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Biomedical subjects

S Kaul

Publications and source records attributed to S Kaul.

At least 289 records · Page 16Linked to original sources
PubMed1992

Myocardial contrast echocardiography and the transmural distribution of flow: a critical appraisal during myocardial ischemia not associated with infarction.

OBJECTIVES: This study was undertaken to determine whether myocardial contrast echocardiography can be used to estimate the transmural distribution of flow. BACKGROUND: Myocardial contrast echocardiography has been shown to reliably measure average transmural blood flow during myocardial ischemia. However, there is controversy regarding its ability to determine the transmural distribution of flow. METHODS: The transmural distribution of flow was measured in 21 open chest anesthetized dogs with use of radiolabeled microspheres and sonicated albumin microbubbles (mean size 4.5 microns). In the 11 Group I dogs, myocardial contrast echocardiography was performed at baseline and during left anterior descending artery stenosis. In five of these dogs, it was also performed during left circumflex artery stenosis. In these dogs large (mean 12 microns) hand-agitated bubbles were also used. In the five Group II dogs, myocardial contrast echocardiography was performed before and 45 s after intracoronary injection of 6 mg of papaverine in the presence of a critical left circumflex artery stenosis. The five Group III dogs were studied during cardiopulmonary bypass at baseline and during left anterior descending artery stenosis. Off-line image analysis of the echocardiographic images was performed and time-intensity curves obtained from these images were correlated with radiolabeled microsphere-derived flows. RESULTS: The ratios of the parameters derived from the endocardium and epicardium during myocardial contrast echocardiography were found to correlate poorly (ranging from R2 = 0 to R2 = 0.35) with radiolabeled microsphere-derived endocardial/epicardial flow ratios over a wide range of flow ratios (0.01 to 2.58). These results were not influenced either by the location of the regions of interest (left anterior descending vs. left circumflex artery bed) or by the size of the bubbles (4.5 vs. 12 microns). CONCLUSIONS: Myocardial contrast echocardiography cannot be used to assess the transmural distribution of flow during myocardial ischemia not associated with infarction.

Animals↗
PubMed1992

Pharmacokinetics of stavudine in patients with AIDS or AIDS-related complex.

The pharmacokinetics of stavudine (d4T; 2',3'-didehydro-3'-deoxythymidine) were studied in patients with AIDS-related complex or AIDS enrolled in a dose-ranging phase I/II study. Twenty-two patients were studied after the first oral dose of 0.67, 1.33, 2.67, or 4 mg/kg of body weight; 17 of them underwent an additional steady-state pharmacokinetic evaluation after thrice-daily dosing of the above doses. Stavudine absorption was rapid, with mean peak concentrations of 1.2-4.2 mg/L over the four dose levels studied. From 34% to 41% of an oral dose was excreted as unchanged drug in the urine. The mean values for plasma elimination half-life ranged from 1 to 1.6 h. The absolute bioavailability of a 4 mg/kg oral dose exceeded 80%. There was no change in pharmacokinetic parameters measured after the first dose and after chronic dosing. Stavudine is a new dideoxynucleoside with more complete and less variable oral absorption than existing nucleosides used for treatment of human immunodeficiency virus infection.

AIDS-Related Complex↗
PubMed1992

Asymmetry of vascular responses of perfused rabbit carotid artery to intraluminal and abluminal vasoactive stimuli.

1. Responses of the carotid artery of rabbits to intraluminal and abluminal administration of purinergic agonists were examined. The carotid artery was perfused in vitro and changes in diameter were recorded. 2. Intraluminal acetylcholine, ADP, and ATP produced pronounced vasodilatation, whereas abluminal acetylcholine, but not ADP and ATP, produced dilatation of phenylephrine-preconstricted arteries. Intra- and abluminal adenosine and nitroprusside produced equipotent vasodilatation. 3. N omega-nitro-L-arginine abolished dilator responses to acetylcholine and adenine nucleotides, and unmasked vasoconstrictor responses to high concentrations of these agonists. Responses to adenosine and nitroprusside were not affected by nitro-L-arginine. 4. Intraluminal, but not abluminal, administration of nucleotidase-resistant adenine nucleotide analogues 2-methylthio-ATP and ADP beta S produced significant vasodilation in arteries preconstricted with phenylephrine. Intra- and abluminal administration of alpha,beta-methylene-ATP, a potent P2X-purinoceptor agonist, did not produce vasodilatation in preconstricted arteries. 5. Abluminal ADP failed to elicit dilatation of phenylephrine-preconstricted arteries even in the presence of the ADPase inhibitor beta,gamma-methylene-ATP (10(-5)M). When P2X-purinoceptors, which mediate adenine nucleotide-induced vasoconstriction, were stimulated with alpha,beta-methylene-ATP (10(-5)M), abluminal ADP produced vasodilatation, presumably because P2X-purinoceptors were occupied, thereby unmasking P2Y-purinoceptor-mediated dilatation. 6. These results suggest that asymmetric vascular responses of rabbit carotid arteries to adenine nucleotides may be due in part to preferential activation of P2Y-purinergic receptors on endothelium and P2X-purinergic receptors on vascular smooth muscle.

Acetylcholine↗
PubMed1992

Auditing and improving notification and chemoprophylaxis in bacterial meningitis.

STUDY OBJECTIVE: The aim was to audit, against agreed standards, the control of bacterial meningitis, in particular completeness of notification and appropriateness of distribution of chemoprophylaxis to contacts; and to implement appropriate changes and monitor their impact. DESIGN: The first phase involved determination, for the years 1983 and 1984, of completeness of notification by comparison with a comprehensive case register. Information about chemoprophylaxis was obtained from case notes, questionnaires to general practitioners and other records. The second phase involved introducing a programme of clinician education in the hospital with the poorest observed notification performance and re-examining performance during 1988. Districtwide education regarding chemoprophylaxis was undertaken and the situation re-examined in 1988. SETTING: The study took place in Mid Glamorgan Health Authority (population 536,000), with four acute hospitals. POPULATION: Consisted of all the residents of Mid Glamorgan Health Authority. MAIN RESULTS: During the first phase of the audit only 28 out of 79 cases of bacterial meningitis were notified (35%). Performance in one hospital was significantly worse than in the other three. Chemoprophylaxis was distributed to 20 out of 26 (77%) cases of meningococcal meningitis but inappropriate drugs were used in four cases and prophylaxis was distributed more widely than is recommended in 10 cases. In the phase 2 re-examination, a significant improvement in notification was observed in the hospital where special measures were taken, with no change in a "control" hospital. Chemoprophylaxis improved throughout the District, although rifampicin continued to be distributed too widely. CONCLUSIONS: As a result of this audit, measurable improvements in both infectious disease notification and chemoprophylaxis practice were obtained by the education of clinicians. The study provides a good example of a completed audit cycle in public health medicine.

Communicable Disease Control↗
PubMed1992

Effect of atherosclerosis on responses of the perfused rabbit carotid artery to human platelets.

Vascular responses to intraluminal and abluminal activation of human platelets were examined in carotid arteries from normal and atherosclerotic rabbits. The carotid artery was perfused in vitro, platelets were activated with thrombin (0.1 unit/ml), and changes in diameter were measured. In vessels from normal animals, intraluminal activation of platelets produced dilatation of preconstricted arteries. The dilator response was attenuated by N omega-nitro-L-arginine (10(-5) M), an inhibitor of synthesis of endothelium-derived relaxing factor-nitric oxide (EDRF-NO), and augmented by LY53,857 (10(-5) M), a 5-HT2-serotonergic antagonist. Abluminal activation of platelets produced modest constriction in quiescent arteries, which was inhibited by LY53,857. Intraluminal but not abluminal ADP produced pronounced dilatation of preconstricted arteries. In vessels from atherosclerotic animals, endothelium-dependent dilatation to intraluminal activation of platelets and to ADP was impaired and dilator responses to sodium nitroprusside were normal. These experiments indicate that 1) intraluminal activation of human platelets produces endothelium-dependent dilatation in perfused carotid arteries, whereas abluminal activation of human platelets produces vasoconstriction, which is mediated primarily by serotonin, and 2) atherosclerosis markedly impairs vasodilator responses to activation of human platelets, probably because vasodilatation to ADP released from platelets is impaired.

Acetylcholine↗
PubMed1992

The effect of interferon on the metabolism of LDLs.

Interferons have been shown to lower low density lipoprotein (LDL) cholesterol concentrations by 20-50%. To evaluate the effect of interferons on LDL metabolic behavior in individuals with normal and mildly elevated LDL cholesterol levels, autologous LDL labeled with 125I was administered to subjects at baseline and during interferon treatment. Interferon beta serine (IFN-beta serine) was administered intravenously at 4.5 x 10(6) units daily for at least 3 weeks before the start of kinetic study and continued for an additional 2 weeks. Results were analyzed by using a multicompartmental model that allows for two intravascular LDL compartments. In normal subjects, IFN-beta serine reduced LDL cholesterol and apolipoprotein (apo) B levels by 25% and 27%, respectively (p less than 0.05); LDL apo B synthesis was decreased by 59% (p less than 0.05). In hypercholesterolemic subjects, IFN-beta serine reduced LDL cholesterol levels by 38% (p less than 0.05); however, apo B concentrations and production rates were not significantly decreased. Clearance of LDL from the first intravascular apo B pool was markedly reduced in these subjects, resulting in a shift in the distribution of LDL apo B from the second to the first intravascular LDL apo B pool. We conclude that interferon's actions on LDL metabolism differ in normocholesterolemic and hypercholesterolemic subjects. In normal subjects, interferon decreased LDL cholesterol and apo B levels through a reduction in the LDL apo B production rate. However, in hypercholesterolemic subjects, interferon reduced LDL cholesterol by altering the distribution of apo B mass between LDL subspecies.

Adult↗
PubMed1992

Independent and incremental prognostic value of tests performed in hierarchical order to evaluate patients with suspected coronary artery disease. Validation of models based on these tests.

BACKGROUND: The additive prognostic value of tests done in a hierarchical order for the detection of coronary artery disease (CAD) is not always known. The principal goal of this study, therefore, was to assess the incremental prognostic value of data obtained in succession (clinical, exercise stress testing, 201Tl imaging, and coronary angiography) in patients with suspected CAD. A second goal was to develop models for determining prognosis based on results of these tests and to test the clinical validity of these models in unrelated patients. METHODS AND RESULTS: Data from two groups of patients who had undergone such evaluation and had been followed for a mean of 4.4 years were analyzed. There were 204 patients from Massachusetts General Hospital (MGH) and 299 from the University of Virginia (UVA). There were 20 deaths and 21 nonfatal infarctions in the MGH group and 41 deaths and nine infarctions in the UVA group. Both univariate and multivariate Cox regression analyses were performed to assess the individual and incremental prognostic value of these tests. In both groups, 201Tl imaging provided significant additional prognostic information compared with clinical and exercise stress test data (p less than 0.05). At MGH, where the lung/heart 201Tl ratio had been analyzed, coronary angiography did not provide additional prognostic information. In this group of patients, the combination of clinical and exercise 201Tl variables provided greater prognostic information than the combination of clinical and angiographic data (p less than 0.001). In the UVA cohort, in which the lung/heart ratio had not been analyzed, coronary angiography provided incremental prognostic information compared with clinical and exercise 201Tl data alone (p less than 0.05). When models developed using data from either sample were applied to the other unrelated sample, there was often close agreement between the overall observed rates and those predicted by the models. This was also true for the low-risk and high-risk subgroups. Some models, however, did not perform as well as other models, which suggests that models that do well in one sample may not always be generalized to other groups. CONCLUSIONS: Tests performed in hierarchical order for the evaluation of suspected CAD provide additional prognostic information. Models developed using clinically relevant combinations of test results obtained from different patient populations are frequently able to predict absolute levels of survival in unrelated but similar samples.

Cohort Studies↗
PubMed1992

Successful and reproducible myocardial opacification during two-dimensional echocardiography from right heart injection of contrast.

BACKGROUND: Myocardial contrast echocardiography currently involves intro-arterial injection of contrast. For this technique to have a broader application, it is necessary that myocardial opacification be achieved from a venous injection of contrast. METHODS AND RESULTS: To achieve myocardial opacification after right-side injection of contrast, two groups of open-chest anesthetized dogs were studied. Group 1 included nine dogs in whom microbubbles of various sizes, concentrations, and volumes were injected into the left atrium to determine microbubble characteristics that influence myocardial opacification. Group 2 included eight dogs in whom the effect of the combination of microbubble characteristics and myocardial blood flow on myocardial opacification was evaluated after right atrial injection of contrast. Background-subtracted time-intensity plots were generated from the myocardium to measure peak videointensity. In the group 2 dogs, digital subtraction and color coding were used to further highlight the contrast effect. The number, concentration, and size of the microbubbles all independently affected (p less than 0.01) peak myocardial videointensity after left atrial injection of contrast on multivariate analysis. Highly concentrated microbubbles (4.4 to 5.1 billion/ml) given during dipyridamole-induced coronary hyperemia was most frequently (88%) associated with myocardial opacification after right atrial injection of contrast and was the best predictor of this result on multivariate analysis (chi 2= 9.01, p = 0.003). No changes were noted in left atrial, left ventricular, and pulmonary artery pressures despite injection of large numbers of microbubbles into the right atrium. CONCLUSIONS: Successful and reproducible myocardial opacification can be achieved during myocardial contrast echocardiography after right atrial injection of contrast. These findings could have far-reaching implications in the use of myocardial contrast echocardiography in acute and chronic ischemic syndromes in humans.

Algorithms↗
PubMed1992

Functional significance of collateral blood flow in patients with recent acute myocardial infarction. A study using myocardial contrast echocardiography.

BACKGROUND: We hypothesized that myocardial contrast echocardiography (MCE) can be used to both measure collateral blood flow as well as assess the functional significance of collaterals in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: MCE was performed in 33 patients with recent AMI (12 +/- 7 days) and an occluded infarct-related artery (IRA), both before and after attempted percutaneous transluminal coronary angioplasty (PTCA). The size of the occluded bed was defined in patients with successful PTCA by injecting contrast directly into the opened IRA and expressed as a percent of the myocardium in the short-axis view. The percent of the perfusion bed supplied by collaterals before PTCA was determined. Transit rates of the microbubbles within the collateralized regions were also measured and were expressed as a percent of the transit rates in the normal adjacent beds. Regional function within the occluded bed was assessed using echocardiography and was graded as 1 (normal) to 5 (dyskinetic). Collaterals were graded on coronary angiography as 0 (none) to 3 (abundant). The perfusion bed size was larger for the left anterior descending (LAD) than for the right (RCA) and left circumflex (LCx) coronary arteries (37 +/- 6% versus 27 +/- 12% of the myocardium, p = 0.02). The percent of the occluded bed supplied by collateral flow was greater for RCA and LCx compared with the LAD (87 +/- 30% versus 72 +/- 22%, p less than 0.01). There was poor correlation between MCE-defined percent of occluded bed supplied by collaterals and angiographic collateral grade (r = 0.13). Regions supplied by collaterals were less likely to show confluent hypoperfused zones after reperfusion compared with those not supplied by collaterals. Similarly, the percent of myocardium not perfused by either anterograde or collateral flow correlated well (r = 0.67, p less than 0.01) with peak creatine kinase levels and was more likely to be associated with Q waves. Finally, although there was poor correlation between angiographic collaterals and regional function (r = 0.20), there was a significant negative correlation between MCE-defined spatial extent of collateral flow and regional function (r = -0.57, p less than 0.01). CONCLUSION: MCE can be used to measure collateral flow in patients with recent AMI and to assess the functional significance of collaterals in these patients. This technique may be ideally suited for the assessment of collateral perfusion in patients undergoing cardiac catheterization.

Angioplasty, Balloon, Coronary↗
PubMed1992

A mathematical model for the quantification of mitral regurgitation. Experimental validation in the canine model using contrast echocardiography.

BACKGROUND: Because the clearance of contrast from the left atrium (LA) relative to the left ventricle (LV) depends on the degree of mitral regurgitation (MR), we hypothesized that a mathematical model can be developed that would provide a quantitative estimation of MR from the washout of contrast from these chambers. METHODS AND RESULTS: After mathematically developing the model, we performed experiments in two groups of dogs with the use of contrast echocardiography. Group 1 consisted of nine dogs in which different degrees of MR were produced by creating ischemic LV dysfunction. Contrast was injected into the LV, and MR was graded visually on a scale of from 0 to 4+. Videointensity plots generated from the LA and LV were provided to the model. There was excellent correlation between visual assessment of MR and model-derived regurgitant fraction in the 33 stages: y = 0.16x + 0.002 (r = 0.97, p less than 0.001, SEE = 0.06). To obtain a more quantitative validation, we placed electromagnetic flow probes on the aorta and just cephalad to the mitral annulus in six dogs (group 2) during cardiopulmonary bypass. Different degrees of MR were produced by chordal traction and/or myocardial ischemia. Regurgitant fraction was calculated at each stage from the flow probe and videointensity data. There was excellent correlation between flow probe and model-derived regurgitant fraction (y = 0.90x + 0.03; r = 0.96, p less than 0.001, SEE = 0.06), and close interobserver and intraobserver correlations were noted using flow probe and contrast echocardiographic data. CONCLUSIONS: A mathematical model that uses the clearance of contrast from the LA relative to the LV can be used to accurately measure the severity of MR. These findings may have important practical implications for the quantification of MR.

Animals↗
PubMed1992

Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis.

PURPOSE: At the time of primary surgery, approximately 90% of all patients with breast cancer are free of metastases, but in the next 5 years almost 50% of them will relapse. We evaluated the significance of the presence of tumor cells in bone marrow of patients with primary breast cancer to investigate their predictive value for relapse. PATIENTS AND METHODS: Two hundred sixty patients with primary breast cancer were examined for tumor cells in bone marrow aspirates taken from six sites of the skeleton. After density centrifugation, cells in interphase were smeared and stained. For the immunocytologic reaction, we used a new monoclonal antibody (2E11) that was reactive with the core protein of the tumor-associated glycoprotein TAG12. TAG12 is secreted by nearly all human breast carcinomas. RESULTS: A significant correlation was found between tumor-cell detection and tumor stage (P < .0001), nodal status (P < .0001), and tumor grading (P = .002). A good relation to progesterone receptor (PR; P = .008) was found, but there was no correlation to estrogen receptor (ER) and menopausal status. Follow-up examinations showed distant metastases in 26 of 211 patients (15%). Twenty-two relapses occurred among the 81 patients with 2E11-positive cells in bone marrow, but only four occurred among the 130 patients without tumor-cell detection. CONCLUSIONS: This study suggests that tumor-cell detection in bone marrow of patients with primary breast carcinoma is a good predictor for all distant relapses (P < .0005, Cox multiple regression analysis) and provides additional information in regard to other prognostic factors. The highest predicting value for distant metastasis results from the combination of nodal status, negative PR, and tumor-cell presence in bone marrow.

Adult↗
PubMed1992

Tissue Na+K+ activated adenosine triphosphatase in retinol deficient albino rats.

The effect of retinol deficiency on Na+K+ ATPase was studied. Retinol deficient rat kidney, liver and spleen revealed a two to three-fold increase in ouabain sensitive Na+K+ ATPase activity in relation to controls. The activity in the controls could be stimulated more by concanavalin A than in the deficient group. The membrane-bound activity in the deficient group was more susceptible to freezing and thawing than the controls. Detergents could enhance the activity in both the groups to different levels. The enzyme revealed a high Km and Vmax for ATP and the cholesterol: phospholipid ratio was markedly decreased in the deficient group.

Animals↗
PubMed1992

On-line intraoperative quantitation of regional myocardial perfusion during coronary artery bypass graft operations with myocardial contrast two-dimensional echocardiography.

We hypothesized that the success of coronary artery bypass graft operations could be assessed by means of on-line quantitative myocardial contrast echocardiography. Accordingly, myocardial contrast echocardiography was performed at baseline and after each placement of venous graft in 21 patients undergoing coronary artery bypass graft operations. Time-intensity plots were generated on-line with the use of a dedicated computer system, and areas under the curve were assessed for each injection. Successful on-line quantitation of myocardial contrast echocardiography data was performed in 17 patients; this allowed comparison before and after coronary artery bypass graft operations for 21 grafts, with agreement between expert visual analysis and quantitative data in 91% of these cases. Three distinct perfusion patterns were noted on myocardial contrast echocardiography: (1) reduced contrast effect before coronary artery bypass graft operations with improvement after coronary artery bypass graft operations (n = 11); (2) adequate contrast effect before coronary artery bypass graft operations with no change after coronary artery bypass graft operations (n = 9) (for patients in group 2, the mean percentage of coronary stenosis was less than the mean for patients in group 1-67% +/- 25% vs. 88% +/- 20%, p = 0.05); and (3) no contrast effect either before or after coronary artery bypass graft operations in one patient with previous infarction. One third of the time (34 of 95 injections), on-line quantitation was unsuccessful. Failure was related three times more often to problems associated with myocardial contrast echocardiography, such as attenuation and inadequate quality of bubbles, than to computer failure. Despite its limitations, on-line quantitative myocardial contrast echocardiography is feasible in patients undergoing coronary artery bypass graft operations and provides important objective information regarding the success of revascularization.

Aged↗