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Biomedical subjects

J Wright

Publications and source records attributed to J Wright.

At least 235 records · Page 13Linked to original sources

Characterization of the effect of dopamine D3 receptor stimulation on locomotion and striatal dopamine levels.

By examining the effect of dopamine (DA) D3 receptor stimulation on locomotor activity and extracellular levels of DA in striatum we show that inhibition of locomotor activity induced by DA D3 receptor-selective agonists is mediated by two interacting mechanisms: (1) directly via the stimulation of DA D3 receptors that inhibit locomotor activity, and (2) indirectly via a decrease in extracellular levels of DA. Thus, the moderately DA D3 receptor-selective agonist R-(+)-7-OH- DPAT (R-(+)-7-hydroxy-2-(N,N-di-n-propylamino)tetralin) decreased locomotor activity after administration of 10 nmol/kg and extracellular DA levels in accumbens and striatum after administration of 30 nmol/kg. A decrease in locomotor activity that coincided with a decrease in extracellular DA levels in striatum was observed after administration of 100 nmol/kg of the DA D3 receptor-selective agonist PD128907 ((+)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3 b]-1,4-oxasin-9-ol. In combination with the partial, DA D3 receptor-selective agonist PD151328 (2-[4[3-(4-phenyl)-1- piperazinyl)propoxy]phenyl]-benzamidazole), a reversal of the attenuating effect of PD128907 on locomotor activity was observed, without an effect on extracellular levels of DA. In combination with a low--10 nmol/kg--dose of haloperidol, a reversal of the inhibitory effect of PD128907 on locomotor activity was observed that coincided with an increase in extracellular levels of DA. In the presence of 0.5 mg/kg amphetamine, PD128907 decreased amphetamine-induced locomotor activity. This effect could be reversed by PD151328.

Animals↗

Health effects of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure: a systematic review of the research evidence.

OBJECTIVE: To examine the research evidence for the health consequences of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure. DESIGN: A systematic review of published research, studies being identified by searching Medline (1966-96), Embase (1974-96), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1982-95); scanning citations; and consulting experts. Studies in all languages were considered which either investigated the association between obstructive sleep apnoea in adults and key health outcomes or evaluated the effectiveness of treatment of obstructive sleep apnoea with continuous positive airways pressure in adults. MAIN OUTCOME MEASURES: Mortality, systematic hypertension, cardiac arrhythmias, ischaemic heart disease, left ventricular hypertrophy, pulmonary hypertension, stroke, vehicle accidents, measures of daytime sleepiness, and quality of life. RESULTS: 54 epidemiological studies examined the association between sleep apnoea and health related outcomes. Most were poorly designed and only weak or contradictory evidence was found of an association with cardiac arrhythmias, ischaemic heart disease, cardiac failure, systemic or pulmonary hypertension, and stroke. Evidence of a link with sleepiness and road traffic accidents was stronger but inconclusive. Only one small randomised controlled trial evaluated continuous positive airways pressure. Five non-randomised controlled trials and 38 uncontrolled trials were identified. Small changes in objectively measured daytime sleepiness were consistently found, but improvements in morbidity, mortality, and quality of life indicators were not adequately assessed. CONCLUSIONS: The relevance of sleep apnoea to public health has been exaggerated. The effectiveness of continuous positive airways pressure in improving health outcomes has been poorly evaluated. There is enough evidence suggesting benefit in reducing daytime sleepiness in some patients to warrant large randomised placebo controlled trials of continuous positive airways pressure versus an effective weight reduction programme and other interventions.

Accidents, Traffic↗

Structure and expression of a cluster of glutathione S-transferase genes from a marine fish, the plaice (Pleuronectes platessa).

Glutathione S-transferases are involved in the detoxification of reactive electrophilic compounds, including intracellular metabolites, drugs, pollutants and pesticides. A cluster of three glutathione S-transferase genes, designated GSTA, GSTA1 and GSTA2, was isolated from the marine flatfish, plaice (Pleuronectes platessa). GSTA and GSTA1 code for protein products with 76% amino acid identity. GSTA2 appears to contain a single nucleotide deletion which would render any product non-functional. All of these genes consist of six exons of similar sizes and greater than 70% nucleotide identity, and are interrupted by five introns of differing sizes. GSTA and GSTA1 mRNAs were present in a range of tissues, while GSTA2 mRNA was no detected. Expression of GSTA mRNA was increased in plaice intestine and spleen by pretreatment with beta-naphthoflavone, and expression of both GSTA and GSTA1 mRNAs was increased in plaice liver and gill by pretreatment with the peroxisome proliferating agent perfluoro-octanoic acid.

Amino Acid Sequence↗

Helping-at-the-nest in Arabian babblers: signalling social status or sensible investment in chicks?

Helping-at-the-nest in Arabian babblers, Turdoides squamicepshas been uniquely explained as an altruistic 'signal' used to 'show-off' and gain 'social prestige' within the group. Evidence from other cooperatively breeding bird species, however, instead suggests that helpers invest in nestlings in order to gain kin-selected benefits. This study investigates patterns of provisioning behaviour among parents and helpers for 27 broods over three breeding seasons, and assesses the potential for chick-feeding to operate as a signal in Arabian babblers. Provisioning rate accounted for much of the variation in fledging brood mass, suggesting that observed provisioning effort had potential fitness consequences for the brood. All group members provisioned at similar rates and made similar adjustments in feeding effort, irrespective of sex and/or dominance rank within the group. Chick age had a positive linear effect, and group size a negative linear effect, upon provisioning rates of all group members. There was no obvious evidence that nestling provisioning operated as a signal within groups in any way. Contrary to earlier reports, individuals did not appear to 'interfere' with the provisioning efforts of subordinates; individuals in larger groups did spend longer in the nest tree before reaching the nest, but this was unaffected by sex, dominance rank and presence of other (more dominant) birds. These results suggest that provisioning by both helpers and parents in Arabian babblers functions not as a signal, but as sensible investment in chicks. In this species, high relatedness within groups may provide helpers with kin-selected benefits via such investment, although possible advantages from augmentation of group size cannot be ruled out.Copyright 1997 The Association for the Study of Animal Behaviour

Journal Article↗

The effect of omeprazole pretreatment on acetaminophen metabolism in rapid and slow metabolizers of S-mephenytoin.

Omeprazole, a widely used and potent gastric proton pump inhibitor, induces cytochrome P450 (CYP) 1A2 in humans. Induction is most pronounced in slow metabolizers of S-mephenytoin because CYP2C19 (S-mephenytoin hydroxylase) is responsible for the elimination of omeprazole. Acetaminophen (INN, paracetamol), a widely used and effective analgesic and antipyretic agent, causes serious hepatic and renal toxicity at high doses by conversion of acetaminophen to the toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI) through CYP1A2, CYP2E1, and CYP3A4. This study evaluated whether omeprazole pretreatment in five rapid and five slow metabolizers of S-mephenytoin could increase thioether (an estimate of NAPQI production) metabolite formation from acetaminophen. The results of this study show that, despite induction of CYP1A2 activity in slow metabolizers (a 75% increase in plasma clearance of caffeine), the formation of NAPQI from acetaminophen was not increased after 7 days of omeprazole administration (40 mg/day). This suggests that induction of CYP1A2 activity by omeprazole is unlikely to increase the risk of acetaminophen hepatotoxicity.

Acetaminophen↗

Septicemia caused by Salmonella infection: an overlooked complication of sickle cell disease.

OBJECTIVES: To describe the characteristics of salmonella infections in sickle cell disease and to compare the features of osteomyelitis and those with bacteremia/septicemia without obvious bone changes. To search for risk factors for osteomyelitis, and to draw attention to the frequency and significance of salmonella bacteremia/septicemia. STUDY DESIGN: A retrospective review of all salmonella isolations from the blood, pus, or aspirates during a 22-year period. SETTING: The sickle cell clinic at the University Hospital of the West Indies, Kingston, Jamaica. SUBJECTS: Patients with all genotypes of sickle cell disease. Incidence data and the frequency of associated cholelithiasis were derived from the cohort study based on follow-up of all children detected by neonatal screening. MAIN OUTCOME MEASURES: Osteomyelitis and bacteremia/septicemia. RESULTS: Of 55 patients with salmonella infections, 25 initially had osteomyelitis and 27 had bacteremia/septicemia. Three of the first group later had bacteremias for a total of 30 episodes of bacteremia/septicemia, and 4 of the second group later had osteomyelitis for a total of 32 episodes of osteomyelitis. The incidence of salmonella infection was 8.6% by 15 years, and 96% of infections occurred before the age of 10 years. Preceding episodes of avascular necrosis of bone were more frequent (p < 0.006) in patients with osteomyelitis. Patients with osteomyelitis were not more prone to gallstones. High fever (temperature > or = 40 degrees C or 104 degrees F) occurred in 41%, and occasionally marked bone marrow suppression mimicked the aplastic crisis. Twenty Salmonella serotypes were isolated; Salmonella enteritidis accounted for 36% of infections, but no serotype difference occurred between those with osteomyelitis and those with bacteremia/septicemia. There were no deaths in the 32 patients with osteomyelitis, but 7 (23%) of 30 patients with septicemia died. CONCLUSIONS: Anti-salmonella prophylaxis requires assessment in the management of bone necrosis. Anti-salmonella agents may be indicated in undiagnosed septic conditions in sickle cell disease pending culture results.

Adolescent↗

Reducing the risk after coronary artery bypass surgery: documentation of risk factors and communication between hospital and general practice.

A retrospective descriptive study of patients who had had coronary artery bypass surgery was carried out to assess the completeness of recording of risk factors in case notes in hospital and in general practice, and to determine the prevalence of documented risk factors in patients who have had coronary artery bypass surgery. Data from reviews of hospital case notes and questionnaires to general practitioners were used to describe the frequency of documenting coronary risk factors and preventative advice in case notes and in correspondence between general practitioners and hospital doctors. Documentation of risk in hospital records revealed that all 102 patients had been assessed for family history, hypertension and current smoking, but 9 (9%) had no record of serum cholesterol, 35 (34%) patients did not have a record of their blood glucose, and in 83 (81%) patients there was no evidence that obesity had been assessed. Documentation of risk factors in general practice records identified that out of 77 patients, all had their blood pressure and smoking status recorded but 29 (38%) had not been assessed for hypercholesterolaemia. From the hospital records, the prevalence of risk factors in the sample population was 41% for hypertension or raised blood pressure, 49% for hypercholesterolaemia, 12% for current smoking and 8% for diabetes mellitus. In conclusion, patients who have had coronary artery bypass surgery have substantial needs for secondary prevention. A more structured approach to risk factor assessment and preventative care should begin as soon as the diagnosis of coronary heart disease is made, and should not be postponed until the patient has deteriorated to the point of needing bypass surgery.

Adult↗

Toxicity assessment of xenobiotic contaminated groundwater using lux modified Pseudomonas fluorescens.

A bacterial bioassay, suitable for rapid screening to assess the relative toxicity of xenobiotic contaminated groundwater has been developed. The quantitative bioassay utilizes a decline in luminescence of the lux marked soil bacterium Pseudomonas fluorescens on exposure to contaminated groundwaters from which effective concentration (EC) values can be assessed and compared. P. fluorescens was most sensitive to semivolatile organics in groundwaters but there was no correlation between EC value and chemical content. The sensitivity and reproducibility of the P. fluorescens bioassay was compared with that of Microtox and results showed that mean EC50 values for diluted ground water replicate samples were 20% and 18% respectively. This suggested that the P. fluorescens bioassay was as applicable to groundwater screening as the widely used Microtox bioassay.

Benzene↗

Societal savings by "fast tracking" lower acuity patients in an urban pediatric emergency department.

To evaluate the cost-effectiveness of a "fast track" system for diverting lower acuity patients away from the pediatric emergency department (ED), 4,060 patients triaged to the fast track area of an urban pediatric ED with the 10 most common discharge diagnoses from 1/1/94 through 12/31/94 were retrospectively evaluated. Patients triaged as having nonurgent concerns qualified for treatment in a separate fast track area for 8 hours per day (fast track patients). These patients were compared with 5,199 seen in the main pediatric ED for the same concerns during the remaining hours when the fast track was not in operation (ED patients). Computer records were reviewed for demographics, acuity levels, diagnosis, and collection ratios (revenues/charges). The societal savings was calculated as sigma $ [(delta mean revenue of diagnosis1-10 in the main ED - mean revenue of diagnosis1-10 in the fast track) x the number of patients seen in fast track for diagnosis1-10] stratified by acuity. Collection ratios were comparable between groups (57% v 62%), but the average charges (physician and facility) were significantly less for patients seen in the fast track by a ratio of 1:2.4 (P < .0001). The average net revenue was also significantly less for all patients seen in the fast track by a ratio of 1:2.6 (P < .0001). When stratified by diagnosis and acuity, the savings to society was $101,313, or an average of $25/patient seen in the fast track ($101,313 per 4,060). A fast track is an effective system for maintaining patient flow at a cost savings to society. It can help the hospital in its negotiations with payors because it curtails charges. It is also a potential means for maintaining overall departmental revenues as payors increasingly deny traditional pediatric ED visits for patients with lower acuity concerns.

Child↗

Evaluation of a fiber optic immunosensor for quantitating cocaine in coca leaf extracts.

A fiber optic evanescent fluoroimmunosensor was used to rapidly detect and quantitate coca alkaloids as cocaine equivalents in leaf extracts of five Erythroxylum species. A monoclonal antibody (mAb) made against benzoylecgonine (BE), a major metabolite of cocaine, was immobilized covalently on quartz fibers and used as the biological sensing element in the portable fluorometer. Benzoylecgonine-fluorescein (BE-FL) was used as the optical signal generator when it bound to the fiber. If present, cocaine competed for the mAb and interfered with the binding of BE-FL, thereby reducing the fluorescence transmitted by the fiber. Calibration curves were prepared by measuring (over 30 s) the rates of fluorescence increase in the absence, or presence of cocaine. Ethanol or acid extracts of dry coca leaves were assayed by this fiber optic biosensor, gas chromatography and a fluorescent polarization immune assay. Biosensor values of cocaine content of leaves from five Erythroxylum species were not significantly different from gas chromatography values, but had higher variance. The biosensor assay was rapid and did not require cleanup of the crude leaf extracts. Cocaine in acid extracts was reduced significantly after 4 weeks at 23 degrees C and after 3 weeks at 37 degrees C. Fibers (mAb-coated), stored at 37 degrees C in phosphate-buffered solution (0.02% NaN3), gave stable responses for 14 days.

Biosensing Techniques↗

Therapeutic touch: nursing activity or form of spiritual healing?

There is a major movement in nursing which is exploring the part that a wide range of complementary therapies can play in expanding the therapeutic role of the nurse. Courses have been developed that will enable nurses to apply these skills to their daily practice (Faltermeyer 1995). Therapeutic Touch (TT) is being advocated as one such therapy, primarily developed and researched by nurses for nurses (Sayre-Adams & Wright 1995). Early writings and thinking on TT speak of origins in the ancient practice of the 'laying on of hands'; the purpose of which was and is to 'heal or encourage healing in a sick person' (Krieger 1979). Its application in practice can be helped or hindered by this statement since this might be interpreted as spiritual healing, a term which can be confusing, open to misinterpretation and can spark controversy.

Holistic Nursing↗

Aptitude-treatment interactions based on clients' assimilation of their presenting problems.

Assigning clients to treatments on the basis of their differential aptitudes for those treatments may reduce variability and improve the mean outcomes of psychotherapy. The assimilation model suggests that in time-limited treatments, clients with well-assimilated problems would do better in cognitive or behavioral therapies than in psychodynamic, experiential, or interpersonal therapies, whereas the reverse should be the case for clients with poorly assimilated problems. Results for high-, moderate-, and low-assimilation subgroups (based on rating the level of assimilation of problems presented in the first 20 min of first sessions) of clients (N = 112) randomly assigned to time-limited cognitive-behavioral or psychodynamic-interpersonal treatment supported the first suggestion but not the second (clients with poorly assimilated problems did equally well in both treatments).

Adult↗

Elevated post-prandial gastric inhibitory polypeptide concentrations in hypertriglyceridaemic subjects.

1. We investigated whether abnormalities of gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1) contribute to the hypertriglyceridaemia and hyperinsulinaemia in hypertriglyceridaemic subjects. Serum triglycerides and plasma glucose GIP, GLP-1 and immunoreactive insulin (IRI) concentrations were measured before and after a mixed meal in 15 hypertriglyceridaemic patients and in eight healthy normotriglyceridaemic control subjects. 2. Integrated post-prandial GIP concentrations were greater than in controls (P < 0.05) and correlated positively with both fasting and integrated post-prandial triglyceride concentrations (P < 0.05 for both). Fasting and integrated post-prandial IRI levels were higher in hypertriglyceridaemic subjects than in controls (P < 0.02 and P < 0.05 respectively) and correlated positively with fasting triglycerides (P < 0.02 and P < 0.001 respectively) and integrated post-prandial triglycerides (P < 0.005 and P < 0.05 respectively). There was no correlation between GIP concentrations and either fasting or post-prandial IRI levels. Fasting and post-prandial concentrations of GLP-1 were similar in patients and controls. 3. Hypertriglyceridaemic subjects have post-prandial hyperGIPaemia in addition to the well-documented hyperinsulinaemia. We found no association between GIP and insulin. There is, however, clear evidence for an association between post-prandial GIP concentrations and triglyceride levels. We suggest that this association may depend on changes in lipoprotein lipase activity and that there may be a feedback loop between GIP and triglyceride lipolysis.

Adult↗

Public health in hospitals: new steps in old directions.

A pilot scheme of hospital epidemiologists in the Northern and Yorkshire region has provided an exciting opportunity to promote a public health perspective among hospital clinicians. Responsibilities and roles of the posts include the promotion of clinical effectiveness and evidence-based practice, epidemiological support for audit, research and clinical evaluation, liaison with primary care and public health colleagues in health authorities, and the development and implementation of clinical guidelines. Although the posts are not restricted to public health specialists, public health training and skills provide an excellent foundation from which to meet the challenges that arise from the posts. We discuss some of the lessons learnt by two public health doctors from the early steps in this new direction.

Career Mobility↗

Phase I trial of etoposide, carboplatin, and GM-CSF in extensive small-cell lung cancer: a Cancer and Leukemia Group B study (CALGB 8832).

The maximum tolerated dose (MTD) of etoposide and carboplatin without growth factor support was previously defined by Cancer and Leukemia Group B (CALGB) as 200 and 125 mg/m2/day x 3, respectively, given every 28 days to previously untreated patients who have extensive, small-cell lung cancer (SCLC). Myelosuppression was dose-limiting. The purpose of this phase I trial was to determine if granulocyte macrophage colony-stimulating factor (GM-CSF) support allows the dosage of the combination of etoposide and carboplatin to be increased above the previously determined MTD. In this CALGB study of 44 evaluable patients with performance status 0-2, cohorts were treated with etoposide and carboplatin given intravenously on days 1-3 followed by GM-CSF (molgramostim) given subcutaneously on days 4-18. Four dose levels of bacteria-derived recombinant GM-CSF (5, 10, 20 microg/kg/day and 5 microg/kg every 12 h), three dose levels of etoposide (200, 250, and 300 mg/m2/day x 3), and two dose levels of carboplatin (125 and 150 mg/m2/day x 3) were evaluated. There was no chemotherapy dose escalation in individual patients. With 5 microg/kg/d GM-CSF, the first etoposide and carboplatin cycle of 300 and 150 mg/m2/day x 3, respectively, could be administered with acceptable toxicity. However, GM-CSF did not allow repeated administration of this dose-escalated regimen every 21 days, since delayed platelet and/or neutrophil recovery was dose limiting in later cycles. These results demonstrate that GM-CSF alone has limited capability to support the repeated administration of high doses of etoposide and carboplatin. CALGB currently is testing the ability of interleukin (IL)-6 given with GM-CSF to ameliorate the cumulative myelosuppression of this intense regimen.

Adult↗

A university-affiliated community hospital inpatient geriatrics program functioning in an administrative and educational capacity.

OBJECTIVE: To demonstrate an unusual form of inpatient geriatric assessment with unique outcomes. DESIGN: A prospective evaluation of patients admitted to a community hospital-based inpatient geriatrics unit utilizing traditional members of the assessment team along with educational assessment of nurses and satisfaction profiles of patients and/or families. SETTING: A non-profit community hospital in Northeast Washington, DC. PARTICIPANTS: All patients older than age 62 admitted to the 42-bed Geriatric Unit during a 4 1/2 year time period. MEASUREMENTS: Number of total and category recommendations taken by attending physicians from the Inpatient Geriatric Assessment Team, periodic evaluation of unit nurses' geriatric knowledge base and certification, and patient satisfaction through periodic surveys. RESULTS: More than 4500 patients have been evaluated during the past 4 1/2 years. The number of recommendations taken by attending physicians has averaged 31.3 to 50.7% during four consecutive chart reviews involving the first 25 consecutive patients for the month each performed every six months (n = 100). The average age of patients evaluated was 77.2 (minimum of 62 and maximum of 97); 67% were females and 33% males. The average number of recommendations communicated per patient was 4.1, and the average number adhered to 1.6/patient. The overall knowledge base and certification in geriatric nursing has increased significantly over a 2.5-year period. Composite monthly unit patient satisfaction survey scores increased as well. CONCLUSIONS: The program is unique in its development, limitations, and outcomes. Other than the cost of limited geriatric nurse practitioner and faculty salary support, the program has been implemented using only current hospital department personnel. The role of the assessment team is to educate attending nurses and staff physicians. It has not yet been possible to measure objective outcomes. However, the current program also serves the purpose of introducing a new medical program to a community hospital in a nonthreatening way and offers opportunities for research. In addition, the program offers further opportunity for expansion and change.

Aged↗