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Biomedical subjects

David Green

Publications and source records attributed to David Green.

At least 19 recordsLinked to original sources

Obtaining informed consent for genetic studies: The multiethnic study of atherosclerosis.

Studies of DNA may yield important information about atherosclerosis. To determine how often study participants' consent to examine DNA is denied and the factors associated with that denial, information was collected on participants in the US Multiethnic Study of Atherosclerosis (MESA) during 2000-2004. Permission was sought for preparation of DNA, transformation of cells into cell lines, evaluation of genes related to heart and other health conditions, and access to DNA by private companies. Of the 5,494 participants at entry, 897 (16.3%) refused consent for some items and 247 (4.5%) completely denied consent. At a second examination 18 months later, 819 (15.0%) partially refused and 229 (4.2%) completely denied consent. Age among men (odds ratio per 10 years = 0.68, 95% confidence interval: 0.54, 0.85; p = 0.004), ethnicity (odds ratio for African American = 2.34, 95% confidence interval: 1.66, 3.32; p < 0.001), and field center (p < 0.001) were associated with complete denial. For those giving partial consent, the most common item refused was access to DNA by private companies (baseline: 99%; second examination: 90%); younger age, male gender, and African-American ethnicity were associated with refusal. The authors concluded that a small percentage of participants in epidemiologic studies refuse consent for DNA studies, and the majority are concerned about sharing their DNA data with industry.

Age Factors↗

Statin use and functional decline in patients with and without peripheral arterial disease.

OBJECTIVES: We determined whether statin use (vs. non-use) is associated with less annual decline in lower-extremity functioning in patients with and without lower-extremity peripheral arterial disease (PAD) over three-year follow-up. BACKGROUND: It is unclear whether statin use is associated with less functional decline in patients with PAD. METHODS: Participants included 332 men and women with an ankle brachial index (ABI) <0.90 and 212 with ABI 0.90 to 1.50. Functional outcomes included 6-min walk distance and usual and rapid-pace 4-m walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for five repeated chair rises into an ordinal score ranging from 0 to 12 (12 = best). RESULTS: Adjusting for age, race, gender, comorbidities, education, health insurance, total cholesterol/high-density lipoprotein level, body mass index, pack-years of smoking, leg symptoms, immediately previous year functioning, statin use/non-use, ABI, and change in ABI, the PAD participants using statins had less annual decline in usual-pace walking velocity (0.002 vs. -0.024 m/s/year, p = 0.013), rapid-pace walking velocity (-0.006 vs. -0.042 m/s/year, p = 0.006), 6-min walk performance (-34.5 vs. -57.9 feet/year, p = 0.088), and the summary performance score (-0.152 vs. -0.376, p = 0.067) compared with non-users. These associations were attenuated slightly by additional adjustment for high-sensitivity C-reactive protein levels. Among non-PAD participants, there were no significant associations between statin use and functional decline. CONCLUSIONS: The PAD patients on statins have less annual decline in lower-extremity performance than PAD patients who are not taking statins.

Aged↗

Functional decline in patients with and without peripheral arterial disease: predictive value of annual changes in levels of C-reactive protein and D-dimer.

BACKGROUND: Inflammation may be a potential mechanism of aging-related functional decline. We determined whether greater annual increases in levels of high sensitivity C-reactive protein (hsCRP) and D-dimer predicted greater decline in functioning among persons with and without lower extremity peripheral arterial disease (PAD). METHODS: We prospectively studied 296 men and women with PAD and 191 without PAD. Objective measures of functioning, hsCRP, and D-dimer were obtained at baseline and annually for 3 years (mean follow-up = 36.3 +/- 6.4 months). RESULTS: Among PAD participants, greater annual increases in hsCRP were associated with greater annual declines in 6-minute walk performance (-2.63 ft/mg/L, p =.039) but not in other functional outcomes. Higher prior year absolute hsCRP levels were associated with greater declines in 6-minute walk (-2.93 ft/mg/L, p =.022), summary performance score (-0.038/mg/L, p =.017), and rapid paced 4-meter walk (-0.29 cm/s/mg/L, p =.026) during the subsequent year. Among participants without PAD, greater annual increases in hsCRP were associated with greater annual declines in 6-minute walk (-7.47 ft/mg/L, p =.002), usual-pace 4-meter walk (-0.33 cm/s/mg/L, p <.001), fast paced 4-meter walk (-0.56 cm/s/mg/L, p =.003), and the summary performance score (-0.029 mg/L, p <.001). There were no consistent associations between D-dimer levels and functional decline. CONCLUSION: These findings suggest that inflammation may play a role in functional decline in persons with and without PAD.

Aged↗

Coagulation cascade.

The coagulation cascade is now recognized to be a series of proteolytic events mainly localized to the surface of activated platelets. Once platelets become activated by exposure to activated endothelium, they release mediators such as P-selectin and von Willebrand factor that promote microvesicle formation and platelet adherence. The microvesicles fuse with the activated platelet membrane, providing tissue factor and its ligand, factor VIIa. Clotting factors bind to adjacent receptors on the membrane, enabling the cascading proteolytic cleavages of zymogens to active enzymes, culminating in thrombin generation. Fibrin formation thus occurs in the sheltered environment of the platelet membrane, where it is localized to the site of injury and protected from circulating inhibitors.

Blood Coagulation↗

Intensity of 18fluorodeoxyglucose uptake in positron emission tomography distinguishes between indolent and aggressive non-Hodgkin's lymphoma.

PURPOSE: (18)Fluorodeoxyglucose positron emission tomography (FDG PET) is widely used for the staging of lymphoma. We investigated whether the intensity of tumor FDG uptake could differentiate between indolent and aggressive disease. MATERIALS AND METHODS: PET studies of 97 patients with non-Hodgkin's lymphoma who were untreated or had relapsed and/or persistent disease and had not received treatment within the last 6 months were analyzed, and the highest standardized uptake value (SUV) per study was recorded. Correlations were made with histopathology. RESULTS: FDG uptake was lower in indolent than in aggressive lymphoma for patients with new (SUV, 7.0 +/- 3.1 v 19.6 +/- 9.3; P < .01) and relapsed (SUV, 6.3 +/- 2.7 v 18.1 +/- 10.9; P = .04) disease. Despite overlap between indolent and aggressive disease in the low SUV range (indolent, 2.3 to 13.0; aggressive, 3.2 to 43.0), all cases of indolent lymphoma had an SUV 10 excluded indolent lymphoma with a specificity of 81%. With a higher cutoff for the SUV, the specificity would have been higher. CONCLUSION: FDG uptake is lower in indolent than in aggressive lymphoma. Patients with NHL and SUV > 10 have a high likelihood for aggressive disease. This information may be helpful if there is discordance between biopsy and clinical behavior.

Adolescent↗

Influence of warfarin on symptoms of fatigue: findings of a randomized trial.

BACKGROUND: Some patients develop fatigue while taking warfarin, but causality is uncertain. OBJECTIVE: To assess whether warfarin use is associated with fatigue. METHODS: This investigation was a substudy of a randomized double-blind trial in 13 outpatient thromboembolism clinics. Subjects who had received one month of open-label warfarin therapy for venous thromboembolism due to a transient risk factor were randomly assigned to receive warfarin or placebo for 2 months and followed for another 9 months after stopping the study drug. Fatigue was measured using a Likert scale, and change of fatigue was measured by the patient's global rating. RESULTS: In 87 subjects, the overall ratings of fatigue were 0.1 unit lower (95% CI 0.6 units lower to 0.4 units higher) while taking warfarin. Global rating for change in fatigue intensity showed no increase of fatigue with warfarin use. CONCLUSIONS: The short-term use of warfarin was not associated with symptoms of fatigue.

Analysis of Variance↗

Fabrication of hydroxyapatite sponges by dextran sulphate/amino acid templating.

We report a new template-directed method for the fabrication of hydroxyapatite (HAp) sponges by using amino-acid-coated HAp nanoparticles dispersed within a viscous polysaccharide (dextran sulfate) matrix, and describe the use of these materials for the viability and proliferation of human bone marrow stromal cells. The nanoparticles were prepared in the presence of excess amounts of aspartic acid, alanine or arginine, and subsequently organised into macroporous frameworks with typical pore sizes of 100-200 microm during thermal degradation of the dextran matrix. The sponge macrostructure was influenced by changes in the heating rate and sintering time, as well as the use of different amino acids or variations in dextran functional groups. Biocompatibility testing showed retention of cell viability, production of extracellular matrix and alkaline phosphatase expression, suggesting that it should be possible to exploit this novel fabrication method for potential applications in cartilage or soft tissue engineering.

Alanine↗

Evolving risk for thromboembolism in spinal cord injury (SPIRATE Study).

OBJECTIVE: To compare the frequency of venous thromboembolism (VTE) in patients examined during 1992-1995 with those examined during 1999-2003. DESIGN: A comprehensive review of the charts of all patients admitted between late 1999 and early 2003 for rehabilitation after spinal cord injury. Only records, including evidence for objective testing for VTE (ultrasound, venography, lung scanning) were included, and patients having inferior vena cava filter placement or previous VTE were excluded. Analysis variables included type and location of spinal cord injury, American Spinal Injury Association classification, concomitant injuries, surgical procedures, complications, preexisting illnesses, and use of antithrombotic prophylaxis. Using univariate optimal discriminant analysis, data from the current group of patients were compared with a previous study of 243 subjects examined between 1992 and 1995. RESULTS: The current sample consisted of 76 persons with acute spinal cord injury, of whom six had VTE (7.9%). As compared with the frequency of VTE in the previous patient sample (21%), this represented a significant decrease (P<0.01). The major differences between the current and previous patient samples were a decrease in the use of unfractionated heparin (15.8% vs. 56.8%, P<0.0001) and an increase in the use of low molecular weight heparin (81.6% vs. 59.7%, P<0.0001). CONCLUSIONS: VTE has been a common and occasionally lethal complication in persons with spinal cord injury. The recent switch from unfractionated heparin to low molecular weight heparin for the prevention of VTE has coincided with a decrease in the frequency of this complication in patients with spinal cord injury.

Adult↗

D-dimer and inflammatory markers as predictors of functional decline in men and women with and without peripheral arterial disease.

OBJECTIVES: To determine whether higher circulating levels of inflammatory and thrombotic markers are associated with greater decline in lower extremity performance. DESIGN: Prospective cohort. SETTING: Academic medical center. PARTICIPANTS: Three hundred thirty-seven men and women with lower extremity peripheral arterial disease (PAD) and 215 without PAD. MEASUREMENTS: Objective measures of leg function, including the 6-minute walk and Short Physical Performance Battery (SPPB), were obtained at baseline and annually for 3 years. D-dimer, high-sensitivity C-reactive protein, serum amyloid A, and fibrinogen levels were measured at baseline. Participants were categorized into one of three groups, ranging from low to high levels of inflammation, depending on the number of individual blood factors in the lowest and highest tertiles for each corresponding blood factor. RESULTS: Adjusting for age, sex, race, ankle brachial index, comorbidities, and other confounders, greater inflammation was associated with greater decline in the SPPB (P=.008). Results were similar when repeated in participants with and without PAD separately (P for trend=.04 for participants with PAD and .07 for participants without PAD). In fully adjusted analyses, there were no significant associations between inflammation group and decline in 6-minute walk performance. CONCLUSION: Higher baseline levels of inflammatory markers and D-dimer were associated with greater decline in the SPPB at 3-year follow-up in persons with and without PAD.

Activities of Daily Living↗

Substance misuse, anxiety and depression and urgency of presentation to a public emergency department in Australia.

OBJECTIVES: To establish the prevalence and comorbidity of substance-related problems and anxiety and depression, among ED presentations, and to compare the prevalence of these conditions among more and less urgent presentations. DESIGN AND SETTING: Cross-sectional survey of ED presentations over a 14 day period (24 h/day) at the Gold Coast Hospital Emergency Department in south-east Queensland, Australia, in October 2002. MEASURES: Usual level of alcohol consumption (Alcohol Use Disorders Identification Test), acute alcohol and illicit drug use (during 24 h prior to interview), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale) and triage category (Australasian Triage Scale). RESULTS: Thirty-one per cent of the sample reported usually consuming alcohol at a hazardous or harmful level. Twenty per cent of participants reported clinically significant levels of anxiety and/or depression, which were in turn significantly associated with hazardous and harmful levels of alcohol use. Hazardous/harmful alcohol consumption was over-represented among less urgent ED presentations, whereas anxiety and depression were more prevalent among more urgent ED presentations. CONCLUSIONS: Emergency departments in Australia are appropriate settings for the detection of both substance use and mental health problems in the wider community. The prevalence of these problems in ED settings is high and there is a need for the development of systematic screening and referral processes. The evidence of a link between urgency of presentation and these problems needs to be further explored.

Adolescent↗

Gender differences in the relationships between alcohol, tobacco and mental health in patients attending an emergency department.

AIMS: There is evidence of a non-linear relationship between alcohol consumption and mental health status, and of an association between tobacco use and poor mental health. This paper examines the nature of the association between usual alcohol consumption, tobacco use and symptoms of anxiety and depression in Emergency Department patients in Queensland, Australia. METHODS: A cross sectional survey of patients aged 16-84 presenting for treatment over a 14 day period to Gold Coast Hospital Emergency Department using socio-demographic items, the Alcohol Use Disorders Identification Test (AUDIT) to measure moderate, hazardous and harmful alcohol consumption, and the Hospital Anxiety and Depression Scale (HADS) to measure state anxiety and depression. RESULTS: 812 patients were interviewed. Gender differences in results were evident. For men, there was a U-shaped relationship between alcohol consumption and anxiety/depression, and a linear association between smoking and anxiety. For women, alcohol consumption and anxiety/depression showed a more linear relationship, but there was no significant relationship between tobacco use and anxiety/depression. CONCLUSIONS: There may be important gender differences in the relationships between alcohol consumption, tobacco use and mental health status. This study supports previous evidence that mental health status of non-drinkers is worse than that of moderate drinkers, but only among males.

Adolescent↗

Inflammatory and thrombotic blood markers and walking-related disability in men and women with and without peripheral arterial disease.

OBJECTIVES: To determine whether higher circulating levels of thrombotic and inflammatory markers are associated with greater disability. DESIGN: Cross-sectional. SETTING: Academic medical center. PARTICIPANTS: A total of 346 men and women with peripheral arterial disease (PAD) and 203 without PAD. MEASUREMENTS: Disability measures were the Walking Impairment Questionnaire (WIQ) distance, speed, and stair-climbing scores and the 36-item Short-Form (SF-36) physical functioning score. The SF-36 and WIQ are scored on a 0 to 100 scale (100=best). RESULTS: In persons with PAD, higher D-dimer levels were associated with lower WIQ speed scores (P<.001), lower stair-climbing scores (P<.04), and poorer SF-36 physical functioning scores (P<.01), adjusting for known and potential confounders. In participants without PAD, higher D-dimer levels were associated with lower WIQ distance scores (P<.03), lower speed scores (P<.05), and poorer SF-36 physical functioning scores (P<.02). Higher high-sensitivity C-reactive protein (hsCRP) levels were associated with lower WIQ distance (P<.02) and speed scores (P<.001) in persons without PAD. Most of these associations were attenuated after additional adjustment for objectively measured functional limitations. CONCLUSION: Higher circulating D-dimer and hsCRP levels are associated with greater disability in walking and physical functioning in individuals with and without PAD. Physiological changes that result in walking disability may mediate these associations.

Aged↗

Inflammatory markers, D-dimer, pro-thrombotic factors, and physical activity levels in patients with peripheral arterial disease.

Men and women with lower extremity peripheral arterial disease (PAD) have reduced physical activity levels compared with persons without PAD. We describe associations between physical activity levels with D-dimer, pro-coagulant factors, and inflammatory markers in patients with PAD. Participants were 188 patients with PAD identified from non-invasive vascular laboratories. Physical activity was measured over 7 days with a vertical accelerometer. We measured the ankle-brachial index (ABI) and levels of D-dimer, C-reactive protein (CRP), fibrinogen, serum amyloid A (SAA), prothrombin 1.2, t-PA antigen, PAI-1, and the t-PA antigen/PAI-1 ratio. Adjusting for age, sex, race, body mass index, ABI, comorbidities, smoking, total cholesterol/HDL ratio and statin use (for CRP only), we found significant inverse linear associations between physical activity levels and log D-dimer (p = 0.002), log CRP (p < 0.001), fibrinogen (p = 0.014), and log SAA (p = 0.012). There were no significant associations between physical activity levels and other blood factors. In an analysis adjusting for all blood factors simultaneously along with known and potential confounders, log D-dimer was the only blood factor associated significantly with physical activity levels (p = 0.036). Based on these findings, future studies should assess whether interventions to increase physical activity in patients with PAD reduce levels of D-dimer and inflammatory markers.

Arterial Occlusive Diseases↗