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Biomedical subjects

D M Murray

Publications and source records attributed to D M Murray.

At least 19 recordsLinked to original sources

Persistent lactic acidosis in neonatal hypoxic-ischaemic encephalopathy correlates with EEG grade and electrographic seizure burden.

BACKGROUND: Predicting at birth which infants with perinatal hypoxic-ischaemic injury will progress to significant encephalopathy remains a challenge. OBJECTIVE: To determine whether lactic acidosis at birth in asphyxiated neonates could predict the grade of EEG encephalopathy by examining the relationship between time taken for the normalisation of lactate, severity of encephalopathy and seizure burden. METHODS: Continuous early video-EEG monitoring was performed in babies at risk for hypoxic-ischaemic encephalopathy. Encephalopathy was graded from the EEG data. Total seizure burden (seconds) was calculated for each baby. Initial blood gas measurements of pH, base deficit and lactate were taken within 30 minutes of delivery. Time to normal serum lactate was determined in hours from birth for each infant. RESULTS: All 50 term infants had raised initial serum lactate (median (lower, upper quartiles) 11.7 (10.2, 14.9)). There were no significant differences between the initial serum lactate, pH and base deficit in infants with normal/mildly abnormal (n = 24), moderately abnormal (n = 14), severely abnormal (n = 5) and inactive EEGs (n = 7). Time to normal lactate varied significantly with EEG grade (median (lower, upper quartile) 6.0 (4.1, 9.5) for mild/normal EEG, 13.5 (6.8, 23.5) moderate EEG, 41.5 (30.0, 55.5) severe group, 12.0 (8.1, 21.5) inactive group; p<0.001). Time to normal lactate correlated significantly with EEG seizure burden (seconds; R = 0.446, p = 0.002). Mean (SD) time to normal lactate was 10.0 (7.2) hours in infants who did not have seizures and 27.3 (19.0) hours in the 13 infants with electrographic seizures (p = 0.002). CONCLUSIONS: Serum lactate levels in the first 30 minutes of life do not predict the severity of the ensuing encephalopathy. In contrast, sustained lactic acidosis is associated with severe encephalopathy on EEG and correlates with seizure burden.

Acidosis, Lactic↗

Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning?

Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. This article is the second report of the nationwide Biomarkers of Oxidative Stress Study using acute CCl4 poisoning as a rodent model for oxidative stress. The time-dependent (2, 7, and 16 h) and dose-dependent (120 and 1200 mg/kg i.p.) effects of CCl4 on concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA), isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), leukocyte DNA-MDA adducts, and DNA-strand breaks were investigated to determine whether the oxidative effects of CCl4 would result in increased generation of these oxidation products. Plasma concentrations of MDA and isoprostanes (both measured by GC-MS) and urinary concentrations of isoprostanes (measured with an immunoassay or LC/MS/MS) were increased in both low-dose and high-dose CCl4-treated rats at more than one time point. The other urinary markers (MDA and 8-OHdG) showed significant elevations with treatment under three of the four conditions tested. It is concluded that measurements of MDA and isoprostanes in plasma and urine as well as 8-OHdG in urine are potential candidates for general biomarkers of oxidative stress. All other products were not changed by CCl4 or showed fewer significant effects.

8-Hydroxy-2'-Deoxyguanosine↗

Biomarkers of oxidative stress study III. Effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in CCl4 poisoning.

Plasma and urinary levels of malondialdehyde-like products (MDA) and isoprostanes were identified as markers of in vivo lipid peroxidation in an animal model of CCl4 poisoning. We sought to determine the extent to which the formation of these oxidation products is influenced by inhibition of the cyclooxygenase enzymes which catalytically generate proinflammatory lipid peroxidation products known as prostaglandins and thromboxane. In the present studies, after induction of oxidant stress in rats with CCl4, lipid peroxidation products measured in plasma and urine demonstrate that isoprostanes and MDA can be partially inhibited by cyclooxygenase inhibitors, albeit to different extents. The lowering of isoprostane and MDA formation, however, may not to due primarily to the diminution of catalytic generation of isoprostanes or MDA by the cyclooxygenases but, rather, may be the result of the suppression of nonenzymatic lipid peroxidation. This is suggested since 8,12-iso-iPF2alpha-VI is also reduced by indomethacin, yet, unlike other isoprostanes and MDA, it is not generated catalytically by the cyclooxygenase. Thus, although the two cyclooxygenase inhibitors we tested have statistically significant effects on the measurements of both isoprostanes and MDA in this study, the results provide evidence that these lipid-degradation products primarily constitute markers of oxidative stress.

Animals↗

A kinematic study of lateral unicompartmental arthroplasty.

When the Oxford unicompartmental meniscal bearing arthroplasty (UCA) is used in the lateral compartment 10% of the bearings dislocate. A fluoroscopic study was performed to investigate if abnormal mid-sagittal plane kinematics was related to bearing dislocation. Video fluoroscopy is an accepted means of determining in-vivo knee kinematics in the sagittal plane. Video fluoroscopy was obtained of 5 Oxford lateral UCAs 10 years post-operatively and of five normal knees. Patellar tendon angle (PTA), derived from dynamic fluoroscopic images, was used to describe the joint kinematics. This in-vivo experiment demonstrated that the PTA/knee relationship for the Oxford lateral UCA is similar to the normal knee. Both the normal knee (r(2)=0.99) and the Oxford lateral UCA (r(2)=0.98) demonstrated a linear relationship between flexion angle and PTA. No significant difference in PTA was found between the normal knee and the Oxford lateral UCA. This study demonstrated normal kinematics, as indicated by PTA, ten years after implantation of the Oxford lateral UCA. It is therefore reasonable to suggest that abnormal kinematics is not a significant factor relating to meniscal bearing dislocation in the lateral compartment.

Adult↗

The characterization of novel, dual ErbB-2/EGFR, tyrosine kinase inhibitors: potential therapy for cancer.

The type I receptor tyrosine kinases constitute a family of transmembrane proteins involved in various aspects of cell growth and survival and have been implicated in the initiation and progression of several types of human malignancies. The best characterized of these proteins are the epidermal growth factor receptor (EGFR) and ErbB-2 (HER-2/neu). We have developed potent quinazoline and pyrido-[3,4-d]-pyrimidine small molecules that are dual inhibitors of ErbB-2 and EGFR. The compounds demonstrate potent in vitro inhibition of the ErbB-2 and EGFR kinase domains with IC(50)s <80 nM. Growth of ErbB-2- and EGFR-expressing tumor cell lines is inhibited at concentrations <0.5 microM. Selectivity for tumor cell growth inhibition versus normal human fibroblast growth inhibition ranges from 10- to >75-fold. Tumor growth in mouse s.c. xenograft models of the BT474 and HN5 cell lines is inhibited in a dose-responsive manner using oral doses of 10 and 30 mg/kg twice per day. In addition, the tested compounds caused a reduction of ErbB-2 and EGFR autophosphorylation in tumor fragments from these xenograft models. These data indicate that these compounds have potential use as therapy in the broad population of cancer patients overexpressing ErbB-2 and/or EGFR.

Animals↗

Weight loss attempts and attitudes toward body size, eating, and physical activity in American Indian children: relationship to weight status and gender.

OBJECTIVE: This study examined dieting, weight perceptions, and self-efficacy to eat healthy foods and engage in physical activity and their relationships to weight status and gender among American Indian elementary schoolchildren. RESEARCH METHODS AND PROCEDURES: Data for this study were collected as part of the baseline examination for the Pathways study. Participants were 1441 second- through third-grade American Indian children in 41 schools representing seven tribes in Arizona, New Mexico, and South Dakota who filled out a questionnaire and had heights and weights taken. RESULTS: Forty-two percent of the children were overweight or obese. No differences were found between overweight/obese and normal weight children for healthy food intentions or self-efficacy. Heavier children (especially those with body mass index > 95th percentile) were more likely to have tried to lose weight or were currently trying to lose weight. No gender differences were found. Normal weight children chose a slightly heavier body size as most healthy compared with overweight/obese children. DISCUSSION: The results indicate that children are concerned about their weight and that weight modification efforts are common among overweight American Indian children. School, community, and family-based programs are needed to help young people adopt lifelong healthful eating and physical activity practices.

Arizona↗

An evaluation of analysis options for the one-group-per-condition design. Can any of the alternatives overcome the problems inherent in this design?

This article addresses the analytic problems associated with a design in which one identifiable group is allocated to each treatment condition and members of those groups are measured to assess the intervention. Such designs are often called quasi-experiments if the groups are not randomized to conditions and group-randomized trials if the groups are randomized. They present special problems, and previous reports have argued against their use in efficacy or effectiveness trials. Even so, this design still appears with surprising frequency. This article presents the results from a new simulation study that underscores the analytic problems associated with this design.

Group Processes↗

Project ARM: alcohol risk management to prevent sales to underage and intoxicated patrons.

Clear policies and expectations are key to increasing responsible service of alcohol in licensed establishments. Few training programs focus exclusively on owners and managers of alcohol establishments to reduce the risk of alcohol service. Project ARM: Alcohol Risk Management is a one-on-one consultation program for owners and managers. Participants received information on risk level, policies to prevent illegal sales, legal issues, and staff communication. This nonrandomized demonstration project was implemented in five diverse bars. Two waves of underage and pseudo-intoxicated purchase attempts were conducted pre- and postintervention in the five intervention bars and nine matched control bars. Underage sales decreased by 11.5%, and sales to pseudo-intoxicated buyers decreased by 46%. Results were in the hypothesized direction but not statistically significant. A one-on-one, outlet-specific training program for owners and managers is a promising way to reduce illegal alcohol sales, particularly to obviously intoxicated individuals.

Administrative Personnel↗

Intraclass correlation for measures from a middle school nutrition intervention study: estimates, correlates, and applications.

This article presents the first estimates of school-level intraclass correlation for dietary measures based on data from the Teens Eating for Energy and Nutrition at School study. This study involves 3,878 seventh graders from 16 middle schools from Minneapolis-St. Paul, Minnesota. The sample was 66.8% White, 11.2% Black, and 7.0% Asian; 48.8% of the sample was female. Typical fruit and vegetable intake was assessed with a modified version of the Behavior Risk Factor Surveillance System questionnaire. Twenty-four-hour dietary recalls were conducted by nutritionists using the Minnesota Nutrition Data System. Mixed-model regression methods were used to estimate variance components for school and residual error, both before and after adjustment for demographic factors. School-level intraclass correlations were large enough, if ignored, to substantially inflate the Type I error rate in an analysis of treatment effects. The authors show how to use the estimates to determine sample size requirements for future studies.

Adolescent↗

Using signs, artwork, and music to promote stair use in a public building.

OBJECTIVES: This study assessed the impact on stair use of improving the attractiveness of a stairwell. METHODS: Observations of stair usage were made in a university building during baseline, 2 interventions, and follow-up. The first intervention involved signs; the second intervention added artwork and music in the stairwell. RESULTS: More participants used the stairs during the music and artwork intervention than at baseline or when signs alone were used. CONCLUSIONS: Improving the aesthetic qualities of a stairwell can increase rates of stair usage in a public building. Designs for buildings should take accessibility and aesthetic issues into consideration.

Art↗

Socioeconomic status, ethnicity, and health care access among young and healthy women.

This study examined: (a) the relationship between socioeconomic status (SES) and health care access among healthy women; (b) which SES variable(s) were most strongly associated with HCA; and (c) whether the SES/HCA relationship was the same for Black and White women. A total of 383 women (57.4% Whites and 42.6% Blacks) participated in the study. Independent variables included family income, education levels, occupation, median income within zip code of participants' residence, and ethnicity. Dependent variables were the total and subscale scores (accessibility, accommodation, and affordability) on a measure of health care access. Family income was the SES variable that showed the strongest positive association with total health care access, and there was a significant interaction between occupation and ethnicity for total health care access. Unique relationships were observed between each SES variable and each subscale on the health care access measure. The overall patterns between SES and health care access were similar for Blacks and Whites. Results suggest that the relationship between health care access and SES should be investigated through a multi-dimensional approach, and that an array of SES variables must be considered when designing interventions to improve health care access among healthy women.

Adolescent↗

The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo.

The epidermal growth factor receptor (EGFR) and ErbB-2 transmembrane tyrosine kinases are currently being targeted by various mechanisms in the treatment of cancer. GW2016 is a potent inhibitor of the ErbB-2 and EGFR tyrosine kinase domains with IC50 values against purified EGFR and ErbB-2 of 10.2 and 9.8 nM, respectively. This report describes the efficacy in cell growth assays of GW2016 on human tumor cell lines overexpressing either EGFR or ErbB-2: HN5 (head and neck), A-431 (vulva), BT474 (breast), CaLu-3 (lung), and N87 (gastric). Normal human foreskin fibroblasts, nontumorigenic epithelial cells (HB4a), and nonoverexpressing tumor cells (MCF-7 and T47D) were tested as negative controls. After 3 days of compound exposure, average IC50 values for growth inhibition in the EGFR- and ErbB-2-overexpressing tumor cell lines were < 0.16 microM. The average selectivity for the tumor cells versus the human foreskin fibroblast cell line was 100-fold. Inhibition of EGFR and ErbB-2 receptor autophosphorylation and phosphorylation of the downstream modulator, AKT, was verified by Western blot analysis in the BT474 and HN5 cell lines. As a measure of cytotoxicity versus growth arrest, the HN5 and BT474 cells were assessed in an outgrowth assay after a transient exposure to GW2016. The cells were treated for 3 days in five concentrations of GW2016, and cell growth was monitored for an additional 12 days after removal of the compound. In each of these tumor cell lines, concentrations of GW2016 were reached where outgrowth did not occur. Furthermore, growth arrest and cell death were observed in parallel experiments, as determined by bromodeoxyuridine incorporation and propidium iodide staining. GW2016 treatment inhibited tumor xenograft growth of the HN5 and BT474 cells in a dose-responsive manner at 30 and 100 mg/kg orally, twice daily, with complete inhibition of tumor growth at the higher dose. Together, these results indicate that GW2016 achieves excellent potency on tumor cells with selectivity for tumor versus normal cells and suggest that GW2016 has value as a therapy for patients with tumors overexpressing either EGFR or ErbB-2.

Animals↗

Associations between exercise and health behaviors in a community sample of working adults.

BACKGROUND: The present study examined the associations between leisure-time exercise and a range of health behaviors and reports of illness and injury in a sample of community working adults. METHODS: The study population included 4907 women and 4136 men who completed surveys in 24 worksites in the Minneapolis-St. Paul metropolitan area. RESULTS: Participants in the study were ranked by gender according to their exercise score and grouped into quartiles. Women and men in the highest activity quartiles were more highly educated and were younger. High-activity men were more likely to be unmarried. Higher levels of leisure-time exercise were positively associated with seat belt use and inversely related to smoking, dietary fat intake, reported stress, and obesity. In men only, leisure-time exercise was related to greater reports of injuries resulting in restriction of usual activities. In women only, leisure-time exercise was positively associated with daily alcohol use. Most of the significant associations were seen in the two highest quartiles of exercise. CONCLUSIONS: These findings suggest that associations between leisure-time exercise and health behaviors occur at the higher levels of exercise and interventions may need to promote this higher level of leisure-time exercise to impact overall public health.

Adult↗

Smokers with multiple behavioral risk factors: how are they different?

OBJECTIVE: The first aim of the present investigation was to examine cross-sectional differences between smokers who engage in additional health risk behaviors (i.e., high-fat diets and low physical activity levels) and those who do not that could affect readiness for smoking cessation treatment and treatment prognosis. The second aim was to examine prospective associations between risk factor status and smoking outcomes (i.e., cessation and quit attempts). DESIGN: Data were derived from baseline and 1-year follow-up surveys for the SUCCESS project, a randomized trial of worksite smoking interventions conducted in 24 worksites in Minneapolis/St. Paul, Minnesota. Included in the analyses were 2,149 study participants who reported smoking at baseline. METHODS: Current smokers were categorized into one of three "risk groups": the "1 additional risk factor" group (i.e., either low physical activity level or high dietary fat intake), the "2 additional risk factor" group (i.e., both low physical activity and high dietary fat intake), and the "smoker only" group (i.e., neither low physical activity nor high dietary fat intake). Mixed model regression analyses examined cross-sectional associations between risk group status and baseline demographic variables, smoking dependency, social environments for smoking, and health problems. Prospective associations between baseline risk group status and 1-year follow-up cessation attempts and quits were also examined. RESULTS: At baseline, risk factor status was associated with smoking dependency for both men and women. Women smokers with at least one additional risk factor reported a greater number of cigarettes smoked per day, higher Fagerstrom Nicotine Dependence scores, and lower self-efficacy for refraining from smoking in a variety of situations compared with smokers with no additional risk factors. Men smokers with at least one additional risk factor reported higher Fagerstrom Nicotine Dependence scores compared with smokers with no additional risk factors. Women smokers with at least one additional risk factor were more likely to report being encouraged to quit by co-workers compared with smokers with no other risk factors. No relationship between risk factor status and social pressure to quit was observed among men. Prospective analyses indicated that baseline risk factor status was marginally related to smoking outcome at 1-year follow-up; however, these relationships were attenuated considerably when controlling for smoking dependence. Relationships between risk factor status and smoking outcomes were stronger for men. CONCLUSION: Results indicated that the presence of multiple health risk behaviors was related to more serious problems with smoking. However, the presence of additional risk factors did not strongly affect prognosis for smoking cessation.

Adult↗

Reconciling conflicting findings regarding postcessation weight concerns and success in smoking cessation.

Correlates of concern about weight gain following smoking cessation and self-efficacy about controlling weight gain were examined in 940 men and 1,166 women who were surveyed on 2 occasions as part of a randomized trial of work-site interventions for smoking cessation. Weight concerns were positively associated with female sex, body weight, dieting for weight control, nicotine addiction, and social encouragement to quit. Bivariate analyses replicated prior findings that elevated weight concerns are associated with a reduced likelihood of quitting smoking, at least in women. Analyses controlling for demographics, nicotine dependence, and social factors replicated prior findings that weight concerns are not negatively related to smoking cessation and that some measures of concern are positively related to cessation. These analyses suggest that conflicting findings found in this literature are due primarily to how weight concerns are defined and whether covariates like nicotine addiction are used in data analyses.

Adolescent↗

Predictors of weight gain in the Pound of Prevention study.

OBJECTIVES: This study examined cross-sectional and prospective relationships between macronutrient intake, behaviors intended to limit fat intake, physical activity and body weight. DESIGN: The overall goal was to identify diet and exercise behaviors that predict and/or accompany weight gain or loss over time. Specific questions addressed included: (a) are habitual levels of diet or exercise predictive of weight change; (b) are habitual diet and exercise levels associated cross-sectionally with body weight; and (c) are changes in diet and exercise associated with changes in body weight over time? PARTICIPANTS: Subjects were a sample of community volunteers (n=826 women, n=218 men) taking part in a weight gain prevention project over a 3-year period. MEASURES: Body weight was measured at baseline and annually over the study period. Self-report measures of diet and exercise behavior were also measured annually. RESULTS: Among both men and women, the most consistent results were the positive association between dietary fat intake and weight gain and an inverse association between frequency of physical activity and weight gain. Individuals who weighed more both ate more and exercised less than those who weighed less. Individuals who increased their physical activity level and decreased their food intake over time were protected from weight gain compared to those who did not. Frequency of high-intensity physical activity was particularly important for both men and women. Additionally, women who consistently engaged in higher levels of moderate physical activity gained weight at a slower rate compared to women who were less active. CONCLUSIONS: Overall results indicated that both cross-sectionally and prospectively, the determinants of weight and weight change are multifactorial. Attention to exercise, fat intake and total energy intake all appear important for successful long term control of body weight.

Adult↗

Communities mobilizing for change on alcohol (CMCA): effects of a randomized trial on arrests and traffic crashes.

AIMS: We previously reported effects of the CMCA intervention in reducing social and commercial access to alcohol by youth, and reducing alcohol use by 18-20-year-olds. This paper reports on effects of CMCA on arrests and car crashes. DESIGN: CMCA was a group-randomized trial that implemented and evaluated a community-organizing effort to change community policies and practices to reduce youth access to alcohol. Seven Midwestern communities were randomly assigned to the intervention condition and eight communities were assigned to the control condition. INTERVENTION: For 2.5 years, a part-time community organizer worked in each of the seven intervention communities with local public officials, enforcement agencies, alcohol merchants, the media, schools and other community groups to reduce youth access to alcohol. MEASUREMENT: We collected annual arrest and quarterly traffic crash data for the years 1987-1995, providing a 6-year baseline and 3 years of data during the intervention. Data were stratified into two target age groups (15-17 and 18-20) and a control group (age 21 and over). Analyses used random-coefficient models because we had repeated observations for each unit of assignment in a group-randomized trial with heterogeneous trends across communities. FINDINGS: We observed net declines in the intervention communities for all arrest and traffic crash indicators. The decline was statistically significant for DUI arrests among 18-20-year-olds and approached significance for DUI arrests and disorderly conduct violations among 15-17-year-olds. CONCLUSIONS: Together with previously published results from this study, the results reported here suggest that a community-organizing approach to limit youth access to alcohol may be effective, at least for selected end-points and subgroups. We conclude that this approach may be useful, but that a longer intervention period is required to increase effectiveness.

Accidents, Traffic↗