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Biomedical subjects

M K Dewanjee

Publications and source records attributed to M K Dewanjee.

At least 19 recordsLinked to original sources

Distribution of mesalamine enemas in patients with active distal ulcerative colitis.

Mesalamine (5-aminosalicylic acid), a topically administered anti-inflammatory agent, is effective treatment by enema for distal ulcerative colitis; it lacks many of the side effects of orally administered sulfasalazine. In this study, we determined the colonic distribution of a 60-ml mesalamine enema in eight patients (five women and three men, 18 to 48 years old) with active distal ulcerative colitis that ranged from 12 to 40 cm proximal to the anal verge. On 3 consecutive days, each patient self-administered a 4-g (60-ml) 5-aminosalicylic acid enema that contained 3.7 MBq of [99mTc]technetium-sulfur colloid. Anterior and posterior images were obtained at 0, 30, 60, 120, and 240 minutes. During the 4-hour study period, all patients retained the enemas. The enemas spread to the sigmoid region in 24 of 24 studies, to the splenic flexure region in 22 of 24, and to the transverse colon in 1 of 24. Most of the enema was retained in the sigmoid colon. Therefore, we conclude that a 60-ml enema, when administered as recommended clinically, routinely flows retrograde as far as the splenic flexure but rarely spreads beyond this point. These results support the use of intrarectally administered 5-aminosalicylic acid for segmental colitis of the descending colon.

Adolescent

Indium 111-labeled leukocyte scintigraphy in evaluating head and neck infections.

This retrospective study looked at the role of indium 111-labeled white blood cell (111In WBC) scintigraphy in head and neck infections. The efficacy of 111In WBCs was compared to gallium 67 citrate (67Ga) and technetium Tc99m methylene diphosphonate (99mTc MDP) scintigraphy in detecting and monitoring the resolution of infection. For 22 active infections, the sensitivities for 111In WBC, 67Ga, and 99mTc MDP scintigraphy were 94%, 56%, and 86%, respectively, and the specificities for 111In WBC, 67Ga, and 99mTc MDP scintigraphy were 100%, 43%, and 0%, respectively. For 8 successfully treated infections, all seven 111In WBC studies became negative after therapy, in as short an interval as 1 month. In contrast, all seven 99mTc MDP images remained positive for as long as 6 months after therapy. The seven 67Ga studies had variable results, with four (57%) remaining positive, including two (28%) positive at 6 months after therapy. These results suggest that 111In WBC scintigraphy should be the initial radionuclide imaging tool in detecting active head and neck infections because of its greater accuracy, and its ability to revert to normal much sooner than 67Ga or 99mTc MDP scintigraphs when applied to a subset of patients with resolved infections.

Adolescent

Technetium-99m-labeled platelets: comparison of labeling with a new lipid-soluble Sn(II)-mercaptopyridine-N-oxide and 99mTc-HMPAO.

Platelets pretinned with a neutral Sn(II)-2-mercaptopyridine-N-oxide (SN-MPO) were labeled with 99mTc and compared to those labeled with 99mTc-HMPAO. The conditions of labeling platelets, e.g. concentrations of platelets and Sn(II)-MPO, 99mTc in ACD-saline or ACD-plasma media, pH and incubation time, were optimized using canine platelets. Moderate labeling efficiency was obtained with 20 micrograms of tin(II) chloride and 30 min incubation with Sn-MPO and pertechnetate. The viability of labeled platelets was determined by platelet recovery and platelet survival times in Beagle dogs. The labeling efficiency with platelets from 43 mL of blood was 62.8 +/- 7.6%. The platelet recovery was 35.7 +/- 5.0% and exponential survival time was 34.6 +/- 3.1 h compared to 43.3 +2- 12.0% and 29.5 +/- 3.3 h for 99mTc-HMPAO-labeled platelets. These values were significantly (P less than 0.01) lower than 111In-labeled platelets. Biodistribution in dogs indicates lower retention in blood, spleen and liver after some initial 99mTc excretion in urine. The platelet deposition with 99mTc platelets (Sn-MPO method) on polyurethane angio-catheters was similar to 99mTc-HMPAO-labeled platelets. This study indicates that the platelets could be successfully labeled with pertechnetate in a cost-effective manner for the evaluation of thromboembolic complications.

Animals

The chemistry of 99mTc-labeled radiopharmaceuticals.

The subject of the chemistry of 99mTc-radiopharmaceuticals consists of a collection of bits and pieces of information without a unifying theme. Since the initial impetus to the field of organ imaging was provided by radiochemists, nuclear chemists, and clinician-investigators, using easily prepared 99mTc-compounds from available off-the-shelf ligands, complete chemical characterization was not carried for the 99mTc-radiopharmaceuticals and their metabolites. The influx of coordination, organic, and analytic chemists and their systematic studies clarified some of the structures of these tracers, and promoted the general synthetic methods of a variety of ligands and the corresponding 99mTc-chelates as well as understanding of the nature of their metabolites. Although major developments for organ-imaging radiopharmaceuticals had been made, future studies will result in the simplified methodology of protein-labeling, fine-tuning of the currently available radiopharmaceuticals for higher organ-extraction, and replacement of expensive 123I-labeled tracers with the corresponding 99mTc-tracers. In general, the Tc-complexes are thermodynamically less stable and kinetically more labile than the corresponding Re-complexes. The well established chemistry of Re-compounds, the similarity of Tc-chemistry to that of Re compounds, and structure-activity relationships of a few classes of 99mTc-labeled compounds, may promote the development of new generation of 99mTc-labeled radiopharmaceuticals.

Animals

The kinetics and quantitation of platelet deposition on control (CPC) and heparin-bonded polyurethane angio-catheter (HBPC) with indium-111 labeled platelets in a dog model.

The dynamics of platelet deposition on CPC and HBPC was evaluated with In-111 labeled platelets (In-PLT) with a computerized gamma camera (CGC). Ten non-heparinized dogs (18-25 kg) were catheterized in both femoral arteries with 10 cm of CPC and HBPC (5 Fr., Cordis, Inc.) 24 hours post-injection of 300-420 microcuries of In-PLT, and imaged for 3 hours with gamma camera. The regional platelet deposition on three segments of catheters and puncture site was determined. The catheters were harvested and radioactivity on the catheter segments (proximal: PROX, middle: MID, distal: DIST and puncture site: PS) of both was determined. From the platelet count in blood, radioactivity in blood and segments of catheters, adjacent artery and area of artery and catheter, the platelet-density [X10(3)] (mean +/- S.D.) on catheter and artery were calculated and tabulated: (table; see text) The large standard deviation of retained platelets is due to embolization. The platelet-density and regional counts on catheter segments were lower in the HBPC than CPC. The rate of platelet-deposition was lower in the HBPC than CPC. Most of the thrombi were lost during pullout of the catheter. Both in vivo (dynamic) and in vitro studies were necessary for evaluation of CPC thrombogenicity.

Animals

Endotoxin testing with limulus amoebocyte lysate in a radiopharmaceutical containing chelated metallic radionuclides and chelating agents.

The gel formation by endotoxin with limulus amoebocyte lysate (LAL) solution requires the presence of free calcium ions. The chelating agents and radiopharmaceuticals prepared from the chelating agents always reduce the available free calcium levels present in the kits used for the testing of apyrogenicity and thus inhibit gel formation of LAL with E. Coli endotoxin (ET). This inhibition of gel formation could be reversed by the addition of excess free calcium ions or the excessive dilution of radiopharmaceuticals and chelating agents. The tests of positive control (0.2 ml ET units and LAL), inhibition control (0.1 ml sample, 0.1 ml ET and LAL), and negative control (0.1 ml sterile saline and LAL) were carried out with the fresh preparation (0.1 ml) of samples (triplicate), tropolone, ACD anticoagulant, and 99mTc-labeled radiopharmaceuticals. In the Ca-supplemented tests, 0.1 ml of 60 mM sterile calcium chloride solution was added to the test solutions and incubated for 60 min at 37 degrees centigrade. The results of gel formation (+ve and -ve) and normalization of inhibition control tests with Ca-supplement indicate that commercial LAL kits need extra calcium ions for the correct testing of the apyrogenicity of chelate-containing radiopharmaceuticals and chelating agents.

Limulus Test

Thrombogenicity of canine free internal mammary artery autografts.

Early patency of free internal mammary artery (IMA) grafts for coronary artery bypass (CAB) is lower than that of in situ IMA grafts, and proximal anastomotic problems have been implicated in the pathogenesis of graft occlusion. To determine whether thrombotic phenomena might account for proximal graft narrowing, we examined platelet and fibrinogen deposition in 23 free IMA grafts in a canine model of CAB. Twelve animals had no antiplatelet therapy and were controls. Eleven animals received dipyridamole, 55 mg p.o. daily, 2 days before and each day after operation; aspirin, 325 mg p.o. daily, was given after CAB. Six of the 12 untreated dogs and 5 of the 11 treated dogs were sacrificed at 1 day after surgery; the remainder of each group was sacrificed on the 14th postoperative day. Platelet and fibrinogen depositions were quantitated by indium-111 tropolone and Iodine-125 labeling, respectively. Grafts were sectioned into five parts: proximal anastomosis (PA), proximal graft (PG), midgraft (MG), distal graft (DG), and distal anastomosis (DA). Platelet deposition was highest at the PA of free IMA grafts, and fibrinogen deposition was high at both anastomoses. Antiplatelet therapy significantly reduced platelet deposition at the PA at 14 days, but not at 1 day; fibrinogen deposition was significantly reduced at the DA at 1 day, and at both the PA and DA at 14 days. The ratio of fibrinogen molecules per platelet was unaffected by antiplatelet therapy, but was observed to increase with time at the DG and DA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Comparison of polyethylene glycol and chromium-51 chloride as nonabsorbable stool markers in calcium balance studies.

The day-to-day variations in stool calcium content during calcium balance studies are usually corrected for by adjusting for the recovery of an orally administered nonabsorbable stool marker. We describe here a simple method for making this correction using chromium-51 chloride hexahydrate (51Cr) in balance studies. This approach was developed because of difficulties encountered with the more widely used marker, polyethylene glycol (PEG). With one batch of PEG, the stool recovery was only 81% (whereas with 51Cr it was 95%). The reason for this poor recovery was contamination of the PEG 4000 with a high molecular weight species (10-15%, wt/wt). Because others have also reported low PEG recoveries and because we found that the chemical abnormality in the PEG was very difficult to detect, we believe that 51Cr is more reliable and should be the preferred stool marker for the calcium balance studies.

Administration, Oral

Effect of platelet inhibitors on platelet and fibrin deposition following transluminal angioplasty of the atherosclerotic rabbit aorta.

Experimental atherosclerosis was induced in a rabbit model by intimal damage of the infrarenal aorta followed by two months cholesterol feeding. The influence of four different antiplatelet drug regimens on acute platelet and fibrin deposition after transluminal angioplasty of the atherosclerotic abdominal aorta was then evaluated. The study group consisted of 32 New Zealand rabbits: 7 controls, 7 treated with prostacyclin (10 mg/kg/min i.v.), 5 treated with low-dose acetylsalicylic acid (2 mg/kg i.v.), 7 treated with acetyl-salicylic acid (5 mg/kg i.v.) and dipyridamole (2 mg/kg i.v.), and 6 treated with low molecular dextran (5 ml/kg). By 2 hours after angioplasty, there was a significant increase of the deposition of platelets (P less than 0.001) as well as fibrin (P less than 0.01) when comparing dilated to non-dilated segments in the control animals. There was no significant difference in the amount of platelets and fibrin deposition among the control and drug treated groups. Thus, in this animal model there appears to be no immediate benefit in using antiplatelet drugs during transluminal angioplasty. Although, this study did not address the potential long-term effects of antiplatelet drug therapy, future evaluation of the clinical benefits of these drugs in conjunction with transluminal angioplasty seems warranted.

Angioplasty, Balloon

Comparison of three platelet markers for measurement of platelet survival time in healthy volunteers.

We studied mean platelet survival times in healthy volunteers with use of [51Cr]disodium chromate, 111In-oxine (in a solution of acid-citrate-dextrose [ACD] and saline), and 111In-tropolone (in ACD-plasma) as markers. Differences found between the 51Cr and 111In labels probably can be attributed to a variation in localization of the label on the cell and of renal handling of the free label after release. The mean platelet survival time with 51Cr was slightly longer than the survival time with both indium labels and showed a sex difference not seen with 111In-oxine. Protein-bound plasma 51Cr was lower than plasma 111In and remained constant throughout the study. Plasma 111In increased with time. For survival time calculations, no correction for free 51Cr is necessary, but correction should routinely be performed when 111In markers are used. Both 111In markers gave similar results with respect to platelet survival time. The somewhat more elaborate plasma labeling procedure with tropolone shows no measurable advantage over the original 111In-oxine method. 111In-tropolone labeling takes less time and maintains platelets in the physiologic environment of plasma during incubation. Biodistribution studies show no difference between the two 111In markers.

Blood Platelets

Deep arterial injury during experimental angioplasty: relation to a positive indium-111-labeled platelet scintigram, quantitative platelet deposition and mural thrombosis.

Although it is not clear why coronary occlusion and restenosis occur after successful coronary angioplasty, factors related to the procedure may influence early and late results. The possible adverse effects of a medial tear documented histologically and produced during balloon angioplasty of the common carotid arteries were studied in 30 fully heparinized (100 U/kg body weight) normal pigs. Scanning electron microscopy showed endothelial denudation and extensive platelet deposition in all dilated arterial segments. Visible macroscopic mural thrombus was present within an hour of the procedure in 29 (91%) of the 32 arteries that had a medial tear documented by histologic study; the tear produced an indium-111-labeled platelet deposition of 116.4 +/- 26.5 X 10(6)/cm2 (mean +/- SE) and total thrombotic occlusion in 2 arteries (4%). None of the 24 arteries without a medial tear had a thrombus, and the mean platelet deposition in that group was 7.0 +/- 0.5 X 10(6)/cm2 (p less than 0.0008). In 12 pigs scanned with a gamma camera, visible thrombus was associated with platelet deposition in excess of 20 X 10(6)/cm2 in 12 arteries, 9 of which had a positive indium-111-labeled platelet scintigram. Thus, arterial angioplasty causes deep arterial injury, which appears to be a major cause of mural thrombosis, heavy platelet deposition, a positive indium-111-labeled platelet scintigram and acute arterial occlusion. A positive indium-111-labeled platelet scintigram was always associated with macroscopic thrombus of at least 20 > 10(6) platelets/cm2 and underlying deep arterial injury.

Angioplasty, Balloon

Quantification of regional platelet and calcium deposition on pericardial tissue valve prostheses in calves and effect of hydroxyethylene diphosphonate.

Mitral valves were replaced with 25 mm bovine pericardial tissue valve prostheses (Ionescu-Shiley) in 45 calves (23 controls and 22 treated daily with hydroxyethylene diphosphonate). Before being killed 1, 14, 30, and 90 days later, the calves received In-labeled autologous platelets intravenously. Regional variations in platelet deposition were measured by a new technique. Thrombus was noted early on the flexion zone of the valve; with time it increased on the free edge and central zone. Platelet deposition was initially high on the flexion zone, attachment zone, sewing ring, and perivalvular tissue but decreased with time. Hydroxyethylene diphosphonate treatment tended to decrease platelet deposition in all zones. Calcium content was high in thrombus and increased in all zones with time, in both groups, but the deposition was less in the group treated with hydroxyethylene diphosphonate. Collagenous tissue and adherent thrombus appear to provide nucleation sites for calcification.

Animals

Pharmacodynamics of stannous chelates administered with 99mTc-labeled chelates.

The pharmacodynamics of several tin compounds were studied in healthy rabbits, rabbits with myocardial infarcts, and isolated myocardial tissue. The results showed that tin chelates of pyrophosphate, HEDP, DTPA, and glucoheptonate are very unstable in vivo, giving rise to free stannous ions. These ions localize mainly in bone, with the rest being primarily excreted in the urine. They also concentrate more in infarcted than in normal myocardium; there they enter the mitochondria. The supernatant of homogenates contains bound and free fractions, demonstrating a subcellular distribution pattern similar to that of calcium ions. Tin chelates have different pharmacodynamics from the corresponding 99mTc chelates.

Animals

Noninvasive radioisotopic technique for detection of platelet deposition in coronary artery bypass grafts in dogs and its reduction with platelet inhibitors.

At 8 and 32 hours after saphenous vein bypass graft surgery in six dogs, in vivo images of the graft were obtained with a gamma camera after intravenous injection, 2 hours postoperatively of autologous platelets labeled with indium-111. Platelet deposition in the grafts could be imaged in vivo from the scintiphotos. In vitro images of the excised heart showed saphenous vein graft uptake confirming the in vivo image. In vitro determination of radioactivity in the graft averaged 17 +/- 14 times greater than in blood and 33 +/- 26 times greater than in the lung. Under identical conditions, in eight dogs treated with dipyridamole (55 mg/day) plus aspirin (325 mg/day), the grafts appeared to have considerably less platelet deposition as estimated by imaging. In vitro determination of radioactivity in the graft averaged 5 +/- 2 times greater than in blood and 8 +/- 4 times greater than in the lung (p less than 0.01). This noninvasive technique may be a promising tool for a better understanding of the role played by platelets in the process of occlusion of saphenous vein bypass grafts in man and its prevention with platelet inhibotors.

Animals

Emission-computed tomography and its application to imaging of acute myocardial infarction in intact dogs using Tc-99m pyrophosphate.

The techniques of emission-computed tomography have been used to obtain in vivo quantitative estimates of the three-dimensional distribution of gamma-emitting radionuclides in dog hearts. Conjugate views, obtained for 60 equiangular projections around 360 degrees by rotating the object in front of a gamma camera, were used to reconstruct multiple-level emission transaxial images for various test objects, and for dogs with surgically induced acute myocardial infarcts. Corrections for attenuation were performed in the backprojection step of the convolution algorithm used for reconstruction. Quantitative estimates of the spatial extent and concentration of activity were obtained to within 10--15% rms error. Correlations were obtained between the radionuclide and histopathologic estimates of the extent and location of infarction.

Animals