Biomedical subjects
Publications and source records attributed to H Sharma.
The gastric emptying of a soluble and an insoluble component of a capsule formulation has been monitored by gamma scintigraphy using a dual isotope technique. There was no significant difference between the emptying rates for the two components or between fasting and non-fasting conditions (P greater than 0.01).
The blood and urinary clearances of cis-diammine 1,1-cyclobutane dicarboxylate platinum(II) (CBDCA, JM8) were determined in four patients with malignancy. A 40 muCi iv injection of 191 Pt/193 Pt (3:1)-labelled CBDCA was followed by serial blood and urine sampling to 72 h. The blood clearance was triphasic, mean values for the fast, intermediate, and slow phases being 10.8 min, 2.5 h, and 125 h, respectively. The fraction of activity excreted in the urine within the first 6 h had a mean value of 66.7%, contrasting with 26.4% for cisplatin. There was only a small fraction of CBDCA excreted by the slow phase (1.5%) as against an average of 20% for CHIP and 27% for cisplatin. The early and rapid renal clearance of CBDCA may account for reduced nephrotoxicity.
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The absorption of 64Cu from closed duodeno-jejunal loops in anaesthetized rats was significantly less in the presence of pancreatic juice compared with that in the presence of saline (9 g sodium chloride/l). The inhibition of 64Cu absorption caused by pancreatic juice was similar to that achieved with bile. Studies using solutions of electrolytes and of pancreatic extracts showed that the inhibitory effect of pancreatic secretions was due to its protein-enzyme content and not to its bicarbonate content. Pancreatic secretion and bile influence Cu absorption and thereby affect Cu homeostasis.
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The blood clearances of three platinum compounds, cis-dichlorodiammine platinum II (DDP), cis, trans-dichloro-dihydroxy-bis-(isopropylamine) platinum IV (CHIP), and cis-dichloro-bis-cyclopropylamine platinum II (CP), were determined in nine patients with malignant disease. The complexes were prepared using radioactive platinum (191Pt and 193Pt). A 10-mu Ci dose of each complex, containing the equivalent of 1-2 mg elemental platinum, was injected IV into groups of three patients. Serial blood and urine samples were collected over 72 h. No obvious difference was found between the three complexes for blood clearance, median t1/2a being 16.8 (range 11.2-23.5) min and median t1/2 beta 89 (range 63.7-127) h. The urinary excretion was greatest for CHIP, 60% of injected dose as against 42.6% for CP and 38.8% for DDP. Differences in renal excretion of DDP analogues could indicate potentially less nephrotoxic agents. The use of radioactive Pt will allow in vivo dynamic imaging of the distribution of platinum compounds in areas of interest.
Thoracic duct lymphocytes were labelled in vitro with 111indium-oxine or 111indium-acetylacetone in order to follow their migration after i.v. injection into syngeneic rats. Under certain conditions both preparations produced results with quantitatively confirmed data obtained by other approaches to the physiological pattern of lymphocyte recirculation. However, three significant difficulties were identified: (1) chemical toxicity by minor contaminants of the preparation; (2) radiation damage indicated by a progressive impairment of the recovery of radioactivity from lymph nodes. A labelling concentration of 20 microCi/10(8) cells was the highest compatible with survival of most lymphocytes for 24 h in vivo as confirmed by autoradiography; (3) rapid loss of 111In in vivo found at labelling concentrations below 1 microCi/10(8) cells. By one week after the injection of lymphocytes labelled at 20 Micro/Ci/10(8) cells most of the 111In had been transferred from lymphocytes to non-recirculating radioresistant cells within the spleen and lymph nodes.
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A method is described whereby large numbers of human lymphocytes are separated from peripheral blood and labelled in vitro with indium-111 oxine. Following autologous reinjection, the distribution within the body is followed by means of serial blood samples, surface-probe counting and gamma camera imaging. The distribution of radioactivity following reinjection of heat-damaged labelled lymphocytes and free indium-111 oxine is different from that of 'normal' lymphocytes. The results suggest that the separation and labelling procedure does not cause significant physical damage to the lymphocytes The importance of restricting the specific lymphocyte activity to 20-40 microCi per 10(8) cells in order to minimize radiation damage to the lymphocytes is emphasized. Good resolution of lymphoid structures is obtained using gamma camera imaging and the changes recorded in organ distribution correlate well with data from animal models of lymphocyte migration. Thus, indium-111 oxine labelling of human lymphocytes provides a non-invasive method whereby the migratory properties of human lymphocytes can be followed.
Clinical studies using indium-111 oxine labelling of human peripheral blood lymphocytes are presented. Data from animal models of lymphocyte migration are compared with results found in healthy subjects and patients with malignant neoplasms. The physiological significance of bone marrow and liver localization on gamma camera imaging is discussed and the importance of considering the surface marker characteristics of the lymphocytes under study, when interpreting results, is emphasized. The possibility that the redistribution of lymphocytes within the body is a cause of the peripheral blood lymphopenia in patients with Hodgkin's disease and other malignancies is suggested, and the usefulness of indium-111 oxine labelling in clarifying this problem is proposed.
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The spread of a steroid-containing foam from the rectum was studied in eight normal controls and eight patients with ulcerative colitis proved by biopsy. A standard dose of foam was labelled with technetium-99m adsorbed on to microspheres of Amberlite resin. Immediately after the foam was administered the extent of spread varied considerably, though in no instance did it extend beyond the rectosigmoid. Further scans at 120 and 240 minutes showed no further spread. It is concluded that a steroid-containing foam has a topical effect only on the rectal mucosa.
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To further evaluate the mechanism of the oliguria of acute renal failure, a model was utilized in which intense and prolonged vasoconstriction produced the unilateral cessation of urine flow. The radioactive microsphere method was used to measure total and regional blood flow before and after the intrarenal infusion of norepinephrine, 0.75 mug/kg/min, for 2 h in the dog. In the control kidney, renal blood flow increased 32% 48 h after norepinephrine in association with a fall in the fractional distribution of flow to the outer cortex. In the experimental kidney, total renal blood flow fell from 190 ml/min before norepinephrine to 116 ml/min at 48 h (P < 0.025) with a uniform reduction in cortical blood flow. After the administration of 10% body wt Ringer's solution, there was a marked redistribution of flow to inner cortical nephrons in both the control and experimental kidney. In addition, there was a marked increase in total blood flow in both kidneys. On the experimental side, flow rose to 235 ml/min, a value greater than in either the control period (P < 0.05) or at 48 h after norepinephrine (P < 0.001). However, in spite of this marked increase in blood flow, there was essentially no urine flow from the experimental kidney. In separate studies, the animals were prepared for micropuncture. In all studies, the surface tubules were collapsed, and there was no evidence of tubular obstruction or leakage of filtrate. Over 99% of the 15-muM spheres were extracted in one pass through the experimental kidney. An analysis of the forces affecting filtration suggested that an alteration in the ultrafiltration coefficient may be responsible, at least in part, for the anuria in this model. In this regard, transmission and scanning electron microscopy revealed a marked abnormality in the epithelial structure of the glomerulus. It is suggested that a decrease in glomerular capillary permeability may be present in this model of acute renal failure.
Differences in alcohol consumption and in sensitivity to the effects of ethanol were investigated in four outbred rat strains: Fischer 344, Long-Evans, Sprague-Dawley and Wistar. Alcohol consumption was measured in all four strains in three separate subgroups for each strain, using three different concentrations of ethanol (5, 10 and 20% v/v). An intermittent forced alternate-day ethanol presentation procedure (ethanol as the sole fluid for one day followed by only water the next day), as well as a two-bottle choice paradigm, were employed for this purpose. Ethanol-induced hypothermia and motor impairment (tilting plane test) were used to assess sensitivity. Significant differences in alcohol consumption were found among these strains. The Long-Evans strain consumed the highest and Fischer 344 the lowest amount of ethanol. Wistar and Sprague-Dawley were intermediate. However, the strains did not differ in sensitivity to ethanol. Similarly, determination of sensitivity to ethanol on day 0 in separate groups of these four strains (same age and weight, and obtained at the same time from the same supplier) did not reveal graded differences in sensitivity (hypothermia and motor impairment) corresponding to differences in alcohol consumption. These results suggest that sensitivity does not correlate with alcohol consumption.
The purpose of this research was to study the effect of pressure on arterial hydration in vitro and the effect of pressure and flow (stirred reagent) on the in vitro transport of 125I-albumin and 125I-LDL into deendothelialized minipig aortas over a 24-hour period. It was found that the arterial hydration (fractional mass of water) was 0.740 +/- 0.0043 SEM for control tissue; after 24 hours this rose to 0.745 +/- 0.0038 for 0 mm Hg, 0.752 +/- 0.0046 for 100 mm Hg, and 0.755 +/- 0.0065 for 200 mm Hg. In the transport studies, the following effects were found. The reagent radioactivity concentration and composition did not change with pressure or stirring over the 24-hour period. For unpressurized tissue, the 24-hour normalized uptake [uptake (M mg cm-2) divided by reagent concentration (co mg cm-3)] of albumin was (4.86 +/- 0.43 cm) X 10(-3) from stirred and (5.46 +/- 0.36 cm) X 10(-3) from nonstirred reagent; that of LDL was (0.31 +/- 0.02 cm) X 10(-3) from stirred and (0.37 +/- 0.02 cm) X 10(-3) from nonstirred reagent. Pressurization (100 mm Hg) of the tissue increased albumin uptake by 52% from stirred and by 125% from nonstirred reagent and the LDL uptake by 52% from stirred and 241% from nonstirred reagent. Pressure increased the intimal surface concentration of albumin and LDL at the nonstirred, but not at stirred, interfaces. The electrophoretic properties of the intimal surface fluid showed only minor differences from those of the bulk reagent. These data demonstrate that pressure causes a slight, but significant, increase in arterial hydration and that radiolabeled albumin and LDL appear to be sieved by the superficial intimal layers of the deendothelialized porcine aorta under the in vitro conditions of this study.
Indium-111 oxine labeling is widely used as a marker of endothelial cell attachment to vascular prostheses. The long term effect of labeling human adult endothelial cells (HAECs) with this isotope has not been determined. In this study the viability of labeled HAECs, leakage of isotope from labeled cells and adherence of circulating isotope to fibronectin coated prostheses were investigated over 24 h. The effect of incubation time on labeling efficiency was also assessed. There were significant differences in cell viability between the labeled and unlabeled groups beyond 4 h (p < 0.005, 2-tailed, unpaired t-test). In the control group cell numbers increased by 42% while in the labeled group this had decreased by 20% at 24 h. Spontaneous leakage increased with time but was maximal in the first 2 h. Adherence of circulating isotope to fibronectin coated expanded polytetrafluoroethylene (ePTFE) grafts was minimal but was significantly greater to gelatin impregnated Dacron (GEL-SEAL) beyond 1 hour (p < 0.05). Incubation times greater than 5 minutes during labeling do not significantly improve labeling efficiency, and may contribute to toxicity by prolonging exposure to oxine. Indium-111 oxine labeling of HAECs is a suitable technique for acute studies of endothelial cell kinetics up to 4 h, but its use in chronic studies may lead to significant underestimations of cell retention.
Urban stormwater runoff contains a broad range of pollutants that are transported to natural water systems. A practice known as biological retention (bioretention) has been suggested to manage stormwater runoff from small, developed areas. Bioretention facilities consist of porous soil, a topping layer of hardwood mulch, and a variety of different plant species. A detailed study of the characteristics and performance of bioretention systems for the removal of several heavy metals (copper, lead, and zinc) and nutrients (phosphorus, total Kjeldahl nitrogen [TKN], ammonium, and nitrate) from a synthetic urban stormwater runoff was completed using batch and column adsorption studies along with pilot-scale laboratory systems. The roles of the soil, mulch, and plants in the removal of heavy metals and nutrients were evaluated to estimate the treatment capacity of laboratory bioretention systems. Reductions in concentrations of all metals were excellent (> 90%) with specific metal removals of 15 to 145 mg/m2 per event. Moderate reductions of TKN, ammonium, and phosphorus levels were found (60 to 80%). Little nitrate was removed, and nitrate production was noted in several cases. The importance of the mulch layer in metal removal was identified. Overall results support the use of bioretention as a stormwater best management practice and indicate the need for further research and development.