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G Sweeney

Publications and source records attributed to G Sweeney.

At least 37 records · Page 2Linked to original sources
PubMed2000

Significant event audit in practice: a preliminary study.

BACKGROUND: While well described and promoted as a useful activity, there remains a paucity of evidence on the process and experience of significant event audit (SEA) in primary care. To date, the most comprehensive evaluation of the process has been produced by comparing SEA with conventional audit. The current study intends to contribute to the debate by examining the attitudes and perceptions of a range of primary care staff who have been involved in the process. OBJECTIVES: The aim of this study was to identify participants' perceptions of the benefits and problems associated with SEA in the context of primary care, and to derive suggestions which might improve the process of SEA. METHODS: Semi-structured interviews of 12 participants from a variety of primary care disciplines were conducted, using grounded theory to analyse the results. RESULTS: A set of six perceptions and seven recommendations for the facilitation of SEA were produced. CONCLUSIONS: SEA constitutes a powerful tool, which can contribute to team building, enhanced communication and improved patient care, and represents a vital contributor to the development of clinical governance in primary care. However, its implementation and sustenance require sensitive handling for optimal benefit and to minimize difficulties. Our research has enabled us to propose suggestions to facilitate these processes.

Adult↗
PubMed2000

Regulation of the Na,K-pump by leptin in 3T3-L1 fibroblasts.

Leptin, the product of the obesity (ob) gene, controls energy intake and expenditure primarily by actions on the central nervous system. However, recently it has become apparent that leptin also elicits a growing and diverse array of effects on peripheral tissues. The Na,K-pump is an electrogenic plasma membrane protein which actively extrudes 3Na+ ions and imports 2K+ ions per molecule of ATP hydrolysed. The pump is responsible for the maintenance of the electrochemical potential of all cells, which in turn drives all ion-coupled transport mechanisms. In this study we use 3T3-L1 fibroblasts to show that leptin inhibits Na,K-pump activity, as assessed by ouabain-sensitive 86Rb+ uptake. Inhibition of the Na,K-pump correlated with increased serine phosphorylation of the catalytic Na,K-pump alpha1 subunit. Upon investigation of leptin-stimulated signalling pathways using specific pharmacological inhibitors, only wortmannin prevented inhibition of the Na,K-pump by leptin. Moreover, leptin stimulated phosphotyrosine-associated PI 3-kinase activity in these cells. In summary, leptin was found to inhibit Na,K-pump activity, likely via PI 3-kinase. We propose that this effect may have wide ranging cardiovascular and metabolic implications and perhaps explain physiological effects of the hormone such as natriuresis.

3T3 Cells↗
PubMed2000

Activation of p38 mitogen-activated protein kinase alpha and beta by insulin and contraction in rat skeletal muscle: potential role in the stimulation of glucose transport.

The stress-activated p38 mitogen-activated protein kinase (MAPK) was recently shown to be activated by insulin in muscle and adipose cells in culture. Here, we explore whether such stimulation is observed in rat skeletal muscle and whether muscle contraction can also affect the enzyme. Insulin injection (2 U over 3.5 min) resulted in increases in p38 MAPK phosphorylation measured in soleus (3.2-fold) and quadriceps (2.2-fold) muscles. Increased phosphorylation (3.5-fold) of an endogenous substrate of p38 MAPK, cAMP response element binder (CREB), was also observed. After in vivo insulin treatment, p38 MAPKalpha and p38 MAPKbeta isoforms were found to be activated (2.1- and 2.4-fold, respectively), using an in vitro kinase assay, in immunoprecipitates from quadriceps muscle extracts. In vitro insulin treatment (1 nmol/l over 4 min) and electrically-induced contraction of isolated extensor digitorum longus (EDL) muscle also doubled the kinase activity of p38 MAPKalpha and p38 MAPKbeta. The activity of both isoforms was inhibited in vitro by 10 micromol/l SB203580 in all muscles. To explore the possible participation of p38 MAPK in the stimulation of glucose uptake, EDL and soleus muscles were exposed to increasing doses of SB203580 before and during stimulation by insulin or contraction. SB203580 caused a significant reduction in the insulin- or contraction-stimulated 2-deoxyglucose uptake. Maximal inhibition (50-60%) occurred with 10 micromol/l SB203580. These results show that p38 MAPKalpha and -beta isoforms are activated by insulin and contraction in skeletal muscle. The data further suggest that activation of p38 MAPK may participate in the stimulation of glucose uptake by both stimuli in rat skeletal muscle.

Animals↗
PubMed1999

An inhibitor of p38 mitogen-activated protein kinase prevents insulin-stimulated glucose transport but not glucose transporter translocation in 3T3-L1 adipocytes and L6 myotubes.

The precise mechanisms underlying insulin-stimulated glucose transport still require investigation. Here we assessed the effect of SB203580, an inhibitor of the p38 MAP kinase family, on insulin-stimulated glucose transport in 3T3-L1 adipocytes and L6 myotubes. We found that SB203580, but not its inactive analogue (SB202474), prevented insulin-stimulated glucose transport in both cell types with an IC50 similar to that for inhibition of p38 MAP kinase (0.6 microM). Basal glucose uptake was not affected. Moreover, SB203580 added only during the transport assay did not inhibit basal or insulin-stimulated transport. SB203580 did not inhibit insulin-stimulated translocation of the glucose transporters GLUT1 or GLUT4 in 3T3-L1 adipocytes as assessed by immunoblotting of subcellular fractions or by immunofluorescence of membrane lawns. L6 muscle cells expressing GLUT4 tagged on an extracellular domain with a Myc epitope (GLUT4myc) were used to assess the functional insertion of GLUT4 into the plasma membrane. SB203580 did not affect the insulin-induced gain in GLUT4myc exposure at the cell surface but largely reduced the stimulation of glucose uptake. SB203580 had no effect on insulin-dependent insulin receptor substrate-1 phosphorylation, association of the p85 subunit of phosphatidylinositol 3-kinase with insulin receptor substrate-1, nor on phosphatidylinositol 3-kinase, Akt1, Akt2, or Akt3 activities in 3T3-L1 adipocytes. In conclusion, in the presence of SB203580, insulin caused normal translocation and cell surface membrane insertion of glucose transporters without stimulating glucose transport. We propose that insulin stimulates two independent signals contributing to stimulation of glucose transport: phosphatidylinositol 3-kinase leads to glucose transporter translocation and a pathway involving p38 MAP kinase leads to activation of the recruited glucose transporter at the membrane.

3-O-Methylglucose↗
PubMed1999

Participation of PI3K and atypical PKC in Na+-K+-pump stimulation by IGF-I in VSMC.

The activity of the Na+-K+-pump is intricately linked to the maintenance of vascular tone. Here we demonstrate that insulin-like growth factor I (IGF-I) increases Na+-K+-pump activity in the vascular smooth muscle cell (VSMC) clone A7r5 in a time- and dose-dependent manner. This stimulatory effect of IGF-I was prevented by the tyrosine kinase inhibitor genistein (5 microM) and by the specific phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin (100 nM) and LY-294002 (25 microM). IGF-I activated a wortmannin-sensitive PI3K and its purported effector, the atypical protein kinase C (PKC)-zeta. Stimulation of PKC-zeta was prevented by the generic PKC inhibitor GF109203x (bisindolylmaleimide, 10 microM). Downregulation of diacylglycerol-sensitive (conventional and novel) PKCs by 24-h pretreatment with 1 microM phorbol 12-myristate 13-acetate had no effect on IGF-I-stimulated Na+-K+-pump activity. Similarly, inhibition of only conventional and novel PKCs with GF109203x (1 microM) had no effect on IGF-I-stimulated Na+-K+-pump activity. In contrast, a concentration of GF109203x (10 microM) that also inhibits the atypical PKCs abolished Na+-K+-pump stimulation by IGF-I. Neither the Na+-K+-2Cl- cotransporter inhibitor bumetanide (100 microM) nor the Na+/H+ exchanger inhibitor HOE-694 (5 microM) affected the Na+-K+-pump stimulation by IGF-I, suggesting that a rise in intracellular Na+ concentration is not necessary for increased Na+-K+-pump activity. These results suggest that IGF-I directly stimulates the Na+-K+ pump via a signaling pathway involving PI3K and atypical PKC (zeta).

Cell Line↗
PubMed1999

The challenge for basic science education in problem-based medical curricula.

There has been intense debate about medical curriculum reform since the early 1950s. The last 25 years have seen a steady shift ward problem-based learning curriculum design in schools of medicine and allied health sciences. This trend has been less challenging for clinical departments than for departments of basic science, where it has often evoked anxiety, antipathy, lack of cooperation, and general mistrust. This appears paradoxical, as problem-based learning (PBL) is promoted as an improved method of integrating scientific concepts, and the advances that drive much of modern medical practice are advances in the basic sciences. While proponents of PBL argue that the approach promotes better integration and use of scientific concepts, the evidence, such as it is, is against this. As well, other evidence suggests that clinicians do not use basic science concepts extensively in their practice. This then questions the utility of scientific knowledge in a medical curriculum. This article examines this notion of utility (the quality or state of being useful), to establish some ground rules for what does, and does not, possess utility, and to present strategies to develop specific objectives from general statements concerning utility. Understanding of biologic and pathologic processes becomes of central importance and arguably possesses utility. If it is both required and evaluated, such understanding necessitates mastery of basic science concepts. Previously, the presentation of the basic sciences in medical curricula has emphasized the acquisition of knowledge rather than its use. Such learning has been perceived to lack utility; strategies to enhance the value of studying basic science concepts are suggested. If the importance of objectives in the basic medical sciences is accepted, these objectives should be achieved early in training, maintained at exit from medical school, and revisited in continuing medical education. The process of change in medical education initiated by Abraham Flexner early in this century remains incomplete. One reason why curricular changes have proved frustrating to basic scientists is that much of clinical medicine remains unnecessarily unscientific. Until clinical medicine itself changes, the utility of science in the training of a physician will remain difficult to demonstrate.

Curriculum↗
PubMed1998

Membrane-permeant esters of phosphatidylinositol 3,4,5-trisphosphate.

Phosphoinositide 3-OH kinases and their products, D-3 phosphorylated phosphoinositides, are increasingly recognized as crucial elements in many signaling cascades. A reliable means to introduce these lipids into intact cells would be of great value for showing the physiological roles of this pathway and for testing the specificity of pharmacological inhibitors of the kinases. We have stereospecifically synthesized di-C8-PIP3/AM and di-C12-PIP3/AM, the heptakis(acetoxymethyl) esters of dioctanoyl- and dilauroylphosphatidylinositol 3,4,5-trisphosphate, in 14 steps from myo-inositol. The ability of these uncharged lipophilic derivatives to deliver phosphatidylinositol 3,4,5-trisphosphate across cell membranes was demonstrated on 3T3-L1 adipocytes and T84 colon carcinoma monolayers. Insulin stimulation of hexose uptake into adipocytes was inhibited by the kinase inhibitor wortmannin and was largely restored by di-C8-PIP3/AM, which had no effect in the absence of insulin. Thus phosphatidylinositol 3,4,5-trisphosphate or a metabolite was necessary but not sufficient for stimulation of hexose transport. In T84 epithelial monolayers, di-C12-PIP3/AM mimicked epidermal growth factor in inhibiting chloride secretion and potassium efflux, suggesting that phosphatidylinositol 3,4, 5-trisphosphate was sufficient to modulate these fluxes and mediate epidermal growth factor's action.

3T3 Cells↗
PubMed1998

Insulin stimulation of K+ uptake in 3T3-L1 fibroblasts involves phosphatidylinositol 3-kinase and protein kinase C-zeta.

Despite the important physiological role of insulin in the regulation of ionic homeostasis, primarily mediated by the Na+/K(+)-ATPase and Na+/K+/2Cl- cotransporter, the intracellular signalling molecules mediating this effect of insulin have not been elucidated. Treatment of 3T3-L1 fibroblasts with insulin increased total 86Rb+ (K+) uptake from 0.8 +/- 0.04 to 1.02 +/- 0.05 nmol.mg-1.protein-1.min-1 (p < 0.005). These changes in K+ flux, though small, can alter the membrane potential. Uptake occurred through both the Na+/K(+)-ATPase and Na+/K+/2Cl- cotransporter and both were stimulated by insulin. Interestingly, when bumetanide was used to inhibit the Na+/K+/2Cl- cotransporter prior to insulin action, no increase in 86Rb+ uptake via the Na+/K(+)-ATPase was observed. The structurally distinct phosphatidylinositol 3-kinase inhibitors wortmannin (50-200 nmol/l) and LY294002 (50 mumol/l) attenuated both total insulin-stimulated 86Rb+ uptake as well as uptake via the Na+/K(+)-ATPase and Na+/K+/2Cl- cotransporter. Neither the inhibitor of p70.S6 kinase activation, rapamycin (30 ng/ml) nor the mitogen activated protein kinase kinase inhibitor, PD098059 (50 mumol/l), had any effect on insulin's stimulation of K+ influx. A 10 mumol/l concentration of the protein kinase C (PKC) inhibitor bisindolylmaleimide attenuated insulin action but at 1 mumol/l it was ineffective, suggesting involvement of the atypical PKC-zeta isoform. We conclude that insulin-stimulated K+ uptake in 3T3-L1 fibroblasts appears to involve concerted regulation of both the Na+/K(+)-ATPase and Na+/K+/2Cl- cotransporter and we show for the first time that this process is signalled via a pathway involving phosphatidylinositol 3-kinase and PKC-zeta.

3T3 Cells↗
PubMed1998

Lack of evidence for systemic toxicity following topical chloramphenicol use.

There has been considerable controversy regarding the safety of topical chloramphenicol in ophthalmic practice. The evidence for associated haematopoietic toxicity in idiosyncratic and dose-dependent forms was reviewed. The 7 cases of idiosyncratic haematopoietic reactions associated with topical chloramphenicol reported in the literature are refutable evidence for the existence of such a response. In Scotland, despite extensive prescription of topical chloramphenicol, the incidence of acquired aplastic anaemia was found to be low, as were associated reports of blood dyscrasias throughout the UK. The epidemiology of acquired aplastic anaemia failed to make an association with topical chloramphenicol use. High-performance liquid chromatography (minimum detection limit 1 mg/l) was used to investigate whether serum accumulation of chloramphenicol occurred after topical therapy in 40 patients. The mean dose of chloramphenicol eye drops used after 1 week of treatment was 8.0 mg, and after 2 weeks, 15.3 mg. As expected, chloramphenicol failed to accumulate to detectable levels. This supported the view that topical chloramphenicol was not a risk factor for inducing dose-related bone marrow toxicity. Calls for the abolition of treatment with topical chloramphenicol based on current data are not supported.

Adult↗
PubMed1998

An audit of therapeutic drug monitoring service provision by laboratories participating in an external quality assessment scheme.

Therapeutic drug monitoring services were investigated in a questionnaire sent to all subscribers to the United Kingdom National External Quality Assessment Scheme for Therapeutic Drug Assays. Questions were posed on assay availability and use, target ranges, and reporting procedures for digoxin, lithium, phenytoin, phenobarbitone, carbamazepine, theophylline, and valproic acid. One hundred fifty-seven laboratories replied and, except for lithium, 45% reported in mass units, 34% in molar units, and 22% a mixture of mass and molar units. Target ranges for lithium, digoxin, carbamazepine, and phenobarbitone were highly variable but ranges for phenytoin, theophylline, and valproic acid were more consistent. Immunoassay was the most popular methodology although high-performance liquid chromatography was commonly used for anticonvulsants. Paper copies of results were provided by 93% of laboratories, 40% reported by telephone, 12% by fax, and 28% by computer. Additional data, mainly dose, time of last dose, and duration of therapy were requested by 55% to 67% of laboratories. Grades of staff authorizing results ranged from nurses to senior consultants, and collaboration with pharmacists occurred in 26% of laboratories. Most laboratories provided a daily analytical service and 73% offered a 24-hour emergency service. This audit unexpectedly identified use of a wide range of target concentrations, particularly for digoxin and lithium.

Drug Monitoring↗
PubMed1998

Temporal activation of p70 S6 kinase and Akt1 by insulin: PI 3-kinase-dependent and -independent mechanisms.

Several studies have suggested that activation of p70 ribosomal S6 kinase (p70 S6 kinase) by insulin may be mediated by the phosphatidylinositol 3-kinase (PI 3-kinase)-Akt pathway. However, by temporal analysis of the activation of each kinase in L6 muscle cells, we report that the activation of the two serine/threonine kinases (Akt and p70 S6 kinase) can be dissociated. Insulin stimulated p70 S6 kinase in intact cells in two phases. The first phase (5 min) of stimulation was fully inhibited by wortmannin (IC50 = 20 nM) and LY-294002 (full inhibition at 5 microM). After this early inhibition, p70 S6 kinase was gradually stimulated by insulin in the presence of 100 nM wortmannin. After 30 min, the stimulation was 65% of the maximum attained in the absence of wortmannin. The IC50 of wortmannin for inhibition of this second phase was approximately 150 nM. In contrast, activation of Akt1 by insulin was completely inhibited by 100 nM wortmannin at all time points investigated. Inhibition of mitogen-activated protein kinase/extracellular signal-regulated protein kinase kinase with PD-098059 (10 microM) or treatment with the protein kinase C inhibitor bisindolylmaleimide (10 microM) had no effect on the late phase of insulin stimulation of p70 S6 kinase. We have previously shown that GLUT-1 protein synthesis in these cells is stimulated by insulin via the mTOR-p70 S6 kinase pathway, based on its sensitivity to rapamycin. We therefore investigated whether the signals leading to GLUT-1 synthesis correlated with the early or late phase of stimulation of p70 S6 kinase. GLUT-1 synthesis was not inhibited by wortmannin (100 nM). In summary, insulin activates p70 ribosomal S6 kinase in L6 muscle cells by two mechanisms, one dependent on and one independent of the activation of PI 3-kinase. In addition, activation of Akt1 is fully inhibited by wortmannin, suggesting that Akt1 does not participate in the late activation of p70 S6 kinase. Wortmannin-sensitive PI 3-kinases and Akt1 are not required for insulin stimulation of GLUT-1 protein biosynthesis.

Androstadienes↗
PubMed1998

Regulation of the Na+/K+-ATPase by insulin: why and how?

The sodium-potassium ATPase (Na+/K+-ATPase or Na+/K+-pump) is an enzyme present at the surface of all eukaryotic cells, which actively extrudes Na+ from cells in exchange for K+ at a ratio of 3:2, respectively. Its activity also provides the driving force for secondary active transport of solutes such as amino acids, phosphate, vitamins and, in epithelial cells, glucose. The enzyme consists of two subunits (alpha and beta) each expressed in several isoforms. Many hormones regulate Na+/K+-ATPase activity and in this review we will focus on the effects of insulin. The possible mechanisms whereby insulin controls Na+/K+-ATPase activity are discussed. These are tissue- and isoform-specific, and include reversible covalent modification of catalytic subunits, activation by a rise in intracellular Na+ concentration, altered Na+ sensitivity and changes in subunit gene or protein expression. Given the recent escalation in knowledge of insulin-stimulated signal transduction systems, it is pertinent to ask which intracellular signalling pathways are utilized by insulin in controlling Na+/K+-ATPase activity. Evidence for and against a role for the phosphatidylinositol-3-kinase and mitogen activated protein kinase arms of the insulin-stimulated intracellular signalling networks is suggested. Finally, the clinical relevance of Na+/K+-ATPase control by insulin in diabetes and related disorders is addressed.

Animals↗
PubMed1997

Phosphodiesterase isoforms in the pulmonary arterial circulation of the rat: changes in pulmonary hypertension.

Phosphodiesterase (PDE) activity was determined in pulmonary arteries removed from control and chronic hypoxia-induced pulmonary hypertensive rats. The main, first-branch, intrapulmonary and resistance pulmonary arteries were studied. We measured total cAMP PDE activity and cGMP PDE activity, as well as that of individual isoforms (PDE1-5). cAMP PDE activity in chronic hypoxic rats was increased in first-branch and intrapulmonary arteries from hypoxic rats. No changes were observed in the main or resistance pulmonary arteries. Similarly, cGMP PDE activity was increased in the main, first-branch and intra-pulmonary arteries of the hypoxic rats. No changes in cGMP PDE activity were observed in resistance arteries. There was evidence for PDE1-5 activity in all pulmonary arteries. The increased cAMP PDE activity in first-branch and intrapulmonary vessels was associated with an increase in cilostimide-inhibited PDE (PDE3) activity. Increased total cGMP PDE in main pulmonary artery was associated with increases in Ca++/calmodulin-stimulated (PDE1) activity. An increase in zaprinast-inhibited (PDE5) activity was observed in first-branch and intrapulmonary arteries. Our results suggest that decreases in intracellular cyclic nucleotide levels in pulmonary arteries from pulmonary hypertensive rats are associated with increased PDE activity. Further, these changes may reflect alterations at the level of specific types of PDE isoforms.

Animals↗
PubMed1996

5-Hydroxytryptamine receptors mediating vasoconstriction in pulmonary arteries from control and pulmonary hypertensive rats.

1. We investigated 5-hydroxytryptamine (5-HT)-receptor mediated vasoconstriction in the main, first branch and resistance pulmonary arteries removed from control and pulmonary hypertensive rats. Contractile responses to 5-HT, 5-carboxamidotryptamine (5-CT, non-selective 5-HT1 agonist), and sumatriptan (5-HT1D-like receptor agonist) were studied. The effects of methiothepin (non-selective 5-HT1 + 2-receptor antagonist) and ketanserin (5-HT2A receptor antagonist) and GR55562 (a novel selective 5-HT1D receptor antagonist) on 5-HT-mediated responses were also studied. Basal levels of adenosine 3':5'-cyclic monophosphate ([cyclic AMP]i) and guanosine 3':5'-cyclic monophosphate ([cyclic GMP]i) were determined and we assessed the degree of inherent tone in the vessels under study. 2. 5-HT was most potent in the resistance arteries. pEC50 values were 5.6 +/- 0.1, 5.3 +/- 0.1, 5.0 +/- 0.2 in the resistance arteries, pulmonary branch and main pulmonary artery, respectively (n = at least 5 from 5 animals). The sensitivity to, and maximum response of, 5-HT was increased in all the arteries removed from the chronic hypoxic (CH) rats. In CH rats the pEC50 values were 5.9 +/- 0.2, 6.3 +/- 0.2, 6.4 +/- 0.2 and the increase in the maximum response was 35%, 51% and 41% in the resistance arteries, pulmonary branch and main pulmonary artery, respectively. Sumatriptan did not contract any vessel from the control rats whilst 5-CT did contract the resistance arteries. In the CH rats, however, they both contracted the resistance arteries (responses to sumatriptan were small) (pEC50: 5-CT; 5.4 +/- 0.2) and the pulmonary artery branches (pEC50: sumatriptan, 5.4 +/- 0.2; 5-CT, 5.4 +/- 0.2). 5-CT also caused a contraction in the main pulmonary artery (pEC50: 6.0 +/- 0.3). 3. Ketanserin (1 nM-1 microM) caused a competitive antagonism of the 5-HT response in all vessels tested. In control rats, the estimated pKb values for ketanserin in resistance arteries, pulmonary branches and main pulmonary artery were 8.3, 7.8 and 9.2, respectively. Methiothepin (1 nM-1 microM) inhibited responses to 5-HT in the first branch (estimated pKb value: 7.8) and main pulmonary artery. In CH rats, the estimated pKb values for ketanserin in resistance arteries, pulmonary branches and main pulmonary artery were 7.7, 8.3 and 9.6, respectively. Methiothepin also inhibited contractions to 5-HT in the pulmonary artery branch and main pulmonary artery with estimated pKb values of 7 and 9.5, respectively. In control animals, GR55562 had no effect on responses to 5-HT in any of the vessels tested. In the CH rats the estimated pKb values for GR55562 were 6.5, 7.8 and 7.0 in the pulmonary resistance arteries, first branch and main pulmonary artery, respectively. 4. Large pulmonary arteries from controls demonstrated inherent tone and this was increased three fold in the CH rats. The resistance arteries from controls demonstrated little inherent tone though this was enhanced in those from the CH rats. 5. [Cyclic AMP]i was 259 +/- 23 pmol mg-1 protein in the pulmonary artery branches removed from control rats and decreased to 192 +/- 11 pml mg-1 protein in the CH rats (P < 0.01, n = 8). [Cyclic GMP]i also decreased in the pulmonary artery branches (from 550 +/- 15, control to 462 +/- 31 pmol mg-1 protein in CH vessels, n = 8, P < 0.01) and in the main pulmonary arteries (from 566 +/- 33, control to 370 +/- 25 pmol mg-1 protein in CH vessels, n = 8, P < 0.001). No changes in either [cyclic AMP]i or [cyclic GMP]i were observed in the resistance arteries. 6. The results suggest that the increased vasoconstrictor response to 5-HT in CH rat pulmonary arteries is due to an increase in 5-HT2A-receptor mediated contraction combined with an increase in r5-HT1B-like receptor-mediated contraction. An increase in vascular tone and decreased levels of [cyclic GMP]i in the large pulmonary arteries may contribute to the observed increase in activity of r5-HT1B-like receptor

Animals↗
PubMed1996

Are schools safer for children than public places?

OBJECTIVE: To investigate the frequency and severity of accidents to children in schools. METHODS: Retrospective analysis of accidents occurring in school over a six month period and resulting in attendance at an accident and emergency department. Comparison was made with accidents occurring in public places, RESULTS: During the study period there were 127 school and 251 public place accidents causing fractures or dislocations requiring hospital treatment in 3-16 year old children; 22.4% (127/567) of all injuries at school resulted in fractures or dislocations, as opposed to 20.8% (251/1197) of those sustained in public places. CONCLUSIONS: Injuries at school are a cause for concern as they occur in a supervised environment and this should be the target of accident prevention measures.

Accident Prevention↗
PubMed1996

Stress experiences of occupational therapists in mental health practice arenas: a review of the literature.

The experience of job stress and burnout in occupational therapy has received only scant attention in the literature, although occupational therapists (OTs) share a number of important characteristics with other health care professionals that leave them vulnerable to the experience of stress. In addition, this group has a number of unique personal and work-related characteristics that could serve to increase its risk profile. Little effort has been directed at delineating work-related stressors or experienced levels of stress within different practice arenas of occupational therapy, even though some specialisms (e.g. mental health, forensic psychiatry, learning disabilities or paediatrics) are likely to be more emotionally demanding than others. There are a number of indicators which confirm that job stress is an issue for OTs, although some of the empirical data suggests that, on average, this occupational group experience less burnout than other human service professionals.

Adaptation, Psychological↗
PubMed1996

Ethanolamine and choline phospholipids in nascent very-low-density lipoprotein particles.

OBJECTIVE: To establish methods to examine the polar lipids of triglyceride-rich lipoproteins (TRLs) and to examine postprandial changes in glycerophosphocholine (PC) and glycerophosphoethanolamine (PE) polar lipids and in the ratio of diacyl to alkenylacyl components. The membrane phospholipids of TRLs have received little attention. PC and PE constitute major fractions and both comprise diacyl- and alkenylacyl-phospholipids. There has been recent interest in possible antioxidant properties of alkenylacyl (plasmalogen) PE. DESIGN: Analysis of PE and PC fractions in blood samples taken from the subjects while fasting and at four 2-h intervals after eating a 4749-kJ breakfast. PARTICIPANTS: Five healthy subjects. OUTCOME MEASURES: Levels of PE and PC fractions isolated from blood samples by ultracentrifugation (to isolate the d < 1.006 fraction of plasma) and reversed-phase chromatography. RESULTS: The concentration of triglyceride in particles of density less than 1.006 g/cm2 in the samples increased rapidly, peaking 4 h after the meal at 0.51 mmol/L above the fasting level. Apolipoprotein B-48 was maximal in the sample taken 2 h after eating and below 1%, as a percentage of apolipoproteins B-48 and B-100, in all other samples. The concentration of PC exceeded that of PE by an order of magnitude, but there was a proportionately greater increase in PE postprandially. PE contained a rapidly cleared alkenylacyl fraction, which was maximal (at a threefold increase over the baseline level) in the sample taken 4 h after eating. CONCLUSIONS: As blood triglyceride levels rise and fall postprandially, the polar lipid composition of the TRLs also changes; these changes are more marked in the PE than in the PC fraction. The fact that the level of the PE fraction peaked later (at 4 h after eating) than that of B-48 apolipoprotein (which peaked at 2 h after eating) suggests that the peak in the PE fraction had a hepatic (very-low-density lipoprotein) origin. Alkenylacyl (plasmalogen) phospholipid accompanied both PE and PC fractions but was about 10 times greater in PE. This result is significant if alkenylacyl PE does indeed function as an antioxidant.

Chromatography, High Pressure Liquid↗