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N Sharma

Publications and source records attributed to N Sharma.

At least 19 recordsLinked to original sources

A randomized controlled clinical trial to evaluate the efficacy, safety, cost-effectiveness and effect on PAI-1 levels of the three low-molecular-weight heparins--enoxaparin, nadroparin and dalteparin. The ESCAPe-END study.

BACKGROUND: Comparative data for efficacy and safety between various low-molecular-weight heparins (LMWHs) in patients with unstable angina is not available. The present study was conducted to compare the efficacy, safety, cost-effectiveness and effects on plasminogen activator inhibitor-1 (PAI-1) levels of three LMWHs--enoxaparin, nadroparin and dalteparin. METHODS: The study was a prospective, randomized, comparative, open with blinded endpoints (PROBE design) assessment with a 30-day follow-up. The primary endpoint of efficacy was a composite of cardiovascular death, myocardial infarction, recurrent angina and need for intervention. Cost-effectiveness was calculated by calculating the incremental cost-effectiveness ratio. Plasma PAI-1 levels were estimated by ELISA. RESULTS: A total of 150 patients were available for intention-to-treat analysis. There was no significant difference at 30 days in the primary endpoint or in any of the individual components in the three groups. The secondary endpoint of silent ischemia was also not significantly different. Adverse events were similar in the three groups. The PAI-1 levels were not significantly different in the three groups. The total cost of treatment in the three groups was similar. CONCLUSION: Any of the three LMWHs evaluated in this study were similar with respect to efficacy, safety, PAI-1 levels and cost-effectiveness.

Adult↗

Altered responses to dopaminergic D2 receptor activation and N-type calcium currents in striatal cholinergic interneurons in a mouse model of DYT1 dystonia.

Early-onset torsion dystonia (DYT1) is an autosomal dominant disease caused by a deletion in the gene encoding the protein torsinA. Recently, a transgenic mouse model of DYT1 has been described, expressing either the human wild-type torsinA (hWT) or mutant torsinA (hMT). We recorded the activity of striatal cholinergic interneurons of hWT, hMT, and control mice. In slice preparations, no significant differences were observed in resting membrane potential (RMP), firing activity, action potential duration or Ih current. Quinpirole, a D2-like dopamine receptor agonist, did not produce detectable effects on RMP of cholinergic interneurons in control mice and hWT mice, but in the hMT mice caused membrane depolarization and an increase in the firing rate. D2 receptor activation inhibits N-type high-voltage-activated calcium currents. We found that, in isolated interneurons from hMT mice, the quinpirole-mediated inhibition of N-type currents was significantly larger than in hWT and controls. Moreover, the N-type component was significantly over-represented in hMT mice. The altered sensitivity of N-type channels in hMT mice could account for the paradoxical excitatory effect of D2 stimulation. Our data support the existence of an imbalance between striatal dopaminergic and cholinergic signaling in DYT1 dystonia.

Acetylcholine↗

Risk factors for postoperative cylindrical prediction error after laser in situ keratomileusis for myopia and myopic astigmatism.

PURPOSE: To study the risk factors for the occurrence of cylindrical prediction error (PE) after laser in situkeratomileusis (LASIK) for myopia and myopic astigmatism. METHODS: The study was a nested case-control study. Five hundred eyes of 252 consecutive patients who underwent LASIK for myopia and myopic astigmatism on the Chiron Technolas 217C laser and completed 6 months of follow-up. There were 435 controls and 65 cases based on the postoperative refractive cylindrical PE. The probable risk factors studied included preoperative sphere and cylinder, keratometry, pachymetry, suction ring used, flap thickness, hinge centeration, optic zone, ablation depth, and intraoperative complications. RESULTS: By univariate analysis, the cylindrical PE was found to be associated with preoperative spherical equivalent higher than -6 D (chi(2)=10.83; P=0.001), preoperative sphere higher than -6 D (chi(2)=6.15, P=0.013), preoperative cylinder more than -0.75 D (chi(2)=6.61; P-value=0.010), and an optic zone less than 5.5 mm (chi(2)=19.3; P=0.001). Risk factors for postoperative astigmatism by stepwise multivariate logistic regression analysis were an optic zone of less than 5.5 mm with an odds ratio (OR) of 2.81 (95% confidence interval (CI)=1.62-4.86) and preoperative cylinder more than -0.75 D with an OR of 1.60 (95% CI=0.92-2.77). CONCLUSION: Postoperative astigmatism (as indicated by the cylindrical PE) is more likely to occur with an optic zone of less than 5.5 mm and a higher preoperative cylindrical error.

Adult↗

Nuclear-mitochondrial genomic profiling reveals a pattern of evolution in epithelial ovarian tumor stem cells.

Analyses of genome orthologs in cancer on the background of tumor heterogeneity, coupled with the recent identification that the tumor propagating capacity resides within a very small fraction of cells (the tumor stem cells-TSCs), has not been achieved. Here, we describe a strategy to explore genetic drift in the mitochondrial genome accompanying varying stem cell dynamics in epithelial ovarian cancer. A major and novel outcome is the identification of a specific mutant mitochondrial DNA profile associated with the TSC lineage that is drastically different from the germ line profile. This profile, however, is often camouflaged in the primary tumor, and sometimes may not be detected even after metastases, questioning the validity of whole tumor profiling towards determining individual prognosis. Continuing mutagenesis in subsets with a mutant mitochondrial genome could result in transformation through a cooperative effect with nuclear genes - a representative example in our study is a tumor suppressor gene viz. cAMP responsive element binding binding protein. This specific profile could be a critical predisposing step undertaken by a normal stem cell to overcome a tightly regulated mutation rate and DNA repair in its evolution towards tumorigenesis. Our findings suggest that varying stem cell dynamics and mutagenesis define TSC progression that may clinically translate into increasing tumor aggression with serious implications for prognosis.

Adenocarcinoma, Papillary↗

Phacoemulsification with nondominant hand.

PURPOSE: Evaluation of on axis phacoemulsification surgery through temporal incision using nondominant hand with surgeon sitting at the head end, inpatients with against-the-rule astigmatism. METHODS: Eighty eyes of 80 patients who underwent phacoemulsification through a temporal clear corneal tunnel for age-related cataract and against-the-rule astigmatism were enrolled and divided into four equal groups. In Group 1A, the surgeon was sitting at the head end for the left eye performing surgery with the left hand (nondominant hand). In group 1B, the surgeon was seated at the temporal side and surgery was performed in the left eye with dominant right hand. In group 2A, the surgeon was sitting at the head end for the right eye and performed surgery holding the phacoemulsification hand piece in his right hand. In group 2B, the surgeon sat on the temporal side of the right eye and performed phacoemulsification with his right hand. The patients were followed up on day 7, 1 month, and 3 months. Parameters evaluated included average phaco power, effective phaco time, uncorrected and best-corrected visual acuity, keratometry, intraocular pressure, surgically induced astigmatism, pachymetry, and endothelial cell counts. RESULTS: The phaco time and phaco power among the four groups were comparable (phaco time: P=0.368; phaco power: P=0.294). The four groups were also comparable on parameters like surgically induced astigmatism (P=0.674), change in postoperative keratometric astigmatism (P=0.584), endothelial cell loss (0.921), change in ultrasonic pachymetry (P=0.476), and intraocular pressure (P=0.942). No intraoperative or postoperative complications were observed in any of the groups. The mean uncorrected visual acuity at 3 months in group 1 was 0.723+/-0.21; in group 2 it was 0.756+/-0.21; in group 3 it was 0.748+/-0.22, and in group 4 it was 0.732+/-0.23. The best-corrected visual acuity was 0.96+/-0.10, 0.97+/-0.11, 0.95+/-0.13, and 0.96+/-0.10 in the four groups at 3 months. CONCLUSION: Phacoemulsification surgery can be successfully performed with nondominant hand with a good surgical outcome. The technique gives an alternative approach where surgeon does not have to shift the position to perform on-axis phacoemulsification.

Aged↗

Modulation of iron transport proteins in human colorectal carcinogenesis.

BACKGROUND AND AIMS: Total body iron and high dietary iron intake are risk factors for colorectal cancer. To date there is no comprehensive characterisation of iron transport proteins in progression to colorectal carcinoma. In this study, we examined expression of iron import (duodenal cytochrome b (DCYTB), divalent metal transporter 1 (DMT1), and transferrin receptor 1 (TfR1)) and export (hephaestin (HEPH) and ferroportin (FPN)) proteins in colorectal carcinoma. METHODS: Perl's staining was used to examine colonocyte iron content. Real time polymerase chain reaction (PCR) and western blotting were used to examine mRNA and protein levels of the molecules of interest in 11 human colorectal cancers. Semiquantitative immunohistochemistry was used to verify protein levels and information on cellular localisation. The effect of iron loading on E-cadherin expression in SW480 and Caco-2 cell lines was examined by promoter assays, real time PCR and western blotting. RESULTS: Perl's staining showed increased iron in colorectal cancers, and there was a corresponding overexpression of components of the intracellular iron import machinery (DCYTB, DMT1, and TfR1). The iron exporter FPN was also overexpressed, but its intracellular location, combined with reduced HEPH levels, suggests reduced iron efflux in the majority of colorectal cancers examined. Loss of HEPH and FPN expression was associated with more advanced disease. Iron loading Caco-2 and SW480 cells caused cellular proliferation and E-cadherin repression. CONCLUSIONS: Progression to colorectal cancer is associated with increased expression in iron import proteins and a block in iron export due to decreased expression and aberrant localisation of HEPH and FPN, respectively. This results in increased intracellular iron which may induce proliferation and repress cell adhesion.

Antigens, CD↗

Risk factors for perforation in microbial corneal ulcers in north India.

AIM: To identify predisposing factors leading to corneal perforation in patients with microbial keratitis. METHOD: Two groups of 60 patients each, with perforated corneal ulcers and healed/healing corneal ulcers, respectively, were recruited in a case-control study conducted in northern India. The cases and controls were matched by age and time of presentation. A standardised proforma was used to identify potential predisposing factors for demographic, social, medical, ocular, and treatment history. All participants underwent a detailed ocular examination. Corneal scrapings were performed where relevant. RESULTS: The characteristics associated with corneal perforation in microbial keratitis were outdoor occupation (p = 0.005), illiteracy (p = 0.02), excessive alcohol use (p = 0.03), history of "something falling into eye" (p = 0.003), trauma with vegetable matter (p = 0.008), vision less than counting fingers at referral (p<0.001), central location of ulcer (p<0.001), lack of corneal vascularisation (p<0.001), delay in starting initial treatment (p<0.001), failure to start fortified antibiotics (p<0.001), and monotherapy with fluoroquinolones (p = 0.002). The lack of corneal vascularisation (OR 6.4, 95% CI 4.2 to 13.5), delay in starting initial treatment (OR 35.6, 95% CI 6.9 to 68.2), and failure to start fortified antibiotics (OR 19.9, 95% CI 2.7 to 64.7) retained significance on a logistic regression model. CONCLUSIONS: This study characterises microbial keratitis cases at increased risk of corneal perforation and reinforces the need for standardised referral and treatment protocols for patients with corneal ulcer on their first contact at primary care level in the developing world.

Adult↗

Laparoscopic total extraperitoneal repair versus anterior preperitoneal repair for inguinal hernia.

Laparoscopic inguinal hernia repair is still not the gold standard for repair although mesh implantation is unequivocally accepted as an integral part of any groin hernia repair. The aim of the study was to compare the results of anterior preperitoneal (APP) mesh repair with totally extra peritoneal (TEP) repair for inguinal hernias. The prospective study was conducted on 241 patients with 247 hernias (from January 2000 to June 2004). Anterior preperitoneal repair was done in 121 patients and 120 patients were subjected to TEP repair. Repair in both groups was done by using Prolene mesh of size 6x4 in. or 6x6 in. intraoperative and postoperative parameters and complications were recorded and the patients were followed up to 1 year post-surgery. For both unilateral and bilateral inguinal hernias, mean operative time was significantly more in patients of TEP repair as compared to APP repair (P<0.001) and significantly more patients had peritoneal tears in the TEP group (P<0.001). Patients undergoing TEP repair, however, had significantly less postoperative pain (P<0.05) and postoperative hospital stay (P<0.05) and return to work was significantly earlier is this group (P<0.01 and P<0.001). There was no difference in the recurrence rate between the two groups. Patients with inguinal hernias undergoing laparoscopic repair recover more rapidly, and have less incidence of postoperative pain. But it takes significantly more time to perform than APP repair and also the incidence of peritoneal tear is higher.

Adolescent↗

Isolation, structure elucidation and in vivo hepatoprotective potential of trans-tetracos-15-enoic acid from Indigofera tinctoria Linn.

The bioassay guided fractionation of the dried aerial part of Indigofera tinctoria Linn. led to the identification of an active fraction labelled as indigotin. On further chemical analysis, a compound isolated from indigotin was identified and characterized as trans-tetracos-15-enoic acid (TCA). The chemical structure of this compound was established on the basis of physical properties and spectral data, including NMR. It afforded significant hepatoprotection against carbon tetrachloride and paracetamol induced hepatotoxicity in experimental models. Silymarin, a well known plant based hepatoprotective agent, and N-acetylcysteine, which has proven efficacy as a replenisher of sulfhydryls, were used for relative efficacy. TCA was found to reverse the altered hepatic parameters in experimental liver damage. In the safety evaluation study the oral LD50 was found to be more than 2000 mg/kg, with no signs of abnormalities or any mortality for the 15 day period of observation after administration of a single dose of drug in mice. The studies revealed significant and concentration dependent hepatoprotective potential of TCA as it reversed the majority of the altered hepatic parameters in experimental liver damage in rats and mice and may be useful in the management of liver disorders.

Acetaminophen↗

Noradrenaline and albumin in paracentesis-induced circulatory dysfunction in cirrhosis: a randomized pilot study.

OBJECTIVE: Therapeutic paracentesis in patients with cirrhosis is associated with a circulatory dysfunction. Intravenous albumin has been used to prevent the circulatory dysfunction; however, the use of albumin is controversial and costly. Splanchnic vasodilation is mainly responsible for circulatory dysfunction in these patients. There are no reports of use of noradrenaline, a vasoconstrictor, on the prevention of paracentesis-induced circulatory dysfunction in patients with cirrhosis. Therefore, we studied the preventive effect of noradrenaline on paracentesis-induced circulatory dysfunction in patients with cirrhosis after therapeutic paracentesis and compared it with that of intravenous albumin in a randomized pilot study. METHODS: Forty patients with cirrhosis and tense ascites underwent therapeutic paracentesis with albumin or noradrenaline in a randomized controlled trial at a tertiary centre. Effective arterial blood volume was assessed by measuring plasma renin activity at baseline and at 6 days after treatment. RESULTS: Effective arterial blood volume as indicated by plasma renin activity before and 6 days after paracentesis did not differ in the two groups (20.62 +/- 10.27-22.02 +/- 10.15 ng mL(-1) h(-1); P = 0.11 in the albumin group and 19.66 +/- 8.91-20.78 +/- 9.41 ng mL(-1) h(-1); P = 0.37 in the noradrenaline group). Plasma aldosterone concentration before and 6 days after paracentesis were also similar in both groups (1196.5 +/- 434.2-1217.0 +/- 405.7 pg mL(-1); P = 0.7 in the albumin group and 1206.0 +/- 522.5-1273.5 +/- 444.8 pg mL(-1); P = 0.22 in the noradrenaline group). The cost of noradrenaline treatment was significantly lower when compared with that of albumin (P < 0.001). CONCLUSIONS: Noradrenaline is as effective as albumin in preventing paracentesis-induced circulatory dysfunction in patients with cirrhosis after therapeutic paracentesis, but at a fraction of the cost.

Adult↗

HIV immunosupression and malaria: is there a correlation?

The human immunodeficiency virus (HIV) epidemic has resulted in an increase in the prevalence of many opportunistic infections and has caused re-emergence of certain diseases in the developing world. In tropical countries, immunosupression due to HIV infection has resulted in changes in the clinical presentation of endemic infections. Although the immune deficiency caused by HIV infection should presumably lead to an increased frequency of clinical malaria in areas with endemic malarial infection, like India, evidence of the association between HIV and malaria in India is scanty, with only a few studies showing a positive correlation. We hereby report a case of concurrent infection with Plasmodium falciparum malaria and human immunodeficiency virus type 1 (HIV-1) in a young male patient.

Adult↗

Prevalence and control of pathogenic contamination in some sewage irrigated vegetable, forage and cereal grain crops.

A total of 344 samples comprising of different vegetables, fodder and grain crops were obtained from a long-term experiment under sewage irrigation. The aerobic bacterial plate counts for vegetables, fodder and grain crops ranged between 2 x 10(6) and 3.5 x 10(7), 6 x 10(6) and 3 x 10(8), 2 x 10(5) and 3.8 x 10(10), respectively, while the corresponding Faecal coliform ranged between < 2 and 9 x 10(5), 9 x 10(2) and 2 x 10(5) and < 2, indicating that the pathogenic loads got reduced below permissible level in the produce that was harvested after sun drying in the field itself, whereas the parts coming in direct contact were the most severely contaminated. The health hazards could be markedly lowered with adoption of some of the low cost practices such as repeated washings, exposure of the produce to sunlight and raising the crops on beds. The coliform counts in vegetables were within permissible limits by two washings with water, exposing these to sunlight for about 4 h and removing the two outmost leaves of cabbage. Also, cutting above some height from ground level (0.10 m) in sorghum reduced the pollution load in fodder crops.

Agriculture↗

Medical treatments for the maintenance therapy of reflux oesophagitis and endoscopic negative reflux disease.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) - reflux of stomach contents +/- bile into the oesophagus causing symptoms such as heartburn and acid reflux - is a common relapsing and remitting disease which often requires long-term maintenance therapy. Patients with GORD may have oesophagitis (inflammation of the oesophagus) or a normal endoscopy (endoscopy negative reflux disease or ENRD). OBJECTIVES: To assess the effects of continuous maintenance therapy in adults with GORD (both ENRD and healed oesophagitis). SEARCH STRATEGY: We searched Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), CINAHL (1982-2003), and the National Research Register (Issue 2, 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Randomised controlled studies comparing PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo in adults with reflux oesophagitis and ENRD. DATA COLLECTION AND ANALYSIS: One author extracted data from included trials and a second author carried out an unblinded check. Two authors independently assessed trial quality. Study authors were contacted for additional information. MAIN RESULTS: Maintenance of patients with healed oesophagitis: For a healing dose of PPI (generally the standard dose given by the manufacturer) versus placebo, the relative risk (RR) for oesophagitis relapse was 0.26 (95% confidence interval (CI) 0.19 to 0.36); versus H2RAs the RR was 0.36 (95% CI 0.28 to 0.46) and versus maintenance PPIs the RR was 0.63 (95% CI 0.55 to 0.73). However overall adverse effects were also more common and headaches were more common when comparing healing PPIs to H2RAs. For a maintenance dose of PPI (half of the standard dose) versus placebo, the RR for oesophagitis relapse was 0.46 (95% CI 0.38 to 0.57) and versus H2RAs the RR was 0.57 (95% CI 0.47 to 0.69). Overall adverse effects were more common.H2RAs were of marginal help but beneficial for symptomatic relief. Prokinetics and sucralfate were also more effective than placebo. For ENRD patients: Limited data with one RCT showed benefit for omeprazole 10 mg once daily over placebo (RR 0.4; 95% CI 0.29 to 0.53). AUTHORS' CONCLUSIONS: The findings in this review support the long-term treatment of oesophagitis to prevent relapse, both endoscopically and symptomatically. Healing doses of PPIs are more effective than all other therapies, although there is an increase in overall adverse effects compared to placebo, and headache occurrence compared to H2RAs. H2RAs prevent relapse more effectively than placebo, demonstrating a role for PPI-intolerant patients. Prokinetics and sucralfate both show benefit over placebo, but the former is no longer licenced. There is only limited data for ENRD.

Adult↗

Adaptogenic activity of glyco-peptido-lipid fraction from the alcoholic extract of Trichopus zeylanicus Gaerten (part II).

Anti-stress activity was carried out on glyco-peptido-lipid (AF) fraction from the alcoholic extract of Trichopus zeylanicus Gaerten and demonstrated against a battery of tests in rats and mice. AF exhibited significant anti-stress activity in dose-related manners in all the parameters studied against different models used to induce non-specific stress viz physical and chemically. The major parameters studied were immobilization induced gastric ulceration, adjuvant-induced trauma (Stress); humoral antibody synthesis in normal and immuno-suppressed mice and delayed type of hypersensitivity (DTH) reaction, chemically stress-induced alteration in hepatic function and anti-oxidant activity. The extract of Withania somnifera root (a commercial preparation available locally, Dabur India ltd.) was used to compare the results. In the safety evaluation study the maximum tolerance dose (MTD) and oral LD50 were found to be more than 3000 mg/kg, with no signs of abnormalities or any mortality observed for 15 days period under observation after single dose of drug administration. Feeding behaviour and fecal output were normal.

Animals↗

Outcome of penetrating keratoplasty in patients with bilateral corneal blindness.

PURPOSE: To evaluate the outcome of penetrating keratoplasty in patients with bilateral corneal blindness. METHODS: Bilaterally blind patients who had undergone optical penetrating keratoplasty (PK) were evaluated on optical and refractive parameters and presence of complications if any. The results at 3 months, 6 months, and 1 year were compared with age-matched and indication-matched unilaterally blind controls. RESULTS: The most common indication for surgery in both the groups was the presence of a corneoiridic scar. Best corrected visual acuity of > or =6/18 was seen in five (16.66%) patients in the study group and in 11 (36.66%) patients in the control group (P = 0.14). In all, 15 (50%) grafts in the study group and six (20%) in the control group failed (P = 0.03). The most common cause of failure was graft infection (40%) in the study group and post-PK glaucoma (20%) in the control group. The percentage of graft rejection as a cause of graft failure was the same in both the groups. A composite socioeconomic status scale based on family literacy and income suggested that 70% of the cases in the study group and 30% in the control group belonged to the low socioeconomic group (P = 0.004). CONCLUSION: The outcome of optical penetrating keratoplasty in patients with bilaterally blinding corneal disease is poorer than those who are unilaterally blind. Low socioeconomic status may be a contributing factor for the poor outcome.

Adult↗

Snake envenomation in a north Indian hospital.

OBJECTIVES: To study the clinical profile of snake envenomation in a tertiary referral north Indian hospital. METHODS: Retrospective case note analysis of all cases of snakebite admitted to the medical emergency from January 1997 to December 2001. RESULTS: Of a total of 142 cases of snakebite there were 86 elapid bites presenting with neuroparalytic symptoms and 52 viper bites having haemostatic abnormalities. Some 60.6% of the cases of snakebite occurred when the patient was asleep. Urban to rural ratio was 1:4.7 and male to female ratio was 4.25:1. Median time to arrival at our hospital after the bite was nine hours and mean duration of hospital stay was eight days. Twenty seven cases had acute renal failure and 75% of all elapid bites required assisted ventilation. Seventeen of 119 patients who received antivenom had an adverse event. The average dose of antivenom was 51.2 vials for elapid bites and 31 vials for viper bites. Overall mortality rate was 3.5%. CONCLUSION: Snakebites are common in the rural population of developing countries. There is a need to educate the public about the hazards of snakebite, early hospital referral, and treatment.

Adolescent↗