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Biomedical subjects

S Kaul

Publications and source records attributed to S Kaul.

At least 379 records · Page 21Linked to original sources
PubMed1986

Prediction of apparent volume of distribution in obesity.

A standard height-weight table permits the separation of the obese body into two compartments: a lean and a fat. Depending upon the physicochemical properties of a drug, such as pKa, apparent partition coefficient and extent of protein binding, the distribution of a drug could either be in the lean compartment or in the whole body. Based on this thesis, several equations, either published in the literature or developed for this report, all based on the physico-chemical properties of a drug and the physiological changes in the obese subject, were used to compare the apparent volume of distribution, Vz as predicted by these equations with the Vz values of several drugs reported in the literature for obese subjects. Duncan's multiple range test was used for testing literature values vs. predicted data. Examples from the literature are reported and discussed. The validity of these equations needs to be verified as more information on pharmacokinetic parameters in obesity becomes available.

Body Height↗
PubMed1986

Influence of peak exercise heart rate on normal thallium-201 myocardial clearance.

Measurement of myocardial clearance rates between initial and delayed images is a major justification for adding computer quantification to the interpretation of exercise 201TI images. To clarify the range of normal thallium clearance and its relationship to the level of exercise achieved, exercise thallium images in 89 normal subjects were analyzed: 45 asymptomatic subjects with less than 1% probability of coronary artery disease (CAD) (Group I), and 44 patients with chest pain found to have no significant CAD on angiography (Group II). Mean initial regional thallium uptake was similar in the two groups, but myocardial thallium clearance (mean +/- 1 s.d.) was slower in Group II, expressed as a longer half-life in the myocardium (8.2 +/- 7.6 hr compared with 3.4 +/- 0.7 hr p less than 0.001). Analysis of variance using ten clinical and exercise variables as covariates showed that the slower clearance in Group II was related to a lower peak exercise heart rate (HR) (154 +/- 27 compared with 183 +/- 11, respectively, p less than 0.001). By linear regression analysis, a decrease in peak HR of 1 beat/min was associated with a slower thallium clearance (longer half-life) of 0.05 hr. Using this formula, the clearance value in each patient was then corrected for peak exercise heart rate by decreasing measured clearance by 0.05 hr multiplied by the amount peak exercise heart rate which was below 183 (the mean value in Group I). There were no differences in the "corrected" clearance between the two groups. We conclude that thallium myocardial clearance after exercise is related in part to factors other than the presence of CAD, being slower when peak exercise HR is lower. Therefore, thallium clearance rates alone uncorrected for peak exercise heart rate should be used with caution when diagnosing CAD.

Adult↗
PubMed1986

Total body water as an index for predicting body fat in rats.

The determinations of total body water, body density, surface area and Lee index were carried out on 15 live Sprague-Dawley rats. The rats were subsequently sacrificed and subjected to carcass analysis by desiccation, gravimetry and ether extraction of body fat. The results of multiple regression using the maximum R2 improvement technique indicated that a strong correlation existed only between body fat and total body water which was statistically significant (P = 0.0001). The regression equation representing such a relationship was % of body fat = 83.167-1.067 X (% total body water). The % body fat computed from density, multiple regression models, and the actual fat content of carcass were not significantly different by the Newman-Keuls range test. The validation of the predicting equation was done using lean and obese Zucker rats. It was found that the predicting equation overestimated body fat by 0.67% for lean rats and underestimate 1 body fat of obese Zucker rats by 3.57%.

Adipose Tissue↗
PubMed1985

Purification and characterization of mammalian DNA methyltransferases by use of monoclonal antibodies.

Previously, we have derived murine hybridomas producing monoclonal antibodies against DNA methyltransferase from human placenta (Kaul, S., Pfeifer, G. P., and Drahovsky, D. (1984) Eur. J. Cell Biol. 34, 330-335). One of these monoclonal antibodies, M2B10, which undergoes immune complex formation also with DNA methyltransferase from P815 mouse mastocytoma cells, was used for the immunoaffinity purification of mouse and human DNA methyltransferases. In sodium dodecyl sulfate-polyacrylamide gels and in immunoblotting studies, the immunoaffinity-purified mouse DNA methyltransferase revealed 5-6 polypeptides of molecular masses 150-190 kDa. The immunoaffinity-purified human placental DNA methyltransferase was characterized by a polypeptide of 158 kDa, presumably representing the native enzyme molecule and by polypeptides of 105-108 kDa and 50-68 kDa, probably generated by a limited proteolysis of the native enzyme molecule. The immunoaffinity-purified DNA methyltransferases preferred hemimethylated DNA substrates over unmethylated ones, and among all unmethylated substrates tested, poly[(dG-dC).(dG-dC)] had the highest methyl-accepting activity. DNA polymers of at least 90 base pairs in length were required for the binding reaction of the immunoaffinity-purified human DNA methyltransferase, and this initial binding was apparently independent of the nucleotide composition of the DNA polymer and of the presence of S-adenosyl-L-methionine.

Animals↗
PubMed1985

Comparison of exercise electrocardiography and quantitative thallium imaging for one-vessel coronary artery disease.

The relative value of exercise electrocardiography and computer analyzed thallium-201 imaging was compared in 124 patients with 1-vessel coronary artery disease (CAD). Of these, 78 had left anterior descending (LAD), 32 right and 14 left circumflex (LC) CAD. In patients with no previous myocardial infarction (MI), thallium imaging was more sensitive than the electrocardiogram (78% vs 64%, p less than 0.01), but in patients with previous MI, sensitivity was similar. Further, thallium imaging was more sensitive only in LAD and LC disease. Redistribution was compared with ST-segment depression as a marker of ischemia. Only in patients with prior MI (76% vs 44%, p less than 0.01) and only in LC and right CAD did redistribution occur more often than ST depression. Thallium imaging was more accurate in localizing stenoses than the electrocardiogram (p less than 0.001), but did not always correctly predict coronary anatomy. Septal thallium defects were associated with LAD disease in 84%, inferior defects with right CAD in 40% and posterolateral lesion defects with LC CAD in 22%. The results indicate the overall superiority of thallium imaging in 1-vessel CAD compared with exercise electrocardiography; however, there is a wide spectrum of extent and location of perfusion defects associated with each coronary artery. Thallium imaging complements coronary angiography by demonstrating the functional impact of CAD on myocardial perfusion.

Adult↗
PubMed1985

Hyperinnervation of the striatum by dorsal raphe afferents after dopamine-depleting brain lesions in neonatal rats.

Dopamine-depleting brain lesions produced in neonatal rats by intraventricular injection of 6-hydroxydopamine (6-OHDA) are known to increase striatal levels of serotonin by adulthood. We now report that such lesions lead to an increased innervation of the striatum by serotonin-containing neurons from the dorsal raphe nucleus. This hyperinnervation was revealed as a 300% increase in the number of retrogradely labeled neurons in the dorsal raphe after horseradish peroxidase was injected into the adult striatum. The degree of hyperinnervation was reduced sharply when serotonin-depleting brain lesions were given to adult animals that had received 6-OHDA as neonates.

5,7-Dihydroxytryptamine↗
PubMed1985

Hemodynamic effects of intravenous flecainide relative to the level of ventricular function in patients with coronary artery disease.

Flecainide, a new antiarrhythmic agent with poorly defined hemodynamic actions, was studied in 22 patients with coronary artery disease. Intravenous infusions of 1 mg/kg and 2 mg/kg resulted in respective increases in right atrial pressure (12%, p less than 0.05; 15%, p less than 0.01), mean pulmonary artery pressure (27%, p less than 0.01; 28%, p less than 0.01), and pulmonary capillary wedge pressure (44%, p less than 0.05; 33%, p less than 0.01). Cardiac index decreased 8% (p less than 0.05) after 1 mg/kg flecainide and 12% (p less than 0.05) after the 2 mg/kg dose. The mean left ventricular ejection fraction decreased by 15% (p less than 0.01) and 16% (p less than 0.01), respectively, 10 minutes after 1 mg/kg and 2 mg/kg of flecainide. Minimal increases in the heart rate (less than 5%) and no significant change in arterial pressure occurred 5 to 10 minutes after flecainide and were associated with borderline and variable increases in pulmonary and systemic vascular resistances. Flecainide diluent did not induce changes in pulmonary capillary wedge pressure or left ventricular ejection fraction. Thus, flecainide exerts a moderate but significant negative inotropic effect which may be clinically significant in patients with severely compromised ventricular function.

Adult↗
PubMed1985

The dominant role of amide group at C-terminus for recognition by antibody in primates against gonadotropin releasing hormone.

A monkey and a baboon immunized with GnRH-tetanus toxoid conjugate developed high anti-GnRH antibody titres which resulted in disruption of cyclicity and low estradiol and progesterone levels indicative of the inhibition of follicular development and ovulation. Sera of both animals reacted with GnRH(NH2) but were devoid of reactivity with peptide sequences, 4-6, 7-10 and 4-10 of GnRH as well as GnRH free acid. Both sera were however reactive with GnRH-Lys-muramyl dipeptide analogue and GnRH-Ala-Ala-Thr-Lys-Pro-Arg-OH. As these compounds differ from GnRH-free acid by the presence of amide linkage at C-terminus of GnRH, these studies point to the importance of the conformation involving amide group at this position for immunoreactivity.

Amino Acid Sequence↗
PubMed1985

Functional and pathologic effects of multiple echocardiographic contrast injections on the myocardium, brain and kidney.

Myocardial contrast echocardiography can define in vivo the area at risk for necrosis after coronary occlusion. However, if this technique is to be used, it cannot be intrinsically toxic to the heart or other critical organs. To determine the functional and pathologic effects of contrast echocardiography, six intracoronary, six intrarenal and six intracarotid artery injections of 2 to 6 cc of a commonly employed contrast agent (agitated Renografin-saline solution) were performed in five dogs. A sixth dog served as a sham to assess any deleterious effects of the model preparation. Two-dimensional echocardiographic images and electrocardiograms were recorded during intracoronary injections, and heart rate, blood pressure, left ventricular end-diastolic pressure and rate of rise of left ventricular pressure (dP/dt) were continuously monitored. At 24 hours, echocardiographic and hemodynamic measurements were repeated, the dogs were killed and the heart, brain and kidneys were removed and prepared for light microscopic examination. Quantitative analysis of left ventricular wall motion was performed on control, peak contrast, post-contrast and 24 hour studies. With each intracoronary injection, there were transient decreases in blood pressure (p = 0.05 versus control) and increases in left ventricular end-diastolic pressure (p = 0.04 versus control). These were associated with depression of wall motion in contrast-enhanced regions (p = 0.01 versus control) and ST-T segment changes on the electrocardiogram. No significant change in heart rate or left ventricular dP/dt was noted. All variables normalized with the clearance of the contrast effect and remained normal to 24 hours. Light microscopic examination revealed no myocardial or cerebral changes attributable to the contrast agent injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Contrast echocardiography in acute myocardial ischemia. II. The effect of site of injection of contrast agent on the estimation of area at risk for necrosis after coronary occlusion.

Myocardial contrast echocardiography has been shown to accurately assess the area at risk for necrosis after acute coronary occlusion in the experimental model. The area at risk as determined by this method, however, has been defined in different ways depending on the model used. Some investigators have injected the contrast agent proximal to the site of coronary occlusion (left main coronary artery or aorta) and defined the area at risk as the segment of myocardium not showing a contrast effect (negative risk area). Others have injected the contrast agent directly into the occluded vessel and have defined the area at risk as that showing contrast enhancement (positive risk area). To evaluate whether the areas at risk determined by these two techniques are identical, six open chest dogs were studied using both methods. The area at risk was slightly but significantly larger when the contrast agent was injected into the occluded vessel than when it was injected proximally into the left main coronary artery (4.98 +/- 1.69 versus 3.97 +/- 1.27 cm2, p less than 0.01). It is concluded that the site of injection of the contrast agent significantly influences the determination of area at risk. Therefore, data obtained by the two techniques should not be used interchangeably, and in a given study the area at risk should be measured consistently using one technique.

Animals↗
PubMed1984

Sources of variability in the radionuclide angiographic assessment of ejection fraction: a comparison of first-pass and gated equilibrium techniques.

Measurements of ejection fractions (EF) determined by first-pass and gated equilibrium radionuclide angiography are widely believed to be equivalent. To compare these measurements in a large group of patients over a wide range of EF values, left ventricular (LV) and right ventricular (RV) EFs at rest were measured in 135 consecutive patients who underwent the 2 methods of radionuclide angiography within 1 hour: first-pass upright with a multi-crystal camera in the anterior projection and gated equilibrium supine with a single-crystal camera in the left anterior oblique projection. The population included 18 normal patients and 117 patients with various cardiac and pulmonary disorders. First-pass and gated equilibrium LVEF correlated well (r = 0.83, p less than 0.001), but the slope of the regression line was different from unity, with the first-pass values lower than the gated equilibrium values (0.51 +/- 0.16 vs 0.56 +/- 0.15, p less than 0.05 [mean +/- standard deviation] ). Among the 45 patients with a gated equilibrium LVEF of less than or equal to 0.50, the correlation (r = 0.84) was better than that for the 90 patients with a LVEF greater than 0.50 (r = 0.44, p less than 0.05). However, in the latter group, the correlation remained good in the 15 patients with cardiomegaly due to aortic or mitral regurgitation (r = 0.80). Inter- and intraobserver error was similar for both methods. In contrast, there was a poor correlation between first-pass and gated equilibrium RVEF, with the first-pass values higher than the gated equilibrium values (0.51 +/- 0.11 vs 0.43 +/- 0.11, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Superiority of supine bicycle over isometric handgrip exercise in the assessment of ischemic heart disease: an evaluation of left ventricular ejection fraction response using radionuclide angiography.

Left ventricular ejection fraction (LVEF) response to supine bicycle and isometric handgrip exercise was evaluated in 15 patients with documented coronary artery disease (CAD) and stress-induced ischemia using radionuclide angiography. For purposes of analysis, the patients were divided into two groups: group I (n = 7) with single-vessel disease and group II (n = 8) with multiple-vessel disease including 3 with left main artery disease. The studies were repeated 18 days later at similar external workloads to assess reproducibility of both tests. LVEF response to bicycle exercise was different for the two groups. The change in LVEF from rest to peak exercise was +0.04 +/- 0.02 for group I and -0.07 +/- 0.04 for group II (p less than .001). LVEP response to isometric handgrip exercise was not different between the two groups. The change from rest to end of handgrip exercise was -0.02 + 0.02 for group I and -0.05 +/- 0.02 for group II. The reproducibility of LVEF response to bicycle exercise at similar workloads on day 1 and day 19 was good (r = 0.85) while it was poor for isometric handgrip testing (r = 0.67). Our data demonstrate that radionuclide angiographic measurement of LVEF response to supine bicycle exercise testing is superior to LVEF response to isometric handgrip testing in the evaluation of patients with CAD.

Adult↗
PubMed1984

Assessment of right ventricular function using two-dimensional echocardiography.

With the use of two-dimensional echocardiography (2DE), we analyzed apical and subcostal four-chamber views for evaluation of right ventricular (RV) function in 30 individuals as compared to RV ejection fraction (RVEF) obtained by radionuclide angiography. In addition to previously reported parameters of changes in areas and chords, a new simple measurement of tricuspid annular excursion was correlated with RVEF. A close correlation was noted between tricuspid annular plane systolic excursion (TAPSE) and RVEF (r = 0.92). The RV end-diastolic area (RVEDA) and percentage of systolic change in area in the apical four-chamber view also showed close correlation with RVEF (r = -0.76 and 0.81); however, the entire RV endocardium could only be traced in about half of our patients. The end-diastolic transverse chord length and the percentage of systolic change in chord length in the apical view showed a poor correlation with RVEF. The correlation between RVEF and both areas and chords measured in the subcostal view was poor. It is concluded that the measurement of TAPSE offers a simple echocardiographic parameter which reflects RVEF. This measurement is not dependent on either geometric assumptions or traceable endocardial edges. When the endocardial outlines could be traced, the apical four-chamber view was superior to the subcostal view in assessment of RV function.

Adult↗
PubMed1984

Comparative effects of oral acebutolol and propranolol at rest and during exercise in ischemic heart disease: double-blind placebo crossover study utilizing radionuclide ventriculography.

Acebutolol is a new investigational beta-antagonist which has intrinsic sympathomimetic and cardioselective properties. In this study its effects on the ischemic consequences following supine bicycle exercise were compared to those of propranolol in 16 patients with chronic stable coronary artery disease (CAD) using a double-blind placebo crossover protocol and equilibrium radionuclide ventriculography. In eight patients (group I), the left ventricular ejection fraction (LVEF) at peak exercise fell under control conditions. During chronic acebutolol therapy (400 mg thrice daily), the exercise-induced LVEF (means +/- 1 SD) was significantly higher (37.1 +/- 15.5% versus 42.2 +/- 14.3%; p less than 0.05). The corresponding values during placebo and during propranolol (80 mg thrice daily) were 39.2 +/- 12.3% versus 43.4 +/- 14.8% (p = 0.07). In eight patients (group II) in whom supine bicycle exercise produced increases in LVEF, both acebutolol (58.8 +/- 5.4% versus 53.8 +/- 4.4%) and propranolol (57.8 +/- 5.7% versus 54.1 +/- 4.9%) attenuated the increases. In neither group was the resting LVEF reduced by acebutolol or propranolol. The data show that acebutolol and propranolol are approximately equipotent in minimizing the radionuclide left ventriculographic manifestations of myocardial ischemia induced by supine bicycle exercise.

Acebutolol↗
PubMed1984

Contrast echocardiography in acute myocardial ischemia: I. In vivo determination of total left ventricular "area at risk".

Myocardial contrast echocardiography has been shown recently to accurately assess the "area at risk" for necrosis after acute coronary occlusion in the experimental model. Risk area quantitation, however, has been studied primarily from single tomographic planes. Because the three-dimensional extent of myocardial necrosis depends on the total volume of myocardium at risk, the total left ventricular "area at risk" was determined in 11 dogs (Group A) with either left anterior descending or left circumflex artery occlusion using contrast echocardiography and compared with risk area determined by technetium autoradiography. An excellent correlation was found between the two methods (r = 0.96%, y = 0.91x + 1.5, p less than 0.001, SEE = 3.17). A comparison of risk area for individual levels of the left ventricle using both methods, however, showed some variation in the degree of correlation, with the poorest fit being apparent at the apex. To identify the source of the variation, errors caused by data registration were minimized in six additional dogs (Group B) by implanting epicardial markers at a single level and measuring "area at risk" at this level using both methods. When no registration error was present, the correlation between the two methods was excellent (r = 0.99, y = 0.92x + 2.6, p less than 0.001, SEE = 0.55). In conclusion, the "area at risk" for infarction after acute coronary occlusion can be determined accurately for the entire left ventricle as well as for a single tomographic slice using myocardial contrast echocardiography. This was validated using technetium autoradiography, which is an established method of determining "area at risk" in the experimental setting.

Animals↗
PubMed1984

Quantitation of myocardial infarct size from thallium-201 images: validation of a new approach in an experimental model.

A new computer-based method has been developed to quantitate myocardial infarct size from the size of the regional thallium-201 deficit. The operator outlines the left ventricular myocardial activity with an ellipse. The program then plots the background-corrected activities of the highest mean value in a 3 pixel myocardial band perpendicular to and within the ellipse. The approach uses a new interpolative background correction. To determine the accuracy of this approach in assessing regional thallium deficit size, acute myocardial infarction was produced in six dogs by 24 hour occlusion of the proximal left anterior descending coronary artery. Infarct size was assessed from planar thallium images of the dog heart in three views, each with the chest opened and closed and with the heart excised and placed in a cradle. Before removal of the heart, triphenyltetrazolium chloride was infused to delineate normal from infarct tissue. Transverse slices of left ventricle were made and thallium images of the slices acquired. Infarct size delineated by triphenyltetrazolium chloride staining was expressed as a percent of the total left ventricular slice surface area (planimetric infarct size). Infarct size from whole heart and left ventricular slice thallium images was expressed as a percent of the total length of the left ventricular perimeter (perimetric infarct size). This was determined from points below a certain percent of normalized peak thallium activity in the computer-generated thallium activity curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗