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Biomedical subjects

S Kaul

Publications and source records attributed to S Kaul.

At least 199 records · Page 11Linked to original sources
PubMed1996

Diagnostic value of echocardiography in suspected endocarditis. An evaluation based on the pretest probability of disease.

BACKGROUND: We hypothesized that for the diagnosis of endocarditis, (1) transthoracic echocardiography (TTE) would be most valuable in patients with an intermediate clinical probability of the disease and (2) transesophageal echocardiography (TEE) would be most useful in patients with an intermediate probability when TTE either does not yield an adequate study or indicates an intermediate probability of endocarditis. We also sought to investigate the influence of echocardiographic results on antibiotic usage and its duration. METHODS AND RESULTS: TTE and TEE were performed in 105 consecutive patients with suspected endocarditis. Patients were classified as having either low, intermediate, or high probability of endocarditis on the basis of clinical criteria and separately on the basis of both TTE and TEE findings. TTE and TEE classified the majority (82% and 85%, respectively) of the 67 patients with a low clinical probability of endocarditis as having a low likelihood of the disease. Of the 14 patients with intermediate clinical probability, 12 had technically adequate TTE studies; 10 of these (83%) were classified as either high or low probability. All patients with intermediate clinical probability were classified as high or low probability by TEE. The majority of the 24 patients with high clinical probability were placed in the low-likelihood category by echocardiography (15 by TTE and 12 by TEE). There was concordance between TTE and TEE in 83% of all cases. TEE was useful for the diagnosis of endocarditis in patients with prosthetic valves and in those in whom TTE indicated an intermediate probability; these constituted < 20% of patients in our study. The course of antibiotic therapy was influenced only by the clinical profile and not by the echocardiographic results. CONCLUSIONS: Echocardiography should not be used to make a diagnosis of endocarditis in those with a low clinical probability of the disease. In those with an intermediate or high clinical probability, TTE should be the diagnostic procedure of choice. TEE for the diagnosis of endocarditis should be reserved only for patients who have prosthetic valves and in whom TTE is either technically inadequate or indicates an intermediate probability of endocarditis.

Adolescent↗
PubMed1996

Bioequivalence assessment of etoposide phosphate and etoposide using pharmacodynamic and traditional pharmacokinetic parameters.

The bioequivalence of etoposide phosphate, a prodrug of etoposide, to etoposide was assessed in a randomized, crossover study in 29 patients with histologically established solid tumors that had failed conventional treatment. Cohorts of patients received one treatment course each of etoposide and etoposide phosphate which consisted of a 100 mg/m2 per day etoposide equivalent dose infused i.v. over 1 hr on a Day 1 to 5 schedule of treatment. The second course was administered 21 days later or on recovery of blood cell counts. Plasma and urine samples were collected over 24 hr on Day 1 of each course and assayed for etoposide content by a validated HPLC/UV method. Resulting data were subjected to noncompartmental pharmacokinetic analysis. Hematology profiles were obtained by collecting blood samples prior to the first course and twice a week after each course. The pharmacodynamics and pharmacokinetics of etoposide were virtually identical after the two treatments. The point estimates (90% confidence intervals) for nadir WBC, granulocytes, hemoglobin, and platelets expressed as % decrease from the baseline, and for the pharmacokinetic parameters, Cmax, and AUC0 infinity, after intravenous etoposide phosphate relative to etoposide were 100% (96%, 105%), 97% (91%, 103%), 95% (82%, 109%), 95% (84%, 106%), 107% (101%, 113%), and 113% (107%, 119%), respectively. Therefore, etoposide phosphate is bioequivalent to etoposide based on pharmacokinetic and pharmacodynamic assessments.

Adult↗
PubMed1996

Specific radioimmunoassays for the measurement of stavudine in human plasma and urine.

Sensitive and specific radioimmunoassays (RIAs) have been developed and validated for the determination of stavudine, a nucleoside analog possessing anti-human immunodeficiency virus (HIV) activity, in human plasma and urine. The hemisuccinate of stavudine was conjugated with histamine and radioiodinated to yield the radiotracer. Antisera were produced by injecting the immunogen, stavudine-hemisuccinate-bovine thyroglobulin, into rabbits. The antisera exhibited high specificity for stavudine as the structurally related analogs and other anti-HIV agents did not interfere in the assays. The methods could reliably quantitate stavudine in plasma from 2.5-100 ng ml-1 and in urine from 5.0-1000 ng ml-1 (after 2.5-fold dilution) with good accuracy and precision. The lower limits of quantitation were 2.5 ng ml-1 in human plasma and 5.0 ng ml-1 in urine (after 2.5-fold dilution). The RIA methods were applied to the analysis of stavudine in plasma and urine obtained from HIV-infected patients receiving the drug in clinical trials.

Animals↗
PubMed1996

Disposition of didanosine in HIV-seropositive patients with normal renal function or chronic renal failure: influence of hemodialysis and continuous ambulatory peritoneal dialysis.

OBJECTIVE: To evaluate the pharmacokinetics of didanosine in patients with normal kidney function or chronic kidney failure. METHODS: Three groups of patients with human immunodeficiency virus (HIV) infection were studied: group I, six men with normal kidney function (creatinine clearance > 90 ml/min/1.73 m2); group II, six men with chronic renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD); and group III, four men and two women with chronic renal failure receiving hemodialysis three times a week. A 300 mg dose of didanosine was administered orally and intravenously according to a two-period randomized crossover design. Patients in group III were studied between hemodialysis sessions during the crossover periods. In addition, patients in group III were studied in a third period after administration of a 300 mg oral dose of didanosine 4 hours before hemodialysis. RESULTS: After intravenous administration in group I, the mean (+/-SD) total clearance (CLT) was 13.0 +/- 1.6 ml/min/kg and the elimination half-life (t 1/2) was 1.56 +/- 0.43 hour. In groups II and III, the CLT decreased significantly to 3.4 +/- 1.2 and 3.2 +/- 1.2 ml/min/kg, respectively, whereas the t1/2 increased to 3.60 +/- 0.82 hours and 3.11 +/- 0.88 hours, respectively. The absolute bioavailability of didanosine in groups I, II, and III was 42% +/- 12%, 52% +/- 6%, and 38% +/- 11%, respectively, and did not differ significantly. CAPD had little effect on the removal of didanosine, whereas approximately 30% of the drug present in the body at the start of dialysis was eliminated by an average 3-hour dialysis session. CONCLUSION: The clearance of didanosine is impaired in patients with chronic renal failure. To compensate, the dose and schedule of administration should be adjusted. It is recommended that one-fourth of the total daily dose of didanosine be administered once a day in this patient population.

Administration, Oral↗
PubMed1996

Infarct size reduction with coronary venous retroinfusion of diltiazem in the acute occlusion/reperfusion porcine heart model.

Calcium channel blockers are commonly used for the treatment of ischemic heart disease, but their effects on myocardial infarct size (IS) after reperfusion are not well known. Enflurane-anesthetized open-chest pigs subjected to 60-min left anterior descending coronary artery (LAD) occlusion followed by 3-h reperfusion were referred to one of the four experimental groups. Beginning 10 min before the onset of reperfusion, pigs in group A received diltiazem (7.5 micrograms/kg/min) retrogradely infused into the coronary vein for 30 min. In group B, the same amount of diltiazem was infused into the right atrium. A corresponding volume of saline was infused into the coronary vein in group C or into the right atrium in group D. IS expressed as a percentage of the myocardium at risk was significantly smaller (p < 0.01) in group A (33 +/- 14%; mean +/- SD) than in groups B (58 +/- 11%), C (58 +/- 11%), and D(63 +/- 10%). After reperfusion, functional recovery of the ischemic myocardium, determined by ultrasound crystals, was significantly more improved (p < 0.05) in group A as compared with other groups. The ischemic and nonischemic regional myocardial blood flow (RMBF), determined by radioactive microspheres, did not differ between four groups. Coronary venous retroinfusion of diltiazem had a myocardial protective effect in the porcine experimental model of acute coronary occlusion/reperfusion, whereas intravenous drug administration was not effective. The protective effect could not be attributed to washout of toxic metabolites from the ischemic area or to improved microcirculation. It was probably related to a pronounced accumulation of the calcium-channel blocker diltiazem in the ischemic myocardium achieved by the coronary venous route of delivery.

Animals↗
PubMed1996

Etoposide bioavailability after oral administration of the prodrug etoposide phosphate in cancer patients during a phase I study.

PURPOSE: The purpose of this study was to determine the bioavailability (F) of etoposide (E;VP-16) after oral administration of the water-soluble prodrug etoposide phosphate (EP;BMY-40481) during a phase I trial in cancer patients. PATIENTS AND METHODS: Twenty-nine patients received oral EP (capsules, 50 to 150 mg/m2/d of E equivalent) for 5 days in week 1 (course 1), followed every 3 weeks thereafter by a daily intravenous (i.v.) infusion for 5 days of E (80 mg/m2, 1-hour i.v. infusion; course 2); in three patients, the i.v. E course was given before oral EP. Plasma and urine E pharmacokinetics (high-performance liquid chromatography [HPLC]) were performed on the first day of oral EP administration and on the first day of i.v. E. RESULTS: Twenty-six of 29 patients completed two courses or more, whereas three patients received only one course due to toxicity. Myelosuppression was dose-dependent and dose-limiting, with grade 4 leukoneutropenia in four of 15 patients at 125 mg/m2 and in five of seven patients at 150 mg/m2. One patient died of meningeal hemorrhage related to grade 4 thrombocytopenia. Other toxicities were infrequent and/or manageable. No objective response was observed. The maximum-tolerated dose (MTD) is therefore 150 mg/m2, and the recommended oral dose of EP for phase II trials in this poor-risk patient population is 125 mg/m2. Twenty-six patients had pharmacokinetic data for both oral EP and i.v. E, whereas three had pharmacokinetic data on the i.v. E course only. After oral administration of EP, the pharmacokinetics of E were as follows: mean absorption rate constant (Ka), 1.7 +/- 1.7 h-1 (mean +/- SD); lag time, 0.3 +/- 0.2 hours; time of maximum concentration (t(max)), 1.6 +/- 0.8 hours; and mean half-lives (t1/2), 1.6 +/- 0.2 (first) and 10.3 +/- 5.8 hours (terminal); the increase in the area under the plasma concentration-versus-time curve (AUC) of E was proportional to the EP dose. After the 1-hour i.v. infusion of E, maximum concentration (C(max)) was 15 +/- 3 micrograms/mL; mean AUC, 88.0 +/- 22.0 micrograms.h/mL; mean total-body clearance (CL), 0.97 +/- 0.24 L/h/m2 (16.2 mL/min/m2); and mean t1/2, 0.9 +/- 0.6 (first) and 8.1 +/- 4.1 hours (terminal). The 24-hour urinary excretion of E after i.v. E was significantly higher (33%) compared with that of oral EP (17%) (P < .001). Significant correlation was observed between the neutropenia at nadir and the AUC of E after oral EP administration (r = .58, P < .01, sigmoid maximum effect [E(max)] model). The mean F of E after oral administration of EP in 26 patients was 68.0 +/- 17.9% (coefficient of variation [CV], 26.3%; F range, 35.5% to 111.8%). In this study, tumor type, as well as EP dose, did not significantly influence the F in E. There was no difference in F of E, whether oral EP was administered before or after i.v. E. Compared with literature data on oral E, the percent F in E after oral prodrug EP administration was 19% higher at either low ( < or = 100 mg/m2) or high ( > 100 mg/m2) doses. CONCLUSION: Similarly to E, the main toxicity of the prodrug EP is dose-dependent leukoneutropenia, which is dose-limiting at the oral MTD of 150 mg/m2/d for 5 days. The recommended oral dose of EP is 125 mg/m2/d for 5 days every 3 weeks in poor-risk patients. Compared with literature data, oral EP has a 19% higher F value compared with oral E either at low or high doses. This higher F in E from oral prodrug EP appears to be a pharmacologic advantage that could be of potential pharmacodynamic importance for this drug.

Administration, Oral↗
PubMed1996

A pharmacodynamic evaluation of hematologic toxicity observed with etoposide phosphate in the treatment of cancer patients.

The pharmacodynamics of etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ), a water-soluble prodrug of etoposide, was evaluated in 39 patients with solid tumors after a 30-minute intravenous infusion of escalating doses (equivalent to 50 to 175 mg/m2 of etoposide) on a day 1, 3, and 5 schedule of treatment. Serial blood samples were collected at predose and throughout the 32 hours following day 1 of treatment to determine the area under the plasma concentration-time curve (AUC) of etoposide phosphate and etoposide. Hematology profiles and serum chemistries were determined at predose and twice weekly for approximately 3 weeks after each treatment cycle. Both linear and nonlinear pharmacodynamic models were used to evaluate the relationship between hematologic toxicity and etoposide AUC and patient factors (age, gender, performance status, prior radiation therapy, prior chemotherapy, baseline albumin, bilirubin, alkaline phosphatase, creatinine, leukocyte count, granulocyte count). Etoposide phosphate was converted rapidly to etoposide in vivo. The ratio of the etoposide phosphate AUC to that of etoposide was < or = 1.2% indicating that etoposide was the main species in the systemic circulation. Myelosuppression was the dose-limiting toxicity, and significant decreases in white blood cell and granulocyte counts were noted. Hematologic toxicity was best described by a stepwise linear regression model consisting of etoposide AUC, serum albumin, and bilirubin. In summary, hematologic toxicity produced by the intravenous administration of etoposide phosphate correlates significantly with etoposide AUC and patient factors (baseline serum albumin and bilirubin) in cancer patients.

Adult↗
PubMed1996

Effects of gender, age, and race on the pharmacokinetics of etoposide after intravenous administration of etoposide phosphate in cancer patients.

The influence of gender, age, and race on the pharmacokinetics of etoposide and on the extent of conversion of etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) to etoposide are summarized. Included in the integrated statistical analyses were 192 patients from six phase I/II studies (102 men and 90 women, 128 aged < or = 65 years and 64 aged > 65 years; 134 were white, 18 were other races, and race was not recorded for 40). The dose of etoposide phosphate ranged from 25 to 200 mg/m2 of etoposide equivalents and was administered as 5-(bolus) to 210-minute intravenous infusions. Total body clearance of etoposide was comparable between men and women. However, significantly lower steady-state volumes of distribution and shorter half-lives were observed in women relative to men. Patients who were older than 65 years had significantly lower etoposide total body clearance and longer half-lives than younger patients. The gender- and age-related differences observed in the pharmacokinetic parameters of etoposide were significant but generally of a small magnitude (< or = 13%), indicating no need for dose adjustment in these patient populations. There were no significant race-related differences in the pharmacokinetic parameters of etoposide. All patients showed rapid conversion of etoposide phosphate to etoposide. The individual area under the plasma concentration-time curve ratio of etoposide phosphate/etoposide was < or = 0.0324, indicating that etoposide was the major circulating moiety after infusion of etoposide phosphate. Significant gender-, age-, or race-related differences in the area under the plasma concentration-time curve ratios were not observed. An evaluation of the area under the plasma concentration-time curve ratios with respect to infusion time suggested that the conversion of etoposide phosphate to etoposide was independent of infusion time.

Adult↗
PubMed1996

Prevalence of tuberculosis in Kishtwar Tehsil of Jammu region in Jammu and Kashmir State.

A study of prevalence of tuberculosis in Kishtwar tehsil of Jammu region was conducted from June 1991 to May 1992. A total of one thousand two hundred ninety-eight rural as well as urban population suffering from various types of lung diseases was studied for prevalence of tuberculosis and a sizeable number (98) of patients were found to be positive of various types of tuberculosis, viz, pulmonary tuberculosis, tuberculous pleural effusion and miliary tuberculosis. Of the population studied 7.55% were found to be positive for tuberculosis and among them 88.76% patients were anaemic and the commonest type of anaemia was normocytic normochromic and normocytic hypochromic. The ESR was raised in almost of all the patients. Of the population, 80.61% were seen to be positive on skiagram chest and 58.16% were found to be positive on other diagnostic tests like Mantoux's tests, sputum for acid-fast bacilli, etc. Mantoux's test was positive in 27.55% cases and sputum was positive in 30.61% cases. All the cases studied were subjected to special investigations. The changes in parameters are consistent with the diagnosis of tuberculosis. Large family size, poverty, excessive smoking, illiteracy, etc, are the major contributing factors.

Adolescent↗
PubMed1995

Myocardial contrast echocardiography in coronary artery disease: potential applications using venous injections of contrast.

The feasibility of studying myocardial perfusion with myocardial contrast echocardiography using intra-aortic or intracoronary injections of contrast medium has been established both in animal models and humans. However, the assessment of myocardial perfusion using venous injection is dependent on the availability of contrast agents that can opacify the left ventricular myocardium following a venous injection. Such agents are currently being evaluated in animal models. Using data from left atrial injections of contrast, this review briefly highlights the principles that govern the study of myocardial perfusion from venous injections of contrast. The value of such an approach in the setting of chronic coronary artery disease and acute myocardial infarction is discussed.

Animals↗
PubMed1995

Technical, economic, interpretative, and outcomes issues regarding utilization of cardiac imaging techniques in patients with known or suspected coronary artery disease.

In this article, the technical and economic issues that determine the utilization of tests used for cardiac imaging in patients with known or suspected coronary artery disease are discussed. The interpretative and outcomes issues that should determine the utilization of such tests are also discussed. In this regard, special emphasis is placed on, among other issues, the level of training and competence, the pretest probability of disease, the incremental value of a test in the context of what is already known about a patient, and whether risk stratification is justified when risk management is not possible.

Coronary Disease↗
PubMed1995

Identification of viable myocardium with contrast echocardiography in patients with poor left ventricular systolic function caused by recent or remote myocardial infarction.

We hypothesized that viable myocardium can be identified in patients with poor left ventricular (LV) systolic function caused by recent or prior infarction using myocardial contrast echocardiography. Accordingly, 39 patients with reduced LV ejection fraction (range 0.10 to 0.40) and recent (n = 30) or remote (n = 9) myocardial infarction were studied. Echocardiography was performed at baseline and at 1 month to assess regional function (1 = normal, 5 = dyskinesia) in 12 segments/patient; the segments were also scored for contrast effect (1 = homogenous, 0.5 = partial, 0 = none) during contrast echocardiography performed in the cardiac catheterization laboratory. Four patients had unsuccessful angioplasty of occluded arteries and were treated medically, 9 were treated medically because of noncritical coronary stenoses (< 80%), and 26 underwent revascularization (16 angioplasty and 10 bypass operation). Twelve segments could not be visualized (2 each in 6 patients), and 30 segments continued to be subserved by totally occluded arteries because of unsuccessful angioplasty in 4 patients. Of the remaining 426 segments, 186 (44%) demonstrated baseline wall motion scores of > or = 3. The best correlate of 1-month wall motion score in these segments was the contrast score (p = -0.62), with better 1-month function noted in segments with more contrast. The overall perfusion status of LV myocardium also correlated (p = -0.59) with global LV systolic function at 1 month. We conclude that myocardial contrast echocardiography can be used during cardiac catheterization to define myocardial segments that are viable in patients with poor LV systolic function caused by recent or remote myocardial infarction.

Adult↗