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Biomedical subjects

J R Mitchell

Publications and source records attributed to J R Mitchell.

At least 19 recordsLinked to original sources
PubMed1992

A randomized placebo-controlled study of the effect of low dose aspirin on platelet reactivity and serum thromboxane B2 production in non-pregnant women, in normal pregnancy, and in gestational hypertension.

OBJECTIVE: To investigate the effect of 60 mg aspirin daily on platelet reactivity and prostaglandin production in various groups of patients. Similar regimens, which are thought to act through inhibition of platelet thromboxane production, are currently undergoing clinical assessment for the prevention of pre-eclampsia and intrauterine growth retardation. DESIGN: A prospective randomized placebo controlled study. SETTING: University Hospital, Nottingham. SUBJECTS: 12 non-pregnant female volunteers, 18 normal primigravidae before 16 weeks gestation and 16 pregnant women admitted with gestational hypertension (GH) at a mean gestation of 38 weeks. INTERVENTIONS: In the non-pregnant women blood samples were taken before and after a 10-day course of 60 mg aspirin daily. The primigravidae had blood samples taken at 16 weeks and then they were randomized to receive either 60 mg aspirin daily or a matched placebo. Further blood samples were obtained at 28, 32 and 36 weeks. MAIN OUTCOME MEASURES: Changes in platelet reactivity and release reaction, and serum thromboxane production, were estimated in whole blood. RESULTS: 60 mg aspirin daily significantly inhibited cyclo-oxygenase dependent platelet aggregation, release reaction and serum thromboxane production in non-pregnant and pregnant women, and in women with GH (P less than 0.01). When adrenaline was used as the aggregating agent, the cyclo-oxygenase pathway was recruited in the increased reactivity seen in the third trimester of normal pregnancy, and was sensitive to inhibition by low dose aspirin. CONCLUSION: Low dose aspirin would appear to be an appropriate agent for the inhibition of platelet reactivity associated with hypertensive pregnancy.

Adult↗
PubMed1992

Regulation of expression of the lipoprotein lipase gene in brown adipose tissue.

The regulation of lipoprotein lipase gene expression in brown adipose tissue was studied. Rats were preacclimated to 21 degrees C. Exposure to cold (4 degrees C) resulted in a rapid increase in the level of lipoprotein lipase mRNA in the tissue. The level peaked (expressed per microgram total RNA) after approximately 8 h and then slowly declined. The increased lipoprotein lipase mRNA level was not due to an increased stability of the mRNA, but, in a transition event from a high to a low expression of the lipoprotein lipase gene, a transcription-dependent process was recruited that accelerated the breakdown of lipoprotein lipase mRNA. Norepinephrine injections increased lipoprotein lipase mRNA levels in the tissue; this effect was mediated via a beta-adrenergic receptor. The effect of cold could be mimicked by norepinephrine injections, and these two effects were not additive, indicating that the cold effect was mediated by norepinephrine. The lipoprotein lipase mRNA level was also increased by insulin injections (into fasted animals); thus an increase in lipoprotein lipase gene expression in brown adipose tissue may be induced via two different stimuli, which, intracellularly, would be mediated via different signaling systems. In all investigated conditions, the changes in lipoprotein lipase mRNA levels observed here were parallelled by alterations in lipoprotein lipase activity reported earlier from this laboratory. It was therefore concluded that, under the conditions studied, lipoprotein lipase activity in brown adipose tissue was primarily regulated at the transcriptional level.

Adipose Tissue, Brown↗
PubMed1991

Activities of enzymes of glycerolipid synthesis in brown adipose tissue after treatment of rats with the adrenergic agonists BRL 26830A and phenylephrine, after exposure to cold and in streptozotocin-diabetes.

1. Measurements were made, relative to tissue DNA, of the activities of enzymes of glycerolipid synthesis in homogenates of interscapular brown adipose tissue. These were: mitochondrial and microsomal forms of glycerolphosphate acyltransferase (GPAT), Mg(2+)-dependent phosphatidate phosphohydrolase (PPH) and fatty acyl-CoA synthetase (FAS). 2. In normal animals, 3 days of cold-exposure (4 degrees C) increased all activities. The increase in mitochondrial GPAT activity was particularly pronounced (5-fold). Administration of the beta-adrenergic agonist BRL 26830A mimicked the effect of cold on microsomal GPAT activity. Mitochondrial GPAT, PPH and FAS activities were unresponsive to BRL 26830A. The alpha-adrenergic agonist phenylephrine significantly decreased activities of GPAT and PPH. 3. Streptozotocin-diabetes decreased mitochondrial GPAT activity, but did not abolish the effect of cold to increase this activity or the activity of microsomal GPAT. Diabetes abolished the effect of cold on PPH and FAS activities. 4. The findings are relevant to signals that drive early events in mitochondriogenesis and cell proliferation in brown adipose tissue on exposure to cold.

Adipose Tissue, Brown↗
PubMed1991

A comparison of the mealtime care given to patients by nurses using two different meal delivery systems.

This study explored the mealtime care given to stroke patients and general patients on the medical wards of two hospitals which operated different meal delivery systems. Overall, nurses in Hospital 1 (in which the patients' food was plated by catering staff in the main hospital kitchen) tended to be less involved in mealtimes than those in Hospital 2 (in which the nurses plated the food on the wards). This was particularly so for the qualified staff and applied to many aspects of mealtime care including meal trolley supervision, the serving and delivery of food, checking patients' well-being, observing their feeding difficulties, providing assistance during mealtimes, and observing the contents of discarded dishes. These differences were not related to staffing levels or the prevalence of feeding problems. It is possible, therefore, that a meal delivery system designed to free nurses from the 'non-nursing' duty of serving food may have an adverse effect on their involvement in other aspects of mealtimes.

Cerebrovascular Disorders↗
PubMed1991

Platelet reactivity and serum thromboxane B2 production in whole blood in gestational hypertension and pre-eclampsia.

OBJECTIVE: To determine the nature and extent of changes in platelet reactivity in gestational hypertension and pre-eclampsia (using whole blood techniques which may be more physiological than those previously employed). DESIGN: Cross-sectional observational study. SUBJECTS: 8 normal primigravidae, 16 women with gestational hypertension and 12 women with pre-eclampsia, studied at around 36 weeks gestation. RESULTS: Platelet reactivity (aggregation and release reaction) induced by stimulation with adrenaline was decreased in the pre-eclamptic group. Serum thromboxane B2 production was unchanged in both hypertensive groups compared with the control group. CONCLUSIONS: In the context of evidence of platelet activation in pre-eclampsia, our findings are interpreted as reflecting platelet exhaustion.

Adult↗
PubMed1991

Physiology of nerve repair: a research update.

Understanding the anatomy and response to injury of the peripheral nerve is important for the surgeon treating peripheral nerve injuries. Appropriate treatment also requires proper classification of the injury. Although great advances have been made in the area of microsurgical repair, results remain unpredictable. Future work in the areas of immunology, nerve conduits, and growth factors will, it is hoped, provide further information to allow for better functional recovery.

Humans↗
PubMed1990

What do we gain by modifying risk factors for coronary disease?

There is no doubt about the association between coronary heart disease (CHD) and smoking, high serum cholesterol and high blood pressure, but association does not mean causation. To prove causation we must mount intervention trials and show that changing a risk marker changes total mortality: a) Trials of dietary reduction of serum lipids: The US Veterans dietary study and the North Karelia project showed no significant reduction in total mortality, nor did the Multiple Risk Factor Intervention Trial (MRFIT) or the WHO "paired-factories" Collaborative Group Study, where other risk factors were also being corrected. In the latter study there was a barely significant reduction in non-fatal CHD but fatal CHD, like total mortality was unchanged. b) Trials of lipid-lowering drugs: The first large-scale study, using clofibrate, showed an increase in total mortality; the screening of 500,000 men and the comparison of cholestyramine with placebo for the top 5% of lipid levels resulted in 68 deaths on the active resin and 71 on placebo. Less expensive measures (alcohol testing; safer roads) could surely do more good to half a million men? These 3 lives "saved" were "lost" in the Helsinki gemfibrozil study where there were 45 deaths in the active group and 42 in the placebo group. c) Effect of blood-pressure reduction. The assumption that reducing a risk marker will reduce CHD was challenged by the massive MRC Mild-to-Moderate Hypertension trial which showed no significant effect of treatment on CHD, CHD death or total mortality, even though stroke mortality was modestly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1990

Parent and peer attachment in early adolescent depression.

Insecure attachment relations have been theorized to play a significant role in the development of depressogenic modes of adaptation and to thus form a vulnerability factor for the emergence of depressive disorder in children. This study examined security of parent and peer attachment among four groups of early adolescents: clinically depressed, nondepressed psychiatric controls, nonpsychiatric controls, and adolescents with resolved depression. Depressed adolescents reported significantly less secure parent attachment than either of the control groups, and less secure peer attachment than the nonpsychiatric control group. Attachment security of adolescents with resolved depression was on a par with the nonpsychiatric control group. Among all psychiatric patients, security of attachment to parents was negatively correlated with severity of depression according to interview and self-report ratings. Less secure attachment to parents, but generally not to peers, was also related to more maladaptive attributional styles, presence of separation anxiety disorder, and history of suicidal ideation.

Adolescent↗
PubMed1990

Communication and sensorimotor functioning in children with autism.

This study examined the relationship between sensorimotor functioning and communicative intent in children with autism. Ten children with autism, four verbal and six nonverbal, served as subjects. Sensorimotor functioning was assessed on object permanence, means-end, causality, vocal and gestural imitation, the construction of objects in space and schemes for relating objects. A 2-hr communication sample was also obtained and analyzed for the number and diversity of pragmatic functions expressed. Object permanence was not significantly related to either the diversity or total number of pragmatic functions. Means-end was significantly related to both of these measures, while vocal imitation was significantly related to the total number of pragmatic functions expressed. In addition, means-end was significantly correlated with performance on the vocal and gestural imitation scales.

Autistic Disorder↗
PubMed1990

A longitudinal study of platelet behaviour and thromboxane production in whole blood in normal pregnancy and the puerperium.

A longitudinal study of platelet behaviour (platelet aggregation and release reaction) in whole blood and of serum thromboxane B2 production was performed before, during and after normal pregnancy. The response of platelets to arachidonic acid and to adrenaline was significantly increased in the third trimester. Six weeks after delivery, values were still modestly increased but return to non-pregnant values was complete by 12 weeks. Serum thromboxane B2 production was unchanged throughout pregnancy and the puerperium.

Arachidonic Acid↗
PubMed1990

Comparison of antioxidant and nonantioxidant lipoxygenase inhibitors on neutrophil function. Implications for pathogenesis of myocardial reperfusion injury.

The activation and accumulation of leukocytes during inflammatory processes such as that initiated by myocardial ischemia and reflow appear to be major determinants of irreversible tissue injury. Myocardial salvage by dual cyclooxygenase/lipoxygenase inhibitors and selective 5-lipoxygenase inhibitors has suggested a role for lipoxygenase (LOX) products, such as the potent chemotactic factor leukotriene B4, in ischemia-reflow injury. However, many LOX inhibitors are antioxidants and several have been shown to directly inhibit neutrophil function in vitro, thereby questioning the role of LOX products in reperfusion injury. To clarify further the protective mechanism of lipoxygenase inhibitors, we have examined the effects of two nonantioxidant inhibitors, SK&F 86002 and REV-5901, on human neutrophil activation and function in vitro. The antioxidant LOX inhibitor nordihydroguiaretic acid, which served as a positive control, exhibited a concentration-dependent inhibition of N-formyl-methionyl-leucyl-phenylalanine (fMLP) and recombinant C5a-induced neutrophil bipolarization, fMLP-induced upregulation of the adherence glycoprotein Mac-1 (CD11b/CD18), fMLP-induced aggregation and neutrophil adherence to and migration through interleukin-1-stimulated human endothelial monolayers. In contrast, neither SK&F 86002 nor REV-5901 (in concentrations up to 50 microM) had any effect on these functions, nor did they inhibit neutrophil oxidative metabolism (phorbol myristate acetate-induced chemiluminescence). Inasmuch as both of these agents have been observed to reduce myocardial ischemia-reflow injury in vivo, their failure to directly inhibit neutrophil function further supports an important role for chemotactic LOX products in the pathogenesis of reperfusion injury.

Antigens, Differentiation↗
PubMed1990

Lipid hydroperoxy and hydroxy derivatives in copper-catalyzed oxidation of low density lipoprotein.

Oxidation of low density lipoprotein (LDL) causes changes in the biological properties of LDL that may be important in atherogenesis. That LDL oxidation is accompanied by lipid peroxidation has been demonstrated, but previous analyses of the products of LDL oxidation have not included measurement of specific lipid hydroperoxy and hydroxy derivatives. In this study, LDL was isolated from plasma of normal volunteers and exposed to oxygenated buffer and 5 microM CuSO4 for 24 h. Oxidized LDL showed decreased linoleate (18:2) and arachidonate (20:4) content with increased concentrations of thiobarbituric acid reactive substances (TBARS) and hydroxy and hydroperoxy 18:2 and 20:4. The electrophoretic mobility of the LDL protein also was increased by oxidation. After reduction, the hydroxy fatty acids were characterized by gas chromatography-mass spectrometric analysis of the trimethylsilyl ether methyl ester derivatives. The hydroperoxy and hydroxy derivatives accounted for approximately 70% of the linoleate consumed during LDL oxidation and represented 45-fold more product than was measured by TBARS analysis. Numerous biological properties, including cytotoxic and chemoattractant activities of hydroperoxy and hydroxy fatty acids, have been reported, but the manner in which they may contribute to atherogenesis requires further study.

Arachidonic Acids↗
PubMed1989

Patients' and general practitioners' satisfaction with information given on discharge from hospital: audit of a new information card.

OBJECTIVE: To determine the attitudes of patients discharged from hospital and their general practitioners to a new information card giving details about admission, diagnosis, and treatment and to assess the completeness of the information on the card. DESIGN: Consecutive patients discharged from the care of three consultant physicians over 16 weeks. SETTING: One general medical ward in a large teaching hospital. PATIENTS: A total of 275 consecutive discharges of 258 patients were studied. The mean age of patients was 60 years and mean duration of admission five days. INTERVENTION: At discharge from the ward all study patients received an information card and a copy of the card in the form of an interim discharge letter to be delivered to their general practitioner. Patients and general practitioners were asked to complete a questionnaire giving their views on the legibility, helpfulness, quality, and quantity of the information they received. Copies of all the information cards were scrutinised for completeness. MAIN RESULTS: The results were based on 208 (76%) forms returned by patients and 214 (78%) forms returned by general practitioners. Information was considered very helpful or quite helpful according to 170 (83%) forms from patients and 197 (92%) forms from general practitioners; sufficient information was provided according to 160 and 182 forms. Most patients and nearly all general practitioners thought it was a good idea to provide this information for patients at discharge. According to 125 forms from patients and 188 from general practitioners the information card was very easy or quite easy to read; 155 patients had read it at least twice and 149 were likely to refer to it again. OTHER RESULTS: The written information about the patient, the diagnosis, and what the patient had been told was generally well completed, although the date of discharge was omitted from 42 (15%) cards. Details of drugs prescribed at discharge were generally thorough. CONCLUSIONS: Giving an information card to all patients at discharge was feasible and favoured by most patients and their general practitioners. Having made minor changes in design, we think that we have produced an information card that is a convenient size and will improve communication between patients, their general practitioners, and hospital doctors. We now issue this card routinely to all patients discharged from our ward and hope that it might be widely adopted.

Attitude of Health Personnel↗
PubMed1989

Glutathione disulfide formation and lipid peroxidation during cardiac ischemia and reflow in the dog in vivo.

The content of glutathione disulfide (GSSG) in tissue, coronary sinus blood plasma, and in cardiac lymph was measured in a well-characterized model of regional cardiac ischemia and reflow in dogs in vivo in order to assess the magnitude of the oxidant stress produced. No increase in GSSG content was observed during 60 min of occlusion of the circumflex or left anterior descending arteries, or during up to 70 min of reflow. The contents of 11-, 12-, and 15-hydroxyeicosatetraenoates (HETEs) in total lipids also were not increased following 60 min of regional ischemia and up to 60 min of reflow. In addition, global ischemia produced by aortic crossclamping and cardiopulmonary bypass did not increase HETE content. In contrast, infusion of tertiary butyl hydroperoxide (tBHP) into the left atrium produced readily measurable increases in GSSG content with or without prior induction of myocardial ischemia. Infusion of tBHP also increased tissue contents of the HETEs. These findings indicate that the canine myocardium subjected to ischemia-reflow conditions does not generate large amounts of reactive oxygen and does not form significant amounts lipid peroxidation products.

Animals↗