Comparison of carbohydrate-deficient transferrin, immunoglobulin A antibodies reactive with acetaldehyde-modified protein and acetaldehyde-modified albumin with conventional markers of alcohol consumption

Carbohydrate-deficient transferrin (CDT) has emerged as the best new marker for alcohol abuse. Recently plasma immunoglobulin A (IgA) reactivity with acetaldehyde (AcH)-modified proteins, or the modified proteins per se, have been proposed as a markers for high levels of alcohol consumption. In this study, we have compared CDT, IgA reactivity with AcH adducts (IgA ASR), and AcH-modified albumin with conventional markers of high alcohol intake in groups with well-defined drinking histories, The plasma activity of ALT, AST, and gamma-glutamyltransferase increased steadily with increasing alcohol consumption, CDT and AcH-modified albumin showed a similar pattern, whereas IgA ASR appeared only to be elevated after a threshold level of consumption had been reached, Neither CDT IgA ASR or AcH-modified albumin correlated strongly with any of the conventional markers or each other. This study shows that CDT, IgA ASR, AcH-modified albumin, and the conventional markers are not related, but suggests that the concurrent use of CDT and IgA ASR may lead to better identification of high alcohol intake.

Patient matching in treatment for alcohol dependence: is the null hypothesis still alive and well?

In the light of Project MATCH, is it reasonable to accept the null hypothesis that there are no clinically signi® cant matching effects between patient characteristics and cognitive± behaviour therapy (CBT), motivational enhancement therapy (MET) and Twelve-Step facilitation therapy (TSF)? The Project MATCH investigators considered the null hypothesis but preferred the alternative hypothesis that further analysis may reveal combinations of patient and therapist characteristics that show more substantial matching effects than any of the variables that they have examined to date.1

Chronic ethanol exposure and withdrawal influence NMDA receptor subunit and splice variant mRNA expression in the rat cerebral cortex

Chronic ethanol exposure and subsequent withdrawal are known to change NMDA receptor activity. This study examined the effects of chronic ethanol administration and withdrawal on the expression of several NMDA receptor subunit and splice variant mRNAs in the rat cerebral cortex. Ethanol dependence was induced by ethanol vapour exposure. To delineate between seizure-induced changes in expression during withdrawal and those due to withdrawal per se, another group of naive rats was treated with pentylenetetrazol (PTZ) injection (30 mg/kg, i.p.). RNA samples from the cortices of chronically treated and withdrawing animals were compared to those from pairfed controls. Changes in NMDA receptor mRNA expression were determined using ribonuclease protection assays targetting the NR2A, -2B, -2C and NR1-pan subunits as well as the three alternatively spliced NR1 inserts (NR1-pan describes all the known NR1 splice variants generated from the 5' insert and the two 3' inserts). The ratio of NR1 mRNA incorporating the 5' insert vs, that lacking it was decreased during ethanol exposure and up to 48 h after withdrawal. NR2B mRNA expression was elevated during exposure, but returned to control levels 18 h after withdrawal. Levels of NR2A, NR2C, NR1-pan and both 3' NR1 insert mRNAs from the ethanol-treated groups did not alter compared with the pair-fed control group. No changes in the level of any NMDA receptor subunit mRNA was detected in the PTZ-treated animals. These data support the hypothesis that changes in NMDA receptor subunit composition may underlie a neuronal adaptation to the chronic ethanol-inhibition and may therefore be important in the precipitation of withdrawal hyperactivity. (C) 1999 Elsevier Science B.V. All rights reserved.

STD syndrome packets: Improving syndromic management of sexually transmitted diseases in developing countries

Objective: To design, introduce, and evaluate STD syndrome packets containing recommended drugs for each syndrome, four condoms, a partner treatment card, and a patient information leaflet, with the goal of improving sexually transmitted disease (STD) case management. Methods: Packet design evolved around available packaging technology, informed by pilot testing with nurses working in primary care clinics, doctors in private medical practices, and patients with an STD, in Hlabisa, South Africa. Evaluation 1 year later included analysis of distribution records and interviews with 16 nurses and 61 patients. Results: A cheap packet (2 U, S, cents each, excluding contents) compatible with current legislation was designed and introduced to six public sector clinics and as a short pilot to five private medical practices, Four thousand eighty-five packets were distributed to the clinics, equivalent to approximately 115% of the STDs reported over that period. All 16 nurses reported using the packets, but only 63% did so all the time because of occasional supply problems, All believed the packets improved treatment by saving time (75%), improving supply of condoms and partner cards (44%), and making treatment easier (56%), Patients also responded positively, and most said they would buy a packet (up to $5) at a pharmacy (84%) or store (63%) if available. Conclusions: The STD syndrome packets have the potential to improve STD syndromic management by standardizing therapy and improving the supply of condoms, partner cards, and information leaflets. Packets are popular with practitioners and patients, but consistent supply is essential for maximal impact, There may be scope for social marketing of the packets, which could further increase use.

Self-efficacy for refusal mediated by outcome expectancies in the prediction of alcohol-dependence amongst young adults

The present study examined the relative importance of outcome expectancies and self-efficacy [1] in the prediction of alcohol dependence [2] and alcohol consumption in a sample of young adult drinkers drawn from a milieu previously reported as supportive of risky drinking. In predicting alcohol dependence, outcome expectancies were found to mediate self-efficacy and the same pattern was found for both males and females. This suggests that male and female drinkers may become more similar as they progress along the drinking continuum from risky drinking to dependent drinking. However, in women, in comparison to men, a greater array of expectancies and self-efficacy scales were found to predict heavy drinking, as measured by quantity and frequency. These results suggest that heavy drinking women are particularly at risk of developing drinking related complications and that preventative education needs to take into account gender differences.

Alcohol- and drug-use disorders in Australia: implications of the National Survey of Mental Health and Wellbeing

Objective: This study reports the prevalence and correlates of ICD-10 alcohol- and drug-use disorders in the National Survey of Mental Health and Wellbeing (NSMHWB) and discusses their implications for treatment. Method: The NSMHWB was a nationally representative household survey of 10 641 Australian adults that assessed participants for symptoms of the most prevalent ICD-10 and DSM-IV mental disorders, including alcohol- and drug-use disorders. Results: In the past 12 months 6.5% of Australian adults met criteria for an ICD-10 alcohol-use disorder and 2.2% had another ICD-10 drug-use disorder. Men were at higher risk than women of developing alcohol- and drug-use disorders and the prevalence of both disorders decreased with increasing age. There were high rates of comorbidity between alcohol- and other drug-use disorders and mental disorders and low rates of treatment seeking. Conclusions: Alcohol-use disorders are a major mental health and public health issue in Australia. Drug-use disorders are less common than alcohol-use disorders, but still affect a substantial minority of Australian adults. Treatment seeking among persons with alcohol- and other drug-use disorders is low. A range of public health strategies (including improved specialist treatment services) are needed to reduce the prevalence of these disorders.

Patterns of alcohol consumption in young Australian women: socio-demographic factors, health-related behaviours and physical health

Objective: To determine which sociodemographic factors. health-related behaviours and physical health conditions are associated with non-drinking, binge drinking and hazardous/harmful drinking in young Australian women. Methods: Cross-sectional data were obtained from the baseline survey of 14,762 young women (aged 18-23 years) enrolled in the Women's Health Australia study in 1996. Associations between a range of drinking patterns and sociodemographic factors, health-related behaviours and health conditions were examined. Results: Half the women were 'low intake' drinkers, a third 'rarely drank' and 9% were non-drinkers; however, 70% reported binge drinking with one-quarter of the binge drinkers doing so at least weekly. Nondrinkers were more likely than drinkers to be married, pregnant, non-smokers, born in non-English speaking countries, to live in the Northern Territory, and to have lower levels of education, employment, and private health insurance. Low intake/binge weekly' drinkers (12%) and 'hazardous/ harmful' drinkers (5%) were more likely than 'low risk' drinkers to be unmarried; to live in shared accommodation, alone or with their parents; to live in rural or remote areas; to have ever had any sexually transmitted infection; to be current smokers or ex-smokers and to have used unhealthy weight-control practices. Conclusions: The results confirm findings from other countries about the importance of social conditions as determinants of alcohol consumption by young women. Implications: Health promotion to reduce young women's alcohol consumption needs to be carefully targeted to take account of their demographies, living environments and beliefs.

Glutamate-mediated transmission, alcohol, and alcoholism

Glutamate-mediated neurotransmission may be involved in the range of adaptive changes in brain which occur after ethanol administration in laboratory animals, and in chronic alcoholism in human cases. Excitatory amino acid transmission is modulated by a complex system of receptors and other effecters, the efficacy of which can be profoundly affected by altered gene or protein expression. Local variations in receptor composition may underlie intrinsic regional variations in susceptibility to pathological change. Equally, ethanol use and abuse may bring about alterations in receptor subunit expression as the essence of the adaptive response. Such considerations may underlie the regional localization characteristic of the pathogenesis of alcoholic brain damage, or they may form part of the homeostatic change that constitutes the neural substrate for alcohol dependence. (C) 2000 Elsevier Science Ltd. All rights reserved.

Exposure of rats to a high but not low dose of ethanol during early postnatal life increases the rate of loss of optic nerve axons and decreases the rate of myelination

Visual system abnormalities are commonly encountered in the fetal alcohol syndrome although the level of exposure at which they become manifest is uncertain. In this study we have examined the effects of either low (ETLD) or high dose (ETHD) ethanol, given between postnatal days 4-9, on the axons of the rat optic nerve. Rats were exposed to ethanol vapour in a special chamber for a period of 3 h per day during the treatment period. The blood alcohol concentration in the ETLD animals averaged similar to 171 mg/dl and in the ETHD animals similar to 430 mg/dl at the end of the treatment on any given day. Groups of 10 and 30-d-old mother-reared control (MRC), separation control (SC), ETLD and ETHD rats were anaesthetised with an intraperitoneal injection or ketamine and xylazine, and killed by intracardiac perfusion with phosphate-buffered glutaraldehyde. In the 10-d-old rat optic nerves there was a total of similar to 145000-165000 axons in MRC, SC and ETLD animals. About 4 % of these fibres were myelinated. The differences between these groups were not statistically significant. However, the 10-d-old ETHD animals had only about 75000 optic nerve axone (P < 0.05) of which about 2.8 % were myelinated. By 30 d of age there was a total of between 75000 90000 optic nerve axons, irrespective of the group examined. The proportion of axons which were myelinated at this age was still significantly lower (P < 0.001) in the ETHD animals (similar to 77 %) than in the other groups (about 98 %). It is concluded that the normal stages of development and maturation of the rat optic nerve axons, as assessed in this study, can be severely compromised by exposure to a relatively high (but not low) dose of ethanol between postnatal d 4 and 9.

Syndrome packets and health worker training improve sexually transmitted disease case management in rural South Africa: randomized controlled trial

Background: Sexually transmitted diseases (STD) are important co-factors in HIV transmission. We studied the impact of health worker training and STD syndrome packets (containing recommended drugs, condoms, partner notification cards and information leaflets) on the quality of STD case management in primary care clinics in rural South Africa. Methods: A randomized controlled trial of five matched pairs of clinics compared the intervention with routine syndromic management. Outcomes were measured by simulated patients using standardized scripts, and included the proportion given recommended drugs; correctly case managed (given recommended drugs plus condoms and partner cards); adequately counselled; reporting good staff attitude; and consulted in privacy. Results: At baseline, the quality of STD case management was similarly poor in both groups. Only 36 and 46% of simulated patients visiting intervention and control clinics, respectively, were given recommended drugs. After the intervention, intervention clinics provided better case management than controls: 88 versus 50% (P < 0.01) received recommended drugs; 83 versus 12% (P < 0.005) were correctly case managed; 68 versus 46% (P = 0.06) were adequately counselled; 84 versus 58% experienced good staff attitude (P = 0.07); and 92 versus 86% (P = 0.4) were consulted privately. A syndrome packet cost US$1.50; the incremental cost was US$6.80. The total intervention cost equalled 0.3% of annual district health expenditure. Interpretation: A simple and affordable health service intervention achieved substantial improvements in STD case management. Although this is a critical component of STD control and can reduce HIV transmission, community-level interventions to influence health-seeking behaviour are also needed. (C) 2000 Lippincott Williams & Wilkins.

Effects of an oral vasopressin receptor antagonist (OPC-31260) in a dog with syndrome of inappropriate secretion of antidiuretic hormone

Objective The syndrome of inappropriate secretion of antidiuretic hormone is a rare disorder in dogs characterised by hypo-osmolality and persistent arginine vasopressin production in the absence of hypovolaemia and/or hypotension. The study describes the efficacy and safety of the nonpeptide selective arginine vasopressin V-2 receptor antagonist OPC-31260 in a dog with the naturally occurring syndrome. Design The detailed case history of a dog with spontaneous syndrome of inappropriate secretion of antidiuretic hormone that received long-term therapy with oral OPC-31260 is presented. Effects of the first dose of OPC-31260 and of a dose administered after a continuous dosing period of 12 days are reported. Procedure Packed cell volume, plasma sodium, total protein, arginine vasopressin, renin activity, atrial natriuretic peptide, urine specific gravity, urine output, heart rate and body weight were monitored for 2 h before, and for 4 h after, the first dose of OPC-31260. The same parameters plus plasma osmolality and urine osmolality were monitored when an identical dose was administered after 12 days of therapy. Results Oral administration of OPC-31260 at 3 mg/kg body weight resulted in marked aquaresis with increased urine output and decline in urine specific gravity within 1 h. Corresponding increases in concentrations of plasma sodium, plasma osmolality and plasma renin activity were recorded over a 4 h period. Arginine vasopressin concentration remained inappropriately elevated throughout the study. Results were similar when the trial procedure was repeated after a stabilisation period of 12 days. Long-term therapy with OPC-31260 at a dose of 3 mg/kg body weight orally every 12 h resulted in good control of clinical signs with no deleterious effects detected during a 3-year follow-up period. Despite sustained clinical benefits observed in this case, plasma sodium did not normalise with continued administration of the drug. Conclusions Treatment of a dog with naturally occurring syndrome of inappropriate secretion of antidiuretic hormone with OPC-31260 at 3 mg/kg body weight orally every 12 h resulted in marked aquaresis and significant palliation of clinical signs with no discernible side-effects detected over a 3-year period. Thus, OPC-31260 appears to offer a feasible medical alternative to water restriction for treatment of dogs with syndrome of inappropriate secretion of antidiuretic hormone. Higher doses of OPC-31260 may be required to achieve and maintain normal plasma sodium in dogs with this syndrome.

Delayed onset of electromyographic activity of vastus medialis obliquus relative to vastus lateralis in subjects with patellofemoral pain syndrome

Objective: To determine whether electromyographic (EMG) onsets of vastus medialis obliquus (VMO) and vastus lateralis (VL) are altered in the presence of patellofemoral pain syndrome (PFPS) during the functional task of stair stepping. Design: Cross-sectional. Setting: University laboratory. Patients: Thirty-three subjects with PFPS and 33 asymptomatic controls. Interventions: Subjects ascended and descended a set of stairs-2 steps, each 20-cm high-at usual stair-stepping pace. EMG readings of VMO and VL taken on middle stair during step up (concentric contraction) and step down (eccentric contraction). Main Outcome Measures: Relative difference in onset of surface EMG activity of VMO compared with VL during a stair-stepping task. EMG onsets were determined by using a computer algorithm and were verified visually. Results: In the PFPS population, the EMG onset of VL occurred before that of VMO in both the step up and step down phases of the stair-stepping task (p < .05). In contrast, no such differences occurred in the onsets of EMG activity of VMO and VL in either phase of the task for the control subjects. Conclusion: This finding supports the hypothesized relationship between changes in the timings of activity of the vastimuscles and PFPS. This finding provides theoretical rationale to support physiotherapy treatment commonly used in the management of PFPs.