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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 91 records · Page 5Linked to original sources

Age-related risk for HIV infection in men who have sex with men: examination of behavioral, relationship, and serostatus variables.

The study examined behavioral, relationship, and serostatus variables that potentially contribute to HIV infection risk in three age groups of men who have sex with men (MSM). MSM recruited in West Hollywood, California self-administered a questionnaire measuring unprotected insertive anal intercourse (UIAI) and unprotected receptive anal intercourse (URAI) with primary and nonprimary partners. The following relationship/serostatus variables were also assessed: recency of HIV testing, knowledge of own HIV serostatus, perception of partner's serostatus, seroconcordance (self and partner seronegative), and self-reported monogamy status. The prevalence of UIAI and URAI was higher with primary than nonprimary partners. These sexual risk behaviors with primary partners were substantially more prevalent among men younger than 25 years of age than among men aged 25 to 30 or over age 30. UIAI and URAI with nonprimary partners were uncommon in each age group, and there were no significant age differences on the serostatus and relationship variables. The findings suggest that young MSM may be at elevated risk for contracting HIV by virtue of their sexual risk behavior with primary partners. Targeted interventions for MSM need to address sexual risk in the context of primary relationships.

AIDS Serodiagnosis↗

Determinants of coronary blood flow after thrombolytic administration. TIMI Study Group. Thrombolysis in Myocardial Infarction.

OBJECTIVES: This study evaluated the determinants of coronary blood flow following thrombolytic administration in a large cohort of patients. BACKGROUND: Tighter residual stenoses following thrombolysis have been associated with slower coronary blood flow, but the independent contribution of other variables to delayed flow has not been fully explored. METHODS: The univariate and multivariate correlates of coronary blood flow at 90 min after thrombolytic administration were examined in a total of 2,195 patients from the Thrombolysis in Myocardial Infarction (TIMI) 4, 10A, 10B and 14 trials. The cineframes needed for dye to first reach distal landmarks (corrected TIMI frame count, CTFC) were counted as an index of coronary blood flow. RESULTS: The following were validated as univariate predictors of delayed 90-min flow in two cohorts of patients: a greater percent diameter stenosis (p < 0.0001 for both cohorts), a decreased minimum lumen diameter (p = 0.0003, p = 0.0008), a greater percent of the culprit artery distal to the stenosis (p = 0.03, p = 0.02) and the presence of any of the following: delayed achievement of patency (i.e., between 60 and 90 min) (p < 0.0001 for both cohorts), a culprit location in the left coronary circulation (left anterior descending or circumflex) (p = 0.02, p < 0.0001), pulsatile flow (i.e., reversal of flow in systole, a marker of heightened microvascular resistance, p = 0.0003, p < 0.0001) and thrombus (p = 0.002, p = 0.03). Despite a minimal 16.4% residual stenosis following stent placement, the mean post-stent CTFC (25.8 +/- 17.2, n = 181) remained significantly slower than normal (21.0 +/- 3.1, n = 78, p = 0.02), and likewise 34% of patients did not achieve a CTFC within normal limits (i.e., <28 frames, the upper limit of the 95th percent confidence interval previously reported for normal flow). Those patients who failed to achieve normal CTFCs following stent placement had a higher mortality than did those patients who achieved normal flow (6/62 or 9.7% vs. 1/118 or 0.8%, p = 0.003). CONCLUSIONS: Lumen geometry is not the sole determinant of coronary blood flow at 90 min following thrombolytic administration. Other variables such as the location of the culprit artery, the duration of patency, a pulsatile flow pattern and thrombus are also related to slower flow. Despite a minimal 16% residual stenosis, one-third of the patients treated with adjunctive stenting still have a persistent flow delay following thrombolysis, which carries a poor prognosis.

Angioplasty, Balloon, Coronary↗

Heat shock protein expression in target cells infected with low levels of replication-competent virus contributes to the immunogenicity of adenoviral vectors.

A significant limitation of adenoviral vectors is their associated immunogenicity. Since we, and others, have shown that the immunogenicity of cells can be increased by the induction of heat shock proteins (hsp), and because infection with several viruses induces hsp, we investigated whether the immunogenicity of adenoviral gene transfer might be mediated through induction of hsp expression. Neither plasmid DNA nor a recombinant retroviral vector induced hsp expression in transduced B16 melanoma cells. However, hsp70 was upregulated after infection with two of six adenoviral vectors; this induction of hsp70 did not correlate with the adenoviral transgene or with the viral backbone (Ad2 or Ad5). In previous assays, no replication-competent adenovirus (RCA) had been detected in any of these viruses. However, using sensitive assays for RCA, induction of hsp70 was found to correlate with the transfer of E1A and low levels of RCA. Moreover, target cells expressing hsp70 at levels similar to those induced by RCA infection protected syngeneic mice against rechallenge with parental cells, demonstrating that cells induced to express hsp70 by inadvertant transfer of RCA will become immunogenic. These results reveal a novel mechanism contributing to the immunogenicity of adenoviral vectors. If careful screening for RCA is not used when using laboratory-prepared viral stocks, the validity of the resulting experimental data might be significantly affected, especially when the immune stimulatory effects of the transgene are being studied.

Adenoviruses, Human↗

Expression of nitric oxide synthase (NOS)-2 following permanent focal ischemia and the role of nitric oxide in infarct generation in male, female and NOS-2 gene-deficient mice.

Considerable evidence implicates nitric oxide (NO) in the pathological events following cerebral ischemia and, depending on the enzyme/cell source, NO is considered to be either damaging or protective. As a role for the enzyme nitric oxide synthase (NOS)-2 in permanent focal ischemia is not clear, we examined its expression following permanent middle cerebral artery occlusion in mice. At 24 h after occlusion, NOS-2 was expressed in cells infiltrating the infarct, while at later times, there was also expression in astrocytes around the infarct. To reveal a role for NO derived from this source, we compared infarct size in male and female mice with littermates in which the NOS-2 gene was disrupted. No differences were found between gender and genotype at 24 h. At 72 h, the infarct was increased in male mice, but not in females or in either gender with the gene disruption. These results suggest that NOS-2 plays a role in the later development of the infarct in male mice. Female mice are protected either against the damaging effects of NO, or because NOS-2 expression/activity is modulated by steroids.

Animals↗

Transcription of the human U2 snRNA genes continues beyond the 3' box in vivo.

The 3' box of the human class II snRNA genes is required for proper 3' processing of transcripts, but how it functions is unclear. Several lines of evidence suggest that termination of transcription occurs at the 3' box and the terminated transcript is then a substrate for processing. However, using nuclear run-on analysis of endogenous genes, we demonstrate that transcription continues for at least 250 nucleotides beyond the 3' box of the U2 genes. Although in vivo footprinting analysis of both the U1 and U2 genes detects no protein-DNA contacts directly over the 3' box, a series of G residues immediately downstream from the 3' box of the U1 gene are clearly protected from methylation by dimethylsulfate. In conjunction with the 3' box of the U1 gene, this in vivo footprinted region causes termination of transcription of transiently transfected U2 constructs, whereas a 3' box alone does not. Taken together, these results indicate that the 3' box is not an efficient transcriptional terminator but may act as a processing element that is functional in the nascent RNA.

Base Sequence↗

Transcriptional activation following cerebral ischemia in mice of a promoter-deleted nitric oxide synthase-2 gene.

Nitric oxide synthase (NOS)-2 is transcriptionally activated in a wide variety of injurious conditions, including cerebral ischemia, and the resulting nitric oxide is implicated both in tissue damage and recovery. Studies in vitro suggest that the proximal region of the NOS-2 promoter is obligatory for gene activation by proinflammatory cytokines. However, following cerebral ischemia in a NOS-2 gene-deficient mouse in which this region and exons 1-4 have been deleted, we find temporal and spatial expression, identical to wild-type, from a previously unidentified promoter region. The resulting protein is predicted to lack the first 113 amino acids and is NOS-2-incompetent. Fortuitously, this gene-deficient mouse presents a unique opportunity to determine more about the mechanisms of NOS-2 gene regulation in vivo.

Animals↗

Exhaled nitric oxide measurements in childhood asthma: techniques and interpretation.

In this review, we outline the role of nitric oxide in airway inflammation in children with asthma. We also discuss the various methods reported for measuring exhaled nitric oxide and provide some insight as to the pros and cons and pitfalls of these techniques. Guidelines for measurements of exhaled nitric oxide based on our experience are provided, as well as suggestions for the use of this technique as a new "airway inflammation test."

Asthma↗

Methodologic drift in the assessment of TIMI grade 3 flow and its implications with respect to the reporting of angiographic trial results. The TIMI Study Group.

BACKGROUND: The Thrombolysis in Myocardial Infarction (TIMI) Study Group originally defined TIMI grade 3 flow (complete perfusion) as antegrade flow into the bed distal to the obstruction that occurs as promptly as antegrade flow into the bed proximal to the obstruction. Recently, several groups have defined TIMI grade 3 flow as opacification of the coronary artery within 3 cardiac cycles. METHODS AND RESULTS: On the basis of heart rate data at the time of the cardiac catheterization and the time for dye to go down the artery (TIMI frame count/30 = seconds), we estimated the number of patients who would meet the 3 cardiac cycle criterion and compared this with the number of patients with TIMI grade 3 flow by using the original definition in 1157 patients from 3 recent TIMI trials (10 A, 10B, and 14). In 74 patients without acute myocardial infarction and normal coronary arteries, the fraction of a cardiac cycle required for dye to traverse the artery was a mean of 0.93 +/- 0.34 cardiac cycles (n = 74) (median 0.80, minimum 0.44, maximum 2.1, none >3.0 cycles). The mean heart rate at 90 minutes after thrombolysis in the TIMI 14 trial was 79.6 +/- 16.8 beats/min (n = 194), and the duration of 3 cardiac cycles was a mean of 2.36 seconds, or a TIMI frame count of 70.8 frames. In all trials, the rate of TIMI grade 3 flow was 57.3% (n = 663/1157) with the original definition and 66.8% (n = 743/1113) with the <3 cardiac cycle definition (P <.001). CONCLUSIONS: A duration of 3 cardiac cycles for dye to traverse the artery lies approximately 6 SD above that observed in normal coronary arteries. A 3 cardiac cycle definition of TIMI grade 3 flow results in rates of normal perfusion that are approximately 10% higher than if the original definition of TIMI grade 3 flow is applied. Application of this simple correction factor may help place data reported with the 3 cardiac cycle definition of TIMI grade 3 flow in context.

Cineangiography↗

Coping responses and posttraumatic stress symptomatology in urban fire service personnel.

Emergency workers, including urban fire fighters and paramedics, must cope with a variety of duty-related stressors including traumatic incident exposures. Little is known about coping responses of emergency workers or whether their coping responses predict future mental health outcomes. The previously formulated Coping Responses of Rescue Workers Inventory (CRRWI) underwent a principal components analysis employing a sample (N = 220) of urban fire fighters and paramedics. Six empirically and theoretically distinct CRRWI components were identified which were relatively stable over a 6-month period. Scores on one of the CRRWI scales, but neither years of service nor their past half year's traumatic incident exposures, predicted future changes in self-reports of posttraumatic stress symptomatology.

Adaptation, Psychological↗

Exposure to traumatic incidents and prevalence of posttraumatic stress symptomatology in urban firefighters in two countries.

Urban firefighters are at risk for posttraumatic stress disorder (PTSD) due in part to their exposure to duty-related trauma. This study compared duty-related trauma exposures and the prevalences of posttraumatic stress in U.S. and Canadian firefighters. Both samples reported relatively numerous and frequent posttrauma symptoms, and the rates of self-reported PTSD prevalence did not differ significantly. However, analysis of departmental records for respondents' previous year on duty revealed significant differences in both frequencies and categories of traumatic incident exposures. Some of the vulnerability and moderating risk factors associated with PTSD caseness differed between the U.S. and Canadian samples. Potential explanations for the observed differences in risk factors for PTSD in these 2 firefighter samples are considered.

Adult↗

Vascular surgical society of great britain and ireland: integrated care pathways for vascular surgery

BACKGROUND: Integrated care pathways (ICPs) represent a multidisciplinary approach to clinical patient care. METHODS: A 1-year prospective trial of the use of ICPs for elective vascular surgical procedures was undertaken. A multidisciplinary group constructed ICPs for patients admitted for open repair of abdominal aortic aneurysm, carotid endarterectomy or femoropopliteal bypass grafting. Patient management followed ICPs on a daily basis with signatures required to confirm that each action had been taken. Variances from the ICPs were carefully recorded. Audit of variance data allowed subsequent revision of the ICPs and hence provision of the best possible nursing and clinical practice. METHODS: A total of 33 patients were entered into the study; 16 had a femoropopliteal bypass graft, eight carotid endarterectomy and nine open repair of an abdominal aortic aneurysm. ICPs were well received by patients and staff. They improved communication, promoted an appreciation of each health group's role in patient care, increased nursing autonomy, reduced calls to junior medical staff, improved patient education and confidence, and caused a marked reduction in length of hospital stay. Overall, patients were discharged 13 per cent earlier after open abdominal aortic aneurysm repair, 22 per cent earlier after carotid endarterectomy and 38 per cent earlier after femoropopliteal bypass grafting. CONCLUSION: ICPs have clear benefits. They improve overall clinical efficiency and enhance clinical governance. Successful use of ICPs depends upon 'clinical champions' and effective project management. Sufficient resources and training are essential.

Journal Article↗

Integrated care pathways for vascular surgery.

OBJECTIVES: a trial of the use of integrated care pathways (ICPs) for elective vascular surgical procedures. DESIGN: a 12-month prospective study, following a multi-disciplinary group construction of current "best practice" ICPs, with changes in practice only occurring following careful audit of results. MATERIALS: patients admitted to a single vascular unit for "open" repair of abdominal aortic aneurysm, carotid endarterectomy or femoropopliteal bypass grafting. METHODS: patients followed ICPs on a daily basis with signatures required to confirm that action had been taken and careful recording of variances from the ICPs. Audit of variance data allowed changes in the ICPs and, hence, provision of the best possible nursing and clinical practice. RESULTS: ICPs were well received by patients and staff. They improved communication, promoted an appreciation of each health group's role in patient care, increased nursing autonomy, reduced calls to junior medical staff, improved patient education and confidence and caused a marked reduction in hospital "length of stay". CONCLUSIONS: ICPs have clear benefits. This study realises that benefits might be maximal for high throughput, high-cost procedures. Successful use of ICPs depends upon "clinical champions" and effective project management. Sufficient resource and training are essential.

Aortic Aneurysm, Abdominal↗

The early days of the MRC Social Medicine Research Unit.

During the 1940s, in Britain, there was great activity in the field of social medicine. This was generated by an upsurge in interest in social issues and a desire to promote occupational health research. In 1948 the Medical Research Council established a Social Medicine Research Unit. The background to the creation of the Unit and its early work are discussed. By the early 1950s, the political atmosphere had changed and criticisms of the Unit's work during the debate about continued funding in 1952 are considered. Important work on the relationship between coronary heart disease and physical exercise, and the results of a study of infant mortality, were published in the mid-1950s. A brief account of the subsequent history of the Unit, until its closure in 1975, is given.

Government Agencies↗

Use of intraosseous blood to assess blood chemistries and hemoglobin during cardiopulmonary resuscitation with drug infusions.

OBJECTIVE: To compare intraosseous with central venous blood samples for biochemical analyses and hemoglobin levels during cardiopulmonary resuscitation (CPR) and during cardiopulmonary resuscitation with infusion of sodium bicarbonate, epinephrine, and saline boluses through the intraosseous site. DESIGN: Prospective, complete repeated measures study. SETTING: An animal laboratory at a university medical center. SUBJECTS: Thirty-two piglets (mean weight, 30 [range, 24-35] kg). INTERVENTIONS: Animals were anesthetized, instrumented, and subjected to hypoxic cardiac arrest. An intraosseous cannula was inserted into the tibia, and animals were randomly assigned to one of five groups: heparinized saline (n = 6), epinephrine infusions only (n = 6), saline infusions only (n = 6), sodium bicarbonate infusions only (n = 8), and epinephrine, saline, and sodium bicarbonate infusions through the same site (n = 6). CPR (chest compressions and mechanical ventilation) was performed in all groups. Simultaneous blood samples were taken from the central venous and intraosseous sites before arrest and after 5 and 30 mins of CPR. MEASUREMENTS AND MAIN RESULTS: There were no differences (p < .05) in sodium, potassium, magnesium, lactate, and calcium values of intraosseous and central venous blood at the baseline and during 5 mins of CPR with infusions through the intraosseous cannula. At 30 mins, differences were apparent in magnesium, potassium, and sodium values between groups when the intraosseous cannula was used for infusions as well as sampling. Intraosseous potassium, glucose, and magnesium values were lower and sodium values were higher than central venous blood levels. No differences were seen at all sampling intervals if small-volume heparinized saline was given through the intraosseous site. Hemoglobin values were lower in the intraosseous group after 30 mins of CPR and infusions through the intraosseous site. After 30 mins of CPR, all hemoglobin values from the intraosseous site were <10 g/100 mL. CONCLUSION: Intraosseous and central venous blood biochemical and hemoglobin values were similar during hemodynamic stability and throughout 30 mins of resuscitation if no drugs were given through the intraosseous site. However, differences existed after 30 mins of CPR and infusions through the intraosseous site. Laboratory values may be erroneous when intraosseous blood is used during periods of resuscitation of >5 mins if drugs and fluid boluses have also been infused through the site. For reliable values, an intraosseous site for sampling only may be reasonable.

Animals↗

Acid-base status of blood from intraosseous and mixed venous sites during prolonged cardiopulmonary resuscitation and drug infusions.

OBJECTIVES: a) To determine the relationship of acid-base balance (pH, PCO2) of blood samples from the intraosseous and the mixed venous route during prolonged cardiopulmonary resuscitation; b) to compare the effect of separate infusions of epinephrine, fluid boluses, or sodium bicarbonate through the intraosseous sites on the acid-base status of intraosseous and mixed venous blood during cardiopulmonary resuscitation; and c) to compare pH and Pco2 of intraosseous and mixed venous blood samples after sequential infusions of fluid, epinephrine, and sodium bicarbonate through a single intraosseous site. DESIGN: Prospective, randomized study. SETTING: Animal laboratory at a university center. SUBJECTS: Thirty-two mixed-breed piglets (mean weight, 30 kg). INTERVENTIONS: Piglets were anesthetized and prepared for blood sampling and cardiopulmonary resuscitation. After anoxic cardiac arrest, ventilation was resumed and chest compression was resumed. Blood gas samples from the pulmonary artery and both intraosseous sites were obtained simultaneously at baseline, at cardiac arrest, and at 5, 10, 15, 20, and 30 mins of cardiopulmonary resuscitation for group 1 (control group) and after drug (epinephrine and sodium bicarbonate) and saline infusions via one of the intraosseous cannulas in groups 2 through 5. MEASUREMENTS AND MAIN RESULTS: We found no differences between intraosseous and mixed venous pH and Pco2 during periods of <15 mins of cardiopulmonary resuscitation. However, this relationship was not maintained during prolonged cardiopulmonary resuscitation and after bicarbonate infusion. After large volume saline infusion, the pH and Pco2 of mixed venous and intraosseous blood were similar. During epinephrine infusion, the relationship between intraosseous and mixed venous pH and Pco2 was similar to that found in the control group. CONCLUSIONS: The intraosseous blood sample could be used to assess central acid-base balance in the early stage of arrest and cardiopulmonary resuscitation of <15 mins. However, during cardiopulmonary resuscitation of longer duration, drug infusions may render the intraosseous site inappropriate for judging central acidosis.

Acid-Base Equilibrium↗