Search PubMed⌕ Search

Biomedical subjects

S Kaul

Publications and source records attributed to S Kaul.

At least 325 records · Page 18Linked to original sources
PubMed1990

Determination of belfosdil, a new calcium channel blocker, in human plasma by capillary gas chromatography with nitrogen-phosphorus detection.

Belfosdil and the internal standard were extracted from human plasma by a double liquid-liquid extraction. After a concentration step, gas chromatographic analysis of the sample was performed using a capillary fused-silica column and a nitrogen-phosphorus detector. The limit of detection of belfosdil was 0.025 ng/ml and the standard curve was linear over the range 0.05-100 ng/ml. The intra-assay and inter-assay precisions were within 7% (relative standard deviation) and the intra-assay and inter-assay accuracy values deviated by less than 5%. The extractability of belfosdil was 79%. The assay method was successfully used for the analysis of plasma samples from clinical studies with dose ranges of 5-100 mg of belfosdil.

Calcium Channel Blockers↗
PubMed1990

Echocardiography in coronary artery disease.

Echocardiography has a major role in the evaluation of patients with CAD. To obtain the maximal amount of information using this technique, certain basic principles relating to regional myocardial mechanics during ischemia and flow-function relations are required. In addition, a detailed knowledge of cardiac anatomy and the three-dimensional orientation of the heart within the chest cavity is required to access meaningful information from two-dimensional planes. Furthermore, skill is also required in acquiring data in proper imaging planes and in separating true (actual pathology) from the false (artifacts, etc.). Echocardiography is not a "mature" technology. It is still developing and it is sometimes difficult to keep up with the advances. However, keeping abreast of these developments is essential to fully exploit the advantages of this technique. In addition, knowledge of the ever-changing aspects of CAD is required in order to correctly interpret visual information in context of a particular patient. Finally, more clinical studies are needed to further define the role of echocardiographic techniques in patients with CAD.

Blood Flow Velocity↗
PubMed1990

Naturally occurring cardiomyopathy in the Doberman pinscher: a possible large animal model of human cardiomyopathy?

Currently there is no large animal model of dilated cardiomyopathy. The smaller animal models of cardiomyopathy, such as the Syrian hamster, cannot be studied with echocardiography and cardiac catheterization, and the relevance of these models to human dilated cardiomyopathy is open to question. On the basis of some initial observations in Doberman pinschers, it was speculated that these dogs could have occult left ventricular dysfunction. Accordingly, studies were performed in 46 apparently healthy Doberman pinschers and in 41 mongrel dogs: two-dimensional echocardiography (30 dogs in each group), cardiac catheterization (16 Doberman pinschers and 12 mongrels) and coronary blood flow studies (13 Doberman pinschers and 6 mongrels). In the awake, unsedated dogs studied with echocardiography, left ventricular wall thickening was significantly less in the Dobermans than in the mongrels (28% versus 36%, p = 0.0003). In the anesthetized dogs undergoing cardiac catheterization, left ventricular ejection fraction was significantly lower in the Dobermans than in the mongrels (0.38 versus 0.63, p = 0.0001). Rest coronary blood flow and coronary blood flow reserve were similar in the two groups. It is concluded that apparently healthy Doberman pinschers have occult left ventricular dysfunction. These dogs may serve as a large animal model of dilated cardiomyopathy and should not be used experimentally to study normal cardiac physiology.

Animals↗
PubMed1990

Intraoperative assessment of regional myocardial perfusion using quantitative myocardial contrast echocardiography: an experimental evaluation.

To test the hypothesis that myocardial contrast echocardiography can be used to quantitate regional myocardial flow in the arrested heart at the time of delivery of cardioplegic solution, data were acquired in 13 dogs on cardiopulmonary bypass. Different degrees of stenosis were placed in random order on the left anterior descending coronary artery. For each stenosis, myocardial contrast echocardiography was performed by injecting sonicated albumin microbubbles into the cross-clamped aortic root at the time of delivery of cardioplegic solution. The resultant echocardiographic images were analyzed on an off-line computer. Background-subtracted time-intensity plots were generated, and an exponential function, f(t) = Ce-alpha t + De- beta t, was applied to each plot. Variables that reflected the total number of microbubbles entering the coronary artery bed, such as the area under the curve and the peak height of the curve, correlated best with radiolabeled microsphere-measured myocardial flow (r = 0.92 and r = 0.91, respectively). Variables that reflected the appearance of contrast microbubbles in the myocardium, such as the initial slope and the slope at 1 s, also had a good correlation with myocardial flow (r = 0.84 and r = 0.89, respectively). Variables that reflected the washout of contrast medium from the myocardium, such as the slope of the descending portion of the curve, had only a fair correlation with myocardial flow (r = 0.65). In six dogs, the technique of injecting contrast medium into the cross-clamped aortic root was also examined. Although continuous infusion of contrast medium produced smaller perturbations in mean aortic and distal left anterior descending artery pressures compared with a bolus injection (p less than 0.01), the correlation between the variables of the time-intensity curves and flow was equally close with both techniques. It is concluded that it is possible to quantitate myocardial flow by using myocardial contrast echocardiography at the time of delivery of cardioplegic solution in dogs on cardiopulmonary bypass. The implementation of this technique in humans might be useful in guiding the sequence of graft placement and thereby improving myocardial preservation during coronary artery bypass operations.

Animals↗
PubMed1990

[The prognostic significance of tumor cell detection in bone marrow of patients with breast cancer].

In 95% of patients with primary breast cancer, the extent of metastases cannot be proven by conventional methods. Nevertheless, more than 50% of these patients have a relapse within five years. To improve the predictive value for recurrency, we examined bone marrow aspirates of 128 patients with primary breast cancer. Bone marrow aspirates from 2-6 sites of the skeleton (iliac crest and sternum) were taken as well as biopsies for histological examination. The immunohistochemical studies were carried out on interphase smears and stained with cytoceratin antibodies (PKK 1) and antibodies against tumor-specific antigen TAG 12 (12 H 12). All patients were screened for distant metastases (X-ray, ultrasound, bone scan). Tumor cells and micrometastases in bone marrow were detected in 41 patients (32%). Their presence was correlated to other prognostic factors (tumor size, lymph node status, oestrogen/progesterone receptors). The median duration of follow-up was 39.5 months. 14 patients (45%) in the tumor cell positive group relapsed, compared to only 4 out of 36 patients in the tumor cell negative group. In 29% we found bone metastases. The relapse free interval was shorter for patients with micrometastases (8 vs. 15.8 months). The presence of tumor cells in bone marrow aspirates detected at the time of primary surgery, is a useful prognostic factor and a good predictor of metastases and may help in selecting patients for systemic adjuvant treatment.

Antibodies, Monoclonal↗
PubMed1990

Assessment of myocardial perfusion with contrast two-dimensional echocardiography.

Myocardial contrast echocardiography (MCE) is a new technique capable of assessing regional myocardial perfusion in vivo in real time. At present, this technique involves the intraaortic or intracoronary injection of microbubbles of air. As these microbubbles traverse the myocardium, they produce opacification of the myocardium in concomitantly performed echocardiographic images. In animal models, MCE has been demonstrated to assess accurately the in vivo risk area (region of the myocardium at risk for necrosis after acute coronary occlusion). It has also been shown to provide quantitative information on regional myocardial blood flow (both antegrade and collateral). This technique has been demonstrated to be safe in humans. In clinical studies it has been shown to be a useful adjunct to cardiac catheterization, particularly in the assessment of coronary blood flow reserve and collateral blood flow. MCE is also used in the operating room to assess regional myocardial perfusion before and after bypass graft operations. The microbubbles used for MCE were shown to opacify the left ventricular cavity after their injection into a peripheral vein. If myocardial opacification after venous injection can be achieved, MCE will have the potential for the simultaneous noninvasive in vivo assessment of regional myocardial perfusion and function in humans.

Animals↗
PubMed1990

Reversible myocardial depression in survivors of cardiac arrest.

Three patients under 40-years old who survived cardiac arrest due to ventricular fibrillation were originally diagnosed as having idiopathic dilated cardiomyopathy. Shortly after cardiac arrest, assessment of myocardial function revealed a globally dilated left ventricle in each patient with an estimated ejection fraction between 20% and 30%. Serial assessment of myocardial function, however, showed either normal or near-normal function by 2 weeks postevent. These findings suggest that myocardial stunning due to hypoperfusion during ventricular fibrillation or the effects of transthoracic shocks may result in profound, reversible myocardial depression in survivors of cardiac arrest. Serial evaluation of left ventricular function may be of value in selected survivors of cardiac arrest in order to evaluate time-dependent resolution of myocardial dysfunction and may prevent misdiagnosis of idiopathic dilated cardiomyopathy.

Adult↗
PubMed1990

Intraoperative assessment of myocardial perfusion using contrast echocardiography.

Myocardial contrast echocardiography is a new technique capable of assessing regional myocardial perfusion in vivo in real time. This article reviews the background, principles, experimental validation, and clinical uses of intraoperative myocardial contrast echocardiography. Data can be derived both for online visual and computer analyses. The technique can be useful in determining the sequence of bypass graft placement and the success of graft anastamoses. Anastamoses can be revised immediately if needed. It is hoped that this technique will improve intraoperative myocardial preservation and will diminish the rate of perioperative myocardial infarction.

Cardioplegic Solutions↗
PubMed1990

Thallium 201 kinetics in stunned myocardium characterized by severe postischemic systolic dysfunction.

The hypothesis tested in this study was that despite the presence of severe postischemic myocardial dysfunction ("stunning"), the extraction and subsequent intracellular washout of thallium 201 should be preserved as long as irreversible sarcolemmal membrane injury was avoided. To produce myocardial stunning, 19 open-chested dogs with a critical left anterior descending coronary artery (LAD) stenosis underwent 10 5-minute periods of total LAD occlusion, each interspersed by 10 minutes of reperfusion by reflow through the critical stenosis. In another 12 control dogs observed for the same time period, no LAD occlusions were performed after placement of the critical stenosis. Hemodynamics, regional myocardial thickening by quantitative two-dimensional echocardiography, and microsphere-determined regional blood flows were serially measured. In 18 stunned dogs, systolic thickening in the LAD zone was markedly reduced to 0.4 +/- 2.4% at 40 minutes after the 10th reperfusion period compared with 32.5 +/- 2.2% thickening (p less than 0.001) in 12 control dogs at a matched time. The 201Tl first-pass extraction fraction determined by a double-isotope method using intracoronary 201Tl administration was comparable after the 10th reflow in a subgroup of 13 stunned (0.78) and six control (0.79) dogs. The T1/2 for the intracellular washout rate was also not significantly different in another group of six stunned (60 +/- 13 minutes) and six control (53 +/- 14 minutes) dogs, nor was the percentage of the 201Tl dose initially distributed in the interstitial compartment (11 +/- 3% vs. 7 +/- 2%). Systemic hemodynamics and regional flows were comparable in the two groups at 40 minutes after the 10th reflow. No dog had evidence of myocardial necrosis by triphenyl tetrazolium chloride staining. Thus, normal myocardial 201Tl extraction and washout kinetics are observed in a canine model of severe postischemic dysfunction (stunning) produced by repetitive brief LAD occlusions. These findings might have important clinical implications concerning the application of rest 201Tl scintigraphy for evaluation of perfusion and viability in patients with coronary artery disease and regional myocardial asynergy that is ultimately reversible.

Animals↗
PubMed1990

Protective effect of coleonol on biochemical changes produced in coronary ligation induced ischemia.

Coleonol, a diterpine prevented biochemical changes induced by coronary artery ligation in rabbits at a dose of 10 mg/kg, iv. It increased the heart mitochondrial oxygen uptake and O ratio, which may be responsible for the stabilization of heart membrane. The decrease in serum creatine phosphokinase, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase phospholipase and lipid peroxide and increase in cytochrome P450, glycogen and superoxide dismutase activity by coleonol treatment could have contributed to restore myocardial integrity and cardiac function disturbed by coronary artery ligation. The cardioprotective activity of coleonol was found to be comparable to propranolol.

Animals↗
PubMed1989

A simplified approach for evaluating multiple test outcomes and multiple disease states in relation to the exercise thallium-201 stress test in suspected coronary artery disease.

This study describes a simplified approach for the interpretation of electrocardiographic and thallium-201 imaging data derived from the same patient during exercise. The 383 patients in this study had also undergone selective coronary arteriography within 3 months of the exercise test. This matrix approach allows for multiple test outcomes (both tests positive, both negative, 1 test positive and 1 negative) and multiple disease states (no coronary artery disease vs 1-vessel vs multivessel coronary artery disease). Because this approach analyzes the results of 2 test outcomes simultaneously rather than serially, it also negates the lack of test independence, if such an effect is present. It is also demonstrated that ST-segment depression on the electrocardiogram and defects on initial thallium-201 images provide conditionally independent information regarding the presence of coronary artery disease in patients without prior myocardial infarction. In contrast, ST-segment depression on the electrocardiogram and redistribution on the delayed thallium-201 images may not provide totally independent information regarding the presence of exercise-induced ischemia in patients with or without myocardial infarction.

Aged↗
PubMed1989

Can the hypotriglyceridemic effect of fish oil concentrate be sustained?

STUDY OBJECTIVE: To determine whether high doses of fish oil concentrate followed by low-dose maintenance therapy can sustain the initial plasma triglyceride reductions. DESIGN: Before-and-after trial with 3-month treatment periods. SETTING: Outpatient lipid clinic at a university medical center. PATIENTS: Sixteen patients with hypertriglyceridemia recruited from the General Internal Medicine Clinics. Five had concomitant hypercholesterolemia (type IIb). INTERVENTION: Fish oil supplementation at two doses. After basal measurements, 9.8 g/d omega-3 fatty acids were provided for study months 1 to 3, and 3.9 g/d were provided for study months 4 to 6. MEASUREMENTS AND MAIN RESULTS: Blood was drawn monthly and plasma was analyzed for levels of triglycerides, low-density-lipoprotein (LDL) cholesterol and apolipoprotein B, high-density-lipoprotein (HDL) cholesterol and apolipoprotein A1, and glucose and glycohemoglobin. During therapy with the higher dose, mean plasma triglyceride levels were reduced from 3.65 +/- 0.35 mmol/L at baseline to 1.85 +/- 0.20 mmol/L at 1 month, but increased by 30% to 2.40 +/- 0.30 mmol/L by the third month of therapy (P less than 0.05): this increase could not be explained by changes in body weight or compliance. Plasma triglyceride levels continued to increase with low-dose therapy and remained only 11% below baseline values by the sixth month of therapy (P = not significant). Although fish oil therapy increased HDL cholesterol levels (+18% at high dose; 99% CI, 5% to 31%), favorable changes were not seen in LDL cholesterol, apolipoprotein B, or apolipoprotein A1 levels. CONCLUSIONS: Fish oil concentrate at high doses followed by low-dose maintenance therapy cannot sustain the initial large plasma triglyceride reductions. Moreover, the efficacy of the higher dose becomes less pronounced after the first month of therapy. This reduced efficacy during prolonged therapy, and the lack of beneficial effect on apolipoprotein and LDL cholesterol levels, may limit the practical benefit of fish oil in the treatment of hypertriglyceridemia.

Adult↗
PubMed1989

Effect of the degree of effort on the sensitivity of the exercise thallium-201 stress test in symptomatic coronary artery disease.

The sensitivity of ST-segment depression on the electrocardiogram during exercise is influenced by the level of effort. Whether such is the case with thallium-201 imaging (initial defect or redistribution) has not been established. Accordingly, the prevalence of these parameters was evaluated in 288 patients (age 59 +/- 10 years, 88% men) with coronary artery disease who underwent both exercise thallium-201 imaging and coronary angiography within 3 months of each other: 159 had a prior myocardial infarction, 72 had 1-vessel, and 216 had multivessel disease. The degree of effort was evaluated by 3 criteria: (1) percentage of maximal predicted heart rate (less than or equal to 65, greater than 65 to 85, greater than 85%); (2) workload during exercise (less than or equal to 4, greater than 4 to 8, greater than 8 METs); and (3) duration of exercise (less than or equal to 3, greater than 3 to 6, greater than 6 minutes). The prevalence of defects on initial images was higher than both redistribution on delayed images and ST-segment depression on the electrocardiogram (p less than 0.01). The overall prevalence of initial defects remained the same for all levels of effort and was not influenced by the presence or absence of a prior infarction. However, it decreased in patients with 1-vessel disease who exercised to higher workloads. The prevalence of redistribution on delayed thallium-201 images was higher than that of ST-segment depression on the electrocardiogram (p less than 0.01), except at higher levels of effort where they were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Prevalence and mechanisms of mitral regurgitation in the absence of intrinsic abnormalities of the mitral leaflets.

Two hundred nineteen consecutive patients referred for echocardiography were analyzed to determine the occurrence of mitral regurgitation (MR) in the absence of intrinsic abnormalities of the mitral leaflets. MR was assessed by means of the pulsed-Doppler technique. There was a higher incidence of MR associated with absence of mitral leaflet abnormalities compared to the presence of these abnormalities (59% vs 41%, p less than 0.01). The most common causes of MR were mitral annular calcification (MAC) and incomplete mitral leaflet closure (IMLC). The extent of calcific deposit in patients with MAC and the distance from the mitral leaflet coaptation point to the mitral annular plane in systole patients with IMLC correlated well with the severity of MR by Doppler technique (rho = 0.91 and 0.71, respectively). To determine the mechanisms of MR in these two conditions, 29 consecutive patients with MAC and 28 with IMLC were referred to the echocardiography laboratory, and 10 age-matched control subjects were prospectively analyzed. Patients with MAC had a 50% reduction in the sphincteric action of the mitral anulus in systole compared to control subjects. All patients with IMLC had poor left ventricular systolic function; most had left ventricular, mitral annular, and left atrial dilation, and only eight had regional wall motion abnormalities. When discriminant function analysis was used, poor left ventricular systolic function was the principal variable that separated patients with IMLC from normal subjects (F = 81.6, p less than 0.0001). We conclude that: (1) MR in adults occurs most commonly in the absence of intrinsic abnormalities of the mitral leaflets, primarily those resulting from MAC and IMLC; (2) MR in patients with MAC results from a reduced sphincteric action of the mitral anulus in systole; and (3) IMLC results from poor left ventricular systolic function, irrespective of the cause.

Aged↗
PubMed1989

A look at 15 years of planar thallium-201 imaging.

Extensive experience has been accumulated over the past 15 years regarding planar thallium-201 imaging. Quantitation of technically superior images provides a high sensitivity and specificity for the detection of CAD. In addition, planar thallium-201 images provide very important prognostic information in different clinical situations. Although single photon emission computerized tomography offers potential theoretical advantages over planar imaging, because of the problems involved in reconstruction, specifically the creation of artifacts, it may not be the ideal imaging modality in all situations. Good quality planar thallium-201 imaging still has an important role in clinical cardiology today.

Coronary Disease↗