Search PubMed⌕ Search

Biomedical subjects

M Murray

Publications and source records attributed to M Murray.

At least 253 records · Page 14Linked to original sources
PubMed1993

Measurement of trypanotolerance criteria and their effect on reproductive performance of N'Dama cattle.

One thousand and twenty-eight cow-year records were available from 260 N'Dama cows each having at least 2 years of monthly matching health and performance data over a 5-year period under a medium natural tsetse challenge in Gabon. Four hundred and fifty-eight calf/dam pairs were also available where the calf had been reared to weaning, both had monthly matching records and each cow had weaned at least two calves. Evaluations were carried out on effects of, and linkages between, environmental and stress factors, number and species of trypanosome infections, curative drug treatments given, anaemia measured by packed red cell volume (PCV), and performance measured by calf weaning weight, cow calving rate and cow weight change over the lactation period. Major findings were that over the period from calf birth to weaning, while calves and their dams grazing together had similar numbers of trypanosome infections detected, the Trypanosoma vivax: T. congolense ratios were very different: 1:0.7 in calves; 1:2.8 in cows. This indicated that some ability to control the development of parasitaemia following T. vivax infection might be being acquired, from weaning onwards. In cows, relationships between lowest PCV recorded and curative drug treatments given suggested that between 20 and 32% of trypanosome-infected cows were not being identified by the buffy coat parasitological diagnostic technique. The high level of curative treatment given (to 13.7% of cows over the calendar year, and to 40% of calves from birth to weaning) will have tended to reduce the variance and linkages between aspects of infection and PCV values, especially in calves. In calves, the influence of trypanosome infections, in both calf and dam, on their respective PCV values and hence on calf weaning weight was apparent. There was a 0.91 +/- 0.40 kg increase in calf weaning weight for each 1% increase in calf average PCV, and a 0.95 +/- 0.39 kg increase for each 1% increase in cow average PCV. In cows, there was a similar pathway of influence of T. congolense infection through the PCV values to calving rate--not significant with T. vivax infection. There was a 3.3 +/- 0.65% increase in calving rate for each 1% increase in average PCV. Repeatabilities of performance traits were in the normal range. Repeatabilities of numbers of trypanosome infections detected by the buffy coat technique were too low to have any practical significance. Repeatability of average PCV at 0.40 +/- 0.03 could allow PCV when infected to be used as one criterion of trypanotolerance.

Age Factors↗
PubMed1993

Kinetic evidence for the involvement of a common enzyme in the microsomal reduction of retinal and androstenedione in rat liver.

Androst-4-ene-3,17-dione (androstenedione) was found to be a potent competitive inhibitor of the NADH-supported reduction of retinal in rat hepatic microsomes (Ki 42 microM, Km/Ki ratio 1.1). Similarly, the NADH-mediated reduction of androstenedione was inhibited in mixed fashion by retinal (Ki 12 microM, Km/Ki ratio 0.34). In subsequent experiments the cofactor NADH exhibited an identical Km (8 microM) in the microsomal reductions of both substrates. Acidic pH markedly stimulated the microsomal reduction of androstenedione to testosterone and was also found to enhance retinal reduction to retinol, although the latter reaction exhibited a distinct pH optimum between 6.0 and 6.5. These results suggest that a common enzyme may participate in the reduction of both substrates but at least one other enzyme probably participates in hepatic microsomal testosterone production.

17-Hydroxysteroid Dehydrogenases↗
PubMed1993

Gender differences in perceptions of cancer.

The purpose of this study was to consider gender differences in laypeople's beliefs about and explanations of cancer. Over 700 adults answered a questionnaire about their perceptions and explanations of the disease. The majority of respondents identified cancer as the most fearful disease. Women were more frightened of cancer than were men, whereas men were more frightened of heart disease than were women. The greatest fear of cancer was its perceived incurability and the associated suffering, whereas the greatest fear of heart disease was perceived susceptibility. Men were more likely than women to hold a more negative attitude toward cancer information. Factor analysis of the perceived causes of cancer identified four causal factors, which were labelled Stress, Environmental, Health-related, and Behavioural. Men were more likely to identify behavioural items as important whereas women were more likely to rate heredity as important. Fear of cancer was highly correlated with the health beliefs but not with the perceived causes of cancer. However, a regression analysis found that these health beliefs explained only a small proportion of the variance in cancer fear. The findings are discussed with reference to cancer education.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Lipid-associated methylpheophorbide-a (hexyl-ether) as a photodynamic agent in tumor-bearing mice.

Liposomes are a potential system for more selective delivery of photosensitizers (PS) to tumors. Pheophorbides are one series of new PS under investigation for use in photodynamic therapy. The pharmacokinetics, anti-tumor response and normal tissue effects of methylpheophorbide-a-(hexyl-ether) (MPH) associated with negatively charged phospholipid vesicles composed of high and low transition temperature lipids were determined in mice. In some preparations monosialoganglioside, which is known to impart long circulation time to liposomes was also included. Normally water-insoluble MPH could be quantitatively incorporated in multilamellar liposomes up to at least 20 mol MPH/mol lipid% for most liposome compositions and sonicated to form clear suspensions. Evidence from electron microscopy and entrapment of aqueous space markers indicated that the particles formed by sonication were not standard liposomes. Anti-tumor responses to light treatment (135 J/cm2, 665 nm argon-dye laser) 24 h after MPH (0.4 mumol/kg) administration were slightly but significantly greater (P < 0.05) for lipid associated MPH compared to MPH solubilized in Tween 80. There were no major differences in tumor uptake and tumor cell photosensitization between lipid or Tween 80 formulations of MPH, whereas, dependent on lipid composition and time after MPH administration, the doses of light required to cause occlusive vascular damage were increased for the lipid formulations. Pharmacokinetic studies showed rapid dissociation between lipids and MPH in vivo. Lipid formulations are useful for solubilizing MPH and may improve the therapeutic effects of this PS.

Animals↗
PubMed1993

Ultrasonographic and histopathological findings in equine superficial digital flexor tendon injury.

The ultrasonographic and histopathological findings in 12 normal and 28 injured superficial digital flexor tendons, with lesions ranging in duration from 2 days to 15 months, were compared. A consistent relationship between the ultrasonographic and histological findings was demonstrated. The echogenicity of lesions, the distinctness of their delineation from the surrounding tissue, and the presence and arrangement of the linear echoes were useful features by which to assess the ultrasonograms. Acute lesions were anechoic, a complex mixture of anechoic and hypoechoic areas, or diffusely hypoechoic. These appearances represented haemorrhage, fibrolysis and early granulation tissue. Fibroplasia and granulation tissue produced well to moderately well defined hypoechoic lesions. Chronic fibrosis was characterised by heterogeneously echogenic areas which were poorly defined from the surrounding tissue and had irregularly-arranged linear echoes on longitudinal images. Intratendinous scar formation resulted in multiple hyperechoic foci. Extensive peritendinous lesions were readily apparent on ultrasonograms, but intertendinous adhesions were more difficult to assess, and produced ill-definition of the borders between the superficial and deep digital flexor tendons.

Animals↗
PubMed1993

Health beliefs, locus of control, emotional control and women's cancer screening behaviour.

Improvements in women's cancer-screening behaviours can lead to a reduction in the incidence of breast and cervical cancer. This paper considers the utility of three social psychological models as predictors of such behaviours. Almost 400 women throughout Northern Ireland completed a questionnaire designed to measure the extent of their cancer-screening behaviour, their health beliefs about cancer, their health locus of control and their emotional control. It was found that several components of the health belief model and of locus of control were predictors of the behaviours. The most important predictor of breast self-examination was confidence in how to practise BSE while the most important predictor of attendance for cervical smears was lack of fear of the consequences of the investigation. The findings are discussed with reference to attempts to promote these practices.

Adolescent↗
PubMed1993

Myocardial metabolic and hemodynamic changes during propofol anesthesia for cardiac surgery in patients with reduced ventricular function.

This study examined the hypothesis that the use of propofol for induction and maintenance of anesthesia in patients with reduced ejection fraction (< 0.5) undergoing coronary artery revascularization would not be associated with a greater degree or incidence of myocardial ischemia as compared to patients receiving a moderate dose sufentanil-enflurane anesthetic technique. Two groups of patients were assigned randomly to receive one of two propofol anesthetic regimes. Group A (n = 21) received propofol 1-2 mg/kg as the induction drug and sufentanil 0.03 micrograms.kg-1.min-1 (fixed rate) plus propofol 50-200 micrograms.kg-1.min-1 (variable rate) infusions for maintenance of anesthesia. Group B (n = 21) received sufentanil 5 micrograms/kg for induction and propofol 50-200 micrograms.kg-1.min-1 (variable rate) infusion for maintenance of anesthesia. For comparison, a third group (Group C, n = 18) was studied subsequently. This group received sufentanil 5 micrograms/kg for induction of anesthesia which was maintained with enflurane. Adverse hemodynamic changes (hypertension, tachycardia) were managed by additional propofol (Groups A and B), sufentanil (Group C), or vasopressors (hypotension). Hemodynamic and myocardial metabolic profiles were measured when awake and sedated and at postinduction, postintubation, postincision, poststernotomy, and precardiopulmonary bypass times. Ischemia was assessed by measuring myocardial lactate production. The incidence of myocardial lactate production was reduced in Group B as compared to Group C (Group A, 45/126; Group B, 23/126; Group C, 58/107; P < 0.05). Myocardial lactate flux declined in all groups as surgery progressed; but apart from the reduction in flux (indicative of increased ischemia) noted in Group C versus Group B postinduction, no between-group differences were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Novel Taxol formulations: Taxol-containing liposomes.

Taxol is a complex diterpenoid natural product under investigation for therapy of colon, ovarian, lung, and breast cancer, as well as for melanoma and lymphoma. One problem associated with the administration of Taxol is its low solubility; the formulation used clinically contains polyethoxylated castor oil (Cremophor EL) and ethanol as excipients. Cremophor EL is implicated in hypersensitivity reactions observed on infusion of Taxol. To eliminate the Cremophor EL vehicle and possibly improve the antitumor efficacy of Taxol, a systematic approach was taken to formulate Taxol in phospholipid suspensions (liposomes). Prototype formulations were developed that have sufficient chemical and physical stability to test the hypothesis that liposomes can alter the pharmacology of Taxol, in addition to providing a biologically compatible carrier in which to administer the drug. In vitro. Taxol liposomes retain the growth-inhibitory activity of free Taxol against a variety of tumor cell lines. In vivo, preliminary results showed no effect of free Taxol (in Cremophor EL) on the growth of Colon-26, a Taxol-resistant murine tumor, when given at doses that included or exceeded the maximum tolerated dose (MTD). In contrast, Taxol liposomes delayed tumor progression at a dose that exceeded the MTD of free Taxol.

Animals↗
PubMed1993

Selectivity and sensitivity of changes in serum bile acids during induction of cirrhosis in rats.

Because some patients with cirrhosis have serum transaminase levels within the normal range, a prospective study was undertaken to determine whether the concentration of individual serum bile acids would be a sensitive indicator of development of cirrhosis. The choline-deficient rat has been used as a model for study of these changes. Using high-performance liquid chromatography, we measured the concentrations of individual serum bile acids at 3, 6, 10, 20 and 30 wk of dietary intake. Serum levels of total glycine- and taurine-conjugated bile acids were elevated at all stages tested as compared with levels in control groups (choline supplemented). Similarly, unconjugated bile acids and, particularly, cholic acid showed significantly higher levels at all stages except with the occurrence of cirrhosis at 30 wk, at which time there was a significantly lower level for unconjugated bile acids (0.48 +/- 0.11 vs. 1.40 +/- 0.36 in controls) and for cholic acid (0.17 +/- 0.05 vs. 0.91 +/- 0.39 in controls). The ratio of serum cholic acid to serum chenodeoxycholic acid changed in temporal relationship to progression in the histological lesions in livers of these rats. The ratio was at its highest at 78 +/- 3 at 3 wk (no histological change) and decreased with increasing time and changes in histological appearance until 30 wk, at which time it was down to 1.6 +/- 0.6. The routinely used markers of liver injury (serum ALT, alkaline phosphatase and bilirubin), however, did not match the progression of hepatic histological changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1993

Growth hormone and vitamin A induce P4502C7 mRNA expression in primary rat hepatocytes.

The effects of growth hormone (GH) and retinoids on P4502C7 mRNA levels were investigated in cultured primary hepatocytes from normal female rats. Northern blot analysis of total nucleic acids from hepatocytes maintained in culture for 90 hr showed low basal levels of P4502C7 mRNA, which were marginally increased after continuous treatment with GH. Retinal treatment gave a slightly higher induction than GH, whereas treatment with all-trans retinoic acid alone or with GH in combination with retinol induced P4502C7 mRNA to levels about one-third of those in normal female rat liver. The effects of retinoids on P4502C7 mRNA were dependent on both the dose and type of retinoid used. All-trans retinoic acid produced a saturable dose-response curve with a 50% maximal induction of P4502C7 mRNA at 1.5 microM. The isomer 9-cis retinoic acid showed a dose-dependent activation of P4502C7 mRNA similar to that of all-trans retinoic acid. Retinol gave a 50% maximal response at approximately 5 microM. In the presence of GH, the induction of P4502C7 mRNA appeared additive to the effect of retinol at all concentrations used and to all-trans retinoic acid at concentrations up to 1 microM. As determined by a quantitative solution hybridization assay, P4502C7 mRNA levels were induced 3-fold by GH, 5-fold by retinol, and 19-fold by all-trans retinoic acid. In the presence of GH, P4502C7 was induced 8-fold by retinol, whereas the induction by saturating concentration of all-trans retinoic acid showed no significant additional effect of GH. The importance of vitamin A for the expression of P4502C7 in vivo was confirmed by the low abundance of P4502C7 mRNA in vitamin A-deficient animals as compared with vitamin A-adequate control rats. Nuclear run-on experiments performed in cultured primary hepatocytes showed that both GH and retinoic acid exert their effects at the transcriptional level. We conclude that both GH and retinoids can induce P4502C7 mRNA in rat liver hepatocytes, retinoic acid being the dominant inducer.

Animals↗
PubMed1993

Inhibition and inactivation of constitutive cytochromes P450 in rat liver by parathion.

Phosphorothioate pesticides, such as parathion (O,O-diethyl-O-4-nitrophenyl phosphorothioate), undergo enzymic oxidation to the active insecticidal agents that are the analogous organophosphorus compounds. In hepatic microsomal fractions, the NADPH-mediated conversion of parathion to paraoxon occurs with concomitant loss of cytochrome P450 (P450) and associated activities. In this study, the capacity of parathion to inactivate specific P450 enzymes was studied in rat hepatic microsomes. Parathion was a potent inhibitor of P450 3A2- and 2C11-mediated androst-4-ene-3,17-dione (androstenedione) 6 beta- and 16 alpha-hydroxylation (Ki values of 13 +/- 2 and 2.3 +/- 0.1 microM, respectively, and Km/Ki ratios of 1.4 +/- 0.2 and 11 +/- 1, respectively). After a 10-min preincubation between parathion and NADPH-supplemented microsomes, to inactivate P450 before androstenedione hydroxylation was carried out, the corresponding Km/Ki ratios were increased to 3.5 +/- 0.4 and 35 +/- 6, reflecting 2.5- and 3.2-fold enhancement of inhibition of P450 3A2- and 2C11-dependent activities. In contrast to these findings, P450 2A1/2-mediated androstenedione 7 alpha-hydroxylation was refractory to inhibition and P450 2C6-mediated progesterone 21-hydroxylation was inhibited but not inactivated by the pesticide. Further studies established that androstenedione 6 beta- and 16 alpha-hydroxylation pathways were inactivated with maximal half-times of 2.59 min and 1.72 min, respectively. Although the incubation of parathion (50 microM) with rat liver microsomes for 10 min led to a 16% decrease in P450 estimated spectrophotometrically, immunoblot analysis revealed no change in the microsomal content of P450 2C11 apoprotein. Finally, NADPH-mediated metabolism of parathion to paraoxon (by desulfuration) and 4-nitrophenol (by oxidative cleavage of the phosphorothioate ester) occurred efficiently in microsomes (4.32 and 4.35 nmol/min/mg of protein, respectively). P450 loss was estimated under the same incubation conditions and, thus, 210 parathion molecules were oxidized for each molecule of holo-P450 lost. These findings establish that parathion is a potent inhibitor and inactivator of the principal constitutive P450s, 3A2 and 2C11, in rat liver, whereas the P450s 2A1 and 2A2 are refractory to either inhibition or inactivation. Another major constitutive enzyme, P450 2C6, is inhibited effectively by parathion but does not appear to be subject to inactivation.

Androstenedione↗
PubMed1993

Social and behavioural predictors of women's cancer screening practices in Northern Ireland.

The aim of this study was to describe the extent of cancer screening practices among women resident in Northern Ireland and to identify the social and behavioural characteristics associated with these practices. The study involved a survey of adults resident in the community in Northern Ireland. Contact was made with a sample of 1162 residents who were asked to complete a questionnaire about preventive health practices and attitudes. This produced a response rate of 65.1 per cent. Of these, 391 were women who were asked questions about breast self-examination (BSE), attendance for cervical screening, and certain social and behavioural factors. Approximately 28 per cent of the women performed BSE regularly, a further 28 per cent performed it occasionally, and the remainder rarely or not at all. Almost 20 per cent of the women had had a smear test once, 48 per cent several times, and the rest never. Performance of BSE and attendance for smear tests and BSE was more common among those women aged 35-54 years, who were married, worked outside the home, and whose religion was Church of Ireland (Anglican). The most frequent reason given for not performing BSE was fear of finding a lump and ignorance of the procedure. The most frequent reason given for non-attendance for a smear test was that it was not thought necessary at their age. Public health strategies designed to promote cancer screening need to consider the value of directing their campaigns at those who are most reluctant to perform these practices.

Adult↗
PubMed1993

Problem drinking in Northern Ireland: results of a community survey using the CAGE questionnaire.

A random sample of over 700 adults resident in Northern Ireland answered a questionnaire about their drinking practices. Approximately one-quarter of the men and almost 40% of the women described themselves as non-drinkers. Logistic regression analyses identified religious denomination, marital status, and age as the most important predictors of drinking. Of the drinkers 15.8% of the men and 5.7% of the women obtained a CAGE score of 3 or 4. Further logistic regression analyses identified gender, marital status, and religious denomination as the most important predictors of problem drinking.

Adolescent↗
PubMed1993

Induction of cytochrome P450 2B1 in rat liver by the aromatase inhibitor aminoglutethimide.

Aminoglutethimide (AG) is an inhibitor of P450 aromatase and is in clinical use for the treatment of estrogen-dependent breast cancer in postmenopausal women. AG produces adrenal insufficiency by inhibition of the adrenal P450 cholesterol side chain cleavage enzyme, but a number of serious pharmacokinetic interactions have been reported between AG and coadministered drugs. The present study was undertaken in the rat to assess the modulatory capacity of AG toward P450 enzyme activities in vitro and in vivo and to identify the P450 subject to such effects. In vivo administration of AG produced a dose-related increase in activities attributable to the hepatic P450 enzyme 2B1. Thus, AG administration (25 and 50 mg/kg, i.p., on 3 consecutive days) resulted in 85 and 100% increases in testosterone 16 beta-hydroxylation and 3.3- and 7.4-fold increases in 7-pentylresorufin O-depentylation (both mediated by P450 2B1) in rat liver; at a dose of 5 mg/kg, no effect on these activities was noted. In addition, microsomes from rats administered high-dose AG catalyzed increased rates of androst-4-ene-3,17-dione 16 beta-hydroxylation (from 0.72 +/- 0.10 nmol/min/mg in control to 3.51 +/- 0.47 nmol/min/mg protein). These findings were confirmed by direct immunoquantification of P450 2B1 in hepatic microsomes, by which it was found that the content of the enzyme in control fractions (2.4 +/- 0.7 micrograms/mg microsomal protein) was increased 2.9- and 6.5-fold by the respective doses of AG. In contrast, there was no evidence for increases in two other similarly inducible proteins, P450 3A or P450 2C6.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoglutethimide↗