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Biomedical subjects

S Wilson

Publications and source records attributed to S Wilson.

At least 19 recordsLinked to original sources
PubMed2006

Histamine H3 receptor antagonists: from target identification to drug leads.

The successful cloning and functional expression of the histamine H(3) receptor in the late 1990 s has greatly facilitated our efforts to identify small molecule, non-imidazole based compounds to permit the evaluation of H(3) antagonists in models of CNS disorders. High-throughput screening identified several series of lead compounds, including a series of imidazopyridines, which led to JNJ-6379490, a compound with high affinity for the human H(3) receptor. Analysis of structural features common to several series of non-imidazole H(3) receptor ligands resulted in a pharmacophore model. This model led to the design of JNJ-5207852, a diamine-based H(3) antagonist with good in vitro and in vivo efficacy but with an undesirable long half-life. However, further modifications of the template provided an understanding of the effect of structural modifications on pharmacokinetic properties, ultimately affording several additional series of compounds including JNJ-10181457, a compound with an improved pharmacokinetic profile. These compounds allowed in vivo pharmacological evaluation to show that H(3) antagonists promote wakefulness, but unlike modafinil and classical psychostimultants, they do not increase locomotor activity or produce any alteration of the EEG power spectral activity in rats. H(3) antagonists also increase extracellular acetylcholine and norepinephrine but not dopamine in rat frontal cortex and show efficacy in various models of learning-memory deficit. In addition, cFos immunoreactivity studies show H(3) antagonists activate neuronal cells in restricted rat brain regions in contrast to widespread activation after modafinil or amphetamine treatment. Therefore, H(3) antagonists are promising clinical candidates for the treatment of excessive day time sleepiness and/or cognitive disorders.

Animals↗
PubMed2006

Range of self-tests available to buy in the United Kingdom: an Internet survey.

We aimed to describe the availability in the United Kingdom of self-tests that are used to diagnose or screen for conditions without involving a health professional. A systematic Internet search identified 104 unique self-tests related to 24 named conditions including cancers, chronic conditions and infections. These self-tests require various samples including blood obtained using a lancet. The samples are processed at home with results available in minutes or sent to a laboratory for processing with results returned to the individual by e-mail or post. Prices per self-test and condition range from < Pounds 1 to Pounds 76. Self-tests are readily available, and further work is needed to assess their impact.

Diagnostic Equipment↗
PubMed2006

Systematic review: the effectiveness of hypnotherapy in the management of irritable bowel syndrome.

AIM: To systematically review the literature evaluating hypnotherapy in the management of irritable bowel syndrome (IBS). METHODS: Electronic databases were searched (Cochrane Library, Medline, CINAHL, AMED, Embase, PsycINFO, CISCOM, TRIP and the Social Science Citation index), bibliographic references scanned and main authors contacted. No restrictions were placed on language or publication year. Eligible studies involved adults with IBS using single-component hypnotherapy. All studies, except single case or expert opinion, were sought and all patient-related outcomes eligible. RESULTS: Out of 299 unique references identified, 20 studies (18 trials of which four were randomized, two controlled and 12 uncontrolled) and two case series were eligible. These tended to demonstrate hypnotherapy as being effective in the management of IBS. Numbers of patients included were small. Only one trial scored more than four out of eight on internal validity. CONCLUSION: The published evidence suggests that hypnotherapy is effective in the management of IBS. Over half of the trials (10 of 18) indicated a significant benefit. A randomized placebo-controlled trial of high internal validity is necessary to establish the effectiveness of hypnotherapy in the management of IBS. Until such a trial is undertaken, this form of treatment should be restricted to specialist centres caring for the more severe forms of the disorder.

Adult↗
PubMed2006

Chronic ocular lesions in tawny owls (Strix aluco) injured by road traffic.

The chronic ocular lesions suffered by 50 tawny owls (Strix aluco) injured by road traffic were investigated. They included non-healing corneal erosions, cataracts and retinal scarring, and periretinal membrane formation. The intraocular pressure was significantly lower in the eyes with intraocular inflammatory pathology and higher in the eyes with irido- or cyclodialysis than in ophthalmically normal eyes. Cicatritial retinal lesions were not associated with high titres of antibodies to Toxoplasma species. The findings correlate with those observed in human beings with eye injuries due to high-speed blunt trauma.

Animals↗
PubMed2006

Multiple vaccine and pyridostigmine interactions: effects on EEG and sleep in the common marmoset.

Following active service during the 1990/1991 Gulf conflict, a number of UK and US veterans presented with a diverse range of symptoms, collectively known as Gulf Veterans' Illnesses (GVI). The administration of vaccines and/or the pretreatment against possible nerve agent poisoning, pyridostigmine bromide (PB), given to Armed Forces personnel during the Gulf conflict has been implicated as a possible factor in the aetiology of these illnesses. The possibility that long-term health effects may result from the administration of these vaccines (anthrax, pertussis, plague, yellow fever, polio, typhoid, tetanus, hepatitis B, meningococcal meningitis and cholera) and/or PB, have been investigated using a non-human primate model, the common marmoset. This paper reports the results from two aspects of the study, brain electrical activity (EEG, collected during performance of a touchscreen mediated discrimination task) and sleep. There were no marked long-term changes in EEG or sleep patterns that could be attributed to vaccines and/or PB administration. The changes that were detected were predominantly time related and independent of treatment. Where statistical differences were detected between treatments, the magnitudes of the difference were relatively minor and therefore not regarded as having long term biological significance.

Animals↗
PubMed2006

Eradication of Helicobacter pylori for non-ulcer dyspepsia.

BACKGROUND: Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear. OBJECTIVES: To determine the effect of H pylori eradication on dyspepsia symptoms in patients with non-ulcer dyspepsia. SEARCH STRATEGY: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies. SELECTION CRITERIA: All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia. DATA COLLECTION AND ANALYSIS: Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms. MAIN RESULTS: Twenty one randomised controlled trials were included in the systematic review. Eighteen trials compared antisecretory dual or triple therapy with placebo antibiotics +/- antisecretory therapy, and evaluated dyspepsia at 3-12 months. Seventeen of these trials gave results as dichotomous outcomes evaluating 3566 patients and there was no significant heterogeneity between the studies. There was a 10% relative risk reduction in the H pylori eradication group (95% CI = 6% to 14%) compared to placebo. The number needed to treat to cure one case of dyspepsia = 14 (95% CI = 10 to 25). A further three trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia. AUTHORS' CONCLUSIONS: H pylori eradication therapy has a small but statistically significant effect in H pylori positive non-ulcer dyspepsia. An economic model suggests this modest benefit may still be cost-effective but more research is needed.

Adult↗
PubMed2006

Altered colonic glycoprotein expression in unaffected monozygotic twins of inflammatory bowel disease patients.

BACKGROUND AND AIMS: Previous chromatographic analysis of colonic mucins from monozygotic twins with inflammatory bowel disease (IBD) suggested a genetic mucin alteration in ulcerative colitis (UC). This study explores this further by assessing mucosal expression of the oncofetal carbohydrate antigen TF (galactose beta1, 3 N-acetylgalactosamine alpha-), among the same IBD twins. MATERIALS AND METHODS: Formalin fixed paraffin embedded rectal biopsies were studied from 22 monozygotic twin pairs with IBD. These included eight UC twin pairs and 14 Crohn's disease (CD) twin pairs, with six pairs concordant for disease and 16 unaffected twin siblings. Closely adjacent sections were assessed by peanut lectin histochemistry for TF expression and immunohistochemically for nuclear factor kappaB (NFkappaB) activation with investigators blinded to the diagnosis. RESULTS: Unaffected twins were almost all TF positive (15/16) compared with 5/29 histologically normal controls (p<0.0001). Unaffected UC (7/8) and CD twins (8/8) were similarly TF positive. TF positivity was confined mainly to the superficial epithelium and absent from the stem cell compartment of the lower crypts, suggesting that glycosylation changes are acquired rather than genetically determined. Activated NFkappaB was present in the surface epithelium of mucosal biopsies from 13/14 unaffected IBD twins but in only 6/22 histologically normal controls (p=0.0004). All 22 affected IBD twins were TF positive and 18 were positive for activated NFkappaB. CONCLUSIONS: Altered mucosal glycosylation in unaffected identical twins of IBD patients was confirmed in this study. This occurred in both UC and CD twins. The changes are probably acquired rather than congenital and may reflect "preinflammatory" NFkappaB activation.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed2006

Factors associated with the use of complementary medicine and non-pharmacological interventions in symptomatic menopausal women.

BACKGROUND: Hormone replacement therapy is now thought to have serious adverse effects; consequently, many menopausal women are seeking to use complementary and alternative medicine (CAM), including non-pharmacological interventions (NPI), to alleviate symptoms. The prevalence and perceived effectiveness of CAM and NPI for ameliorating menopausal symptoms are not widely known and factors likely to predict CAM and NPI utilization for menopausal symptom management have not been comprehensively documented. OBJECTIVES: The objectives of this study were to (1) determine the prevalence of using CAM and NPI for menopausal symptoms; (2) describe the perceived effectiveness of CAM and NPI for symptom management; and (3) investigate lifestyle and demographic factors associated with CAM/NPI use among menopausal women with vasomotor symptoms. METHODS: Women aged 46-55 years were recruited via six socioeconomically diverse general practices. Participants completed a postal questionnaire that contained items relating to demographics, lifestyle factors, weight, height, exercise behavior, menopausal status, vasomotor symptoms and utilization and perceived effectiveness of a range of CAM/NPI for symptom management. RESULTS: Of 1,206 women who responded, 563 (47%) were symptomatic. The most commonly used CAM/NPI for symptom management were diet/nutrition (44.3%), exercise/yoga (41.5%), relaxation/stress management (27.4%) and homeopathic/naturopathic remedies (25.4%). Of women who used these interventions, large proportions reported them to be helpful. The characteristics that were independently associated with use of CAM/NPI were White ethnicity, being physically active, and not smoking. CONCLUSIONS: Many menopausal symptomatic women are using a wide range of CAM/NPI and report these to be effective, particularly those who are white, physically active and do not smoke.

Alcohol Drinking↗
PubMed2006

Vaginal vault smears after hysterectomy for reasons other than malignancy: a systematic review of the literature.

BACKGROUND: Vaginal vault smears are used to detect persisting neoplasia of the lower genital tract after hysterectomy. Recent data suggest both widespread use and uncertain evidence of their effectiveness. OBJECTIVES: To identify and synthesise evidence on the use and effectiveness of vaginal vault smears and to assess the quality. SEARCH STRATEGY 'vault smear' OR 'vaginal vault smear' OR 'cervical vault smear' OR ('Hysterectomy') AND ('Follow up' OR 'Smear'). SELECTION CRITERIA Primary research, women who had a hysterectomy and were followed up by vault cytology. DATA COLLECTION AND ANALYSIS: Systematic search (eight electronic databases), supplemented by contact with experts and review of bibliographies. Two independent reviewers determined eligibility/validity and extracted data concerning test performance characteristics. Quality was assessed according to the established criteria. RESULTS: Of 441 unique references, only 19 were suitable. Quality of studies varied considerably and few were of 'high' methodological quality. Studies were geographically diverse, and were published over more than 40 years in 16 journals. From the higher scoring papers, there were 11 659 hysterectomies [6546, benign; 76, cervical intraepithelial neoplasia (CIN) I/CIN II; 5037, CIN III]. Proportions of abnormal vault smears and abnormal biopsies during follow up increased with worsening histology at hysterectomy (P < 0.0001 and P = 0.0001). There was only one report of vaginal cancer subsequent to hysterectomy for CIN and insufficient data to allow for reliable meta-analysis. CONCLUSIONS: Vault smears cause anxiety, consume resources and their value is largely unproven. Inconsistency of study design and limited methodological quality means that the value of vault smears could not be established. High-quality research is required to ensure that the guidelines are evidence based.

Female↗
PubMed2006

Inflammatory cells in the airways in COPD.

Airway inflammation is central to the pathogenesis of both airway remodelling and parenchymal destruction in chronic obstructive pulmonary disease (COPD). Neutrophils, macrophages, and CD8+ T lymphocytes have been implicated in a number of studies, but a detailed profile of disease-phenotype specific inflammation has yet to emerge. The heterogeneity of the disease has hindered data interpretation while extrapolation of the results of relatively non-invasive studies to the actual pathology found in the distal lung is difficult. Moreover, prominent studies have had frequently conflicting results. Further investigations are needed to marry the different clinical phenotypes of COPD to their respective inflammatory profiles in the airways and thus improve our understanding of the pathogenesis of the disease as a whole.

Bronchitis↗
PubMed2006

The 2000 canine distemper epidemic in Caspian seals (Phoca caspica): pathology and analysis of contributory factors.

More than 10,000 Caspian seals (Phoca caspica) were reported dead in the Caspian Sea during spring and summer 2000. We performed necropsies and extensive laboratory analyses on 18 seals, as well as examination of the pattern of strandings and variation in weather in recent years, to identify the cause of mortality and potential contributory factors. The monthly stranding rate in 2000 was up to 2.8 times the historic mean. It was preceded by an unusually mild winter, as observed before in mass mortality events of pinnipeds. The primary diagnosis in 11 of 13 seals was canine distemper, characterized by broncho-interstitial pneumonia, lymphocytic necrosis and depletion in lymphoid organs, and the presence of typical intracytoplasmic inclusion bodies in multiple epithelia. Canine distemper virus infection was confirmed by phylogenetic analysis of reverse transcriptase-polymerase chain reaction products. Organochlorine and zinc concentrations in tissues of seals with canine distemper were comparable to those of Caspian seals in previous years. Concurrent bacterial infections that may have contributed to the mortality of the seals included Bordetella bronchiseptica (4/8 seals), Streptococcus phocae (3/8), Salmonella dublin (1/8), and S. choleraesuis (1/8). A newly identified bacterium, Corynebacterium caspium, was associated with balanoposthitis in one seal. Several infectious and parasitic organisms, including poxvirus, Atopobacter phocae, Eimeria- and Sarcocystis-like organisms, and Halarachne sp. were identified in Caspian seals for the first time.

Animals↗
PubMed2005

Soil, water, and pasture enrichment of antimony and arsenic within a coastal floodplain system.

Moderate levels of enrichment with environmental contaminants, such as arsenic (As) and antimony (Sb), have received less attention than gross contamination related to obvious point sources of pollution. Within the Macleay floodplain of north-eastern NSW it was found that approximately 90% of the floodplain is enriched in As and Sb, and 6-8% of the floodplain contains As and Sb levels greater than current Australian soil environmental investigation levels. Variation in surface and depth distributions indicated flood deposition of As and Sb across major environmental floodplain environments, with highest accumulation in modern swamp depositional environments. The soil enrichment was reflected by pasture uptake (up to 6.4 and 2.2 mg kg(-1) for As and Sb, respectively) and elevated surface water concentrations (up to 10 and 21 times drinking guideline values and 2.9 and 6.9 times freshwater trigger values for protection of 95% of species for As and Sb, respectively) of these metalloids. Significant relationships between pasture and total soil levels imply higher relative availability than is typical at grossly contaminated sites. Implications for metalloid mobility and availability in acid sulfate soil environments in the floodplain are discussed.

Agriculture↗
PubMed2005

Eradication of Helicobacter pylori for non-ulcer dyspepsia.

BACKGROUND: Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear. OBJECTIVES: To determine the effect of H pylori eradication on dyspepsia symptoms in patients with non-ulcer dyspepsia. SEARCH STRATEGY: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies. These searches were updated in October 2004. SELECTION CRITERIA: All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia. DATA COLLECTION AND ANALYSIS: Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms. MAIN RESULTS: Seventeen randomised controlled trials were included in the systematic review. Fourteen trials compared antisecretory dual or triple therapy with placebo antibiotics +/- antisecretory therapy, and evaluated dyspepsia at 3-12 months. Thirteen of these trials gave results as dichotomous outcomes evaluating 3186 patients and there was no significant heterogeneity between the studies. There was a 8% relative risk reduction in the H pylori eradication group (95% CI = 3% to 12%) compared to placebo. The number needed to treat to cure one case of dyspepsia = 18 (95% CI = 12 to 48). A further three trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia. AUTHORS' CONCLUSIONS: H pylori eradication therapy has a small but statistically significant effect in H pylori positive non-ulcer dyspepsia. An economic model suggests this modest benefit may still be cost-effective but more research is needed.

Adult↗
PubMed2005

Clinical and cost effectiveness of mechanical support for severe ankle sprains: design of a randomised controlled trial in the emergency department [ISRCTN 37807450].

BACKGROUND: The optimal management for severe sprains (Grades II and III) of the lateral ligament complex of the ankle is unclear. The aims of this randomised controlled trial are to estimate (1) the clinical effectiveness of three methods of providing mechanical support to the ankle (below knee cast, Aircast brace and Bledsoe boot) in comparison to Tubigrip, and (2) to compare the cost of each strategy, including subsequent health care costs. METHODS/DESIGN: Six hundred and fifty people with a diagnosis of severe sprain are being identified through emergency departments. The study has been designed to complement routine practice in the emergency setting. Outcomes are recovery of mobility (primary outcome) and usual activity, residual symptoms and need for further medical, rehabilitation or surgical treatment. Parallel economic and qualitative studies are being conducted to aid interpretation of the results and to evaluate the cost-effectiveness of the interventions. DISCUSSION: This paper highlights the design, methods and operational aspects of a clinical trial of acute injury management in the emergency department.

Ankle Injuries↗