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Biomedical subjects

J J Carr

Publications and source records attributed to J J Carr.

At least 19 recordsLinked to original sources
PubMed2006

QTL-specific genotype-by-smoking interaction and burden of calcified coronary atherosclerosis: the NHLBI Family Heart Study.

BACKGROUND: Calcified coronary plaque (CCP) is a complex trait influenced by both genes and environment, and plausibly an interaction between the two. Because the familial aggregation of CCP has been demonstrated and smoking is a significant, independent predictor of CCP, we assessed the evidence for genotype-by-smoking interaction and conducted linkage analysis of quantitative Agatston CCP scores in participants of the NHLBI Family Heart Study (FHS). METHODS: During standardized clinical exams smoking habits were ascertained and CCP was quantified with cardiac computed tomography (CT). Among 4387 relationship pairs from 2128 Caucasian examinees variance component analysis was implemented in SOLAR to examine: (1) additive genotype-by-smoking status interaction using a variance component approach; (2) linkage analysis in the full sample and among smoking subsets defined by individual smoking exposure; (3) QTL-specific genotype-by-smoking interaction in the regions that appeared to differentiate between smoking strata. RESULTS: The prevalence of CCP (and median Agatston score) was 75% (184.6) in men and 48% (51.0) in women. We detected four genome-wide significant logarithm of odds (LOD) scores in samples stratified by individual smoking exposure: chromosome 4 at 122cM (nearest marker D4S2297; robust adjusted LOD=3.1; q=0.053), chromosome 6 at 99cM (nearest marker D6S1056; robust adjusted LOD=3.3; q=0.053), chromosome 11 at 19cM (nearest marker D11S199; robust adjusted LOD=4.0; q=0.02) and chromosome 13 at 77cM (nearest marker D13S892; robust adjusted LOD=3.1; q=0.053). Additive and QTL-specific genotype-by-smoking interaction was detected on chromosomes 4, 6, 11 and 13; all P<0.05. Three of the four QTLs identified in this report have been previously linked to atherosclerosis and harbor interesting candidate genes. CONCLUSIONS: These findings demonstrate the importance of considering complex interactions in the search for genes that influence the pathogenesis of CCP.

Adult↗
PubMed2006

Type 2 diabetes is not independently associated with spinal trabecular volumetric bone mineral density measured by QCT in the Diabetes Heart Study.

The purpose of this study was to investigate the association between type 2 diabetes mellitus (DM2) and trabecular volumetric bone mineral density (vBMD) of the thoracic and lumbar spine measured by quantitative computed tomography (QCT) in 483 female (410 with DM2) and 398 male (365 with DM2) adults (age 36-86 years, BMI 16-58, 88% with DM2) in the Diabetes Heart Study. After accounting for familial correlation using generalized estimating equations (GEE), lumbar spine vBMD was positively associated with BMI (r = 0.24, P < 0.0001) and inversely associated with age (r = -0.51, P < 0.0001). In women, age-adjusted thoracic spinal vBMD (mg/ml, mean +/- SE) was higher in diabetics (147.6 +/- 2.3) compared to unaffected individuals (138.6 +/- 3.4) (P = 0.02), with age-adjusted lumbar spinal vBMD showing a similar but non-significant trend (132.9 +/- 2.1 in diabetics vs. 127.2 +/- 3.6 in unaffected individuals, P = 0.15). In contrast, in men, age-adjusted lumbar and thoracic vBMD were not different between diabetics and unaffected controls (lumbar vBMD = 125.0 +/- 1.8 in diabetics and 125.8 +/- 5.6 in unaffected individuals, P = 0.89; thoracic vBMD = 137.4 +/- 2.1 in diabetics vs. 134.2 +/- 5.5 in controls, P = 0.56). After multivariate analysis adjusting for age, sex, race, BMI, physical activity, dietary intake, smoking, and alcohol use, interaction between diabetes status and trabecular vBMD of the spine was no longer observed. In women only, age-adjusted areal BMD (determined by dual X-ray absorptiometry (DXA)) of the spine and hip were significantly higher in diabetics than non-diabetic (all P < 0.05), although the differences disappeared after additional adjustment for BMI. These data suggest that areal BMD measured by DXA and trabecular volumetric BMD measured by QCT are not associated with type 2 diabetes independently from BMI.

Adult↗
PubMed2006

Association analysis of genes in the renin-angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: the Diabetes Heart Study.

AIMS: Cardiovascular disease (CVD) is a major complication of Type 2 diabetes mellitus. The renin-angiotensin system (RAS) and nitric oxide production are both important regulators of vascular function and blood pressure. Genes encoding proteins involved in these pathways are candidates for a contribution to CVD in diabetic patients. We have investigated variants of the angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AT1R) and endothelial nitric oxide synthase (NOS3) genes for association with subclinical measures of CVD in families with Type 2 diabetes mellitus (T2DM). METHODS: Atherosclerosis was measured by carotid intima-media thickness and calcification of the carotid and coronary arteries in 620 European Americans and 117 African Americans in the Diabetes Heart Study. Because of the role of these systems in blood pressure regulation, blood pressure was also investigated. RESULTS: Compelling evidence of association was not detected with any of the SNPs with any outcome measures after adjustments for covariates despite sufficient power to detect relatively small differences in traits for specific genotype combinations. CONCLUSIONS: Genetic variation of the RAS and NOS3 genes do not appear to strongly influence subclinical cardiovascular disease or blood pressure in this diabetic population.

Adult↗
PubMed2006

Hormone replacement therapy is associated with increased C-reactive protein in women with Type 2 diabetes in the Diabetes Heart Study.

AIMS: Increased levels of inflammatory biomarkers, especially C-reactive protein (CRP), are associated with increased risk for cardiovascular disease (CVD) events, such as myocardial infarction, stroke, peripheral vascular disease, and sudden cardiac death. Medical interventions that increase CRP levels, such as hormone replacement therapy (HRT) in post-menopausal women, are under increasing scrutiny. The effect of HRT on CRP levels in women with Type 2 diabetes (T2DM) is not well documented, and conflicting conclusions have been reported. The aim of this study was to determine the influence of HRT on women with diabetes in a large cross-sectional study. METHODS: Three hundred and twenty-seven post-menopausal women with T2DM from the Diabetes Heart Study participated. Current use of HRT was determined and serum CRP levels were measured using a high-sensitivity ELISA kit. Generalized estimating equation methods were used to assess the relationship of multiple clinical and lifestyle (e.g. smoking) measures on CRP levels including differences between women taking HRT (HRT+) and not taking HRT (HRT-). RESULTS: Overall serum CRP levels were strongly associated with body mass index (P < 0.0001) and age (P < 0.0001). Of the women, 243 were not using HRT and 84 were using HRT. HRT+ and HRT- women did not differ significantly in measures of clinical traits, with the exception of higher mean low-density lipoprotein cholesterol in HRT- women (P = 0.004). In all models tested, HRT+ women had significantly higher circulating CRP levels, with P-values ranging from 0.0045 to 0.010. CONCLUSIONS: In this study of serum CRP concentration as a function of HRT in women with Type 2 diabetes, there was consistent evidence for increased circulating CRP levels in women receiving oestrogen-containing HRT. Whether HRT-induced increases in CRP can account for the adverse cardiovascular effects of HRT remains to be established; however, based on these data, there is little reason to believe that diabetic women would be spared from such an effect.

Body Mass Index↗
PubMed2005

The impact of ethnicity and sex on subclinical cardiovascular disease: the Diabetes Heart Study.

AIMS/HYPOTHESIS: African-Americans with type 2 diabetes and access to adequate healthcare are at lower risk of clinical coronary artery disease than are white diabetic patients. We evaluated whether ethnic differences in subclinical cardiovascular disease, coronary and carotid artery calcified plaque and carotid artery intima-medial thickness (IMT) were present in members of The Diabetes Heart Study families. SUBJECTS AND METHODS: In a bi-racial cohort of 1,180 individuals from families enriched for members with type 2 diabetes, we calculated coronary and carotid artery calcified plaque using fast-gated helical computed tomography, and measured carotid artery IMT and clinical risk factor profiles. Generalised estimating equations were used to test for an association between measures of subclinical cardiovascular disease and ethnicity and sex. RESULTS: After adjustment for age, ethnicity and kidney function, African-Americans had significantly lower amounts of coronary artery calcified plaque (mean+/-SE) (866+/-158 vs 1,915+/-135, respectively; p=0.0466) and carotid artery calcified plaque (179+/-51 vs 355+/-27, respectively; p=0.0240) relative to whites, despite having increased carotid IMT (0.71+/-0.01 vs 0.67+/-0.004 cm, respectively; p=0.0007), and higher blood pressure, albuminuria and HbA1c. Sex-specific analyses revealed that African-American men had significantly lower coronary and carotid artery calcified atheroma than white men. In women, ethnic differences in calcified carotid artery plaque, but not coronary artery plaque, were observed. CONCLUSIONS/INTERPRETATION: In families enriched for members with type 2 diabetes, African-American men had markedly lower levels of coronary and carotid artery calcified plaque than white men, despite increased carotid artery IMT and conventional risk factors. These findings suggest that susceptibility to subclinical cardiovascular disease differs markedly according to ethnicity and sex.

Adult↗
PubMed2005

Association of genes of lipid metabolism with measures of subclinical cardiovascular disease in the Diabetes Heart Study.

BACKGROUND: Dyslipidaemia is a well known risk factor for cardiovascular disease (CVD). Lipid metabolism is affected by a range of genes and proteins. This study investigated whether some of these genes are associated with measures of subclinical CVD. METHODS: Polymorphisms of paraoxonase 1 and 2, cholesteryl ester transfer protein, hepatic lipase, and lipoprotein lipase were tested for associations with measures of subclinical CVD including carotid intima-media thickness measured by B-mode ultrasound and carotid and coronary arterial calcification measured by computed tomography. Analysis was performed in 620 European American participants in the Diabetes Heart Study, 83% of whom had type 2 diabetes mellitus. Associations of genotypes with subclinical CVD were tested by computing a series of generalised estimating equations. RESULTS: The Q192R variant of paraoxonase 1 and rs285 of lipoprotein lipase were associated with carotid artery calcium (p values = 0.002 and 0.005, respectively). Paraoxonase 2 S311C was associated with coronary artery calcium (p value = 0.037). CONCLUSIONS: There is evidence for modest, but significant, association of multiple single nucleotide polymorphisms in lipid genes with measures of subclinical CVD.

Aged↗
PubMed2004

Heritability of spinal trabecular volumetric bone mineral density measured by QCT in the Diabetes Heart Study.

The heritability of trabecular volumetric bone mineral density (BMD) determined by quantitative computed tomography (QCT) has not yet been reported. The purpose of this study was to investigate the heritability of BMD as determined by QCT and DXA in 124 women and 120 men (age 39-83 years, BMI 17-75, 84% type 2 diabetics) from 101 families (232 sibling pairs) in the Diabetes Heart Study. Volumetric BMD had a heritability (h2) estimate of 0.73 (SE = 0.15, P < 0.0001) at the lumbar spine and 0.71 (SE = 0.15, P < 0.0001) at the thoracic spine. Areal BMD heritability estimates were 0.56 for PA spine, 0.43 for total hip, 0.43 for femoral neck, 0.45 for distal radius, 0.42 for mid-radius, and 0.52 for whole body (all P < 0.01). After accounting for familial correlation using generalized estimating equations, volumetric BMD was inversely associated with age (r = -0.52, P < 0.0001) and duration of diabetes (r = -0.24, P < 0.01) and positively associated with body weight (r = 0.25, P < 0.01). In multivariate analysis, adjustment for age, sex, and race lowered the h2 estimates for volumetric BMD at the lumbar (h2 = 0.41, P < 0.01) and thoracic (h2 = 0.48, P < 0.001) spine, increased the h2 estimate for areal BMD at the mid radius (h2 = 0.58, P < 0.0001), and had little effect on the h2 estimate for areal BMD at other sites (h2 = 0.41-0.55, all P < 0.01). Additional adjustment for BMI, duration of diabetes, and physical activity had little effect on the h2 estimates for volumetric BMD or areal BMD except at the hip where they were lowered (h2 = 0.31-0.33, all P < 0.05). These data suggest that, like areal BMD, volumetric BMD is highly heritable and may be used in designing linkage studies to locate genes governing bone metabolism.

Absorptiometry, Photon↗
PubMed2003

Adiponectin as a novel determinant of bone mineral density and visceral fat.

Growing evidence suggests that positive associations between fat mass (FM) and bone mineral density (BMD) are mediated by not only biomechanical but also biochemical factors. Adiponectin is a novel adipocyte-derived hormone that regulates energy homeostasis and has anti-inflammatory and anti-atherogenic effects. Unlike other adipokines such as leptin, adiponectin levels decrease in obesity and type 2 diabetes. The purpose of our study was to investigate associations of serum adiponectin with BMD (DXA and QCT), FM (DXA and QCT), and serum leptin and soluble leptin receptor levels in 38 women and 42 men (age 39-81, BMI 17-55, 86% with type 2 diabetes). After adjusting for age, gender, race, smoking, and diabetes status, serum adiponectin was inversely associated with areal BMD (r = -0.20 to -0.3, all P < 0.01), volumetric BMD (r = -0.35 to -0.44, all P < 0.01), and visceral fat volume (r = -0.30, P < 0.01). These associations remained significant after adjusting for whole body fat mass. The associations of adiponectin with subcutaneous fat volume, whole body FM, and serum leptin level were not significant (all P > 0.1). These data suggest that adiponectin may play a role in the protective effects of visceral fat on BMD.

Adiponectin↗
PubMed2001

Coronary artery calcium quantification with retrospectively gated helical CT: protocols and techniques.

Current generation Helical Computed Tomography, when coupled with cardiac gating can be used to measure coronary vascular calcium. In this article we review the development of retrospectively gated helical computed tomography on a single slice HCT system and its relation to electron beam CT. The impact of heart rate on selection of helical pitch for the creation of a diastolic image set is detailed, as well as, scanning and post-processing techniques are discussed. The development and initial experience of cardiac gating with multidetector CT systems is presented.

Calcium↗
PubMed2001

Coronary calcium: the case for helical computed tomography.

This article provides the rationale for using helical (aka spiral, conventional, and mechanical) computed tomography (CT) systems from measuring coronary calcium. The current state and active research concerning measuring coronary calcium with single- and multi-slice systems is reviewed. The components of image quality, which are important to cardiac imaging with CT, are discussed. Companion articles will review electron beam CT (EBCT) for measuring coronary calcium and perhaps most importantly the scientific data relating coronary calcium to coronary heart disease and atherosclerosis.

Calcinosis↗
PubMed2001

Familial aggregation of coronary artery calcium in families with type 2 diabetes.

Type 2 diabetes is widely recognized as a major risk factor for atherosclerotic cardiovascular disease, including subclinical atherosclerosis as measured by noninvasive procedures. However, the role of genetic factors that contribute to various measures of subclinical atherosclerosis is largely unknown. We hypothesize that subclinical atherosclerosis, measured as coronary artery calcification (CAC), will be extensive in individuals with type 2 diabetes and that its presence depends on both genetic and environmental factors. The genetic factors should result in the familial aggregation of CAC. To determine the extent of familial aggregation of CAC in the presence of type 2 diabetes, we studied 122 individuals with type 2 diabetes (mean age 60 years) and 13 individuals without diabetes in 56 families. CAC was measured by fast-gated helical computed tomography. Other measured factors included blood pressure, body size, lipids, HbA1c, and self-reported medical history. To test for an association between CAC and these factors while accounting for the potential familial correlation of CAC, generalized estimating equations were used. CAC was detectable in 80% of individuals with diabetes (median score 84, range 0-5,776). Extent of CAC, adjusted for age, was positively associated with male sex (P = 0.0003), reduced HDL (P = 0.02), albumin-to-creatinine ratio (P = 0.008), and cigarette pack-years (P = 0.03). CAC was also positively associated with a history of angina, myocardial infarction, stroke, and vascular procedures (all P < 0.01). HbA1c and fasting glucose were positively, but nonsignificantly, associated with the extent of CAC (P = 0.14 and 0.08, respectively). CAC, adjusted for age, sex, race, and diabetes status, was heritable (h2 = 0.50; P = 0.009). In multivariate analysis with additional adjustment for HDL, BMI, hypertension, and smoking, h2 = 0.40 (P = 0.038). These results suggest that strong (independent) genetic factors as well as environmental factors contribute to the variance of CAC in individuals with type 2 diabetes. In these data, CAC seems heritable and may serve as an important feature in designing studies to map genes contributing to both atherosclerosis and type 2 diabetes.

Aged↗
PubMed2000

Requirements management: keeping your technology acquisition project under control.

Whether you are acquiring clinical or business information systems, patient monitoring systems, or therapeutic and diagnostic systems, the odds are good that the project will be delivered late, will cost far more than predicted, and will not provide all the features promised. The principal reason for project failure is improper management of the requirements of the system. Requirements engineering and management is a skill from the systems engineering profession that can be learned by nearly any professional who is managing a technology acquisition project. The author discusses what requirements engineering and management is and how it is done.

Equipment and Supplies, Hospital↗
PubMed2000

The length of time necessary to break even after converting to digital mammography.

The cost differences between film-based mammography (FBM) and digital mammography (DM) were estimated after discussions with hospital personnel and industry representatives. Human resource costs were not included. The fixed cost of FBM per machine was estimated to be $50,000 and the variable cost $4.60 per examination. The fixed cost of DM per machine was estimated to be $102,000 and the variable cost $0.10 per examination. The total number of examinations required to break even was therefore 11,556. At a rate of 15 examinations per machine per day and with 251 working days per year, it would take 3.1 years to break even. In the first year after the break-even point had been attained, $16,943 would be saved for every 3765 examinations performed. Extrapolating to the USA as a whole, in which 23 million mammographic examinations are performed each year, suggests that the annual savings from going filmless would be more than $103 million.

Breast Neoplasms↗
PubMed2000

Evaluation of subsecond gated helical CT for quantification of coronary artery calcium and comparison with electron beam CT.

OBJECTIVE: Since its introduction early in the 1990s, helical CT has become the predominant technology for obtaining CT images for medical applications. Recent improvements in the temporal resolution of helical CT (subsecond) and the addition of retrospective cardiac gating are combined in this report evaluating cardiac-gated helical CT for quantifying coronary artery calcium. We compare total calcium scores determined on subsecond gated helical CT with the current reference for coronary calcium evaluation, electron beam CT. MATERIALS AND METHODS: We compared total calcium scores obtained using a general purpose, unmodified helical CT scanner with scores obtained using electron beam CT in 36 individuals who were 68+/-11 years old (age range, 41-85 years). RESULTS: Correlation coefficients ranged from 0.97 to 0.98 (Pearson's product moment) and from 0.95 to 0.96 (Spearman's rank order), depending on the coronary calcium scoring method used. Agreement in the classification of participants as "healthy" or "diseased" at threshold total calcium scores of 10, 100, 160, 200, 400, and 680 was, respectively, 94%, 97%, 89%, 92%, 94%, and 100% using the conventional electron beam CT scoring method and an equivalent method with helical CT. CONCLUSION: A general purpose, current generation helical CT scanner equipped for retrospective cardiac gating can accurately quantify coronary calcium, and the results are highly correlated to scores obtained with electron beam CT. As an alternative method for measuring coronary calcium, gated subsecond cardiac helical CT offers greater availability and lower cost, thereby making population-based screening for coronary artery calcium more feasible.

Adult↗
PubMed1999

Sonohysterography: the next step in the evaluation of the abnormal endometrium.

Sonohysterography is a simple ultrasound (US) procedure that may be used to evaluate the endometrium. The technique involves placement of a 5-F catheter into the endometrial canal with subsequent instillation of sterile saline solution under US guidance. Fifty patients successfully underwent sonohysterography because of apparent abnormal endometrial thickening at transvaginal US, a nonspecific finding. Patients tolerated this procedure well, and no complications were encountered. In the 39 patients who proved to have endometrial pathologic conditions, sonohysterography demonstrated focal processes (polyps, carcinoma, hamartoma) in 15, diffuse processes (hyperplasia, secretory endometrium) in 21, and both focal and diffuse pathologic conditions in three. If a focal process can be delineated, a visually directed biopsy may be necessary. However, if the process is diffuse, a blind aspiration biopsy may be performed on an outpatient basis. In the majority of patients, the diffuse or focal nature of the disease could not be predicted on the basis of initial transvaginal US. Because sonohysterography allows distinction between diffuse and focal abnormalities, it provides physicians with a cost-effective way to plan the next step in case management.

Adult↗
PubMed1994

Patient screening prior to MR imaging: a practical approach synthesized from protocols at 15 U. S. medical centers.

The article by Boutin et al. [1] in this issue of the AJR documents a surprinsingly great variation in the MR screening procedures used at different academic centers throughout the United States. Although considerable literature now exists concerning the MR imaging of patients with ferromagnetic implants, devices, and foreign bodies [2-4], no uniform screening protocol to identify such patients has yet been adopted. The Safety Committee of the Society for Magnetic Resonance Imaging (SMRI) has recommended that "each imaging site should develop a standardized policy for screening patients with suspected metallic foreign bodies" [5]. To date, however, the SMRI has neither proposed nor endorsed a specific screening protocol for general use.

Academic Medical Centers↗