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Biomedical subjects

James R Murphy

Publications and source records attributed to James R Murphy.

14 recordsLinked to original sources
PubMed2006

Variant IRAK-1 haplotype is associated with increased nuclear factor-kappaB activation and worse outcomes in sepsis.

RATIONALE: The IL-1 receptor-associated kinase (IRAK-1) plays a central role in TLR2- and TLR4-induced activation of nuclear factor (NF)-kappaB, a critical event in the transcriptional regulation of many sepsis-associated proinflammatory mediators. There are two haplotypes for the IRAK-1 gene in Caucasians, with the variant haplotype consisting of five intron single-nucleotide polymorphisms (SNPs) and three exon SNPs. OBJECTIVES: To examine the functional significance of the IRAK-1 variant haplotype in modifying nuclear translocation of NF-kappaB and affecting outcomes from sepsis. MEASUREMENTS AND MAIN RESULTS: One hundred fifty-five Caucasian patients with sepsis were included. Twenty-one (14%) were homozygous for the IRAK-1 variant haplotype as determined by a SNP in which T is replaced with C at nucleotide 1,595 within exon 12 of the IRAK-1 gene. The IRAK-1 variant haplotype was associated with increased nuclear levels of NF-kappaB in LPS-stimulated peripheral blood neutrophils from patients with sepsis compared with that found in patients with wild-type IRAK-1 haplotype (p=0.0009). There was an increased incidence of shock (p=0.047) (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.1-7.7), greater requirement for more prolonged mechanical ventilator support (p=0.04) (OR, 2.7; 95% CI, 1.05-6.9), and higher 60-d mortality (p=0.05) (OR, 2.7; 95% CI, 1.0-6.8) in patients with the IRAK-1 variant haplotype compared with wild type. CONCLUSIONS: These results indicate that the IRAK-1 variant haplotype is functionally significant in patients with sepsis, being associated with increased nuclear translocation of NF-kappaB, more severe organ dysfunction, and higher mortality.

Adolescent↗
PubMed2006

In vitro pH effects on in vivo recovery and survival of platelets: an analysis by the BEST Collaborative.

BACKGROUND: The pH environment of stored platelet (PLT) products is recognized as an important factor and is generally used as a key surrogate measure of PLT viability. It is the only in vitro measurement that has been translated into industry standards and regulatory rules or specifications for storage of PLT products. The objective of this study was to evaluate the effect of in vitro pH on the in vivo recovery and survival of autologous PLT products. STUDY DESIGN AND METHODS: Data from individual autologous radiolabeled PLT kinetic studies were solicited from independent laboratories. PLTs stored for at least 5 days in 100 percent autologous plasma with a pH(22 degrees C) of at least 6.2 were analyzed. Data were fit to a mixed-effects regression model with fixed effects of pH(22 degrees C), time of storage, and preparation method-storage bag combination. RESULTS: Eight research laboratories reported 476 individual recovery and survival results with associated pH before labeling from a variety of autologous, radiolabeled PLT kinetic studies from September 1999 to March 2005. These results are from 254 individual subjects who donated a total of 386 PLT units, with up to nine collections per subject reported. The effect of pH on either PLT recovery (p = 0.86) or survival (p = 0.55) was not significant. Time of storage and the method-bag combination both had significant effects on these outcomes (p < 0.0001). CONCLUSION: These data suggest that there is no relationship between in vitro pH at a pH(22 degrees C) of at least 6.2 and in vivo PLT viability as measured by radiolabeled recovery and survival of autologous PLTs.

Blood Platelets↗
PubMed2006

A new tool to assess sarcoidosis severity.

STUDY OBJECTIVES: Sarcoidosis is a granulomatous disorder primarily affecting the lung, but with frequent extrapulmonary organ involvement. There are no comprehensive scoring systems for sarcoidosis disease severity. Our goal was to develop and validate an objective and comprehensive sarcoidosis disease severity scoring system. DESIGN: Three sarcoidosis experts reviewed clinical data on 104 patients with biopsy-confirmed sarcoidosis. Each expert independently scored disease severity using a visual analog scale. Interrater agreement was assessed. Univariate analysis was performed, and those variables with p values < or = 0.25 were used in backward regression multivariable analysis. A model was obtained including variables with a p value of < or = 0.15 to predict severity scores. This model was subsequently validated using an independent panel of three additional international experts. SETTING: Granuloma clinic at National Jewish Medical and Research Center. PATIENTS: A total of 104 patients with biopsy-confirmed sarcoidosis. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Pairwise assessment of interrater agreement yielded high degrees of correlation with Spearman correlation coefficients of 0.86 to 0.89 and an intraclass correlation coefficient of 0.87. Univariate analysis showed that smoking status, immunosuppressive therapy, percent predicted for diffusing capacity of the lung for carbon monoxide (Dlco), FEV1, FVC, and total lung capacity, FEV1/FVC ratio, disease duration, sites of organ involvement, and African-American race were associated with mean severity score. The multivariable model included cardiac and neurologic involvement, current therapy with noncorticosteroid immunosuppressive agents, Dlco percent predicted, FEV1/FVC ratio, African-American race, FVC percent predicted, and skin involvement. This model was validated using additional reviewer scores yielding Spearman correlation coefficients of 0.66 to 0.76 and an intraclass correlation coefficient of 0.74. CONCLUSIONS: We derived an objective disease severity scoring system that incorporates data on demographics, pulmonary function, and organ involvement to produce a whole-body sarcoidosis assessment. This preliminary tool has potential applicability in the assessment of disease severity in sarcoidosis research.

Adolescent↗
PubMed2005

Importance of the personal endotoxin cloud in school-age children with asthma.

BACKGROUND: A number of studies have observed associations between the amount of endotoxin in urban dust and chronic asthma severity, but a direct relationship between personal exposure to household endotoxin and acute asthma worsening has not yet been defined. OBJECTIVE: We sought to investigate the relationship between day-to-day changes in personal endotoxin exposure and asthma severity. METHODS: In the winter and spring of 1999 through 2000, endotoxin exposures were monitored in asthmatic schoolchildren by using portable, as opposed to stationary, monitors designed to measure inhalable and respirable particulate matter less than or equal to 2.5 and 10 microm in diameter. Children were followed with daily measurements of FEV(1) and asthma symptoms. RESULTS: Over a 24-hour period, median daily personal endotoxin exposures ranged from 0.08 EU/m(3) (measured at a particulate matter size range </=2.5 microm in diameter) to 0.37 EU/m(3) (measured at a particulate matter size range </=10 microm in diameter). Personal exposures were significantly (P < .001) higher than endotoxin measurements from either indoor or outdoor stationary monitors. Moreover, individual exposures did not correlate with stationary measurements, suggesting that exposures derived from sources in close proximity to the children's personal activities might be better correlated with disease severity. Increases in personal endotoxin exposures were associated with decreased FEV(1) values and increased symptoms. CONCLUSIONS: These findings demonstrate the importance of using personal monitoring to both measure and correlate endotoxin exposure with asthma severity.

Air Pollutants↗
PubMed2005

Community-associated methicillin-resistant Staphylococcus aureus in pediatric patients.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections increased from 2000 to 2003 in hospitalized pediatric patients in Houston. CA-MRSA was associated with greater illness than was infection with methicillin-susceptible strains. Children with CA-MRSA were younger and mostly African American. Of MRSA isolates, 4.5% had the inducible macrolide-lincosamide-streptogramin B phenotype.

Adolescent↗
PubMed2004

Progression of asthma measured by lung function in the childhood asthma management program.

From the Childhood Asthma Management Program cohort, which was randomly assigned to receive budesonide, nedocromil, or placebo for 4-6 years, we determined the prevalence of and factors associated with at least 1% per year loss in postbronchodilator FEV(1)% predicted. Participants who had a significant reduction in postbronchodilator FEV(1)% predicted (SRP), comprised 25.7% of the cohort (n = 990). Using logistic regression, predictors of SRP at baseline were younger age (p = 0.0005), male sex (p < 0.0001), clinic (p = 0.02), and higher postbronchodilator FEV(1)% predicted (p = 0.02). Examination of the SRPs indicated that the effect of baseline lung function was such that the higher the lung function, the less steep the reduction in postbronchodilator FEV(1)% predicted (p < 0.0001). A similar proportion of SRPs was found in each treatment group. Among the SRPs, the rate of reduction in postbronchodilator FEV(1)% predicted was similar in all treatment groups. At a single site where biomarker assessment was performed, SRPs also had more prominent eosinophilic inflammation during the washout period. The course and mechanisms of lung function reduction or slow lung growth velocity in children with asthma must be defined.

Administration, Inhalation↗
PubMed2004

Effects of wintertime ambient air pollutants on asthma exacerbations in urban minority children with moderate to severe disease.

BACKGROUND: Urban minority children with asthma are at higher risk for severe exacerbations leading to hospitalizations and deaths. Because multiple studies have reported associations between air pollution and asthma worsening, elevated levels of air pollution are cited as a possible trigger for increased asthma morbidity in urban areas. Few studies have prospectively followed panels of urban children with asthma to determine whether air pollution levels are associated with clinically relevant outcomes such as asthma exacerbations. OBJECTIVE: To determine the association between levels of ambient air pollutants and asthma exacerbations in urban poor children with moderate to severe asthma. METHODS: A school-based panel of children with difficult-to-control disease was followed over a period of 3 consecutive winters in Denver, Colo. The panel consisted of predominantly urban African American children with moderate to severe asthma. Levels of Environmental Protection Agency criteria air pollutants were measured on a daily basis with concurrent monitoring of lung function, bronchodilator use, symptoms, and asthma exacerbations. RESULTS: After controlling for time-varying factors such as upper respiratory infections and meteorologic factors, a weak association was found between ambient carbon monoxide levels and bronchodilator use. Ozone levels were associated with daytime symptoms only. No association was observed between daily air pollution concentrations and daily levels of FEV 1 , peak flow, nighttime symptom scores, or asthma exacerbations over the 3-year period. CONCLUSION: Ambient levels of Environmental Protection Agency criteria air pollutants in Denver do not lead to clinically significant asthma worsening in urban children with moderate to severe asthma during winter months when children are primarily indoors.

Air Pollutants↗
PubMed2004

Statistical errors in immunologic research.

Medical research articles have always been subject to errors in reporting statistical results. Although most of these are minor, they raise questions about the integrity of medical research. Most of the errors come from a misunderstanding about the tools used in statistical analysis. This article discusses some of the most frequent errors and provides examples of how to deal with them correctly.

Allergy and Immunology↗
PubMed2004

Poliomyelitis-like syndrome in a child with West Nile virus infection.

West Nile virus (WNV) infections of the central nervous system are very uncommon in U.S. children. We report a child with a poliomyelitis-like presentation in which WNV was the only detected pathogen. WNV has not previously been associated with a poliomyelitis-like presentation in children.

Child↗
PubMed2004

Beryllium medical surveillance at a former nuclear weapons facility during cleanup operations.

Despite increasing need to remediate beryllium-contaminated buildings in industry, little is known about the magnitude of risk associated with beryllium abatement or the merits of beryllium medical surveillance for cleanup workers. We examined beryllium lymphocyte proliferation tests and reviewed medical evaluations on workers at a nuclear weapons facility during the process of decontamination and decommissioning. Of 2,221 workers, 19 (0.8%) were beryllium sensitized based on two or more abnormal beryllium lymphocyte proliferation tests. Eight of 19 sensitized individuals underwent full clinical evaluation, of whom two were diagnosed with chronic beryllium disease (CBD). Notably, seven beryllium sensitized and CBD cases were hired after the start of cleanup operations. Beryllium medical surveillance detects sensitization and CBD in cleanup workers. Exposure controls and medical surveillance need to be 'broad-based' to include all cleanup workers involved in beryllium-contaminated building remediation.

Adolescent↗
PubMed2003

Minimizing attrition in a long-term clinical trial of pediatric asthma.

BACKGROUND: Despite increased attention focused on the need to prevent patient attrition in long-term clinical trials, high dropout rates have threatened the success of numerous studies. OBJECTIVE: To evaluate the disease, demographic, and psychological factors associated with missed visits and study dropout to help improve patient management in long-term clinical trials. METHODS: Predictors of attrition were examined within the Childhood Asthma Management Program (CAMP), a large, multicenter clinical trial that followed up 1,041 children with asthma for 4 to 6 years. RESULTS: Eighty-two percent of patients attended all study visits. The tendency to miss visits was increased among older children with milder asthma, lower intellectual and social competence, and more symptoms of behavioral problems and emotional distress. Forty-two patients who missed 3 or more visits in a row and did not attend the final visit were considered study dropouts; these patients at baseline had milder asthma; lower cognitive, academic, and social competence skills; and more family conflict and distress than found among participants who remained in the study. The 49 children who had erratic attendance but did not drop out also had lower intellectual and academic skills and less family social support. CONCLUSIONS: The 4% dropout rate in CAMP was lower than reported in any previous long-term asthma trial. The findings of milder disease, decreased psychological resources, and increased distress in problem-attendance patients can assist in identifying patients who are at risk for missed visits or dropout during the trial either to block their entry into the trial or to focus efforts at maintaining their attendance once enrolled in the trial.

Anti-Asthmatic Agents↗
PubMed2003

Hygiene hypothesis: fact or fiction?

The hygiene hypothesis of asthma and allergy has recently received a swell of popularity and published supporting evidence, and has been extended to autoimmune conditions of childhood. Broadly stated, naturally occurring infections and microbial exposures might essentially immunize against the development of asthma and allergic and autoimmune diseases. If true, then reductions in nature's immunotherapy over the past century might be a major factor in the global increase of these conditions (eg, the higher prevalence of asthma and allergies in urban metropolitan areas compared with rural and farm communities) and might lead to new therapies for these conditions. Although such a unifying hypothesis has great appeal, currently it is only speculation about what might be at the end of the investigative road. How close are the current studies to establishing a causal relationship between microbial exposures and a reduction in allergic, asthmatic, and autoimmune disease prevalence? A systematic epidemiologic appraisal of the current hygiene hypothesis evidence can provide a critical analysis of what is currently known and an investigative blueprint for future studies that can ultimately prove causation and improve recommendations, interventions, and therapies.

Asthma↗
PubMed2003

Double-blind, placebo-controlled study of the efficacy of trazodone in alcohol post-withdrawal syndrome: polysomnographic and clinical evaluations.

Alcohol detoxification is accompanied by sustained difficulties in sleep initiation and maintenance. These difficulties are thought to be an important cause of relapse to alcohol use. However, the treatment of sleep problems with hypnotic drug is made difficult by cross-tolerance between benzodiazepines and alcohol. In this report, we evaluated the capacity of trazodone (TRZ), a second-generation antidepressant with anxiolytic and sedative properties, to increase the sleep efficiency in alcohol-dependent patients after detoxification. Sixteen patients completed the TRZ (n = 8) or the placebo (PL; n = 8) treatment arms. Polysomnographies were performed at baseline, after the 1st drug dose, and after 4 weeks of treatment. The main outcome was sleep efficiency. Secondary outcomes included changes in other sleep parameters, Hamilton Depression Rating and Clinical Global Impression scales. Sleep efficiency was increased in the TRZ group when it was computed after sleep onset, both immediately after 1st administration of the drug and after 4 weeks of treatment. No benefit was observed in the PL group. Sleep improvement under TRZ also included the number of awakenings, intermittent wake sleep time, and non-rapid eye movement sleep. Hamilton and Clinical Global scales were better for the TRZ group. TRZ is thus a potential option in the treatment of alcohol post-withdrawal insomnia.

Adolescent↗