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Biomedical subjects

R Williams

Publications and source records attributed to R Williams.

At least 73 records · Page 4Linked to original sources
PubMed2003

Tumour necrosis factor alpha is an important mediator of portal and systemic haemodynamic derangements in alcoholic hepatitis.

BACKGROUND: The role of proinflammatory cytokines in the pathogenesis of portal hypertension is unclear. AIMS AND METHODS: This study tests the hypothesis that tumour necrosis factor alpha (TNF-alpha) is an important mediator of the circulatory disturbances in alcoholic hepatitis (AH) and evaluates the acute and short term effect of a single infusion of the monoclonal chimeric anti-TNF-alpha antibody (Infliximab) on portal and systemic haemodynamics in 10 patients with severe biopsy proven AH. Cardiovascular haemodynamics, hepatic venous pressure gradient (HVPG), and hepatic and renal blood flow were measured before, 24 hours after Infliximab, and prior to hospital discharge. RESULTS: Serum bilirubin (p<0.05), C reactive protein (p<0.001), and white cell count (p<0.01) were reduced significantly, as were plasma levels of interleukin (IL)-6 and IL-8 after treatment. Of the 10 patients, nine were alive at 28 days. Mean HVPG decreased significantly at 24 hours (23.4 (2.8) to 14.3 (1.9) mm Hg; p<0.001) with a sustained reduction prior to discharge (12.8 (1.9) mm Hg; p<0.001). Mean arterial pressure and systemic vascular resistance increased significantly (p<0.001and p<0.01, respectively), mirrored by a reduction in cardiac index (5.9 (0.5) to 4.7 (0.5) l/min/m(2); p<0.05) prior to discharge. Hepatic and renal blood flow also increased significantly (506.2 (42.9) to 646.3 (49.2) ml/min (p=0.001) and 424.3 (65.12) to 506.3 (85.7) ml/min (p=0.001), respectively) prior to discharge. CONCLUSION: The results of this study illustrate that anti-TNF-alpha treatment in AH patients produces a highly significant, early, and sustained reduction in HVPG, possibly through a combination of a reduction in cardiac output and intrahepatic resistance. In addition, there was a reduction in hepatic inflammation and improved organ blood flow, suggesting an important role for TNF-alpha in mediating the circulatory disturbances in AH.

Adult↗
PubMed2003

Indirect enzyme-linked immunosorbent assay for the detection of antibody against Rift Valley fever virus in domestic and wild ruminant sera.

An indirect enzyme-linked immunosorbent assay (I-ELISA) for the detection of specific IgG immunoglobulins against Rift Valley fever virus (RVFV) was validated in-house. A total of 3055 sera from sheep (n = 1159), goats (n = 636), cattle (n = 203), African buffalo (n = 928), and other wild ruminants (n = 129), including eland, kudu, and black wildebeest, was used. Sera from domestic ruminants were collected in West (n = 10), South (n = 1654) and East Africa (n = 334), and sera from wild ruminants (n = 1064) were collected in South Africa. In addition, 136 sera from eight experimentally RVFV-infected sheep, taken during a period of 28 days post infection (dpi), were used to study the kinetics of RVFV antibody production. Field sera were tested by the serum neutralization (VN) test and experimental sera by VN and haemagglutination-inhibition (HI) test. Based on VN test results, negative sera were regarded as reference controls from RVFV-free, and positive sera were regarded as reference controls from RVFV-infected subpopulations of animals. ELISA data were expressed as the percentage positivity (PP) of an internal high positive control. The two-graph receiver operating characteristics approach was used for the selection and optimization of I-ELISA cut-offs including the misclassification costs term and Youden index (J). In addition, cut-off values were determined as the mean plus two-fold standard deviation of the result observed with the RVFV-free subpopulations. Established optimal cut-offs were different for each of the data sets analyzed, and ranged from 1.65 PP (buffalo) to 9.1 PP (goats). At the cut-off giving the highest estimate of combined measure of diagnostic accuracy (highest J value), the I-ELISA test parameters were determined as follows: (1) Diagnostic sensitivity (%): cattle--84.31, buffalo--94.44, sheep--98.91, goats--99.18. (2) Diagnostic specificity (%): cattle--99.34, buffalo--98.28, sheep--99.16, goats--99.23 and other game ruminants--99.26. In the group of RVFV-experimentally infected sheep, seroconversion In all individuals was detected by VN on 4-6 dpi, by HI on 5-7 dpi, and by I-ELISA on 6-7 dpi. All tests showed the same kinetic pattern of immunological response. Antibody levels were low for a very short period before increasing to high titres, after which it was easily detectable by all tests. Compared to traditional tests, the lower sensitivity of I-ELISA in the detection of the earliest stage of immunological response may be practically insignificant, particularily when this assay is used in population-based, disease-surveillance programmes. The high sensitivity and specificity of I-ELISA established in this study, especially for the statistically more representative subpopulations of animals tested, seem to support this prediction. Test parameters determined in this study should, however, be regarded as in-house diagnostic decision limits, for which further updating is recommended, particularly for specimens from other countries, and preferably by applying a standardized method for sampling of new subpopulations of animals to be targeted by the assay.

Animals↗
PubMed2002

Employers and policy makers can make a difference to the employment of persons with disabilities.

PURPOSE: The purpose of this article is to discuss what employers and policy makers can do to promote employment success for persons with disabilities. A study carried out in Rehabilitation Science at McMaster University, Ontario, Canada identified a number of themes, definitions of success and recommendations for change. METHOD: This article is a descriptive review of the study outcomes as well as a discussion of how the literature contributes to the position that employers and policy makers can do more to ensure that persons with disabilities achieve success in paid employment. RESULTS: The author proposes strategies that employers and policy makers can use that have been recommended both in the study and other more recent documents. CONCLUSIONS: Despite attempts to move the employment agenda for persons with disabilities forward, the results in both North America and Europe appear to be dismally low. There is evidence to suggest that employer activity in this regard is still minimal and that policy makers are not working together to ensure that there are opportunities for this population to succeed. Professionals working in this field need to be more actively involved with both employers and policy makers in order for the environment to change in a significant way.

Canada↗
PubMed2002

Assessing the impact of complications on the costs of Type II diabetes.

AIMS/HYPOTHESIS: 'The Cost of Diabetes in Europe - Type II (CODE-2) study' provides the first coordinated attempt to assess the total costs of managing people with Type II (non-insulin-dependent) diabetes mellitus in Europe. Type II diabetes is associated with a number of serious long-term complications, which are a major cause of morbidity, hospitalisation and mortality in diabetic patients. METHODS: Patients were divided into four broad categories defining their complication status in terms of no complications, one or more microvascular complications, one or more macrovascular complications or one or more of each microvascular and macrovascular complication. The prevalence of complications and associated costs were assessed retrospectively for 6 months. RESULTS: In total, 72% of patients in the CODE-2 study had at least one complication, with 19% having microvascular only, 10% having macrovascular only and 24% of the total having both microvascular and macrovascular complications. Of patients with microvascular complications, 28% had neuropathy, 20% renal damage, 20% retinopathy and 6.5% required treatment for eye complications. Among the patients with macrovascular complications, 18% had peripheral vascular disease, 17% angina, 12% heart failure and 9% had myocardial infarction. Percutaneous transluminal coronary angioplasty, coronary artery bypass graft or stroke occurred in 3%, 4% and 5% of the patients, respectively. In patients with both microvascular and macrovascular complications, the total cost of management was increased by up to 250% compared to those without complications. CONCLUSION/INTERPRETATION: Complications have a substantial impact on the costs of managing Type II diabetes. This study has confirmed that the prevention of diabetic complications will not only benefit patients, but potentially reduce overall healthcare expenditure.

Amputation, Surgical↗
PubMed2002

An analysis of the forces required to drag sheep over various surfaces.

Some occupational health and safety hazards associated with sheep shearing are related to shearing shed design. One aspect is the floor of the catching pen, from which sheep are caught and dragged to the shearing workstation. Floors can be constructed from various materials, and may be level or gently sloping. An experiment was conducted using eight experienced shearers as participants to measure the force exerted by a shearer when dragging a sheep. Results showed that significant changes in mean dragging force occurred with changes in both surface texture and slope. The mean dragging forces for different floor textures and slopes ranged from 359 N (36.6 kg) to 423N (43.2 kg), and were close to the maximum acceptable limits for pulling forces for the most capable of males. The best floor tested was a floor sloped at 1:10 constructed of timber battens oriented parallel to the path of the drag, which resulted in a mean dragging force 63.6N (15%) lower than the worst combination.

Animal Husbandry↗
PubMed2002

Vasorelaxant properties of isolated human radial arteries: comparison with internal mammary arteries.

Radial arteries, used in revascularisation surgery, are prone to spasm. We have examined the ability of nitrovasodilators, calcium channel blockers, and K(ATP) channel openers to cause vasodilation, and to attenuate contractions due to depolarisation and receptor activation in radial and mammary arteries used in coronary artery bypass graft surgery. Two to three millimetre rings of artery obtained from patients at surgery were studied in organ baths in vitro. Constriction to KC1 and phenylephrine was examined before and again after treatment of the rings with drug or vehicle. Calcium channel blockers were the only compounds to inhibit contractions to both KC1 and phenylephrine. Sodium nitroprusside attenuated constriction to phenylephrine but not KC1 in both vessels. K(ATP) channel openers similarly attenuated constriction to phenylephrine in radial arteries but were much less effective in mammary arteries. These studies support the continued use of calcium blockers after revascularisation with radial artery but suggest that other classes of drug may be as effective at minimising spasm due to receptor mediated constriction.

Adult↗
PubMed2002

Costs incurred by families having Type 1 diabetes in a developing country--a study from Southern India.

The aim of the study was to estimate the direct family costs of Type 1 diabetes in India. The study was carried out with the participation of the families of 209 Type 1 DM patients (M:F 126:83, mean age 26.6+/-12.7 years). The annual family income varied from Rs. 10,000 to 600,000/- (US$ 212-12,765) with a median of Rs. 60,000/- (US$ 1276). A median figure of Rs. 13,980 (US$ 310) was spent annually on diabetes by the families of patients; range Rs. 2046-87,150 (US$ 45-1936). Fifty six percent of patients were not earning. The median percentage of income spent on diabetes was 22% for the entire group, varying from 59% in the low socioeconomic group, 32% in the middle socioeconomic group, 18% in the upper middle income group and 12% in the high-income group. Patients managed on an outpatient basis alone incurred an expenditure of 16% of income while 23% of income was spent on those requiring hospitalisation.

Costs and Cost Analysis↗
PubMed2002

Review article: the molecular adsorbents recirculating system (MARS) in liver failure.

In recent years different artificial liver support systems are being developed for use in patients with acute decompensation of chronic liver disease or acute liver failure. The molecular adsorbents recirculating system (MARS), a device in which patient's blood is dialysed across an albumin-impregnated membrane against a recirculated albumin-containing solution, seems to be effective in removing albumin-bound toxins, such as fatty acids, bile acids and bilirubin. Although the clinical experience with MARS is scarce, some pilot studies have reported its effectiveness at improving liver function and hepatic encephalopathy in patients with acute decompensation of chronic liver disease, and renal function in patients with hepatorenal syndrome type I. Data regarding MARS experience in acute liver failure and in primary graft dysfunction are encouraging but limited. Its real usefulness in these settings is, at present, under evaluation in randomized controlled clinical trials.

Humans↗
PubMed2002

The effect of thermocycling on five adhesive luting cements.

The importance of bond strengths between dental luting cements and dental restorative materials has become increasingly important as a result of the adhesive technologies that have been developed over recent years. This study investigated the effect on tensile bond strength at the metal to cement interface for a semiprecious alloy for different prepared surfaces, cements and ageing regimes. At 24 h following preparation, silicoating and C & B Metabond appear to have distinct advantages in terms of interfacial bond strength, which was also noted after storage for 7 days in buffered saline. After thermocycling only silicoating conferred greater interfacial tensile strength, and any advantage that the 4-Methacryloxyethyltrimellitic anhydride (4-META) chemistry may have had at 24 h was no longer apparent. The poorest performing cement regardless of the ageing regime was Aquacem, although in relative terms its performance improved after 24 h. This preliminary investigation indicated that in vitro environmental ageing including thermocycling erodes the claimed advantages of some more novel dental adhesives. This may have important clinical consequences in their usage, although it must be appreciated that current thermocycling methodology may not be an accurate predictor of in vivo performance.

Acrylic Resins↗
PubMed2002

Multi-disciplinary working in a forensic mental health setting: ethical codes of reference.

This paper reports on a small research project on multidisciplinary team-working within a medium secure forensic unit in the United Kingdom. Although multidisciplinary team working is widely accepted as an effective strategy for the delivery of healthcare services in modern society it is also recognized that interdisciplinary problems can also occur. This study developed two questionnaires, one being delivered to a number of groups and teams in the secure unit, whilst the second one was geared to individuals. A thematic analysis was employed to develop category building and concept formation. The results highlighted a three-level ethical code referencing system that was employed by both individuals and groups. Within this, three domains, or trajectories, were identified that were polarized continuums of main tensions for multidisciplinary staff working in forensic practice.

Clinical Competence↗
PubMed2002

Association of British Clinical Diabetologists (ABCD) survey of secondary care services for diabetes in the UK, 2000. 1. Methods and major findings.

OBJECTIVE: To examine the provision, and variations in, secondary care diabetes services in the UK. METHODOLOGY AND PARTICIPANTS: A postal survey of all 238 identified secondary care providers of diabetes services in 2000. RESULTS: Following two reminders, a 77% response rate was achieved. Major deficiencies in core staffing levels were recorded, with 36% of services provided by only one consultant physician with an interest in diabetes. The provision of diabetes specialist nurses was less than recommended in 87% of responses, whereas podiatry and dietetic support was unavailable in 3% and 27% of responses, respectively. Diabetes registers were not present in 28%, and a co-ordinated retinopathy screening programme unavailable in 26% of responses. Key biochemical measurements were unavailable in 9% (microalbuminuria) to 18% (HDL-cholesterol) of responses. A 'Well-Resourced Service' score was devised taking account of levels of personnel, facilities and specialized clinical services. There was a significant geographical variation in this score (P < 0.001), with the lowest score (least well-resourced services) in the Eastern NHS Region of England, and the highest score in the North-west NHS Region of England. The 'Well-Resourced Service' score was also significantly lower (P < 0.05) where there were less than two whole-time consultant physicians providing diabetes services. In contrast to other aspects of service provision, availability of dieticians and a combined diabetes-ophthalmology service had declined since 1990. Of 245 recorded bids for resources and service improvements for diabetes care, the success rate overall was 44%, and lowest where bids were made for dietetic and podiatry support. CONCLUSIONS: There is presently a major shortfall in provision of secondary care diabetes services throughout the UK, with evidence that there is significant regional variation and less facilities and resources where there are less than two consultants providing specialized diabetes services. On average bids for service improvements were only successful in < 50% of cases, most usually where the service was relatively better provided for. Considerable development and investment are required nationally to ensure equitable access to specialized diabetes services, a vital component in reducing adverse diabetes outcomes.

Delivery of Health Care↗
PubMed2002

Intussusception in an adult patient with severe hyperglycaemia--a case report.

AIMS: To report a case of adult intussusception associated with and possibly induced by acute hyperglycaemia. METHODS: We present the first case report of adult intussusception with severe hyperglycaemia. Clinical and laboratory data together with radiological findings are presented with a brief review of the literature. RESULTS: A 20-year-old man with no past medical history presented with abdominal pain for 2 days. The patient was severely hyperglycaemic with blood glucose of 72.7 mmol/l (normal 3.3-6.1 mmol/l), a pH of 7.2 and serum potassium of 6.5 mmol/l (normal 3.5-5.0 mmol/l). He had a computed tomography (CT) scan of the abdomen that revealed small bowel intussusception. Upon treatment of his hyperglycaemia, the patient's abdominal pain completely resolved. Follow up abdominal CT revealed complete resolution of the previously detected intussusception. CONCLUSION: Clinicians should be aware of the potential for the occurrence of intussusception in severely hyperglycaemic patients. Correction of hyperglycaemia could lead to resolution of the intussusception without surgical intervention. Possible effects of hyperkalaemia and/or acidosis on gastrointestinal motility should also be considered.

Abdominal Pain↗
PubMed2002

Esophageal pneumatic dilation for postfundoplication dysphagia: safety, efficacy, and predictors of outcome.

OBJECTIVE: Persistent dysphagia occurs in 5-10% of patients after fundoplication. The cause is obscure in most cases, and the management has not been well established. The aim of this study is to evaluate the clinical outcomes and the predictors of success for esophageal pneumatic dilations in patients with dysphagia after fundoplication. METHODS: We retrospectively reviewed 14 patients who underwent pneumatic dilation for persistent postfundoplication dysphagia. All patients had esophageal manometry before dilations. RESULTS: There were nine responders to pneumatic dilations (30-40-mm balloons). The nadir lower esophageal sphincter (LES) relaxation pressure was the only significant predictor for successful dilation and was higher among the responders than nonresponders (median 10 mm Hg vs 5 mm Hg). All six of 14 patients with nadir LES pressure > or = 10 mm Hg had a good response. There was no significant difference in the LES basal pressure between the responders and nonresponders (median 20 mm Hg vs 12 mm Hg). The median distal peristaltic amplitude (74 mm Hg vs 69 mm Hg), percent of failed peristalsis (8% vs 45%), and ramp pressure (19 mm Hg vs 17 mm Hg) did not differ significantly between the responders and nonresponders. No perforations occurred. CONCLUSIONS: Pneumatic dilation is a reasonably safe and effective treatment for patients with postfundoplication dysphagia. Raised nadir LES relaxation pressure seems to be a useful predictor of successful outcome.

Aged↗
PubMed2002

Effect of margins of excision on recurrence after local excision of ductal carcinoma in situ of the breast.

AIMS: To determine important factors influencing recurrence after local excision of duct carcinoma in situ (DCIS) of the breast. MATERIALS AND METHODS: The extent (size) in millimetres, classification (by cytonuclear grade (NHSBSP system), by extent of necrosis, and by the Van Nuys system), and excision margins of 115 cases of screen detected DCIS treated by local excision were measured. A prognostic index was calculated by the addition of the Van Nuys classification (low grade, 1; moderate grade, 2; high grade, 3), margin score (> or = 10 mm, 1; 1-9 mm, 2; < 1 mm, 3), and size score (< or = 15 mm, 1; 16-40 mm, 2; and > or = 41 mm, 3), giving a total score of 3-9. RESULTS: Classification using cytonuclear grade, extent of necrosis, or the Van Nuys system did not correlate significantly with recurrence. The excision margin (in millimetres) was associated with recurrence (p = 0.027) and if excision margin status was simplified using the scoring system (> or = 10 mm, 1; 1-9 mm, 2; < 1 mm, 3), the margin score was significantly associated with recurrence (p = 0.03). A prognostic index based on the Van Nuys score, margin status, and size was significantly associated with recurrence (p = 0.003). CONCLUSION: The results support the hypothesis that the margin of excision is the most important factor predicting the recurrence of DCIS after local excision.

Aged↗
PubMed2002

Antibiotic resistant tuberculosis in the United Kingdom: 1993-1999.

BACKGROUND: The re-emergence of tuberculosis as a global health problem over the past two decades, accompanied by an increase in tuberculosis drug resistance, prompted the development of a comprehensive national surveillance system for tuberculosis drug resistance in 1993. METHODS: The UK Mycobacterial Resistance Network (Mycobnet), which includes all mycobacterial reference and regional laboratories in the UK, collects a minimum dataset on all individuals from whom an initial isolate of Mycobacterium tuberculosis complex has been isolated and submitted by source hospital laboratories. Data sought include susceptibility to first line antibiotics, demographic, geographical, and risk factor information. RESULTS: There were 25 217 reports of initial isolates of M tuberculosis complex in the UK between 1993 and 1999. All were tested for sensitivity to isoniazid, rifampicin, and ethambutol and 12 692 of the isolates were also tested for sensitivity to pyrazinamide and streptomycin. A total of 1523 (6.1%) isolates were resistant to one or more drugs, 1397 isolates (5.6%) were resistant to isoniazid with or without resistance to other drugs, and 299 (1.2%) were multidrug resistant. Although the numbers of drug resistant isolates increased over the period, the proportions remained little changed. Certain groups of people were at a higher risk of acquiring drug resistant tuberculosis including younger men, residents of London, foreign born subjects, patients with a previous history of tuberculosis and those infected with HIV. CONCLUSION: Although the proportion of drug resistant tuberculosis cases appears to be stable in the UK at present, more than one in 20 patients has drug resistant disease at diagnosis and more than one in 100 has multidrug resistant disease. Tuberculosis control measures should be strengthened to minimise the emergence of drug resistance through rapid diagnosis, rapid identification of drug resistance, supervised treatment, and maintenance of comprehensive surveillance.

AIDS-Related Opportunistic Infections↗
PubMed2001

The LIM domain gene LMO4 inhibits differentiation of mammary epithelial cells in vitro and is overexpressed in breast cancer.

LMO4 belongs to a family of LIM-only transcriptional regulators, the first two members of which are oncoproteins in acute T cell leukemia. We have explored a role for LMO4, initially described as a human breast tumor autoantigen, in developing mammary epithelium and breast oncogenesis. Lmo4 was expressed predominantly in the lobuloalveoli of the mammary gland during pregnancy. Consistent with a role in proliferation, forced expression of this gene inhibited differentiation of mammary epithelial cells. Overexpression of LMO4 mRNA was observed in 5 of 10 human breast cancer cell lines. Moreover, in situ hybridization analysis of 177 primary invasive breast carcinomas revealed overexpression of LMO4 in 56% of specimens. Immunohistochemistry confirmed overexpression in a high percentage (62%) of tumors. These studies imply a role for LMO4 in maintaining proliferation of mammary epithelium and suggest that deregulation of this gene may contribute to breast tumorigenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Liver transplantation in adults coinfected with HIV.

OBJECTIVE: To report our experience of prospectively identifying and transplanting livers into HIV-positive patients. DESIGN: Liver transplantation in HIV-positive patients remains controversial. The finding of HIV is usually considered a contraindication to any form of transplantation. Previously reported cases are few and refer to patients who tested HIV positive after they had their liver transplantations or who seroconverted in the posttransplantation period. This is, to our knowledge, the only report of patients who were known to be HIV positive at the time of decision for listing for transplantation. METHODS: The medical records of five HIV-positive patients who received liver transplants in King's College Hospital, London, during a 5-year period (January 1995-December 1999) were reviewed. All five were known to be HIV positive at the time of listing for liver replacement. Three of them had end-stage liver disease due to hepatitis C (two of them had underlying Hemophilia A) while the other two had acute liver failure, one due to hepatitis B infection and one due to nonA-nonB-nonC hepatitis. In all but one patient the HIV infection had been asymptomatic. RESULTS: All patients survived the immediate posttransplantation period, but the three patients with hepatitis C died of complications of recurrent hepatitis C between 6 and 25 months posttransplantation. The other two patients are currently alive 4 and 34 months posttransplantation with good graft function and without complications from their HIV infection. CONCLUSION: The early outcome of liver transplantation in HIV seropositive patients can be good, and patients should not be excluded from transplantation if their liver disease determines their prognosis. More effective antiviral therapy for hepatitis C given posttransplantation, and for hepatitis B reinfection, should improve the longer-term outcome of HIV patients with end-stage liver disease due to hepatitis.

Adolescent↗