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Biomedical subjects

A M Arnold

Publications and source records attributed to A M Arnold.

At least 19 recordsLinked to original sources
PubMed2006

Soluble intracellular adhesion molecule-1 is associated with cardiovascular disease risk and mortality in older adults.

BACKGROUND: Intracellular adhesion molecule-1 (ICAM-1) regulates leukocyte-endothelial attachment, a process crucial to atherosclerosis. Circulating soluble ICAM-1 (sICAM-1) may serve as a marker of cardiovascular disease (CVD) progression. OBJECTIVES: We examined the association of sICAM-1 with measures of subclinical CVD and risk of incident CVD events and death in older men and women (age > or = 65 years) from the Cardiovascular Health Study. METHODS: Selected participants were free of clinical CVD at baseline. Non-exclusive incident case groups were angina (n = 534), myocardial infarction (n = 304), stroke (n = 327), and death (n = 842; CVD death = 310). A total 643 subjects were free of events during follow-up. RESULTS: sICAM-1 was positively associated with C-reactive protein, interleukin-6 and fibrinogen and measures of subclinical CVD in these older men and women. In Cox regression models adjusted for age, gender, and race, increasing levels of sICAM-1 were associated with increased risk of all cause mortality in men and women. Hazard ratios (95% confidence intervals) for a one standard deviation increase in sICAM-1 (89.7 ng mL(-1)) were 1.3 (1.1-1.4) in men and 1.2 (1.1-1.3) in women. sICAM-1 was associated with increased risk of CVD death in women (1.2; 1.0-1.5), but not men (1.1; 0.9-1.3). There were no associations of sICAM-1 with non-fatal CVD events. CONCLUSIONS: While sICAM-1 was associated with death in older men and women, there was a more marked association between sICAM-1 and CVD death in women.

Aged↗
PubMed2003

Lack of association of the plasminogen activator inhibitor-1 4G/5G promoter polymorphism with cardiovascular disease in the elderly.

Elevated circulating plasminogen activator inhibitor-1 (PAI-1) may increase risk of cardiovascular disease (CVD). The 4G allele of the 4G/5G PAI-1 promoter polymorphism is associated with higher levels of PAI-1. We examined the association of PAI-1 4G/5G genotype and CVD events in the elderly participants of the Cardiovascular Health Study (CHS). We measured 4G/5G genotype in a nested case-control study within the CHS. Cases included incident angina, myocardial infarction (MI), and stroke. 4G/5G genotype was not found to be associated with markers of fibrinolysis or CVD risk in the selected elderly cohort. There were no differences in genotype frequencies by case-control status (5G/5G frequency 16-22%; chi2P= 0.07). The 5G allele was not associated with incident CVD events when individuals with at least one 5G allele were compared to 4G/4G homozygotes. The presence of at least one 4G allele was likewise not associated with incident CVD when those with 4G/4G and 4G/5G genotypes were compared to 5G/5G homozygotes. Our results suggest that the PAI-1 4G/5G promoter polymorphism is not associated CVD risk factors or incident CVD events in the elderly.

Aged↗
PubMed2001

Cardiovascular disease and mortality in older adults with small abdominal aortic aneurysms detected by ultrasonography: the cardiovascular health study.

BACKGROUND: Persons with abdominal aortic aneurysm are more likely to have a higher prevalence of risk factors for and clinical manifestations of cardiovascular disease. It is unknown whether these factors explain the high mortality rate associated with abdominal aortic aneurysm. OBJECTIVE: To describe the risk for mortality, cardiovascular mortality, and cardiovascular morbidity in persons screened for abdominal aortic aneurysm. DESIGN: Longitudinal cohort study. SETTING: Four communities in the United States. PARTICIPANTS: 4734 men and women older than 65 years of age recruited from Medicare eligibility lists. MEASUREMENTS: Abdominal ultrasonography was used to measure the aortic diameter and the ratio of infrarenal to suprarenal measurement of aortic diameter in 1992-1993. Abdominal aortic aneurysm was defined as aortic diameter of 3 cm or greater or infrarenal-to-suprarenal ratio of 1.2 or greater. Mortality, cardiovascular disease mortality, incident cardiovascular disease, and repair or rupture were assessed after 4.5 years. RESULTS: The prevalence of aneurysm was 8.8%, and 87.7% of aneurysms were 3.5 cm or less in diameter. Rates of total mortality (65.1 vs. 32.8 per 1000 person-years), cardiovascular mortality (34.3 vs. 13.8 per 1000 person-years), and incident cardiovascular disease (47.3 vs. 31.0 per 1000 person-years) were higher in participants with aneurysm than in those without aneurysm; after adjustment for age, risk factors, and presence of other cardiovascular disease, the respective relative risks were 1.32, 1.36, and 1.57. Rates of repair and rupture were low. CONCLUSIONS: Rates of total mortality, cardiovascular disease mortality, and incident cardiovascular disease were higher in participants with abdominal aortic aneurysm than in those without aneurysm, independent of age, sex, other clinical cardiovascular disease, and extent of atherosclerosis detected by noninvasive testing. Persons with smaller aneurysms detected by ultrasonography should be advised to modify risk factors for cardiovascular disease while under surveillance for increase in the size of the aneurysm.

Aged↗
PubMed2001

Factors associated with healthy aging: the cardiovascular health study.

OBJECTIVES: To identify factors associated with remaining healthy in older adults. DESIGN: Longitudinal cohort study. SETTING: Data were collected at the four Cardiovascular Health Study field centers. PARTICIPANTS: 5,888 participants age 65 years and older in the Cardiovascular Health Study. MEASUREMENTS: Presence of chronic disease was assessed at baseline and over a maximum 7-year follow-up period. Participants who were free of chronic disease (no cardiovascular disease (CVD), chronic obstructive pulmonary disease, or self-reported cancer, except nonmelanoma skin cancer) at the baseline examination were then monitored for the onset of incident cancer, cardiovascular disease, and fatal outcomes. RESULTS: A high proportion of these older adults was healthy at the initial examination and remained healthy over the follow-up period. Numerous behavioral factors were associated with continued health, including physical activity, refraining from cigarette smoking, wine consumption (women), higher educational status, and lower waist circumference. A number of CVD risk factors and subclinical disease measures were associated with continued health, including higher high-density lipoprotein (HDL) cholesterol, lack of diabetes, thinner common carotid intimal nmedial thickness, lower blood pressure, lower C-reactive protein, and higher ankle-arm blood pressure ratio. Among the behavioral factors, exercise, not smoking, and not taking aspirin remained significant predictors of health even after controlling for CVD risk factors and subclinical disease in older adults. CONCLUSIONS: These data suggest that a number of modifiable behavioral factors (physical activity, smoking, and obesity) and cardiovascular risk factors (diabetes, HDL cholesterol, and blood pressure) are associated with maintenance of good health in older adults.

Aged↗
PubMed2000

Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study.

OBJECTIVES: We sought to characterize the predictors of incident congestive heart failure (CHF), as determined by central adjudication, in a community-based elderly population. BACKGROUND: The elderly constitute a growing proportion of patients admitted to the hospital with CHF, and CHF is a leading source of morbidity and mortality in this group. Elderly patients differ from younger individuals diagnosed with CHF in terms of biologic characteristics. METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of 5,888 elderly people >65 years old (average 73 +/- 5, range 65 to 100) at four locations. Multiple laboratory measures of cardiovascular structure and function, blood chemistries and functional assessments were obtained. RESULTS: During an average follow-up of 5.5 years (median 6.3), 597 participants developed incident CHF (rate 19.3/1,000 person-years). The incidence of CHF increased progressively across age groups and was greater in men than in women. On multivariate analysis, other independent predictors included prevalent coronary heart disease, stroke or transient ischemic attack at baseline, diabetes, systolic blood pressure (BP), forced expiratory volume 1 s, creatinine >1.4 mg/dl, C-reactive protein, ankle-arm index <0.9, atrial fibrillation, electrocardiographic (ECG) left ventricular (LV) mass, ECG ST-T segment abnormality, internal carotid artery wall thickness and decreased LV systolic function. Population-attributable risk, determined from predictors of risk and prevalence, was relatively high for prevalent coronary heart disease (13.1%), systolic BP > or =140 mm Hg (12.8%) and a high level of C-reactive protein (9.7%), but was low for subnormal LV function (4.1%) and atrial fibrillation (2.2%). CONCLUSIONS: The incidence of CHF is high in the elderly and is related mainly to age, gender, clinical and subclinical coronary heart disease, systolic BP and inflammation. Despite the high relative risk of subnormal systolic LV function and atrial fibrillation, the actual population risk of these for CHF is small because of their relatively low prevalence in community-dwelling elderly people.

Aged↗
PubMed1999

Effect of institutional volume and academic status on outcomes of coronary interventions: the IMPACT-II experience.

BACKGROUND: Rates of morbidity and mortality after interventional procedures are reported to be inversely associated with institutional volume. METHODS: This study assessed both procedural volume and academic status at the 82 US centers that participated in the IMPACT-II trial. Interventional volumes at the sites ranged from 90 to 3300 cases per year. Patients were randomly assigned to a platelet glycoprotein IIb/IIIa inhibitor (eptifibatide) or placebo during procedures done by experienced operators. The primary end point was the composite of death, myocardial infarction, nonelective repeat coronary intervention, or nonelective coronary artery bypass surgery at 30 days, or placement of an intracoronary stent for abrupt closure during the initial procedure. RESULTS: Baseline patient characteristics and median length of stay were similar between the academic and nonacademic centers. In univariable analysis, volume as a continuous variable had a nonlinear relation with the incidence of the composite end point, with better outcomes noted at the highest volume institutions. Academic status did not predict outcome. When added to a predictive model that contained the variables unstable angina, weight, prior coronary artery bypass grafting, heart rate, and platelet count, procedural volume continued to be associated with the composite outcome (P =.04). CONCLUSIONS: We conclude that among hospitals participating in this trial, there is a nonlinear relation between annual interventional volume and outcomes. This relation is complex, involving variations in periprocedural infarction rates and additional, undefined institutional differences (other than academic status) that result in differences in procedural outcome.

Academic Medical Centers↗
PubMed1999

The relationship of fibrinogen and factors VII and VIII to incident cardiovascular disease and death in the elderly: results from the cardiovascular health study.

Little is known about the prospective associations of fibrinogen, factor VII, or factor VIII with cardiovascular disease (CVD) and mortality in the elderly. At baseline in the Cardiovascular Health Study (5888 white and African American men and women; aged >/=65 years), we measured fibrinogen, factor VIII, and factor VII. We used sex-stratified stepwise Cox survival analysis to determine relative risks (RRs) for CVD events and all-cause mortality (up to 5 years of follow-up), both unadjusted and adjusted for CVD risk factors and subclinical CVD. After adjustment, comparing the fifth quintile to the first, fibrinogen was significantly associated in men with coronary heart disease events (RR=2.1) and stroke or transient ischemic attack (RR=1.3), and also with mortality within 2.5 years of follow-up (RR=5.8) and later (RR=1.7). Factor VIII was significantly associated in men with coronary heart disease events (RR=1.5) and mortality (RR=1.8), and in women with stroke/transient ischemic attack (RR=1.4). For both factors, values were higher in those who died, whether causes were CVD-related or non-CVD-related, but highest in CVD death. Factor VII exhibited associations with incident angina (RR=1.44) in men and with death in women (RR, middle quintile compared with first=0.66). However, in general, factor VII was not consistently associated with CVD events in this population. We conclude that, if confirmed in other studies, the measurement of fibrinogen and/or factor VIII may help identify older individuals at higher risk for CVD events and mortality.

Aged↗
PubMed1998

Left ventricular diastolic filling in the elderly: the cardiovascular health study.

Changes in left ventricular (LV) diastolic function (e.g., as measured by transmitral flow velocity) are known to occur with aging. In addition, impaired LV diastolic function plays an important role in such cardiovascular disorders common in the elderly as hypertension, ischemic heart disease, and congestive heart failure (CHF). Participants in the Cardiovascular Health Study, a multicenter study of community-dwelling men (n=2,239) and women (n=2,962) > or = 65 years of age, underwent an extensive baseline evaluation, including echocardiography. Early diastolic LV Doppler (transmitral) peak filling velocity decreased, and peak late diastolic (atrial) velocity increased with age in multivariate analyses (all p <0.001). Early and late diastolic peak filling velocities were both significantly higher in women than in men, even after adjustment for body surface area (or height and weight). In multivariate models in the entire cohort and a healthy subgroup (n=703), gender, age, heart rate, and blood pressure (BP) were most strongly related to early and late diastolic transmitral peak velocities. Early and late diastolic peak velocities both increased with increases in systolic BP and decreased with increases in diastolic BP (p <0.001). Doppler transmitral velocities were compared among health status subgroups. In multiple regression models adjusted for other covariates, and in analysis of variance models examining differences across subgroups adjusted only for age, the subgroup with CHF had the highest early diastolic peak velocities. All clinical disease subgroups had higher late diastolic peak velocities than the healthy subgroup, with the subgroups with either CHF or hypertension having the highest age-adjusted means. The subgroup with hypertension had the lowest ratio of early-to-late diastolic peak velocity, and men with CHF had the highest ratio. These findings are consistent with previous reports that hypertensive subjects exhibit an abnormal relaxation pattern, whereas patients with CHF develop a pattern suggestive of an increased early diastolic left atrial-LV pressure gradient.

Aged↗
PubMed1997

Transforming growth factor-beta 3 is expressed in nondividing basal epithelial cells in normal human prostate and benign prostatic hyperplasia, and is no longer detectable in prostate carcinoma.

BACKGROUND: We investigated the role of the transforming growth factor beta (TGF-beta) family in the neoplastic progression of the human prostate. METHODS: Expression of TGF-beta mRNA was measured by Northern blot analysis of tissue extracts, and TGF-beta protein by immunohistochemical analysis of tissue sections. Proliferating cells were detected by their expression of Ki-67 antigen. RESULTS: The level of TGF-beta 1 mRNA was equal among normal prostate, benign prostatic hyperplasia (BPH), and prostate carcinoma. TGF-beta 2 mRNA was not detectable, and TGF-beta 3 mRNA was expressed 20-fold lesion in carcinoma compared to BPH and normal prostate. TGF-beta 1 protein was expressed in the stromal cells in all three tissues and TGF-beta 3 protein in the basal layer of epithelial cells, but not in carcinoma. Proliferating epithelial cells fail to express TGF-beta 3. CONCLUSIONS: TGF-beta 1 and TGF-beta 3 are independently regulated, and carcinoma of the prostate is characterized by the loss of basal epithelial cells expressing TGF-beta 3.

Adult↗
PubMed1997

Sulcal, ventricular, and white matter changes at MR imaging in the aging brain: data from the cardiovascular health study.

PURPOSE: To determine the distribution of changes in sulcal size, ventricular size, and white matter signal intensity depicted on cranial magnetic resonance (MR) images, with stratification according to age, race, and sex. MATERIALS AND METHODS: Ventricular size, sulcal size, and white matter signal intensity changes were graded on cranial MR images of 3,660 community-living, elderly participants in the Cardiovascular Health Study. A healthier subgroup was also defined. Summary statistics for both groups were generated for age, race, and sex. RESULTS: Regression models of the entire imaged cohort showed higher grades of all variables with increasing age, and higher ventricular and sulcal grades in men and in nonblack individuals. White matter grade was greater in women and in black individuals. Regression models of the healthier subgroup showed similar associations, except for a lack of association of sulcal and ventricular size with race. CONCLUSION: Sulcal width, ventricular size, and white matter signal intensity change with age, sex, and race. Knowledge of these changes is important in appropriate interpretation of MR images of the elderly.

Aged↗
PubMed1997

Effect of testosterone on differential muscle growth and on protein and nucleic acid concentrations in muscles of growing lambs.

Growth, nucleic acid, and protein concentrations were measured in three muscles of 20 rams, 20 wethers, and 20 wethers implanted with testosterone. Two lambs from each group were slaughtered at 14-d intervals from 49 to 133 d, and then at 28-d intervals until 217 d, for a total of 10 slaughter ages. Immediately after slaughter, the semitendinosus, splenius, and triceps brachii muscles were removed, trimmed of adhering fat, and weighed. The DNA, RNA, and protein concentrations of these muscles were determined. Testosterone increased combined weight of the three muscles. The splenius muscles of rams and wethers implanted with testosterone were heavier and had a biphasic growth pattern as the combined muscle weight increased, whereas the splenius muscle of wethers had a single growth phase. Rams and implanted wethers had greater splenius muscle DNA and RNA concentrations than wethers as muscle weight increased. This model could be used to study the gene regulation of testosterone-induced muscle growth with the possibility of invoking similar effects in more economically important muscles.

Analysis of Variance↗
PubMed1996

Ultrasound imaging of the radial artery following its use for cardiac catheterization.

Our experience suggests transradial arterial access with 5Fr catheters can be used for cardiac angiography with a low incidence of clinical complications, and supports the findings of previous investigators. Subclinical complications at the catheterization site were infrequent in this study (1 patient with asymptomatic radial artery occlusion). The presence of a palpable radial pulse may not be a reliable estimate of artery patency as evidenced by our patient with a palpable pulse due to retrograde flow. The theoretical advantage of the procedure is derived from the dual vascular supply to the hand. Radial artery occlusion, while uncommon, results in no ischemic sequelae in the setting of a patent ulnar artery.

Aged↗
PubMed1996

Differential expression of IGFBPs by normal and hypertrophic scar fibroblasts.

Insulin-like growth factor-I (IGF-I) is a potent fibroblast mitogen which influences wound healing. IGF action is regulated by a family of six IGF-binding proteins (IGFBPs). The purpose of this study was to determine if expression of IGFBPs is altered in hypertrophic scarring, a wound-healing condition commonly associated with deep dermal injury. Fibroblast populations from the superficial and deep dermal layers of normal human skin (SN and DN, respectively) and from superficial and deep layers of hypertrophic scars (SSc and DSc, respectively) were established and cultured in serum-free medium with or without several growth factors known to modulate wound healing, including basic fibroblast growth factor, the BB isoform of platelet-derived growth factor, IGF-I, and transforming growth factor-beta (TGF-beta). IGFBP release was analyzed by radioligand blot assays of culture media. Two main forms of IGFBPs were released, IGFBP-3 and a 24-kDa form which comigrated with serum IGFBP-4. DSc fibroblasts accumulated significantly more IGFBP-3 into serum-free culture medium than did SN, DN, or SSc fibroblasts in all conditions except TGF-beta treatment and confluence. Additionally, comparisons of IGFBP-3 release by each cell type with and without TGF-beta revealed TGF-beta stimulated IGFBP-3 accumulation by SN and DN fibroblasts but not by SSc or DSc fibroblasts. DN and DSc fibroblasts accumulated significantly more of the 24-kDa IGFBP species than SN or SSc fibroblasts in all conditions except TGF-beta or IGF-I treatment. These findings indicate that superficial and deep dermal fibroblasts are heterogeneous with respect to IGFBP release, and suggest that hypertrophic scar fibroblasts may represent a population of cells with regulatory properties distinct from those of normal dermal fibroblasts.

Cell Count↗
PubMed1996

Role of intimal hyperplasia and arterial remodeling after balloon angioplasty: an experimental study in the atherosclerotic rabbit model.

The arterial response to injury appears to be an important factor in the development or restenosis. Traditionally, intimal hyperplasia has been thought to be the primary mechanism responsible for restenosis. However, recent studies have found that arterial remodeling is a major determinant of lumen loss after balloon angioplasty. In this study, we evaluated the actual separate contributions of intimal hyperplasia and arterial remodeling to the restenotic process after balloon angioplasty in the atherosclerotic rabbit model. One month after induction of focal atherosclerotic lesions, femoral arteries were randomized to receive treatment with either two or six balloon inflations. One group of rabbits was euthanized immediately after angioplasty to evaluate the initial degree of injury with each dilation strategy ("acute group"), and the rest were euthanized 28 days after angioplasty ("chronic group"). Arteries that had been treated with six inflations had a higher injury score than those treated with two (4.0+/-3.0 versus 1.9+/-1.5, P<.05). In the chronic group, there was a significant increase in intimal area in the six inflation-treated arteries compared with the two-inflation group (0.617+/-0.06 versus 0.432+/-0.05 mm2, P<.004). However, there was no significant difference in lumen cross-sectional area between groups. By multivariate analysis, the most important independent predictor of lumen area was the external elastic lamina (EEL) area, although the degree of intimal thickening was also a significant independent predictor. There was a strong, positive correlation between intimal area and EEL area: the larger the intimal area, the larger the EEL area (r=.703, P<.0001). The intimal area was similar in both restenotic and nonrestenotic lesions. In contrast, EEL area was significantly larger (due to remodeling) in nonrestenotic lesions. This study confirms previous findings that the degree of injury determines the degree of neointimal proliferation and supports recent findings that chronic arterial remodeling plays a major role in the final lumen area. Understanding and controlling the remodeling process rather than concentrating solely on intimal hyperplasia may yield better results after balloon angioplasty in the future.

Angioplasty, Balloon↗
PubMed1996

Ontogeny of growth hormone, insulin-like growth factor-I, estradiol and cortisol in the growing lamb: effect of testosterone.

Exogenous sex steroids have altered growth hormone secretion in some domestic species. This study examined whether different physiological concentrations of testosterone alter muscle growth in sheep through modification of the somatotropic axis. The effects of testosterone on growth hormone (GH), insulin-like growth factor-I (IGF-I), estradiol (E2) and cortisol concentrations in growing lambs were evaluated in 20 rams, 20 wethers and 20 wethers receiving subcutaneous testosterone replacement therapy. Two animals from each of the three testosterone status groups were slaughtered at 14-day intervals from 49 to 133 days of age, and then at 28-day intervals until 217 days of age for a total of 10 slaughter ages. Animals were sampled every 10 min for an 8-h period 1 day prior to slaughter to characterize the episodic patterns of GH and testosterone. Immediately after slaughter, the semitendinosus, splenius and triceps brachii muscles were removed, trimmed of adhering fat and connective tissue, and weighed. Testosterone increased the combined muscle weight. GH concentrations decreased during the course of the experiment. However, there was no effect of testosterone on GH mean, baseline, amplitude or GH pulse frequency measured by PULSAR. IGF-I concentrations increased in response to testosterone treatment. Testosterone had no effect on cortisol levels while E2 levels were increased after 133 days. Increased muscle growth due to testosterone appeared to be caused either by a direct effect or by increased levels of IGF-I independent of circulating GH concentrations.

Animals↗
PubMed1995

Photocoagulation treatment for clinically significant radiation macular oedema.

Macular oedema is a leading cause of vision loss in patients with radiation retinopathy. In an effort to find an effective treatment for this vision threatening complication, 12 eyes (eight patients) were treated with photocoagulation for clinically significant radiation macular oedema (CSRMO) defined as central macular thickening, exudates threatening the macular centre, or one disc area of thickening in the macula. Median visual acuity improved from 20/100 preoperatively to 20/90 at the initial postoperative examination (mean follow up 5 months) and to 20/75 at the final postoperative examination (mean follow up 39 months). At the final postoperative examination, visual acuity had improved in eight (67%) eyes and six (50%) eyes had complete resolution of the CSRMO; two (17%) other eyes had improved anatomically in that fewer CSRMO criteria were present. These results suggest that macular photocoagulation is effective in decreasing macular oedema and improving vision in eyes with CSRMO.

Adolescent↗
PubMed1995

Inhibition of radiation cataractogenesis by WR-77913.

The radioprotective drug S-3-amino-2-hydroxypropylphosphorothioic acid (WR-77913) has been tested as an inhibitor of radiation cataractogenesis. Animals treated with 15 Gy whole-head 137Cs gamma radiation developed mature cataracts 10-12 weeks after irradiation. Intraperitoneal pretreatment with 815 mg/kg WR-77913 30 min before irradiation delayed the development of cataracts; mature cataracts required 42 weeks for development. Doses as low as 350 mg/kg, substantially below the toxic range, resulted in graded but incomplete protection and a significant delay in the development of cataracts. Drug treatment combined with radiation doses of 12.5 or 10 Gy showed less pronounced protection. The optimum time of drug delivery was found to be between 30 min and 2 h before irradiation; protective action diminished if longer times were used or if the drug was given after irradiation. These results are discussed in relation to those obtained with other chemical radioprotective agents and in terms of possible mechanisms of the action of the drug.

Amifostine↗