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Biomedical subjects

J Orme

Publications and source records attributed to J Orme.

13 recordsLinked to original sources
PubMed2003

AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2.

The PDH (pyruvate dehydrogenase) multi-enzyme complex catalyses a key regulatory step in oxidative glycolysis. Phosphorylation of the E1 subunit of the complex on serine residues results in the inactivation of enzyme activity. A family of four dedicated PDH kinase isoenzymes exists, each of which displays a distinct tissue-specific expression profile. AZD7545 is one of a series of PDH kinase inhibitors developed for the treatment of type 2 diabetes. The isoenzyme-selectivity profile of AZD7545 and related compounds is described and the consequences for their in vivo mode of action are discussed.

Animals↗
PubMed2001

Evaluation of a primary school drug drama project: methodological issues and key findings.

This paper describes the impact evaluation of a primary school drug drama project developed by a health promotion service and a theatre's education department in England. The project targeted 10-11 year olds in 41 schools with an interactive drama production and workshop day on attitudes, choices, decisions and risks of alcohol, tobacco and illegal drug use. Parents were also involved in parents' evenings and watching children's performances. The research consisted of both process evaluation, consultation with pupils, teachers, parents, actors and health promotion staff on the project itself, and impact evaluation which looked at potential changes in children's knowledge, attitudes and decision-making skills. This paper reports findings of the impact evaluation, from six of the schools participating in the project. The impact evaluation consisted of pre- and post-project testing using a 'draw and write' and a problem-solving exercise. These findings suggest that the project had a significant impact on the children's knowledge of names of specific illegal drugs, and on their awareness that alcohol and cigarettes were also drugs, and secondly encouraged the children to think in less stereotypical terms about drugs and drug users. The problem-solving exercise, involving decision-making scenarios, showed small but positive trends between pre- and post-project solutions in more than half of the response categories. Methodological difficulties relating to evaluating such a project are discussed.

Child↗
PubMed1998

Selection of T-DNA-tagged male and female gametophytic mutants by segregation distortion in Arabidopsis.

As a strategy for the identification of T-DNA-tagged gametophytic mutants, we have used T-DNA insertional mutagenesis based on screening for distorted segregation ratios by antibiotic selection. Screening of approximately 1000 transgenic Arabidopsis families led to the isolation of eight lines showing reproducible segregation ratios of approximately 1:1, suggesting that these lines are putative gametophytic mutants caused by T-DNA insertion at a single locus. Genetic analysis of T-DNA transmission through reciprocal backcrosses with wild type showed severe reductions in genetic transmission of the T-DNA through the male and/or female gametes. Direct evidence for mutant phenotypes in these lines was investigated by DAPI staining of mature pollen grains and by the analysis of seed set and embryo sac morphology in cleared ovules. One line, termed limpet pollen, showed a novel pollen phenotype in that the generative cell failed to migrate inward after pollen mitosis I, such that the generative or sperm cells remained against the pollen wall. Two other lines, andarta and tistrya, were defective in female transmission and showed an early arrest of embryo sac development with the viable megaspore not initiating the nuclear division cycles. These data demonstrate the efficacy of a segregation ratio distortion strategy for the identification of T-DNA-tagged gametophytic mutants in Arabidopsis.

Arabidopsis↗
PubMed1994

Ethical implications of standardization of ICU care with computerized protocols.

Ethical issues related to the use of computerized protocols to control mechanical ventilation of patients with Acute Respiratory Distress Syndrome (ARDS) are identical to the ethical issues surrounding the use of any therapy or intervention. Four ethical principles must be considered: nonmaleficence, beneficence, autonomy, and distributed justice. The major ethical challenges to computerized protocol use as a specific application of clinical decision support tools are found within the principles of nonmaleficence and of beneficence. The absence of credible outcome data on which ARDS patient survival probabilities with different therapeutic options could be based is a constraint common to most ICU clinical decision making. Clinicians are thus deprived of the knowledge necessary to define benefit and are limited to beneficent intention in clinical decisions. Computerized protocol controlled decision making for the clinical management of mechanical ventilation for ARDS patients is ethically defensible. It is as well supported as most ICU therapy options.

Clinical Protocols↗
PubMed1993

K(+)-channel blockers and coronary vasoconstriction in guinea-pig perfused hearts in-vitro.

Glibenclamide, glipizide and phentolamine, three drugs which have been reported to block ATP-dependent potassium channels, increased the coronary perfusion pressure in guinea-pig isolated hearts perfused at constant flow. Blockers of other types of potassium channels, 4-aminopyridine and UK-66,914, did not significantly increase perfusion pressure. Exposing hearts to a single concentration of 3 microM glibenclamide caused a greater degree of vasoconstriction than when this was preceded by lower concentrations. The 3 microM glibenclamide-induced vasoconstriction was reduced by prazosin (1 microM), mepyramine (0.1 microM) and ranitidine (10 microM) but not by a combination of mepyramine and ranitidine or by ritanserin (0.01 microM). These results suggest that a component of the vasoconstriction induced by glibenclamide may result indirectly from the release of vasoactive mediators.

4-Aminopyridine↗
PubMed1992

Effects of drugs on ventricular fibrillation and ischaemic K+ loss in a model of ischaemia in perfused guinea-pig hearts in vitro.

In a perfused guinea-pig heart model of myocardial ischaemia, reducing coronary flow by 95% for four successive 6 min periods caused a reproducible net loss of K+ into the coronary perfusate. This was reduced in a concentration-dependent manner by ATP dependent K+ channel blockers (glibenclamide and glipizide) and calcium channel blockers (verapamil and nifedipine). Other K+ channel blockers (UK-66,914, 4-aminopyridine, R56865 and phentolamine) and beta 1-adrenoceptor and beta 2-adrenoceptor antagonists (betaxolol and ICI118551) did not reduce this loss significantly. A single 30 min low-flow period reliably induced K+ release and ventricular fibrillation in control hearts. Glibenclamide, glipizide and phentolamine suppressed ventricular fibrillation but not ischaemic K+ loss in this model. R56865 and 4-aminopyridine and coadministration of betaxolol and ICI118551 yielded similar results while UK-66,914 suppressed neither. In our model, modulation of ischemic K+ loss and suppression of ventricular fibrillation were not closely associated and appeared to occur via separate mechanisms.

4-Aminopyridine↗
PubMed1992

A trial of health education aimed to reduce cigarette smoking among pregnant women.

Three hundred and forty-six women who reported smoking one or more cigarettes per day prior to the 20th week of gestation were recruited into a trial of health educational counselling to stop or reduce cigarette smoking. Counselling was begun at the first prenatal visit and then continued subsequently in the home. Among the 319 women included in analysis, at first follow-up visit those who received counselling smoked 1.7 fewer cigarettes a day than control women (P less than 0.05) and 10.4% had stopped smoking, compared to 5.4% in the control group (NS). Similar but not significant differences were noted at the end of pregnancy. Study effects were limited to the 284 women smoking five or more cigarettes a day at booking. This report refers primarily to them. At first follow-up visit the proportion of such women in the counselled group who ceased smoking (9.3%) was significantly greater than in the control group (2.6%; P less than 0.05). The magnitude of this difference persisted through late pregnancy (11.8% vs. 4.3%; NS) and delivery (10.6% vs. 4.7%; NS). The differences between counselled women and controls in numbers of cigarettes reported smoked at first and last prenatal follow-up visits (2.4 and 2.1) and at delivery (2.0) were all statistically significant. While there was no effect of counselling on either serum thiocyanate or end expiratory carbon monoxide, the counselled group gained slightly more weight than controls during the study (0.47 vs. 0.44 kg per week among controls; NS), and their infants had modestly higher birthweight (44 g; NS).

Breath Tests↗
PubMed1989

Problems in assessing the risks of mixtures of contaminants in drinking water.

In conducting risk assessments on drinking water contaminants, the U.S. Environmental Protection Agency (EPA) attempts to evaluate all available toxicity data to develop Health Advisory (HA) and Maximum Contaminant Level Goal (MCLG) values. The EPA often has grappled with the issues surrounding the toxicity of chemical mixtures, including radioactive contaminants, nitrate/nitrite, and trihalomethanes (THMs). In evaluating the toxicity of chemical mixtures, the EPA's immediate concern is whether the individual HA values and MCLGs are protecting public health when multiple contaminants are present in drinking water. Potential toxic interactions between drinking water contaminants are difficult to predict because experimental studies are generally performed only at high doses relative to environmental levels. Although the contamination of drinking water involves mixtures of contaminants, drinking water regulations are generally based on an assessment of the risks of individual contaminants. This paper discusses three issues of major concern to the EPA: the synergistic effects of solvent mixtures, vehicle effects in laboratory studies, and setting standards for essential trace nutrients where the absorption and/or toxicity are affected by an individual's nutritional status or other dietary components.

Animals↗
PubMed1989

Teenage smoking and health education.

Whilst recent OPCS surveys in 1984 and 1986 have revealed that the proportion of smokers in secondary schools is decreasing, smoking continues to remain at alarming levels. Therefore, it is of importance to identify why, when, where and what adolescents smoke in order to produce appropriate packages of health education material. Numerous studies have sought to highlight factors and features of importance. Youthscan data provides an analysis of 16-17 year-olds which will supplement information already available.

Adolescent↗
PubMed1986

A baseline evaluation of family support programs.

This paper presents a baseline evaluation of four demonstration family support programs located in communities identified as having a disproportionate number of families at risk for malfunctioning. In this baseline evaluation, a one year cohort of 422 family support participants were assessed along key dimensions of parenting known to contribute to child well-being and potentially to the incidence of child abuse or child neglect. These dimensions include parents' attitudes toward child rearing, knowledge of child development, level of perceived social support, and level of depression. Black participants and teenage parents had more punitive attitudes toward child rearing, less knowledge of child development, and less perceived social support than white or older parents. Overall, attitudes, knowledge, level of perceived social support and depression are interrelated in accordance with previous clinical observations and developmental theory, e.g., depressed parents are less knowledgeable, more punitive and have less support than nondepressed parents. The results of the baseline evaluation suggest that the demonstration projects are successful in reaching some subgroups of families at risk for parenting problems.

Adolescent↗
PubMed1985

Effects of chlorine dioxide on thyroid function in neonatal rats.

Chlorine dioxide (ClO2), an alternative to chlorine for drinking water disinfection, has been implicated as a potential antithyroid agent (Bercz et al., 1982). Because antithyroid compounds are known to alter neurobehavioral development, the present study was designed to determine if perinatal exposure to ClO2 affects behavioral activity in rat pups. The activity cage system was designed to monitor the development of locomotor activity of a litter of pups between ages 14-21 d. Pups were exposed to ClO2 either directly, by gavaging 14 mg/kg . from age 5 to 20 d, or indirectly via their dams' drinking water in concentrations of 2, 20, or 100 mg/l from gestation to weaning (21 d postpartum). Although the activity of the indirectly exposed group was not different from controls, the gavaged group showed significantly depressed activity for d 18 and 19 postpartum. The T4 levels of the 21-d-old pups was significantly depressed in the 100-mg/l ClO2 group. The gavaged pups showed an even greater T4 depression, which correlates with their activity levels. These data support the hypothesis that ClO2 affects thyroid function and suggests that a slight depression in T4 can result in developmental delays.

Administration, Oral↗