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Biomedical subjects

E Murphy

Publications and source records attributed to E Murphy.

At least 55 records · Page 3Linked to original sources
PubMed2000

Effects of changes in body weight on carbohydrate metabolism, catecholamine excretion, and thyroid function.

BACKGROUND: Weight gain and loss increases and decreases energy expenditure, respectively, out of proportion to changes in metabolic mass. OBJECTIVE: We hypothesized that changes in energy expenditure associated with weight gain or loss were due in part to changes in catecholamine release, thyroid hormones, carbohydrate utilization, or a combination thereof. METHODS: Urinary catecholamine excretion, serum thyroid hormone concentrations, and results of 3-h oral-glucose-tolerance tests were examined in obese and never-obese subjects at their usual weights, during weight loss or gain, and at stable weights 10-20% below or 10% above usual. RESULTS: Urinary norepinephrine excretion decreased significantly during and after weight loss and increased during and after weight gain. Serum concentrations of reverse triiodothyronine increased significantly during and after weight loss, whereas serum concentrations of triiodothyronine increased significantly (by approximately 0%) during and after weight gain. Serum insulin and glucose concentrations during the oral-glucose-tolerance test increased significantly after weight gain in obese subjects. The percentage change in urinary norepinephrine excretion and in serum concentrations of triiodothyronine were significantly correlated with percentage changes in energy expenditure and with each other. CONCLUSIONS: Changes in body weight were associated with changes in catecholamine excretion and thyroid hormones, which might-by virtue of the effects on energy expenditure-have favored a return to usual body weight. Weight gain induced more apparent insulin resistance in the obese than the never-obese subjects, suggesting a threshold effect of total body fat on this phenomenon.

Adult↗
PubMed2000

Hepatitis B, vaccination and healthcare workers.

Hepatitis B viral infection is transmitted in adults by transfer of body fluids containing the virus. The outcomes following infection can be significant in terms of both health and employment. It is for these reasons that effective preventative health care is the goal of occupational health practitioners. This evidence-based review of the literature provides a basis upon which practice can be established and highlights some of the issues that may confront practitioners of the future.

Adolescent↗
PubMed2000

Is in vivo nuclear magnetic resonance spectroscopy currently a quantitative method for whole-body carbohydrate metabolism?

In vivo nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for noninvasive metabolic research. NMR studies of tissue glycogen metabolism and glucose utilization have generated results with major implications for normal glucose homeostasis and the pathophysiology of type 2 diabetes mellitus. A key question for clinicians and physiologists reading these highly technical studies is: How accurate for whole-body carbohydrate metabolism is NMR spectroscopy? We review this topic and discuss technical, metabolic, and interpretive factors that may limit quantitative accuracy of this modality. We conclude that seeing is not yet believing regarding in vivo NMR spectroscopy; there are still important limitations to quantification of whole-body carbohydrate metabolism.

Carbohydrate Metabolism↗
PubMed2000

Human T-cell lymphotropic virus type 1 gag indeterminate western blot patterns in Central Africa: relationship to Plasmodium falciparum infection.

To gain insight on the significance of human T-cell lymphotropic virus type 1 (HTLV-1) indeterminate serological reactivities, we studied villagers of South Cameroon, focusing on a frequent and specific HTLV-1 Gag indeterminate profile (HGIP) pattern (gag p19, p26, p28, and p30 without p24 or Env gp21 and gp46). Among the 102 sera studied, 29 from all age groups had a stable HGIP pattern over a period of 4 years. There was no epidemiological evidence for sexual or vertical transmission of HGIP. Seventy-five percent of HGIP sera reacted positively on MT2 HTLV-1-infected cells by immunofluorescence assay. However, we could not isolate any HTLV-1 virus or detect the presence of p19 Gag protein in cultures of peripheral blood mononuclear cells obtained from individuals with strong HGIP reactivity. PCR experiments conducted with primers for HTLV-1 and HTLV-2 (HTLV-1/2 primers) encompassing different regions of the virus did not yield HTLV-1/2 proviral sequences from individuals with HGIP. Using 11 peptides corresponding to HTLV-1 or HTLV-2 immunodominant B epitopes in an enzyme-linked immunosorbent assay, one epitope corresponding to the Gag p19 carboxyl terminus was identified in 75% of HGIP sera, while it was recognized by only 41% of confirmed HTLV-1-positive sera. A positive correlation between HTLV-1 optical density values and titers of antibody to Plasmodium falciparum was also demonstrated. Finally, passage of sera through a P. falciparum-infected erythrocyte-coupled column was shown to specifically abrogate HGIP reactivity but not the HTLV-1 pattern, suggesting the existence of cross-reactivity between HTLV-1 Gag proteins and malaria-derived antigens. These data suggest that in Central Africa, this frequent and specific Western blot is not caused by HTLV-1 infection but could instead be associated with P. falciparum infection.

Adult↗
PubMed2000

Elevated ceramide is downstream of altered calcium homeostasis in low serum-induced apoptosis.

Two immortalized cell lines, sup (+) and sup (-), derived from mutagenized Syrian hamster embryo cells, were used to study the relationship and temporal order between calcium and ceramide signals during apoptosis. The early preneoplastic cells, termed sup (+), suppress tumorigenicity when hybridized with tumor cells, whereas later-stage sup (-) cells do not. In reduced serum conditions, sup (+) cells cease proliferating and undergo apoptosis; in contrast, sup (-) cells continue slow growth and undergo necrosis. In sup (+) cells, decreased endoplasmic reticulum (ER) calcium occurs 4 h after low serum treatment and precedes apoptosis. Significant elevations in ceramide are observed 16 h after reduced serum treatment of sup (+) cells but are not found in sup (-) cells. Inhibiting ER calcium depletion in low serum-treated sup (+) cells by treating with high levels of calcium prevents both ceramide generation and apoptosis. Conversely, inducing ER calcium depletion in sup (-) cells by treating with low serum plus thapsigargin results in elevated ceramide levels and apoptosis. Furthermore, C(6)-ceramide treatment induced apoptosis of sup (-) cells in low serum, a condition that does not normally cause apoptosis. C(6)-ceramide treatment did not induce apoptosis in either sup (+) or sup (-) cells in 10% serum but did cause G(2)/M arrest. These studies show that ceramide production is downstream of ER calcium release.

Animals↗
PubMed2000

Insulin sensitiser drugs.

Insulin resistance is the predominant early pathological defect in Type 2 diabetes. As well as being a risk factor for the development of Type 2 diabetes, insulin resistance is also associated with increased cardiovascular risk and other metabolic disturbances including visceral adiposity, hyperinsulinaemia, impaired glucose tolerance, hypertension and dyslipidaemia [1-4]. The newest approach to oral antidiabetic therapy is to target improvements in insulin sensitivity at muscle, adipose tissue and hepatic level. This results in improvements in glycaemic control and other features of the insulin resistance syndrome, with potential long-term benefits in preventing/delaying the onset of diabetic complications and macrovascular disease.

Animals↗
PubMed2000

Evidence for complement-dependent and -independent inhibition of insulin secretion from clonal beta-cells incubated in the presence of sera of newly diagnosed IDDM patients.

There are conflicting reports on the effect of serum from patients with insulin-dependent diabetes mellitus (IDDM) or normal human serum on beta-cell function and insulin secretion. Here, we report that the sera of newly diagnosed IDDM patients potently suppresses insulin secretion from a clonal rat pancreatic beta-cell line (BRIN-BD11), but do not alter cell viability. Indeed, the viability of the beta-cells was not significantly different between cells cultured in 10% (v/v) IDDM sera, normal human sera, or fetal calf serum after 24, 48 and 72 h. Alanine-stimulated insulin secretion from cells cultured for 24 h in (10% v/v) IDDM patient sera was reduced to 48% of that secreted from cells cultured in (10% v/v) normal human sera. After depletion of the complement components C1q and C3, the inhibition of insulin secretion induced by IDDM patient sera was significantly reversed (no significant difference was observed between cells cultured in complement-depleted IDDM patient sera and cells cultured in normal human sera or complement-depleted normal human sera). The concentration of glutamic acid decarboxylase (GAD) autoantibodies was markedly increased in the sera of six out of nine newly diagnosed IDDM patients in this study, whereas insulin auto-antibodies (IAA) were detected in the sera of three of the nine patients and islet-cell antibodies (ICA) in the sera of five of them. In addition, the concentration of soluble terminal complement complexes (SC5-9) was greater in some of the beta-cell culture media samples after 24 h incubation when the incubation medium was supplemented with IDDM patient sera than when supplementation was with normal human sera. We propose that the mechanism of sera-induced inhibition of insulin secretion from clonal beta-cells may involve complement- and cytokine-stimulated intracellular events that attenuate the metabolite-induced secretory process.

Adolescent↗
PubMed2000

Factors influencing discussion of smoking between general practitioners and patients who smoke: a qualitative study.

BACKGROUND: Anti-smoking advice from general practitioners (GPs) is effective and recent evidence-based guidelines urge GPs to advise all patients against smoking at every opportunity. GPs do not exploit many opportunities to discuss smoking with patients and the reasons for this are unclear. AIM: To elicit, relate, and interpret GPs' accounts of why they discuss smoking with some patients and not others. METHOD: Thirty-nine Leicestershire GPs were purposively selected so as to have a range of attitudes towards discussing smoking with patients. Each GP had one surgery session video-recorded and afterwards participated in a qualitative, semi-structured interview. Prior to each interview, GPs were shown a video-recording of one of their consultations with a smoker to enhance their recall of events. RESULTS: Being aware of patients' smoking status did not necessarily result in GPs discussing smoking with patients. GPs were keen to preserve good doctor-patient relationships and avoid negative responses from patients once the topic of smoking had been raised, and this was felt to be best achieved by restricting most discussions about smoking to situations where patients presented with smoking-related problems and in circumstances where the doctors perceived the doctor-patient relationship was strong. Doctors also thought it important to address patients' agendas relating to the current consultation before discussing smoking. CONCLUSIONS: General practitioners have strong reasons for preferring to discuss smoking when patients present with smoking-related problems. Those wishing to increase the amount of advice-giving by GPs might be more successful if they encouraged GPs to make greater use of problem-orientated opportunities to discuss smoking.

Attitude of Health Personnel↗
PubMed2000

The patient room of the future.

In the future, patient rooms will use high-tech to a human advantage. Learn how the new model provides a soothing, healing environment that increases nursing efficiency.

Environment Design↗
PubMed1999

Overexpression of the cardiac beta(2)-adrenergic receptor and expression of a beta-adrenergic receptor kinase-1 (betaARK1) inhibitor both increase myocardial contractility but have differential effects on susceptibility to ischemic injury.

Cardiac beta(2)-adrenergic receptor (beta(2)AR) overexpression is a potential contractile therapy for heart failure. Cardiac contractility was elevated in mice overexpressing beta(2)ARs (TG4s) with no adverse effects under normal conditions. To assess the consequences of beta(2)AR overexpression during ischemia, perfused hearts from TG4 and wild-type mice were subjected to 20-minute ischemia and 40-minute reperfusion. During ischemia, ATP and pH fell lower in TG4 hearts than wild type. Ischemic injury was greater in TG4 hearts, as indicated by lower postischemic recoveries of contractile function, ATP, and phosphocreatine. Because beta(2)ARs, unlike beta(1)ARs, couple to G(i) as well as G(s), we pretreated mice with the G(i) inhibitor pertussis toxin (PTX). PTX treatment increased basal contractility in TG4 hearts and abolished the contractile resistance to isoproterenol. During ischemia, ATP fell lower in TG4+PTX than in TG4 hearts. Recoveries of contractile function and ATP were lower in TG4+PTX than in TG4 hearts. We also studied mice that overexpressed either betaARK1 (TGbetaARK1) or a betaARK1 inhibitor (TGbetaARKct). Recoveries of function, ATP, and phosphocreatine were higher in TGbetaARK1 hearts than in wild-type hearts. Despite basal contractility being elevated in TGbetaARKct hearts to the same level as that of TG4s, ischemic injury was not increased. In summary, beta(2)AR overexpression increased ischemic injury, whereas betaARK1 overexpression was protective. Ischemic injury in the beta(2)AR overexpressors was exacerbated by PTX treatment, implying that it was G(s) not G(i) activity that enhanced injury. Unlike beta(2)AR overexpression, basal contractility was increased by betaARK1 inhibitor expression without increasing ischemic injury, thus implicating a safer potential therapy for heart failure.

Adenosine Triphosphate↗
PubMed1999

Mother-to-child transmission of human T-cell-leukemia/lymphoma virus type I: implication of high antiviral antibody titer and high proviral load in carrier mothers.

In order to gain new insights into the risk factors influencing human-T-cell-leukemia/lymphoma-virus-type-I (HTLV-I) mother-to-child transmission, a retrospective study of HTLV-I infection among children born to HTLV-I-seropositive women was carried out in a highly HTLV-I-endemic population of African origin living in French Guyana. The study covered 81 HTLV-I-seropositive mothers and their 216 children aged between 18 months old and 12 years old. All plasma samples were tested for the presence of HTLV-I antibodies by ELISA, immunofluorescence assay and Western blot. HTLV-I provirus was detected, in the DNA extracted from peripheral-blood mononuclear cells, by polymerase chain reaction (PCR) using primers specific for 3 different HTLV-I genomic regions (LTR, gag and pX) and quantified by a competitive PCR assay. Out of the 216 children, 21 were found to be HTLV-I-seropositive, giving a crude HTLV-I transmission rate of 9.7%, while among the 180 breast-fed children 10.6% were HTLV-I-seropositive. Perfect concordance between serological and PCR results was observed, and none of the 195 HTLV-I-negative children was found HTLV-I-positive by PCR. In conditional (by family) logistic-regression models, HTLV-I seropositivity in children was associated with an elevated maternal anti-HTLV-I-antibody titer (OR 2.2, p = 0.0013), a high maternal HTLV-I proviral load (OR 2.6, p = 0.033) and child's gender, girls being more frequently HTLV-I-infected than boys: OR 3.6, p = 0.0077 in the model including maternal anti-HTLV-I-antibody titer and OR 4.1, p = 0.002 in the model including the maternal HTLV-I proviral load.

Breast Feeding↗
PubMed1999

Seroepidemiological and molecular studies of human T cell lymphotropic virus type II, subtype b, in isolated groups of Mataco and Toba Indians of northern Argentina.

We studied plasma samples from 2082 Mataco Indians living in 22 different communities in the western part of Formosa Province, northern Argentina. Samples were screened for HTLV-I/II antibodies by particle agglutination assay. All positive or borderline samples were then tested by an immunofluorescence assay (IFA) on C19 HTLV-II-producing cells. Western blot was used for confirmation of all IFA-positive plasma samples. The crude HTLV-II seroprevalence was 3.0% (62 of 2051), and 0.9% (5 of 588) in children less than 10 years old. The latter result suggests ongoing mother-to-child transmission, probably by breast feeding. There was a marked increase in HTLV-II seroprevalence with age (0.9%, 0-10 years; 1.6%, 11-20 years; 4.4%, 21-30 years; 3.4%, 31-40 years; 7.2%, 41-50 years; 5.7%, >50 years) in both male (p = 0.002) and female subjects (p = 0.00002). None of the 80 non-Indian inhabitants tested was HTLV-I/II seropositive. In a second study, among 105 Toba Indians from a village (Primavera) of the eastern part of this region, 23 were HTLV-II seropositive with a seroprevalence of 59% in those more than 40 years old. From seven of the Indians from Primavera, three others from neighboring regions (including two Tobas and one Pilaga), and one intravenous drug user (IVDU) from Rosario, DNA was extracted from peripheral blood mononuclear cells, and the gp21 transmembrane-encoding gene (590 bp) was amplified by PCR, cloned, and sequenced. LTR sequences were also obtained from the Pilaga, the IVDU, and one Toba. Molecular and phylogenetic analyses revealed that the Indians were all infected with closely related HTLV-II molecular strains belonging to the b subtype, while the IVDU was infected with an HTLV-II subtype a variant. Such data help to make a phylogenetic atlas of HTLV-II among Amerindian tribes and are crucial to gain new insights into the origin and modes of dissemination of this human retrovirus in the Americas.

Adolescent↗
PubMed1999

Reduced capacitative calcium entry correlates with vesicle accumulation and apoptosis.

A preneoplastic variant of Syrian hamster embryo cells, sup(+), exhibits decreased endoplasmic reticulum calcium levels and subsequently undergoes apoptosis in low serum conditions (Preston, G. A., Barrett, J. C., Biermann, J. A., and Murphy, E. (1997) Cancer Res. 57, 537-542). This decrease in endoplasmic reticulum calcium appears to be due, at least in part, to reduced capacitative calcium entry at the plasma membrane. Thus we investigated whether inhibition of capacitative calcium entry per se could reduce endoplasmic reticulum calcium and induce apoptosis of cells. We find that treatment with either SKF96365 (30-100 microM) or cell-impermeant 1,2-bis(o-amino-5-bromophenoxy)ethane-N,N,N', N'-tetraacetic acid (5-10 mM) is able to induce apoptosis of cells in conditions where apoptosis does not normally occur. Because previous work has implicated vesicular trafficking as a mechanism of regulating capacitative calcium entry, we investigated whether disruption of vesicular trafficking could lead to decreased capacitative calcium entry and subsequent apoptosis of cells. Coincident with low serum-induced apoptosis, we observed an accumulation of vesicles within the cell, suggesting deregulated vesicle trafficking. Treatment of cells with bafilomycin (30-100 nM), an inhibitor of the endosomal proton ATPase, produced an accumulation of vesicles, decreased capacitative entry, and induced apoptosis. These data suggest that deregulation of vesicular transport results in reduced capacitative calcium entry which in turn results in apoptosis.

Animals↗
PubMed1999

A multicenter, randomized trial of percutaneous coronary intervention versus bypass surgery in high-risk unstable angina patients. The AWESOME (Veterans Affairs Cooperative Study #385, angina with extremely serious operative mortality evaluation) investigators from the Cooperative Studies Program of the Department of Veterans Affairs.

This multicenter, prospective randomized trial was designed to test the hypotheses that percutaneous coronary intervention (PCI) is a safe and effective alternative to coronary artery bypass grafting (CABG) for patients with refractory ischemia and high risk of adverse outcomes. As a comparison of revascularization strategies, the trial specifically allows surgeons and interventionists to use new techniques as they become clinically available. After 42 months of this 72-month trial, 17,624 patients have been screened and 2022 met eligibility requirements: 341 have been randomized to either CABG or PCI, and the remaining 1681 are being prospectively followed in a registry. The 3-year overall survival of patients in the registry and randomized trial is comparable. To enhance accrual into the randomized trial, site visits were conducted, a few low-accruing hospitals were put on probation and/or replaced, eligibility criteria were reviewed at annual meetings of investigators, and the accrual period was extended by 1 year. These data demonstrate that a prospective randomized trial and registry of coronary revascularization for medically refractory high-risk patients is feasible.

Age Factors↗
PubMed1999

Preverbal, Early Verbal Pediatric Pain Scale (PEPPS): development and early psychometric testing.

The Pre-Verbal, Early Verbal Pediatric Pain Scale (PEPPS) is conceptualized to measure the established pain response in toddlers, a pediatric group void of pain assessment scales. It consists of seven categories, each with weighted indicators. Scores can range from 0 to 26. Using a blinded, cross-sectional design, 40 children, aged 12 to 24 months, were videotaped throughout their postoperative stay in the postanesthesia care unit. Vignettes were randomly selected and viewed by four experienced pediatric nurses. Results indicated that the PEPPS was easy to use and demonstrated acceptable inter-rater and intrarater reliability. Early evidence of construct validity was established by statistically significant differences in premedication and postmedication pain scores.

Child Development↗