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Biomedical subjects

V Bhargava

Publications and source records attributed to V Bhargava.

At least 37 records · Page 2Linked to original sources

Positive fraction of systematic biopsies predicts risk of relapse after radical prostatectomy.

OBJECTIVES: To determine whether the positive fraction of systematic sextant biopsies contributes to the prediction of serologic relapse after radical prostatectomy. METHODS: A retrospective review of patients who underwent transrectal ultrasound-guided systematic sextant biopsy and radical prostatectomy was performed. No patients received neoadjuvant or adjuvant therapy. The relationship between the positive fraction of systematic biopsies and risk of prostate-specific antigen recurrence was assessed with Kaplan-Meier and multivariate analyses. RESULTS: Patients with three or fewer positive sextant biopsies were at a significantly lower risk of relapse after radical prostatectomy than patients with four or more positive biopsies. Tumor grade and systematic biopsy results were the most powerful predictors of serologic relapse. CONCLUSIONS: The positive fraction of systematic biopsies contributes to the prediction of risk of relapse after radical prostatectomy.

Aged↗

Evaluation of dynamic changes in microvascular flow during ischemia-reperfusion by myocardial contrast echocardiography.

BACKGROUND: Dynamic changes of myocardial blood flow have been observed after reperfusion of an occluded coronary artery. MCE performed by intracoronary contrast injection can provide an estimate of microvascular flow. We hypothesized that MCE performed using intravenous infusion of a new generation contrast agent and electrocardiogram-gated harmonic imaging would be able to assess serial changes of microvascular perfusion. OBJECTIVE: To study the potential of myocardial contrast echocardiography (MCE) to assess serial changes of microvascular flow during ischemia-reperfusion. METHODS: Sixteen dogs underwent 90 or 180 min of left anterior descending coronary occlusion, followed by 180 min of reperfusion. Regional blood flow (RBF) was measured with fluorescent microspheres at baseline, during coronary occlusion, and at 5, 30, 90, and 180 min during reperfusion. At the same time points, MCE was performed with intravenous infusion of AF0150 (4 mg/min). Gated end-systolic images in short axis were acquired in harmonic mode and digitized on-line. Background-subtracted videointensity measured from MCE and RBF obtained from fluorescent microspheres were calculated for the risk area and for a control area, and were expressed as the ratio of the two areas. RESULTS: After initial hyperemia, a progressive reduction in flow was observed during reperfusion. MCE correctly detected the time course of changes in flow during occlusion-reperfusion. Videointensity ratio significantly correlated with RBF data (r=0.79; p < 0.0001). CONCLUSIONS: The progressive reduction in blood flow occurring within the postischemic microcirculation was accurately detected by MCE. This approach has potential application in the evaluation and management of postischemic reperfusion in humans.

Animals↗

In response to the article by R. Leischik et al.: Reproducibility of stress echocardiography using intravenous injection of ultrasound contrast agent (BY963) (see volume 13/5: 387-394)

Many contrast agents will soon be available to the clinicians, but as is evident, contrast echocardiography and the development of agents is still in its infancy. For successful clinical use of contrast echocardiography requires integration of: the development of contrast agents; modifications to ultrasound machines; development and validation of the specific clinical application software.

Analysis of Variance↗

Locally recurrent prostate tumors following either radiation therapy or radical prostatectomy have changes in Ki-67 labeling index, p53 and bcl-2 immunoreactivity.

PURPOSE: We compare the biological phenotype of recurrent prostatic tumors after definitive local therapy (radiation or radical prostatectomy) with that of the same tumors before treatment. MATERIALS AND METHODS: Cellular proliferation (Ki-67 labeling index), p53 nuclear reactivity and bcl-2 immunoreactivity were determined in pretreatment and posttreatment tumor specimens from 13 patients with local tumor recurrence following radiation, and in 18 patients with local tumor recurrence following radical prostatectomy. RESULTS: Mean Ki-67 labeling index increased approximately 2-fold in locally recurrent tumors after radiation (10.5 versus 5.6%, p=0.0008) or surgery (6.0 versus 3.2%, p=0.0025) when compared with pretreatment tumors. We noted p53 nuclear reactivity in a significantly higher proportion of recurrences than in pretreatment tumors following radiation (54 versus 8%, p=0.032) and surgery (39 versus 5%, p=0.022). Although bcl-2 immunoreactivity was also seen in a higher proportion of recurrent tumors, this difference did not reach statistical significance for either radiation or surgery. CONCLUSIONS: Recurrent tumors following either radiation or surgery differ significantly from the corresponding pretreatment tumors with respect to cellular proliferation and p53 nuclear reactivity.

Adenocarcinoma↗

Prospective evaluation of lateral biopsies of the peripheral zone for prostate cancer detection.

PURPOSE: We evaluate the usefulness of adding 4 lateral biopsies of the peripheral zone to the routine sextant biopsy regimen for prostate cancer. MATERIALS AND METHODS: A total of 273 consecutive patients referred for abnormal digital rectal examination and/or prostate specific antigen 4 ng./ml. or greater underwent transrectal ultrasound and systematic biopsy. Lateral biopsies of the peripheral zone taken just medial to the lateral border of the prostate were added to the routine lesion directed and systematic sextant biopsy regimen. Comparisons between positive and negative biopsy groups as well as among various biopsy schemes were performed. RESULTS: Of the patients 44% had cancer on biopsy (121 of 273). While routine sextant biopsies detected 82% of cancers, 77% (17 of 22) of missed cancers were detected on lateral biopsies. Overall, lateral biopsies detected 70% of cancers, and tended to be positive in patients with small prostates and high grade tumors. A significant correlation was found between hypoechoic lesions on transrectal ultrasound and positive lateral biopsies (Fisher's exact test p = 0.0005). Cancer was found in 74 of 147 patients with lesions on transrectal ultrasound (50%). Routine sextant biopsies detected 76% of cancers (56 of 74 patients) while lateral biopsies detected 80% (59). Of these patients 15 (20%) had positive lateral and negative sextant biopsies. Routine sextant biopsies detected 91% of cancers in 121 patients without lesions on ultrasound (43 of 47). CONCLUSIONS: The addition of lateral peripheral zone biopsies increases the sensitivity for cancer detection while nearly eliminating the need for lesion directed biopsies.

Aged↗

The influence of coronary collateral flow on the assessment of myocardial perfusion by videodensitometry.

OBJECTIVES: Coronary collateral flow often mitigates the effects of coronary artery obstruction and has a significant impact on the prognosis of patients with coronary artery disease. In the presence of variable degrees of coronary collateral flow, digital radiographic assessment of myocardial blood flow has not been quantitatively validated. METHODS: A distal coronary arterial collateral path was created into the left anterior descending coronary artery (LAD) bed in 8 anesthetized pigs. Both LAD and collateral paths were pump-perfused and corresponding flows measured. A number of commonly used digital indices and parametric images of myocardial perfusion were then extracted from the sequence of images filmed before and during the injection of contrast. Data were acquired at 5 levels of total flow (LAD flow + collateral flow): 100, 85, 70, 55 and 40% of maximally vasodilated, baseline flow. At each level of total flow, data were acquired at 4 levels of collateral flow ratios (collateral flow/total flow): 0, 10, 25 and 50%. RESULTS: Regional percent segment shortening, reflecting myocardial blood flow, decreased as total flow fell, and remained unaltered when coronary collateral ratio alone was altered without change in total flow. On the other hand, linear regression between total flow and digital indices at 10, 25 and 50% coronary collateral flow ratios, compared with 0%, showed a successive and significant downward displacement, documenting an underestimation of flow by all digital indices in the presence of collateral flow. CONCLUSIONS: In the absence of a collateral pathway and during maximal coronary vasodilation with adenosine, digital radiographic indices of myocardial perfusion, based upon indicator dilution theory, show a relatively good correlation with regional transmural myocardial blood flow. However, due to underestimation of total transmural blood flow, these indices have limited utility when myocardial perfusion is provided in part by a collateral pathway. The effect is probably related to an alteration in the regional vascular volume into which iodinated contrast is injected.

Adenosine↗

Extranodal head and neck lymphomas in Guatemala: high frequency of Epstein-Barr virus-associated sinonasal lymphomas.

Sinonasal lymphomas of T cell or natural killer cell (T/NK cell) phenotype represent a subset of extranodal head and neck lymphomas. T/NK cell sinonasal lymphomas have been described in diverse geographic settings, including China, Japan, Peru, Northern Europe, and North America. The frequency of these lymphomas is highly dependent on the geographic location in which they occur, their incidence being low in Europe and North America and relatively high in Asian countries and in Peru. Regardless of their geographic location, they are typically associated with the Epstein-Barr virus (EBV). Few studies have addressed the relative frequency of sinonasal lymphoma within the group of extranodal head and neck lymphomas. We investigated the anatomic distribution, immunophenotypical profile, and EBV status of 33 cases of extranodal head and neck lymphoma from patients in Guatemala. The anatomic distribution of these lymphomas is similar to that seen in Asian countries: 17 (52%) in the sinonasal area, five (15%) in the palate, and 11 (33%) in other locations. Fifteen (88%) of the 17 sinonasal lymphomas showed a T or null cell phenotype with a strong association with EBV by in situ hybridization. Most Guatemalan patients with these lymphomas were of Mayan descent. In Guatemala, the relative frequency of sinonasal lymphomas within the group of head and neck lymphomas is significantly higher than that reported for Western countries. In addition, the relative frequency of T/NK versus B cell sinonasal lymphomas is higher than that described in North America and similar to that observed in Asian countries and Peru.

Adolescent↗

MIC2, TdT, bcl-2, and CD34 expression in paraffin-embedded high-grade lymphoma/acute lymphoblastic leukemia distinguishes between distinct clinicopathologic entities.

We propose that 12E7 (CD99) expression, along with TdT, bcl-2, and CD34 reactivity in lymphoblastic lymphoma (LyL)/acute lymphoblastic leukemia (ALL), distinguishes this group of neoplasms from small noncleaved cell lymphomas (SNCLs) in both pediatric and adult patients, thereby narrowing the differential diagnosis of high-grade non-Hodgkin's lymphomas and acute lymphoblastic leukemias in paraffin sections. 12E7 (CD99) is one of a group of available antibodies that recognizes the product of the mic-2 gene, which was originally identified in ALL. Despite this, most clinicopathological research has focused on the reactivity of 12E7 in a subset of the small round cell tumors of childhood. Although TdT is widely used in the subtyping of blastic leukemias, its use in the distinction of high-grade lymphomas in paraffin sections has been limited. We collected 24 cases of LyL/ALL (13 B-cell and 11 T-cell) and 15 cases of SNCL from 1984 through 1993. We confirmed the diagnoses using morphology and analysis of immunologic data. We performed immunohistochemistry with the 12E7 antibody, TdT, bcl-2, and CD34 on formalin-fixed, paraffin-embedded material. The patients' ages ranged from 4 to 81 years; nine of the study patients were children. Sixteen of the 24 LyL/ALLs stained with 12E7. In contrast, none of the 15 cases of SNCL reacted with this antibody (chi-square P < .0001). A larger percentage of T-cell LyL/ALLs reacted with 12E7 than did B-cell LyL/ALLs (82% v 54%). Sixteen of 20 LyL/ALLs reacted with the anti-TdT antibody, as compared with none of 11 SNCLs (chi-square P < .0001). Six LyL/ALLs were CD34 positive (of 23), and none of the SNCLs were CD34 positive (0 of 12) (chi-square P = .0519). Bcl-2-positive cases were found among both LyL/ ALLs and SNCLs, although they were more prevalent among LyL/ ALLs (92% v 25%; chi-square P < .0001). When one considers the differential diagnosis of a high-grade lymphoma/acute lymphoblastic leukemia, positive reactions with 12E7, TdT, bcl-2, and CD34 support the diagnosis of LyL/ALL over SNCL. Moreover, we present data that suggests that evaluating for TdT in formalin-fixed paraffin-embedded tissue is a more sensitive test than using either 12E7, bcl-2 or CD34 alone.

Adult↗

Systematic sextant biopsies in the prediction of extracapsular extension at radical prostatectomy.

OBJECTIVES: To evaluate the clinical utility of transrectal ultrasound-guided systematic sextant needle biopsies in the prediction of extracapsular extension (ECE) at radical prostatectomy. METHODS: A retrospective analysis of 104 men who underwent systematic biopsy and radical prostatectomy at our institution was performed. All patients underwent preoperative staging by transrectal ultrasound and transrectal ultrasound-guided systematic sextant biopsy. The presence of pathologic ECE was correlated to the number of positive core biopsies on each side of the prostate by chi-square analysis. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios (LRs) were calculated for both positive (two or three biopsies positive per side) and negative (no or one positive biopsy per side) test results. RESULTS: Forty-two (20.2%) of 208 sides demonstrated evidence of ECE at radical prostatectomy. Chi-square analysis demonstrated a significant correlation between the number of positive biopsies and the presence of ECE at radical prostatectomy (P = 0.001). Overall, the finding of multiple positive core biopsies (two or three per side) had predictive value with regard to the presence of ECE (sensitivity 62%, specificity 77%, positive predictive value 40%, negative predictive value 89%). The corresponding LRs were 2.5 for a positive and 0.5 for a negative test result. CONCLUSIONS: The probability of ECE at radical prostatectomy can be more accurately assessed preoperatively by the combined use of transrectal ultrasound and systematic sextant needle biopsies.

Aged↗

Prospective evaluation of prostate specific antigen and prostate specific antigen density in the detection of carcinoma of the prostate: ethnic variations.

PURPOSE: We evaluated prospectively the ethnic variations in prostate specific antigen (PSA) and prostate specific antigen density in the detection of carcinoma of the prostate. MATERIALS AND METHODS: A total of 297 consecutive patients with an elevated serum PSA and/or abnormal digital rectal examination underwent transrectal ultrasound with lesion directed and systematic biopsy (6 if the prostatic volume was 50 cc or less and 12 if it was greater than 50 cc). Receiver operating characteristic curves, predictive values and likelihood ratios were calculated for PSA and PSA density for white and black patients. Ethnic analysis was performed for the entire group, patients with a normal digital rectal examination, and those with a normal digital rectal examination and PSA of 4 to 10 ng./ml. RESULTS: Of the 297 patients 131 (44%) had cancer, including 48 of 97 black (50%) and 83 of 200 white (42%) patients. Median PSA, PSA density and prostate size did not differ between the positive or negative biopsy groups, or between the ethnic groups in any of the analyses. If all digital rectal examinations were considered PSA density was superior to PSA by receiver operating characteristic analysis for cancer detection in both ethnic groups when all values or PSA of 4 to 10 ng./ml. were considered. However, the significance was lost if only patients with a normal digital rectal examination were considered. In general, predictive values were greater in black patients. Likelihood ratios for a negative test result in black patients demonstrated significant changes in the post-test probability if a PSA density cutoff of 0.1 was used to determine the need for biopsy. Many unnecessary biopsies could be avoided and few cancers would be missed. CONCLUSIONS: A PSA density cutoff of 0.1 may be warranted in determining the need for prostate biopsy in black men with a normal digital rectal examination.

Aged↗

Multiple myeloma arising from monoclonal gammopathy of undetermined significance in a patient with Gaucher's disease.

We report the case of a 64-year-old woman who, 12 years after receiving a diagnosis of Gaucher's disease with concurrent monoclonal gammopathy of undetermined significance, developed worsening thrombocytopenia and bone pain. Bone marrow biopsy at this time revealed 50% plasma cells with a serum monoclonal immunoglobulin A-lambda level of 3.2 g/L. Roentgenography revealed a lytic clavicular lesion, and a diagnosis of multiple myeloma was made. To our knowledge, this case is the first to document the evolution of a monoclonal gammopathy of undetermined significance to multiple myeloma in a patient with Gaucher's disease. The importance of investigating cytopenias and increased bone pain in such patients, perhaps by bone marrow biopsy, to rule out potentially malignant plasma cell dyscrasias is stressed.

Bone Marrow↗

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↗

A new method of calibrating left ventricular pressure tracings obtained from micromanometers.

An improved method of calibrating indwelling, or acutely inserted high fidelity micromanometers is presented. The proposed technique consists of linear regression of pressure data obtained from a fluid filled lumen with those obtained from a micromanometer and applying this regression equation to the data obtained from the micromanometer. The conventional calibration technique of matching systolic and late diastolic pressures was developed before analog to digital converters were available on-line in most laboratories. This method can result in erroneous hemodynamic measurements derived from the high fidelity recordings depending on the amount of ringing observed in the pressure recordings from a fluid filled transducer.

Blood Pressure Determination↗

Distortion of intravascular ultrasound images because of nonuniform angular velocity of mechanical-type transducers.

The purpose of this study was to quantify nonuniform rotation in a current mechanical intravascular ultrasound (IVUS) instrument and its effect on arc, area, and diameter measurements. The accurate reconstruction of IVUS two-dimensional images is dependent on uniform rotation of the catheter tip. Prior investigations suggested that bends in the catheter driveshaft may be responsible for poor torque transmission, nonuniform rotation, and consequent errors in IVUS measurements. Eight 30 MHz mechanically driven IVUS catheters were evaluated in a model simulating the catheter course through the aorta and coronary ostium in a clinical study. Angular velocity and posi-ion profiles of the transducer, image angle, and diameter and area measurement errors were obtained from each catheter by imaging a vascular phantom with eight equispaced echogenic markers from concentric and eccentric positions. Six catheters also were tested for comparison in a simple curvature model. Rotational error was found in all catheters tested and worsened in the aortic model. Maximal angular error, defined as the largest angle between actual and presumed transducer direction, increased when measured in the aortic model as compared with the simple curvature model (17 +/- 12 degrees to 45 +/- 25 degrees; p < 0.05). Angles of 45 degrees were misrepresented with a mean range of values of 26 to 63 degrees. With eccentric catheter placement, area and diameters had average maximal absolute errors of 26% +/- 7.8% and 23% +/- 10%, respectively. In conclusion, nonuniform rotation of mechanical IVUS transducers constitutes a significant potential source of error in IVUS measurement of arcs of calcification, and lumen shape, area, and diameter.

Humans↗

Mechanisms of venous return and ventricular filling in elasmobranch fish.

The current concept of ventricular filling in the elasmobranch fish (sharks and rays) is that a subambient pericardial pressure establishes a negative diastolic pressure gradient for the atrium and that ventricular end-diastolic volume is exclusively determined by atrial systole. In contrast, recent findings using echo-Doppler and digital imaging techniques have demonstrated two filling phases in the elasmobranch ventricle. In this study, simultaneous atrial and ventricular pressure measurements made on sharks with an open or intact pericardium establish that atrial pressure is above ventricular diastolic pressure until the onset of ventricular systole. A positive biphasic atrioventricular pressure gradient thus ensures ventricular filling during early diastole, as a result of ventricular relaxation, as well as during atrial systole. Although a reduction in pericardial pressure resulted in a decline in the atrial and ventricular pressure, a positive atrioventricular pressure gradient is conserved. The finding that atrial diastolic pressure is not lower than ventricular diastolic pressure, when combined with previous results showing that pericardial pressure is generally at or above ambient and that ventricular filling is biphasic, constitutes a strong body of evidence favoring the operation of a direct venous inflow as the mechanism by which the elasmobranch heart fills.

Animals↗