Biomedical subjects

S Kaul

Publications and source records attributed to S Kaul.

At least 433 records · Page 24Linked to original sources

PubMedDate not supplied

Pharmacokinetics of nefazodone following multiple escalating oral doses in the dog.

The single and multiple dose pharmacokinetics of nefazodone (NEF) were investigated in a dose-escalating study in which 4 beagle dogs (weighing approximately 10 kg) were orally administered 100 mg nefazodone hydrochloride on days 1-7, 500 mg on days 8-14 and 1000 mg on days 15-20 once daily. Serial blood samples were collected over a 24 h period following administration of the first (day 1) and last (day 7) doses for the 100 mg/day dose and the last dose for the 500 (day 14) and 1000 mg/day (day 20) doses. Blood samples were also collected for trough level (Cmin) determination on the morning of the 5th, 6th and 7th day of 100 and 500 mg/day dosing regimens and the 3rd, 5th and 6th day of 1000 mg/day regimen. Plasma was analyzed for NEF and 3 metabolites [hydroxynefazodone (HO-NEF), m-chlorophenylpiperazine (mCPP) and p-hydroxynefazodone (p-HO-NEF)] by a validated HPLC assay. There were no significant differences between the 100 mg single and 100 mg/day multiple dose pharmacokinetic parameters for NEF, HO-NEF and mCPP. However, for p-HO-NEF, single dose elimination half life (T1/2) and area under the plasma concentration-time curve (AUC) extended to infinity were significantly smaller (P < or = 0.05) than the multiple dose T1/2 and AUCTAU, respectively. Based on Cmin data, steady state was reached by the 5th day of 500 mg/day and 1000 mg/day multiple dosing. Mean multiple dose AUCTAU values for NEF increased in a 1:9:26 ratio for a 1:5:10 increase in dose. Due to extensive variability and small number of animals used in the study, the statistical analysis indicated that AUCTAU values were dose-proportional. However, metabolite formation decreased significantly with increasing dose as indicated by AUCTAU ratios for metabolite:NEF. These data suggest that NEF exhibits nonlinear pharmacokinetics within 100-1000 mg/kg dose range in dogs.

Administration, Oral↗

PubMedDate not supplied

Quantitative structure--pharmacokinetic relationship of a series of sulfonamides in the rat.

The pharmacokinetics of a series of sulfonamides were investigated after intravenous administration of a 7 mg/kg dose of individual sulfonamides to cannulated female lean Zucker rats. The concentrations of the sulfonamides in blood were determined by colorimetry. The blood concentration-time curves were fitted to a biexponential equation. The partition coefficient, log P, and pKa values of the sulfonamides were taken from the literature, log P and pKa values differed markedly across the series. The extent of protein binding varied enormously, increasing with partition coefficient. There was no significant relationship between the volume of distribution and partition coefficient. However, when the influence of protein binding on volume of distribution was eliminated, a significant linear relationship emerged. Total clearance formed a relatively complex nonlinear relationship with partition coefficient. The relationship of elimination half-life and partition coefficient was inverse of that between clearance and partition coefficient because of a lack of significant relationship between volume of distribution and partition coefficient.

Animals↗

PubMedDate not supplied

Possible mechanisms for reducing memory confusion during sleep.

Confusion readily occurs in memory processes between patterns that overlap substantially. Possible mechanisms are considered that might operate in an automatic manner to reduce such confusion. One such mechanism is the recall of patterns in a distorted way, so that they are enriched with greater activity in distinctive elements of experienced patterns than in overlapping elements. Selective consolidation based on such enriched patterns would reduce confusion in long-term recall and might benefit discrimination learning. It is shown how automatic algorithms could achieve this through a process with two phases. In the first phase, somewhat analogous to slow-wave sleep, it is necessary for the normal tendency of the nervous system to learn correlations of associated activity to be disabled. The second phase must occur while the cells most active in the first phase are relatively inexcitable. Enriched patterns would be generated during this phase through recall, which might be triggered by bursts of activity such as occur in rapid eye movement sleep. Selective consolidation would take place during the second phase. If such processes do occur in the nervous system, it seems likely that they would have evolved to occur during sleep.

Animals↗

PubMedDate not supplied

Stimulation of low density lipoprotein receptor activity in liver membrane of guggulsterone treated rats.

Chronic feeding of guggulsterone to rats showed hypolipidaemic activity in blood serum and liver membrane lipids. The decrease in serum cholesterol is associated with enhanced uptake of LDL by the liver through receptor mediated endocytosis, located on the surface of the cell membrane. In the present communication it has been shown that membranes prepared from liver of guggulsterone treated rats exhibit up to 87% increase in binding sites for human 125I-LDL. Significant decrease in lipid levels of serum as well as of membrane were observed. Lipid lowering activity of the drug in relation to LDL catabolism and other possible mechanisms have been explained.

Administration, Oral↗

PubMedDate not supplied

Integrated backscatter and digital acquisition during myocardial contrast echocardiography: is there an advantage over conventional echocardiography for intracoronary injections?

This study was designed to answer the question of whether, despite their theoretic superiority, integrated backscatter imaging (IBS) and digital data acquisition (DA) offer any advantage over conventional echocardiography (CE) during quantitative myocardial contrast echocardiography. In vitro experiments were performed (1) to determine the microbubble concentration versus videointensity relationships for CE and IBS and (2) to define the relationship between flow through and microbubble transit rates for CE and IBS. These data were stored on videotape. In vivo experiments were performed whereby microbubbles were injected into the left anterior descending artery at different flow rates in 14 dogs and IBS and CE data were stored both in digital format and on videotape. Although the level of compression did not affect the microbubble concentration versus videointensity plots during IBS compared with CE, in practical terms the mean transit rate, peak intensity, and area under the curve were not affected by the level of compression for both forms of imaging as long as the postprocessing used for CE imaging was linear and the microbubble dose was small. In addition, although DA resulted in higher peak intensity and area under the curve compared with storage on videotape because of its broader dynamic range, the correlation between these measurements was excellent with both forms of image storage. We conclude that, although differences exist between CE and IBS and between Da and analog acquisition, these differences do not significantly affect the derivation of parameters from time-intensity plots during myocardial contrast echocardiography when contrast material is injected into a coronary artery.

Animals↗

PubMedDate not supplied

Relationship between left ventricular wall thickness and left atrial size: comparison with other measures of diastolic function.

We postulated that in patients with essential hypertension and normal left ventricular (LV) systolic function, left atrial (LA) size correlates with LV wall thickness by better reflecting the chronicity and duration of LA hypertension than the commonly used hemodynamic and Doppler measures of LV diastolic function. Accordingly, hemodynamic, Doppler, and two-dimensional echocardiographic measurements were performed in 30 subjects with no cardiovascular abnormalities other than essential hypertension (mean systolic blood pressure of 150 +/- 29 mm Hg). The mean LV wall thickness was 0.57 +/- 0.14 cm/m2 and the mean LV ejection fraction was 0.62 +/- 0.12. Hemodynamic and Doppler measures including pulmonary capillary wedge and LV end-diastolic pressures, isovolumic LV pressure relaxation, LV chamber elastic stiffness, and E/A ratio (E and A waves on the pulsed Doppler signal of the mitral valve) correlated poorly (r = 0.01 to -0.52) with LV wall thickness. Both E/A ratio and isovolumic LV pressure relaxation correlated better (p = 0.05) with patient age than with LV wall thickness. In contrast, LA area (in the apical four-chamber view) had a good correlation (r = 0.77 for LA area in atrial diastole and r = 0.86 for LA area in atrial systole) with LV wall thickness. Multiple regression analysis revealed LA area in atrial systole to be the best correlate of LV wall thickness. We conclude that because the left atrium is a thin-walled structure, its size may increase with an increase in LA pressure. In the absence of mitral valve disease and atrial fibrillation, LA size may reflect the chronicity and duration and thus the history of LA hypertension. LA size in the apical four-chamber view may, therefore, provide a simple noninvasive assessment of the degree of LV diastolic dysfunction.

Adult↗

PubMedDate not supplied

Technical factors that influence the determination of microbubble transit rate during contrast echocardiography.

The calculation of mean microbubble transit rate (MMTR) during contrast echocardiography provides information regarding the flow through and blood volume of a vascular system. Several technical factors can impact on the accuracy of MMTR determination. In this study, with computer simulation and in vitro and in vivo data, we systematically examined four such factors: the relationship between microbubble concentration versus videointensity, the size of the region of interest and the sampling rate used to derive time-intensity plots, and the method of deriving MMTR (direct numeric calculation vs use of a mathematic model). The results indicate that the effect of these technical factors on the estimation of MMTR can be significant.

Albumins↗

PubMedDate not supplied

Transpulmonary transit of microbubbles during contrast echocardiography: implications for estimating cardiac output and pulmonary blood volume.

We postulated that the pulmonary transit rate of sonicated albumin microbubbles, which have an intravascular rheology similar to that of red blood cells, would be directly proportional to cardiac output (CO) and inversely proportional to pulmonary blood volume (PBV). Accordingly, 4 ml of Albunex ultrasound contrast agent (0.5 billion/ml of 4.3 mu bubbles) was injected into the right atrium of six dogs (Group I) during simultaneously performed two-dimensional echocardiography, and the time between the initial appearance of the bubbles in the right and left ventricle, respectively, was measured. CO was either increased (by intravenous infusion of 15 micrograms/kg/min of dobutamine) or decreased (by producing left ventricular ischemia or by administering 2 mg of intravenous propranolol) in a random order and microbubbles were injected again. At each stage, thermodilution CO was measured. There was a close linear relation between CO and pulmonary transit rate of Albunex in each dog with the correlation coefficient ranging from 0.79 to 0.99, with a mean of 0.92. Pulmonary blood volume was derived in each dog from the reciprocal of the slope of the regression between CO and pulmonary transit rate and varied from 106 to 261 ml in the six dogs with a mean value of 178 +/- 64 ml. There was excellent interobserver and intraobserver correlation (r = 0.99 each) for determining the pulmonary transit rate of Albunex. The reproducibility of pulmonary transit rate estimation from repeated contrast injections at the same hemodynamic state in another group of six dogs (Group II) was also good (r = 0.99). It is concluded that the pulmonary transit rate of Albunex ultrasound contrast agent can be used to assess directional changes in CO and to measure pulmonary blood volume. This method may have clinical applications.

Albumins↗

PubMedDate not supplied

Attenuation deforms time-intensity curves during contrast echocardiography: implications for assessment of mean transit rates.

The mean transit rate of microbubbles of air obtained from time-intensity curves during contrast echocardiography can be used to evaluate flow through a vascular system, provided the volume of distribution of the system remains constant. We hypothesized that attenuation commonly associated with contrast echocardiography distorts the time-intensity curves, producing an error in the estimation of the mean transit rate of the microbubbles. The purpose of this study was to characterize this distortion with computer simulations and to study the effect of attenuation on the estimation of mean transit rate in an in vitro experiment. We also sought to determine if removing the data points from the time-intensity plots that visually can be attributed to attenuation before curve fitting can minimize the error in the estimation of mean microbubble transit rate. In both computer simulations and experimentally acquired in vitro data, attenuation distorted the time-intensity curves, producing an underestimation of mean microbubble transit rates. The mean microbubble transit rate decreased with an increase in microbubble concentration. Removing the points that visually were attributed to attenuation before curve fitting did not correct this error completely in the computer-simulated data and failed to correct it at all in the experimental data. These results have major practical implications in assessing mean microbubble transit rates during contrast echocardiography.

Albumins↗

PubMedDate not supplied

Value of two-dimensional echocardiography for determining the basis of hemodynamic compromise in critically ill patients: a prospective study.

We postulated that because the first step in the management of critically ill patients with hypotension, pulmonary edema, or both is to determine whether the cause is cardiac or noncardiac, direct visualization of the heart with two-dimensional echocardiography would be useful for determining the basis of hemodynamic compromise in such patients. Accordingly, 49 consecutive patients (33 men and 16 women; mean age 61 +/- 15 years) underwent two-dimensional echocardiography within 2 hours of placement of a pulmonary artery flotation catheter for determining the reason for hypotension, pulmonary edema, or both. To discriminate between cardiac and noncardiac causes, hemodynamic and two-dimensional echocardiographic data were evaluated independently by two to three blinded interpreters based on predetermined criteria. There was complete agreement between pulmonary artery catheter and two-dimensional echocardiographic data in 36 (86%) of the 42 patients in whom interpretable data were available in terms of cardiac versus noncardiac causes. The two modalities agreed in all patients with hypotension alone and disagreed in 2 of the 20 patients with pulmonary edema alone and 4 of the 14 patients with combined hypotension and pulmonary edema. In cases of discordance, the two tests provided complimentary information, particularly in patients with sepsis in whom the stroke volume may be normal to high but left ventricular systolic function may be depressed. The time taken for pulmonary artery catheter placement was 63 +/- 45 minutes versus 19 +/- 7 minutes for two-dimensional echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheterization, Swan-Ganz↗

PubMedDate not supplied

A computer-aided approach for the quantitation of regional left ventricular function using two-dimensional echocardiography.

Quantitation of regional left ventricular function is becoming increasingly important in this era of interventional cardiology. In this article we describe a computer-assisted approach for the assessment of regional left ventricular function that integrates three features. First, it measures left ventricular wall thickening and endocardial motion and curvature during an entire systolic contraction sequence. Second, it allows us to easily define endocardial and epicardial borders without actually having to manually trace the entire border. Third, it displays complex data in a simple format for easy assimilation. We believe that this approach is practical and comprehensive and can be used to quantitate regional left ventricular function with two-dimensional echocardiography.

Color↗

PubMedDate not supplied

Utility of transesophageal echocardiography in the diagnosis of aortic conduit endocarditis in patients who have undergone the Cabrol procedure.

The Cabrol procedure is being increasingly performed in patients with aortic pathologic conditions. Transesophageal echocardiography can help in the prompt diagnosis of endocarditis in these patients. In this report we present transesophageal echocardiographic features of two patients in whom endocarditis developed after they underwent the Cabrol procedure for ascending aortic aneurysm caused by Marfan's syndrome.

Adult↗

PubMedDate not supplied

Method for the quantitation of myocardial perfusion during myocardial contrast two-dimensional echocardiography.

This article describes the hardware and software components of two systems designed for quantitative analysis of data obtained during myocardial contrast two-dimensional echocardiography. One system is meant for off-line analysis of data, whereas the other is designed for on-line analysis, especially in the operating room. The algorithms used for data transfer, selection of appropriate frames, data alignment, derivation of time-intensity plots, and curve-fitting and parameter generation are described in some detail. It is hoped that this information will be of use to others who work in the field of myocardial perfusion imaging.

Algorithms↗

PubMedDate not supplied

Correlation between left ventricular risk area and clinical, electrocardiographic, hemodynamic, and angiographic variables during acute myocardial infarction.

Since the area at risk for necrosis is the most important determinant of ultimate infarct size, knowledge of its size would be helpful in making therapeutic decisions during acute myocardial infarction. We hypothesized that indirect estimations of the risk area by use of clinical, electrocardiographic, hemodynamic, or angiographic variables are inaccurate in the setting of acute myocardial infarction. Accordingly, these variables were correlated with an echocardiographically derived risk area in 24 patients experiencing their first acute myocardial infarction. These patients underwent cardiac catheterization and echocardiography within 3 hours of hospital admission. The clinical (Killip class) and electrocardiographic findings (number of leads with ST segment changes) correlated poorly with the size of the risk area (r = 0.28 and r = -0.10, respectively). Hemodynamic data (which included right atrial, pulmonary artery, and pulmonary capillary wedge, aortic, and left ventricular end-diastolic pressures) and cardiac output, systemic and pulmonary vascular resistance, and heart rate demonstrated a poor correlation (r less than or equal to 0.47) with the risk area. The left ventricular ejection fraction and the number of diseased vessels determined by angiography also correlated poorly with the risk area (r = -0.47 and r = 0.10, respectively). Patients with multivessel disease were more likely to have abnormal wall motion remote from the infarct zone compared to patients with single-vessel disease (45% versus 8%, p less than 0.05). The left ventricular ejection fractions were lower in the group of patients with multivessel disease (0.43 versus 0.51, p = 0.06) and correlated better with the total extent of abnormal wall motion on echocardiography compared to patients with single-vessel disease (r = -0.67 versus r = -0.007). We conclude that clinical, electrocardiographic, hemodynamic, and angiographic variables do not provide an accurate estimate of the size of the left ventricular risk area during acute myocardial infarction. A direct visualization of left ventricular dynamics may provide a more accurate assessment of the size of the risk area and the total extent of left ventricular dysfunction.

Angiography↗

PubMedDate not supplied

Albunex: a safe and effective commercially produced agent for myocardial contrast echocardiography.

Microbubble solutions of sonicated human serum albumin have been shown to be effective echocardiographic contrast agents free from adverse effects on coronary blood flow, left ventricular function, and systemic hemodynamics. Albunex is a commercially prepared solution of air-filled albumin microspheres prepared from sonicated 5% human serum albumin. The effects of Albunex on coronary blood flow, left ventricular function, and systemic hemodynamics, as well as contrast enhancement were evaluated in 10 open chest, anesthetized dogs. After an intracoronary injection, Albunex did not alter left atrial, left ventricular systolic or end-diastolic, or mean aortic pressures. It did not cause a coronary hyperemic response, alter left ventricular systolic thickening, or lower the peak positive left ventricular dp/dt. It did not alter these measurements even in the presence of a critical coronary stenosis. The contrast opacification produced by Albunex microbubbles was dose dependent (optimal dose range of 0.033 to 0.5 ml/kg), with attenuation occurring at higher doses. In conclusion, although Albunex provides adequate contrast enhancement, intracoronary injection of Albunex does not significantly alter coronary blood flow, left ventricular function, or systemic hemodynamics. Because of the standardized size and concentration of the microspheres, Albunex may be an ideal agent for myocardial contrast echocardiography.

Albumins↗

PubMedDate not supplied

Outcomes issues regarding utilization of echocardiography in patients with known or suspected coronary artery disease.

In this opinion paper, outcomes issues that should determine the utilization of echocardiography in patients with known or suspected coronary artery disease is discussed. The issues discussed are the level of training and competence in performing and interpreting echocardiographic studies, sensitivity and specificity of the test in various conditions, ability to deal with artifacts, the pretest probability of disease, incremental value of a test in context of what is already known about a patient, cost-benefit analysis, and whether risk stratification is justified when risk management is not possible. Concepts, rather than an exhaustive view of the literature, are discussed and areas that require further investigation are mentioned.

Artifacts↗

PubMedDate not supplied

Insights into the assessment of myocardial perfusion offered by different cardiac imaging modalities.

Myocardial perfusion may be very broadly defined as the tightly regulated nutrient delivery to cardiac tissue. The different components of perfusion are myocardial blood flow, oxygen delivery, myocardial oxygen consumption, and myocardial blood volume. Historically, focus has been placed mostly on the assessment of blood flow. In many instances, knowledge of flow without information about these other aspects is inadequate. This review discusses the various cardiac imaging techniques used for the assessment of myocardial perfusion that represent diverse physiologic measures of "perfusion." Their strengths and limitations are discussed as is their relevance to specific clinicopathologic conditions. Significant work still needs to be performed before all the aspects of myocardial perfusion can be precisely measured in human beings.

Blood Volume↗

PubMedDate not supplied

Assessment of myocardial viability with two-dimensional echocardiography and magnetic resonance imaging.

In a patient with coronary artery disease, clinical, electrocardiographic, and angiographic information is often inadequate for determining the presence of viable tissue. The presence of wall thickening, even if reduced, indicates that the myocardium is viable. When wall thickening is absent, the myocardium may or may not be viable. The basis for the underlying myocardial dysfunction may be multifactorial in a single patient or even in a single myocardial segment. Cardiac imaging techniques are most useful in defining the mechanisms of underlying myocardial dysfunction and assist in selecting the optimal management strategy for patients. This review discusses the role of two-dimensional echocardiography and magnetic resonance imaging for the assessment of myocardial viability.

Coronary Disease↗