Search PubMed⌕ Search

Biomedical subjects

J Wright

Publications and source records attributed to J Wright.

At least 127 records · Page 7Linked to original sources

Photochemical dimerization of acephenanthrylene and the heavy atom effect

The solution-phase photodimerization of acephenanthrylene (1) in cyclohexane, chloroform, dibromomethane, and ethyl iodide with visible light (lambda = 419 nm) occurs to form cis (2) and trans (3) photodimers in ratios that vary with the solvent and with the presence or absence of oxygen. The photodimerization exhibits a significant heavy atom effect and also is sensitive to selective quenching by dissolved oxygen, in which only cis stereoisomers are produced. Irradiation of the dimers (lambda = 254 nm) shows that the trans dimers cleave more rapidly than the cis dimers. This is attributed to stabilization of the excited state in the cis dimers.

Journal Article↗

Far, far away

Explore the source record for details and available documents.

Journal Article↗

Continuous positive airways pressure for obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is the periodic reduction (hypopnoea) or cessation (apnoea) of breathing due to narrowing or occlusion of the upper airway during sleep. The mainstay of nocturnal treatment is continuous positive airway pressure (CPAP) therapy at home at night to prevent the resulting apnoea, hypoxia and sleep fragmentation which are believed to cause the symptoms of OSA. A number of clinical trials have evaluated the effectiveness of nasal CPAP) as a treatment. OBJECTIVES: The objective was to review the effects of CPAP in the treatment of obstructive sleep apnoea in adults. SEARCH STRATEGY: We searched Medline 1966 to 1996, Embase 1974 to 1996, Cinahl 1982 to 1995 and the reference lists of articles. We consulted experts in the field. SELECTION CRITERIA: Randomised trials comparing nocturnal CPAP with placebo or other treatments in adults with obstructive sleep apnoea and an apnoea/hypopnoea index greater than five per hour. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for missing information. MAIN RESULTS: Seven trials involving 177 people were included. All the studies had some methodological shortcomings. Six trials were of crossover design. Compared with placebo, CPAP showed significant improvements in several quality of life and depression measures. Patients preferred CPAP to placebo (odds ratio 0.4, 95% confidence interval 0.2 to 0.8). There was no significant effect on blood pressure or measures of sleepiness and sleep quality. Compared with oral appliances, CPAP significantly improved the apnoea/hypopnoea index (weighted mean difference -7.3, 95% confidence interval -10.0 to -4.7) and minimum oxygen saturation during sleep. Patients strongly preferred the oral appliance to CPAP (odds ratio 9.5, 95% confidence interval 4.3 to 21.1). REVIEWER'S CONCLUSIONS: CPAP appears to be more effective than placebo in improving some quality of life measures for people with obstructive sleep apnoea. It appears to be more effective than oral appliances in improving respiratory disturbances. People appear to prefer oral appliances over CPAP, but prefer CPAP over placebo.

Adult↗

Echoplanar imaging in GI clinical practice: assessment of gastric emptying and antral motility in four patients.

Gastric emptying, frequency of antral contractions, and speed of antral contraction propagation were assessed in four patients using echoplanar imaging techniques. The results obtained and their impact on the diagnosis and management of the patients are presented and discussed. This shows that echoplanar evaluation of gastric function is noninvasive, well-tolerated by patients, detects clinically relevant abnormalities, and has the potential of becoming a valuable examination in the clinical gastrointestinal practice.

Adult↗

Vertebral morphometry: repeat scan precision using the Lunar Expert-XL and the Hologic 4500A. A study for the 'WISDOM' RCT of hormone replacement therapy.

On radiation safety grounds there is concern about the morbidity attributable to routine radiographs of the spine for the identification of new fractures in large-scale trials of fracture prevention. However, the role of the potentially safer low-radiation-dose technique of vertebral morphometry performed by third generation dual-energy X-ray absorptiometry equipment requires evaluation for use in clinical trials. We have therefore investigated the short-term inter-scan imprecision as well as the imprecision attributable to different-day analyses by the same operator and differences in analyses by different operators. The volunteer subjects were participants in a pilot study for a randomized controlled trial of hormone replacement therapy (Women's International Study of long Duration Oestrogen after Menopause, WISDOM). Each subject had two morphometric X-ray analysis scans separated by 2-4 weeks. Exclusions were women with densitometrically defined osteoporosis, as defined by the WHO criterion, and women with a body mass index exceeding 30.9 kg/m2. On average, the women were 58.7 years of age and had bone mineral density values in the lumbar spine which were about 0.7 SD units higher than a reference US female age-matched population. Scans were assessed from vertebrae T7 through L4. In the study there were no clinically significant differences in performance between the Hologic QDR 4500A and the Lunar Expert XL equipment. Between-scan imprecision was significantly worse than imprecision attributable to reanalysis of the same scan by a different operator or the same operator after an interval. Vertebral level had an effect on measurement uncertainty, especially at the level of the diaphragm and at T7. Coefficients of variation, expressed as percentages of mean values, were better for absolute height measurements than for height ratios, ranging from 1.75% to 3.40% for the three heights measured on three separate machines and from 2.34% to 4.11% for the two height ratios. These results compared favorably with the equivalent figures from a parallel study of morphometry precision undertaken using standard lateral radiographs of the thoracic and lumbar spine (3.1-3.6% and 3.8-3.9%, respectively). We conclude that in trials of prevention therapy in women (or men) selected for not having osteoporosis, low-dose vertebral morphometry using the Hologic 4500A, the Lunar Expert XL or similar equipment is preferable on safety grounds to the classical technique based on standard radiographs, although conventional radiology may still be required in those with prevalent or incident deformities to exclude causes other than osteoporosis. The place of this low-dose technique in trials performed on patients with osteoporosis requires further study.

Absorptiometry, Photon↗

Pretreatment with ranitidine does not reduce the bioavailability of orally administered topotecan.

PURPOSE: The purpose of this randomized, two-period crossover study was to determine the pharmacokinetics of orally administered topotecan in the presence and absence of oral ranitidine. METHODS: Patients with solid malignant tumors refractory to standard treatment were given topotecan orally on a daily times five schedule repeated every 21 days. Topotecan was given initially at 2.3 mg/m2 per day; dose adjustments were permitted after the first dose of course 2 if necessary. Blood samples for pharmacokinetic assessments were drawn at protocol-specified times for up to 10 h following oral administration of topotecan on day 1 of courses 1 and 2. Patients were randomly assigned to receive a total of nine doses of ranitidine: 150 mg twice daily for 4 days before day 1 of one of the first two courses and 150 mg given 2 h before the first topotecan dose. Plasma samples were assayed for concentrations of active topotecan lactone (TPT-L) and total topotecan (TPT-T, lactone plus open-ring carboxylate form) using high-performance liquid chromatography with fluorescence detection. After completion of courses 1 and 2, patients could continue on therapy for days 1-5 of every 21 days if not withdrawn due to unacceptable toxicity, disease progression, protocol violation, or by request. Patients continued on treatment for a maximum of six courses. RESULTS: No pharmacokinetic parameter for either TPT-L or TPT-T differed significantly during administration of topotecan with ranitidine compared with topotecan alone (n = 13). Geometric mean ratios (95% confidence intervals, CIs) of areas under the curve in the presence and absence of ranitidine were 0.94 (0.80, 1.10) for TPT-L and 0.97 (0.80, 1.16) for TPT-T. Corresponding ratios (CIs) of peak plasma concentrations in the presence and absence of ranitidine were 1.06 (0.78, 1.44) for TPT-L and 1.07 (0.84, 1.38) for TPT-T. The median difference in time to peak plasma concentration was 0.0 h for TPT-L and -0.5 h for TPT-T (i.e. slightly faster in the presence of ranitidine). CONCLUSIONS: Administration of ranitidine prior to oral topotecan resulted in a similar extent of absorption. A slightly faster rate of absorption of topotecan was also observed, which is unlikely to be of clinical significance. Dosage adjustments of orally administered topotecan should not be necessary in patients who are pretreated with ranitidine, an H2 antagonist, or another agent that comparably raises gastric pH.

Administration, Oral↗

How is good and poor sleep in older adults and college students related to daytime sleepiness, fatigue, and ability to concentrate?

We compared good sleepers with minimally and highly distressed poor sleepers on three measures of daytime functioning: self-reported fatigue, sleepiness, and cognitive inefficiency. In two samples (194 older adults, 136 college students), we tested the hypotheses that (1) poor sleepers experience more problems with daytime functioning than good sleepers, (2) highly distressed poor sleepers report greater impairment in functioning during the day than either good sleepers or minimally distressed poor sleepers, (3) daytime symptoms are more closely related to psychological adjustment and to psychologically laden sleep variables than to quantitative sleep parameters, and (4) daytime symptoms are more closely related to longer nocturnal wake times than to shorter sleep times. Results in both samples indicated that poor sleepers reported more daytime difficulties than good sleepers. While low- and high-distress poor sleepers did not differ on sleep parameters, highly distressed poor sleepers reported consistently more difficulty in functioning during the day and experienced greater tension and depression than minimally distressed poor sleepers. Severity of all three daytime problems was generally significantly and positively related to poor psychological adjustment, psychologically laden sleep variables, and, with the exception of sleepiness, to quantitative sleep parameters. Results are used to discuss discrepancies between experiential and quantitative measures of daytime functioning.

Adaptation, Psychological↗

A population-based study of the prevalence, clinical characteristics and effect of ethnicity in epilepsy.

UNLABELLED: The aim of this study was to determine the prevalence and clinical characteristics of epilepsy and seizure disorders in Bradford. The method used was a community-based cross-sectional study. Case ascertainment was by review of medical records identified by searching practice databases using diagnostic codes and from repeat prescribing data. A specialist epilepsy nurse reviewed the records in 39 practices covering a population of 225 439. Clinical review was undertaken where there was limited information available in the records. In total, 1643 cases of epilepsy were identified (prevalence 7.3/1000). The prevalence of epilepsy increased with age. Classification of patients by internationally agreed definitions showed 1013 (62%) of cases with active epilepsy (prevalence 4. 5/1000); 421 (26%) with epilepsy in remission on treatment and 209 (13%) with epilepsy in remission off treatment. The standardized rate for all patients of South Asian origin was 3.6/1000 compared to 7.8/1000 in the rest of the population (OR 0.46; 95% CI 0.38, 0.57). An underlying aetiology was identified in 29.5% of cases. Cerebrovascular disease and head injuries were the commonest causes. CONCLUSIONS: The prevalence of epilepsy supports previous epidemiological estimates and highlights the public health importance of epilepsy. The low prevalence in the South Asian population is a surprising finding and further research into cultural attitudes to epilepsy and the impact of stigma in the South Asian population in the UK is required.

Adolescent↗

Merkel cell carcinoma: report of 10 cases and review of the literature.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare primary neuroendocrine skin tumor that usually arises in the head and neck or the extremities of elderly patients. Because of the limitation of retrospective data, optimal treatment is not well defined. OBJECTIVE: Our purpose was to present the clinical course and treatment of 10 patients with MCC and review the published literature on MCC. METHOD: We conducted a retrospective analysis and obtained detailed clinical information for all 10 patients treated for MCC at our institution from 1986 through 1998. The medical literature was also reviewed for natural history and treatment recommendations using MEDLINE search. RESULTS: Five men and 5 women received their treatment between 1986 and 1998 for MCC (5 had stage IA disease, 4 stage IB, 1 stage II). The mean age was 70.3 years (range, 47-86 years). Seven tumors were located on the head and neck and 3 on extremities. Five of 10 patients had a relapse (mean time before recurrence, 5.7 months) (range, 2 weeks-20 months); one patient had local recurrence, one had regional lymph node recurrence, and 3 had both local and regional lymph node recurrence. In 4 patients systemic metastases developed. Long survival is also noted (6 to > 164 months); 4 patients died of MCC. After initial surgery, 9 patients received radiotherapy at some point and 3 patients also received chemotherapy. Five of 10 patients had 13 previously treated or coexisting malignant neoplasms. In one patient MCC developed in a previously irradiated field. Review of 875 cases showed a male/female ratio of 1.5:1; location of tumors was as follows: head and neck, 47%; extremities, 40%; trunk, 8%; unknown primary site, 5%. Local recurrence was observed in 25%, regional lymph node involvement in 52%, distant metastasis in 34%, and MCC was a cause of death in 34%. CONCLUSION: MCC has a high incidence of locoregional recurrence with distant metastases that is more common with higher stage lesions. Early local management of smaller lesions results in good long-term survival. It is not known whether prophylactic lymph node dissection and/or radiation and adjuvant radiation increases survival. Long survival can be achieved after treating locoregional recurrence. The role of chemotherapy is still controversial and should be considered in patients with advanced disease and those not thought to be candidates for surgery.

Aged↗

Cellular pharmacology of the D- and L-enantiomers of beta-5-o-carboranyl-2'-deoxyuridine.

The cellular pharmacology of the D- and L-enantiomers of beta-5-o-carboranyl-2'-deoxyuridine (CDU), compounds designed for boron neutron capture therapy (BNCT), were studied using human CEM lymphoblast and U-251 glioblastoma cells, at a physiologically achievable concentration (1 microM). Accumulation of the enantiomers was rapid and indistinguishable, reaching cellular concentrations > 40-fold higher than extracellular levels, with approximately 5% persisting in cells after incubation in fresh medium for more than 2 hr. Uptake was not affected by nucleoside uptake inhibitors, but was inhibited by the purine base uptake inhibitor papaverine.

Biological Transport↗

Gastric response to increased meal viscosity assessed by echo-planar magnetic resonance imaging in humans.

Normal meals are highly viscous, and viscosity is a key factor in influencing gastric emptying of food. However, the process of meal dilution and mixing is difficult to assess with the use of conventional methods. The aim of this study was to validate an in vivo, novel, noninvasive, echo-planar magnetic resonance imaging (EPI) technique, capable of monitoring the viscosity of a model meal, and to use this to investigate the effects of viscosity on gastric emptying, meal dilution and satiety. Healthy volunteers (n = 8) ingested 500 mL of locust bean gum (0.25, 0.5, 1.0 or 1.5 g/100 g), nonnutrient, liquid meals of varying viscosities, and labeled with a nonabsorbable marker, phenol red. Meal viscosity was calibrated against the water proton transverse relaxation rate (T(2)(-1)) in vitro before ingestion, thus viscosity was measured in vivo via EPI measurements of T(2)(-1). Viscosity and dilution were also measured directly using nasogastric aspirates. Gastric volumes as measured by EPI, fullness, appetite and hunger were also assessed serially. Before ingestion, the log of initial meal viscosity was linearly related to T(2)(-1) (n = 8, r(2) = 0.95). Similarly, T(2)(-1) measured in vivo was also linearly related to the viscosity of the aspirates (r(2) = 0.88). All meals underwent rapid dilution, leading to a reduction in viscosity, which was greatest for the most viscous meal (P < 0.01). Surprisingly, despite the fact that the initial meal viscosity varied 1000-fold, there was only a small delay in gastric emptying (P for trend < 0.05). The area under the curve for satiety increased with initial meal viscosity, whereas that for hunger decreased (P < 0.05). In conclusion, the viscosity of a meal in vivo can be measured noninvasively using EPI. The stomach responds to meal ingestion by rapid intragastric dilution, causing a reduction of meal viscosity, and gastric emptying is minimally delayed. However, increased viscosity is associated with more prolonged satiety.

Adult↗

Promoting effective practice in secondary care.

BACKGROUND: This qualitative study aimed to explore the views of key stakeholders regarding the role that public health professionals have or should have in the provision of effective health care within the National Health Service. METHODS: A national (England) questionnaire survey generated a sample for qualitative telephone interviews and two site case studies. The interviews were conducted in three stages: first, 27 interviews were based on assessed reported levels of organizational activity, including non-respondents; next, views in six areas were consolidated by extra interviews; finally, two extra areas were visited for individual and group interviews. The interviews were analysed for salient themes. RESULTS: There was a widespread view that public health had not delivered its potential. Many Trusts currently wanted public health to have influence over commissioning, provide health needs assessments and epidemiological skills, and provide a strategic focus and unbiased advice. Evaluation of actual activity varied widely; local history and congruent personalities seemed to be associated with perceived success. In some cases there was mutual suspicion between Health Authorities and Trusts. Public health was often perceived by Trusts to have been marginalized. This perception was not shared by Public Health Consultants, who highlighted lack of resources as a reason for lack of involvement. The contribution of public health professionals working in Trusts was highly regarded. Barriers included overcoming initial prejudice and combating isolation within Trusts. There were four categories of response in respect of the potential future role for public health in implementing effective health care: no role; collaborative working between Health Authority Public Health Departments and Trusts; deployment of public health workers within Trusts, and an undecided group. Overall, the skills of public health, especially strategic vision and population perspectives, were seen as valuable but as yet unrealized. CONCLUSIONS: Public health skills (but not necessarily professionals) may be valuable in implementing effective health care in Trusts. However, public health professionals must refocus and market their skills to Trusts if the discipline is to play a key role in this task.

Attitude of Health Personnel↗

The Center for Outcome Measurement in Brain Injury (COMBI): An Internet resource you should know about.

OBJECTIVE: This article describes the Center for Outcome Measurement in Brain Injury (COMBI), an Internet resource that provides information on brain injury outcome measures. Funded by the National Institute on Disability and Rehabilitation Research (NIDRR), the COMBI is a collaborative project of eight Traumatic Brain Injury (TBI) Model System centers. Information the COMBI provides includes rating scales and form(s) syllabus and administration guidelines, descriptions of properties, references in the literature, a frequently asked questions (FAQ) section, training and testing materials, and contact information. CONCLUSIONS: As a dissemination effort, the results of the COMBI project have been outstanding with over 1,500 users accessing information every month. The project has a truly international scope, with 20% of its users being outside the United States.

Brain Injuries↗

Total parenteral nutrition and enteral nutrition in diabetes.

A quarter or more of critically ill patients are likely to have carbohydrate intolerance or frank diabetes, either pre-existing or secondary to the stress of illness. Those patients who require parenteral nutrition should be treated using regimens similar to those used in nondiabetic patients, along with sufficient insulin (given by separate infusion) to maintain near-normal glycaemia. The role of novel substrates in diabetes remains to be established. In patients who require enteral nutrition, there is accumulating evidence that high-fat (as monounsaturated fatty acid) formulations achieve better overall metabolic control than conventional high-carbohydrate preparations. In view of the fact that macrovascular disease is the major cause of morbidity and mortality in type 2 diabetes in particular, and the fact that the risk of macrovascular complications is relatively unaffected by glycaemic control, the improved lipid and haemostatic profile achieved with preparations that are high in monounsaturated fatty acids is of particular importance in patients on long-term nutritional support.

Diabetes Mellitus↗

Tuberculosis in Swaziland: a health needs assessment in preparation for a community-based programme.

This study was undertaken to assess the healthcare needs of people with tuberculosis (TB) in the rural district of Lubombo in Swaziland, with a view to improving the delivery of healthcare services. Qualitative and quantitative methodologies were used to describe the knowledge, attitudes and behaviour of TB patients, the epidemiology of TB, and the strengths and weaknesses of the current TB control programme. The incidence of TB is rising rapidly in this rural region of Swaziland. Poor treatment completion rates indicate low levels of knowledge about the importance of compliance with TB treatment among many other factors. If local health services are to cope with future rising demands, then efforts must be made to implement a community-based TB treatment strategy. Key practical steps in establishing such a programme are discussed, and the experience from Lubombo is used to demonstrate the steps in performing a health needs assessment in a developing country.

Adolescent↗

Phase I and pharmacologic study of irinotecan administered as a 96-hour infusion weekly to adult cancer patients.

PURPOSE: We conducted a phase I and pharmacologic study of a weekly 96-hour infusion of irinotecan to determine the maximum-tolerated dose, define the toxicity profile, and characterize the clinical pharmacology of irinotecan and its metabolites. PATIENTS AND METHODS: In 26 adult patients with solid tumors, the duration and dose rate of infusion were escalated in new patients until toxicity was observed. RESULTS: In 11 patients who were treated with irinotecan at 12.5 mg/m(2)/d for 4 days weekly for 2 of 3 weeks, dose-limiting grade 3 diarrhea occurred in three patients and grade 3 thrombocytopenia occurred in two patients. The recommended phase II dose is 10 mg/m(2)/d for 4 days given weekly for 2 of 3 weeks. At this dose, the steady-state plasma concentration (Css) of total SN-38 (the active metabolite of irinotecan) was 6.42 +/- 1.10 nmol/L, and the Css of total irinotecan was 28.60 +/- 17.78 nmol/L. No patient experienced grade 3 or 4 neutropenia during any cycle. All other toxicities were mild to moderate. The systemic exposure to SN-38 relative to irinotecan was greater than anticipated, with a molar ratio of the area under the concentration curve (AUC) of SN-38 to irinotecan of 0.24 +/- 0.08. One objective response lasting 12 months in duration was observed in a patient with metastatic colon cancer. CONCLUSION: The recommended phase II dose of irinotecan of 10 mg/m(2)/d for 4 days weekly for 2 of 3 weeks was extremely well tolerated. Further efficacy testing of this pharmacologic strategy of administering intermittent low doses of irinotecan is warranted.

Adult↗