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P Murphy

Publications and source records attributed to P Murphy.

At least 55 records · Page 3Linked to original sources
PubMed2001

Molecular diagnosis of infective endocarditis--a new Duke's criterion.

The molecular approach of PCR amplification of specific gene targets and universal loci for bacteria (16S rRNA) and fungi (18S, 28S and 5.8S rRNA) and subsequent sequencing was used to identify the possible causal microbial agent(s) in blood culture (47 patients) and heart valve material (30 patients) from patients with suspected infective endocarditis (IE). Culture and molecular results were analysed with respect to the patients' clinical background and the Duke Criteria. The findings demonstrated that: (i) all patients who were definite or possible cases were positive by PCR, even patients whose blood culture and valve material were culture-negative; and (ii) all patients who were rejected as having IE were also negative by PCR, with the exception of 1 patient who had bacteraemia from another source and 5 patients whose blood culture material was believed to contain an environmental contaminant. Direct molecular identification of the aetiological agents responsible for IE from blood culture material may enable specific treatment to commence at an earlier stage of the disease and hence reduce the need for valve replacement. Such a molecular approach may aid in the diagnosis of IE and should therefore be included as an additional major criterion in the Duke's classification scheme.

Bartonella↗
PubMed2001

Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23.

We have performed genetic linkage analysis in 13 large multiply affected families, to test the hypothesis that there is extensive heterogeneity of linkage for genetic subtypes of schizophrenia. Our strategy consisted of selecting 13 kindreds containing multiple affected cases in three or more generations, an absence of bipolar affective disorder, and a single progenitor source of schizophrenia with unilineal transmission into the branch of the kindred sampled. DNA samples from these families were genotyped with 365 microsatellite markers spaced at approximately 10-cM intervals across the whole genome. We observed LOD scores >3.0 at five distinct loci, either in the sample as a whole or within single families, strongly suggesting etiological heterogeneity. Heterogeneity LOD scores >3.0 in the sample as a whole were found at 1q33.2 (LOD score 3.2; P=.0003), 5q33.2 (LOD score 3.6; P=.0001), 8p22.1-22 (LOD score 3.6; P=.0001), and 11q21 (LOD score 3.1; P=.0004). LOD scores >3.0 within single pedigrees were found at 4q13-31 (LOD score 3.2; P=.0003) and at 11q23.3-24 (LOD score 3.2; P=.0003). A LOD score of 2.9 was also found at 20q12.1-11.23 within in a single family. The fact that other studies have also detected LOD scores >3.0 at 1q33.2, 5q33.2, 8p21-22 and 11q21 suggests that these regions do indeed harbor schizophrenia-susceptibility loci. We believe that the weight of evidence for linkage to the chromosome 1q22, 5q33.2, and 8p21-22 loci is now sufficient to justify intensive investigation of these regions by methods based on linkage disequilibrium. Such studies will soon allow the identification of mutations having a direct effect on susceptibility to schizophrenia.

Chromosome Aberrations↗
PubMed2001

Local anesthetics potentiate nitric oxide synthase type 2 expression in rat glial cells.

Expression of the calcium-independent nitric oxide synthase (NOS2) contributes to damage in neurologic disease and trauma. The effects of local anesthetics on NOS2 expression have not been examined. The authors tested the effects of four local anesthetics on the expression of NOS2 in immunostimulated rat C6 glioma cells. Incubation with local anesthetics alone did not induce nitrite accumulation; however, the nitrite production induced by stimulation with bacterial endotoxin lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) was increased in a dose-dependent manner by bupivacaine (maximal 3-fold at 360 microM), tetracaine (maximal 7-fold at 360 microM), and lidocaine at higher doses (5-fold increase at 3.3 mM). Significant increases in nitrite production were observed in concentrations of bupivacaine or tetracaine as low as 120 microM, which correspond to 30 microg/mL (.003% weight/volume). In contrast, ropivacaine had little effect on nitrite production (160% of control values) and only at the highest concentration (3.3 mM, corresponding to 890 microg/mL or 0.089% w/v) tested. Increased nitrite production was not caused by cytotoxic effects of the drugs used, as assessed by release of intracellular lactate dehydrogenase. Increased nitrite production was accompanied by increased NOS2 catalytic activity, steady state mRNA levels, and promoter activation. These results demonstrate that submillimolar doses of two commonly used local anesthetics can increase glial NOS2 expression.

Anesthetics, Local↗
PubMed2001

Framing the nicotine debate: a cultural approach to risk.

This study examined Congressional testimony concerning regulation of tobacco advertising by 3 policy factions representing industry, government, and lay activists. On the basis of the cultural theory of risk, policy disputants were divided into entrepreneurial, bureaucratic, and egalitarian communities, each with a distinct cosmology that impedes discourse among the groups. The authors examined ways in which the 3 policy factions framed the tobacco advertising issues to see the extent to which such unique cosmologies were expressed or whether mutual frames might signal opportunities for negotiation among the interest groups. Major themes in the testimony were identified through semantic network analysis and clustering of associated words that revealed discourse patterns peculiar to each group and reflective of their cultural biases toward health risk. Semantic network analysis can be a tool to clarify these presuppositions and unmask relations among factions, thereby bridging policy solutions across interest groups.

Advertising↗
PubMed2001

Assessment clues.

Explore the source record for details and available documents.

Decision Making↗
PubMed2001

You did what? Clinical errors in EMS.

It was late and you were exhausted. You ran a call that didn't go the way you would have liked. Errors occurred. What actions do you take when your partner is making mistakes? When do you step in? Do you step in? What if there's more to the errors than you realize? This article provides guidelines for EMS personnel to consider when dealing with a scenario that contains clinical errors. Although not an all-inclusive list, the examples and solutions may be beneficial to providers, including rookies and veterans.

Communication↗
PubMed2001

Faith conquers all? Beliefs about the role of religious factors in coping with depression among different cultural-religious groups in the UK.

How effective is religious activity believed to be in coping with depression? This study assessed the perceived effectiveness of different religious activities--previously identified as important in coping--among 282 people in the UK. The mean age was 25 years, and participants were either Christian, Hindu,Jewish, Muslim, other religion, or no religion. Relative to other kinds of help for depression, religious activity was not seen as particularly helpful for depression. Religious activity was seen as less helpful by the ever-depressed than by the never-depressed and as less helpful by women than by men. Among religious activities, faith and prayer were seen as the most helpful. Muslims believed more strongly than other groups in the efficacy of religious coping methods for depression, were most likely to say they would use religious coping behaviour, and were least likely to say they would seek social support or professional help for depression. Other differences between groups were also observed, and comparisons with qualitative material obtained in an earlier study were made. The implications of these findings for help-seeking are considered.

Adaptation, Psychological↗
PubMed2000

Reduction of Abeta accumulation in the Tg2576 animal model of Alzheimer's disease after oral administration of the phosphatidyl-inositol kinase inhibitor wortmannin.

The abnormal accumulation of the amyloid beta protein (Abeta) has been implicated as an early and critical event in the etiology and pathogenesis of Alzheimer's disease (AD). Compounds that reduce Abeta accumulation may therefore be useful therapeutically. In cell-based screens we detected a significant reduction in Abeta concentration after treatment with the phosphatidylinositol kinase inhibitors wortmannin and LY294002. To determine the effect of this class of compounds on in vivo Abeta accumulation, we administered wortmannin to the Tg2576 mouse model of AD. Oral administration of wortmannin over four months resulted in a significant, non-overlapping 40%-50% reduction in the number of senile plaques, one of the pathological hallmarks of AD. Sandwich ELISA analysis of formic acid extractable Abeta in the brain of treated animals indicates that both Abeta40 and the longer, more amyloidogenic form of the peptide, Abeta42, were significantly reduced. These data provide the first direct evidence that compounds identified by their ability to reduce Abeta concentration in vitro can reduce Abeta accumulation and deposition in the brain, thus establishing a basic paradigm for the identification and evaluation of additional compounds that lower Abeta accumulation.

Administration, Oral↗
PubMed2000

The regulation of leptin gene expression in the C6 glioblastoma cell line.

The hormone leptin is implicated in the regulation of appetite and body weight in rodents, primates and humans. We reported that the leptin gene (ob) is expressed in the brain, but the factors which control ob expression in the central nervous system are not known. We previously showed that brain-derived rat C6 glioblastoma cells express ob mRNA and protein. In the present study we examined the regulation of ob expression in C6 cells. Leptin and leptin receptor immunoreactivity was detected in C6 cells, suggesting a possible autocrine role for leptin. The identity of the leptin immunoreactivity (OB-ir) in C6 cells was confirmed by immunoprecipitation and Western blotting using two leptin specific polyclonal antibodies. Using RT-PCR analysis a product of the expected size for the short, but not the long, leptin receptor isoform was detected in C6 cells. Cells were maintained in serum-free (SF) media for 0-24 h in the presence of various regulators of leptin expression. Leptin mRNA levels were significantly higher in cells treated with dbcAMP (1 mM), IGF 1 (100 ng/ml) or insulin (5 microg/ml) compared to SF controls. In contrast, corticosterone (10(-7)M) reduced leptin mRNA. In the presence of dbcAMP, C6 cells undergo a dramatic alteration in morphology which is coincident with an apparent increase in the number of leptin-ir nuclei and an increase in leptin immunoreactivity. In contrast to C6 cells, glucocorticoids are reported to increase leptin levels in adipocytes/adipose tissue, while increases in intracellular cAMP levels are reported to reduce leptin levels. Overall, our in vitro data suggest that the regulation of leptin gene expression in C6 glioblastoma cells is different from that in adipocytes.

Animals↗
PubMed2000

Predictors of ovarian follicle number.

OBJECTIVE: To identify factors associated with ovarian follicle density in women of reproductive age. DESIGN: Women undergoing incidental oophorectomy responded to structured interviews. Grossly normal ovaries were sectioned and assessed for follicle density. SETTING: University hospital. PATIENT(S): 102 women undergoing hysterectomy with incidental oophorectomy who had morphologically normal ovaries. MAIN OUTCOME MEASURE(S): Follicle density, age, parity, oral contraceptive use, body size, smoking, and alcohol consumption. RESULT(S): Follicle density decreased with age and with current or past cigarette smoking. Other factors were not associated with follicle density, although the study had adequate power to detect only strong associations. CONCLUSION(S): Some of the adverse effects of smoking on reproductive health may be due to irreversible follicular depletion.

Adult↗
PubMed2000

Expression of the bZIP transcription factor TCF11 and its potential dimerization partners during development.

TCF11 (also known as Nrf1 and LCR-F1) is a basic-region leucine-zipper (b-ZIP) transcription factor that is essential during embryonic development. We have carried out expression analysis at a number of developmental stages and find that while there is some localized elevated expression between 8 and 9 days post coitum (dpc), the gene is widely expressed with a constant level of mRNA transcripts detectable in all tissues and at all stages examined. However, this does not reflect the specific nature of a TCF11 mutant phenotype (EMBO J. 17 (1998) 1779) which shows an essential role in foetal liver haematopoiesis. The specificity of TCF11 function may be controlled at a post-transcriptional level including availability of, and specific interaction with, a range of potential heterodimerization partners. We therefore carried out expression analysis of four candidate partner molecules; the three small Maf genes and another bZIP transcription factor found to bind to TCF11 in a two-hybrid screen, ATF4. We show different patterns of expression for the three Maf genes during development with MafG being widely expressed, MafK expressed only later in development and in specific tissues, and no detection of MafF. ATF4 shows evidence of complex regulation during development and shows elevated expression in many of the same sites as TCF11.

Activating Transcription Factor 4↗
PubMed2000

A novel alpha-amylase gene is transiently upregulated during low temperature exposure in apple fruit.

An alpha-amylase gene product was isolated from apple fruit by reverse-transcriptase PCR using redundant primers, followed by 5' and 3' RACE. The gene is a member of a small gene family. It encodes a putative 46.9 kDa protein that is most similar to an alpha-amylase gene from potato (GenBank accession M79328). In apple fruit this new gene was expressed at low levels, as detected by reverse-transcriptase PCR, in a number of plant tissues and during fruit development. Highest levels of mRNA for this transcript were observed 3 to 9 days after placing apple fruit at 0.5 degrees C. Phylogenetic analysis of amino acid sequence places the potato and apple proteins as a distinct and separate new subgroup within the plant alpha-amylases, which appears to have diverged prior to the split between monocotyledonous and dicotyledonous plants. These two divergent alpha-amylases lack the standard signal peptide structures found in all other plant alpha-amylases, and have sequence differences within the B-domain and C-domain. However, comparisons with structures of known starch hydrolases suggest that these differences are unlikely to affect the enzymatic alpha-1,4-amylase function of the protein. This is the first report of upregulation of a dicotyledonous alpha-amylase in response to low temperature, and confirms the presence of a new family of alpha-amylases in plants.

Amino Acid Sequence↗
PubMed2000

Intravenous clonidine infusion in critically ill children: dose-dependent sedative effects and cardiovascular stability.

Clonidine is used for analgesia and sedation in paediatric anaesthesia, but there are no data on its sedative properties and side effects in critically ill children. We studied 30 ventilated children aged 10 yr and under to determine an effective i.v. dosing range and to assess its cardiovascular effects. Twenty non-paralysed, ventilated children were given a background infusion of midazolam 50 micrograms kg-1 h-1 combined with a variable clonidine infusion (0.1-2 micrograms kg-1 h-1) to maintain optimal sedation. The effects of clonidine 1 microgram kg-1 h-1 on cardiac index were measured in 10 postoperative cardiac patients using a reverse Fick method. Dose-dependent sedation was achievable (713 out of 861 h) without cardiovascular side effects, but an infusion limit of clonidine 1 microgram kg-1 h-1 was inadequate in two patients. An increased dose limit of 2 micrograms kg-1 h-1 combined with midazolam 50 micrograms kg-1 h-1 achieved satisfactory sedation scores for 602 out of a total of 672 h studied with no failures. Clonidine in combination with midazolam at 1 microgram kg-1 h-1 was not associated with significant changes in heart rate arterial pressure or cardiac index.

Adrenergic alpha-Agonists↗
PubMed2000

Acute neurologic deterioration following lumbar puncture in an epidural abscess occurring 14 months after epidural catheter placement.

We report the case of a 19-year-old girl admitted to the hospital with a 2-month history of back pain and a 1-week history of severe weakness, who underwent a diagnostic lumbar puncture which was swiftly followed by acute neurologic deterioration requiring ventilation. She was subsequently shown to have an epidural abscess extending from the second cervical to the fifth lumbar vertebrae. She had received uneventful epidural analgesia for childbirth 14 months previously. The case is unusual in both the acute deterioration following lumbar puncture, and also in the length of time from epidural siting to abscess formation, if this were indeed the source of the infection.

Adult↗