bluuebunny/crossref_metadata_2025 huggingface dataset:
Dimeric cystic fibrosis transmembrane conductance regulator exists in the plasma membrane
Authors: RAMJEESINGH Mohabir , KIDD Jackie F. , HUAN Ling Jun , WANG Yanchun , BEAR Christine E.
Published: September 2003

CFTR (cystic fibrosis transmembrane conductance regulator) mediates chloride conduction across the apical membrane of epithelia, and mutations in CFTR lead to defective epithelial fluid transport. Recently, there has been considerable interest in determining the quaternary structure of CFTR at the cell surface, as such information is a key to understand the molecular basis for pathogenesis in patients harbouring disease-causing mutations. In our previous work [Ramjeesingh, Li, Kogan, Wang, Huan and Bear (2001) Biochemistry 40, 10700–10706], we showed that monomeric CFTR is the minimal functional form of the protein, yet when expressed in Sf 9 cells using the baculovirus system, it also exists as dimers. The purpose of the present study was to determine if dimeric CFTR exists at the surface of mammalian cells, and particularly in epithelial cells. CFTR solubilized from membranes prepared from Chinese-hamster ovary cells stably expressing CFTR and from T84 epithelial cells migrates as predicted for monomeric, dimeric and larger complexes when subjected to sizing by gel filtration and analysis by non-dissociative electrophoresis. Purification of plasma membranes led to the enrichment of CFTR dimers and this structure exists as the complex glycosylated form of the protein, supporting the concept that dimeric CFTR is physiologically relevant. Consistent with its localization in plasma membranes, dimeric CFTR was labelled by surface biotinylation. Furthermore, dimeric CFTR was captured at the apical surface of intact epithelial cells by application of a membrane-impermeable chemical cross-linker. Therefore it follows from the present study that CFTR dimers exist at the surface of epithelial cells. Further studies are necessary to understand the impact of dimerization on the cell biology of wild-type and mutant CFTR proteins.
Malleable conformation of the elastic PEVK segment of titin: non-co-operative interconversion of polyproline II helix, β-turn and unordered structures
Authors: MA Kan , WANG Kuan
Published: September 2003

To understand the structural basis of molecular elasticity and protein interaction of the elastic PEVK (Pro-Glu-Val-Lys) segment of the giant muscle protein titin, we carried out a detailed analysis of a representative PEVK module and a 16-module PEVK protein under various environmental conditions. Three conformational states, polyproline II (PPII) helix, β-turn and unordered coil were identified by CD and NMR. These motifs interconvert without long-range co-operativity. As a general trend, the relative content of PPII increases with lower temperature and higher polarity, β-turn increases with lower temperature and lower polarity, and unordered coil increases with higher temperature and higher polarity. NMR studies demonstrate that trans-proline residues are the predominant form at room temperature (22 °C), with little trans-to-cis isomerization below 35 °C. Ionic strength affects salt bridges between charged side chains, but not the backbone conformation. We conclude that titin PEVK conformation is malleable and responds to subtle environmental changes without co-operativity. This gradual conformational transition may represent a regulatory mechanism for fine-tuning protein interactions and elasticity.
The transcriptional repressor protein PRH interacts with the proteasome
Authors: BESS Kirstin L. , SWINGLER Tracey E. , RIVETT A. Jennifer , GASTON Kevin , JAYARAMAN Padma-Sheela
Published: September 2003

PRH (proline-rich homeodomain protein)/Hex is important in the control of cell proliferation and differentiation. We have shown previously that PRH contains two domains that can bring about transcriptional repression independently; the PRH homeodomain represses transcription by binding to TATA box sequences, whereas the proline-rich N-terminal domain can repress transcription by interacting with members of the Groucho/TLE (transducin-like enhancer of split) family of co-repressor proteins. The proteasome is a multi-subunit protein complex involved in the processing and degradation of proteins. Some proteasome subunits have been suggested to play a role in the regulation of transcription. In the present study, we show that PRH interacts with the HC8 subunit of the proteasome in the context of both 20 and 26 S proteasomes. Moreover, we show that PRH is associated with the proteasome in haematopoietic cells and that the proline-rich PRH N-terminal domain is responsible for this interaction. Whereas PRH can be cleaved by the proteasome, it does not appear to be degraded rapidly in vitro or in vivo, and the proteolytic activity of the proteasome is not required for transcriptional repression by PRH. However, proteasomal digestion of PRH can liberate truncated PRH proteins that retain the ability to bind to DNA. We discuss these findings in terms of the biological role of PRH in gene regulation and the control of cell proliferation.
Identification of the mitochondrial pyruvate carrier in Saccharomyces cerevisiae
Authors: HILDYARD John C. W. , HALESTRAP Andrew P.
Published: September 2003

Mitochondrial pyruvate transport is fundamental for metabolism and mediated by a specific inhibitable carrier. We have identified the yeast mitochondrial pyruvate carrier by measuring inhibitor-sensitive pyruvate uptake into mitochondria from 18 different Saccharomyces cerevisiae mutants, each lacking an unattributed member of the mitochondrial carrier family (MCF). Only mitochondria from the YIL006w deletion mutant exhibited no inhibitor-sensitive pyruvate transport, but otherwise behaved normally. YIL006w encodes a 41.9 kDa MCF member with homologous proteins present in both the human and mouse genomes.
Trials, tribulations and finally, a transporter: the identification of the mitochondrial pyruvate transporter
Authors: SUGDEN Mary C. , HOLNESS Mark J.
Published: September 2003

Pyruvate occupies a central role in energy homoeostasis, and dysregulation of its cellular disposition underlies many metabolic disturbances. Although the mitochondrial membrane pyruvate transporter has been characterized, its molecular identity has proved elusive. Recent work has now identified a single candidate protein for the mitochondrial pyruvate carrier in yeast, opening the way for further studies in mammalian systems, which may have important therapeutic applications within the context of metabolic disease.
Increased myocardial perfusion and sympathoadrenal activation during mild core hypothermia in awake humans
Authors: FRANK Steven M. , SATITPUNWAYCHA Patricia , BRUCE Simon R. , HERSCOVITCH Peter , GOLDSTEIN David S.
Published: September 2003

Potential mechanisms of cold-induced myocardial ischaemia are sympathetically mediated coronary vasoconstriction and/or catecholamine-induced increases in cardiac work. To examine these parameters, 11 human volunteers were each studied on one day with, and on another day without, β-adrenoceptor blockade. On each day, warm (37 °C) saline (control) and cold (4 °C) saline (hypothermia) were given intravenously. Myocardial perfusion was assessed by positron emission tomography using H215O, and coronary vascular resistance was calculated. Plasma catecholamines were measured to assess sympathoadrenal activation. The core temperature decreased by 1.0 ± 0.2 °C with the cold saline, and was unchanged with warm saline. Myocardial perfusion increased by 20% (P = 0.01) and the rate–pressure product by 33% (P = 0.0004) with cold saline compared with warm saline. β-Blockade eliminated these increases. Coronary vascular resistance was similar with warm and cold saline, and was unaffected by β-blockade. Plasma adrenaline increased by 120% and noradrenaline by 251% during cold saline, but were unchanged during warm saline. In conclusion, core hypothermia triggers β-adrenoceptor-mediated increased cardiac work, sympathoadrenal activation and increased myocardial perfusion. There is no evidence for hypothermia-induced coronary vasoconstriction.
Effects of common polymorphisms in the α1A-, α2B-, β1- and β2-adrenoreceptors on haemodynamic responses to adrenaline
Authors: SNAPIR Amir , KOSKENVUO Juha , TOIKKA Jyri , ORHO-MELANDER Marju , HINKKA Susanna , SARASTE Markku , HARTIALA Jaakko , SCHEININ Mika
Published: September 2003

Common naturally occurring polymorphisms have been identified in the coding regions of the α1A-, α2B-, β1- and β2-adrenoceptor (AR) genes [α1A-AR R492C, α2B-AR insertion/deletion (I/D), β1-AR R389G, β2-AR G16R and β2-AR Q27E] and are associated with modified in vivo and in vitro functionality. We tested their possible effects on the haemodynamic responses to intravenous adrenaline (20, 40, 80 and 160ng/kg of body weight per min; 5min for each infusion rate) before and after β-blockade (propranolol) in 16 young healthy men. We monitored changes in heart rate, blood pressure (BP), ECG, coronary flow velocity and plasma adrenaline and noradrenaline. The Cys/Cys (CC) genotype of the α1A-AR R492C polymorphism was associated with a longer ECG PR interval before and during the adrenaline infusions. The deletion/deletion (D/D) genotype of the α2B-AR I/D polymorphism was associated with blunted coronary blood flow increases during the adrenaline infusion before β-blockade. The β1-AR R389G polymorphism was not associated with modified responses to infused adrenaline. Subjects carrying the Gly/Gly (GG) genotype of the β2-AR G16R polymorphism demonstrated increases in diastolic BP upon adrenaline infusion, whereas diastolic BP was decreased in the other genotype groups. These results suggest that, upon acute adrenaline infusion, the α2B-AR D/D genotype confers increased vasoconstriction and that the β2-AR GG genotype confers reduced vasodilatation.
Functional implications of genetic variation in non-coding DNA for disease susceptibility and gene regulation
Authors: KNIGHT Julian C.
Published: September 2003

The role of host genetic variation in determining susceptibility to complex disease traits is the subject of much research effort, but it often remains unclear whether disease-associated genetic polymorphisms are themselves functionally relevant or acting only as markers within an extended haplotype. Experimental approaches to investigate the functional impact of polymorphisms in non-coding regulatory DNA sequences for gene expression are discussed, including the role of gel-shift assays, DNA footprinting and reporter gene analysis. The limitations of different experimental approaches are presented together with future prospects for in vivo analysis. The strategic application of these functional approaches is discussed and illustrated by analysis of the role of genetic variation in the tumour necrosis factor promoter region in determining susceptibility to severe malaria.
Role of nitric oxide and oxidative stress in baroreceptor dysfunction in patients with chronic heart failure
Authors: NIGHTINGALE Angus K. , BLACKMAN Daniel J. , FIELD Rachel , GLOVER Natalie J. , PEGGE Nicholas , MUMFORD Catherine , SCHMITT Matthias , ELLIS Gethin R. , MORRIS-THURGOOD Jayne A. , FRENNEAUX Michael P.
Published: September 2003

Abnormalities of autonomic control of the cardiovascular system are seen in chronic heart failure (CHF) and confer a poor prognosis. Nitric oxide appears to be important in the regulation of baroreflex control in health and in disease states. The antioxidant vitamin C increases nitric oxide bioavailability in CHF. We evaluated the effects of vitamin C on baroreceptor sensitivity (BRS) by sequence analysis in 100 CHF patients and 44 control subjects. Groups of 55 CHF patients and 22 controls were randomly allocated to receive a single intravenous injection of vitamin C (2 g) or placebo. In addition, 45 CHF patients were randomly allocated to receive a 4-week course of oral vitamin C (4 g/day) or placebo. An age-related reference range for BRS was developed in 22 healthy controls matched for age and gender to the CHF group. BRS was significantly impaired in the CHF group compared with age-matched older controls and young controls (6.9 ± 3.1, 12.5 ± 4.9 and 21.7 ± 9.1 mmHg/ms respectively; P < 0.001 between groups). Intravenous vitamin C acutely improved BRS in CHF patients by 24% (by 1.8 ± 4.1 mmHg/ms; P < 0.05), but not in controls. There was no improvement in BRS in CHF patients given chronic oral vitamin C. Thus acute intravenous, but not chronic oral, vitamin C improved BRS in CHF patients. There was no effect of intravenous vitamin C in healthy subjects, suggesting that the mechanism was either by free radical scavenging or due to central effects.
Novel insights into how purines regulate pituitary cell function
Authors: REES D. Aled , SCANLON Maurice F. , HAM Jack
Published: September 2003

Purine nucleosides and nucleotides are widely distributed substances that exhibit a diverse range of effects in a number of tissues, acting as important extracellular signalling molecules in addition to their more established roles in cellular metabolism. They mediate their effects via activation of distinct cell surface receptors, termed adenosine (or P1) and P2 purinergic receptors. Although roles for adenosine and adenine nucleotides have been described previously in the pituitary gland, the distribution of the receptor subtypes and the effects of their activation on pituitary function are not well defined. Recent evidence, however, has emerged to describe a complex signalling system for purines in the pituitary gland. Data from a variety of studies have shown that the expression pattern, number and affinity of adenosine and/or P2 receptors may be cell-type specific and that non-endocrine in addition to endocrine cells elaborate these receptors. These variations, along with the diverse range of signalling pathways activated, dictate the response of individual cell types to extracellular purines, with roles now emerging for these substances in the regulation of hormone release, pituitary cell proliferation and cytokine/growth factor expression. In this review, we discuss these advances and examine some implications for pituitary growth control and the response of the hypothalamic–pituitary–adrenal axis to stress and inflammation.
Five‐year outcomes of a brief alcohol intervention for adult in‐patients with psychiatric disorders
Authors: Hulse Gary K. , Tait Robert J.
Published: September 2003

Aims  To compare 5 year outcomes (general hospital and mental health morbidity and mortality) among general hospital psychiatric in‐patients randomized to receive either an alcohol reduction motivational interview (MI) or information pack (IP), and compare these to matched controls.

Design  We recruited 120 patients aged 18–64 years who scored ≥8 on the Alcohol Use Disorders Identification Test (AUDIT). We selected matched controls from in‐patients not recruited but who reached the same AUDIT threshold. At 5 years, follow‐up data were collected via a state‐wide hospital record system.

Findings  There were no significant differences between the MI and IP groups in terms of ‘survival’ to their first alcohol‐related, other general hospital or mental health admission over 5 years. Matched controls had significantly more mental health in‐patient episodes (F[1,226] 4.4, P < 0.05) and greater length of hospital stay (F[1,226] 4.8, P < 0.05) than the combined MI‐IP group. Furthermore, the MI‐IP group had longer ‘survival’ times to both first general hospital (mean 583 versus 392 days) and mental health in‐patient (mean 788 versus 580 days) events. Collapsed across groups, dependent and harmful consumers had shorter ‘survival’ times than hazardous consumers (AUDIT classifications).

Conclusions  Alcohol interventions have medium‐term health benefits for those with mental health and alcohol use problems. Importantly, there were no differences in outcome between the intervention groups. The low cost of providing an IP makes it attractive as an alcohol intervention. The AUDIT provided an effective means of identifying those who are at risk of subsequent alcohol‐related admissions and may benefit from intervention.
Substance abuse treatment and pressures from the criminal justice system: data from a provincial client monitoring system
Authors: Rush Brian R. , Wild T. Cameron
Published: September 2003

Aims  Compulsory treatment is discussed increasingly as a way to reduce the population burden of addictive behaviours. This study explores the extent to which social control strategies exercised through the criminal justice system are used to bring people into substance abuse treatment at a system level. We also assessed whether particular subgroups may be more or less likely to be brought into treatment in this manner.

Design  We employed a secondary analysis of data from a client‐based information system which captured demographic, referral and substance use characteristics from people seeking treatment for substance abuse.

Participants  A census of clients (n = 45123) entering specialized Ontario addiction treatment programmes between 1 April 1999 and 31 March 2000.

Findings  Some 28.9% of clients reported legal problems at treatment intake, and 13.9% had an explicit corrections‐related condition of treatment contact. Logistic regression analyses indicated that legal problems and corrections‐related conditions of treatment were more prevalent among younger, unmarried and unemployed males, who had not completed high school. A number of important interactions were identified between these factors and substance of abuse.

Conclusions  Implications for equity, accessibility and effectiveness of substance abuse treatment are discussed in relation to the tendency of treatment mandates from criminal justice system to disproportionately affect the entry of this segment of substance‐abusing clients.
A 60‐year follow‐up of alcoholic men
Authors: Vaillant George E.
Published: September 2003

Aims  To study the course of male alcohol abuse from age 20 to age 70–80 years.

Design  A prospective multi‐disciplinary follow‐up of two community cohorts of adolescent males from 1940 until the present.

Setting and participants  Two hundred and sixty‐eight former Harvard undergraduates (college sample) and 456 non‐delinquent, socially disadvantaged Boston adolescents (core city sample).

Measurements  Since adolescence these cohorts have been followed by repeated interview, questionnaires and physical examination. The college cohort has been followed until age 80 and the younger core city cohort until age 70. DSM‐III criteria were used to ascertain alcohol abuse and alcohol dependence. At some point during their lives, 54 (20%) of the college men and 140 (31%) of the core city men met criteria for alcohol abuse. Outcome categories were mortality, continued alcohol abuse and stable remission.

Findings and conclusions  These socially divergent cohorts resembled each other in four respects. First, by age 70 chronic alcohol dependence was rare; this was due both to death and to stable abstinence. By age 70, 54% of the 72 successfully followed alcohol‐dependent core city men had died, 32% were abstinent, 1% were controlled drinkers and only 12% were known to be still abusing alcohol. By age 70, 58% of the 19 successfully followed college alcohol‐dependent men had died, 21% were abstinent, 10.5% were controlled drinkers and only 10.5% were known to be still abusing alcohol. Secondly, in both samples alcohol abuse could persist for decades without remission, death or progression to dependence. Thirdly, among both samples prior alcohol dependence and AA attendance were the two best predictors of sustained abstinence. Fourthly, few life‐time symptoms of alcohol abuse were the best predictor of sustained return to controlled‐drinking.
Alcohol consumption increases attractiveness ratings of opposite‐sex faces: a possible third route to risky sex
Authors: Jones Barry T. , Jones Ben C. , Thomas Andy P. , Piper Jessica
Published: September 2003

Aims  To measure the effect of moderate alcohol consumption on males’ and females’ attractiveness ratings of unfamiliar male and female faces.

Participants  Eighty undergraduate volunteers were used in each of three experiments.

Design  Participants’ ratings on a 1–7 scale was the dependent variable. A three‐factor mixed design was used. For experiments 1 and 2: one within‐factor, sex‐of‐face to be rated (male/female); two between‐factors, sex‐of‐rater (male/female) and alcohol status of rater (0 UK units/1–6 UK units). For experiment 3, the two levels of sex‐of‐face were replaced by two levels of a non‐face object. In experiment 1, the faces were rated for attractiveness; in experiment 2, the faces were rated for distinctiveness and in experiment 3, the non‐face objects were rated for attractiveness.

Setting  Quiet, prepared corners of bars and licensed eating areas on a civic university campus.

Method  For each experiment, 118 full‐colour photographic images were presented randomly on a laptop computer screen, each remaining until a rating response was made.

Findings  There was a significant alcohol consumption enhancement effect only for attractiveness ratings of opposite‐sex faces in experiment 1. This indicates that the opposite‐sex enhancement effect is not due simply to alcohol consumption causing the use of higher points of ratings scales, in general.

Conclusion  Since Agocha & Cooper have shown that the likelihood of intentions to engage in risky sex increases as the facial attractiveness of the potential sexual partner increases, through the opposite‐sex enhancement effect we identify a new possible link between risky sex and alcohol consumption.
The role of genes in tobacco smoking during adolescence and young adulthood: a multivariate behaviour genetic investigation
Authors: White Victoria M. , Hopper John L. , Wearing Alexander J. , Hill David J.
Published: September 2003

Aims  To incorporate a psychosocial model of tobacco smoking into a behaviour genetic design to examine genetic and environmental influences on variation in smoking involvement.

Design  Longitudinal twin study.

Setting and participants  Twins initially aged between 13 and 18 years and registered with the Australian Twin Registry were surveyed three times between 1988 and 1996. A total of 414 pairs of identical and same‐sex fraternal twin pairs participated in all three surveys, aged between 20 and 25 at wave 3. Biometric modelling estimated the influence of genetic and environmental factors in determining variation in smoking at each wave, both before and after adjusting for perceived smoking behaviours of peers and parents.

Measurements  Twins answered a questionnaire on their own smoking status and reported on the use of tobacco by parents and friends as they perceived it, at each survey wave.

Findings  At all three surveys, current smokers were more likely to have parents who smoked and to have smokers among their peers. Genes and environmental factors, both common and unique, contributed to variation in smoking behaviours. However, after controlling for the smoking behaviours of peers and parents, the role of genes in determining variation in smoking involvement was reduced by 100% at wave 1 and by 30% at wave 2. Friends’ smoking reduced the magnitude of the common environment variance by 11%, 30% and 40% at waves 1, 2 and 3, respectively. Parents’ smoking behaviours explained part of the common environment. Biometric modelling of the covariation between smoking involvement and peer smoking suggested that genes might influence smoking involvement at wave 1 by influencing choice of peers.

Conclusion  Environmental factors play the greatest role in determining variation in tobacco smoking among adolescents and young adults. Among adolescents, genes may influence variation in smoking behaviours indirectly by influencing choice of peers. However, genes seem to have a direct influence on variations in the smoking behaviours of young adults.
Development and psychometric evaluation of the Benzodiazepine Craving Questionnaire
Authors: Mol A. J. J. , Voshaar R. C. Oude , Gorgels W. J. M. J. , Breteler M. H. M. , Van Balkom A. J. L. M. , Van De Lisdonk E. H. , Van Der Ven A. H. G. S. , Zitman F. G.
Published: September 2003

Aim  To assess the scalability, reliability and validity of a newly constructed self‐report questionnaire on craving for benzodiazepines (BZs), the Benzodiazepine Craving Questionnaire (BCQ).

Setting and participants  The BCQ was administered once to a sample of 113 long‐term and 80 former long‐term general practice BZ users participating in a large BZ reduction trial in general practice.

Measurements  (1) Unidimensionality of the BCQ was tested by means of the Rasch model. (2) The Rasch‐homogeneous BCQ items were assessed for subject and item discriminability. (3) Discriminative and construct validity were assessed.

Findings  The BCQ met the requirements for Rasch homogeneity, i.e. BZ craving as assessed by the scale can be regarded as a unidimensional construct. Subject and item discriminability were good. Construct validity was modest. Highest significant associations were found with POMS depression (Kendall's tau‐c = 0.15) and Dutch Shortened MMPI negativism (Kendall's tau‐c = 0.14). Discriminative validity was satisfactory. Highest discriminative power was found for a subset of eight items (Mann–Whitney U Z = − 3.6, P = 0.000). The first signs of craving are represented by the acknowledgement of expectations of positive outcome, whereas high craving is characterized by direct intention to use.

Conclusions  The BCQ proved to be a reliable and psychometrically sound self‐report instrument to assess BZ craving in a general practice sample of long‐term BZ users.
Four‐year follow‐up of smoke exposure, attitudes and smoking behaviour following enactment of Finland's national smoke‐free work‐place law
Authors: Heloma Antero , Jaakkola Maritta S.
Published: September 2003

Aims  This study evaluated the possible impact of national smoke‐free work‐place legislation on employee exposure to environmental tobacco smoke (ETS), employee smoking habits and attitudes on work‐place smoking regulations.

Design  Repeated cross‐sectional questionnaire surveys and indoor air nicotine measurements were carried out before, and 1 and 3 years after the law had come into effect.

Setting  Industrial, service sector and office work‐places from the Helsinki metropolitan area, Finland.

Participants  A total of 880, 940 and 659 employees (response rates 70%, 75% and 75%) in eight work‐places selected from a register kept by the Uusimaa Regional Institute of Occupational Health to represent various sectors of public and private work‐places.

Measurements  Reported exposure to ETS, smoking habits, attitudes on smoking at work and measurements of indoor air nicotine concentration.

Findings  Employee exposure to ETS for at least 1 hour daily decreased steadily during the 4‐year follow‐up, from 51% in 1994 to 17% in 1995 and 12% in 1998. Respondents’ daily smoking prevalence and tobacco consumption diminished 1 year after the enforcement of legislation from 30% to 25%, and remained at 25% in the last survey 3 years later. Long‐term reduction in smoking was confined to men. Both smokers’ and non‐smokers’ attitudes shifted gradually towards favouring a total ban on smoking at work. Median indoor airborne nicotine concentrations decreased from 0.9 µg/m3 in 1994–95 to 0.1 µg/m3 in 1995–96 and 1998.

Conclusions  This is the first follow‐up study on a nationally implemented smoke‐free work‐place law. We found that such legislation is associated with steadily reducing ETS exposure at work, particularly at work‐places, where the voluntary smoking regulations have failed to reduce exposure. The implementation of the law also seemed to encourage smokers to accept a non‐smoking work‐place as the norm.
Health service utilization and benzodiazepine use among heroin users: findings from the Australian Treatment Outcome Study (ATOS)
Authors: Darke Shane , Ross Joanne , Teesson Maree , Lynskey Michael
Published: September 2003

Aims  To determine levels of health service utilization among heroin users, the types of prescription drugs obtained by heroin users and the contribution of benzodiazepine use in health service utilization and prescribed drug use.

Design  Cross‐sectional survey.

Setting  Sydney, Australia.

Participants  A total of 615 current heroin users recruited for the Australian Treatment Outcome Study (ATOS).

Findings  Sixty per cent of subjects had consulted a general practitioner (GP) and 7% a specialist in the preceding month. An ambulance had attended 11% of subjects in the preceding month. Forty‐eight per cent of subjects had prescriptions dispensed for medication in the preceding month. Thirty‐nine per cent of participants had prescriptions dispensed for psychotropic medications, representing 80% of all prescriptions. Twenty per cent of subjects had prescriptions dispensed for non‐psychotropic medications (20% of prescriptions). The most commonly prescribed drugs were benzodiazepines (59% of prescriptions), which had been obtained by 30% of subjects. Benzodiazepine users had more GP and psychiatrist visits, were more likely to have had an ambulance attendance and had significantly more dispensed prescriptions.

Conclusions  There were high levels of health utilization among heroin users. Prescription drug use was common, and dominated by psychotropic drugs. Benzodiazepine use was a dominant factor in the use of services and in prescriptions dispensed. Despite increased awareness of the harms associated with benzodiazepines, they continue to be prescribed widely to heroin users.
Post‐Vietnam heroin use and injection by returning US veterans: clues to preventing injection today
Authors: Robins Lee N. , Slobodyan Sergey
Published: September 2003

Aims  To seek clues in the Vietnam study of 30 years ago that might shed light on which previous users of heroin are at special risk of relapsing and, among relapsers, to identify those likely to begin or return to injecting heroin.

Design  To analyse information in military records and in two interviews given in the first 3 years after return from Vietnam to find predictors of post‐Vietnam injection by soldiers who had used heroin while in Vietnam in 1970–71.

Participants  A total of 374 Vietnam veterans who had used heroin while in Vietnam and had been interviewed twice since their return from Vietnam.

Measurements  Post‐Vietnam heroin injection was determined in either of two post‐Vietnam interviews. Possible predictors came from interviews and military records and describe pre‐Service and in‐Vietnam status and behavior. Included are region of residence, race, antisocial behavior, type and level of drug use and association with illicit drug users. Possible post‐Vietnam correlates of heroin injection were no job or school enrollment, alcohol problems, depression, absent or transient marriage, association with illicit drug users and other Vietnam veterans.

Findings  Only a minority of those who used heroin in Vietnam had ever injected it there. Most smoked or snorted it. After their return, most of the men who had used heroin in Vietnam used it very occasionally or not at all. Among those who did use heroin more than five times after their return, most had tried injecting it. Significant predictors of post‐Vietnam injection included living on the east or west coast, deviant behavior both before and in Vietnam, opiate use before Vietnam, serious involvement with heroin in Vietnam, use of non‐opiate drugs before and in Vietnam, and associating with drug users before Service. The variables that increased significantly the probability of injection among men who relapsed to heroin use after return to the United States were living on the east or west coast and having a history of using non‐opiate illegal drugs before they entered Service. Blacks who returned to heroin use after return were less likely to inject than were non‐blacks.

Conclusions  These results suggest that a high‐risk group for intervention to prevent future injection would consist of people with a history of past heroin use who are currently either in remission or using without injection and who reside on either coast, have a history of antisocial behavior and have used a variety of illicit drugs other than heroin.
Ether: a forgotten addiction
Authors: Krenz Sonia , Zimmermann Grégoire , Kolly Stéphane , Zullino Daniele Fabio
Published: September 2003

Among abused inhalants, ether has recently received little attention. The case of a patient suffering from ether dependence is reported. Whereas several features of DSM‐IV dependence were fulfilled, no physical withdrawal signs were observed.
Needle sharing among southern Thai drug injectors
Authors: Perngmark Pajongsil , Celentano David D. , Kawichai Surinda
Published: September 2003

Aim  To examine factors associated with needle sharing among injecting drug users (IDU) in southern Thailand.

Design  Using a cross‐sectional survey, 272 active IDU were interviewed about their socio‐economic background, needle sharing and drug use patterns at six drug‐treatment clinics in southern Thailand.

Findings  Ninety‐one per cent of IDU gave a past history of ever sharing injecting equipment: of these, 23% currently injected but did not share and 68% still shared. Only 5% of participants knew that bleaching needles could reduce HIV transmission risks. Recent needle sharing was correlated with number of IDU friends (OR 12.23; CI, 5.24–28.51), engaging in illegal jobs (OR 2.74; CI, 1.13–6.67), being unable to use new needles at all times (OR 2.89; CI, 1.17–7.14) and believing that cleaning contaminated shared needles with at least plain water could reduce HIV transmission (OR 3.32; CI, 1.16–6.68).

Conclusions  Our data suggest that AIDS prevention efforts should focus on approaches to reduce needle sharing. Needle exchange programs, HIV counseling and testing and bleach distribution may reduce levels of needle‐sharing risks.
Pilot randomized double blind placebo‐controlled study of dexamphetamine for cocaine dependence
Authors: Shearer James , Wodak Alex , Van Beek Ingrid , Mattick Richard P. , Lewis John
Published: September 2003

Aims  To establish the feasibility of conducting a placebo‐controlled clinical trial of dexamphetamine replacement therapy for cocaine dependence and to obtain preliminary data.

Design  Double‐blind randomized placebo‐controlled trial.

Participants  Thirty cocaine‐dependent injecting drug users.

Intervention  Subjects were assigned randomly to receive 60 mg/day dexamphetamine (n = 16) or placebo (n = 14) for 14 weeks.

Measurements  Immunoassay and mass spectrometric techniques were used to identify cocaine metabolites in urine. Subjects were screened using the Composite International Diagnostic Interview and DSM‐IV. The Opiate Treatment Index, Brief Symptom Inventory, Severity of Dependence Scale and visual analogue craving scales were used to collect pre‐ and post‐self‐report data.

Findings  Treatment retention was equivalent between groups; however, outcomes favoured the treatment group with no improvements observed in the placebo control group. The proportion of cocaine‐positive urine samples detected in the treatment group declined from 94% to 56% compared to no change in the placebo group (79% positive). While the improvements were not significant between groups, within‐group analysis revealed that the treatment group reduced self‐reported cocaine use (P = 0.02), reduced criminal activity (P = 0.04), reduced cravings (P < 0.01) and reduced severity of cocaine dependence (P < 0.01) with no within‐group improvements found in the placebo group.

Conclusions  A definitive evaluation of the utility of dexamphetamine in the management of cocaine dependence is feasible and warranted.
The Italian Association on Addiction Psychiatry (SIPDip), formerly The Italian Association on Abuse and Addictive Behaviours
Authors: Carrà Giuseppe , Clerici Massimo
Published: September 2003

The Italian Association on Addiction Psychiatry (SIPDip) is a special section of the Italian Psychiatric Association (SIP). It started, under the name of the Italian Association on Abuse and Addictive Behaviours (SICAD), in 1989 from the awareness that the addiction field had been starved of a psychiatrists’ contribution since 1975. SIPDip aims to improve and implement study, clinical, research and educational topics about substance abuse and addictive behaviours. The National Board composition aims to provide an equal distribution of psychiatrists working in psychiatric and addiction facilities inside the National Health System, and private non‐profit agencies. All psychiatrists and members of the Italian Psychiatric Association can become SIPDip ordinary members, while other health professionals working in psychiatric and addiction fields can become associate members. SIPDip has its National Congress every second year. In 2001 it promoted a network called the National Council of Addiction Disorders. It is recognized officially by the Drug Policy National Department and was created under the direct authority of the Prime Minister. In this, SIPDip is particularly involved in review groups relating to ethical issues, substitutive therapies and dual diagnosis. Furthermore, it organized the first Consensus Conference on Dual Diagnosis, under the sponsorship of the Italian Psychiatric Association. This was held in June 2003 to implement relevant national guidelines. The SIPDip main topics that will be addressed in the near future are: psychiatric comorbidity in substance related disorders; intervention efficacy assessment; and special populations and novel addictions. The National Board meeting on 15 December 2002 decided to submit to the General Assembly in April 2003, a motion to modify the Association's byelaws and to rename the organization ‘The Italian Association of Addiction Psychiatry’.
Most smokeless tobacco use is not a causal gateway to cigarettes: using order of product use to evaluate causation in a national US sample
Authors: Kozlowski Lynn T. , O'Connor Richard J. , Quinio Edwards Beth , Flaherty Brian P.
Published: September 2003

Aims To evaluate non‐causal and causal patterns of smokeless tobacco (SLT) and cigarette use; to assess the prevalence of ‘non‐gateway’ and possible ‘gateway’ patterns of SLT use.

Design and setting Data from the Cancer Control Supplement to the 1987 National Health Interview Survey, a representative survey of non‐institutionalized adults in the United States. From reported age at first use, participants were categorized by type and sequence of tobacco product use. SUDAAN 8.0.1 was used for statistical analyses.

Participants Males aged 18–34 (n = 3454), weighted to provide estimates of the US population. A subsample of males aged 23–34 (n = 2614) was analyzed to minimize the possibility of future product switching.

Measurements Smoking status, smokeless tobacco (snuff, chewing tobacco, both) use status, age at regular use of cigarettes, age at first use of smokeless tobacco.

Findings Of those 23–34‐year‐olds who had ever used SLT with or without cigarettes, 77.2% (95% CI: 71.3, 83.3) were classifiable as non‐gateway users in that 35.0% (95% CI: 29.9, 40.1) had only used SLT and 42.2% (95% CI: 36.8, 47.7) had used cigarettes first. Cigarette use in younger cohorts was less common, despite increased SLT use. Those who used cigarettes before moist snuff were 2.1 times more likely to have quit smoking (95% CI 1.21,6.39) than cigarette‐only users.

Conclusions The large majority of SLT users are non‐gateway users. Causal gateway effects should be of minor concern for policy. SLT may be more likely to prevent smoking than cause it.
Intravenous drug users and broken needles—a hidden risk?
Authors: Norfolk Guy A. , Gray Selena F.
Published: September 2003

Aims  To determine the frequency with which intravenous drug users (IDUs) experience broken needles during their injecting careers.

Design  Cross‐sectional survey.

Participants  Seventy intravenous drug users held in police custody in Bristol between May and September 2002.

Measurements  Self‐reported history of experience of broken needles.

Findings  Fourteen (20%, 95% CI 11–29%) had experienced a needle breaking while injecting. The total number of broken needles was 23, of which 14 (61%) were recovered, four by surgical intervention, and the remainder as a result of direct action by the individual. Of the 23 broken needles, nine (39%) were reported to be fresh needles, whereas the remainder were being re‐used.

Conclusions  IDUs may well experience, directly or indirectly, incidents involving broken needles during the course of their injecting careers. Given the potential for embolization and the risk of subsequent complications when this occurs, we recommend that harm minimization guidance should include advice about this potential hazard and the need for early action to retrieve broken needles.
Intentionally reduced smoking among untreated general population smokers: prevalence, stability, prediction of smoking behaviour change and differences between subjects choosing either reduction or abstinence
Authors: Meyer Christian , Rumpf Hans‐Jürgen , Schumann Anja , Hapke Ulfert , John Ulrich
Published: September 2003

Aims  To compare data from the general population on intentionally reduced smoking and smoking cessation.

Design  Longitudinal observation study.

Setting  Northern German region.

Subjects  Randomly sampled residents aged 18–64 (T1; n = 4075, response rate 70%). Daily cigarette smokers (n = 1520) were followed up after 30 (T2; n = 913) and 36 months (T3; n = 786).

Measures  Self‐reported smoking‐related and socioeconomic variables. Participants were explicitly asked for reduction attempts (reducing cigarettes per day) and maintenance of reduction, which was defined independently of consumption measures.

Findings  Between T1 and T2, reduction attempts (39%) were more frequent than quit attempts (33%), and according to self‐report, reduction was more likely to be maintained for up to 12 months. Smokers maintaining reduction for up to 6 months had reduced their consumption at T3 by 34% compared with T2. Between T1 and T2, the occurrence of both a reduction and a quit attempt was most frequent (22%), followed by subjects exclusively trying to reduce (17%) and subjects exclusively trying to quit (4%). Subjects who exclusively tried to reduce had a significantly increased probability of further reduction attempts at T3 (OR = 4.4, 95% CI 2.0–10.1), while the probability of quit attempts was equal compared with subjects not attempting to reduce or quit (OR = 1.1, 95% CI 0.3–3.2). DSM‐IV nicotine dependence was less common in subjects who exclusively tried to reduce. Other smoking‐related and socioeconomic variables did not predict whether individuals attempted to reduce or attempted to quit.

Conclusions  A considerable proportion of general population smokers attempt to reduce, and are able to maintain reduction of, cigarette consumption over time. Reduction attempts did not reduce the probability of a subsequent cessation attempt.
Allergen‐specific immunotherapy with a monophosphoryl lipid A‐adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy‐induced blocking antibodies
Authors: Mothes N. , Heinzkill M. , Drachenberg K. J. , Sperr W. R. , Krauth M. T. , Majlesi Y. , Semper H. , Valent P. , Niederberger V. , Kraft D. , Valenta R.
Published: September 2003

Background
Allergen‐specific immunotherapy represents a causal form of treatment for IgE‐mediated allergies. The allergen extract‐based analyses of immunotherapy‐induced effects yielded highly controversial results regarding a beneficial role of therapy‐induced IgG antibodies.

Objective
We analysed allergen‐specific IgE, IgG subclass, and IgM responses in patients treated with a grass pollen allergy vaccine adjuvanted with monophosphoryl lipid A (MPL), a Th1‐inducing agent, and in a placebo group using recombinant timothy grass pollen allergen molecules (rPhl p 1, rPhl p 2, rPhl p 5).

Results
The strong induction of allergen‐specific IgG1 and IgG4 antibodies observed only in the actively treated group was associated with significant clinical improvement. Therapy‐induced allergen‐specific IgM and IgG2 responses were also noted in several actively treated patients. An inhibition of allergen‐dependent basophil histamine release was only obtained with sera containing therapy‐induced allergen‐specific IgG, but not with sera obtained before therapy or from placebo‐treated patients. Moreover, patients with therapy‐induced allergen‐specific IgG antibodies showed a reduced induction of allergen‐specific IgE responses during seasonal grass pollen exposure.

Conclusion
Successful immunotherapy with the MPL‐adjuvanted grass pollen allergy vaccine is associated with the production of allergen‐specific IgG antibodies. These blocking antibodies may have protective effects by inhibiting immediate‐type reactions and systemic increases of IgE responses caused by seasonal allergen exposure.
Residential characteristics predict changes in Der p 1, Fel d 1 and ergosterol but not fungi over time
Authors: Matheson M. C. , Dharmage S. C. , Forbes A. B. , Raven J. M. , Woods R. K. , Thien F. C. K. , Guest D. I. , Rolland J. M. , Haydn Walters E. , Abramson M. J.
Published: September 2003

Background
Allergen and fungal exposures are important risk factors for asthma. We conducted a longitudinal analysis of allergen levels in Melbourne homes between 1996 and 1998 to examine the effects of changing residential characteristics on allergen and fungal levels. We also examined the changes in levels of indoor allergens.

Methods
The subjects were participants in the European Community Respiratory Health Survey (ECRHS) in Melbourne. In 1996, 485 subjects participated in a follow‐up study, which involved both home and laboratory visits. Dust and air samples were collected from participants' bedrooms and a validated residential questionnaire was administered. In 1998, 360 participants underwent further follow‐up. House dust mite (Der p 1) and cat allergens (Fel d 1) and ergosterol were measured in dust.

Results
We observed moderate within home correlations between 1996 and 1998 in floor Der p 1 (intraclass correlation ICC=0.48), bed Der p 1 (ICC=0.61), Fel d 1 (κ=0.53) and ergosterol (ICC=0.28) levels. We found that the floor Der p 1 levels decreased from 1996 to 1998 in the homes of participants who moved to an attached home, moved their bedrooms to the first floor, removed fitted carpet or central heating. Replacing or vacuuming the mattress more than twice per year reduced levels of Der p 1 in the bed. Ergosterol levels were reduced by removing visible mould and fitted carpet.

Conclusions
These findings provide evidence to support current advice with regard to allergen avoidance in patients with dust mite and fungal allergies.