Smoking cessation in the workplace.

BACKGROUND: The workplace is an important setting for reaching potentially large numbers of smokers. AIMS: To review the evidence about smoking cessation in the workplace. METHODS: Literature review including a synthesis of findings from recent systematic reviews and meta-analyses of workplace smoking cessation programmes, a separate review of the qualitative evidence, case studies and an expert panel assessment. RESULTS: We found advantages, identified or confirmed from the mixed methods used in this work to holding smoking cessation programmes in the workplace. These included: (i) easy access to large numbers of worker populations for large workplaces, (ii) the potential improved recruitment to such programmes given this, (iii) the opportunity to access young men, traditionally difficult to achieve, (iv) access to occupational health and other staff who can assist with support and delivery and (v) ability for workers to attend relatively easily. Evidence on the importance of developing peer support at work was mixed. The simple provision or availability of programmes and interventions was unlikely to provide any beneficial behaviour change. Interventions should target workers that actively want to stop smoking, use elements that workers have identified as useful or focus on altering beliefs about smoking and the need to stop. CONCLUSIONS: Smoking cessation programmes at work can provide useful support for workers wishing to stop smoking. They are only likely to be effective if participants have moved beyond the contemplation stage regarding smoking cessation, so that stopping smoking is a personal priority.

Interaction between human CD2 and CD58 involves the major beta sheet surface of each of their respective adhesion domains.

The CD58 binding site on human CD2 was recently shown by nuclear magnetic resonance structural data in conjunction with site-directed mutagenesis to be a highly charged surface area covering approximately 770A2 on the major AGFCC'C" face of the CD2 immunoglobulin-like (Ig-like) NH2-terminal domain. Here we have identified the other binding surface of the CD2-CD58 adhesion pair by mutating charged residues shared among CD2 ligands (human CD58, sheep CD58, and human CD48) that are predicted to be solvent exposed on a molecular model of the Ig-like adhesion domain of human CD58. This site includes beta strand residues along the C strand (E25, K29, and K30), in the middle of the C' strand (E37) and in the G strand (K87). In addition, several residues on the CC' loop (K32, D33, and K34) form this site. Thus, the interaction between CD2 and CD58 involves the major beta sheet surface of each adhesion domain. Possible docking orientations for the CD2-CD58 molecular complex are offered. Strict conservation of human and sheep CD58 residues within the involved C and C' strands and CC' loop suggests that this region is particularly important for stable formation of the CD2-CD58 complex. The analysis of this complex offers molecular insight into the nature of a receptor-ligand pair involving two Ig family members.

The clinical effectiveness of negative pressure wound therapy: a systematic review.

OBJECTIVE: To estimate the efficacy of negative pressure wound therapy (NPWT), on the basis of a systematic review of reported randomised controlled trials (RCTs). METHOD: A systematic literature search for relevant RCTs was carried out. The credibility of the outcome of each study was evaluated using a specially constructed instrument. RESULTS: We identified 17 RCTs, of which five had not been included in previous reviews or health technology assessments. For diabetic foot ulcers (seven RCTs), there was consistent evidence of the benefit of NPWT compared with control treatments. For pressure ulcers (three RCTs), results were conflicting. In trials involving mixed wounds (five RCTs), evidence was encouraging but of inadequate quality. Significant complications were not increased. CONCLUSION: There is now sufficient evidence to show that NPWT is safe, and will accelerate healing, to justify its use in the treatment of diabetes-associated chronic leg wounds. There is also evidence, though of poor quality, to suggest that healing of other wounds may also be accelerated.

Responding to health impacts of climate change in the Australian desert.

Climate change is likely to have a significant effect on the health of those living in the 70% of Australia that is desert. The direct impacts on health, such as increased temperature, are important. But so too are the secondary impacts that will occur as a result of the impact of climate change on an uncertain and highly variable natural environment and on the interlinking social and economic systems. The consequence of these secondary impacts will appear as changes in the incidence of disease and infections, and on the psychosocial determinants of health. Responding to the impacts of climate change on health in desert Australia will involve the active participation of a variety of interest groups ranging from local to state and federal governments and a range of public and private agencies, including those not traditionally defined as within the health sector. The modes of engagement required for this process need to be innovative, and will differ among regions on different trajectories. To this end, a first classification of these trajectories is proposed.

Altered G-protein expression and adenylate cyclase activity in platelets of non-insulin-dependent diabetic (NIDDM) male subjects.

Adenylate cyclase activity and levels of guanine nucleotide regulatory proteins (G-proteins) were compared in platelets from normal and non-insulin-dependent diabetic (NIDDM) male subjects. Whilst no differences were noted in basal and NaF-stimulated adenylate cyclase activities the degree of stimulation achieved by both forskolin and prostaglandin, E1 was lower by some 34 and 52% respectively, in platelet membranes from diabetic subjects compared with those from normal control subjects. Altered alpha 1-adrenoceptor-mediated inhibition of prostaglandin E1-stimulated adenylate cyclase activity was evident; it being some 34% lower in platelet membranes from diabetic subjects compared to controls. Analysis of G-protein alpha-subunits, using specific anti-peptide antisera, showed that platelets from all subjects exhibited the Gi-2 and Gi-3, but not the Gi-1 forms of the inhibitory G-protein 'Gi' and all expressed the 42 kDa species of alpha-subunit of the stimulatory G-protein Gs. Whilst platelets of diabetic subjects had levels of Gs which were comparable to those found in control subjects their levels of Gi-2 and Gi-3 were some 49 and 75%, respectively, of those found in platelets from control subjects. It is suggested that changes in adenylate cyclase functioning and G-protein expression may contribute to altered platelet functioning in non-insulin-dependent diabetic subjects.

Analysis of the relationship between side-chain conformation and secondary structure in globular proteins.

The relationship between the preferred side-chain dihedral angles and the secondary structure of a residue was examined. The structures of 61 proteins solved to a resolution of 2.0 A (1 A = 0.1 nm) or better were analysed using a relational database to store the information. The strongest feature observed was that the chi 1 distribution for most side-chains in an alpha-helix showed an absence of the g- conformation and a shift towards the t conformation when compared to the non-alpha/beta structures. The exceptions to this tendency were for short polar side-chains that form hydrogen bonds with the main-chain which prefer g+. Shifts in the chi 1 preferences for residues in the beta-sheet were observed. Other side-chain dihedral angles (chi 2, chi 3, chi 4) were found to be influenced by the main-chain. This paper presents more accurate distributions for the side-chain dihedral angles which were obtained from the increased number of proteins determined to high resolution. The means and standard deviations for chi 1 and chi 2 angles are presented for all residues according to the secondary structure of the main-chain. The means and standard deviations are given for the most popular conformations for side-chains in which chi 3 and chi 4 rotations affect the position of C atoms.

Chronic care clinics for diabetes in primary care: a system-wide randomized trial.

OBJECTIVE: To evaluate the impact of primary care group visits (chronic care clinics) on the process and outcome of care for diabetic patients. RESEARCH DESIGN AND METHODS: We evaluated the intervention in primary care practices randomized to intervention and control groups in a large-staff model health maintenance organization (HMO). Patients included diabetic patients > or = 30 years of age in each participating primary care practice, selected at random from an automated diabetes registry. Primary care practices were randomized within clinics to either a chronic care clinic (intervention) group or a usual care (control) group. The intervention group conducted periodic one-half day chronic care clinics for groups of approximately 8 diabetic patients in their respective doctor's practice. Chronic care clinics consisted of standardized assessments; visits with the primary care physician, nurse, and clinical pharmacist; and a group education/peer support meeting. We collected self-report questionnaires from patients and data from administrative systems. The questionnaires were mailed, and telephoned interviews were conducted for nonrespondents, at baseline and at 12 and 24 months; we queried the process of care received, the satisfaction with care, and the health status of each patient. Serum cholesterol and HbA1c levels and health care use and cost data was collected from HMO administrative systems. RESULTS: In an intention-to-treat analysis at 24 months, the intervention group had received significantly more recommended preventive procedures and helpful patient education. Of five primary health status indicators examined, two (SF-36 general health and bed disability days) were significantly better in the intervention group. Compared with control patients, intervention patients had slightly more primary care visits, but significantly fewer specialty and emergency room visits. Among intervention participants, we found consistently positive associations between the number of chronic care clinics attended and a number of outcomes, including patient satisfaction and HbA1c levels. CONCLUSIONS: Periodic primary care sessions organized to meet the complex needs of diabetic patients imrproved the process of diabetes care and were associated with better outcomes.

Evidence for a role for α6(∗) nAChRs in l-dopa-induced dyskinesias using Parkinsonian α6(∗) nAChR gain-of-function mice.

l-Dopa-induced dyskinesias (LIDs) are a serious side effect of dopamine replacement therapy for Parkinson's disease. The mechanisms that underlie LIDs are currently unclear. However, preclinical studies indicate that nicotinic acetylcholine receptors (nAChRs) play a role, suggesting that drugs targeting these receptors may be of therapeutic benefit. To further understand the involvement of α6ß2(∗) nAChRs in LIDs, we used gain-of-function α6(∗) nAChR (α6L9S) mice that exhibit a 20-fold enhanced sensitivity to nAChR agonists. Wildtype (WT) and α6L9S mice were lesioned by unilateral injection of 6-hydroxydopamine (6-OHDA, 3µg/ml) into the medial forebrain bundle. Three to 4wk later, they were administered l-dopa (3mg/kg) plus benserazide (15mg/kg) until stably dyskinetic. l-dopa-induced abnormal involuntary movements (AIMs) were similar in α6L9S and WT mice. WT mice were then given nicotine in the drinking water in gradually increasing doses to a final 300µg/ml, which resulted in a 40% decline AIMs. By contrast, there was no decrease in AIMs in α6L9S mice at a maximally tolerated nicotine dose of 20µg/ml. However, the nAChR antagonist mecamylamine (1mg/kg ip 30min before l-dopa) reduced l-dopa-induced AIMs in both α6L9S and WT mice. Thus, both a nAChR agonist and antagonist decreased AIMs in WT mice, but only the antagonist was effective in α6L9S mice. Since nicotine appears to reduce LIDs via desensitization, hypersensitive α6ß2(∗) nAChRs may desensitize less readily. The present data show that α6ß2(∗) nAChRs are key regulators of LIDs, and may be useful therapeutic targets for their management in Parkinson's disease.

Myocardial ischemia. Towards better use of the coronary care unit.

The coronary care unit is an expensive facility. Attempts to prove its value have not been successful, and the difficulty of doing so is considerable. In the absence of proof, it is nevertheless still necessary to establish a reasonable approach to the use of this facility. Such an approach and the evidence in its support are summarized. Pending the acquisition of more accurate predictors of risk, the following arbitrary guidelines are suggested. The coronary care unit is an appropriate environment for the management of dangerous arrhythmias and the major complications of infarction, for the management of resting angina until asymptomatic for 24 hours, and for the management of uncomplicated infarction in the absence of all predictors of risk for a period of 24 hours after the last episode of ischemic pain. Longer observation may be desirable for patients with certain predictors of short-term risk.

Pathogenesis of angina pectoris and role of nitrates in relief of myocardial ischemia.

The pathophysiologic mechanism of angina of effort has been understood for one and three-quarter centuries. However, the mechanisms underlying angina at rest are still largely unknown. Coronary spasm, whatever its mechanism, clearly causes Prinzmetal's variant angina. However, evidence that spasm is the cause of all angina at rest is wanting. Rather than spasm, it is suggested that most attacks may be the result of normal fluctuations in the tone of conductive coronary arteries in the presence of critical levels of organic obstruction. The nitrates both relieve coronary spasm and diminish normal coronary tone. They also affect the systemic circulation, so as to favorably influence the level of energy demand.

Acetylcholine receptor antibodies in the elderly and in Down's syndrome.

Serum antibodies to the acetylcholine receptor (anti-AChR) have been reported in Japanese individuals who were elderly or had Down's syndrome at frequencies of 18% and 24%, respectively. We have measured serum anti-AChR in 3 Caucasoid groups: 53 elderly patients (aged 65-92 years) with miscellaneous (non-myasthenic) disorders, 30 individuals with Down's syndrome, and 40 elderly patients (aged 71-93 years) known to have strongly positive thyroid autoantibodies. A raised titre (greater than 0.2 nmol/l) was confined to 3 patients in the third group (7.5%). We conclude that an increased frequency of anti-AChR antibodies is not a feature of Caucasians who are elderly or have Down's syndrome, and that, even in an elderly group with a high titre of another autoantibody, the frequency of anti-AChR is lower than in elderly Japanese individuals.

Levodopa/carbidopa for childhood amblyopia.

PURPOSE: To evaluate the efficacy and tolerance of two low doses of levodopa/carbidopa (25/6.25 mg, 50/12.5 mg) and placebo (Tums) in 20 children with amblyopia between the ages of 4 and 14 years. METHODS: A double-masked placebo-controlled randomized 8-hour study was performed during which subjects received one of two doses of levodopa/carbidopa or placebo, combined with occlusion of the dominant eye. Visual acuity was measured at baseline and at 1 and 5 hours after capsule ingestion. Tolerance was assessed by questionnaire and physical examination. RESULTS: Visual acuity significantly improved by one line, from an overall average of 20/121 to 20/96, in the amblyopic eyes of both groups that received levodopa/carbidopa. Visual acuity did not significantly change in the placebo group. Tolerance was similar among all three groups. CONCLUSION: Average dose levels of 0.95/0.24 mg/kg and 1.94/0.49 mg/kg of levodopa/carbidopa were found to be well tolerated and efficacious at temporarily improving visual acuity in amblyopic eyes of children.

Possible interactions of indomethacin and nitrates in angina pectoris.

Intravenous indomethacin has been reported to diminish coronary flow in patients with angina. There is also evidence that indomethacin attenuates or abolishes the coronary dilator and venodilator effects of nitroglycerin. In 11 patients with stable angina of effort, prior administration of 100 mg of indomethacin appeared to increase (0.10 greater than p greater than 0.05), rather than reduce, the work load achieved compared with placebo on a double-blind basis. The increase in work load when patients were given nitroglycerin was not significantly changed after they were given indomethacin. Therefore, this study does not support the suggestion either that prostaglandins play a significant role in coronary vasoregulation on effort or that prostacyclin is an important mediator of the therapeutic action of nitroglycerin. From a practical therapeutic viewpoint, there is apparently no danger of aggravating stable, exercise-induced angina or of abolishing the benefit normally expected from nitroglycerin when patients with angina are given indomethacin in doses comparable to those used in this study.

Validity of the hepatojugular reflux as a clinical test for congestive heart failure.

This study describes observations designed to test the validity of the hepatojugular reflux as an indicator of actual or incipient heart failure. The central venous pressure (CVP) could be predicted from the height of the jugular venous pulsations in 44 of 48 comparisons. In the remaining comparisons, discrepancies ranged from 5 to 7 mm Hg. In patients with normal resting cardiac function, abdominal compression did not cause an increase in CVP of greater than 2 mm Hg (2.7 mm H2O). In 16 of 19 patients with impaired function, CVP increased by greater than or equal to 3 mm Hg. The increase in CVP was estimated from neck veins to within 2 mm Hg in all but 3 instances. CVP stabilized by 10 seconds and did not change over the subsequent 60 seconds. Abdominal compression caused no consistent change in cardiac output. Changes in venous pressure could not be attributed to changes in esophageal pressure or to compression of the heart by elevation of the diaphragm. Observations were consistent with the hypothesis that an increase in right-sided cardiac filling pressures resulting from abdominal compression carried out as described here, reflects both the volume of blood in the abdominal veins and the ability of the ventricles to respond to increased venous return, and constitutes a useful clinical test for detecting congestive cardiac failure. An increase of 3 cm in the height of neck vein distention is a reasonable upper limit of normal.

Combination of theophylline and salbutamol for arrhythmias in severe COPD.

We conducted a single-bind placebo controlled study using 24-hour continuous ambulatory electrocardiographic recordings. The arrhythmogenic potential of the combination of salbutamol and theophylline was investigated in 25 ambulatory subjects with severe chronic airflow obstruction (mean age 65 +/- 8 SD, mean FEV1 31 percent +/- 13 SD predicted). Asymptomatic arrhythmias were very prevalent in the study population: 76 percent of the patients had runs of supraventricular tachycardia while 24 percent had runs of ventricular tachycardia. Individual arrhythmia frequency showed greater between-test variability than previously described in non-COPD subjects. The mode of administration of salbutamol may have affected arrhythmia frequency in that subjects using aerosol nebulizers had more ventricular extrasystoles than those using metered dose inhalers. Although the addition of theophylline to salbutamol significantly increased heart rate and supraventricular extrasystoles, there was no statistically significant increase in ventricular arrhythmias.

CO2 capture by means of an enzyme-based reactor.

We report a means for efficient and selective extraction of carbon dioxide (CO(2)) at low to medium concentration from mixed gas streams. CO(2) capture was accomplished by use of a novel enzyme-based, facilitated transport contained liquid membrane (EBCLM) reactor. The parametric studies we report explore both structural and operational parameters of this design. The structural parameters include carbonic anhydrase (CA) concentration, buffer concentration and pH, and liquid membrane thickness. The operational parameters are temperature, humidity of the inlet gas stream, and CO(2) concentration in the feed stream. The data show that this system effectively captures CO(2) over the range 400 ppm to at least 100,000 ppm, at or around ambient temperature and pressure. In a single pass across this homogeneous catalyst design, given a feed of 0.1% CO(2), the selectivity of CO(2) versus N(2) is 1,090 : 1 and CO(2) versus O(2) is 790 :1. CO(2) permeance is 4.71 x 10(-8) molm(-2) Pa(-1) sec(-1). The CLM design results in a system that is very stable even in the presence of dry feed and sweep gases.

The use of nicotinamide in the prevention of type 1 diabetes.

Nicotinamide can protect the NOD mouse from diabetes if given early enough and in sufficient dose. The effect partly wanes with time. There is reduced islet inflammation. Similar protective effects can be demonstrated in quasi-experimental interventions in humans--both diabetes related and unrelated deemed at risk of developing diabetes by reason of having islet cell antibodies. Nicotinamide protects isolated islets in vitro from the toxicity of a number of agents, but only in doses that produce significant PARP inhibition, and increased intracellular levels of NAD. It is unlikely that the protective effect demonstrated in humans is due to significant PARP inhibition, as the levels of nicotinamide achieved with the doses used are too low. Other effects of the vitamin are more likely, e.g., increase in NAD pool size by de novo synthesis, or inhibition of free radical generation. The drug appears to be safe in the doses employed in humans.

No evidence of infection with porcine endogenous retrovirus in recipients of encapsulated porcine islet xenografts.

Transplantation of pig tissues into humans has the potential for cotransferring pig infections. Knowledge of the epidemiology of pig infections transmissible to humans allows the development of risk limitation strategies at the source herd level, but potentially infectious pig endogenous retrovirus (PERV) is ubiquitous in all domestic pigs and therefore is not avoidable. Using a specific and sensitive RT-PCR and nested PCR for PERV nucleic acids with primers, the screening of pigs from New Zealand herds for the presence and expression of the PERV was conducted. The presence of PERV proviral DNA (pol and env region) and viral RNA was demonstrated in all tested pig tissues including pancreas, liver, spleen, brain, heart, and PBMC. Using the same assays it was established that different tissues (liver, spleen, and heart) of nude and nonobese diabetic (NOD) mice previously transplanted with nonencapsulated pig islets were PERV DNA and RNA negative. Alginate polylysine capsules prepared with encapsulated pig islets were tested for possible leakage of viral particles or viral nucleic acids. RNA was extracted from the supernatant of viable encapsulated pig islet cells grown in culture for 2 months. No evidence of PERV RNA or of cellular nucleic acids could be found. Two adult type I diabetic subjects were transplanted with 1 x 10(6) neonatal pig islets encased in alginate capsules into the peritoneal cavity. One patient was immunosuppressed. Both showed evidence of graft function (up to 34% reduction in insulin dose, corresponding increase in serum pig C-peptide) for up to 2 years. DNA and RNA were extracted from PBMC and blood plasma of both patients at 19 months posttransplant. No evidence of PERV proviral DNA or RNA could be detected. Piglet islets contain PERV DNA and RNA, but this does not traverse the capsules used or produce any evidence of infection in nude and nonobese diabetic (NOD) mice or humans.

Cost effectiveness of screening for primary open angle glaucoma.

OBJECTIVES AND SETTING: To determine the cost effectiveness of screening for glaucoma. METHODS: Information on treatment efficacy, diagnostic methods, epidemiological characteristics of glaucoma, and costs were determined from the literature, from administrative databases, and from experts. Scenarios with different screening frequency, age, participation in screening, compliance with treatment, treatment efficacy, and diagnostic tests were examined. RESULTS: The initial scenario comprised three-yearly screening of subjects aged 40-79 by funduscopy and tonometry, followed by perimetry when abnormalities were discovered. The assumption of levels of participation in screening and of compliance with treatment of 75%, and treatment efficacy of 50% resulted in a cost of $C100,000 per year of blindness prevented. A scenario in which screening was restricted to subjects aged 65-79, with the same input variables, would prevent 81% of the cases of blindness prevented with scenario 1, at a cost of $C42,000 per year of blindness prevented. Screening with tonometry only as the initial diagnostic test in subjects aged 65-79 would result in a cost of $C36,000 per year of blindness prevented, but would only prevent 59% of the cases prevented with scenario 1. CONCLUSIONS: There is as yet no proof that treatment of glaucoma or of high intraocular pressure will arrest the progression of glaucoma to blindness. Even when treatment efficacy is assumed to be as high as 50%, however, the cost effectiveness of most glaucoma screening programmes considered would not be competitive.