Biomedical subjects
H Sharma
Publications and source records attributed to H Sharma.
An unusual dislocation of the foot.
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Osteoarthritis: a review.
A brief review of osteoarthritis including its clinical features, laboratory tests and management has been discussed with review of literature.
An investigation of the parameters influencing the bioadhesive properties of Myverol 18-99/water gels.
An in vitro assessment was undertaken of the parameters influencing the bioadhesive strength of lyotropic liquid crystalline gels formed by the monoglyceride blend Myverol 18-99 and water. The gels were found to bind more strongly to a dry Perspex surface than to moist mucosal tissue and were shown to be weaker bioadhesives than Carbopol 934P and sodium alginate. The works of adhesion and forces of detachment were independent of contact time, were reduced by the presence of surface water and increased with an increase in the compression force, suggesting that interpenetration was not the mechanism of bioadhesion. The bioadhesion of Myverol 18-99/water gels appeared to be due to secondary chemical bonds, such as van der Waals forces, but was limited by their cohesive strength. An in vivo gel retention assessment by gamma scintigraphy showed that the gels were retained within the vaginal cavity for a period of at least 6 h.
Interleukin (IL) 15/IL-T production by the adult T-cell leukemia cell line HuT-102 is associated with a human T-cell lymphotrophic virus type I region /IL-15 fusion message that lacks many upstream AUGs that normally attenuates IL-15 mRNA translation.
We reported previously that the human T-cell lymphotrophic virus type I (HTLV-I)-associated adult T-cell leukemia line HuT-102 produces a cytokine designated interleukin (IL) T that requires interleukin (IL) 2 receptor beta-subunit expression for its action. Using anti-cytokine antibodies, we demonstrated that IL-T is identical to the simultaneously described IL-15. When compared to activated monocytes, IL-15 mRNA expression was 6- to 10-fold greater in HuT-102 cells. The predominant IL-15 message from HuT-102 is a chimeric mRNA joining a segment of the R region of the long terminal repeat of HTLV-I and the 5'-untranslated region (UTR) of IL-15. Normally, by alternative splicing, this 118-nucleotide R element represents the most 5' region of several HTLV-I transcripts including tax, rex, and env. The introduction of the R element eliminated over 200 nucleotides of the IL-15 5'-UTR, including 8 of 10 upstream AUGs that are present in normal IL-15 messages. On analysis of the 5'-UTR of normal IL-15, we demonstrated that the presence of these 10 upstream AUGs interferes with IL-15 mRNA translation. Thus, IL-15 synthesis by the adult T-cell leukemia line HuT- 102 involves an increase in IL-15 mRNA transcription and translation secondary to the production of an HTLV-I R element fusion message that lacks many upstream AUGs.
Endothelial cell seeding kinetics under chronic flow in prosthetic grafts.
Improved patency of endothelial cell seeded grafts relies on good initial adherence and cell retention when the circulation is restored. In this study human adult endothelial cells (HAECs) were used to evaluate the suitability of commercially available prostheses for seeding. Acutely seeded indium-111 oxine labeled HAECs were used to measure cell adherence to plain and fibronectin (FN)-coated expanded polytetrafluoroethylene (ePTFE), gelatin-impregnated Dacron (Gelseal), and collagen-impregnated Dacron (Hemashield) grafts. Cell loss from FN-coated prostheses, when exposed to a simulated human arterial blood flow of 200 ml/min in an artificial pulsatile circulation, was quantified from the loss of gamma activity from the graft over 24 hours, pressure in the circulation being reduced to 15 mm Hg to reduce fluid loss. Initial HAEC adherence (mean [SD]) to plain grafts was 3(1)%, 47(9)%, and 53(9)% for ePTFE, Gelseal, and Hemashield, respectively. This improved significantly with FN coating (78[6]%, 60[8]%, and 76[4]%). Cell retention after 24 hours of flow to FN-coated grafts was 16(10)%, 25(5)%, and 65(4)% and was confirmed qualitatively by scanning electron microscopy and environmental scanning electron microscopy. FN significantly improved initial cell adherence with Dacron grafts showing the better adherence. Cell retention after 24 hours of flow was better with FN-coated Dacron than with ePTFE but was best with Hemashield grafts.
Antidepressant-induced hyponatraemia in the aged. Avoidance and management strategies.
Antidepressant-induced hyponatraemia, while relatively uncommon, is an important clinical problem with serious consequences. Most antidepressants have been associated with hyponatraemia. Although the exact mechanism by which abnormalities of serum sodium level are produced is not known, most of the patients described in case reports meet the accepted criteria for the syndrome of inappropriate antidiuretic hormone secretion. Symptoms of hyponatraemia can mimic depression or psychosis, so awareness of this syndrome and periodic monitoring of serum electrolytes are important for early recognition. Stopping the medication and assuring normal extracellular fluid volume are the mainstay of treatment; rarely, intravenous infusion of hypertonic saline is required. After correcting the metabolic abnormalities, options for treatment of depression include: rechallenging with the same medication or initiating another antidepressant while carefully monitoring serum sodium level, or considering electroconvulsive therapy, if warranted by the clinical condition.
Molecular manifestations of cardiac hypertrophy in the spontaneously hypertensive rat effects of antihypertensive treatments.
Antihypertensive treatments were given to young and adult SHRs, to prevent and reverse hypertension, respectively. Cardiac hypertrophy and the steady state level of the "fetal" genes, ANP, alpha-skeletal actin (alpha-skA), and beta myosin heavy chain (beta-MHC) mRNAs were assessed. Our findings show that the reduction of blood pressure does not consistently result in a similar regression of the "fetal gene program".
Chronic hydronephrosis: renographic drainage patterns and renal morphology in an animal model.
OBJECTIVE: To develop an animal model of chronic progressive hydronephrosis; to establish patterns of diuretic renography during development of the condition; and to relate renographic abnormality to morphological change in the renal parenchyma. MATERIALS AND METHODS: The cellophane sclerosis technique was used to produce a hydronephrosis in the left kidney of six rabbits. Post-operatively MAG3 diuretic renography was performed at weekly intervals. When a steady renographic trend was noted the rabbits were killed and the kidneys examined histologically. RESULTS: Four rabbits had persistent type II renographic curves on the left for 12 weeks. The measured split renal function fell steadily to < 20% in this time. Morphologically there was hydronephrosis with marked structural changes in the parenchyma seen on histological examination. Two rabbits had stable type IIIa renographic drainage patterns on the left with preserved renal function. Morphologically there was hydronephrosis but histologically the kidneys were normal. There were no renographic or structural changes in a control rabbit after a sham laparotomy. CONCLUSIONS: The cellophane sclerosis technique can be used to create a reproducible chronic progressive hydronephrosis. In this animal model hydronephrosis and a persistent type II curve are associated with renographic evidence of deteriorating renal function and disruption of renal architecture histologically. Hydronephrosis and a type IIIa curve are associated with preservation of normal renal function and histological structure.
Splenic hemangiomatosis with osseous involvement.
A rare case of splenic hemangiomatosis with bone involvement in the upper extremity is presented. The findings on ultrasonography and CT scan abdomen were suggestive of splenic hemangiomatosis. X-ray of left forearm showed findings characteristic of osseous hemangiomatosis, which was subsequently confirmed on histology.
Fibronectin binding to gelatin-impregnated Dacron (Gelseal) prostheses.
Endothelial cell adherence to uncoated gelatin-impregnated Dacron (Gelseal) is poor but can be significantly improved by precoating with a suitable basement membrane such as fibronectin. To assess the suitability of fibronectin-coated Gelseal for endothelial cell seeding, fibronectin binding to Gelseal and its dissociation kinetics were investigated. Fibronectin binding was quantified by radiolabeling human fibronectin with iodine 125, concentrations of 10, 25, 50, 150, and 250 micrograms/ml being used to coat Gelseal at 30, 60, and 90 min of incubation. The amount of fibronectin bound was directly proportional to the concentration used and increased with time of incubation (p < 0.05). However, the percentage attachment decreased with increasing concentration (p < 0.001). The number of molecules bound per centimeter squared of graft was calculated. In the first 30 min, 75% of bound fibronectin was lost after exposure to a flow rate of 200 ml/min in a pulsatile artificial circulation; thereafter, the fibronectin-Gelseal bond was stable for up to 2 h.
The response of rapidly formed adult human endothelial-cell monolayers to shear stress of flow: a comparison of fibronectin-coated Teflon and gelatin-impregnated Dacron grafts.
Endothelial cells labeled with indium 111-oxine were seeded in supraconfluent densities onto fibronectin-coated expanded polytetrafluoroethylene (ePTFE) and gelatin-impregnated Dacron graft segments. These grafts with rapidly formed endothelial-cell monolayers were then exposed to varying shear stresses at flow rates of 200 and 300 ml/min, using tissue culture medium in an artificial flow circuit. As the loss of radioactivity represented endothelial-cell loss, cell retention was calculated by the ratio of counts recorded at different time points during 2 hours of flow to initial counts. Although initial cell adherence to gelatin-impregnated Dacron graft segments was poor compared to ePTFE, once cells were attached they resisted shear stress of flow better at 200 ml/min and equally well at 300 ml/min. The cell retention on fibronectin-coated ePTFE was 55.4 +/- 12.9% at 200 ml/min and 56.5 +/- 15.2% at 300 ml/min; cell retention for gelatin-impregnated Dacron graft segments was 69.0 +/- 6.0% and 66.5 +/- 5.5%, respectively. Qualitatively scanning electron microscopy of both ePTFE and gelatin-impregnated Dacron graft segments showed patchy coverage of grafts with cells. There was preferential attachment of endothelial cells to the nodes on ePTFE, although on gelatin-impregnated Dacron graft segments, cells conformed to the Dacron fibers at different levels and directions with evidence of bridging in the gaps between individual fibers. This study shows conclusively that rapidly formed endothelial-cell monolayers on ePTFE and gelatin-impregnated Dacron graft segments resisted a shear stress of flow equal to that seen in a femoropopliteal vein graft with significant cell retention at 2 hours.
Comparison of different vascular prostheses and matrices in relation to endothelial seeding.
Thin-walled expanded polytetrafluoroethylene (ePTFE), woven Dacron and gelatin-impregnated Dacron (Gelseal) vascular grafts were compared, the grafts being coated with three different matrices: collagen IV, fibronectin and preclot matrix. In addition, untreated ePTFE and Gelseal were examined. The graft segments, coated with these matrices, were incubated with radiolabelled adult human endothelial cells for 30, 60 and 90 min. Endothelial cell adherence was calculated from the ratio of radioactive counts in the grafts to counts in grafts plus supernatants. Endothelial cell attachment to untreated grafts was poor, but a suitable matrix significantly improved adherence. All three matrices tested gave good results, although preclot was best; 30-60 min incubation was sufficient for optimum cell attachment. Cell adherence to both Dacron and ePTFE was significantly better than to Gelseal. The type of prosthetic polymer and the substrate protein coating used to promote endothelial cell adherence are two important factors which may determine the ultimate success of endothelial seeding in the operating room.
Comparative intraperitoneal pharmacokinetics of three platinum analogues.
The pharmakokinetic profiles of intraperitoneally infused platinum analogues were determined in 13 women exhibiting minimal residual disease following surgery and systemic chemotherapy for epithelial ovarian cancer or fallopian tube carcinoma by following the disposition of tracer doses of 195mPt radiolabel. Six patients received iproplatin, four were given cisplatin and three received carboplatin. The present data demonstrate no difference in the disposition of total platinum between these three analogues, but differences in the kinetics of free platinum may exist.
Initial sensitivity, acute tolerance and alcohol consumption in Fischer 344 and Long Evans rats.
In separate groups of Fischer 344 and Long Evans rats, initial sensitivity and acute tolerance to ethanol were determined in a jumping test. Sensitivity measurements in each strain were carried out in separate subgroups at ethanol doses of 1.5, 2.0, and 2.5 g/kg IP. Similarly, acute tolerance was measured in different subgroups of each strain using the method of two successive doses of ethanol (2 + 0.4 g/kg; 2 + 0.7 g/kg and 2 + 1.0 g/kg, respectively). After completion of sensitivity and acute tolerance measurement, acute tolerance was then tested in all rats. Based on their acute tolerance values, they were divided into three groups: high, medium, and low. Two weeks after the last acute tolerance test, six rats from each group (i.e., the six highest and six lowest from the high and low acute tolerance groups, respectively, and six from the mid-range of the medium tolerance group) were tested for voluntary ethanol drinking in the limited access model. Long Evans rats had lower initial CNS sensitivity to ethanol-induced impairment of jumping performance than Fischer 344 rats. Long Evans rats also drank significantly more alcohol than the Fischer 344 but there was no significant difference in acute tolerance development between these two strains. Moreover, within each strain the rats differing in acute tolerance development (i.e., high, medium, and low) showed no difference in alcohol consumption. These results suggest that acute tolerance development is not the main determinant of differences in ethanol drinking.
The effect of varying fibronectin concentration on the attachment of endothelial cells to polytetrafluoroethylene vascular grafts.
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In vitro adherence and kinetics studies of adult human endothelial cell seeded polytetrafluoroethylene and gelatin impregnated Dacron grafts.
Lining the luminal surface of small diameter vascular prostheses with living endothelial cells reduces thrombogenicity, decreases infection and improves patency. In vitro adherence and kinetics studies of adult human endothelial cell seeded Polytetrafluoroethylene (ePTFE) and Gelatin impregnated Dacron (Gelseal) were performed. Endothelial cell adherence on ePTFE and Gelseal coated with collagen IV, fibronectin and preclot matrices was compared. Untreated ePTFE and Gelseal were also used. Ten graft segments in each group coated with these matrices were incubated with radio-labelled adult human endothelial cells for 30, 60 and 90 min. Labelled endothelial cells seeded in supra-confluent densities on fibronectin coated ePTFE and Gelseal grafts were used for kinetic studies. Resultant endothelial cell monolayers were then exposed to varying shear stress at flow rates of 200 and 300 ml/min in an artificial flow circuit. Endothelial cell attachment to untreated grafts was poor and a suitable matrix significantly improved adherence with fibronectin and preclot but less so with collagen. A 30 min incubation was sufficient for optimum cell attachment. Cell adherence to ePTFE was significantly better than Gelseal. Scanning electron micrographs (SEM) of ePTFE showed preferential attachment to the nodes whilst on Gelseal, cells conformed to Dacron fibres at different levels and directions. Rapidly formed endothelial cell monolayers on ePTFE and Gelseal grafts resisted shear stress of flow with significant cell retention at 2 h. There was patchy coverage of both grafts with evidence of bridging of gaps between individual fibres in Gelseal.
Expression of intercellular adhesion molecule 1 (ICAM-1) on human articular cartilage chondrocytes.
Monoclonal antibodies have been used to demonstrate the induction of intercellular adhesion molecule 1 (ICAM-1) on chondrocytes in human articular cartilage. ICAM-1 was found not to be constitutively expressed but could be induced by exogenous interleukin 1 alpha(IL1- alpha) at concentrations ranging from 0.01 to 20 ng/ml during in vitro culture. Maximum expression was observed with 2-5ng/ml. In time-course experiments ICAM-1 was not expressed after 4h in culture with IL1 alpha. Expression was induced by 16h and was sustained for a minimum of 6 days in the continued presence of the cytokine. The endothelial leukocyte adhesion molecule (ELAM-1) was not expressed on chondrocytes and was not induced by IL1-alpha.