Search PubMed⌕ Search

Biomedical subjects

R Taylor

Publications and source records attributed to R Taylor.

At least 55 records · Page 3Linked to original sources
PubMed2002

CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours.

We have recently shown that the CHEK2*1100delC mutation acts as a low penetrance breast cancer susceptibility allele. To investigate if other CHEK2 variants confer an increased risk of breast cancer, we have screened an affected individual with breast cancer from 68 breast cancer families. Five of these individuals were found to harbour germline variants in CHEK2. Three carried the 1100delC variant (4%). One of these three individuals also carried the missense variant, Arg180His. In the other two individuals, missense variants, Arg117Gly and Arg137Gln, were identified. These two missense variants reside within the Forkhead-associated domain of CHEK2, which is important for the function of the expressed protein. None of these missense variants were present in 300 healthy controls. Microdissected tumours with a germline mutation showed loss of the mutant allele suggesting a mechanism for tumorigenesis other than a loss of the wild type allele. This study provides further evidence that sequence variation in CHEK2 is associated with an increased risk of breast cancer, and implies that tumorigenesis in association with CHEK2 mutations does not involve loss of the wild type allele.

Adult↗
PubMed2002

Direct assessment of muscle glycogen storage after mixed meals in normal and type 2 diabetic subjects.

To understand the day-to-day pathophysiology of impaired muscle glycogen storage in type 2 diabetes, glycogen concentrations were measured before and after the consumption of sequential mixed meals (breakfast: 190.5 g carbohydrate, 41.0 g fat, 28.8 g protein, 1253 kcal; lunch: 203.3 g carbohydrate, 48.1 g fat, 44.0 g protein, 1497.5 kcal) by use of natural abundance (13)C magnetic resonance spectroscopy. Subjects with diet-controlled type 2 diabetes (n = 9) and age- and body mass index-matched nondiabetic controls (n = 9) were studied. Mean fasting gastrocnemius glycogen concentration was significantly lower in the diabetic group (57.1 +/- 3.6 vs. 68.9 +/- 4.1 mmol/l; P < 0.05). After the first meal, mean glycogen concentration in the control group rose significantly from basal (97.1 +/- 7.0 mmol/l at 240 min; P = 0.005). After the second meal, the high level of muscle glycogen concentration in the control group was maintained, with a further rise to 108.0 +/- 11.6 mmol/l by 480 min. In the diabetic group, the postprandial rise was markedly lower than that of the control group (65.9 +/- 5.2 mmol/l at 240 min, P < 0.005, and 70.8 +/- 6.7 mmol/l at 480 min, P = 0.01) despite considerably greater serum insulin levels (752.0 +/- 109.0 vs. 372.3 +/- 78.2 pmol/l at 300 min, P = 0.013). This was associated with a significantly greater postprandial hyperglycemia (10.8 +/- 1.3 vs. 5.3 +/- 0.2 mmol/l at 240 min, P < 0.005). Basal muscle glycogen concentration correlated inversely with fasting blood glucose (r = -0.55, P < 0.02) and fasting serum insulin (r = -0.57, P < 0.02). The increment in muscle glycogen correlated with initial increment in serum insulin only in the control group (r = 0.87, P < 0.002). This study quantitates for the first time the subnormal basal muscle glycogen concentration and the inadequate glycogen storage after meals in type 2 diabetes.

Blood Glucose↗
PubMed2002

Factors determining mean ICP in hydrocephalic patients with Hakim-programmable valve: implications of the parallel arrangement of the CSF outflow resistance and shunt.

OBJECTIVE: Measurement of CSF pressure is used clinically to test shunt function in vivo in hydrocephalic patients. Criteria for appropriate shunt function have never been validated. METHOD: Hakim-Programmable valve was tested in a model of CSF circulation with variable resistance to CSF outflow (from 12 to 50 mm Hg/ml/min), increased hydrodynamic compliance (> 1.5 ml/mm Hg), and constant perfusion of a rate of 0.4 ml/min, i.e. conditions typical for hydrocephalus. The main question was how the simulated CSF pressure was influenced by the shunt setting and the residual resistance to CSF outflow. RESULTS: Measured baseline CSF pressure correlated well with shunt operating pressure only when high resistance to CSF outflow (50 mm Hg/(ml/min)) was used. For the medium resistance (20 mm Hg/(ml/min)) operating pressure was strongly affected by system's absorption capacity. For low resistance (12 mm Hg/(ml/min)) operating pressure through the valve was independent on valve's settings and no fluid drainage through the valve was recorded. CONCLUSION: Patients with moderately elevated resistance to CSF outflow (12-18 mm Hg/(ml/min)) cannot possibly react to changes of the valve's settings above 100 mm H2O. Mean CSF pressure results both from shunt setting and patient's own re-absorption capacity.

Cerebrospinal Fluid Shunts↗
PubMed2002

Measuring the success of treatment for chronic obstructive pulmonary disease--patient, physician and healthcare payer perspectives.

The success of treatments for chronic obstructive pulmonary disease (COPD) is evaluated by measuring the impact on a range of health outcomes. However, outcome measures differ in their relative importance to the various stakeholder groups. Patients are most interested in the impact on quality of life and on mortality, while physicians also value information about the effect of treatments on lung function and disease progression. In contrast to patients and physicians, healthcare payers take a population perspective, and need to balance the health gains achieved and the costs of treatment. If the management of COPD is to be improved, it is important, first, to understand the outcomes of importance to each relevant stakeholder group, and then second, to refocus the measures in terms that all stakeholders can value.

Attitude of Health Personnel↗
PubMed2002

Decision-making by healthcare payers.

Healthcare payers are faced with the need to allocate finite resources to maximize population health. To assist in decision-making, healthcare payers are increasingly using health outcomes information and economic analyses. Healthcare payers are often under pressure to make early decisions (around the time of product launch), when the evidence available is imperfect. They must also consider the equitable distribution of resources between therapeutic areas. Tools to help healthcare payers reach transparent and objective decisions include cost-utility analysis and decision modelling. In practice, healthcare payers in different countries (for example, Ireland, France and Canada) vary in the approaches taken to reimbursement and formulary listing decisions. The key to decision-making among healthcare payers is the provision of appropriate evidence, comparing any new treatment approach to current best practice, in situations corresponding to real life. When data assumptions have to be made, these should be clearly stated with consideration of the impact of varying the assumptions. The impact on budgets should also be considered.

Attitude of Health Personnel↗
PubMed2002

Birth cohort effects in New South Wales suicide, 1865-1998.

OBJECTIVE: To examine birth cohort effects in New South Wales (NSW) suicide data (1865-1998). METHOD: Aggregate suicide data were examined after controlling for age and period using descriptive statistics and Poisson regression modelling. Three approaches were applied to address the non-identification of age, period and cohort in age-period-cohort (APC) models of suicide. RESULTS: Apparent cohort effects in male and female suicide using a minimum constraints APC model of age, period and cohort were no longer present in female suicide when a surrogate period APC model was used, and were absent in both male and female suicide when identifiable cohort effects were isolated using a 'drift' adjusted approach to APC modelling. CONCLUSION: Increases in youth suicide rates in NSW occurring since the 1960s cannot be attributed to cohort effects, such as family influences on development. The causes of youth suicide are thus effects operating contemporaneously.

Age Factors↗
PubMed2002

Sirolimus steady-state trough concentrations are not affected by bolus methylprednisolone therapy in renal allograft recipients.

AIMS: To determine whether bolus doses of methylprednisolone affect the steady-state trough concentrations of sirolimus. METHODS: Fourteen renal transplant recipients received concentration-controlled sirolimus therapy in combination with azathioprine and steroids (n=8) or mycophenolate mofetil and steroids (n=6). Bolus doses of methylprednisolone (mean total dose over 1-5 days, 1694 mg; range, 500-3000 mg) were given for the treatment of acute rejection. For each patient, the sirolimus dose (mean, 24.1 mg; range, 3.3-52.5 mg) was the same before and during methylprednisolone therapy. RESULTS: Mean sirolimus whole blood trough concentrations before and after treatment with methylprednisolone were 28.8 ng ml-1 (range, 13.9-45.3 ng ml-1), and 28.5 ng ml-1 (range, 13.0-47.9 ng ml-1), respectively (P=0.85; 95% confidence interval on the difference -3.3, 4.0 ng ml-1). CONCLUSIONS: Bolus methylprednisolone treatment does not affect steady-state sirolimus trough concentrations.

Adult↗
PubMed2002

Use of the St Gallen classification for patients with node-negative breast cancer may lead to overuse of adjuvant chemotherapy.

BACKGROUND: The 1998 St Gallen classification was devised to guide clinicians in the use of adjuvant systemic therapy for women with early breast cancer. In this study, the classification was applied to a historical group of patients with node-negative breast cancer who were treated without adjuvant therapy. METHODS: The St Gallen classification was applied to 421 women with breast cancer treated with conservative surgery and radiotherapy alone between 1979 and 1994. Primary tumour characteristics were reviewed centrally. RESULTS: When the most stringent version of the St Gallen classification was applied (grade 2 or 3 tumours classified as "high risk"), only 10 per cent of patients were "low risk", with a 10-year distant relapse-free survival (DRFS) rate of 100 per cent, and 15 per cent were at "intermediate risk" (10-year DRFS rate of 94 per cent). The high-risk group (75 per cent of women) had a 10-year DRFS rate of 77 per cent (P < 0.01). If the St Gallen classification had been applied to all patients in this series who were aged less than 70 years, up to 91 per cent would have been recommended to have chemotherapy. CONCLUSION: The St Gallen classification is an inaccurate measure of prognosis for patients with node-negative breast cancer and should be used with caution.

Adult↗
PubMed2002

The impact of a practice development project on the quality of in-patient small group therapy.

In 1993 a mental health service in South-east England initiated a practice development project that aimed at continuously improving the quality of in-patient small group therapy provided within its four acute wards. From the outset it was intended that the project and the practice it focused on should be robust and research based. In support of this an evaluative study was carried out in 1998. The evaluation covered a 6-month period and coincided with concerns being reported elsewhere about the adequacy of therapeutic activity within acute psychiatric settings across the country. Data collected for the evaluation focused on the quality dimensions of effectiveness, relevance to need, social acceptability, accessibility, efficiency and economy, and equity. Quantitative and qualitative methods were deployed and data were collected at three points in time over the evaluation period to provide a picture of change within each ward. The quantitative data gathered were mainly obtained through two self-report questionnaires that were developed specifically for the study. Both instruments were tested and found to have a high degree of internal consistency. The qualitative data gathered were collected using semistructured interviews. Analysis of the qualitative and quantitative data sets indicated that practice quality diminished rather than improved during the 6-month study period. Factors that emerged from the data as having influenced this outcome were: increases in ward team's overall workload, inadequate staffing levels and changes in expectations placed on those providing small group therapy. The findings are consistent with a national trend of deteriorating quality in in-patient care and point to some of the limitations of action learning as a practice development method. They also point to service factors that work against effective practice development.

Female↗
PubMed2002

Quality assurance in screening for sight-threatening diabetic retinopathy.

AIMS: There is a need for continuous evaluation of screening services for diabetic retinopathy against agreed performance standards. We describe a quality assurance programme implemented in Newcastle in January 1999 and report on outcomes at 18 months. METHODS: Annual retinal screening is performed using combined retinal photography and direct ophthalmoscopy in two streams. Diabetologists perform screening in the Hospital Screening Programme, which serves patients whose diabetes is managed in specialist clinics, and trained retinal screeners perform screening in the District Screening Programme, which serves patients whose diabetes is managed in the community. Reference standard examination of dilated fundoscopy with a slit-lamp and condensing lens was performed by an ophthalmologist at periodic sessions on consecutive patients attending for screening. RESULTS: Six hundred and nine (6.4%) of 9468 patients screened underwent reference standard examination. The sensitivity and specificity of detection of sight-threatening diabetic retinopathy (STDR) was 82.5% and 98%, respectively, for the Hospital Screening Programme; 85.7% and 95.7%, respectively, for the District Screening Programme; and 83.3% and 96.8% for both services combined. One hundred and ten (18.1%) of 609 patients audited were referred to ophthalmology as a result of screening, and this led to 16 patients (2.6%) receiving laser photocoagulation for STDR. Reference standard examination identified a further four patients (0.7%) who required laser photocoagulation. CONCLUSIONS: Preliminary data indicate that satisfactory performance standards are being achieved. The National Service Framework for Diabetes requires that all units institute quality assurance for retinal screening, and we report the practical implementation of this in one district.

Diabetic Retinopathy↗
PubMed2002

Block allografts in revision total hip arthroplasty.

We report on 61 consecutive cemented acetabular revisions in which block allografts were used to reconstruct large defects. After a mean follow-up of 6.5 years, we observed satisfactory results when grafts had been rigidly fixed. Additional buttress-plates can improve the outcome. Paprosky type 3B defects had a double risk of failure. Cup migration had a 56% predictive value for failure. Several metal-backed cups failed, although the graft remained intact. There was a good improvement in functional outcome, which did not deteriorate up to a maximum follow-up of 11 years. Cemented revision total hip arthroplasty with the use of block allografts can give acceptable results in the medium to long term.

Acetabulum↗
PubMed2002

A laboratory model of testing shunt performance after implantation.

Constant rate infusion tests are used clinically to test shunt function in vivo in hydrocephalic patients. The criteria for appropriate shunt function have never been validated in the laboratory. Nine of the most commonly used types of hydrocephalus valves construction were selected and tested in a model of the CSF circulation incorporating increased resistance to CSF outflow [24 mmHg/(ml/min)] and decreased hydrodynamic compliance (<2 ml/mmHg), that are typical conditions in hydrocephalus. The aim was to document the pressure response to constant rate infusion of a model of CSF circulation with different valves and to define which measures are useful in shunt testing in vivo. The pressure-course of simulated CSF pressure was established and proved to be equivalent to clinical results. The baseline CSF pressure failed to correlate with shunt operating pressure for medium pressure valves (R = 0.14, p > 0.05). End-equilibrium pressure recorded during infusion correlated strongly with the opening pressure (R = 0.94, p = 0.0001) and the shunt's resistance (R = 0.86, p = 0.0026). The infusion test is able to assess shunt function. End-equilibrium pressure recorded during the test has been confirmed to correlate with the shunt's performance.

Cerebrospinal Fluid Pressure↗
PubMed2002

A prospective study of thalamic deep brain stimulation for the treatment of movement disorders in multiple sclerosis.

The place for neurosurgical management of movement disorders in multiple sclerosis is unclear. To evaluate the potential benefits of unilateral thalamic deep brain stimulation (DBS) a prospective study was performed. Fifteen patients with confirmed MS and chronic, severe, drug-resistant movement disorders underwent stereotactic surgery to implant a thalamic DBS electrode using CT image guidance and intra-operative neurophysiological testing. The primary outcome measures were reduction in tremor severity and improvement in tests of hand function when the DBS electrode was turned on, 12 months after surgery. Secondary outcome measures included indices of disability, handicap, neuropsychological function and independence. Thirty-seven patients were assessed for treatment, but only 15 underwent surgery. In the 10 patients in whom implantation of the complete DBS system was carried out there was a significant reduction in the severity of tremor (p = 0.02) and improvement in hand function (p = 0.02). There were no benefits in any of the secondary outcome measures. Two patients had thalamocapsular haemorrhages at the site of electrode implantation and two had seizures in the follow-up period. Thalamic stimulation significantly reduced the tremor associated with MS and improved hand function in the targeted upper limb. However, there can be difficulties with identifying an optimal implantation site during operation, significant procedural morbidity and difficulty in predicting immediate outcome. It is also likely that the insignificant benefits of DBS on disability and handicap reflect persisting cerebeller dysmetria, and both the severity and diffuse nature of the disease process in this patient cohort.

Adult↗
PubMed2002

Management of hyperemesis gravidarum: the importance of weight loss as a criterion for steroid therapy.

BACKGROUND: Although the effectiveness of prednisolone therapy for severe hyperemesis gravidarum has been demonstrated, there is no consensus on how to assess severity to justify such treatment, nor any information on whether such therapy affects birth weight. AIM: To document the effect of prednisolone therapy in women with defined severity of hyperemesis gravidarum. DESIGN: Single centre, observational study of 30 consecutive pregnancies complicated by hyperemesis and weight loss of >5% of pre-pregnant weight between April 1995 and July 2000. Comparison of birth weight with a contemporaneous control series of women admitted with hyperemesis that was judged insufficiently severe to require steroids. RESULTS: Treatment with prednisolone 10 mg tid rapid resolved nausea and vomiting, allowing discharge in 3 (range 1-6.5) days. Steroid therapy, which was reduced in a stepwise manner, was discontinued at a median gestation of 20 weeks. Maternal weight gain in pregnancy was restored to normal. Median birth weight in the severe, steroid-treated group was 3.33 (range 2.80-3.27) kg vs. 3.27 (range 3.04-3.53) kg in the less severe group. CONCLUSION: Weight loss >5% served as a criterion to define a subset of women with severe hyperemesis gravidarum. In these women, steroid therapy was uniformly successful resulting in the prompt resolution of symptoms. Steroid therapy did not affect birth weight.

Adult↗