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Biomedical subjects

A Williams

Publications and source records attributed to A Williams.

At least 181 records · Page 10Linked to original sources

Interleukin 13 is secreted by and stimulates the growth of Hodgkin and Reed-Sternberg cells.

Gene expression patterns can provide vital clues to the pathogenesis of neoplastic diseases. We investigated the expression of 950 genes in Hodgkin's disease (HD) by analyzing differential mRNA expression using microarrays. In two independent microarray experiments, the HD-derived cell lines L428 and KMH2 were compared with an Epstein-Barr virus (EBV)-immortalized lymphoblastoid B cell line, LCL-GK. Interleukin (IL)-13 and IL-5 were found to be highly expressed in the HD-derived cell lines. Examination of IL-13 and IL-5 expression by Northern blot analysis and enzyme-linked immunosorbent assay confirmed these results and revealed the expression of IL-13 in a third HD-derived cell line, HDLM2. Control LCL and EBV-negative non-Hodgkin lymphoma-derived cell lines did not express IL-13. In situ hybridization of lymph node tissue from HD patients showed that elevated levels of IL-13 were specifically expressed by Hodgkin/Reed-Sternberg (H/RS) tumor cells. Treatment of a HD-derived cell line with a neutralizing antibody to IL-13 resulted in a dose-dependent inhibition of H/RS cell proliferation. These data suggest that H/RS cells produce IL-13 and that IL-13 plays an important role in the stimulation of H/RS cell growth, possibly by an autocrine mechanism. Modulation of the IL-13 signaling pathway may be a logical objective for future therapeutic strategies.

Cell Division↗

Microglial cells respond to amyloidogenic PrP peptide by the production of inflammatory cytokines.

The scrapie isoform of the prion protein (PrPres) induces neurodegeneration and gliosis in the central nervous system. These features may be reproduced in vitro on exposure of neuronal and glial cultures to PrPres and the peptide HuPr P106-126. In the present study, we investigated the role of microglial cells and astrocytes in the pathological process by studying their molecular response to PrP 106-126 exposure. PrP 106-126 elicited a specific overproduction of pro-inflammatory cytokines IL1beta and IL6 in microglial cells (but not increased expression of TNFalpha, IL10, and TGFbeta1) and over-expression of GFAP in astrocytes. These effects were strictly dependent on the ability of the peptide to form amyloid fibrils. These data strongly suggest that microglial cells contribute to prion-related neurodegenerative processes by producing proinflammatory cytokines in the brain areas of amyloid PrP deposition.

Animals↗

Valuing quality of life: results for New Zealand health professionals.

AIMS: To illustrate the means by which health state preferences, which are required in the calculation of QALYs, may be generated. To elicit health state values from a sample of New Zealand health professionals, and to compare these with those evident from a sample of health professionals and of the general population overseas. METHODS: This research employed a questionnaire (EQ-5D) developed by the EuroQol group which elicits preferences for health states described in terms of three levels within each of five dimensions of health-related quality of life. This questionnaire was administered to groups of students enrolled in a postgraduate Diploma of Public Health course in Auckland (1993-1995), Wellington and Dunedin (1993-1998), and Christchurch (1993-1997). RESULTS: The health state preferences for the New Zealand sample are similar to those evident for samples of health professionals in Sweden and, to a lesser extent, those evident from a sample of the English general public. CONCLUSIONS: The EQ-5D represents a means of readily eliciting health state preferences in the form required to facilitate cost utility analysis. Further research is required in New Zealand to generate a "tariff of health state preferences from the general public across all health states and to explore hypotheses specific to New Zealand, including the possibility that there may be significant differences between Maori and non-Maori with regards to health state preferences.

Activities of Daily Living↗

Aerosol route enhances the contamination of intact eggs and muscle of experimentally infected laying hens by Salmonella typhimurium DT104.

Commercial laying hens were infected with Salmonella typhimurium DT104 strain 16 alternatively via the crop (10(7) cfu per bird) or by an aerosol delivered directly to the beaks using a Collison nebuliser and Henderson apparatus (2 x 10(2) or 2 x 10(4) cfu per bird). Infection by both routes caused systemic infection and prolonged contamination of faeces. Contamination rates of eggs and muscle were much higher following the aerosol challenges despite the much lower doses given by this route. The frequency of Salmonella isolation from eggs rose from 1.7% following oral challenge to 14% and 25%, for each of the aerosol challenges respectively, and the frequency of isolation from muscle rose from 0% following the oral challenge to 27% following each of the aerosol challenges.

Aerosols↗

Do the same genes predispose to Gilles de la Tourette syndrome and dystonia? Report of a new family and review of the literature.

Gilles de la Tourette syndrome (TS) and idiopathic focal torsion dystonia are both movement disorders in which the pathologic process is thought to arise within the basal ganglia. However, despite their possible functional links, they are clinically distinct and are generally considered to have different underlying etiologies. There are several reports in the literature that suggest a relationship between eye winking tics, excessive blinking, and blepharospasm and a report of the coexistence of tics and dystonia. We describe a three-generation family in which TS and dystonias cosegregate. In total, eight patients were affected, five with dystonia and three with TS/facial tics. One of the patients with historic evidence of dystonia subsequently died of motor neuron disease. The identification of this family further strengthens the evidence in favor of an etiologic relationship between some cases of Gilles de la Tourette syndrome and focal dystonia.

Adult↗

Use of vector volume manometry and endoanal magnetic resonance imaging in the adult female for assessment of anal sphincter dysfunction.

PURPOSE: This study compared conventional water-perfused and vector volume anal manometry in female patients with neurogenic fecal incontinence and chronic anal fissure and in healthy female volunteers. We used endoanal magnetic resonance (MR) imaging to measure internal and external sphincter lengths and thicknesses and contrasted these with the manometric findings in the different anorectal conditions. METHODS: One hundred thirty-three female subjects were studied over an eight-month period, including 33 control volunteers, 83 patients with neurogenic fecal incontinence, and 17 patients with chronic anal fissure. Conventional manometry was contrasted with automated vector volume-derived parameters. Endoanal magnetic resonance images were obtained using a previously described internal coil with a 0.5 T Asset scanner measuring quadrantal internal sphincter thickness and averaged coronal internal and external sphincter lengths. RESULTS: There was a statistically significant relationship between parameters measured by conventional manometry and those variables derived from vector volume manometry at rest and squeeze. There was no difference in sectorial vector-derived pressures within any anorectal condition and no correlation between quadrantal internal sphincter thickness measurements and sectorial pressures at rest. Patients with chronic anal fissure and neurogenic fecal incontinence had constitutionally shorter superficial and subcutaneous external sphincters than healthy control subjects (P < 0.001). CONCLUSIONS: There is no association between manometric findings and morphologic sphincter measurement; however, the shorter distal external sphincter in patients with fissure might render the lower anal canal relatively unsupported after internal sphincterotomy in the female patient.

Adult↗

One-stop surgery: evolving approach to pediatric outpatient surgery.

PURPOSE: Maximizing patient satisfaction is of prime importance in today's competitive outpatient surgery market. The authors recently devised a system, one-stop surgery, which simplifies outpatient surgery for pediatric patients and their families by combining the traditionally separate preoperative evaluation and subsequent operation into one visit. This report describes our initial experience with one-stop surgery. METHODS: Umbilical hernia repair, circumcision, and portacath removal were considered surgical procedures appropriate for our one-stop surgery pilot study. Medical information obtained by phone or fax from referring physicians was used to identify potential candidates. Families were contacted, precertified for their surgical procedure, and given nothing by mouth instructions. The day of surgery the child was evaluated by the attending pediatric surgeon. If the diagnosis was confirmed, and no contraindications to surgery were identified, the child immediately underwent the prescheduled surgical procedure. RESULTS: From April through October 1997, 61 children were scheduled for one-stop surgery. Nine patients (15%) were no shows, and one additional family opted not to proceed with circumcision. The remaining 51 children (83%) underwent their one-stop surgical procedure: umbilical hernia repair (n = 23), circumcision (n = 19), portacath removal (n = 8), and inguinal hernia repair (n = 1). No child had an anesthetic contraindication to surgery, and only one minor postoperative complication (wound hematoma) occurred. CONCLUSIONS: This pilot study has demonstrated that with appropriate patient screening and cooperation of the entire surgical team, a variety of outpatient surgical procedures can be handled using this one-stop surgery method. By combining one-stop surgery with our previously reported phone follow-up system, many minor surgical procedures can be managed with only one visit to the hospital. Decreasing the "hassle factor" of outpatient surgery for children and their families, who frequently live far from their closest children's hospital, while providing the highest quality of specialized surgical and anesthetic care, may potentially be a very powerful marketing tool for pediatric surgical specialists.

Adolescent↗

Models and measurements of depression in chronic pain.

The main aspects of the most common models describing depression in chronic pain patients are reviewed. It is suggested that dualistic thinking provides neither a satisfactory model of chronic pain, nor of depression, and relies on questionable assumptions of homogeneous, diagnostically defined entities. Models of depression based in cognitive psychology, although apparently more suitable, cannot be applied to populations of pain patients without clarifying the relationship between pain and depression. Furthermore, commonly used depression measurement instruments are criticized for criterion contamination, lack of external reference, and lack of sensitivity when applied to these groups, all of which further obscure the relationship. Finally, we suggest more promising directions for research in this area.

Chronic Disease↗

Systematic review and meta-analysis of randomized controlled trials of cognitive behaviour therapy and behaviour therapy for chronic pain in adults, excluding headache.

A computer and a hand search of the literature recovered 33 papers from which 25 trials suitable for meta-analysis were identified. We compared the effectiveness of cognitive-behavioural treatments with the waiting list control and alternative treatment control conditions. There was a great diversity of measurements which we grouped into domains representing major facets of pain. Effect sizes, corrected for measurement unreliability, were estimated for each domain. When compared with the waiting list control conditions cognitive-behavioural treatments were associated with significant effect sizes on all domains of measurement (median effect size across domains = 0.5). Comparison with alternative active treatments revealed that cognitive-behavioural treatments produced significantly greater changes for the domains of pain experience, cognitive coping and appraisal (positive coping measures), and reduced behavioural expression of pain. Differences on the following domains were not significant; mood/affect (depression and other, non-depression, measures), cognitive coping and appraisal (negative, e.g. catastrophization), and social role functioning. We conclude that active psychological treatments based on the principle of cognitive behavioural therapy are effective. We discuss the results with reference to the complexity and quality of the trials.

Adult↗

Radial artery harvest technique, use and functional outcome.

OBJECTIVE: To develop a simple harvest technique for radial artery (RA). To investigate the morbidity and functional outcome of RA harvest. METHODS: The neurovascular fascia surrounding the RA is divided. Only loose areolar tissue surrounds this artery making harvest of RA simple and allowing minimal trauma to the RA and surrounding muscles. Topical and intraluminal vasodilators but no systemic vasodilators are used. RESULTS: RA harvest commenced in December 1994. Between 1996 and 30 June 1998, 2167 RA were harvested and used to construct 3105 coronary anastomoses. A dramatic rise in RA use occurred during 1996. More than 80% of patients undergoing coronary artery bypass surgery (CABG) have RA harvested since this time. Total arterial revascularization rate also rose dramatically and is currently 80% of all CABG. This rate has been assisted by a rapid rise in the use of composite arterial grafting where aortic anastomoses can be avoided and currently represents 40% of all CABG. Hand strength was tested in 328 non-selected patients and was not reduced by RA harvest when hand dominance was taken into account. Objective sensation loss was present in 0.3% for the superficial radial nerve and 2.1% for the lateral cutaneous nerve of forearm. Pulse oximetry observations detected statistically significant but clinically irrelevant differences. Scar hypersensitivity occurred in 20%. Only two patients of all patients undergoing RA harvest reported late hand ischaemia. CONCLUSIONS: Harvest of the RA within the neurovascular plane is simple and associated with low morbidity.

Aged↗

Guthrie house: a rural community organizing for wellness.

This paper is interested in the issue of community participation and empowerment in health care provision and decision-making. In Canada, the present scope for public involvement in planning or managing the state's health and social services system is limited. This poses a particular problem for rural communities--places where the provision of health care services has historically been limited when compared to urban locations. These rural communities are now facing a double burden as public policy moves increasingly towards a retrenchment of the welfare state. This paper examines one rural community's response to this double burden. The village of Elgin in rural Ontario recently established Guthrie House, a community-based resource center for health and wellness services. Community participation in this case involved a level of control whereby local citizens together defined the health and social care services that they saw as best meeting the needs of their community. This form of community participation is considerably different from the forms of public involvement in the established medical system and represents a critical link to 'empowering' the local community as partners in health care. Through an examination of Guthrie House, the paper presents a review of some critical 'characteristics' which mark successful community self-help organizations and concludes with a discussion of the policy implications for greater community participation. It is argued that such community participation in health care is a policy option which government should be paying particular attention to in these times of fiscal constraint, increasing health care needs and increasing consumer dissatisfaction with government service provision mechanisms.

Community Health Planning↗

Inequalities in health and intergenerational equity.

In the popular folklore three-score-years-and-ten is treated as a fair innings for people, and thereby serves as an informal reference point for judgements about distributive justice within a community. But length of life alone is an insufficient basis for such judgements--a person's health-related quality-of-life also needs to be taken into account. If one of the objectives of public policy is to reduce inequalities in lifetime health, it will be demonstrated that this is very likely to require systematic discrimination against the older members of a community. The notion of community solidarity will also be tested, because a decision will need to be made as to whether the same fair innings applies to all members of the community, or whether some are entitled to more than others. The strength of the fair innings principle is that it brings these issues to the fore in a systematic way which should aid their resolution in a practical context.

Age Factors↗

Scrapie replication in lymphoid tissues depends on prion protein-expressing follicular dendritic cells.

The immune system is central in the pathogenesis of scrapie and other transmissible spongiform encephalopathies (TSEs) or 'prion' diseases. After infecting by peripheral (intraperitoneal or oral) routes, most TSE agents replicate in spleen and lymph nodes before neuroinvasion. Characterization of the cells supporting replication in these tissues is essential to understanding early pathogenesis and may indicate potential targets for therapy, for example, in 'new variant' Creutzfeldt-Jakob disease. The host 'prion' protein (PrP) is required for TSE agent replication and accumulates in modified forms in infected tissues. Abnormal PrP is detected readily on follicular dendritic cells (FDCs) in lymphoid tissues of patients with 'new variant' Creutzfeldt-Jakob disease, sheep with natural scrapie and mice experimentally infected with scrapie. The normal protein is present on FDCs in uninfected mice and, at lower levels, on lymphocytes. Studies using severe combined immunodeficiency (SCID) mice, with and without bone marrow (BM) grafts, have indicated involvement of FDCs and/or lymphocytes in scrapie pathogenesis. To clarify the separate roles of FDCs and lymphocytes, we produced chimeric mice with a mismatch in PrP status between FDCs and other cells of the immune system, by grafting bone marrow from PrP-deficient knockout mice into PrP-expressing mice and vice versa. Using these chimeric models, we obtained strong evidence that FDCs themselves produce PrP and that replication of a mouse-passaged scrapie strain in spleen depends on PrP-expressing FDCs rather than on lymphocytes or other bone marrow-derived cells.

Animals↗

Changing roles and identities in primary health care: exploring a culture of uncertainty.

This paper highlights a key area of analysis emerging from research undertaken in order to explore cultural differences between medicine and nursing, and implications for primary care. Concerns about the role of nursing in primary health care within the UK are of particular interest to the authors. A specific concern centres on the movement of health care work from one group of health workers to another, in particular from doctors to nurses. A number of studies show that work is moving from doctors to nurses and explore the policy drivers, notably the pressure to improve the cost-effectiveness of care. However, few studies reflect on how ideas, values and beliefs are being challenged, confirmed and used to justify new roles and identities. We are interested in exploring this latter aspect of the movement of health care work, and argue that changing roles and identities create a culture of uncertainty which has important implications for the future of primary health care nursing.

Cross-Cultural Comparison↗

Synergy: working together with volunteers in community well woman clinics.

Despite promotion of the participation of volunteers in community and primary care services, there are few British studies which have explored the benefits and challenges of collaborative working between volunteer and paid workers, and in particular, women's experiences of volunteering within the National Health Service (NHS). The study presented here seeks to add to the limited, existing knowledge in this area. The experiences of volunteer and paid workers working together in two community well woman clinics are discussed, focusing on the benefits of working together for volunteers, paid workers and clients. Discussion is based on data collected over an 18-month period of participant observation in two community well woman clinics, interviews with 26 volunteer and paid workers and a review of the clinics' operational policy documents. Drawing on the concept of synergy, relationships between volunteer and paid workers are illuminated. In this paper it is argued that working together renders the opportunity for volunteer and paid workers to share insights, perspectives and approaches which enhance clients' health assessments. It provides an added value dimension to client care and yields benefits for the service provider. The implications of the study for practice and policy are considered.

Female↗