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Biomedical subjects

T Lancaster

Publications and source records attributed to T Lancaster.

At least 37 records · Page 2Linked to original sources
PubMed2002

Quantitative and functional differences in CD8+ lymphocyte responses in resolved acute and chronic hepatitis C virus infection.

CD8+ T lymphocyte responses are important in the clearance of viral infections. In chronic infections they may contribute to pathogenesis. To investigate the role of CD8+ T lymphocyte responses in viral clearance and chronic hepatitis C we have compared hepatitis C virus (HCV) specific cytotoxicity and interferon-gamma (IFN-gamma) production in patients with resolved-acute, and chronic HCV infection. CD8+ T cell responses to a panel of 13 HCV T cell peptide epitopes were studied using Elispot assays of IFN-gamma production and chromium release cytotoxicity assays. Responses of seven patients with resolved acute HCV infection were compared with those of 14 chronically infected patients. HCV-specific cytotoxicity differentiated the two populations of patients. The majority (71%) of patients with resolved acute infection tested positive to 42% of relevant peptides compared with the minority (28%) of patients with chronic hepatitis C (P=0.03) who responded to only 8% of relevant peptides (P=0.0009). In contrast, HCV-specific IFN-gamma production was detected in 86% of patients with either resolved or chronic infection in response to 42% and 35%, respectively, of relevant peptides tested (not significant). In patients with chronic infection the magnitude of the HCV-specific IFN-gamma production was inversely correlated to viral load (R2=0.52; P=0.042). Failure to clear HCV infection may be attributable to the presence of noncytolytic IFN-gamma producing CD8+ T lymphocytes in chronically infected patients. However these CD8+ T cells may play a beneficial role in contributing to the control of viral load in chronic hepatitis C.

Acute Disease↗
PubMed2002

Changes in the motility of B16F10 melanoma cells induced by alterations in resting calcium influx.

Alterations in the extracellular Ca(2+) or K(+) concentration had significant influences on the motility of B16F10 melanoma cells measured in the absence of exogenous integrins using a conventional Boyden chamber assay. At normal K(+) concentrations, motility increased slightly when the concentration of Ca(2+) was increased 10-fold. At normal Ca(2+) concentrations, motility increased by 290% when the extracellular K(+) concentration was reduced 10-fold (from control of 5.4 mM to 0.54 mM), and increased to 250% of control levels when the K(+) concentration was increased between 30 and 54 mM, but was relatively uninfluenced at K(+) concentrations between 5 and 30 mM. Simultaneous application of low concentrations (20 microM) of GdCl(3) completely prevented the effects of low and high K(+) on motility. Exposure to Gd(3+) or Tb(3+) also produced a flattening of the cells and enhanced cell attachment. Although the steady state intracellular Ca(2+) concentration was not significantly influenced by the K(+) concentration, the resting permeability to divalent cations, determined from Mn(2+) quench rates in fura-loaded cells, was significantly increased by a reduction in the K(+) concentration. These results indicate that resting Ca(2+) influx is critical to the movement of B16F10 melanoma cells, and demonstrate that lanthanides, which block resting Ca(2+) influx pathways, are potent antimotility agents.

Calcium↗
PubMed2001

Updating a systematic review--what difference did it make? Case study of nicotine replacement therapy.

AIMS: To examine the effect of updating a systematic review of nicotine replacement therapy on its contents and conclusions. METHODS: We examined the effects of regular updating of a systematic review of nicotine replacement therapy for smoking cessation. We considered two outcomes. First, we assessed the effect of adding new data to meta-analyses, comparing results in 2000 with the results in 1994. Second, we assessed qualitatively the ways in which the nature of the questions addressed by the review had changed between the two dates. For the first outcome, we compared the number of trials, the pooled estimate of effect using the odds ratio, and the results of pre-specified subgroup analyses, for nicotine gum and patch separately. Using a test for interaction, we assessed whether differences between estimates were statistically significant. RESULTS: There were ten new trials of nicotine gum between 1994 and 2000, and the meta-analytic effect changed little. For the nicotine patch the number of trials increased from 9 to 30, and the meta-analytic effect fell from 2.07 (95% CI 1.64 - 2.62) to 1.73 (95% CI 1.56 - 1.93). Apparent differences in relative effect in sub-groups found in 1994 were not found in 2000. The updated systematic review addressed a number of questions not identified in the original version. CONCLUSIONS: Updating the meta-analyses lead to a more precise estimate of the likely effect of the nicotine patch, but the clinical message was unchanged. Further placebo controlled NRT trials are not likely to add to the evidence base. It is questionable whether updating the meta-analyses to include them is worthwhile. The content of the systematic review has, however, changed, with the addition of data addressing questions not considered in the original review. There is a tension between the principle of identifying the important questions prior to conducting a review, and keeping the review up to date as primary research identifies new avenues of enquiry.

Humans↗
PubMed2001

Use of systematic reviews in clinical practice guidelines: case study of smoking cessation.

OBJECTIVE: To examine the extent to which recommendations in the national guidelines for the cessation of smoking are based on evidence from systematic reviews of controlled trials. DESIGN: Retrospective analysis of recommendations for the national guidelines for the cessation of smoking. MATERIALS: National guidelines in clinical practice on smoking cessation published in English. MAIN OUTCOME MEASURES: The type of evidence (systematic review of controlled trials, individual trials, other studies, expert opinion) used to support each recommendation. We also assessed whether a Cochrane systematic review was available and could have been used in formulating the recommendation. RESULTS: Four national smoking cessation guidelines (from Canada, New Zealand, the United Kingdom, and the United States) covering 105 recommendations were identified. An explicit evidence base for 100%, 89%, 68%, and 98% of recommendations, respectively, was detected, of which 60%, 56%, 59%, and 47% were based on systematic reviews of controlled studies. Cochrane systematic reviews could have been used to develop between 39% and 73% of recommendations but were actually used in 0% to 36% of recommendations. The UK guidelines had the highest proportion of recommendations based on Cochrane systematic reviews. CONCLUSIONS: Use of systematic reviews in guidelines is a measure of the "payback" on investment in research synthesis. Systematic reviews commonly underpinned recommendations in guidelines on smoking cessation. The extent to which they were used varied by country and there was evidence of duplication of effort in some areas. Greater international collaboration in developing and maintaining an evidence base of systematic reviews can improve the efficiency of use of research resources.

Controlled Clinical Trials as Topic↗
PubMed2001

Telephone counselling for smoking cessation.

BACKGROUND: Telephone services can provide information and support for smokers. Counselling may be provided proactively or offered reactively to callers to smoking cessation helplines. OBJECTIVES: To evaluate the effect of proactive and reactive telephone support to help smokers quit. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register for studies using free text term 'telephone*' or the keywords 'telephone counselling' or 'Hotlines' or 'Telephone'. Date of the most recent search: August 2000. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in which proactive or reactive telephone counselling to assist smoking cessation was offered to smokers or recent quitters. DATA COLLECTION AND ANALYSIS: Trials were identified and data extracted by one person and checked by a second. The main outcome measure was abstinence from smoking after at least six months follow-up. We used the most rigorous definition of abstinence in each trial, and biochemically validated rates where available. Participants lost to follow-up were considered to be continuing smokers. Where interventions were similar, we performed meta-analysis using a fixed effects model to give an odds ratio. MAIN RESULTS: Twenty three trials met inclusion criteria. Ten trials compared proactive counselling to a minimal intervention control. There was statistical heterogeneity, with three trials showing a significant benefit, and seven showing non significant differences. Four trials adding telephone support to a face to face intervention control failed to detect a significant effect on long term quit rates. Four trials failed to detect an additional effect of telephone support in users of nicotine replacement therapy. Providing access to a hotline showed a significant benefit in one trial and no significant difference in two. Varying the type of counselling provided has not been shown to affect outcome. REVIEWER'S CONCLUSIONS: Proactive telephone counselling can be effective compared to an intervention without personal contact. There was heterogeneity between trials so the size of effect is uncertain. The available evidence neither confirms nor rules out a benefit of telephone counselling as an adjunct to face to face counselling or pharmacotherapy. Further trials randomising access to helplines are unlikely to be done but indirect evidence suggests they can be a useful part of a smoking cessation service.

Counseling↗
PubMed2001

Opioid antagonists for smoking cessation.

BACKGROUND: The reinforcing properties of nicotine may be mediated through release of various neurotransmitters both centrally and systemically. Smokers report positive effects such as pleasure, arousal, and relaxation as well as relief of negative affect, tension, and anxiety. Opioid (narcotic) antagonists are of particular interest to investigators as potential agents to attenuate the rewarding effects of cigarette smoking. OBJECTIVES: To evaluate the efficacy of opioid antagonists in promoting long-term smoking cessation. The drugs include naloxone and the longer-acting opioid antagonist naltrexone. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register for trials of naloxone, naltrexone and other opioid antagonists and conducted an additional search of Medline using '"Narcotic antagonists" and smoking terms in March 2001. We also contacted, when possible, investigators for information on unpublished studies. SELECTION CRITERIA: We considered randomized controlled trials comparing opioid antagonists to placebo or an alternative therapeutic control for smoking cessation. We included only trials reporting data on abstinence of a minimum of 6 months in the meta-analyses. We also reviewed, for descriptive purposes, results from short-term laboratory-based studies of opioid antagonists designed to evaluate psychobiological mediating variables associated with nicotine dependence. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of study population, the nature of the drug therapy, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was cotinine or carbon monoxide verified abstinence from smoking after at least six months follow-up in patients smoking at baseline. Where appropriate, we performed meta-analysis using a fixed effects model (Peto method). MAIN RESULTS: Two trials of naltrexone met inclusion criteria for meta-analyses for long term cessation. Both trials failed to detect a significant difference in quit rates between naltrexone and placebo. In a pooled analysis there was no significant effect of naltrexone on long-term abstinence, and confidence intervals were wide (OR 1.34, 95% CI 0.49,3.63). No trials of naloxone or buprenorphine reported long term follow-up REVIEWER'S CONCLUSIONS: Based on limited data from two trials it is not possible to confirm or refute whether naltrexone helps smokers quit. The confidence intervals are compatible with both clinically significant benefit and possible negative effects of naltrexone in promoting abstinence. Data from larger trials of naltrexone are needed to settle the question of efficacy for smoking cessation.

Buprenorphine↗
PubMed2001

Helping parents to stop smoking: which interventions are effective?

Parental smoking increases children's risk of respiratory illness. Encouraging parents not to smoke in the home helps, but stopping smoking altogether is more effective in reducing children's exposure. The prevalence of smoking increases with higher levels of social disadvantage and is therefore a major contributor to widening inequalities in health. Randomised trials have shown that adults can be helped to stop with simple advice from health professionals, behavioural support, nicotine replacement and antidepressants.

Adult↗
PubMed2001

Interventions for smoking cessation in hospitalised patients: a systematic review.

BACKGROUND: An admission to hospital provides an opportunity to help people stop smoking. Individuals may be more open to help at a time of perceived vulnerability, and may find it easier to quit in an environment where smoking is restricted or prohibited. Providing smoking cessation services during hospitalisation may help more people to attempt and sustain an attempt to quit. The purpose of this paper is to systematically review the effectiveness of interventions for smoking cessation in hospitalised patients. METHODS: We searched the Cochrane Tobacco Addiction Group register, CINAHL, and the Smoking and Health database for studies of interventions for smoking cessation in hospitalised patients. Randomised and quasi-randomised trials of behavioural, pharmacological, or multi-component interventions to help patients stop smoking conducted with hospitalised patients who were current smokers or recent quitters were included. Studies of patients admitted for psychiatric disorders or substance abuse, those that did not report abstinence rates, and those with follow up of less than 6 months were excluded. Two of the authors extracted data independently for each paper, with assistance from others. RESULTS: Intensive intervention (inpatient contact plus follow up for at least 1 month) was associated with a significantly higher cessation rate compared with controls (Peto odds ratio (OR) 1.82, 95% CI 1.49 to 2.22). Any contact during hospitalisation followed by minimal follow up failed to detect a statistically significant effect on cessation rate, but did not rule out a 30% increase in smoking cessation (Peto OR 1.09, 95% CI 0.91 to 1.31). There was insufficient evidence to judge the effect of interventions delivered only during the hospital stay. Although the interventions increased quit rates irrespective of whether nicotine replacement therapy (NRT) was used, the results for NRT were compatible with other data indicating that it increases quit rates. There was no strong evidence that clinical diagnosis affected the likelihood of quitting. CONCLUSIONS: High intensity behavioural interventions that include at least 1 month of follow up contact are effective in promoting smoking cessation in hospitalised patients.

Adult↗
PubMed2000

Phage display of ScFv peptides recognizing the thymidine(6-4)thymidine photoproduct.

Solar ultraviolet (UV) radiation induces DNA photoproducts in skin cells and is the predominant cause of human skin cancers. To understand human susceptibility to skin cancer and to facilitate the development of prevention measures, highly specific reagents to detect and quantitate UV-induced DNA adducts in human skin will be needed. One approach towards this end is the use of monoclonal antibody-based molecular dosimetry methods. To facilitate the development of photoproduct-specific antibody reagents we have: (i) cloned and sequenced a single chain variable fragment (ScFv) gene coding for one such high affinity monoclonal antibody, [alpha]UVssDNA-1 (mAb C3B6), recognizing the thymidine(6-4)thymidine photoproduct; (ii) expressed and displayed the cloned ScFv gene on the surface of phage; (iii) selected functional recombinant phage by panning; (iv) purified the ScFv peptide; (v) shown that the purified ScFv peptide binds to UV-irradiated polythymidylic acid but not unirradiated polythymidylic acid. This is the first demonstration of the use of phage display to select a ScFv recognizing DNA damage. In addition, this is the initial step towards immortalizing the antibody gene for genetic manipulation, structure-function studies and application to human investigations.

Amino Acid Sequence↗
PubMed2000

Anxiolytics and antidepressants for smoking cessation.

BACKGROUND: There are two reasons to believe antidepressants and anxiolytics might help in smoking. First, anxiety and depression are symptoms of nicotine withdrawal, and smoking cessation sometimes precipitates depression. Second, smoking appears to be due, in part, to deficits in dopamine, serotonin and norepinephrine, all of which are increased by anxiolytics and antidepressants. OBJECTIVES: The aim of this review is to assess the effectiveness of such drugs in aiding long term smoking cessation. The drugs include bupropion; buspirone; diazepam; doxepin; fluoxetine; imipramine; meprobamate; moclobemide; nortriptyline; tryptophan; ondansetron; venlafaxine and the beta-blockers metoprolol, oxprenolol and propanolol. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register which includes trials indexed in Medline, Embase, SciSearch and PsycLit, and meetings abstracts. SELECTION CRITERIA: We considered randomized trials comparing anxiolytic or antidepressant drugs to placebo or an alternative therapeutic control for smoking cessation. We excluded trials with less than 6 months follow-up. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of study population, the nature of the drug therapy, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed effects model. MAIN RESULTS: There was one trial each of the anxiolytics diazepam, meprobamate, metoprolol and oxprenolol. There were two trials of the anxiolytic buspirone. None of these showed evidence of effectiveness in helping smokers to quit. There was one trial each of the antidepressants fluoxetine and moclobemide, two of nortriptyline, and four trials of bupropion. Nortriptyline and bupropion increased cessation and other antidepressants might also be effective. One trial found combined bupropion and nicotine patch produced higher quit rates than patch alone. REVIEWER'S CONCLUSIONS: There is little evidence that anxiolytics aid smoking cessation. Some antidepressants (bupropion and nortriptyline) can aid smoking cessation. It is not clear whether these effects are specific for individual drugs, or a class effect.

Anti-Anxiety Agents↗
PubMed2000

Nicotine replacement therapy for smoking cessation.

BACKGROUND: The aim of nicotine replacement therapy (NRT) is to replace nicotine from cigarettes. This reduces withdrawal symptoms associated with smoking cessation to help resist the urge to smoke cigarettes. OBJECTIVES: The aims of this review were to determine the effectiveness of the different forms of nicotine replacement therapy (chewing gum, transdermal patches, nasal spray, inhalers and tablets) in achieving abstinence from cigarettes; to determine whether the effect is influenced by the clinical setting in which the smoker is recruited and treated, the dosage and form of the NRT used, or the intensity of additional advice and support offered to the smoker; and to determine whether combinations of NRT are more effective than one type alone. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register. SELECTION CRITERIA: Randomized trials in which NRT was compared to placebo or no treatment, or where different doses of NRT were compared. We excluded trials which did not report cessation rates, and those with follow-up of less than six months. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of subjects, the dose and duration and form of nicotine therapy, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed effects model. MAIN RESULTS: We identified 49 trials of nicotine gum, 32 of transdermal nicotine patch, four of intranasal nicotine spray, four of inhaled nicotine and two of nicotine sublingual tablet. Three trials compared combinations of two forms of nicotine therapy with one form alone. The odds ratio for abstinence with NRT compared to control was 1.72 (95% confidence interval 1.60 to 1.84), The odds ratios for the different forms of NRT were 1.63 for gum, 1.77 for patches, 2.27 for nasal spray, 2.08 for inhaled nicotine and 1.73 for nicotine sublingual tablet. These odds were largely independent of the intensity of additional support provided or the setting in which the NRT was offered. Eight weeks of patch therapy was as effective as longer courses and there was no evidence that tapered therapy was better than abrupt withdrawal. Wearing the patch only during waking hours (16 hours/day) was as effective as wearing it for 24 hours/day. The odds ratio for abstinence in the trials which directly compared 4 mg versus 2 mg gum in highly dependent smokers found a significant benefit in favour of 4 mg gum (odds ratio 2.67, 95% confidence interval 1.69 to 4.22). There is no strong evidence that combinations of forms of NRT are more effective. Only one study directly compared NRT against another pharmacotherapy (bupropion) and found that the latter was significantly more effective either alone or used in combination with nicotine patch than if nicotine patch was used alone. REVIEWER'S CONCLUSIONS: All of the commercially available forms of NRT (nicotine gum, transdermal patch, and in some countries, the nicotine nasal spray, nicotine inhaler and nicotine sublingual tablets) are effective as part of a strategy to promote smoking cessation. They increase quit rates approximately 1.5 to 2 fold regardless of setting. The effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the smoker. Since all the trials of NRT reported so far have included at least some form of brief advice to the smoker, this represents the minimum which should be offered in order to ensure its effectiveness. Provision of more intense levels of support, although beneficial in facilitating the likelihood of quitting, is not essential to the success of NRT. There is promising evidence that bupropion may be more effective than NRT (either alone or in combination). (ABSTRACT

Administration, Cutaneous↗
PubMed2000

Silver acetate for smoking cessation.

BACKGROUND: Silver acetate produces an unpleasant taste when combined with cigarettes, thereby producing an aversive stimulus. It has been marketed in various forms with the aim of extinguishing the urge to smoke, by pairing the urge with an unpleasant stimulus. OBJECTIVES: The aim of this review was to determine the effectiveness of silver acetate products (gum, lozenge, spray) in promoting smoking cessation. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register. SELECTION CRITERIA: We included randomised trials of silver acetate for smoking cessation with reports of smoking status at least six months after the beginning of treatment. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of subjects, the dose and form of silver acetate, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was biochemically validated abstinence from smoking after at least six months follow-up in patients smoking at baseline. Subjects lost to follow-up were counted as continuing smokers. Where appropriate, we performed meta-analysis using a fixed effects model. MAIN RESULTS: Two studies provided long-term follow-up data on patients randomised to silver acetate or placebo. In one of these studies, there was a third arm, randomised to 2mg nicotine gum. The combined odds ratio for quitting for silver acetate vs placebo was 1.05 (95% confidence interval 0.63 to 1.73). REVIEWER'S CONCLUSIONS: Existing trials show little evidence for a specific effect of silver acetate in promoting smoking cessation. The confidence intervals for the ratio are quite wide. However, the upper limit of the confidence intervals for a positive effect equates to an absolute increase in the smoking cessation rate of about 4%. Any effect of this agent is therefore likely to be smaller than nicotine replacement therapy. The lack of effect of silver acetate may reflect poor compliance with a treatment whose rationale is to create an unpleasant stimulus.

Acetates↗
PubMed2000

Training health professionals in smoking cessation.

BACKGROUND: There is good evidence that brief interventions from health professionals can increase rates of smoking cessation. A number of trials have examined whether specific skills training for health professionals leads them to have greater success in helping their patients who smoke. OBJECTIVES: The aim of this review was to assess the effectiveness of training health care professionals to deliver smoking cessation interventions to their patients, and to assess the additional effects of prompts and reminders to the health professional to intervene. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register for studies relating to training. SELECTION CRITERIA: Randomised trials in which the intervention was training of health care professionals in smoking cessation. Trials were considered if they reported outcomes for patient smoking rates at least six months after the intervention. We reported on process outcomes, but we excluded trials that reported effects only on process outcomes and not smoking behaviour. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of health professionals, the nature of and duration of the training, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measures were 1. Rates of abstinence from smoking after at least six months follow-up in patients smoking at baseline. 2. Rates of performance of tasks of smoking cessation by health care professionals including offering counselling, setting quit dates, giving follow-up appointments, distributing self-help materials and recommending nicotine gum. MAIN RESULTS: Healthcare professionals who had received training were more likely to perform tasks of smoking cessation than untrained controls. Of eight studies that compared patient smoking behaviour between trained professionals and controls, six found no effect of intervention. The effects of training on process outcomes increased if prompts and reminders were used. REVIEWER'S CONCLUSIONS: Training health professionals to provide smoking cessation interventions had a measurable effect on professional performance. There was no strong evidence that it changed smoking behaviour.

Health Personnel↗