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Biomedical subjects

J Wright

Publications and source records attributed to J Wright.

At least 199 records · Page 11Linked to original sources
PubMed1998

Quantitative analysis of a cysteine351glycine mutation in the G protein Gi1alpha: effect on alpha2A-adrenoceptor-Gi1alpha fusion protein activation.

Fusion proteins were constructed between the porcine alpha2A-adrenoceptor and either wild-type (Cys351) or a pertussis toxin-resistant (Gly351) form of the G protein Gi1alpha. Addition of adrenaline to membranes expressing the fusion proteins resulted in concentration-dependent stimulation of their high affinity GTPase activity. The alpha2A-adrenoceptor-wild type Gi1alpha fusion protein produced substantially higher maximal stimulation of GTPase activity in response to adrenaline than that containing Gly351 Gi1alpha. Treatment of the fusion proteins as agonist-regulated enzymes allowed measurement of Vmax and turnover number for adrenaline-stimulation of the GTPase activity of each fusion construct. The turnover number of the alpha2A-adrenoceptor-Cys351 Gly Gi1alpha fusion protein was only 44'S, of that for the alpha2A-adrenoceptor-wild type Gi1alpha fusion protein. These data provide the first direct quantitative evaluation of the effects of a mutation of a G protein on the capacity of an agonist-occupied receptor to activate the mutant.

Animals↗
PubMed1998

(-)-3 beta-Substituted ecgonine methyl esters as inhibitors for cocaine binding and dopamine uptake.

Ten 3 beta-ecgonine analogues were synthesized and characterized by 1H and 13C NMR, MS, and elemental analysis. The compounds were synthesized as (-)-stereoisomers from (-)-cocaine. These compounds were assessed for their ability to inhibit [3H]cocaine binding to rat striatal tissue and to inhibit [3H]DA uptake into rat striatal synaptosomes. In this series of compounds, the length of the spacer between the aryl group and the tropane skeleton ranged from 1 to 4 bond distances, and conformational flexibility of the linkage and orientation of the aryl ring system were controlled by various types of linkages. The most potent of the analogues was methyl-(1R-2-exo-3-exo)-8-methyl-3-(beta-styrenyl)-8-azabicyclo[3. 2.1] octane-2-carboxylate. One of the less potent compounds was found to inhibit [3H]cocaine binding and [3H]DA uptake with significantly different IC50 values, in contrast to 14 other 3 beta-substituted analogues. Molecular modeling and CoMFA analysis were used to obtain a rigorous structure-function relationship for the studied compounds. The results showed that the potencies of these 3 beta-substituted ecgonine methyl esters were dominated by steric effects and were acutely sensitive to the distance between the aryl ring and the tropane skeleton and to the orientation of the aryl ring system relative to the tropane skeleton. The current study provides a clearer picture of the shape and size of the putative hydrophobic binding pocket for the 3 beta substituent at the cocaine receptor as well as emphasizing the importance of a drug's free energy of solvation in obtaining structure-activity relationships.

Animals↗
PubMed1998

An examination of DNA strand breakage in the comet assay and antioxidant capacity in diabetic patients.

There are two forms of diabetes, insulin-dependent Diabetes mellitus (IDDM) and non-insulin dependent Diabetes mellitus (NIDDM). There is evidence to suggest that reactive oxygen is involved in the pathogenicity and complications arising from IDDM, but there is little to suggest a role of oxidative stress in the pathogenesis of NIDDM. In order to investigate this hypothesis further, peripheral blood samples were taken from control individuals and IDDM and NIDDM patients and examined for antioxidant capacity and in the Comet assay for DNA strand breakage. The individuals answered a questionnaire to provide information relating to lifestyle factors in case such factors might have a confounding effect. There were 20 controls, 22 IDDM patients and 23 NIDDM patients. No differences could be detected in control and diabetic patient groups in terms of creatinine levels and antioxidant capacity. DNA damage in the Comet assay was at a lower level than in the control in the IDDM patients and a slightly lower level in the NIDDM patients, which might indicate that these cells are handling more oxidative damage on a regular basis. As expected, there were differences in glycosylated haemoglobin (HbA(1C)) levels. The confounding factors (smoking, drinking and vitamin intakes, etc.) appeared to have no effect.

Adult↗
PubMed1998

Delayed gastric emptying occurs following acarbose administration and is a further mechanism for its anti-hyperglycaemic effect.

The therapeutic effect of acarbose is generally attributed to inhibition of amylase and brush border glucosidases and consequent impaired digestion and absorption of carbohydrates. We have investigated the possibility that acarbose may also influence the rate of gastric emptying by comparing plasma glucose and gastrointestinal hormone responses to an oral sucrose load with and without acarbose in 11 healthy subjects. Gastric emptying was assessed indirectly by measuring circulating paracetamol concentrations following administration of paracetamol along with the sucrose load. Peak plasma glucose, insulin, and glucose-dependent insulinotropic polypeptide (GIP) responses were reduced when sucrose was given with acarbose. There was a significant reduction in post-sucrose paracetamol levels with acarbose suggestive of a significant delay in gastric emptying. The failure of acarbose to induce change in circulating paracetamol concentrations until after 60 min is indicative of a delay in gastric emptying rather than an osmotic malabsorption. The exaggerated and sustained release of glucagon-like peptide-1 (7-36)amide (GLP-1) seen when sucrose was given with acarbose may play a part in the inhibition of gastric emptying. This study indicates that a significant delay in gastric emptying may be an added mechanism contributing to the therapeutic effect of acarbose.

Acarbose↗
PubMed1998

Archive selection for the MICAS, a multi-vendor incremental approach to PACS.

From the time a decision was made to purchase an archive until a purchase order was issued took approximately 10 months. During this period an RFI was developed, issued and the results analyzed. Technical discussions were held and site visits were made. To ensure that current information was available, a complete review of available multi-modality DICOM compliant archives were made at the 1997 RSNA. With this information in-hand and the future development path for MICAS specified, a detailed RFQ was developed, responses were received and evaluated. A purchase order was to be issued by the end of the first quarter 1998. The archive vendor will have been selected by the time this paper appears in print. The oral presentation of this work will review the responses of the archive vendors and present the basis for selection. It is planned to publish our findings. The archive is the heart and brains of PACS. It controls information acquisition, distribution and storage plus work flow. It is critical that DICOM compliance and interoperability between all components of the PACS be an absolute requirement, especially for the archive.

Academic Medical Centers↗
PubMed1998

The ageing entero-insular axis.

Ageing is one of the major risk factors for glucose intolerance including impaired glucose tolerance and Type II (non-insulin-dependent) diabetes mellitus. Reduced insulin secretion has been described as part of normal ageing although there is no information on age-related changes in the secretion of the major insulinotropic hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (7-36 amide) (GLP-1). We assessed the entero-insular axis in 6 young premenopausal and 6 older postmenopausal women following treatment with oral carbohydrate. Insulin and glucose integrated responses were similar in the younger and older groups. Total integrated responses for GIP and GLP-1 were considerably greater in the older subjects. A positive correlation between age and total integrated responses for glucose (r = 0.65; p < 0.02) as well as GLP-1 (r = 0.85; p < 0.001) was seen. We hypothesise that an age-related impairment of insulin secretion to insulinotropic hormones, GIP and GLP-1, contributes to a reduction in glucose tolerance in this age group. The pronounced compensatory increase in postprandial secretion of GIP and GLP-1 provides further evidence not only for the negative feedback relation between incretin and insulin secretion but also for the importance of the entero-insular axis in the regulation of insulin secretion.

Acetaminophen↗
PubMed1998

Differences in postprandial lipaemic response between Northern and Southern Europeans.

Postprandial lipaemic responses to two test meals were investigated in 30 Northern (15 British and 15 Irish), and 30 Southern (Greeks from Crete) healthy male Europeans. The meals were a saturated fatty acid (SFA) meal, which resembled the fatty acid composition of an average UK diet, and a monounsaturated fatty acid (MUFA) meal in which the fat consisted of olive oil. Habitual diets of the two groups differed, with higher total fat, (P < 0.03) and MUFA (P < 0.0001) and lower polyunsaturated fatty acid (PUFA) (P < 0.0001) intakes in Southern than Northern Europeans. Levels of total MUFA (P < 0.02) and oleic acid (P < 0.004) were also higher in adipose tissue of Southern in comparison to Northern Europeans. In both European groups there were no significant differences in postprandial triglyceride response between the two meal types, SFA or MUFA. However, Northern and Southern Europeans showed significant differences in their patterns of postprandial response in plasma triglycerides (P < 0.0001), apolipoprotein B-48 (P < 0.0001), NEFA (P < 0.0001), insulin (P < 0.0007), and factor VII activity (P-0.03). In the case of NEFA, areas under the response curve were higher following the SFA than the MUFA meal for both groups, (P < 0.003) and were greater in Southern than Northern Europeans (P < 0.002) and apo B-48 responses were lower (P < 0.005). Some of these differences may reflect differences in fasting levels since fasting apolipoprotein B-48 levels were lower (P < 0.01) and fasting NEFA (P < 0.02) and insulin (P < 0.005) were higher in the Southern than in the Northern Europeans. In addition, 9 h postprandial post-heparin lipoprotein lipase activity was lower in the Southern than in the Northern Europeans (P < 0.0006). This is the first report of differences in postprandial lipid, factor VII and insulin responses in Southern and Northern Europeans which may be of importance in explaining the different susceptibilities of these two populations to risk of coronary artery disease.

Adipose Tissue↗
PubMed1998

The evaluation of Franco-Quebec victims of child sexual abuse and their mothers: the implementation of a standard assessment protocol.

OBJECTIVE: There were two aims: first, to evaluate the feasibility of applying a standard assessment protocol to Franco-Quebec victims of child sexual abuse and nonoffending mothers; and second, to compare results from an initial sample with available data from English-speaking samples. METHOD: A standard individual case study design was used for victims and mothers; and the satisfaction of the nine participating youth workers was assessed. Four self-report instruments for victims and five for mothers were chosen on the bases of workers' priorities, sensitivity to the impact of CSA, and the availability of published norms on English-speaking samples. Results are reported on 48 confirmed victims and 40 nonoffending mothers. RESULTS: The protocol was favorably received by the CPS workers, supervisors and all mothers and victims. Percentages of clinically distressed victims varied from highs of 68% on the externalization difficulties of the Child Behavior Checklist and 67% for 2- to 6-year-olds on the Child Sexual Behavior Inventory, to lows of 10% on hostility symptoms and 13% on the Dissociation Scale of the Trauma Symptom Check for Children. The rate of symptom-free children was lower (19%) and that of revictimization higher (30%) than most published estimates (Kendall-Tackett, Williams, & Finkelhor, 1993). Most mothers reported elevated emotional distress (depression, 59%) and symptoms of post-traumatic stress (intrusiveness, 67%). Although 87% of mothers believed the allegations, only 45% offered adequate emotional support. CONCLUSION: The implementation phase of this research was successful, given the positive reactions of workers and clients. Results on standard instruments from this French-speaking sample were similar to profiles of English-speaking victims and their mothers but firm conclusions on appropriate norms will require larger samples, cross cultural contrasts, and the evaluation of additional variables.

Canada↗
PubMed1998

Polycyclic aromatic hydrocarbon (PAH) dispersion and deposition to vegetation and soil following a large scale chemical fire.

Polycyclic aromatic hydrocarbons (PAHs) were determined in soil and vegetation following a large scale chemical fire involving 10,000 ton of polypropylene. In comparison with sites outside the plume from the fire, PAH concentrations were elevated in grass shoots (by up to 70-fold) and in soil (by up to 370-fold). The pattern of PAH dispersion under the plume was dependent on the physical-chemical properties of individual PAHs. The lighter, least hydrophobic PAHs were dispersed into the environment at greater distances than heavier, more hydrophobic PAHs. At the most distant sampling point (4.5 km) under the plume, the low molecular weight PAHs were still considerably elevated in vegetation samples compared to control sites. Dispersion appeared to be regulated by the compounds partitioning between the vapour and particulate phase, with dry particulate deposition occurring closer to the fire source than gaseous deposition. For all PAHs, the fire resulted in greater contamination of soils compared to grasses, with the relative ratio of plant/soil contamination decreasing as hydrophobicity increased.

Journal Article↗
PubMed1998

Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension.

Two multicenter, double-blind, placebo-controlled, parallel group studies were conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of the angiotensin II receptor (AT1 subtype) antagonist irbesartan. The effect of irbesartan withdrawal and the effect of adding hydrochlorothiazide (HCTZ) to irbesartan were also assessed. After a placebo lead-in phase, all patients were randomized to 8 weeks of double-blind therapy with either placebo (n = 158) or irbesartan at doses of 1, 5, 10, 25, 50, 100, 200, or 300 mg (n = 731 total) orally once daily. Irbesartan reduced blood pressure in a dose-related manner. Reductions from baseline in trough seated diastolic blood pressure ranged from 7.5 mm Hg for 50 mg irbesartan to 11.6 mm Hg for 300 mg irbesartan. At week 8, statistically significant reductions over placebo were observed in trough seated blood pressure with all irbesartan doses > or = 50 mg. These reductions reached statistical significance versus placebo within 2 weeks with 100, 200, and 300 mg irbesartan. Plasma irbesartan concentrations correlated with dose. Angiotensin II and aldosterone levels generally showed dose-related changes, consistent with AT1 receptor blockade. In patients not controlled at 8 weeks, the addition of 12.5 mg HCTZ resulted in further dose-related reductions in blood pressure. Irbesartan demonstrated a placebo-like safety profile and no dose-related toxicity. Irbesartan, administered alone or in combination with HCTZ, was well tolerated. Withdrawal of irbesartan did not result in rebound hypertension or adverse events. Thus, once-daily irbesartan is both an effective and safe antihypertensive agent for the treatment of mild-to-moderate hypertension.

Aged↗
PubMed1998

Female nurses' perceptions of acceptable female body size: an exploratory study.

A review of the literature indicated that women are often dissatisfied with their body size and weight. Feminist research has suggested that the images of the 'perfect' female body are socially constructed. The research conducted was exploratory in nature and aimed to focus on female nurses' perceptions of acceptable female body size. The choice of female nurses was deliberate in order to explore if they experienced dual pressures as health care workers and women. The study consisted of semistructured interviews which were conducted with a convenience sample of 10 nurses drawn from several specialities and hospitals throughout the Southern Health and Social Services Board (Northern Ireland). The research sample was small and therefore the findings cannot be generalized to the nursing profession as a whole. Many interesting questions were raised, which suggest that this topic is fertile ground for further research. The research findings indicate that assessment of female patients body size is arbitrary in nature and advice given to patients judged to be overweight is less than empirically based. Several of the nurses displayed discomfort with their role as intermediaries between patients and doctors when advising on weight control behaviours. In addition, there was strong evidence to suggest that there are discriminatory practices towards overweight female patients by doctors. The study concludes with recommendations for future practice and research in this area.

Adult↗
PubMed1998

Cost of extracorporeal life support in pediatric patients with acute respiratory failure.

OBJECTIVES: To determine the impact of extracorporeal life support (ECLS) on mortality in pediatric patients with acute hypoxemic respiratory failure (AHRF) at our institution; and to calculate the hospital charges associated with the use of ECLS. DESIGN: Retrospective review of medical records and hospital charges. SETTING: Pediatric intensive care unit (ICU) of a university-affiliated children's hospital. PATIENTS: Twenty patients admitted to the pediatric ICU between 1991 and 1995 for AHRF who received ECLS as a part of their hospital course. INTERVENTIONS: Predicted mortality was calculated using the Pediatric Respiratory Failure score and was compared with survival at the time of hospital discharge. Hospital charges were used as a proxy for resource utilization. Cost-per-life-year-saved calculations were performed based on a normal life expectancy for survivors. MEASUREMENTS AND MAIN RESULTS: Twenty patients were identified. The median age was 4.83 yrs. The median duration of ECLS was 9 days, with 19.5 days in the pediatric ICU and 23.5 days for the entire hospital length of stay. The observed mortality rate for these patients was 20%. Median predicted mortality rate based on the Pediatric Respiratory Failure score calculation was 83%. The hospital charges incurred by these patients was a median of $199,096. Based on a normal life expectancy for survivors, this results in a cost of $4,190/life-year. CONCLUSIONS: ECLS for the pediatric patient with AHRF is done at a considerable cost. However, ECLS affects survival favorably, and compares favorably when considering cost/life-year calculations. The data presented in this study may serve as a benchmark for comparison with newer therapies (i.e., liquid ventilation, nitric oxide). These data also provide a framework for cost-based analyses at other ECLS institutions.

Adolescent↗