studies of outcome following oral disulfiram and 14 following implanted disulfiram were identified for review from MEDLINE and PsycINFO databases and by manual searching for the period 1967–95. The methodological rigour of these studies teas generally poor, albeit not as poor as that of earlier studies (not reviewed here). An overall assessment of the results of research in this field is hampered by the diversify of both the methods used and the subject populations studied. However, it is dear that support for the general use of oral disulfiram is equivocal, mostly being found in the form of reduced quantity of alcohol consumed and a reduced number of drinking days. Evidence for an effect in increasing the proportion of patients who achieve abstinence is surprisingly lacking. Where it is prescribed, disulfiram use should be supervised and it should be employed as one pan of a comprehensive treatment programme. There is no good evidence in favour of implanting disulfiram tablets, but the possibility of a depot injection is intriguing.
Drug abusers in Danish mental hospitals
Authors: HANSEN SØREN SØBERG
Published: January 2006

The purpose of this study was to investigate trends in drug abuse among psychiatric inpatients in Denmark. The investigation was based on data collected from The Danish Psychiatric Case Register. The findings show that drug abusers occupy an increasing number of beds in Danish psychiatric hospitals and departments. Moreover, an increase in the number of patients with schizophrenic or borderline diagnoses combined with drug abuse was found. Furthermore, the drug abuse found among psychiatric patients now is frequently more serious than previously. Finally, an increased number of young males admitted with drug abuse was discovered. Young males are also more frequently diagnosed as illegal, or polydrug abusers, as opposed 10 older males and females.
Alcohol, the individual and society: what history teaches us
Authors: ROOM ROBIN
Published: January 2006

Drinkers derive both pleasure and pain from drinking, but harm may come also to others. Through religious or secular rules, societies have sought to limit these “externalities” of drinking. Societal reactions have primarily focused on social harms from drinking; policy attention to casualties and chronic health effects is fairly recent. Drinking behaviour varies greatly according to the cultural framing of alcohol; societal policies tend to vary accordingly. Ecological constraints and social norms on preparation and use meant that alcohol was often available only sporadically in tribal and village societies. Alcohol production has been increasingly industrialized and marketing increasingly globalized in the modem era. Now, free trade agreements and the doctrine of consumer sovereignty increasingly limit the scope of national alcohol control policies. On the other hand, modem society demands exacting standards of attention and care incompatible with intoxication, for instance when driving a car or minding children. Managing the conflict between these and alcohol's ready availability is seen as a wholly individual rather than a societal responsibility. Those who fail the task are defined as alcoholics, and modem states have increasingly provided treatment for them. While there is a renewed public health concern about the externalities of drinking, substantial availability reductions have historically often required the mobilization of strong popular movements of remoralization.
Trends in alcohol production, trade and consumption
Authors: WALSH BRENDAN
Published: January 2006

This paper is a survey of the structure and significance of international trade in alcoholic beverages in the contemporary world economy. It presents data on the level of trade in the main alcoholic beverages for the period since 1970. The constant‐dollar value of this trade grew by a factor of 2.1 between 1975 and 1992. It represents approximately one half of the one per cent of the value of world trade in all commodities. This proportion has remained very stable over the past 20 years. International trade in beer, wine and spirits has greatly extended the range of alcoholic beverages available around the world and reduced their cost. It has played a large part in the tendency for convergence in the patterns of alcohol consumption, as countries diversify away from their dependence on locally produced beverages. Traditional spirits‐drinking and beer‐drinking countries have witnessed very rapid increases in the consumption of wine, while heavy wine drinking countries have seen rapid growth of the consumption of beer. While imported beverages remain relatively unimportant in total consumption of alcoholic beverages, they have played a significant role in the growth and diversification of alcohol consumption in many countries.
Population level policies on alcohol: are they still appropriate given that ‘alcohol is good for the heart’?
Authors: CASSWELL SALLY
Published: January 2006

The research finding that a reduced risk of coronary heart disease is associated with alcohol use has been widely disseminated. This paper addresses the significance of this research finding for decisions about what kind of alcohol harm reduction policies it is appropriate to implement. The public policies of greatest concern to the vested interest groups are population‐based policies such as taxation and restrictions on availability. Other public policies which impact on the drinkers' environment are minimum drinking age laws, drink drive deterrence, prevention of intoxication in public drinking places and restrictions on advertising. A review of the effectiveness of the available strategies provided strong support for environmentally focused approaches rather than education targeting high‐risk drinkers. Many of these environmental strategies seem unlikely to have significant direct effect of reducing ‘heart healthy’ drinking by older people. Furthermore, the impact of alcohol on premature mortality among the older sectors of the population has to be weighed against any possible impact on younger drinkers resulting in loss of or disability in many years of life. Given the relative effectiveness of environmental strategies for reducing harm and the likely low level of impact of these strategies on the heart healthy drinking of older people it is concluded that the evidence of reduced risk of coronary heart disease does not preclude their implementation.
Gamma‐hydroxybutyrate: an emerging drug of abuse that causes physical dependence
Authors: GALLOWAY GANTT P. , FREDERICK S. L. , STAGGERS FRANK E. , GONZALES MARCO , STALCUP S. ALEX , SMITH DAVID E.
Published: January 2006

Gamma‐hydroxybutyrate (GHB) is a compound found in mammalian brain which meets many criteria of a neurotransmitter. GHB has been investigated as a Tool for inducing absence (petit mal) seizures, for use as an anesthetic, and for treatment of narcolepsy, alcohol dependence and opiate dependence. Since 1990 GHB has been abused in the United States for euphoric, sedative and anabolic effects. Coma and seizures have been reported following abuse of GHB, but dependence liability has received little attention. The neuropharmacology, potential therapeutic uses and acute adverse effects of GHB are reviewed, followed by a case series of eight people using GHB. Adverse effects of GHB may include prolonged abuse, seizure activity and a withdrawal syndrome. This withdrawal syndrome includes insomnia, anxiety and tremor; withdrawal symptoms resolve in 3‐12 days. GHB has the potential to cause a significant incidence of abuse and adverse effects. Prolonged use of high doses may lead to a withdrawal syndrome, which resolves without sequelae. Educational efforts should address the narrow therapeutic index, possible physical dependence and dangers of combining GHB with other drugs of abuse.
Decreased nociceptive sensitivity: a biological risk marker for opiate dependence?
Authors: LEHOFER MICHAEL , LIEBMANN PETER M. , MOSER MAXIMILIAN , LEGL THOMAS , PERNHAUPT GÜNTER , SCHAUENSTEIN KONRAD , ZAPOTOCZKY HANS GEORG
Published: January 2006

In recent studies using a cold pressor tea we could show that former opiate addicts are persistently less pain‐sensitive than healthy controls, indicating a neurophysiologic dysfunction in these patients. In the present study we addressed the issue of whether this dysfunction was caused by the drug abuse or already existed prior to the heroin addiction, and whether it ii restricted to pain sensitivity or affects somatosensory or nociceptive sensitivity in general. After validating the method we obtained retrospective ratings for the pain, cold and warmth sensitivity for the time before addiction, during addiction and during detoxification. Ex‐addicts perceive themselves less pain‐ and cold‐sensitive than healthy controls, and no difference was detectable between the pre‐addiction and the rehabilitation ratings, although nociceptive sensitivity is highly increased during detoxification. Warmth sensitivity was not different to healthy controls and was not affected by drug withdrawal. Our findings suggest that a decreased nociceptive sensitivity may already precede opiate addiction pointing to physiological dysfunctions in heroin pre‐addicts.
Ethics of alcohol policy in a saturated society
Authors: Sulkunen Pekka
Published: January 2006

Alcohol policy in modern society has been embedded in three of its great ideals: progress, individualistic universalism and nationalism. The total consumption theory and the idea of the public good have been the culmination of modern thinking in the prevention of alcohol problems. The modern ideals have today become achieved. Saturated modernity has led from a political society to a mass society, in which modern sociological theories are powerless, and ethical reflection is required. Two contradicting moral resources offer themselves: the ethics of the rule and the culture of authenticity. The modernist idea of the public good is related to the ethics of the rule but its viability is questioned. The Durkheimian idea that ethical decisions are inherently social is suggested as a solution.
Setting goals for drug policy: harm or use reduction? reduction
Authors: Caulkins Jonathan P. , Reuter Peter
Published: January 2006

Historically, United States drug policy has focused on use reduction; harm reduction is a prominent alternative. This paper aims to provoke and inform more debate about the relative merits of these two. Since harm is not necessarily proportional to use, use reduction and harm reduction differ. Both terms are somewhat ambiguous; precisely defining them clarifies thinking and policy implications. Measures associated with use reduction goals are poor; those associated with harm reduction are even worse. National goals influence the many decentralized individuals who collectively make drug policy; clearly enunciating goals makes some policy choices transparent and goals serve a variety of purposes besides guiding programmatic decisions. We recommend that the overall objective be to minimize the total harm associated with drug production, distribution, consumption and control. Reducing use should be seen as a principal means of attaining that end.
Unintended consequences and professional ethics: criminalization of alcohol and tobacco use by youth and young adults
Authors: Wolfson Mark , Hourigan Mary
Published: January 2006

This paper describes how widespread legal changes appear to have affected law enforcement practices concerning youth tobacco and alcohol use in the United States. We argue that the threat of criminalization was seldom addressed in scientific and public policy discussions of the drinking age, and only sporadically addressed in discussions of measures to regulate youth access to tobacco. We argue that unintended consequences are an important ethical issue for professionals involved in advocating, developing, implementing and evaluating public policy concerning substance abuse.
Responsibility for crime and injury when drunk
Authors: Bergman Bo
Published: January 2006

The aim of this paper is to highlight the complexity in the connection between alcohol intoxication and responsibility for crime from a multidisciplinary approach comprising medical, legal and criminological perspectives. There is no doubt that there is a connection between violent behaviour and alcohol intoxication. However, several investigations show that alcohol heightens aggressiveness only when the drunken person is provoked. A case which may serve as a model when discussing legal responsibility for acts carried out when drunk is outlined. Ethical considerations are discussed and exemplified concerning the motive, as well as the principles, of punishing an intoxicated perpetrator. However, there are no definite solutions concerning what is right or wrong, and each reader will have his own opinion, which may well differ from that of the author.
Rates and predictors of relapse after natural and treated remission from alcohol use disorders
Authors: Moos Rudolf H. , Moos Bernice S.
Published: January 2006

Aims  This study examined the rates and predictors of 3‐year remission, and subsequent 16‐year relapse, among initially untreated individuals with alcohol use disorders who did not obtain help or who participated in treatment and/or Alcoholics Anonymous in the first year after recognizing their need for help.

Design and measures  A sample of individuals (n = 461) who initiated help‐seeking was surveyed at baseline and 1 year, 3 years, 8 years and 16 years later. Participants provided information on their life history of drinking, alcohol‐related functioning and life context and coping.

Findings  Compared to individuals who obtained help, those who did not were less likely to achieve 3‐year remission and subsequently were more likely to relapse. Less alcohol consumption and fewer drinking problems, more self‐efficacy and less reliance on avoidance coping at baseline predicted 3‐year remission; this was especially true of individuals who remitted without help. Among individuals who were remitted at 3 years, those who consumed more alcohol but were less likely to see their drinking as a significant problem, had less self‐efficacy, and relied more on avoidance coping, were more likely to relapse by 16 years. These findings held for individuals who initially obtained help and for those who did not.

Conclusions  Natural remission may be followed by a high likelihood of relapse; thus, preventive interventions may be indicated to forestall future alcohol problems among individuals who cut down temporarily on drinking on their own.
Prevalence of HIV, hepatitis C and syphilis among injecting drug users in Russia: a multi‐city study
Authors: Rhodes Tim , Platt Lucy , Maximova Svetlana , Koshkina Evgeniya , Latishevskaya Natalia , Hickman Matthew , Renton Adrian , Bobrova Natalia , McDonald Tamara , Parry John V.
Published: January 2006

Objectives  To estimate the prevalence of HIV, hepatitis C virus (HCV) and syphilis in injecting drug users (IDUs) in Russia.

Methods  Unlinked anonymous cross‐sectional survey of 1473 IDUs recruited from non‐treatment settings in Moscow, Volgograd and Barnaul (Siberia), with oral fluid sample collection for HIV, HCV antibody (anti‐HIV, anti‐HCV) and syphilis testing.

Results  Prevalence of antibody to HIV was 14% in Moscow, 3% in Volgograd and 9% in Barnaul. HCV prevalence was 67% in Moscow, 70% in Volgograd and 54% in Barnaul. Prevalence of positive syphilis serology was 8% in Moscow, 20% in Volgograd and 6% in Barnaul. Half of those HIV positive and a third of those HCV positive were unaware of their positive status. Common risk factors associated with HIV and HCV infection across the cities included both direct and indirect sharing of injecting equipment and injection of home‐produced drugs. Among environmental risk factors, we found increased odds of anti‐HIV associated with being in prison in Moscow, and some association between official registration as a drug user and anti‐HIV and anti‐HCV. No associations were found between sexual risk behaviours and anti‐HIV in any city.

Conclusions  HIV prevalence among IDUs was markedly higher than city routine surveillance data suggests and at potentially critical levels in terms of HIV prevention in two cities. HCV prevalence was high in all cities. Syphilis prevalence highlights the potential for sexual risk and sexual HIV transmission. Despite large‐scale testing programmes, knowledge of positive status was poor. The scaling‐up of harm reduction for IDUs in Russia, including sexual risk reduction, is an urgent priority.
Long‐term follow‐up of chronic hepatitis C patients with sustained virological response to various forms of interferon‐based anti‐viral therapy
Authors: FORMANN E. , STEINDL‐MUNDA P. , HOFER H. , JESSNER W. , BERGHOLZ U. , GURGUTA C. , FERENCI P.
Published: January 2006

Background  Combination anti‐viral therapy achieves a sustained virological response (defined as HCV‐RNA negativity 6 months after the end of therapy) of 56% of patients with chronic hepatitis C. Little is known about long‐term durability of HCV‐RNA negativity in patient treated with pegylated interferon.

Aim To evaluate the durability of virologic response in patients with sustained virological response to anti‐viral therapy treated at our centre.

Methods  A total of 187 sustained virological responses (50% genotype 1, 42% genotype 2 or 3 and 8% genotype 4; 20% with cirrhosis) with a follow‐up of >12 months post‐therapy were studied. Twelve patients received monotherapy with interferon‐alpha2a or −2b. One hundred and seventy‐five received combination therapy with ribavirin and standard interferon‐alpha (n = 73) or pegylated interferon‐alpha2a or 2b (n = 102). Qualitative serum HCV‐RNA was tested by COBAS AMPLICOR HCV test, v2.0.

Results  Median follow‐up time was 29 months (range 12–172). Recurrence of HCV infection was not observed in any of the 187 sustained virological responders. Alanine aminotransferase values were normal in 90% and two patients showed minimal elevation of alpha‐fetoprotein levels.

Conclusions  No recurrence of HCV infection was seen in any patient. Thus, long‐term prognosis in chronic hepatitis C patients with a sustained virological response to therapy with pegylated interferon ± ribavirin is promising, but long‐term studies need to continue.
Review article: infliximab therapy for inflammatory bowel disease – seven years on
Authors: RUTGEERTS P. , VAN ASSCHE G. , VERMEIRE S.
Published: January 2006

Infliximab, the chimeric monoclonal IgG1 antibody to tumour necrosis factor, is indicated for refractory luminal and fistulizing Crohn's disease and extra‐intestinal manifestations of inflammatory bowel disease. Recently, the active ulcerative colitis trials (ACT) studies have shown that infliximab is also efficacious to treat ulcerative colitis resistant to standard therapy. Induction with 5 mg/kg infliximab at weeks 0, 2 and 6 is advocated.

The response to infliximab is improved when concomitant immunosuppressive therapy is given. As the majority of patients will relapse if not retreated, a long‐term strategy is necessary. Although episodic therapy can be used, the optimal strategy is systematic maintenance treatment with 5 mg/kg intravenous (i.v.) every 8 weeks. Long‐term maintenance therapy with infliximab results in a reduction of the rate of complications, hospitalizations and surgeries associated with Crohn's disease.

Safety problems with the monoclonal antibody infliximab treatment mainly concern the formation of antibodies to infliximab, which may lead to infusion reactions, loss of response and serum sickness‐like delayed infusion reactions. Latent tuberculosis needs to be screened for. The rate of other opportunistic infections is slightly increased mainly in patients treated concomitantly with immunosuppression. There is no evidence that malignancy rates in patients treated with antitumour necrosis factor strategies are increased.
Construction of a medium‐density horse gene map
Authors: Perrocheau M. , Boutreux V. , Chadi S. , Mata X. , Decaunes P. , Raudsepp T. , Durkin K. , Incarnato D. , Iannuzzi L. , Lear T. L. , Hirota K. , Hasegawa T. , Zhu B. , de Jong P. , Cribiu E. P. , Chowdhary B. P. , Guérin G.
Published: January 2006

A medium‐density map of the horse genome (Equus caballus) was constructed using genes evenly distributed over the human genome. Three hundred and twenty‐three exonic primer pairs were used to screen the INRA and the CHORI‐241 equine BAC libraries by polymerase chain reaction and by filter hybridization respectively. Two hundred and thirty‐seven BACs containing equine gene orthologues, confirmed by sequencing, were isolated. The BACs were localized to horse chromosomes by fluorescent in situ hybridization (FISH). Overall, 165 genes were assigned to the equine genomic map by radiation hybrid (RH) (using an equine RH5000 panel) and/or by FISH mapping. A comparison of localizations of 713 genes mapped on the horse genome and on the human genome revealed 59 homologous segments and 131 conserved segments. Two of these homologies (ECA27/HSA8 and ECA12p/HSA11p) had not been previously identified. An enhanced resolution of conserved and rearranged chromosomal segments presented in this study provides clarification of chromosome evolution history.
Albinism in the domestic cat (Felis catus) is associated with a tyrosinase (TYR) mutation
Authors: Imes D. L. , Geary L. A. , Grahn R. A. , Lyons L. A.
Published: January 2006

Albino phenotypes are documented in a variety of species including the domestic cat. As albino phenotypes in other species are associated with tyrosinase (TYR) mutations, TYR was proposed as a candidate gene for albinism in cats. An Oriental and Colourpoint Shorthair cat pedigree segregating for albinism was analysed for association with TYR by linkage and sequence analyses. Microsatellite FCA931, which is closely linked to TYR and TYR sequence variants were tested for segregation with the albinism phenotype. Sequence analysis of genomic DNA from wild‐type and albino cats identified a cytosine deletion in TYR at position 975 in exon 2, which causes a frame shift resulting in a premature stop codon nine residues downstream from the mutation. The deletion mutation in TYR and an allele of FCA931 segregated concordantly with the albino phenotype. Taken together, our results suggest that the TYR gene corresponds to the colour locus in cats and its alleles, from dominant to recessive, are as follows: C (full colour) > cb (burmese)  cs (siamese) > c (albino).
QT interval prolongation associated with sibutramine treatment
Authors: Harrison‐Woolrych Mira , Clark David W. J. , Hill Geraldine R. , Rees Mark I. , Skinner Jonathan R.
Published: January 2006

Aims

To investigate a possible association of sibutramine with QT interval prolongation.

Methods

Post‐marketing surveillance using prescription event monitoring in the New Zealand Intensive Medicines Monitoring Programme (IMMP) identified a case of QT prolongation and associated cardiac arrest in a patient taking sibutramine for 25 days. This patient was further investigated, including genotyping for long QT syndrome. Other IMMP case reports suggesting arrhythmias associated with sibutramine were assessed and further reports were obtained from the World Health Organisation (WHO) adverse drug reactions database.

Results

The index case displayed a novel mutation in a cardiac potassium channel subunit gene,KCNQ1, which is likely to prolong cardiac membrane depolarization and increase susceptibility to long QT intervals. Assessment of further IMMP reports identified five additional patients who experienced palpitations associated with syncope or presyncopal symptoms, one of whom had a QTcat the upper limit of normal. Assessment of reports from the WHO database identified three reports of QT prolongation and one fatal case of torsade de pointes in a patient also taking cisapride.

Conclusions

This case series suggests that sibutramine may be associated with QT prolongation and related dysrhythmias. Further studies are required, but in the meantime we would recommend that sibutramine should be avoided in patients with long QT syndrome and in patients taking other medicines that may prolong the QT interval.
Simvastatin does not influence the intestinal P‐glycoprotein and MPR2, and the disposition of talinolol after chronic medication in healthy subjects genotyped for the ABCB1, ABCC2 and SLCO1B1 polymorphisms
Authors: Bernsdorf Annika , Giessmann Thomas , Modess Christiane , Wegner Danilo , Igelbrink Stefanie , Hecker Ute , Haenisch Sierk , Cascorbi Ingolf , Terhaag Bernd , Siegmund Werner
Published: January 2006

Aims

To evaluate whether simvastatin influences (i) the intestinal expression of P‐glycoprotein (P‐gp) and MRP2, and (ii) the disposition of the β1‐selective blocker talinolol, a substrate of these transporter proteins.

Methods

The disposition of talinolol after intravenous (30 mg) and single or repeated oral administration (100 mg daily) was monitored before and after chronic treatment with simvastatin (40 mg daily) in 18 healthy subjects (10 males, eight females, body mass index 19.0–27.0 kg m−2) genotyped for ABCB1, ABCC2 and SLCO1B1 polymorphisms. The steady‐state pharmacokinetics of simvastatin was evaluated before and after repeated oral talinolol administration. The duodenal expression of ABCB1 and ABCC2 mRNA before and after simvastatin treatment was quantified using real‐time reverse transcriptase‐polymerase chain reaction (TaqMan®).

Results

Simvastatin did not influence the expression of duodenal ABCB1 and ABCC2. There was no significant pharmacokinetic interaction between simvastatin and talinolol. Duodenal ABCB1 mRNA content was significantly correlated with the AUC0–∞ (r = 0.627, P = 0.039) and Cmax (r = 0.718, P = 0.013) of oral talinolol. The ABCB1 and ABCC2 gene polymorphisms did not influence simvastatin and talinolol disposition. The half‐life of the latter was significantly shorter in the nine carriers with a SLCO1B1*1b allele compared with the seven subjects with the wild‐type SLCO1B1*1a/*1a genotype (12.2 ± 1.6 h vs. 14.5 ± 1.4 h, P = 0.01).

Conclusions

Simvastatin does not influence the intestinal expression of P‐gp and MRP2 in man. There was no pharmacokinetic interaction between talinolol and simvastatin during their chronic co‐administration to healthy subjects.
Low‐molecular weight and unfractionated heparins induce a downregulation of inflammation: decreased levels of proinflammatory cytokines and nuclear factor‐κB in LPS‐stimulated human monocytes
Authors: Hochart Hélène , Vincent Jenkins P. , Smith Owen P. , White Barry
Published: January 2006

Unfractionated heparin (UFH) and low‐molecular weight heparin (LMWH) are well defined anticoagulant agents. Recent data suggest that both LMWH and UFH may also have potent anti‐inflammatory properties; however, their mechanism of action responsible for the anti‐inflammatory effect is not yet fully elucidated. This study was designed to assess the effect of LMWH and UFH on human monocytes production of inflammatory markers and nuclear translocation of nuclear factor (NF)‐κB. Cultured monocytes were pretreated for 15 min with LMWH or UFH (10 μg and 1 μg/million cells) before stimulation with lipopolysaccharide (LPS) at a dose of 1 ng/million cells. Proinflammatory cytokines tumour necrosis factor (TNF)‐α, interleukin (IL)‐8, IL‐6 and IL‐1β release were subsequently measured by enzyme‐linked immunosorbent assay at 6 h, and nuclear translocation of the proinflammatory NF‐κB was assessed at 2 h. Treatment with pharmacological doses of LMWH and UFH significantly attenuated LPS‐induced production of TNF‐α, IL‐8, IL‐6 and IL‐1β as well as NF‐κB translocation. These results indicate equivalent and significant heparin anti‐inflammatory properties at low doses on monocyte‐mediated immune response. The inhibition of NF‐κB activation certainly represents one of the mechanisms by which heparin exerts its anti‐inflammatory effect. LMWH and UFH therefore appear as potential therapeutic inhibitors of inflammation.
Serum levels of osteoprotegerin and osteoprotegerin polymorphisms in Gaucher disease
Authors: Magal Itai , Lebel Ehud , Altarescu Gheona , Itzchaki Menachem , Rudensky Bernard , Joseph Foldes A. , Zimran Ari , Elstein Deborah
Published: January 2006

Bone involvement in Gaucher disease causes disability and reduced quality of life; loss of function and pain are important indications for enzyme replacement therapy. The purpose of this study was to ascertain whether osteoprotegerin (OPG), which decreases osteoclast activity, is indicative of incipient bone involvement by comparing OPG serum levels to Gaucher disease severity (SSI) and bone mineral density (BMD), and to correlate bone and disease markers to OPG polymorphisms: OPG1‐2(A163G), OPG3‐4(T129C) and OPG5‐6(C1217T). Of 554 patients, 173 Ashkenazi Jewish patients with non‐neuronopathic Gaucher disease were enrolled and 32 healthy Ashkenazi Jews served as controls. Serum OPG levels were detected by enzyme‐linked immunosorbent assay and BMD was obtained by dual X‐ray absorptiometry. OPG polymorphisms were determined in 63 randomly chosen patients. Serum OPG values for patients were not greater than in controls, but showed a statistically significant trend to increase with age (P = 0·057). No correlation existed between OPG levels and BMD or with genotype or other disease markers. A significant correlation was noted between OPG5‐6 genotype and SSI. A significant difference was found between the allele distributions of each OPG polymorphism when compared with Caucasians and Ashkenazi Jews. OPG levels probably do not predict BMD in Gaucher disease and hence are not indicative of osteoporosis in Gaucher disease.
Evaluation of allergenicity of genetically modified soybean protein extract in a murine model of oral allergen‐specific sensitization
Authors: Gizzarelli F. , Corinti S. , Barletta B. , Iacovacci P. , Brunetto B. , Butteroni C. , Afferni C. , Onori R. , Miraglia M. , Panzini G. , Di Felice G. , Tinghino R.
Published: January 2006

Background
With the development of genetically modified crop plants there has been a growing interest in the approaches available to assess the potential allergenicity of novel gene products. For additional assessment of the potential allergenicity of expressed proteins, informative data can be generated using animal models. Soybean is one of the major source of protein in human and animal nutrition, and has also been well characterized as a major allergenic source. Advances in biotechnology have resulted in an increasing number of genetically engineered foods, and among these soybean is one of the most widespread.

Objective
To develop and characterize a murine model of IgE‐mediated soybean sensitization induced by intragastric immunization, in the presence of Cholera Toxin, with wild‐type soybean extract (wt‐SE) or with genetically modified soybean extract (gm‐SE).

Methods
Balb/c mice born in our animal facilities, from females fed on soy‐free food, were fed with the same soy‐free food and used in all the experiments. Mice were sensitized by gavages with soybean extracts, and allergen‐specific IgE and IgG responses were studied by direct ELISA and ELISA inhibition. Antigen‐specific cell proliferation and cytokine production were evaluated in spleen cell cultures.

Results
Sensitization with both soybean extracts induced high levels of antigen‐specific IgE and IgG1 and low levels of specific IgG2a. Both wt‐SE and gm‐SE were able to inhibit the binding of specific IgE from mice immunized with gm‐SE to the same antigen used for the ELISA coating. A comparable proliferative response was obtained with the homologous as well as with the heterologous extracts.

Conclusion
In sensitized mice, we observed a predominantly T‐helper type 2 (Th2)‐type immune response, with increased soybean‐specific IgE and IgG1 antibodies and a concomitant increase of IL‐4 and IL‐5 production. Results obtained by specific IgE ELISA inhibition and by antigen‐specific T cell proliferation demonstrated that wt‐SE and gm‐SE shared B and T epitopes. The present murine model of soybean sensitization established by the oral route should provide valuable information about risk assessment for food allergy from new proteins of genetically modified foods.