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V Bhargava

Publications and source records attributed to V Bhargava.

At least 19 recordsLinked to original sources
PubMed1996

Atheroma morphology and distribution in proximal left anterior descending coronary artery: in vivo observations.

OBJECTIVES: This study sought to examine, in vivo, the shape and position of atheroma in the proximal left anterior descending coronary artery. BACKGROUND: The prevalence, shape and location of atheromas involving the proximal left anterior descending artery have implications regarding the role of disturbed shear forces in the genesis of atherosclerosis. However, no data are available regarding in vivo findings or advanced disease. METHODS: Forty-two consecutive high quality intravascular ultrasound images were examined from patients with atherosclerotic disease in the proximal left anterior descending artery just distal to the left main bifurcation. Lesion percent area stenosis and maximal, minimal and flow divider intimal-medial thickness were measured at the region immediately after the circumflex takeoff. The angle formed by the midpoint of the flow divider, the human center of gravity and the maximal plaque thickness were determined. RESULTS: Eccentricity of vessel wall atheroma was observed such that the maximal wall thickness (1.42 +/- 0.50 mm [mean +/- SD]) differed significantly from minimal wall thickness (0.17 +/- 0.098 mm). Further, the region of vessel wall manifesting maximal thickness was greater than the flow divider thickness (0.26 +/- 0.16 mm). Maximal plaque thickness spared the region of the flow divider in 100% of cases and was positioned at a mean angle of 193 +/- 49 degrees from the center of the flow divider. Eccentric morphology was maintained across the 24% to 80% range of area stenosis. CONCLUSIONS: Atheromas in the very proximal left anterior descending artery are located opposite the circumflex takeoff, spare the flow divider and maintain eccentricity across a wide range of vessel stenoses. These in vivo morphologic data support the potential role of fluid dynamic mechanical factors in atherogenesis and have implications regarding the success of catheter-based interventional procedures at the site.

Adult↗
PubMed1995

Pharmacokinetics of dolasetron following single- and multiple-dose intravenous administration to normal male subjects.

Dolasetron, Anzemet, a 5-hydroxytryptamine receptor antagonist, is under investigation as an antiemetic agent. The keto-reduced metabolite of dolasetron has been identified in human plasma and is probably responsible for the majority of the antiemetic activity. This study evaluated the pharmacokinetics of dolasetron and the reduced metabolite following single and multiple intravenous (IV) infusions of dolasetron mesylate in healthy male subjects. Four groups of subjects (six active/two placebo) received either dolasetron mesylate or placebo in single IV doses ranging from 0.30 to 0.60 mg kg-1 on day 1 and multiple IV doses ranging from 0.60 to 1.20 mg kg-1 d-1 on days 2-9. Dolasetron could be detected for less than 1 h, while the reduced metabolite appeared rapidly in the plasma, reaching a maximal plasma concentration in less than 1 h. Reduced metabolic maximal plasma concentration was proportional to the dose and the area under plasma concentration curve was linear based on regression analysis. The half-life of reduced metabolite ranged from 3.82 to 7.46 h. The mean renal clearance of reduced metabolite was 2.20-4.43 mL min-1 kg-1 and was dose independent. All of the evidence supports dose independent pharmacokinetics for the reduced metabolite. Upon multiple dosing, the reduced metabolite AUC can be predicted from the single-dose pharmacokinetics of this metabolite.

Adult↗
PubMed1995

Subintimal wire position during angioplasty of a chronic total coronary occlusion: detection and subsequent procedural guidance by intravascular ultrasound.

We report a case of intravascular ultrasound (IVUS) imaging of a chronic total coronary artery occlusion angioplasty initially complicated by subintimal wire penetration. IVUS provided unique images of wire position and a "double-barrel" lumen that complemented angiographic data in initial diagnosis and in subsequent guidance of the procedure.

Adult↗
PubMed1995

Value and limitations of intravascular ultrasound imaging in characterizing coronary atherosclerotic plaque.

Intravascular ultrasound uses a high-frequency, miniaturized, ultrasound transducer positioned on the tip of a coronary catheter to provide detailed cross-sectional images of the coronary vessel wall. Unlike angiography, which details only luminal encroachment, this imaging technique has the unique potential to provide an image of the atherosclerotic plaque, characterize its composition, and assess stenosis severity. Lipid-filled "soft" plaque, dense fibrous "hard" plaque, calcification, and thrombosis have all been identified on intravascular ultrasound images. Individual lesion types have been associated with specific clinical ischemic syndromes and with different responses to catheter-based intervention. By means of analyzing tissue composition, intravascular ultrasound may permit identification of high-risk lesions that may eventually rupture and cause unstable coronary ischemic syndromes. This article reviews the current approaches to plaque characterization by two-dimensional intravascular ultrasound imaging and addresses clinical implications, technical limitations, and future promise of the technique.

Calcinosis↗
PubMed1995

Heterogeneity of vasomotor response to acetylcholine along the human coronary artery.

OBJECTIVES: In view of the segmental occurrence of coronary atherosclerosis, we postulated that acetylcholine may cause heterogeneous vasomotion, depending on the extent of vessel analyzed, criteria for change in vessel caliber and dose of drug administered. BACKGROUND: Previous studies have reported that acetylcholine causes constriction of atherosclerotic arteries. This dysfunction of endothelium-dependent dilation may be seen without angiographically detectable disease. METHODS: We developed algorithms to quantitate the dimensions of a single coronary artery over virtually its entire length during a control state and during graded doses of intracoronary acetylcholine. On the basis of triplicate control angiograms, the limit of detection of a change from control diameter was 0.31 mm (> or = 2 SD). RESULTS: Analysis of multiple segments (each 5.6 +/- 1.1 [mean +/- SD] mm) along a single coronary artery revealed a heterogeneous response to acetylcholine in 27 of 31 patients at the 10(-4) mol/liter dose and in 29 of 31 patients when responses at 10(-6), 10(-5) and 10(-4) mol/liter doses were combined; in this latter analysis, constriction and dilation in the same vessel occurred in 45% of the patients. With acetylcholine, most of 349 segments demonstrated no change, but the greatest frequency of vasoconstriction (24.6%) and vasodilation (6.9%) was seen at the 10(-4) mol/liter dose. Inducible vasomotion was observed as far distally as 7.3 cm from the site of acetylcholine infusion. CONCLUSIONS: Response to intracoronary acetylcholine with mild coronary disease is heterogeneous; disparate dimensional responses may occur in different segments of the same vessel. Inclusion of all analyzable regions of a coronary artery and the use of a reproducibility limit for quantitative angiography are optimal for assessment of segmental coronary vasomotion.

Acetylcholine↗
PubMed1995

An outbreak of multidrug resistant. Salmonella typhimurium in a nursery.

A nursery epidemic caused by multidrug resistant Salmonella typhimurium is reported. In total, 21 infants developed symptomatic illness; of these, 17 had septicemia (7 blood culture positive) and 4 had diarrhea alone. Asymptomatic carrier state was identified in 13 infants. Male sex and birth asphyxia increased the risk for symptomatic illness. Fever, lethargy, and diarrhea were the most common clinical features. Amongst the septicemic infants there was no difference in clinical profile whether the blood culture was positive or negative for S. typhimurium. In the symptomatic group, S. typhimurium was isolated from feces in 19 cases and from blood in 7 cases. In both symptomatic and asymptomatic infants, all isolates of S. typhimurium, whether obtained from feces and/or from blood, were resistant to ampicillin, chloramphenicol, and trimethoprim, and a significant number (almost one-fifth) of them also showed resistance to third generation cephalosporins. More than 90% of isolates were sensitive to aminoglycosides and ciprofloxacin. On a combination of third generation cephalosporin (cefotaxime or ceftriaxone) and amikacin, 17 (81%) infants recovered, 2 succumbed to their illness, and 2 failed to improve and required ciprofloxacin. The origin of epidemic was traced to a carrier staff nurse working in nursery.

Anti-Bacterial Agents↗
PubMed1994

Molecular and physiological alterations in murine ventricular dysfunction.

The present study reports the development and characterization of a murine model of right ventricular dysfunction following graded constriction in the pulmonary artery via microsurgical approaches. To analyze in vivo ventricular function, a technique of x-ray contrast microangiography was developed to allow the quantitative analysis of ventricular volumes and of ejection fraction in normal and pressure-overloaded right ventricle. Severe, chronic pulmonary arterial banding for 14 days resulted in right ventricular dilatation and dysfunction, associated with right atrial enlargement, and angiographic evidence of tricuspid regurgitation. These effects were dependent on the extent of hemodynamic overload, since more moderate pulmonary arterial constriction resulted in hypertrophy with maintenance of right ventricular function. With severe pulmonary artery constriction, the murine right ventricle displays a failing heart phenotype including chamber dilation with reduced function that resembles right ventricular dysfunction in man during chronic pulmonary arterial hypertension. Northern and immunoblot analyses demonstrate a marked down-regulation of phospholamban mRNA and its corresponding protein with both levels of constriction, while a less pronounced but significant depression of sarcoplasmic reticulum Ca(2+)-ATPase protein was observed with severe overload, suggesting that this pattern is an early genetic marker of ventricular dysfunction. By coupling mouse genetics with this murine model and the ability to assess cardiac function in vivo, one should be able to test the role of the down-regulation of phospholamban and other defined alterations in the cardiac muscle gene program in the onset of the failing heart phenotype.

Adenosine Triphosphatases↗
PubMed1994

Loss of heterozygosity and p53 gene mutations in breast cancer.

Immunopositivity for the p53 tumor suppressor gene product was evaluated in 133 breast cancers and compared to loss of heterozygosity (LOH) at various chromosomal loci. The validity of p53 immunopositivity as an indicator for p53 mutations was verified using two molecular assays of p53 mutations: single stranded conformational polymorphism (32 cases) and/or direct sequencing (14 cases). Immunopositivity was highly specific for mutations, since all of 15 strongly immunopositive tumors (> 10% of the cells are positive) and seven of nine cases with borderline immunopositivity had mutations by molecular analysis but were somewhat lower in sensitivity, p53 mutations being also detected in three of 23 (13%) immunonegative cases. LOH was measured at loci on the following chromosomes (1p,q; 2p; 3p; 7q; 11p,q; 13q; 16q; 17p; 18p,q; and 22q) by Southern blotting, polymerase chain reaction amplification of restriction fragment length polymorphisms, or repetitive cytidine and adenine stretches (CA repeats). There was no association between p53 mutations and one measure of genomic instability, namely, high incidence of overall LOH. In contrast, p53 mutations strongly associated with LOH at two specific loci, 3p24-26 (P < 0.001) and 7q31 (P < 0.05). There was no association between p53 mutations and LOH at 17p (site of the p53 gene), suggesting that breast cancers often have only one defective allele of the p53 gene.

Base Sequence↗
PubMed1994

In vivo assessment of left ventricular remodelling after myocardial infarction by digital video contrast angiography in the rat.

OBJECTIVE: The aim was to develop a digital video contrast angiographic method for assessing global left ventricular function and volume in vivo in the rat and then to apply it to a study of ventricular remodelling after coronary occlusion, with and without reperfusion. METHODS: Digital contrast angiography was performed on 29 rats, including the following groups: sham operated (n = 11), non-transmural myocardial infarction produced by reperfusion (n = 8), and transmural infarction produced by permanent occlusion (n = 10). Under anaesthesia three weeks later, biplane fluoroscopic images were acquired following venous contrast injection. Levophase images were digitised, and left ventricular end diastolic and end systolic volumes and ejection fractions were obtained using an area-length method. Left ventricular ejection fraction data also were calculated by videodensitometry from video density curves. RESULTS: Compared to the sham operated group, the reperfused group showed a significant decrease in left ventricular ejection fraction, at 53(SD 7) v 70(5)% (p < 0.01), and an increase in end diastolic volume. The permanent occlusion group showed a further decrease in the ejection fraction [40(8)%] and a further significant increase in end diastolic volume compared to the reperfused group (p < 0.01). Left ventricular ejection fraction correlated inversely with percent infarct size (r = 0.882) and showed a positive correlation with the spared epicardial area (r = 0.721). Most haemodynamic variables, including maximum left ventricular dP/dt, failed to discriminate between the groups. The methods showed reasonable accuracy when tested in vitro using contrast filled balloons. In vivo, the left ventricular ejection fraction calculated by densitometry showed adequate interobserver variability (2 SD +/- 8.5 percentage points), but the area-length method showed somewhat more scatter. CONCLUSIONS: Digital video contrast angiography is a feasible method for the assessing global left ventricular function in the rat and should be useful in other small animal models. Significant differences in left ventricular volumes and ejection fractions were detected between reperfused and permanent occlusion groups, whereas haemodynamic variables showed non-significant trends. Reperfusion after 45 min of occlusion caused sparing of the epicardium, prevented unfavourable remodelling, and improved the ejection fraction compared to permanent occlusion.

Angiography, Digital Subtraction↗
PubMed1994

The association of p53 immunopositivity with tumor proliferation and other prognostic indicators in breast cancer.

Abnormal accumulation of the p53 tumor suppressor gene product was analyzed in 198 primary invasive human breast carcinomas. In 47 of these cases, single-strand conformational polymorphism was used to detect mutations in the highly conserved exons 5-9 of the gene. Mutations as determined by single-strand conformational polymorphism were found in 15 of 15 strongly immunopositive cases (100%) and 3 of 23 immunonegative cases (13%). There were also nine cases with < 1% immunopositive cells (borderline immunopositivity); p53 mutations were detected in seven of these cases. The results suggest that p53 immunopositivity is a highly specific, albeit somewhat insensitive surrogate for p53 mutations. p53 accumulation, detected by immunohistochemical methods using antibody PAb 1801, was noted in 29.8% of the cases and was associated with estrogen receptor (ER) negativity (P = 0.0003), progesterone receptor (PR) negativity (P = 0.008), and high histological grade (P = 0.037) by univariate analysis. Incorporation of bromodeoxyuridine was used to determine the percentage of cells synthesizing DNA (proliferative fraction). When bromodeoxyuridine was administered either in vivo (n = 93) or in vitro (n = 79), p53 accumulation was only marginally related to proliferative fraction (P = 0.067 by chi 2; P = 0.055 by Mann-Whitney). When tumors were segregated by ER status, the aforementioned associations of p53 immunopositivity with PR negativity, high histological grade, and increased proliferation rate lost their significance. p53 accumulation did not correlate with tumor size, clinical stage, axillary node metastases, or age at diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Bcl-2 immunoreactivity in breast carcinoma correlates with hormone receptor positivity.

The protein encoded by the Bcl-2 proto-oncogene has been shown to inhibit programmed cell death and has been primarily studied in hematolymphoid malignancies. Recent work ahs elucidated Bcl-2 expression in nonhematolymphoid malignancies of the lung, prostate, and nasopharynx. Studies of Bcl-2 expression in prostate carcinoma have suggested that its expression may be related to hormonal control. To determine its presence and possible significance in breast carcinoma, a malignancy in which therapy is influenced by hormone receptor status, we used a monoclonal antibody directed against the Bcl-2 gene product to examine Bcl-2 immunoreactivity in a series of paraffin-embedded primary breast tumors. Benign breast tissue showed Bcl-2 positivity in the basal layer and in superficial cells. Twenty-four of 41 (58%) carcinomas were Bcl-2 positive. Staining for Bcl-2 was equivocal in two cases. We identified a strong correlation between Bcl-2 expression and hormone receptor positivity as 23 of 24 (96%) cases that were Bcl-2 positive were estrogen receptor (ER) positive (P = 0.0001) and 21 of 24 (87.5%) were positive for progesterone receptor PR (P = 0.0001). Of 15 Bcl-2-negative cases, 14 (93%) were ER negative and all were PR negative. One case of mucinous carcinoma was ER positive and Bcl-2 negative. Grade 1 and 2 tumors (Scarff-Bloom-Richardson scale) were almost three times as likely to be Bcl-2 positive (90%) as grade 3 tumors (33%) (P = 0.0057). Bcl-2 reactivity appears to be more prevalent in well-differentiated tumors, suggesting that its presence may diminish with loss of differentiation, a hypothesis that is further supported by a subset of cases that were ER negative, Bcl-2 negative, and of poor histological grade. These may be tumors that do not require Bcl-2 inhibition of apoptosis and respond to hormonally independent proliferation factors. Our findings support the hypothesis that Bcl-2 expression may be related to hormonal regulation in breast carcinoma.

Adult↗
PubMed1993

Acoustic impedance of the maternal abdomen.

Contact sensors to monitor fetal heart, breathing, and movement sounds with increased sensitivity and bandwidth are under development. To understand the inherent acoustical properties of the maternal abdomen and its interaction with these sensors, the driving-point impedance Z(j omega) was measured in nine women during their last trimester of pregnancy. An electromechanical shaker with a contact area of 2.85 cm2 produced abdominal vibrations between 10 and 500 Hz, and the resulting force and acceleration were measured. After digitally integrating the acceleration signal to obtain the velocity and removing the massive effects of the coupling between the shaker and the abdomen, Z(j omega) was estimated using spectral techniques. The imaginary part of Z(j omega) depicted a dominant compliance effect at low frequencies, a resonance at a frequency of 28 +/- 16 Hz (mean +/- s.d.), and a dominant mass effect at higher frequencies. The real part of Z(j omega) increased steadily with frequency. A series resistance-mass-compliance (R-M-C) circuit modeled these characteristics of Z(j omega) well when R was allowed to exactly mimic the frequency dependence of the real part of Z(j omega). Estimated element values of 6.6 +/- 2.2 x 10(-3) kg for M, 2.1 +/- 1.4 x 10(-3) m/N for C, and roughly 10 Ns/m for R (at resonance) were similar to those estimated for other body tissues such as the thigh but quite different from that of the often-studied chest wall.

Abdomen↗
PubMed1993

Increased afterload intensifies asynchronous wall motion and impairs ventricular relaxation.

To clarify whether impaired left ventricular relaxation elicited by increased afterload is attributable to regional dyssynchrony, we analyzed in dogs simultaneous left ventricular contrast ventriculography and pressure before and during angiotensin II infusion. Regional shortening was measured by a centerline method and a video-intensity method that served to define asynchronous motion. During angiotensin II, peak left ventricular pressure increased 35 +/- 6 mmHg, and the isovolumic pressure time constant (tau) was prolonged from 32.7 +/- 4.1 to 39.2 +/- 7.6 ms (P < 0.01). During increased afterload, early diastolic asynchrony, confined to the apical (5 of 7) and inferior regions (2 of 7), was detected in all dogs. Early systolic asynchrony was detected in the apical (5 of 7) and inferior (1 of 7) regions in six dogs. At control, systolic excursion was lower in the anteroapical than in the anterobasal region (P < 0.05). During angiotensin II, excursion of all regions was reduced, with the apical region lower than other regions (P < 0.01). In the normal dog heart, impaired relaxation with augmented afterload is coincident with asynchronous wall motion, especially in the apical-inferior region. Temporal dispersion of regional contraction may explain delayed left ventricular relaxation associated with increased afterload.

Angiotensin II↗
PubMed1993

Comparative outcome of low birth weight babies.

One hundred and fifty six babies with birth weight between 1500-2000 g and 103 full term-appropriate for gestational age (FT-AGA) babies delivered at University Hospital, District Hospital and village homes were included for a comparative study of mortality, morbidity and growth pattern. The low birth weight (LBW) babies from the three centres had similar birth weight and gestational age. Neonatal mortality rates for the LBW babies were similar at the three centres. The main cause of death were infections and aspiration with rates again being similar. Diarrhea and respiratory tract infections were common causes of morbidity. The mortality rates for the LBW babies were significantly higher as compared to FT-AGA babies irrespective of the place of delivery. The incidence of morbidities like diarrhea and respiratory infections were also higher in LBW babies. However, the differences were statistically significant mostly in the preterm group. The weight gain of all LBW babies was similar up to 3 months of age. The findings of an identical outcome for the LBW babies at village level to those managed at hospitals is an encouraging trend to increasing domiciliary care for LBW babies.

Fetal Growth Retardation↗