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Biomedical subjects

R K Sharma

Publications and source records attributed to R K Sharma.

At least 289 records · Page 16Linked to original sources
PubMed1994

Differentiation of malignant and degenerative bone lesions using dexamethasone interventional 3- and 24-hour bone scintigraphy.

Seventy-seven adult patients with suspected skeletal metastases were divided into two groups. In group A (n = 30), following intravenous administration of 20 mCi (740 MBq) of technetium-99m methylene diphosphonate (99mTc-MDP), 3- and 24-h scintigraphy of bone lesions was performed. The 24/3 h lesion to bone background radiouptake ratio (RUR) was calculated for each lesion. In group B (n = 47), the same procedure was followed with dexamethasone intervention (10 mg in 24 h) following the 3-h acquisition. In group A, after determination of the critical point, malignant and degenerative bone lesions could be separated with a sensitivity, specificity and accuracy of 0.76, 0.72 and 0.73, respectively. The mean RUR of the malignant lesions was 1.20 +/- 0.23, and that of the benign lesions, 0.95 +/- 0.15. In group B cases, significantly increased sensitivity, specificity and accuracy of 0.87, 0.94 and 0.92, respectively, were found (P < 0.001). The mean RUR of the malignant lesions was 1.48 +/- 0.34, and that of degenerative lesions, 0.88 +/- 0.19. Dexamethasone interventional bone scintigraphy seems to be a new cost-effective method for differentiating malignant from degenerative bone lesions using the RUR.

Bone Diseases↗
PubMed1994

Intravenous pulse cyclophosphamide--a new regime for steroid-resistant minimal change nephrotic syndrome.

The treatment of steroid-resistant minimal change nephrotic syndrome (MCNS) continues to pose a therapeutic challenge. We conducted a randomised prospective controlled trial to evaluate the efficacy of i.v. cyclophosphamide compared with oral cyclophosphamide in 13 children with biopsy-proven steroid-resistant MCNS. All 7 patients receiving i.v. cyclophosphamide achieved remission; this was sustained in 4 patients, while 3 relapsed. However, even these 3 patients subsequently became steroid sensitive. Of the 6 patients who received oral cyclophosphamide, 2 dropped out, 1 responded and 3 children continued to remain steroid resistant. The children who received IV cyclophosphamide had more sustained remissions, longer periods without proteinuria and fewer significant side effects; this was achieved at a lower cumulative dose.

Administration, Oral↗
PubMed1994

Intracorporeal lithotripsy with the Swiss lithoclast.

OBJECTIVE: To evaluate the use of the Swiss lithoclast in the management of urinary calculi. PATIENTS AND METHODS: Between January and November 1993, 60 patients with a total of 61 urinary calculi were treated with the Swiss lithoclast. Forty patients had a ureteric calculus, two had a ureterocele with a calculus, one a steinstrasse, 16 a vesical stone and two a urethral calculus. Eighty per cent of patients were treated on a day-care basis. RESULTS: Fragmentation of the urinary calculi was successful in 59 of the 60 patients. Both patients with a urethral calculus and 15 of 16 with a vesical calculus were stone-free after the procedure. All those with a ureteric calculus were stone-free at 6 weeks. There were no intra-operative or long-term complications directly related to the use of the Swiss lithoclast. CONCLUSION: The results of this study show that the Swiss lithoclast is a simple, safe, reliable and economical method of endoscopic lithotripsy for the treatment of urinary tract calculi. Although the lithoclast's use is limited to rigid or semi-rigid endoscopes there is now a suction facility for the immediate removal of small stone fragments.

Adolescent↗
PubMed1994

Steroid response pattern in Indian children with nephrotic syndrome.

The steroid response pattern to standard prednisolone therapy is of immense diagnostic, therapeutic and prognostic value for the treating physician in managing children with nephrotic syndrome. None of the studies from our country has analysed the clinical, biochemical and histopathological profile in different steroid response categories. To address this problem we conducted a study comprising 127 children with nephrotic syndrome referred to our institute. They were treated with oral prednisolone according to the APN protocol. Based on the subsequent response these children were classified into different steroid response categories on follow-up. Of the 116 children with follow-up of more than six months, infrequent relapsers constituted the majority (37.9%). The frequency of other steroid response categories was as follows: frequent relapsers (21.6%), steroid-dependent (18.1%), initial non-responders (17.3%) and subsequent non-responders (5.1%). The factors predicting a poor response to standard prednisolone therapy in our study were age of onset more than eight years, male sex, hypertension, microscopic haematuria and presence of non-minimal change nephrotic syndrome lesions on histopathology.

Child↗
PubMed1994

99m Tc DTPA scan as a diagnostic marker of acute rejection in renal transplantation.

Forty renal transplant recipients were subjected to 99m Technicium Diethylene triamine pentacetic acid (DTPA)scans at regular intervals & whenever there was suspection of rejection. Serial scans of a group of 15 recipients from immediate post transplant period till withdrawal of cyclosporine were analysed separately & the results compared to with single scan analysis. The sensitivity & specificity of DTPA scan in the absence of acute tubular necrosis (ATN) was 94.1% & 87.5%, while the positive & negative predictive values were 88.8 & 93.3% respectively. Sensitivity & specificity of serial scan analysis (88.8% and 75%) in early post transplant period was higher than that of interpretation of single scan (75% & 66%). Serial scan changes predated clinical rejection during cyclosporine withdrawal period. We conclude that DTPA scan is both a sensitive & specific non-invasive diagnostic marker of acute rejection in absence of ATN & serial scans during early post transplant period & at the time of cyclosporine withdrawal are helpful in detecting the rejection accurately & at the earliest.

Adult↗
PubMed1994

Should elderly donors be accepted in a live related renal transplant program?

It is a matter of concern that the elderly donor may have increased risks in the peri-operative period due to age-related changes in various organ. Nephrosclerosis, atherosclerosis and low GFR of an elderly kidney may portend a poor graft outcome. A retrospective analysis of our live related renal transplant program (from June 1989 to December 1993) revealed that 27 of the donors were above 60 years of age. 21 of the recipients have been followed up for more than 1 year. These patients were compared with a cohort of 25 patients (donor age < 45 years) with similar HLA match, immunosuppressive protocol, and follow-up period more than 1 year. Graft survival at 1 year was 86% and 88% in the recipients from elderly and younger donors respectively; 1 patient in the control group died of fulminant sepsis. Mean follow-up was 21.6 months in the study group and 22.8 months in the control group. Allograft function was evaluated by serum creatinine and differential GFR by Tc DTPA scan. Serum creatinine (mg%) was 1.3 +/- 0.2 and 1.4 +/- 0.2 in the study group and 1.3 +/- 0.3, 1.2 +/- 0.3 in the control group at 3 and 12 months respectively. Glomerular filtration rate (ml/min) was 36.5 +/- 11.6 and 43.7 +/- 12.4 in the recipients from elderly donors whereas those from the younger donors had GFR (ml/min) of 40.6 +/- 9.6 and 49.6 +/- 14.2 at 3 and 12 months respectively, GFR continued to improve in both groups with follow-up. There was no difference in incidence or severity of ATN In the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Treatment of nephrotic syndrome.

There are well defined therapeutic protocols for childhood nephrotic syndrome. Appropriate therapy helps in minimizing side effects besides decreasing referrals to tertiary care centres. We have analysed the appropriateness of therapy of primary care physicians in 111 children with nephrotic syndrome referred to our Institute from January 1989 to December 1991. Prednisone was administered in adequate doses in 51 (52.6%), and for adequate duration in 41 children (42.2%). Adjunctive cyclophosphamide therapy was administered in the recommended doses and duration in 33% of the cases. On evaluation of the therapy it was observed that inappropriate treatment had been administered by 39.4% of the pediatricians, 59% of internists and 80% of general practitioners. This study highlights the lacunae in the current state of knowledge amongst the primary physicians and highlights the need for creating greater awareness regarding the therapy of children with nephrotic syndrome.

Adolescent↗
PubMed1994

Pattern of acute renal failure at a referral hospital.

Fifty two children (upto 12 years age) with acute renal failure (ARF) admitted to the Nephrology services between January, 1989 to August, 1992 were studied to determine the cause and outcome. Of these, 39 were boys and 13 girls; 27 (51.9%) patients were below 4 years of age. Hemolytic uremic syndrome (HUS) was the commonest cause of ARF (30.8%) followed by acute tubular necrosis (ATN) in 28.84% and acute glomerulonephritis in 19.23%. All patients had severe renal involvement with anuria in 53.6% and oliguria in 46.4% at presentation. HUS was the leading cause of anuria (53.6%), followed by obstructive uropathy (21.4%). Thirty five patients required dialytic support for a median duration of 18 days (2-90 days). The mortality was 34.6%. Seven patients of HUS, 4 patients of ARF following surgery, 3 patients each of ATN and glomerulonephritis and one patient of obstructive uropathy died. Anuria at onset, central nervous system or respiratory complications and delay in institution of dialytic support were bad prognostic factors. We conclude that early referral and prompt institution of dialytic support may be helpful in decreasing the mortality.

Acute Kidney Injury↗
PubMed1994

Molecular interaction between cAMP and calcium in calmodulin-dependent cyclic nucleotide phosphodiesterase system.

The second messenger molecules cAMP and Ca2+ regulate a large number of eukaryotic cellular events. cAMP acts on protein kinases, and Ca2+ works through a ubiquitous calcium-binding protein, calmodulin. The 2 systems are not independent, however, but interact in several important fashions. These interactions can be demonstrated by calmodulin-dependent phosphodiesterase. The bovine heart calmodulin-dependent phosphodiesterase can be phosphorylated by cAMP-dependent protein kinase, resulting in a decrease in the enzyme's affinity for calmodulin. The phosphorylation of calmodulin-dependent phosphodiesterase is blocked by Ca2+ and calmodulin, and reversed by the calmodulin-dependent phosphatase (calcineurin). The dephosphorylation is accompanied by an increase in the affinity of the phosphodiesterase for calmodulin. Results from this study suggest that the activity of this phosphodiesterase is precisely regulated by cross-talk between Ca2+ and cAMP signalling pathways.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Effects of 2-deoxy-D-glucose on the photosensitisation-induced bioenergetic changes in Saccharomyces cerevisiae as observed by in vivo NMR spectroscopy.

Haematoporphyrin (HP), a photosensitiser used for photodynamic therapy (PDT) of tumours, has been observed to affect the cellular energy metabolism both in the absence and presence of light. The effects of HP alone and in combination with 2-deoxy-D-glucose (2-DG) on photosensitisation-induced bioenergetic changes in yeast (Saccharomyces cerevisiae) were monitored and compared using in vivo NMR spectroscopy. Presence of HP was seen to reduce polyphosphates and inorganic phosphate in the dark. Upon photo-irradiation, polyphosphates and sugar phosphates decrease drastically with concomitant rise in inorganic phosphates. Presence of 2-DG in the medium also induced a decrease in polyphosphates and nucleotide triphosphates and the build-up of 2-deoxy-D-glucose-6-phosphate (2-DG-6-P) was clearly detectable. The combination of 2-DG and HP followed by photo-irradiation, however, induced a significant reduction in intracellular pH and beta phosphate of ATP/inorganic phosphate (beta-ATP/Pi) ratio decreased to a larger extent as compared to similar treatment without 2-DG. These observations confirm that polyphosphates are utilised as phosphogen, as phosphate store to be used during phosphate deprivation and as alternative energy source under conditions of energy deficiency induced by HP-PDT and/or 2-DG. The present results further suggest that photodynamic therapy could be made more effective in conjunction with 2-DG administration.

Deoxyglucose↗
PubMed1994

Development of anti-idiotypic antibodies to HLA antigens during pregnancy.

Thirty one pregnant women whose sera were initially positive for anti HLA antibodies were retested for lymphocytotoxicity 7-9 months after delivery. In the second testing 10 women were found to have lost the cytotoxic antibodies. These sera were tested for presence of anti-idiotypic antibodies by complement dependent cytotoxicity (CDC). In all ten sera tested, CDC blocking antibody was detected by inhibition technique at different dilutions. These antibodies directed specifically against the HLA antigen of the spouse. This CDC blocking factor could be the anti-idiotypic antibody (Ab2) directed against the cytotoxic anti-HLA antibody (Ab1). In one woman who conceived a second time, repeat sample obtained at the 7th month of the second pregnancy showed reappearance of the specific anti-HLA antibody. This may suggest that the Ab1-Ab2 network is under dynamic regulation.

Antibodies, Anti-Idiotypic↗
PubMed1994

Double-blind comparison of intranasal fluticasone propionate, 200 micrograms, once daily with 200 micrograms twice daily in the treatment of patients with severe seasonal allergic rhinitis to ragweed.

In a single-center, double-blind, crossover study of 90 subjects, fluticasone propionate aqueous nasal spray, 200 micrograms, once daily was compared with 200 micrograms twice daily in severe seasonal allergic rhinitis to ragweed. The mean percentage of days free of nasal itching and eye symptoms was significantly higher with twice daily fluticasone propionate (P = .004, P = .005, respectively). There were no significant differences between the two treatment groups for nasal blockage, rhinorrhea (runny nose), and sneezing. The median symptom scores for nasal itching were lower during twice daily treatment (P = .008) but there was no significant difference for the other symptoms. There were no significant differences between the groups in the use of rescue medication. Adverse events were infrequent, and similar in both groups. Most were considered unrelated to the treatment. Twice daily treatment with fluticasone propionate may be preferable for some patients with severe seasonal allergic rhinitis.

Administration, Intranasal↗
PubMed1993

The glycine residue of ATP regulatory module in receptor guanylate cyclases that is essential in natriuretic factor signaling.

Atrial natriuretic factor (ANF) and C-type natriuretic peptide (CNP)-activated guanylate cyclases are single-chain transmembrane-spanning proteins, containing both ligand binding and catalytic activities. In both proteins, ligand binding to the extracellular receptor domain activates the cytosolic catalytic domain, generating the second messenger cyclic GMP. Obligatory in this activation process is an ATP-dependent step. ATP directly binds to a defined ATP-regulatory module (ARM) sequence motif in the cyclases and through ARM bridges the events of ligand binding and signal transduction. These ARM sequence motifs are respectively represented by Gly503-Xa-Gly505-Xa-Xa-Xa-Gly509 and Gly499-Xa-Xa-Xa-Gly503 in the case of ANF receptor guanylate cyclase (ANF-RGC) and CNP receptor guanylate cyclase (CNP-RGC). Through genetic remodeling techniques, we now show that ARM-Gly505 in ANF-RGC and the corresponding ARM-Gly499 in CNP-RGC are critical for ANF and CNP signaling, and other ARM-Gly residues have minimal effect in the respective signaling processes.

Adenosine Triphosphate↗
PubMed1993

Membrane-associated N-myristoyltransferase activity is reduced in obese (fa/fa) Zucker rat liver.

N-Myristoyltransferase is the enzyme that catalyses the transfer of myristate from myristoyl-CoA to the NH2-terminal glycine residue of a number of protein of diverse functions. Many of the known myristoylated proteins are important in signal transduction. We have compared the activity of rat liver N-myristoyltransferase from lean and obese (fa/fa) Zucker rats (a model for non-insulin dependent diabetes mellitus, NIDDM). N-myristoyltransferase activity isolated from the particulate fraction of obese (fa/fa) Zucker rat liver was approximately 4.7-fold lower than the corresponding activity observed in either the controls or the vanadate-treated obese rat livers. This pattern was only observed in the particulate fraction; the homogenate and soluble N-myristoyltransferase activities were not significantly different to the control activities. N-myristoyltransferase activity isolated from the brain of the four groups showed no significant variations. These results, and previous work [King, M. J., Pugazhenthi, S., Khandelwal, R. L. and Sharma, R. K. (1993) Biochim. Biophys. Acta. 1165, 259-262], would indicate that the rat liver particulate N-myristoyltransferase activity appears to be inversely proportional to the level of plasma insulin, implicating insulin in the control of N-myristoylation. The specific activity of the particulate liver N-myristoyltransferase was approximately 10-fold higher than that of the soluble liver N-myristoyltransferase, raising the possibility that N-myristoyltransferase exists in 2 populations, with the active form of N-myristoyltransferase residing in the membranous fraction. This situation could provide a system whereby N-myristoylation is regulated by the translocation of N-myristoyltransferase from the cytosol to its active site in the membranes.

Acyltransferases↗