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Biomedical subjects

A R Patel

Publications and source records attributed to A R Patel.

At least 19 recordsLinked to original sources
PubMed2006

Low levels of high-density lipoprotein cholesterol are associated with vascular remodeling in cardiac transplant recipients.

BACKGROUND: Early atherosclerosis may be associated with compensatory vessel enlargement, termed positive remodeling. Enlarged brachial artery diameter has been reported in patients with risk factors for atherosclerosis and in individuals with coronary atherosclerosis, indicating that brachial artery enlargement is a marker for the presence of atherosclerotic changes. Cardiac transplant recipients often have abnormal lipid levels, but the effect of specific lipid abnormalities on vascular remodeling in this population has not been evaluated. This study examined the relationship between lipid levels and brachial artery diameter in cardiac transplant recipients. METHODS: Thirty-five stable cardiac transplant recipients underwent high-resolution brachial artery ultrasound to evaluate resting brachial artery diameter. Levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were determined and the presence of other cardiac risk factors was assessed. RESULTS: Brachial artery diameter was larger (4.3 +/- 0.1 mm) in subjects with low levels of HDL-C (< 40 mg/dL, n = 11) compared to subjects with high HDL-C (> or = 40 mg/dL, n = 24), who had a mean brachial artery diameter of 3.7 +/- 0.1 mm (P = .006). Neither high LDL-C (> or = 100 mg/dL) nor high triglycerides (> or = 200 mg/dL) were associated with differences in brachial artery diameter. Multivariate analysis demonstrated that the relationship between low HDL-C and increased brachial artery diameter was independent of body surface area or statin use. CONCLUSIONS: Low levels of HDL-C are an independent predictor of brachial artery enlargement in stable cardiac transplant recipients. These findings suggest that suboptimal HDL-C levels may be associated with the development of vascular remodeling and atherosclerosis in this population.

Adult↗
PubMed2006

Noninvasive testing for coronary artery disease in women.

Coronary artery disease is a major cause of morbidity and mortality for women in North America and Europe. Given the significance of coronary disease as a public health problem among women, accurate diagnosis of this condition is of great importance. Several noninvasive testing modalities are available for the diagnosis of coronary heart disease. An understanding of gender-based differences related to noninvasive cardiac testing is useful in order to optimally utilize these tests and improve detection and clinical outcomes in women.

Carotid Arteries↗
PubMed2004

Bupivacaine provides rapid, effective periprostatic anaesthesia for transrectal prostate biopsy.

OBJECTIVE: To examine the effectiveness of the longer acting agent bupivacaine in providing periprostatic anaesthesia during transrectal ultrasonography (TRUS)-guided biopsy, as the periprostatic injection of lidocaine has been shown to significantly alleviate the pain of this procedure. PATIENTS AND METHODS: Seventy-five patients were randomized to receive a periprostatic injection with either bupivacaine, a lidocaine/bupivacaine (1/1) combination, or no local anaesthesia. Immediately before biopsy 5 mL of the anaesthetic was injected under TRUS guidance into the periprostatic nerves bilaterally. After taking a 10-core biopsy the patients were given a visual analogue scale (VAS; 0-10) to assess their pain during the procedure. RESULTS: The mean VAS scores were 2.04 in the bupivacaine group and 4.46 in the control (no local anaesthetic) group (P < 0.001). CONCLUSIONS: Bupivicaine provides significant, immediate periprostatic anaesthesia for TRUS biopsy.

Anesthetics, Combined↗
PubMed2001

Lower body negative pressure: a test of cardiovascular autonomic function.

Lower body negative pressure (LBNP) may provide an alternative test of cardiovascular autonomic function for patients unable to perform the Valsalva maneuver (VM). LBNP at -40 mmHg for 30 s was compared to the VM at 40 mmHg for 15 s with heart rate and blood pressure measured continuously in three age groups: 10-25 years; 26-40 years; and 41-55 years. Heart rate and blood pressure responses were comparable, with moderately diminished changes in blood pressure and heart rate in the LBNP test. When heart response to LBNP was converted to a ratio similar to that calculated for the VM, a high degree of correlation was found (R(2) = 0.5711). The LBNP test shows promise as an alternative test of cardiovascular autonomic function based on studies in normal subjects. The less marked changes may relate to the more passive nature of the applied stress. Future work should improve the device's accessibility and establish values for patients with autonomic disorders.

Adolescent↗
PubMed2001

Role of tensile stress and strain in the induction of cell death in experimental vein grafts.

Tensile stress and strain are known to induce vascular cell proliferation, a process that is physiologically counterbalanced by cell death. Here we investigate whether tensile stress and strain regulate vascular-cell death by using an end-to-end anastomosed rat vein graft model. In such a model, the circumferential tensile stress in the graft wall was increased by approximately 140 times immediately after surgery compared with that in the venous wall. This change was associated with an increase in the percentage of TUNEL-positive cells at 1, 6, 24, 120, 240, and 720h with two distinct peaks at 1 and 24h (10.1+/-3.5 and 14.4+/-3.2%, respectively) compared with that in control jugular veins (0.4+/-0.5 and 0.5+/-0.5% at 1 and 24h, respectively). When tensile stress and strain in the vein graft wall were reduced by using a biomechanical engineering approach, the rate of cell death was reduced significantly (3.6+/-1.1 and 1.6+/-0.5% at 1 and 24h, respectively). Furthermore, DEVD-CHO, a tetrapeptide aldehyde that inhibits the activity of caspase 3, significantly suppressed this event. These results suggest that a step increase in tensile stress and strain in experimental vein grafts induces rapid cell death, which is possibly mediated by cell death signaling mechanisms.

Anastomosis, Surgical↗
PubMed2001

Heart failure etiology affects peripheral vascular endothelial function after cardiac transplantation.

OBJECTIVES: The goal of this study was to examine the effect of heart failure etiology on peripheral vascular endothelial function in cardiac transplant recipients. BACKGROUND: Peripheral vascular endothelial dysfunction occurs in patients with heart failure of either ischemic or nonischemic etiology. The effect of heart failure etiology on peripheral endothelial function after cardiac transplantation is unknown. METHODS: Using brachial artery ultrasound, endothelium-dependent, flow-mediated dilation (FMD) was assessed in patients with heart failure with either nonischemic cardiomyopathy (n = 10) or ischemic cardiomyopathy (n = 7), cardiac transplant recipients with prior nonischemic cardiomyopathy (n = 10) or prior ischemic cardiomyopathy (n = 10) and normal controls (n = 10). RESULTS: Patients with heart failure with either ischemic cardiomyopathy or nonischemic cardiomyopathy had impaired FMD (3.6 +/- 1.0% and 5.1 +/- 1.2%, respectively, p = NS) compared with normal subjects (13.9 +/- 1.3%, p < 0.01 compared with either heart failure group). In transplant recipients with antecedent nonischemic cardiomyopathy, FMD was markedly higher than that of heart failure patients with nonischemic cardiomyopathy (13.0 +/- 2.4%, p < 0.001) and similar to that of normal subjects (p = NS). However, FMD remained impaired in transplant recipients with prior ischemic cardiomyopathy (5.5 +/- 1.5%, p = 0.001 compared with normal, p = 0.002 vs. transplant recipients with previous nonischemic cardiomyopathy). CONCLUSIONS: Peripheral vascular endothelial function is normal in cardiac transplant recipients with antecedent nonischemic cardiomyopathy, but remains impaired in those with prior ischemic cardiomyopathy. In contrast, endothelial function is uniformly abnormal for patients with heart failure, regardless of etiology. These findings indicate that cardiac transplantation corrects peripheral endothelial function for patients without ischemic heart disease, but not in those with prior atherosclerotic coronary disease.

Adult↗
PubMed2001

Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease.

OBJECTIVES: We studied whether assessment of endothelium-dependent vasomotion (EDV) with brachial artery ultrasound (BAUS) imaging predicts the presence or absence of coronary artery disease (CAD) as defined by exercise myocardial perfusion imaging (ExMPI). BACKGROUND: Abnormalities in EDV can be detected in arteries before the development of overt atherosclerosis, and its presence may predict poor long-term prognosis. Brachial artery ultrasound during reactive hyperemia is a noninvasive method of assessing peripheral EDV. METHODS: Clinically-indicated ExMPI along with BAUS were performed in 94 subjects (43 women, 51 men). Coronary artery disease was defined by myocardial ischemia or infarction on single photon emission computed tomography images. Flow-mediated dilation (FMD) after upper arm occlusion was defined as the percent change in arterial diameter during reactive hyperemia relative to the baseline. RESULTS: Subjects with CAD by ExMPI (n = 23) had a lower FMD (6.3 +/- 0.7%) than those without CAD by ExMPI (n = 71) (10.5 +/- 0.6%; p = 0.0004). Flow-mediated dilation was highly predictive for CAD with an odds ratio of 1.32 for each percent decrease in FMD (p = 0.001). Based on a receiver-operator analysis, an FMD of 10% was used as a cut-point for further analysis. Twenty-one of 23 subjects who were positive for ExMPI had an FMD < 10% (sensitivity 91%), whereas only two of 40 subjects with an FMD > or =10% were ExMPI-positive (negative predictive value: 95%). There was a correlation between the number of cardiac risk factors and FMD. Individuals with an FMD < 10% exercised for a shorter duration than those with an FMD > or =10% (456 +/- 24 vs. 544 +/- 31 s, respectively; p = 0.02). CONCLUSIONS: Assessment of EDV with BAUS has a high sensitivity and an excellent negative predictive value for CAD and, thus, has the potential for use as a screening tool to exclude CAD in low-risk subjects. Further standardization of BAUS is required, however, before specific cut-points for excluding CAD can be established.

Brachial Artery↗
PubMed2000

Mitral regurgitation: comprehensive assessment by echocardiography.

Two-dimensional and Doppler echocardiography have become the major modalities for the assessment of mitral regurgitation. The combined use of these techniques provides information regarding the morphology of the valvular apparatus as well as the severity of regurgitation. Transesophageal and three-dimensional echocardiography provide a more-detailed evaluation of valve morphology, which can be valuable in determining suitability for valve repair. In patients with severe mitral regurgitation, echocardiographic assessment of ventricular size and function plays a critical role in determining the optimal timing of surgery.

Echocardiography↗
PubMed1999

Polyamine depletion is associated with an increase in JunD/AP-1 activity in small intestinal crypt cells.

Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of protooncogene (Jun and Fos) subunits that bind to a common DNA site, the AP-1 binding site. The proteins of c-Jun, JunB, and Fos are essential for initiation of the cell cycle. Conversely, the activation of the junD gene slows cell growth in some cell types. The current study tests the hypothesis that polyamines influence cell growth by altering the balance of positive and negative Jun/AP-1 activities in intestinal epithelial cells. Studies were conducted in the IEC-6 cell line derived from rat small intestinal crypt cells. Administration of alpha-difluoromethylornithine (DFMO), a specific inhibitor for polyamine synthesis, for 4 and 6 days completely depleted cellular polyamine levels, while AP-1 binding activity was significantly increased. Spermidine, when given together with DFMO, restored AP-1 binding activity toward normal. The increased AP-1 complexes in polyamine-deficient cells were dramatically supershifted by the anti-JunD antibody but not by antibodies against c-Jun, JunB, or Fos proteins. There were significant increases in JunD mRNA and protein in DFMO-treated cells, although expression of the c-fos, c-jun, and junB genes decreased. The increase in JunD/AP-1 activity in DFMO-treated cells was associated with a significant decrease in cell division. Exposure of control quiescent cells to 5% dialyzed serum increased c-Jun/AP-1 but not JunD/AP-1 activities. DFMO prevented the stimulation of c-Jun/AP-1 activity induced by 5% dialyzed serum. These results indicate that 1) polyamine depletion is associated with an increase in AP-1 binding activity and 2) the increase in AP-1 activity in the DFMO-treated cells was primarily contributed by an increase in the JunD/AP-1. These findings suggest that polyamines regulate cell growth at least partially by modulating the balance of positive and negative Jun/AP-1 activities in the intestinal mucosa.

Animals↗
PubMed1998

Echocardiographic analysis of regional and global left ventricular shape in Chagas' cardiomyopathy.

Chagas' heart disease is a common form of cardiomyopathy in Latin America and an important cause of cardiac morbidity and mortality there. Left ventricular (LV) apical aneurysm and LV dysfunction are frequent findings in Chagas' cardiomyopathy. Because cardiac shape has important implications for LV function, we sought to characterize regional and global changes in LV geometry in Chagas' heart disease. Quantitative shape analysis was performed on 2-dimensional echocardiograms from 43 patients with Chagas' cardiomyopathy. Regional shape was quantitated by measuring endocardial curvature and global shape was evaluated by Fourier shape analysis of the endocardial contour. Data from 22 age- and sex-matched normal test subjects were used for comparison. Regional shape analysis demonstrated decreased apical curvature (consistent with blunting of normal apical shape) in the group with Chagas' disease compared with controls (apical 2-chamber view: 19 +/- 1 vs 24 +/- 1 [p = 0.0039] at end-diastole and 20 +/- 2 vs 29 +/- 3 [p = 0.0019] at end-systole). Fourier shape power index was decreased in the Chagas' group, consistent with a more spherical ventricle (apical 2-chamber view: 9 +/- 1 vs 17 +/- 2 [p <0.0001] at end-diastole and 12 +/- 1 vs 35 +/- 3 [p <0.0001] at end-systole). Shape changes among the population with Chagas' disease were further evaluated in those with end-diastolic volumes equal to or greater than the median for the group (104 ml) and those < 104 ml. Global shape did not differ between patients with dilated ventricles and those with relatively nondilated ventricles. Diastolic Fourier shape power index = 8 +/- 2 in dilated ventricles compared with 9 +/- 5 in nondilated ventricles (p = 0.53); systolic Fourier shape power index = 10 +/- 2 in dilated versus 14 +/- 2 in nondilated ventricles (p = 0.15) (apical 2-chamber view). In Chagas' cardiomyopathy, LV apical deformation results in disruption of the optimal global prolate-ellipsoid shape, even in patients with relatively preserved LV volumes.

Adult↗
PubMed1998

Differences in transglutaminase mRNA after polyamine depletion in two cell lines.

Polyamines serve as natural substrates for the transglutaminase that catalyzes covalent cross-linking of proteins and is involved in cellular adhesion and proliferation. This study tests the hypothesis that intracellular polyamines play a role in the regulation of transglutaminase expression in rat small intestinal crypt cells (IEC-6 cell line) and human colon carcinoma cells (Caco-2 cell line). Treatment with alpha-difluoromethylornithine (DFMO; a specific inhibitor of polyamine synthesis) significantly depleted the cellular polyamines putrescine, spermidine, and spermine in both cell lines. In IEC-6 cells, polyamine depletion was associated with a decrease in the levels of transglutaminase mRNA. In Caco-2 cells, however, polyamine depletion significantly increased the levels of transglutaminase mRNA and enzyme activity. In both cell lines, ornithine decarboxylase mRNA levels increased and protooncogene c-myc mRNA decreased in the presence of DFMO. Addition of polyamines to cells treated with DFMO reversed the effect of DFMO on the levels of mRNA for these genes in both lines. There was no significant change in the stability of transglutaminase mRNA between control and DFMO-treated IEC-6 cells. In contrast, the half-life of mRNA for transglutaminase in Caco-2 cells was dramatically increased after polyamine depletion. Spermidine, when given together with DFMO, completely prevented increased half-life of transglutaminase mRNA in Caco-2 cells. These results indicate that 1) expression of transglutaminase requires polyamines in IEC-6 cells but is inhibited by these agents in Caco-2 cells, 2) polyamines modulate transglutaminase expression at the level of mRNA through different pathways in these two cell lines, and 3) posttranscriptional regulation plays a major role in the induction of transglutaminase mRNA in polyamine-deficient Caco-2 cells.

Animals↗
PubMed1998

Synergistic induction of ornithine decarboxylase by asparagine and gut peptides in intestinal crypt cells.

The objective of this study was to determine whether the amino acid asparagine stimulated the activity of ornithine decarboxylase (ODC) synergistically with epidermal growth factor (EGF) or gastrin in IEC-6 cells, a line of normal rat small intestinal crypt cells. Cells were grown in DMEM containing 5% dialyzed fetal bovine serum, and serum was deprived for 24 h before experiments. Exposure to EGF or gastrin alone increased ODC activity 4.5- to 6-fold. Asparagine alone increased the enzyme activity 10- to 13-fold in IEC-6 cells. Simultaneous addition of asparagine and EGF or gastrin, however, increased ODC activity more than 40-fold. In contrast, there was no synergistic induction of ODC activity when gastrin and EGF were added together. Increased ODC activity in cells treated with asparagine and EGF or gastrin was associated with an increase in ODC mRNA and protein levels. The rate of transcription of the ODC gene was significantly increased by exposure to EGF or gastrin. Asparagine alone had little or no effect on the rate of transcription of the ODC gene. When given together with EGF or gastrin, asparagine also had no additional effect on the transcription rate of the ODC gene. The half-life of mRNA for ODC in unstimulated IEC-6 cells was approximately 30 min and increased to more than 2 h in cells exposed to asparagine, although neither gastrin nor EGF prolonged the stability of ODC mRNA. The half-life of mRNA for ODC after combined addition of asparagine and EGF or gastrin was extended to approximately 2 h, similar to asparagine alone. Combined addition of asparagine and EGF or gastrin also significantly increased DNA synthesis compared with cells exposed to each of the three agents alone. In conclusion, 1) simultaneous addition of asparagine and EGF or gastrin increases ODC activity in a synergistic manner and 2) asparagine increases ODC mRNA levels through completely distinct mechanisms from EGF or gastrin. EGF or gastrin specifically stimulates transcription of the ODC gene, whereas asparagine affects a posttranscriptional process.

Animals↗
PubMed1998

Expression of the transforming growth factor-beta gene during growth inhibition following polyamine depletion.

Polyamine depletion and cytokine transforming growth factor-beta (TGF-beta) inhibit cell proliferation. The current study tests the hypothesis that polyamine depletion results in growth inhibition by altering expression of the TGF-beta gene in intestinal epithelial cells. Studies were conducted in the IEC-6 cell line derived from rat small intestinal crypt cells. Cells were grown in DMEM in the presence or absence of alpha-difluoromethylornithine (DFMO), a specific inhibitor of polyamine biosynthesis, for 6 and 12 days. Administration of DFMO not only depleted intracellular polyamines but also significantly increased the mRNA levels of TGF-beta. Increased TGF-beta mRNA in DFMO-treated cells was paralleled by an increase in TGF-beta content. Depletion of intracellular polyamines by DFMO had no effect on the rate of TGF-beta gene transcription, as measured by nuclear run-on assay. The half-life of mRNA for TGF-beta in normal cells was approximately 65 min and increased to >16 h in cells treated with DFMO for 6 or 12 days. Exogenous polyamine, when given together with DFMO, prevented the increased half-life of TGF-beta mRNA in IEC-6 cells. TGF-beta added to the culture medium significantly decreased the rate of DNA synthesis and final cell number in normal and polyamine-deficient cells. Furthermore, growth inhibition caused by polyamine depletion was partially but significantly blocked by addition of immunoneutralizing anti-TGF-beta antibody. These results indicate that 1) depletion of intracellular polyamines induces the activation of the TGF-beta gene through posttranscriptional regulation and 2) increased expression of the TGF-beta gene plays an important role in the process of growth inhibition following polyamine depletion.

Animals↗
PubMed1997

Right ventricular dilation in primary amyloidosis: an independent predictor of survival.

This study was designed to characterize the geometry and function of the right ventricle and its prognostic significance in patients with primary (AL) cardiac amyloidosis. AL amyloidosis is an infiltrative systemic disease that can result in thickening of heart structures and rapidly progressive congestive heart failure due to restrictive ventricular physiology and eventual systolic dysfunction. Thirty-seven patients with AL amyloid heart involvement and 20 normal control subjects were evaluated using 2-dimensional and Doppler echocardiography. Based on the ratio of left-to-right end-diastolic ventricular chamber areas, patients were classified into 2 groups: 25 patients with disproportionate right ventricular (RV) dilation (left ventricular to RV ratio < or = 2) and 12 with a ventricular area ratio > 2. Patients with a relatively dilated right ventricle (ratio < or = 2) had a shorter median survival (4 months) compared with patients with an area ratio > 2 (10 months, p <0.003). Of multiple clinical, echocardiographic, and Doppler features entered into a multifactorial model, a ventricular area ratio < or = 2 remained the only independent predictor of survival. Patients with AL amyloid heart disease represent a heterogeneous population with regard to both prognosis and the relative degree of right to left ventricular dilation. RV dilation in patients with amyloid heart disease appears to be associated with more severe involvement and is associated with a very poor prognosis with a median survival of only 4 months.

Aged↗
PubMed1997

Nitric oxide, the kidney and hypertension.

1. According to the renal body fluid feedback mechanism for long-term control, persistent hypertension can only occur as a result of a reduction in renal sodium excretory function or a hypertensive shift in the pressure natriuresis relationship. Although an abnormal relationship between renal perfusion pressure and renal sodium excretion has been identified in every type of hypertension where it has been sought, factors responsible for this effect are still unclear. 2. Nitric oxide (NO) is produced within the kidney and plays an important role in the control of many intrarenal processes that regulate the renal response to changes in perfusion pressure and, thus, help determine systemic vascular volume and blood pressure. Numerous studies have shown that long-term inhibition of NO synthesis results in a chronic hypertensive shift in renal pressure natriuresis. 3. Recent studies have shown that certain animal models of genetic hypertension and forms of human hypertension areas are associated with a decrease in NO synthesis. Reductions in NO synthesis reduce renal sodium excretory function, not only through direct action on the renal vasculature, but through modulation of other vasoconstrictor processes and through direct and indirect alterations in tubular sodium transport. 4. The causes and consequences of the disregulation of NO in hypertension and other renal disease processes remain an important area of investigation.

Animals↗