Biomedical subjects

P V Kulkarni

Publications and source records attributed to P V Kulkarni.

At least 19 recordsLinked to original sources

PubMed1999

Transient adhesion of platelets in pump-oxygenator systems: influence of SMA and nitric oxide treatments.

We employed gamma scintigraphy to quantify the transient accumulations of platelets in pump-oxygenator systems employed in cardiopulmonary bypass (CPB). A flat sheet microporous polypropylene membrane oxygenator (Cobe Duo) was employed, with and without siloxane/caprolactone oligomer coating (SMA) (n = 8 each). The effect of nitric oxide gas infusion on platelet deposition was also evaluated for the uncoated Cobe Duo system (n = 10 each). Scintigraphic images of radiolabelled cells were obtained and converted to numbers of all platelets, labeled and unlabeled, adhering to the pump and oxygenator surfaces. These numbers were compared, by study group, for a 90-min period of normothermic CPB in the adult pig, employing standard prime and anticoagulation regimens. Platelets adhered in large numbers to control oxygenators, reaching maxima (> 20% of the circulating platelet mass) 30 min following institution of CPB, and decreasing for the duration of CPB. SMA treatment significantly decreased platelet adhesion following a 5-10-min transient accumulation period. Nitric oxide infusion significantly reduced platelet adhesion throughout the CPB period. Platelet accumulations on the high fluid shear centrifugal pump surfaces increased monotonically to maxima at about the same time as for the oxygenators, but did not decrease thereafter. Higher platelet surface densities were observed on the centrifugal pump surfaces than on the oxygenator surfaces. CPB with the untreated circuit tended to reduce circulating platelet counts vs theoretical values based on hemodilution alone. In contrast, SMA significantly increased the circulating platelet count versus the untreated control group. These results indicate that platelet adherence to the foreign surfaces of CPB equipment are influenced in characteristic ways by time and fluid shear. SMA treatment and nitric oxide infusion both reduce platelet adhesion to oxygenator surfaces. SMA treatment spares these cells for the circulation.

Animals↗

PubMed1998

Simultaneous intracellular and extracellular pH measurement in the heart by 19F NMR of 6-fluoropyridoxol.

6-Fluoropyridoxol (6-FPOL) was evaluated as a simultaneous indicator of intracellular and extracellular pH and, hence, pH gradient in perfused rat hearts. After infusion, 19F NMR spectra rapidly showed two well-resolved peaks assigned to the intracellular and extracellular compartments, and pH was calculated on the basis of chemical shift with respect to a sodium trifluoroacetate standard. To demonstrate use of this molecule, dynamic changes in myocardial pH were assessed with a time resolution of 2 min during respiratory and metabolic alkalosis or acidosis and ischemia. For a typical heart, intracellular pH (pHi) = 7.14+/-0.01 and extracellular pH (pHe) = 7.52+/-0.02. In response to metabolic alkalosis, pHi remained relatively constant and the pH gradient increased. In contrast, respiratory challenge caused a significant increase in pHi. Independent measurements using pH electrodes and 31P NMR confirmed validity of the 19F NMR results.

Alkalosis, Respiratory↗

PubMed1998

Development of novel 19F NMR pH indicators: synthesis and evaluation of a series of fluorinated vitamin B6 analogues.

We have synthesized a series of novel fluorinated vitamin B6 analogues (6-fluoropyridoxol derivatives) as potential 19F NMR pH indicators for use in vivo. Modifications included addition of aldehyde, carboxyl or aminomethyl groups at the 4- or 5-ring position, and examination of a trifluoromethyl moiety as an internal chemical shift standard. The variation in chemical shift with respect to acid-base titration showed pKa values in the range 7.05-9.5 with a chemical shift sensitivity in the range 7.4-12 ppm. Several of the molecules readily cross cell membranes providing estimates of both intra- and extra-cellular pH in whole blood. 6-Fluoropyridoxamine (6-FPAM) exhibits a pKa = 7.05, which is closer to normal physiological pH than the parent molecule 6-fluoropyridoxol (6-FPOL) (pKa = 8.2), and should thus, be useful for precise and accurate measurements of pH in vivo. Enhanced spectral resolution for 6-FPAM over 6-FPOL is demonstrated in whole blood and the perfused rat heart.

Animals↗

PubMed1998

SPECT electronic collimation resolution enhancement using chi-square minimization.

An electronic collimation technique is developed which utilizes the chi-square goodness-of-fit measure to filter scattered gammas incident upon a medical imaging detector. In this data mining technique, Compton kinematic expressions are used as the chi-square fitting templates for measured energy-deposition data involving multiple-interaction scatter sequences. Fit optimization is conducted using the Davidon variable metric minimization algorithm to simultaneously determine the best-fit gamma scatter angles and their associated uncertainties, with the uncertainty associated with the first scatter angle corresponding to the angular resolution precision for the source. The methodology requires no knowledge of materials and geometry. This pattern recognition application enhances the ability to select those gammas that will provide the best resolution for input to reconstruction software. Illustrative computational results are presented for a conceptual truncated-ellipsoid polystyrene position-sensitive fibre head-detector Monte Carlo model using a triple Compton scatter gamma sequence assessment for a 99mTc point source. A filtration rate of 94.3% is obtained, resulting in an estimated sensitivity approximately three orders of magnitude greater than a high-resolution mechanically collimated device. The technique improves the nominal single-scatter angular resolution by up to approximately 24 per cent as compared with the conventional analytic electronic collimation measure.

Algorithms↗

PubMed1998

Analytic treatment of resolution precision in electronically collimated SPECT imaging involving multiple-interaction gamma rays.

The widely applied single-interaction analytic expression characterizing the energy resolution component of the angular resolution precision for an electronically collimated point source is extended to include multiple-interaction Compton scatter sequences as well as sequences terminated by photoelectric absorption. The analytic formulation is developed using the statistical variance of the mean for components comprising composite, multivariate resolution precision estimators. It is demonstrated that enhanced resolution precision in the incident interaction scatter angle is attained when use is made of information from multiple interactions. An improvement in the resolution precision of up to approximately 40% is observed for triple Compton scatter. Comparison of the analytic estimates with Monte Carlo/chi-square results shows good agreement.

Chi-Square Distribution↗

PubMed1996

Profile of malignancies at Medical College, Ambajogai--(15 years retrospective study).

Present study comprises of a preliminary analysis of malignant lesions, diagnosed and confirmed by histopathological examination, carried out in Department of Pathology, S. R. T. R. Medical College, Ambajogai, from August 1976 to July 1991. 30,168 specimens were received for histopathological examination out of which 2,663 cases were diagnosed as malignant lesions (8.82%). 163 cases of leukemias were diagnosed by peripheral smear and bone marrow examination. Our of 2826 patients with malignant lesions 1,566 (55.41%) were males and 1,260 (44.59%) were females with M:F ratio as 1.24:1. Analysis of all malignant lesions showed more predilection towards genital organs (26.22%), gastrointestinal tract (13.72%) and breast (10.47%). Penis (11.36%), gastrointestinal tract (16.73%), oral cavity and tongue with pharynx (20.81%) and skin (11.11%) were leading sites in males where as cervix (30.63%) breast (22.46%), gastrointestinal tract (10.00%), skin (6.82%) and lymphoma, leukaemias (7.30%) were common sites for malignancies in females. The higher incidence of genital and skin tumours is discussed in the paper. Available data is compared with data from Tata Memorial Cancer Hospital Bombay and Cancer Hospital at Barshi in Solapur District of Maharashtra.

Adult↗

PubMed1995

Detection of alterations in left ventricular fatty acid metabolism in patients with acute myocardial infarction by 15-(p-123I-phenyl)-pentadecanoic acid and tomographic imaging.

15-(p-iodine 123-phenyl)-pentadecanoic acid (IPPA) is a synthetic radiolabeled fatty acid with kinetics similar to palmitate. Fourteen patients who had had an acute myocardial infarction 7 +/- 6 days earlier and 9 normal volunteers were studied after being injected with IPPA. The volunteers were remarkable for homogeneous uptake and metabolism of IPPA; 13 of 14 infarct patients showed areas of decreased uptake > 2 SDs below the mean of the volunteers. Metabolism was homogeneous in the volunteers (14.2% +/- 5.8%) and was significantly higher than in regions identified as infarcted (3.9% +/- 12.1%, p < 0.001). Noninfarcted regions in the patients demonstrated significantly increased rates of IPPA metabolism compared to rates in volunteers (23.0% +/- 9.6% p < 0.001). We conclude that patients with recent myocardial infarction have abnormalities of fatty acid metabolism such as decreased uptake and clearance of fatty acid in regions of infarction and normal uptake but relatively increased fatty acid clearance in unaffected regions of the myocardium.

Adult↗

PubMed1994

6-Fluoropyridoxol: a novel probe of cellular pH using 19F NMR spectroscopy.

6-Fluoropyridoxol was evaluated as an intracellular pH indicator. This molecule exhibits exceptional sensitivity to changes in pH (approximately 10 ppm acid/base shift) and a pKa approximately 8.2 appropriate for physiological investigations. Using 19F NMR spectroscopy we determined both intra- and extracellular pH in whole blood and confirmed the measurements using traditional techniques: ion-electrodes and 31P NMR spectroscopy.

Animals↗

PubMed1994

Synthesis and evaluation of a new class of technetium-99m monocationic radiotracers from dithienyldiazalkanes.

Monocationic 99mTc complexes, [99mTcO2 (THEN)]+ and [99mTcO2(THPN)]+ derived from a new class of N2S2 chelators diethienyldiazalkanes, namely 1,6-di(2-thienyl)-2,5-diazahexane (THEN) and 1,7-di- (2-thienyl)-4,4-dimethyl-2,6-diazaheptane (THPN), have been synthesized using Sn(II) tartrate reduction of [99mTc]pertechnetate at pH 9 and extraction of the complexes as ion pairs with trifluoromethane sulfonate anion (CF3SO3-) in high radiochemical yield (approximately 90%). Radiochemical analysis of the 99mTc complexes using chromatography (Whatman Cellulose CEL300 DEAE anion exchange strip, MEK) and paper chromatography (Whatman I, acetone) revealed high radiochemical purity (> 90%). High octanol-saline partition coefficients (> 37) of [99mTcO2(THEN)]+ and [99mTcO2(THPN)]+ indicated a lipophilic nature of the complexes. Relative stability of the 99mTc complex was high as measured by DTPA challenge studies. Biodistribution of [99mTcO2(THEN)]+ and [99mTcO2(THPN)]+ in rats at 15 min post-injection showed heart-to-blood activity ratios of 0.26 and 0.46, respectively, with rapid blood clearance. Further studies involving the variation of substituents on the basic core structure of this new class of 99mTc complexes may provide radiotracers suitable for myocardial imaging.

Animals↗

PubMed1992

Recombinant antibody-metallothionein: design and evaluation for radioimmunoimaging.

We have produced a chimeric antibody (Ab) in which metallothionein, a well-characterized biological chelator of metals, was genetically fused to the F(ab') domain of the S107 Ab heavy chain. Coexpression with the Ab light chain that conveys specificity for the synthetic antigen phosphocholine was achieved in plasmacytoma cells. Metal- and antigen-binding domains of the Ab-metallothionein hybrid function with normal avidity and specificity. Ab-metallothionein can be efficiently loaded with 99mTc and used to specifically bind phosphocholine-haptenated cells in vitro or to localize plasma-cell ascites tumors in mice. The approach offers potential advantages for producing radiolabeled Ab for targeted radiotherapy and diagnostic imaging.

Animals↗

PubMed1992

Synthesis and evaluation of technetium-99m monocationic mixed ligand complexes of phenyl substituted/condensed tetradentate Schiff's bases and trimethylphosphine.

Tc-99m monocationic mixed ligand complexes of phenyl substituted/condensed Schiff's bases, N,N'-ethylene-bis-(benzoylacetone imine) (Lb) or N,N'-ethylene-bis-(salicylaldehyde imine) (Lc) or N,N'-ethylene-bis-(2-hydroxyacetophenone imine) (Ld) and trimethylphosphine were synthesized to determine the influence of the presence of a phenyl group in these tracers on their heart uptake in rats. A new formulation procedure using aq. beta-hydroxypropylcyclodextrin (HPB) solution was developed for intravenous administration of nonpolar 99mTc complexes. Comparison of biodistribution data for the reference 99mTc complex from N,N'-ethylene-bis-(acetylacetone imine) and trimethylphosphine using HPB formulation and alternate formulation (0.9% saline) showed the same results. Biodistribution of the title 99mTc complexes, [99mTc Lb (PMe3)2]+, [99mTc Lc (PMe3)2]+ and [99mTc Ld (PMe3)2]+ showed heart-to-blood activity ratios of 1.7, 2.1 and 1.7, respectively, at 15 min post-injection in rats.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1991

Recent developments in 99mTc and 123I-radiopharmaceuticals for SPECT imaging.

Availability of 123I of high radionuclidic purity has encouraged the development of 123I-based radiopharmaceuticals for the assessment of myocardial fatty acid metabolism, myocardial neuronal activity, and for receptor and antibody imaging. Advances in the chemistry of technetium have resulted in the development of novel agents for myocardial and cerebral perfusion and renal function studies. Monoclonal antibodies labeled with 99mTc show promise for imaging neoplastic lesions, myocardial infarcts, and thrombus localization. Recent developments in 123I and 99mTc agents for myocardial and brain imaging studies are discussed.

Animals↗

PubMed1990

Radioiodinated tracers for myocardial imaging.

Recent advances in the efficient production of high purity radioiodine (123I) and new efficient radiolabeling techniques have allowed the development of new classes of cardiovascular radiopharmaceuticals. These include 123I-labeled fatty acids to assess myocardial metabolism, 123I-metaiodobenzylguanidine (MIBG) for myocardial neuronal activity, labeled monoclonal antibodies for myocardial necrosis, and labeled lipoproteins for receptor concentration. 123I-labeled fatty acids and MIBG are under clinical investigation with encouraging results. 123I- and 111In-labeled fragments of monoclonal antibodies to myosin have been used for imaging myocardial necrosis in humans. The development of radiotracers for imaging of cholinergic and adrenergic receptors is still in the experimental stage. Recent advances in imaging instrumentation and radiopharmaceuticals have resulted in cardiac imaging applications beyond blood pool ventriculography, perfusion, and infarct-avid imaging. Developments of radioiodine (123I)-labeled agents promise to play an important role in the assessment of myocardial metabolism, neuronal activity, and receptor concentration. The chemistry of iodine is well defined compared with that of 99mTc; therefore, iodine isotopes are well suited for labeling biologically important molecules. Among the iodine isotopes, 123I has nearly ideal nuclear properties for nuclear medical applications with a 13.3-hour half-life (T1/2) and 159 keV gamma emission (83%). Despite the nearly ideal chemical and nuclear properties of 123I, the widespread application of 123I-based radiopharmaceuticals in clinical practice has been limited by high production costs (123I is produced in a cyclotron), relatively limited availability, and the presence of undesirable radionuclidic impurities (124I, T1/2 = 4.2 days; 125I, T1/2 = 60 days; 126I, T1/2 = 13.1 days). The relatively long T1/2 and beta particle emission can substantially increase the higher radiation burden to the patient. High energy gamma rays (greater than 600 KeV) from these impurities can degrade images obtained using low energy collimators. Recent developments in production techniques have greatly reduced the levels of the undesirable radionuclides in 123I. Ready availability of pure 123I at modest cost, in concentrations suitable for the radio-labeling of a variety of useful biomolecules, should enhance the clinical applications of 123I-labeled compounds. Molecules labeled with 123I that are useful in cardiac imaging studies are fatty acid analogs, monoclonal antibodies, receptor binding agents, and norepinephrine analogs. This article will discuss developments in radioiodine (123I)-labeled radiotracers for myocardial imaging.

Heart↗

PubMed1990

Iodine-123 phenylpentadecanoic acid myocardial scintigraphy in patients with left ventricular hypertrophy: alterations in left ventricular distribution and utilization.

Regional alterations in myocardial substrate uptake and/or utilization have been demonstrated in rats with hypertension. To determine whether alterations in left ventricular fatty acid uptake and/or utilization are present in patients with left ventricular hypertrophy (LVH), we compared the results of rest and exercise iodine-123 phenylpentadecanoic acid (IPPA) myocardial scintigraphy in 10 patients with hypertension who had concentric LVH without evidence of coronary artery disease and in 15 normal subjects. Patients with LVH had more heterogeneous left ventricular activity of IPPA compared to normal subjects after exercise but not at rest (23 +/- 8% versus 13 +/- 5% difference in maximum segmental activity at 4 minutes after exercise; p = 0.005). Although IPPA clearance was similar in both patients with LVH and normal subjects, postexercise washout in segments showing decreased initial IPPA uptake was reduced compared to washout at rest in patients with LVH (11.7 +/- 7.5% versus 21.5 +/- 8.4% at 20 minutes after injection, n = 15; p = 0.005). Exercise thallium-201 (TI-201) scintigraphy was normal in all seven patients with LVH tested. Patients with LVH showed significantly greater heterogeneity in IPPA uptake compared to TI-201 uptake immediately after exercise (25 +/- 5% versus 16 +/- 6%; p = 0.013). We conclude that (1) compared to normal subjects, patients with LVH show heterogeneous myocardial IPPA activity after exercise but not at rest; (2) postexercise washout of IPPA was decreased in segments with reduced uptake after exercise in patients with LVH; and (3) the distribution of IPPA is more heterogeneous than that of TI-201 immediately after exercise in patients with concentric LVH. The postexercise heterogeneity in IPPA uptake and delayed washout in segments with reduced initial uptake is consistent with exercise-induced myocardial ischemia in patients with LVH.

Adult↗

PubMed1989

Synthesis and antimicrobial activity of new substituted 10-methyl-1,2-dihydro-1-oxo-1,2,4-triazino(4,5-a)indoles.

Ten new 4,8-disubstituted 10-methyl-1,2-dihydro-1-oxo-1,2,4-triazino(4,5-a)indoles (5 and 6) were prepared by refluxing various 5-substituted indole-2-carbohydrazides (4) with triethylorthoformate or triethylorthoacetate in dimethylformamide. These derivatives were evaluated for their antimicrobial activity. Some of the title compounds possess fairly potent antimicrobial activity.

Anti-Bacterial Agents↗

PubMed1989

In vivo nuclear magnetic resonance imaging of myocardial perfusion using the paramagnetic contrast agent manganese gluconate.

Previous nuclear magnetic resonance (NMR) imaging studies have indicated that coronary occlusion does not produce sufficient changes in standard tissue relaxation times to allow the detection of acute ischemia. To identify acute myocardial perfusion abnormalities, the use of the paramagnetic agent manganese gluconate combined with calcium gluconate (MnGlu/CaGlu) was investigated in canine models of acute coronary artery occlusion. In vitro studies showed that MnGlu/CaGlu was a more efficient relaxing agent than gadolinium-DTPA (relaxivity of 7.8 versus 5.1 s-1 mM-1) and demonstrated affinity for normal myocardium. The distribution of MnGlu/CaGlu as measured by manganese-54 tracer studies was proportional to myocardial blood flow in both normal and ischemic tissue. Hearts excised from dogs after coronary artery occlusion and administration of 0.035 mM/kg MnGlu/CaGlu were imaged ex vivo using a relatively spin-lattice relaxation time (T1)-weighted gradient reversal technique (repetition time [TR] 50 ms and echo time [TE] 9 ms). These images showed increased signal intensity in the normally perfused myocardium with a mean signal intensity ratio of hypoperfused to normal myocardium of 0.55 +/- 0.12 (mean +/- SD). In vivo images obtained in nine dogs after coronary artery occlusion and administration of the same dose of MnGlu/CaGlu demonstrated the region of hypoperfused myocardium in six dogs with a signal intensity ratio of hypoperfused to normal myocardium of 0.64 +/- 0.23 (p less than 0.05 versus control). When a higher dose of 0.1 mM/kg MnGlu/CaGlu was utilized and in vivo imaging was performed using a relatively spin-spin relaxation time (T2)-weighted (TR gated, TE 60 ms) spin-echo sequence in six dogs, the signal intensity of normal myocardium was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Quantitative rotational tomography with 201Tl and 99mTc 2-methoxy-isobutyl-isonitrile. A direct comparison in normal individuals and patients with coronary artery disease.

We tested the hypothesis that 99mTc 2-methoxy-isobutyl-isonitrile (99mTc MIBI), a new radiopharmaceutical for myocardial perfusion imaging, provides accurate noninvasive detection of coronary artery disease (CAD). Imaging in patients after exercise and at rest with 99mTc MIBI was compared with imaging after exercise and redistribution with 201Tl in 12 normal subjects and 38 patients with angiographic documentation of CAD (greater than or equal to 50% diameter stenosis). We used single-photon emission computed tomography (SPECT) and computer quantitation of regional tracer distribution. The quality of reconstructed images with 99mTc MIBI judged visually was superior to that of 201Tl in 88% of all studies performed and was comparable in the others. With the limits of normal as 2.5 SD below the mean of gender-matched normal volunteers, 201Tl SPECT identified 32 and 99mTc MIBI identified 36 patients with CAD (p = 0.2). 201Tl SPECT identified 45 of 75 (60%) and 99mTc MIBI identified 59 of 75 (79%) stenosed coronary arteries (p less than 0.05). The quantitative severity of perfusion defects was similar for the two tracers. 201Tl SPECT identified 104 reversibly ischemic myocardial segments compared with 134 with 99mTc MIBI (p less than 0.05). Thus, SPECT myocardial perfusion imaging with 99mTc MIBI and computer quantitation provides an accurate method for the noninvasive detection of significant coronary artery disease. Furthermore, image quality is generally superior to 201Tl, and reversibly ischemic myocardial segments may be better identified with 99mTc MIBI.

Adult↗

PubMed1988

Abnormal myocardial fatty acid metabolism in dilated cardiomyopathy detected by iodine-123 phenylpentadecanoic acid and tomographic imaging.

The radioidinated synthetic fatty acid iodine-123 phenylpentadecanoic acid (IPPA) has proven useful in the identification of regional abnormalities of cardiac metabolism in patients with myocardial ischemia. The present study was performed to test the hypothesis that the myocardial distribution and turnover of fatty acids, assessed noninvasively with IPPA, are altered in patients with cardiomyopathy. Nine normal volunteers and 19 patients with dilated cardiomyopathy of various etiologies underwent cardiac imaging with single-photon emission computed tomography (SPECT) after intravenous injection of IPPA. Apical short-axis and basal short-axis sections were reconstructed and quantitatively analyzed for relative IPPA activity distribution and washout. Patients with congestive cardiomyopathy demonstrated significantly greater heterogeneity of IPPA uptake than normal subjects (maximal percent variation of activity 27 +/- 11 vs 18 +/- 4, p less than 0.01). They also demonstrated a more rapid percent washout rate than control subjects (24 +/- 8 vs 17 +/- 6 for the apical short-axis section, p less than 0.05; 26 +/- 7 vs 18 +/- 5 for the basal short-axis section, p less than 0.01). These abnormalities of fatty acid distribution and turnover were independent of the etiology of the cardiomyopathy. The degree of heterogeneity of IPPA uptake was significantly related to the patients' New York Heart Association functional class (r = 0.64, p less than 0.01). Thus, compared with normal myocardium, the myocardium of patients with congestive cardiomyopathy demonstrates a more heterogeneous distribution of fatty acid uptake, which parallels the clinical severity of the disease. Furthermore, patients with congestive cardiomyopathy demonstrate a more rapid myocardial clearance of the labeled fatty acid, as assessed with SPECT imaging.

Adult↗