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Biomedical subjects

S Wilson

Publications and source records attributed to S Wilson.

At least 127 records · Page 7Linked to original sources

A G protein-coupled receptor for UDP-glucose.

Uridine 5'-diphosphoglucose (UDP-glucose) has a well established biochemical role as a glycosyl donor in the enzymatic biosynthesis of carbohydrates. It is less well known that UDP-glucose may possess pharmacological activity, suggesting that a receptor for this molecule may exist. Here, we show that UDP-glucose, and some closely related molecules, potently activate the orphan G protein-coupled receptor KIAA0001 heterologously expressed in yeast or mammalian cells. Nucleotides known to activate P2Y receptors were inactive, indicating the distinctly novel pharmacology of this receptor. The receptor is expressed in a wide variety of human tissues, including many regions of the brain. These data suggest that some sugar-nucleotides may serve important physiological roles as extracellular signaling molecules in addition to their familiar role in intermediary metabolism.

GTP-Binding Proteins↗

The impact on retention of expansion of an Australian public methadone program.

Although rapid expansion of methadone programs has occurred in many countries, there are few studies of the impact on treatment success. The one public methadone maintenance program in Canberra was expanded from 85 places in 1991 to 350 places in late 1992. While this responded to a real need, it also led to a temporary increase in drop-outs. Retention was considerably improved in 1996 when clients began to be transferred from the public program to fee-for-service primary health care, but the improvement was also not sustained. In recent years, one-quarter to one-half of clients dropped out before stabilization. Multiple entries into treatment were common and overall retention was not affected by previous treatment episodes or length of time between episodes. Methadone programs should monitor retention as part of on-going evaluation and improvement of treatment policy.

Australia↗

Increased dendritic MAP2 expression in the hippocampus in schizophrenia.

Microtubule associated proteins (MAPs) are central to the development of normal neuronal cytoarchitecture and have been reported to be altered in schizophrenia. In 12 schizophrenic (DSM-III-R criteria) and 12 control hippocampi, we estimated the MAP2 immunoreactive dendritic length using antibodies that recognize total MAP2 (MAP2-T), and a non-phosphorylated form of MAP2 (MAP2-NP). Within the corona ammonis (CA) subregions, and the subiculum, we estimated, for each antibody, the length of the immunoreactive dendritic arborisation using a stereological length estimation technique based on Bouffon's Needle principle and image analysis computer software. Controlling for the confounding effects of age and post-mortem delay, we have found an elevation in overall MAP2-NP immunoreactive dendritic length among schizophrenic subjects in the CA3 (F=5.9, p=0.03), CA2 (F=6.5, p=0.02), CA1 (F=8.3, p=0.01) and subicular (F=9.5, p=0.008) hippocampal subregions. Similar analyses of MAP2-T immunoreactive dendritic length demonstrated significant elevations in the CA1 (F=8.3, p=0.02), CA4 (F=4.9, p=0.04) and subicular (F=7.4, p=0.01) regions. The findings of this quantitative study of increased MAP2 immunoreactive dendritic arborisation in schizophrenia are most likely to reflect either an altered dendritic arborisation or a generalised increase in levels of MAP2 with the hippocampal pyramidal neurons. These findings add to the growing literature indicating the presence of synaptodendritic abnormalities in schizophrenia.

Adult↗

Initial management strategies for dyspepsia.

BACKGROUND: This review considers management strategies (combinations of initial investigation and empirical treatments) for dyspeptic patients. OBJECTIVES: To determine the effectiveness, acceptability, and cost effectiveness of the following initial management strategies for patients presenting with dyspepsia (a) initial pharmacological therapy (including endoscopy for treatment failures) (b) early endoscopy (c) testing for Helicobacter pylori and endoscope only those positive (d) H.pylori eradication therapy with or without prior testing. SEARCH STRATEGY: Trials were located through electronic searches and extensive contact with trialists. SELECTION CRITERIA: All randomised controlled trials of dyspeptic patients presenting in primary care. DATA COLLECTION AND ANALYSIS: Data was collected on dyspeptic symptoms, quality of life and use of resources. MAIN RESULTS: Ten papers reporting 12 comparisons were found. Trials comparing proton pump inhibitors (PPI) with antacids (2 trials) and H2 receptor antagonists (3 trials), and of early endoscopy compared with initial acid suppression (3 trials) were pooled. PPIs were significantly more effective than both H2RA s and antacids. Relative risks (RR) and 95% CI were, for PPI: antacid 0.72 (0.64-0.80), PPI: H2RA 0.63 (0.47-0.85). Results for other drug comparisons were either absent or inconclusive. Early endoscopy was not more effective than initial prescribing (RR 0.90 (0.77-1.04), but current studies lack power. No eligible trials of H.pylori test and endoscopy or test and eradicate were found. REVIEWER'S CONCLUSIONS: PPIs are effective in the treatment of dyspepsia in these trials which may not adequately exclude patients with gastro-oesophageal reflux disease. The relative efficacy of H2RA and PPI is uncertain. Early investigation may benefit some patients with dyspepsia. The review will be updated shortly with several large trials that have recently been completed.

Anti-Bacterial Agents↗

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 and quality of life scores 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: Seven randomised controlled trials were included in the systematic review. Five trials compared proton pump inhibitor dual or triple therapy with a proton pump inhibitor + placebo antibiotics, and evaluated dyspepsia at 6-12 months in 1,385 patients. H pylori eradication was significantly superior to placebo in treating non ulcer dyspepsia (relative risk reduction = 7%; 95% CI = 1% to 12%; p=0.02) and there was no significant heterogeneity between the studies. The number needed to treat to cure one case of dyspepsia = 19 (95% CI = 11 to 132). A further two 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. REVIEWER'S CONCLUSIONS: H pylori eradication may be an effective therapy for H pylori positive non-ulcer dyspepsia. This result is not robust and further evidence on the efficacy of H pylori eradication in non ulcer dyspepsia would be helpful. The effect is modest and economic models would help establish whether this approach is cost-effective. This review will be updated as results from other ongoing trials (Malfertheiner 2000) are made available.

Anti-Bacterial Agents↗

Schistosoma japonicum: interactions of successive infections in pigs and mice using polymerase chain reaction-based identification of individual worms.

The study reported here investigated acquired resistance of mice and pigs to challenge-infections with Schistosoma japonicum. Two morphologically indistinguishable isolates of the parasite (from the Anhui and Zhejiang provinces of China), which could be typed by polymerase chain reaction-linked restriction fragment length polymorphism analysis (PCR-RFLP), were used for the infections. In two parallel infection studies, 60 female outbred NMRI mice and 29 Danish Landrace/Yorkshire/Duroc crossbred pigs were used. Two of the groups received a primary infection with either the Anhui or the Zhejiang isolate, respectively. The remaining groups received a primary infection with the Zhejiang isolate and challenge-infections with the Anhui isolate at either week 2, 3, 4 or 6 post primary infection. The results of the study indicated that both mice and pigs are partially resistant to challenge-infection from week 4 post primary infection. Resistance appeared to decrease in pigs 6 weeks after primary infection, while it remained effective in mice. These results suggest that the mechanism responsible for acquired resistance in mice and pigs may not be the same and support the theory that worm burdens in pigs receiving repeated infection are in a balance between acquisition and loss of worms.

Animals↗

Pharmacologic behavior management for pediatric dental treatment.

Sedatives are an important and necessary management technique for some children during dental procedures. Sedation can be administered safely and efficiently by competent practitioners who have special training in the use of the technique in children and who adhere to sedation guidelines. Nonetheless, some children present with special needs, such as medically compromising conditions, or multiple carious teeth in a child who is fearful or whose family must travel a long distance for care. Sedation cannot always safely and adequately meet the needs of these children. In these cases, general anesthesia in a hospital, ambulatory care facility, or office is indicated and must be provided by an appropriately licensed and trained physician or dentist.

Analgesics↗

The prevalence and clonal diversity of penicillin-resistant Streptococcus pneumoniae in Kuwait.

Penicillin-resistant Streptococcus pneumoniae (PRSP) is widespread all over the world, including countries previously free of PRSP. This study was undertaken to determine the prevalence, the common serotypes and the clonality of PRSP isolated over a period of 1 year, from various clinical samples from three major hospitals in Kuwait. Strains were identified by standard methods and their antibiotic susceptibility was determined by the agar dilution method. The clonality of the isolates was determined by repetitive extragenic palindromic sequence polymerase chain reaction (REP-PCR) genomic profiling and pulsed field gel electrophoresis (PFGE). Serotyping was done by Quellung reaction using specific antisera. We found that 55% of the S. pnuemoniae were resistant to penicillin (46% and 9% exhibited intermediate and full resistance, respectively). Nearly 41% were resistant to sulfamethoxazole-trimethoprim, 9% to cefotaxime and ceftriaxone, 15% to amoxycillin-clavulanate, 17% to cefuroxime, 77 % to cefaclor, and 14% to clindamycin. The commonest serotypes among the PRSPs were 6A, 6B, 14, 19F, 23F and nontypable. PFGE and REP-PCR patterns showed a large diversity of genetic clones of the PRSP. Serotypes 6B, 14, 19F and 23F were more clonally related than the others. Our data showed that the prevalence of PRSP was high, the serotypes were diversified and different genetic clones make up the population of circulating PRSP in Kuwait.

DNA, Bacterial↗

Bronchial angiogenesis in severe glucocorticoid-dependent asthma.

To examine the role of the bronchial microvasculature and adhesion molecule expression in severe asthma, the authors have performed an immunohistochemical study on bronchial biopsies comparing 15 glucocorticoid-dependent asthmatics, 15 mild asthmatics and eight control subjects. Serially cut glycol methacrylate-embedded sections were stained with monoclonal antibodies identifying the vessel marker EN-4, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, E- and P-selectin. Sections were also stained for lymphocyte function associated antigen (LFA)-1 and very late antigen (VLA)-4. By comparison with mild asthma and nonasthma, severe asthma was characterized by increased numbers of submucosal vessels (p=0.009) which was associated with increased numbers of vessels expressing ICAM-1 (p=0.005). A highly significant correlation was found between the total number of EN-4+ vessels and the vessels expressing ICAM-1 (r=0.85, p=0.01). In contrast, E-selectin expression was lower in severe as compared with mild asthma (p=0.01) but not different from normal. No differences were found between the three groups in the expression of VCAM-1 and P-selectin nor in numbers of LFA-1+ and VLA-4+ cells. The results of this study support the notion that mucosal neovascularization is an important feature of airways remodelling in severe asthma. This is associated with a relatively higher density of vessels expressing intercellular adhesion molecule-1, although the expression of this adhesion molecule per vessel was not raised.

Adolescent↗

Low-dose methotrexate treatment in severe glucocorticoid-dependent asthma: effect on mucosal inflammation and in vitro sensitivity to glucocorticoids of mitogen-induced T-cell proliferation.

The authors have investigated whether the steroid-sparing effect of methotrexate (MTX) in severe orally glucocorticoid-insensitive asthmatics may be accounted for by the ability of this drug to increase the T-cell responsiveness sensitivity to dexamethasone in vitro. In addition the authors have investigated whether low-dose MTX treatment is associated with anti-inflammatory effects in peripheral blood and the bronchial mucosa. In eight patients with severe atopic asthma, using > or =15 mg x day(-1) prednisolone, the inhibitory effect of dexamethasone on mitogen stimulated peripheral blood mononuclear cells (PBMC) in vitro was tested before and after 8 weeks of uncontrolled treatment with MTX. Endobronchial biopsies were taken before and after MTX therapy in seven subsequent patients, and analysed using immunohistochemistry. In eight patients, serum was drawn for measuring levels of free interleukin (IL)-8. The in vitro sensitivity of PBMC to dexamethasone (at 1.6 x 10(-9) and 3.2 x 10(-10) mol x L(-1)) was significantly lower in the asthmatics before treatment when compared with the control subjects (p=0.03 and =0.001) but increased significantly after MTX treatment (p=0.04 and =0.02) to normal responsiveness. This was not associated with a decrease in peripheral blood T-cell numbers or activation. Except for a significant increase in the numbers of CD3+ (p=0.04), no significant numerical changes in activated T-cells, eosinophils, or mast cells were found (p>0.05). However, MTX treatment was associated with a significant fall in serum levels of free IL-8 (p=0.03). It is hypothesized that the steroid-sparing effect of methotrexate originates from increased sensitivity of lymphocytes to the inhibitory effects of glucocorticoids. The absence of an inhibitory effect on inflammatory cells in blood and mucosa suggests that this effect is achieved by modulating cell function rather than cell number.

Adolescent↗

Environmental health and genomics: visions and implications.

The relationship between genes and the environment can be compared to a loaded gun and its trigger. A loaded gun by itself causes no harm; it is only when the trigger is pulled that the potential for harm is released. Genetic susceptibility creates an analogous situation, where the loaded gun is one or a combination of susceptibility genes (alleles) and the trigger is an environmental exposure. The key objective of the Environmental Genome Project is to identify alleles that confer susceptibility to the adverse effects of environmental agents. Here we discuss the goals of the Environmental Genome Project, its implications and, in particular, its potential effect on our ability to assess human disease risk in the future.

Animals↗

Women's experience of breast conserving treatment for breast cancer.

The implementation of the National Breast Screening Programme in the UK, and subsequent increase in early detection of small cancers, has facilitated breast conserving treatment for more women with a breast cancer diagnosis than ever before. While a substantial body of literature has evolved regarding psychosocial morbidity and support needs of women at diagnosis and during treatment, there are specific gaps in the current knowledge base. The purpose of this study was to describe the experiences of women who had breast conserving treatment for early breast cancer, focusing on issues related to diagnosis, surgery, and radiotherapy. The study was designed within the context of clinical audit, with a view to informing service development. Seventy-six women who had undergone breast conserving surgery within the last 3-12 months, completed a self-report questionnaire. Findings indicated that although the majority of women expressed satisfaction with their treatment overall, a number of specific areas require attention from healthcare professionals. Further research is required to validate these findings and to explore: potential implications of different referral routes; information and support needs preceding definitive diagnosis; particular needs of those women with ductal carcinoma in situ (DCIS) vs. invasive disease; 'end of treatment' and ongoing information and support needs.

Adult↗

European survey of primary care physician perceptions on heart failure diagnosis and management (Euro-HF).

AIMS: To survey a random sample of primary care physicians across six European countries regarding their perceptions of diagnostic and prescribing issues in heart failure, and to consider factors that might be associated with physician under-performance. METHODS AND RESULTS: Qualitative, postal questionnaire-based, validated survey in the native tongue of a random sample of 200 primary care physicians in each of five European countries (France, Germany, Italy, The Netherlands and Spain) and of 250 U.K. primary care physicians. Respondents provided: details of practice characteristics; the usual way a diagnosis of heart failure was established; access to investigations; names of drugs prescribed in heart failure, with estimates of the proportion of patients supplied with particular classes; and physician attitudes regarding the evidence base (in terms of benefits and risks) for treatments used. Outcomes were physician perceptions and attitudes about heart failure diagnosis and treatment. Adjusted response rates varied from 17% (France) to 56% (Britain). Primary care physicians underestimate the prevalence of heart failure. Most patients are diagnosed on symptoms and signs alone, with only 32% having further investigations or referral. Although most primary care physicians stated they prescribe ACE inhibitors in heart failure, this was for only 47-62% of patients, and at doses below those identified as effective in trials. Most prescribing doctors (91%) believe there is strong evidence of reduced mortality in heart failure patients using ACE inhibitors, but 51% also consider ACE inhibitors have substantial risks with their use. CONCLUSION: Limitations of the data include the general problem of questionnaires, whether responses accord with actual clinical practice, and, specific to these data, the low response rate in some countries (although the study does provide information from nearly 300 randomly selected primary care physicians across Europe). New preliminary insights include exposition of the 'low tech' approach to heart failure diagnosis across Europe: doctors report the use of symptoms and signs alone; the lack of direct (open) access to objective investigations, such as echocardiography, which almost guarantees that misdiagnoses will occur; and the under-utilization and under-dosing with ACE inhibitors. The main factor influencing under-use would appear to be the exaggerated perceptions of treatment risk amongst primary care physicians that dominate the widespread and accurate knowledge of treatment benefits.

Cardiac Output, Low↗

Evaluation of low-pressure arterial and venous clamps: electron microscopic study and possible clinical applications.

These authors report on validating their choice of disposable clamps in arterial and venous microsurgery in a comparative and experimental study using the scanning electron microscope. This appears to be the first evaluation of venous endothelial clamping lesions. Early intimal clamping lesions were studied using three different clamps and two protocols in 18 femoral arteries and veins in rabbits. Results were evaluated using a new classification that can be applied to both arterial and venous lesions: Grade I: cellular disorientation and disorganization; endothelial lamination; and absent or very few platelet deposits; Grade II: alterations of the cytoplasmic membranes in fusiform cells; presence of at least one breach of endothelial continuity; and moderate number of platelet deposits; Grade III: presence of endothelial detachment; and large numbers of platelet deposits. They showed that in arteries, all the clamps tested caused only low-grade lesions. In contrast, in veins, they demonstrated both the very fragile nature of the endothelium, and also the comparative safety of the low-pressure venous clamp. Their choice of specific clamps for venous anastomoses was validated.

Animals↗

Mothers and their disabled children: refining the concept of normalization.

Normalization refers to behaviors and intentions of the disabled to integrate into society by living life as do those without a disability. Although normal is assumed to be a desired state, the concept has not been explored from the perspective of disabled children and mothers and other family members. The objective of this study is to determine "what is normal" from the perspective of the person with the disability. Participant observation was conducted in a 6-day summer camp for 17 children with chronic, severe, life-threatening physical disabilities. The children normally received home care and were ventilator dependent. Data consisted of observations, field notes, photographs, and videos. To obtain data about the children's home life, audiotaped telephone interviews with their primary caregiver (16 mothers and 1 father) were conducted before and after the camp. This group had two distinct social reference groups: the "disabled world" of the disabled-as-normal and the "outside" world of the everyday-as-normal. Mothers identified with both reference groups according to the child's needs, abilities and capabilities, and the risk involved. Children with disabilities who normalize compare their abilities and capabilities to identify both within a disabled world ("like me") and the outside world, according to their needs. Normalization includes processes of identification with both the cultural dominant perceived as normal (with whom these children could identify cognitively) and handicapped children (with whom these children could identify both physically and cognitively).

Adaptation, Psychological↗

Understanding peer education: insights from a process evaluation.

In the UK, peer education has become an increasingly popular way of carrying out health promotion work with young people but evaluations of its effectiveness remain largely unpublished. In particular, illuminative evaluations using qualitative methods are rarely reported both in the UK and other countries. This paper presents insights from the process evaluation of a peer education project in Fife, Scotland which was funded to explore new ways of working with young people in the areas of sexual health, HIV/AIDS and drugs. The interactive approach of the evaluation and its responsiveness to the development of the project are outlined. Factors influencing the peer education process, such as recruitment, setting, organizational context and personal development of participants, are described. Aspects of the formal and informal work carried out by the peer educators are discussed. It is hoped that the paper may provide a starting point for developing more reflective understandings about the processes involved when peers educate peers.

Adolescent↗

Comparison of the structural motifs of acetoacetanilides and related azo pigments

The structures of three methyl-substituted acetoacetanilides and of an azo pigment derived from one of them are presented and discussed together with a review of related known crystal structures. By considering the position of any aromatic substituents it is possible to predict whether the simple acetoacetanilides adopt planar structures with intramolecular hydrogen bonding or twisted structures featuring intermolecular hydrogen bonding. However, we find that the same crystal engineering rules cannot be applied to the related azo pigments: this is apparently due to the presence of an sp(2) atom which facilitates the adoption of planar conformations. The thermal properties of the acetoacetanilides were measured by DSC and are discussed with reference to their crystal structures.

Journal Article↗