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Biomedical subjects

R Sharma

Publications and source records attributed to R Sharma.

At least 739 records · Page 41Linked to original sources

Safe separation of sputum cells from mucoid glycoprotein.

OBJECTIVE: To compare the safety and efficacy of homogenizing sputum with deoxyribonuclease I (DNAse I), dithiothreitol (DTT), N-acetyl-L-cysteine, sodium EDTA and trypsin against standard mechanical blending to provide mucus-free, single-cell suspensions for quantitative analysis. STUDY DESIGN: Clinical sputum specimens or cultured human bronchogenic carcinoma cells were preserved in 2% polyethylene glycol/50% ethanol, divided into aliquots, counted and stained (Papanicolaou and avidin-biotin complex immunostained) at baseline. Cells of each aliquot were separated from mucus by the standard physical blending method or by chemical or enzymatic mucus liquefaction. After staining, washing and resuspending in the original volume of polyethylene glycol/ethanol mixture, aliquots were again counted and stained. RESULTS: Cell counts, Papanicolaou staining and immunostaining showed that homogenization of induced, preserved sputum with 0.5 mM DTT is safe and provides mucus-free monolayers for immunocytochemistry and single-cell suspensions for flow cytometry. Mucolysis with 0.5 mM DTT resulted in a significant (16%) increase in cells available. In contrast, mechanical blending resulted in up to a 24% reduction in specimen cellularity. CONCLUSION: Homogenization with low-concentration DTT will probably facilitate the exploration of sputum for protein and gene markers of carcino genesis.

Bronchial Neoplasms↗

Growth inhibitory effects of pMC540 and merodantoin on established MCF-7 human breast tumor xenografts.

The effect of preactivated merocyanine 540 (pMC540) and one of its chemically synthesized active isolate merodantoin on established human MCF-7 human breast tumor xenografts was investigated. Preactivation is a novel photochemical method for the production of chemotherapeutic compounds that exert their biological effects independent of light. These compounds thus produced, are cytotoxic to human breast cancer cells in vitro and in vivo but only minimally cytotoxic towards normal cells. Nude mice bearing established breast tumors (with or without exogenous estradiol) received injections of pMC540 (250 mg/kg) or merodantoin (75 mg/kg) with or without concurrent treatment with tamoxifen. Treatment with pMC540 and merodantoin caused a 74% and 84% inhibition of tumor growth respectively. Combination of these drugs with tamoxifen did not produce a significant enhancement of growth inhibition. In the absence of exogenous estradiol, identical treatment with pMC540 and merodantoin resulted in 41% and 25% inhibition of tumor growth respectively. Both agents caused a significant (59%) inhibition of growth of estrogen independent human breast tumors established from MDA-MB-435 cells. These results show that photochemically generated novel compounds in pMC540 are effective in suppressing the growth of established human MCF-7 and MDA-MB-435 breast tumor xenografts.

Animals↗

Congenital heart disease among school children in Shimla hills.

A stratified random sample of 15,080 school going children out of 40,950 children in the age group of 5 to 16 years were screened for the prevalence of congenital heart disease and rheumatic fever/rheumatic heart disease. Thirty children were found to be suffering from definite congenital heart disease giving a prevalence of 2.25 per thousand. Atrial septal defect was the commonest lesion (38.2%) with a prevalence of 0.87 per thousand followed by ventricular septal defect (32.2%) with a prevalence of 0.73 per thousand. The prevalence of congenital heart disease was found to be significantly more in female (3.3 per thousand) than in male children (1.4 per thousand) (p < 0.05). Three (8.8%) cases had a family history of congenital heart disease. Rheumatic fever/rheumatic heart disease was found to have a significant prevalence among cases with congenital heart disease (8.8%) as compared to children without congenital heart disease (0.3%) (p < 0.001). The findings suggest the need for screening of family members of those suffering from congenital heart disease and that special attention be paid to the occurrence of rheumatic fever/rheumatic heart disease in cases of congenital heart disease.

Adolescent↗

Neuropharmacological studies on identified central neurones of the snail, Helix aspersa.

Central neurones of the snail, Helix aspersa, possess both synaptic and somatic receptors to a wide range of classical transmitters and neuroactive peptides. The range of receptors and the type of response is reasonably constant for a specific neurone. This review will provide data concerning the pharmacology of acetylcholine, serotonin, dopamine, noradrenaline, octopamine, glutamate, GABA and purine receptors on identified neurones. Many of these neurones also respond to neuroactive peptides including molluscan peptides, e g, AMPMLRLamide, LSSFVRIamide, SGQSWRQGRPFamide, FMRFamide; coelenterate peptides, e g, pQGRFamide; echinoderm peptides, e g, GFNSALMFamide; and nematode peptides, e g, KNEFIRFamide, KHEYLRFamide, SDPNFLRFamide. Using this data, the pharmacological profiles of identified neurones will be summarised.

Animals↗

Correlation between DNA topoisomerase II activity and cytotoxicity in pMC540 and merodantoin sensitive and resistant human breast cancer cells.

We have shown previously that preactivated merocyanine 540 (pMC540) and merodantoin appear to mediate their cytotoxic effects via interaction with Topo II. Now, we demonstrate a correlation between DNA Topo II activity and drug-sensitive (MCF-7) and -insensitive (MDA-MB-231) breast cancer cell lines. Further studies indicate that MDA-MB-231 cells are insensitive to the cytotoxic and DNA cleavage effects of pMC540 and merodantoin. This loss of sensitivity is not associated with M(r) 170,000 P-glycoprotein over expression. However, in drug insensitive cells, the Topo II catalytic activity in crude nuclear extract was reduced two- to-three-fold and in cellular extracts was virtually absent as determined by decatenation of kDNA. Topoisomerase I activities appeared similar in extracts from MCF-7 and MDA-MB-231 cell lines. Drug-induced DNA cleavage was reduced two-to-threefold in nuclear extracts from MDA-MB-231. m-AMSA was more effective in inhibiting the decatenation activity in the nuclear extracts from MDA-MB-231 as compared to MCF-7 cells. Western blot analysis of whole-cell lysates revealed undetectable immunoreactivity of Topo II in the drug-insensitive cells. These data indicate that insensitivity of MDA-MB-231 to pMC540 and merodantoin is in part due to the reduced drug-induced formation of the cleavage complex and Topo II (170 kD) enzyme content.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The effect of short-term administration of theophylline on erythropoietin levels in healthy adults.

A previous study demonstrated suppression of erythropoietin production in patients treated with long-term theophylline. This effect could exacerbate anemia of prematurity in neonates receiving this drug for apnea of prematurity. In this pilot project we evaluated the effect of short-term theophylline administration on serum erythropoietin in healthy adults. Six subjects were given a bolus followed by a continuous infusion of theophylline targeted to achieve a serum level of at least 10 micrograms/ml, followed by oral theophylline for 36 hours. Serum erythropoietin and theophylline levels were measured before, during, and after drug infusion. Complete hemograms were performed before and after completion of the infusion. No significant changes in serum erythropoietin levels were seen at any time (F = 1.57, p = 0.12). Hematologic values also remained unaltered. We conclude that short-term administration of theophylline is unlikely to have any effect on serum erythropoietin levels in healthy adults.

Administration, Oral↗

Analysis of symptomatic patients after cholecystectomy: is the term post-cholecystectomy syndrome an anachronism?

Of 171 patients who were followed-up prospectively for 2.8 years after cholecystectomy, 31 developed postcholecystectomy symptoms, 24 of them being mild to moderate and 7 severe. Symptomatic patients mostly had functioning gall bladders preoperatively and longer duration of symptoms prior to cholecystectomy. The causes of postcholecystectomy symptoms could be identified in all of them except 9 patients who were labelled as having "essential dyspepsia". The symptoms in the latter syndrome as well as in other conditions diagnosed in the symptomatic postcholecystectomy patients appeared unrelated to the absence of gallbladder. Hence, we feel the term postcholecystectomy syndrome is an anachronism and should be redefined.

Cholangiopancreatography, Endoscopic Retrograde↗

Patient perception of the diskus inhaler: a comparison with the turbuhaler inhaler.

Asthmatic patients who were regular and experienced users of the metered-dose inhaler (MDI) but with no history of powder inhaler use were interviewed by questionnaire. Most (71%) of the 159 adults recruited had suffered from asthma for more than five years; 89% had used an MDI for more than one year. In all, 153 (97%) found their current MDI easy or very easy to handle. Effectiveness in delivering the drug and ease of operation were the two features of the device they were most satisfied with. The two features 'of an ideal inhaler' rated most highly were the presence of a dose counter and ease of use during an attack (58% and 72% of respondents, respectively). Other important features included hygiene, sensation that a dose had been taken, and small size. When attitudes towards the Diskus inhaler and the Turbuhaler inhaler were compared, 108 (68%) would have been quite or very happy to have a Diskus inhaler prescribed for them, and 79 (50%) a Turbuhaler inhaler. The Diskus inhaler scored significantly better than the Turbuhaler inhaler for knowing how many doses were left, the presence of an attached cover, attractiveness (p < 0.001), hygiene, shape, weight (p = 0.001), and perceived ease of use (p = 0.002). The Turbuhaler inhaler scored significantly better in terms of size (p < 0.001). Overall, the Diskus inhaler was preferred by 104 of 159 patients (p < 0.001), with perceived ease of use, the dose counter, and shape cited as the main reasons for preference.

Adolescent↗

Right ventricle to pulmonary artery connections.

From March 1988 through June 1995, 80 patients underwent repair for right ventricle (RV) to pulmonary artery (PA) discontinuity. Of these, 30 patients received homograft conduits, while the remaining 50 underwent repair without the use of a homograft. Handmade pericardial valved vascutek conduits (n = 18), non-valved vascutek tubes (n = 13) and non-conduit procedures like the rev operation (n = 12) and extended pericardial gusset (n = 5) were mainly used. The indications for repair for RV-PA discontinuity included ventricular septal defect with pulmonary atresia (VSD PA) (n = 36), truncus arteriosus (n = 18), ventricular septal defect with pulmonary and major aorto-pulmonary collaterals (VSD PA MAPCA) with staged repair (n = 5), congenitally corrected transposition of the great arteries with ventricular septal defect and pulmonic stenosis (CCTGA VSD PS) (n = 5) and double outlet left ventricle with ventricular septal defect and pulmonic stenosis (DOLV VSD PS) (n = 5). The choice of the procedure was governed by various factors, including type of cardiac defect, pulmonary artery pressure and morphology, previous operation, socio-economic constraints and availability of appropriate sized homografts. Non-circuit operations may prevent future reoperations in these patients.

Adolescent↗

Single lung Rastelli repair.

A four year old severely cyanotic child was diagnosed to have double outlet right ventricle, large subpulmonic ventricular septal defect, severe pulmonic valve stenosis with absent left pulmonary artery and bilateral superior vena cavae without any connecting vein. A Rastelli type repair was performed utilizing the right pulmonary artery as the only run-off for the right ventricle. Immediate post-pump right ventricular (RV) pressures were 90 percent of the systemic. Six months later, echocardiographically estimated RV pressure was 60 percent of the systemic. The child is doing well at 6 months follow-up.

Child, Preschool↗