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Biomedical subjects

LeRoy E Rabbani

Publications and source records attributed to LeRoy E Rabbani.

11 recordsLinked to original sources
PubMed2005

Anti-human leukocyte antigen antibodies are associated with restenosis after percutaneous coronary intervention for cardiac allograft vasculopathy.

BACKGROUND: Percutaneous coronary intervention (PCI) to palliate cardiac allograft vasculopathy (CAV) has been associated with high restenosis rates, possibly related to increased inflammation associated with this disease. Whether markers of immunologic rejection are associated with restenosis in this population is unknown. The goal of the study was to determine the predictors of restenosis after PCI for CAV. METHODS: Records were reviewed retrospectively from a single, high-volume cardiac transplant center. Clinical, angiographic, and immunologic data were collected on all patients postorthotopic heart transplantation (OHT) that had subsequent PCI. Restenosis was defined as greater than 50% stenosis at the previous intervention site. RESULTS: PCI was successfully performed on 62 de novo lesions in 40 patients an average of 6.8+/-3.9 years after OHT. Angiographic follow-up data was available for 79%, with an average follow-up of 1.54+/-1.22 years. The 1-year restenosis rate was 49% (64% for balloon percutaneous transluminal coronary angioplasty and 33% for coronary stenting [P=0.09 for difference]). The frequency of immunoglobulin (Ig)G antibody to major histocompatibility complex (MHC) class I antigen was highly associated with risk of restenosis (hazard ratio [HR] 11.33, P=0.01). Greater stenosis severity and smaller target vessel diameter were also predictors of restenosis as in the nontransplant population. CONCLUSIONS: The findings suggest that in patients postPCI for CAV, humoral allo-immunity may contribute to restenosis and that IgG antibodies to MHC class I antigen may help predict the risk of restenosis after PCI in this population.

Angioplasty, Balloon, Coronary↗
PubMed2004

A rationale for the use of anticoagulation in heart failure management.

Heart failure is a major public health concern for which treatment options have continued to evolve. While specific therapies such as beta blockers and angiotensin converting enzyme inhibitors have been shown to decrease hospitalizations and improve survival, the benefits of anticoagulation are less clear. Clinical guidelines detailing the appropriate use of anticoagulation for the management of atrial fibrillation and embolic stroke exist, but similar recommendations for their use in isolated cardiac dysfunction are lacking. Epidemiologic studies have documented increased risk of thrombus formation and stroke occurrence in patients with cardiomyopathy that is inversely related to ejection fraction. However, it remains at the clinician's discretion to determine at what degree of left ventricular dysfunction the potential benefits of stroke reduction outweigh the risks of undesirable bleeding with anticoagulation. This paper summarizes the pathophysiology of thrombus formation in heart failure patients; reviews previous studies and current recommendations for anticoagulation; provides a clinical rationale for anticoagulation when conclusive data are lacking; and discusses ongoing clinical trials designed to clarify these issues.

Anticoagulants↗
PubMed2004

Evidence for C-reactive protein's role in (CRP) vascular disease: atherothrombosis, immuno-regulation and CRP.

For clinicians plasma C-reactive protein (CRP) levels are the only widely available tests that provide a tangible link between inflammation and atherosclerosis. New AHA/CDC joint guidelines from 2002-03 now include the measurement of CRP as a class IIa recommendation for stratifying patients with known cardiovascular disease (CVD) at a moderate (10-20%) 10-year event risk and a class IIb recommendation for patients without known CVD [1]. While the association of CRP and atherosclerosis is by now accepted, the molecular biology behind the association is evolving rapidly into a fascinating story. While some of the story remains obscure, this review aims to bridge the clinical and basic science and identify what is known about the role of this ancient molecule in atherosclerosis. The review covers CRP's interaction with atherosclerosis' major ingredients and cell types including the endothelium, monocytes and neutrophils, lipoproteins and the complement system. Taken together, the clinical and basic science leave the tantalizing impression that CRP has a fundamental role in atherogenesis, and hint at a more complex immunomodulatory effect which transforms the acute inflammatory response to vascular injury into the chronic inflammation seen in atherosclerosis.

Animals↗
PubMed2004

Dynamic variability of hemostatic and fibrinolytic factors in young women.

This prospective study was designed to characterize the time course and variability of hemostatic and fibrinolytic risk factors over the course of a menstrual cycle in normal premenopausal women. Plasminogen activator inhibitor (PAI-1), tissue plasminogen activator, von Willebrand factor, fibrinogen, and fibrin D-dimer predict risk of coronary heart disease. Yet there is limited information describing the status of endogenous hormone concentrations and hemostatic and coagulation factors in premenopausal women. Twenty premenopausal women, mean age 34 +/- 7 yr, underwent testing over a cycle to measure endogenous hormones and hemostatic factors: estradiol and progesterone, FSH, LH; PAI-1, tissue plasminogen activator, von Willebrand factor, fibrin D-dimer, and fibrinogen as well as lipids: total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides. There was cyclical variability in estradiol (P < 0.01) and progesterone (P < 0.001) during the follicular and luteal phases. Moreover, there was intra- and interindividual cyclical variation in hemostatic risk factors. Measures of PAI-1 (P < 0.01) and D-dimer (P < 0.05) differed during the follicular and luteal phases. As estradiol concentration increased, PAI-I decreased. There was a significant correlation between total cholesterol and PAI-1 (r = 0.56, P < 0.05), low-density lipoprotein-cholesterol and PAI-1 (r = 0.50, P < 0.05) as well as between total cholesterol and fibrinogen (r = 0.61, P < 0.05). There is significant cyclical variability in estradiol, FSH, and progesterone as well as the hemostatic factors, PAI-1 and fibrin D-dimer. Characterization of emerging hemostatic risk factors enhances understanding of normal physiology, provides insight into the relation between estrogen and hemostatic factors, and raises the potential for predicting coronary heart disease even in relatively young women.

Adult↗
PubMed2003

Value of definitive diagnostic testing in the evaluation of patients presenting to the emergency department with chest pain.

The optimal diagnostic evaluation of patients presenting to the emergency department (ED) with chest pain but without myocardial infarction or unstable angina is controversial. We performed a prospective, nonrandomized, observational study of 1,195 consecutive patients presenting to the ED with chest pain but who had normal or nondiagnostic electrocardiograms and negative cardiac biomarkers. Patients (mean +/- SD age 61 +/- 15 years; 55% women) were admitted to the hospital and a standard protocol for evaluation and treatment was suggested. The use of stress myocardial perfusion imaging (MPI) or cardiac catheterization during their index hospitalization, and the 3-month incidence of coronary angiography, percutaneous cardiac intervention, coronary artery bypass surgery, re-presentation to our institution's ED for chest pain, myocardial infarction, or death were followed. Five hundred nine of 1,195 patients (43%) underwent provocative stress MPI during their index hospitalization; 37% had perfusion defects (predominantly ischemia). Fifty-six of 1,195 patients (4%) underwent cardiac catheterization without stress MPI for their primary diagnostic evaluation. Six hundred thirty of 1,195 patients (53%) had neither MPI or cardiac catheterization during their index hospitalization. During the 3-month follow-up period, patients with a normal stress perfusion study during their index hospitalization had fewer return visits (4%) compared with patients with abnormal perfusion studies (19%), those who underwent catheterization directly (16%), or patients with no initial diagnostic evaluation (15%) (p <0.001). In addition, patients who had a diagnostic evaluation during their index hospitalization had a lower incidence of either acute myocardial infarction (0.9% vs 2.1%) or death (0.4% vs 3.0%, p <0.001) in the 3-month follow-up period. Accordingly, we strongly advocate provocative stress MPI early after presentation for chest pain in all patients with risk factors for coronary artery disease.

Age Factors↗
PubMed2003

Reverse CPR: a pilot study of CPR in the prone position.

BACKGROUND: Cardiopulmonary resuscitation (CPR), as described in 1960, remains the cornerstone of therapy for cardiopulmonary arrest. Recent case reports have described CPR in the prone position. We hypothesized rhythmic back pressure on a patient in the prone position with sternal counter-pressure (termed reverse CPR here) would increase intra-thoracic pressure and in turn systolic blood pressure (SBP) during cardiac arrest versus standard CPR. METHODS AND RESULTS: Six patients from Columbia Presbyterian Medical Center's Cardiac and Medical Intensive Care Units (CICU and MICU) were enrolled. Eligible patients had suffered circulatory arrest and failed standard CPR for at least 30 min. After enrollment the patients received 15 additional min of standard CPR and then reverse CPR for 15 min. The study's primary endpoint, mean SBP, significantly improved from 48 mmHg during standard CPR to 72 mmHg during reverse CPR (mean improvement=23+/-14 mmHg). Mean calculated mean arterial pressure (MAP) was also improved significantly from 32 mmHg during standard CPR to 46 mmHg during reverse CPR (mean improvement=14+/-11 mmHg). The mean diastolic blood pressure (DBP) improved from 24 mmHg during standard to 34 mmHg during reverse CPR (mean improvement=10+/-12 mmHg). This difference did not meet statistical significance. No patients had return of spontaneous circulation. CONCLUSIONS: Reverse CPR generates higher mean SBP and higher mean MAP during circulatory arrest than standard CPR. These novel findings justify further research into this technique.

Adult↗
PubMed2003

Minocycline inhibits smooth muscle cell proliferation, migration and neointima formation after arterial injury.

The tetracyclines are antimicrobials that also inhibit expression of certain matrix metalloproteinases (MMPs). We conducted a series of experiments to determine if minocycline could inhibit MMP expression and limit human aortic smooth muscle cell (SMC) proliferation and migration. Analysis of SMC proliferation was performed after cells were grown in minocycline-incubated media. SMC migration activity was assayed in a micro-Boyden chamber. Western blotting revealed that minocycline reduced SMC production of MMP-2 in a dose dependent manner. Increasing doses of minocycline progressively reduced SMC proliferation to 49% of control values and limited SMC migration to 15% of control. When administered to rats with balloon injured carotid arteries, intraperitoneal doses of minocycline (70-100 mg/kg) reduced neointima formation by 76%, but were associated with liver toxicity. Higher doses were lethal and lower doses were ineffective. Minocycline, applied to injured arteries in a pluronic gel with a low pH, was also ineffective. In summary, minocycline lowers MMP-2 expression, reduces SMC proliferation and migration, and inhibits neointimal hyperplasia, but its efficacy is limited by systemic toxicity.

Angioplasty, Balloon↗
PubMed2002

Oral conjugated equine estrogen increases plasma von Willebrand factor in postmenopausal women.

OBJECTIVES: We sought to test whether one month of daily oral conjugated equine estrogen (CEE) or transdermal estradiol alters hemostatic factors in postmenopausal subjects. BACKGROUND: Estrogen replacement therapy and hormonal replacement therapy (HRT) effect an early increase in cardiovascular events in postmenopausal women. Circulating plasma von Willebrand factor (vWF) antigen is a marker of generalized endothelial dysfunction and atherothrombosis. METHODS: Thirty-eight healthy postmenopausal women (average 59 +/- 7 years) were randomized to receive daily oral CEE, 0.625 mg (n = 21); transdermal estradiol, 0.1 mg/day (n = 7); or oral placebo (n = 10) for one month. Blood samples were collected at baseline and after two weeks and four weeks of therapy for measurement of circulating plasma hormones, lipid concentrations, and hemostatic factors. RESULTS: Oral CEE decreased total cholesterol (p < 0.01) and low-density lipoprotein cholesterol (p < 0.01), although it increased both triglycerides (p < 0.05) and high-density lipoprotein cholesterol (p < 0.01). Transdermal estradiol had no significant effect on lipids. Plasminogen activator inhibitor-1 antigen declined in both oral CEE and transdermal estradiol users, but did not achieve statistical significance. Fibrin D-dimer antigen did not vary significantly in any group. However, oral CEE users had a significant increase in vWF from baseline to four weeks (p < 0.03) and a decrease in tissue-type plasminogen activator antigen from baseline to four weeks (p < 0.004), which was significantly different from the change observed in the transdermal estradiol group (p < 0.05). CONCLUSIONS: These data suggest that the oral CEE-mediated increase in plasma vWF may have clinical relevance given the early atherothrombotic effects of HRT in postmenopausal women.

Administration, Cutaneous↗
PubMed2002

Tumor necrosis factor receptor levels are associated with carotid atherosclerosis.

BACKGROUND AND PURPOSE: Recent evidence suggests that atherosclerosis is an inflammatory condition. Serum levels of inflammatory markers may serve as measures of the severity of atherosclerosis and risk of stroke. We sought to determine whether tumor necrosis factor-alpha (TNF-alpha) and TNF receptor levels are associated with carotid plaque thickness. METHODS: The Northern Manhattan Stroke Study is a community-based study of stroke risk factors. For this cross-sectional analysis, inflammatory marker levels, including TNF-alpha and TNF receptors 1 and 2, were measured by immunoassay in stroke-free community subjects undergoing carotid duplex Doppler ultrasound. Maximal carotid plaque thickness (MCPT) was measured for each subject. Analyses were stratified by age < 70 and > or =70 years. Simple and multiple linear regression analyses were used to calculate the association between marker levels and MCPT. Multiple logistic regression was used to calculate odds ratios and 95% CIs for the association of inflammatory markers with MCPT > or =1.5 mm (>75th percentile), after adjustment for demographic and potential medical confounding factors. RESULTS: The mean age of the 279 subjects was 67.6+/-8.5 years; 49% were men; 63% were Hispanic, 17% black, and 17% white. Mean values for TNF-alpha and its receptors were as follows: TNF-alpha, 1.88+/-3.97 ng/mL; TNF receptor 1, 2.21+/-0.99 ng/mL; and TNF receptor 2, 4.85+/-2.23 ng/mL. Mean MCPT was elevated in those in the highest quartiles compared with lowest quartiles of TNF receptor 1 and 2 (1.24 versus 0.79 mm and 1.23 versus 0.80 mm, respectively). Among those aged < 70 years, TNF receptor 1 and 2 were associated with an increase in MCPT (mean difference=0.36 mm, P=0.01 for TNF receptor 1 and mean difference=0.10 mm, P=0.04 for TNF receptor 2). After adjustment for sex, race-ethnicity, hypertension, diabetes mellitus, LDL cholesterol, smoking, and body mass index, associations remained (mean difference=0.36 mm, P=0.001 for TNF receptor 1 and mean difference=0.09 mm, P=0.051 for TNF receptor 2). There was no association for TNF receptors in those aged > or = 70 years old and no association for TNF-alpha in either age group. Among those aged < 70 years, each unit increase in TNF receptor level increased the odds of the participant's having MCPT > or =1.5 mm (adjusted odds ratio=4.7; 95% CI, 1.7 to 15.4 for TNF receptor 1; odds ratio=1.9; 95% CI, 1.3 to 2.9 for TNF receptor 2). CONCLUSIONS: Relative elevation in TNF receptor levels, but not TNF-alpha, is associated with carotid atherosclerosis among individuals aged < 70 years in this multiethnic, urban population. Chronic subclinical infection or inflammation may account for this association, and modification of these inflammatory pathways may provide a novel approach to stroke prevention.

Age Factors↗
PubMedDate not supplied

Interleukin-6 is associated with cognitive function: the Northern Manhattan Study.

BACKGROUND AND PURPOSE: Inflammation has been linked to cognitive decline and dementia but the mechanism is not clear and few studies have included Hispanic and black subjects that may be at increased risk of these disorders. METHODS: We performed a cross-sectional analysis of the association between inflammatory marker levels and cognition in the stroke-free population-based cohort of the Northern Manhattan Study. Mini Mental State Exam (MMSE) scores were the continuous outcome and we adjusted for sociodemographic and vascular risk factors as well as subclinical atherosclerosis. RESULTS: Of the inflammatory markers, only interleukin (IL)-6 levels were associated with the MMSE. In univariate analysis age, hypertension, diabetes, smoking, moderate alcohol use, total homocysteine, carotid intima media thickness, and body mass index were positively associated with IL-6 levels. Hispanics compared to whites, those with less than a high school education, hypertension, cardiac disease, and total homocysteine were associated with lower MMSE scores. In a multivariate linear regression model, IL-6 was negatively associated with MMSE score adjusting for sociodemographic and vascular risk factors. CONCLUSIONS: IL-6 levels were negatively associated with performance on the MMSE in this multiethnic cohort. Adjusting for vascular disease and subclinical atherosclerosis did not attenuate the association, suggesting a direct effect on the brain.

Journal Article↗