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Biomedical subjects

R K Sharma

Publications and source records attributed to R K Sharma.

At least 91 records · Page 5Linked to original sources
PubMed2001

Cyclosporin A withdrawal in live related renal transplantation: long-term results.

Cyclosporin A (CsA) withdrawal after 1 yr of stable graft function has been shown to be beneficial in cadaveric renal transplantation. This strategy could be even more suitable for 'immunologically advantaged' grafts as in live related renal transplantation. We report the long-term outcome of patients in a live related transplantation programme undergoing early (between 1989 and 1992) and late (1993 onwards) CsA withdrawal as compared with those on long-term low dose CsA (1993 onwards). Two-hundred and fifty-two patients were divided into three groups based on the following immunosuppressive protocol: group ECyW (n=99), early CsA withdrawal (9 months after transplantation); group LCyW (n=44), late CsA withdrawal (median 16 months, range 13--22 months after transplantation); and group LDCy (n=109), long-term low dose CsA. The median period of follow-up was 66 months after transplantation (range 43--84 months). There was no difference in the actuarial 6-yr patient or graft survival among the three groups. Acute rejection episodes were more frequent in ECyW (54.4%) than in LDCy (31.8%) and LCyW (23.8%) (p=0.001). The risk of developing late (> or =9 months) acute rejection was highest in ECyW 32/99 (32.3%) as compared with LCyW 8/44 (18.4%; p=0.08) and LDCy 8/109 (7.3%; p=0.0001). Of the 32 ECyW patients who developed acute rejection episodes after CsA withdrawal, 13 (40.6%) lost their grafts either due to uncontrolled acute rejection or to chronic rejection. Chronic rejection was higher in ECyW (24%) than in LCyW (11%; p=0.04) and LDCy (17%; p=0.17). Antihypertensive requirement was highest in patients maintained on low dose CsA. Graft function, as measured by serum creatinine levels, was significantly better in LCyW (1.24+/-0.4 mg%) as compared with ECyW (1.49+/-0.5 mg%) and LDCy (1.48+/-0.6 mg%). Early CsA withdrawal after live related renal transplantation is associated with a significant risk of acute rejection and subsequent chronic rejection. Slow withdrawal after 1 yr is safe and more economical than the long-term administration of low dose CsA.

Acute Disease↗
PubMed2001

Prognostic factors for persistent distal renal tubular acidosis after surgery for posterior urethral valve.

Risk factors, including age at presentation, age at surgery, time between presentation and surgery, urodynamic abnormalities, and vesicoureteric reflux, were prospectively studied for the development of distal renal tubular acidosis (DRTA) before surgery and persistent DRTA after surgery in 24 boys with posterior urethral valve (PUV) with normal serum creatinine levels. DRTA was persistent in 11 of 17 boys (65%) at the end of follow-up after intervention. For the development of DRTA before surgery, only a longer time between presentation and surgery (intervening period) turned out to be a significant risk factor on multivariate analysis (beta = -0.13; P = 0.04). Boys with persistent DRTA after surgery had older age at presentation (P = 0.03), older age at surgery (P = 0.001), a longer intervening period (P = 0.0007), and bilateral or severe unilateral reflux (P = 0.04) before surgery. On univariate logistic regression, age at surgery (beta = -0.07; P = 0.04) and intervening period (beta = -0.13; P = 0.02) were found to be significant risk factors for persistent DRTA, but on multivariate analysis, only intervening period was found to be significant (beta = -0.13; P = 0.02). A delay in intervention after noticing voiding symptoms can predict a high incidence of DRTA before intervention and persistent DRTA after surgery in boys with PUV.

Acidosis, Renal Tubular↗
PubMed2001

Decreased expression of high-molecular-weight calmodulin-binding protein and its correlation with apoptosis in ischemia-reperfused rat heart.

A cardiac high-molecular-weight calmodulin-binding protein (HMWCaMBP) was previously identified as a homologue of the calpain inhibitor, calpastatin. In the present study, we investigated the expression of HMWCaMBP and calpains in rat heart after ischemia and reperfusion. Western blot analysis of normal rat heart extract with a polyclonal antibody raised against bovine HMWCaMBP indicated a prominent immunoreactive band of 140kDa. Both the expression and the activity of HMWCaMBP were decreased by ischemia reperfusion. Immunohistochemical studies showed strong-to-moderate HMWCaMBP immunoreactivity in normal heart and poor immunoreactivity in ischemia-reperfused heart muscle. However, the expression of micro-calpain and m-calpain in ischemia-reperfused heart was increased as compared to normal heart. The calpain inhibitory activity of ischemia-reperfused heart tissues was significantly lower as compared to normal heart tissues. The pre-ischemic and post-ischemic perfusion of hearts with a cell-permeable calpain inhibitor suppressed the increase in calpain expression but increased the HMWCaMBP expression. In-vitro HMWCaMBP was proteolyzed by micro-calpain and m-calpain. We also measured apoptosis in normal and ischemia-reperfused tissues. An increase in the number of apoptotic bodies was observed with increased duration of ischemia and reperfusion. Bcl-2 expression did not change in any of the groups, whereas Bax expression increased with ischemia-reperfusion and correlated well with the degree of apoptosis. Our findings suggest that HMWCaMBP may sequester calpains from its substrates in the normal myocardium, but it is susceptible to proteolysis by calpains during ischemia-reperfusion. Thus, decreased expression of HMWCaMBP may play an important role in myocardial injury.

Animals↗
PubMed2001

Expression of Bcl-2 during the development of rabbit retina.

AIM: Programmed cell death or apoptosis plays an important role in retinal development. Bcl-2 is one of the genes whose endproducts regulate apoptosis. This study has examined the expression of Bcl-2 during the development of rabbit retina. METHOD: Bcl-2 was detected by immunohistochemistry in developing rabbit retinas from embryonic day (E) 15, 22, 26, 29 and postnatal day (PN) 0, 3, 7, 15 and adults. RESULTS: Faint immunoreactivity in the anuclear layer was observed at E 15, which increased in E 19. Immunoreactivity in certain radially aligned neuroepithelial cells/immature Müller cells could be recognized at E 22 and it progressively increased until in mature Müller cells radial processes were immunoreactive beyond the outer plexiform layer in PN 15 retinas. Immunoreactivity was already present in the optic nerve at E 15 but it decreased with increasing age until it disappeared at the time of birth. CONCLUSIONS: Observations suggest that Bcl-2 is transiently expressed by ganglion cell axons during embryonic development. Detection of Bcl-2 immunoreactivity in the endfeet and proximal processes of radially aligned neuroepithelial cells/immature Müller cells early during the development, and its persistence in the endfeet and much of radial processes of Müller cells in adult life suggest that these cells possibly play a role in the development of the retinal ganglion cells, and also in the maintenance of the retinal neurons in the adults.

Animals↗
PubMed2001

Development and survival of tyrosine hydroxylase containing neurons in RCS rat retinae.

AIM: Dopamine serves a variety of functions in the retina. Abnormalities of the retinal dopaminergic system have been described in the Royal College of Surgeons (RCS) rat as well as other models of retinal degeneration. Dopamine has been implicated in several retinal dysfunctions of retinitis pigmentosa. Dopaminergic amacrine cells respond to light by increasing their tyrosine hydroxylase (TH) activity and the rate of dopamine turnover. This study has, therefore, examined the ontogenesis of TH containing cells in the RCS rat retina to assess whether progressive photoreceptor degeneration affects the development or survival of TH containing cells in any way. METHODS: TH immunoreactivity in developing dystrophic RCS rat retinae (postnatal day (PN) 0, 3, 6, 14, 18, 26, 32, 56, 85, 91, 12 month and 15 month) and normal retina (PN day 0, 6, 14, 19, 26, 30, 33, 54 and adults) was compared. RESULTS: TH immunoreactivity in dystrophic retina closely resembled that in normal retina. In both groups, very faintly immunoreactive cells were detected in the proximal retina at PN 0. Immunoreactivity increased until PN 14, when faintly immunoreactive interplexiform (IP) fibers and fibers in the outer plexiform layer could be observed. In both groups, the IP connections reached their mature level of development at about PN 30. Thus the developmental expression of TH immunoreactive cells resembled that of non-dystrophic retina in both chronology as well as types of cells. These cells survived even in the advanced stages of degeneration. CONCLUSIONS: The results suggest that the abnormalities in the dopaminergic system of the RCS retinae are not associated with abnormal ontogeny or survival of TH synthesizing cells.

Aging↗
PubMed2001

A study of quetiapine: efficacy and tolerability in psychotic adolescents.

OBJECTIVE: To study the effectiveness, safety, and tolerability of quetiapine in adolescents with psychotic disorders. METHODS: This study was an 8-week, open trial using quetiapine with 15 adolescents, ages 13-17 years, mean age 15.1 years, with a diagnosis of a psychotic disorder. Our primary instruments focused on psychotic symptomatology as measured by the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), Positive and Negative Syndrome Scale (PANSS), and the Young Mania Rating Scale (YMRS). Other measures included adverse events, clinical laboratory tests, vital signs, electrocardiogram (ECG), extrapyramidal (EPS) measures, and ophthalmologic examination. RESULTS: Quetiapine significantly reduced psychotic symptoms as measured by the BPRS, PANSS, YMRS, CGI, and CGI Severity of Illness scale. The average weight gain was 4.1 kg. After correction for expected weight gain, the mean weight gain over the 8-week period was 3.4 kg. Prolactin and cholesterol remained unchanged. Trends were found for a decrease in T4 and an increase in thyroid-stimulating hormone. Common adverse effects were somnolence, agitation, drowsiness, and headache. No significant findings were noted on repeat ECGs, EPS measures, or ophthalmic examination. The final average treatment dose was 467 mg/day (range 300-800 mg/day). CONCLUSIONS: Quetiapine is suggested to be effective treatment of youths with psychotic disorders and to have a favorable side-effect profile.

Adolescent↗
PubMed2001

Characterization of subsets of human spermatozoa at different stages of maturation: implications in the diagnosis and treatment of male infertility.

BACKGROUND: Reactive oxygen species (ROS)-induced damage of membrane phospholipids and DNA in human spermatozoa has been implicated in the pathogenesis of male infertility. In this study, variations in ROS production, DNA structure (as measured by the sperm chromatin structure assay) and lipid composition, were studied in human spermatozoa at different stages of maturation. METHODS: Sperm subsets were isolated by discontinuous density gradient centrifugation of semen samples obtained from healthy donors and from infertility patients. RESULTS: DNA damage and ROS production were highest in immature spermatozoa with cytoplasmic retention and abnormal head morphology, and lowest in mature spermatozoa. Docosahexaenoic acid and sterol content were highest in immature germ cells and immature spermatozoa, and lowest in mature spermatozoa. The relative proportion of ROS-producing immature spermatozoa in the sample was directly correlated with DNA damage in mature spermatozoa, and inversely correlated with the recovery of motile spermatozoa. There was no correlation between DNA damage and sperm morphology in mature spermatozoa. CONCLUSIONS: The high levels of ROS production and DNA damage observed in immature spermatozoa may be indicative of derangements in the regulation of spermiogenesis. DNA damage in mature spermatozoa may be the result of oxidative damage by ROS-producing immature spermatozoa during sperm migration from the seminiferous tubules to the epididymis.

Cellular Senescence↗
PubMed2001

Differential production of reactive oxygen species by subsets of human spermatozoa at different stages of maturation.

BACKGROUND: Reactive oxygen species (ROS)-mediated damage to human spermatozoa has been implicated in the pathogenesis of male infertility. Although ROS production by human spermatozoa has been extensively studied, the cell-to-cell variation in ROS production by spermatozoa at different stages of maturation has never been investigated. METHODS: In this study, we determined ROS production by subsets of human spermatozoa at different stages of maturation isolated by density gradient centrifugation of ejaculated spermatozoa obtained from healthy donors and from patients attending a clinic for infertility screening. RESULTS: Four different fractions were obtained. ROS production was highest in immature spermatozoa with abnormal head morphology and cytoplasmic retention and lowest in mature spermatozoa and immature germ cells (P < 0.01). ROS production was highest in immature spermatozoa from males with abnormal semen parameters compared with donors (P < 0.0001) or patients with normal semen parameters (P = 0.015). ROS production by immature spermatozoa was inversely correlated with the recovery of motile, mature spermatozoa in the high density fraction 4 (P = 0.01). CONCLUSIONS: The results of this study indicate that there is significant cell-to-cell variation in ROS production in subsets of spermatozoa at different stages of maturation and that oxidative damage of mature spermatozoa by ROS-producing immature spermatozoa during sperm migration from the seminiferous tubules to the epididymis may be an important cause of male infertility.

Cellular Senescence↗
PubMed2001

Pulse cyclophosphamide therapy in frequently relapsing nephrotic syndrome.

BACKGROUND: The treatment of frequently relapsing (FR) and steroid-dependent (SD) idiopathic nephrotic syndrome (INS) with oral cyclophosphamide (OCP) poses problems of compliance, side-effects and infections. METHODS: We prospectively evaluated the usefulness of intravenous cyclophosphamide (IVCP) in children with steroid sensitive INS who were frequent relapsers or steroid dependent. Fifty-one children were included in the study of whom 22 were FR and 29 were SD. IVCP was administered in a dose of 500 mg/m(2)/month for 6 months after achieving a steroid-induced remission. The response to IVCP was evaluated in terms of remission, change in the steroid response status of the patient, duration of remission (i.e. proteinuria-free days), side effects and compliance with therapy. RESULTS: The proteinuria-free days (mean 19.9+/-3.5 before IVCP therapy vs 1256+/-167 days after IVCP therapy) (P<0.00001), and serum albumin levels (23+/-1.6 g/l before IVCP therapy vs 34+/-2 g/l after IVCP therapy) (P<0.001) were significantly higher following IVCP therapy. The cumulative remission rate in the study group was 49% at 5 years and was comparable to that achieved with oral cyclophosphamide at a 40% lower cumulative dose. CONCLUSIONS: We conclude that IVCP is a safe and effective therapeutic modality in children with INS who are FR and SD. Its efficacy is comparable to the results obtained with oral cyclophosphamide based on historical comparisons with previous studies.

Adolescent↗
PubMed2001

Split gluteus maximus island flaps for concomitant closure of ischial and sacral pressure sores.

The author presents an innovation in the use of the gluteus maximus musculocutaneous flap that allows one to repair both sacral and ischial pressure sores concomitantly in a paraplegic patient. The musculocutaneous unit is divided into superior and inferior halves, each of which is supplied by their respective gluteal arteries. The "islanded" flaps can be moved in different directions independent of one another to cover both the sacral and ischial regions at the same time. The donor area can be closed primarily. Three patients were operated using this method. The 1-year follow-up of 1 patient is presented.

Debridement↗
PubMed2001

Allosteric regulatory step and configuration of the ATP-binding pocket in atrial natriuretic factor receptor guanylate cyclase transduction mechanism.

The atrial natriuretic factor (ANF) signal transduction mechanism consists of the transformation of the signal information into the production of cyclic GMP. The binding of ANF to its receptor, which is also a guanylate cyclase, generates the signal. This cyclase has been termed atrial natriuretic factor receptor guanylate cyclase, ANF-RGC. ANF-RGC is a single transmembrane-spanning protein. The ANF receptor domain resides in the extracellular region of the protein, and the catalytic domain is located in the intracellular region at the C-terminus of the protein. Thus, the signal is relayed progressively from the receptor domain to the catalytic domain, where it is converted into the formation of cyclic GMP. The first transduction step is the direct binding of ATP with ANF-RGC. This causes allosteric regulation of the enzyme and primes it for the activation of its catalytic moiety. The partial structural motif of the ATP binding domain in ANF-RGC has been elucidated, and it has been named ATP regulatory module (ARM). In this presentation, we provide a brief review of the ATP-regulated transduction mechanism and the ARM model. The model depicts a configuration of the ATP-binding pocket that has been experimentally validated, and the model shows that the ATP-dependent transduction process is a two- (or more) step event. The first step involves the binding of ATP with its ARM. This partially activates the cyclase and prepares it for the subsequent steps, which are consistent with its being phosphorylated and attaining the fully activated state.

Adenosine Triphosphate↗
PubMed2001

Isolated tubercular splenic abscess.

Splenic abscess due to tuberculosis is extremely rare in immunocompetent individuals. We report a case of tubercular splenic abscess (TSA) in an immunocompetent individual for its rarity.

Abscess↗
PubMed2001

Nutrition in dialysis patients.

Adequate nutrition is very important for dialysis patients for a better overall outcome. Protein energy malnutrition is highly prevalent (25-50%) among dialysis patients and is associated with increased morbidity and mortality. Causes of malnutrition in dialysis patients include anorexia (inadequate calorie or protein intake), metabolic acidosis (stimulation of amino acid and protein degradation), and infection/inflammation (stimulation of protein degradation). Anorexia resulting into decreased intake is probably the most important factor. Nutritional assessment can be done by anthropometric measurements, laboratory parameters, subjective global assessment, dialysis malnutrition score, near infra-red interactance and other methods. Subjective global assessment is currently the most accepted one and classifies patients into three nutritional categories: Well nourished, moderately malnourished, and severely malnourished. Prevention of malnutrition by proper dietary counselling and adequate dietary intake starting from redialysis days is probably the most effective therapeutic approach. Other therapeutic approaches include adequate dialysis delivery, avoidance of acidaemia, aggressive treatment of catabolic illnesses and food supplements: Oral, enteral or parenteral, particulary intradialytic parenteral nutrition. Experimental approaches for treatment of malnutrition in dialysis patients include amino acids in peritoneal or haemodialysate, appetite stimulants and use of recombinant human growth hormone and insulin like growth factor I. There are few randomised controlled trials unequivocally proving the efficacy of any treatment modality. Large scale, randomised trials are urgently needed to establish effective therapy for malnutrition in dialysis patients. This applies more so for Indian patients.

Humans↗
PubMed2001

Multiple myeloma presenting as proptosis and sixth nerve palsy.

Cranial and intracranial locations are rare in multiple myeloma (MM). But their occurrence has a particular significance. Proptosis and 6th nerve palsy is very uncommon presentation. We report a case of MM with presenting features as proptosis and 6th nerve palsy.

Abducens Nerve Diseases↗
PubMed2001

Analysis of quantitative relationship between viability determination in leprosy by MFP, ATP bioluminescence and gene amplification assay.

Two hundred twenty-one untreated, borderline lepromatous/lepromatous (BL/LL) leprosy patients have been investigated for viability by the mouse foot pad method (MFP), adenosine triphosphate (ATP) and polymerase chain reaction (PCR). The biopsies were collected at the beginning of and 12/24 months after treatment. The patient group was treated with a) immunotherapy (BCG/Mw) + MDT; b) MDT + pyrazinamide; c) control MDT; d) MDT + minocycline 100 mg once a month supervised + ofloxacin 400 mg once a month supervised. Biopsies were divided in three parts for use in the mouse foot pad, molecular and ATP investigations. In untreated and treated patients (at 12 and 24 months), there was a general agreement among all three techniques, and PCR and ATP showed higher positivity as compared to MFP. Further, there was good correlation among the viable biomass estimated by bacillary ATP levels, PCR assay and growth in mouse foot pads. The positivity was observed by MFP as well as PCR assay (18-kDa and 36-kDa) from all of the specimens when the ATP content was more than 3.6 pg/million. When the ATP content was below 3.5 pg/million, the positive takes in MFP decreased but the PCR positivity correlated with ATP bioluminescence up to 0.04 pg/million. When the ATP content was even lower, the uptake in the MFP was possibly a matter of chance, while PCR positivity was observed in 96% of the cases. For specimens with undetectable ATP, positivity was seen in 1% of the cases, showing the inability of ATP bioluminescence method to detect low background due to host ATP. PCR signals in some cases could be due to the higher sensitivity of the method or persistence of DNA after bacterial death in some cases. On the whole, the PCR methods even though targeting DNA have shown good correlations with biomass which confirm their usefulness in monitoring therapeutic responses in leprosy.

Adenosine Triphosphate↗