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Biomedical subjects

A Sharma

Publications and source records attributed to A Sharma.

At least 55 records · Page 3Linked to original sources
PubMed2001

Protein kinase C activation and cardioprotective effect of preconditioning with oxidative stress in isolated rat heart.

The present study is designed to investigate the effect of myocardial preconditioning with oxidative stress induced by pyrogallol or H2O2, on ischaemia-reperfusion induced myocardial injury. Isolated perfused rat heart was subjected to global ischaemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analysed for LDH and CK release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using TTC staining. Four episodes of preconditioning induced by pyrogallol or hydrogen peroxide (H2O) or ischaemia markedly reduced LDH and CK release in coronary effluent and decreased myocardial infarct size. Administration of polymyxin B, a protein kinase C (PKC) inhibitor, during pyrogallol, H2O2 or ischaemic preconditioning markedly attenuated the cardioprotective effect of preconditioning produced with oxidative stress or ischaemia. These results suggest that preconditioning with oxidative stress may provide cardioprotection similar to ischaemic preconditioning, against ischaemia-reperfusion injury and this cardioprotective effect may be mediated through activation of PKC.

Animals↗
PubMed2001

Concurrent use of reteplase and lepirudin in the treatment of acute anterior wall myocardial infarction.

A 61-year-old male with a history of severe heparin-induced thrombocytopenia (HIT) type II after aorto-femoral bypass surgery presented to the emergency department within 8 hours of development of substernal chest pain radiating to the left arm. Electrocardiogram (ECG) on arrival and at 3 hours showed no acute changes; cardiac enzymes revealed minimal MB elevation. Echocardiogram showed normal left ventricular systolic function with mild mitral and tricuspid regurgitation and trace aortic insufficiency. Five hours after arrival, the patient reported a recurrence of severe chest pain. ECG showed marked ST elevations consistent with acute myocardial infarction. Reteplase was administered with concomitant lepirudin. Follow-up ECG showed improvement in ST-segment elevation and eventual resolution to pre-event tracing; cardiac enzymes showed slight elevations. Catheterization revealed 90% midstenosis of the left anterior descending artery, which was successfully treated with percutaneous transluminal coronary angioplasty (PTCA) and stent placement. Repeat PTCA was performed 10 days postdischarge due to intraluminal stent occlusion. The patient was doing well at 6 months follow-up.

Angioplasty, Balloon, Coronary↗
PubMed2001

Phase I dose-finding and pharmacokinetic trial of irinotecan (CPT-11) administered every two weeks.

OBJECTIVES: This trial was performed to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetic profile of irinotecan (CPT-11) when administered on a once-every-2-week schedule. PATIENTS AND METHODS: CPT-11 was administered to successive cohorts of patients at progressively increasing starting doses ranging from 125 to 350 mg/m2. The MTD and DLTs were determined both for CPT-11 alone and for CPT-11 followed by filgrastim (G-CSF). Plasma samples were obtained during the first 24 hours after initial dosing to determine the total concentrations (lactone + carboxylate forms) of CPT-11; of the active metabolite SN-38; and of SN-38 glucuronide (SN-38G). RESULTS: Neutropenic fever was the DLT for CPT-11 at the 300 mg/m2 dose level. When G-CSF was added, dose escalation beyond 350 mg/m2 could not be achieved due to grade 2-3 toxicities that prevented on-time retreatment with CPT-11. Severe, late diarrhea was uncommon on this schedule. Peak plasma concentrations of SN-38 and SN-38G were approximately 2.5% and 4.2% of the corresponding peak plasma concentration for CPT-II, respectively The harmonic mean terminal half-lives for CPT-11, SN-38, and SN-38G were 7.1 hours, 13.4 hours, and 12.7 hours, respectively. No predictive correlation was observed between CPT-11 or SN-38 peak concentration or AUC and first-cycle diarrhea, neutropenia, nausea, or vomiting. Across the range of doses studied, mean CPT-11 clearance was 14.0 +/- 4.0 l/h/m2 and volume of distribution was 146 +/- 45.9 l/m2. CONCLUSIONS: When administered every two weeks, the recommended phase II starting dose of CPT-11 is 250 mg/m2 when given alone and 300 mg/m2 when supported by G-CSF. This every-two-week regimen offers a tolerable and active alternative to weekly or every-three-week single-agent CPT-11 therapy.

Adult↗
PubMed2001

Mucor endophthalmitis.

PURPOSE: To report on a case of type 2 diabetes, with eyelid gangrene and endophthalmitis as a presenting manifestation of rhino-orbito-cerebral mucormycosis. RESULTS: CECT head showed proptosis, mucosal thickening in the ethmoid sinus and hypodense lesions in the frontal and occipital lobes. Vitreous tap showed right angle branched aseptate hyphae consistent with mucormycosis. CONCLUSIONS: A diabetic patient presenting with sudden loss of vision, eyelid gangrene and endophthalmitis, involvement by an angio-invasive fungus-like mucormycosis is an important consideration.

Anti-Bacterial Agents↗
PubMed2001

Influence of cyclodextrin ring substituents on folding-related aggregation of bovine carbonic anhydrase.

A common obstacle to proper renaturation of an unfolded protein is aggregation, an intermolecular side reaction of immense importance in biotechnology and in the pathogenesis of several neurodegenerative diseases. Cyclic sugars known as cyclodextrins have been used as protein-folding aids. The effect of cyclodextrin chemistry on aggregation and refolding of carbonic anhydrase was evaluated in this study. Size-exclusion HPLC showed that cyclodextrins inhibit aggregate formation without interfering with the correct renaturation of carbonic anhydrase. PAGE of refolded enzyme provides further evidence of inhibition of folding-related aggregation by natural and chemically modified cyclodextrins. Although the amount of aggregate formed and recovery of active enzyme was dependent on cavity size, the nature of the chemical substituents found on the rims of the sugar molecule seems to play a more important role in cyclodextrin-assisted refolding of carbonic anhydrase. In general, neutral or cationic cyclodextrins with small cavities were found to be better folding aids than anionic cyclodextrins with larger holes. Although the exact prediction of the effect of a cyclodextrin substitution on protein refolding is not possible at present, these results clearly show that modified cyclodextrins can be designed that effectively inhibit protein aggregation.

Animals↗
PubMed2001

Cisapride improves gallbladder emptying and bile lipid composition in patients with gallstones.

BACKGROUND AND AIM: Biliary cholesterol supersaturation, gallbladder stasis and delayed intestinal transit are the key events in cholesterol gallstone formation. We studied the effect of cisapride, a prokinetic drug, on gallbladder emptying and bile composition in patients with gallstone disease undergoing cholecystectomy. METHODS: Gallbladder emptying, cholesterol saturation index (CSI) and nucleation time were studied in 21 patients with gallstone disease. Eleven patients (cisapride group, age 41.9 +/- 2.9 years) received tablet cisapride 10 mg t.i.d. for 2 weeks, while 10 patients (placebo group, age 42.1 +/- 1.9 years) received placebo for the same duration. Gallbladder emptying was repeated in all patients after a 2-week treatment with cisapride or placebo. Gallbladder bile was obtained at the time of surgery for the measurement of CSI and nucleation time. RESULTS: Residual volume of the gallbladder decreased (mean +/- SE, 18.6 +/- 2.5 mL vs 10.0 +/- 1.1 mL, P = 0.007), and the ejection fraction increased (43.5 +/- 5.3% vs 60.0 +/- 3.2%, P = 0.007) in patients in the cisapride group, while no change was observed in placebo group patients. Nucleation time was higher in the cisapride group than in the placebo group (14.9 +/- 1.3 days vs 8.0 +/- 0.9 days, P = 0.003). Patients in the cisapride group had a significantly lower cholesterol concentration (molar percentage, 5.1 +/- 0.3% vs 6.8 +/- 0.8%, P = 0.049) and CSI (1.0 +/- 0.1 vs 1.36 +/- 0.11, P = 0.034) than patients in the placebo group. CONCLUSION: Cisapride improves gallbladder emptying and bile lithogenicity in patients with gallstone disease.

Adult↗
PubMed2001

Relationship between dopamine-stimulated phospholipid methylation and the single-carbon folate pathway.

In a previous study we demonstrated the ability of dopamine (DA) to stimulate phospholipid methylation (PLM) via a novel mechanism involving the D4 dopamine receptor (D4R) in which single-carbon folates appeared to be the primary source of methyl groups. To further understand the relationship between D4R-mediated PLM and folate metabolism, we examined the effect of several folate pathway interventions on the level of basal and DA-stimulated incorporation of [14C]-labeled formate into phospholipids in cultured SH-SY5Y neuroblastoma cells. These interventions included: (i) Overexpression of methenyltetrahydrofolate synthetase (MTHFS). (ii) Treatment with 5-formylTHF. (iii) Treatment with the MTHFS inhibitor 5-formyltetrahydrohomofolic acid (5-formylTHHF). (iv) Growth in nucleoside-free media. 31P-NMR was also used to follow DA-induced changes in cell phospholipid composition. MTHFS overexpression and 5-formylTHHF treatment, both of which lower 5-methylTHF levels, each reduced basal PLM and its stimulation by DA. In contrast, 5-formylTHF, which increases 5-methylTHF, caused a dose-dependent increase in both basal and DA-stimulated PLM. Growth in nucleoside-free media caused time-dependent changes in PLM, which were due to the absence of purine nucleosides. While basal PLM was maintained at a reduced level, DA-stimulated PLM was initially increased followed by a later decrease. Together, these findings indicate a close functional relationship between single-carbon folate metabolism and DA-stimulated PLM, consistent with a role for 5-methylTHF as the methyl donor for the D4R-mediated process.

Carbon Radioisotopes↗
PubMed2001

Chromosomal aberrations in a series of large-cell neuroendocrine carcinomas: unexpected divergence from small-cell carcinoma of the lung.

Large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) are high-grade neuroendocrine tumors of the lung. Despite different morphologic appearances, loss of heterozygosity and oncogene studies on LCNEC to date suggest genetic similarities. We analyzed 13 LCNEC and 5 mixed SCLC/LCNEC tumors by comparative genomic hybridization and subsequently compared our results with previously published data on 32 SCLCs. Comparison with SCLC showed several shared chromosomal aberrations, specifically losses of 3p, 4q, 5q, and 13q and gains of 5p. However, these aberrations are no special feature of neuroendocrine lung tumors but can also be found in other high-grade lung carcinomas. From this point of view, genetic similarities of LCNEC and SCLC are less important than the nonrandom changes that differ between these 2 tumor types. A gain of 3q observed in 66% of all SCLCs was detected only once in the LCNEC group. In contrast to the pure LCNEC, all mixed types with a SCLC component had a gain of 3q. Gains of 6p occurred more frequently in LCNEC. Deletions of 10q, 16q, and 17p were less frequent in LCNEC than in SCLC.

Biomarkers, Tumor↗
PubMed2001

Ten years' experience in zygomycosis at a tertiary care centre in India.

OBJECTIVE: To define the spectrum of zygomycosis due to mucorales in an Indian scenario. METHODS: One-hundred and twenty-nine patients with zygomycosis due to mucorales diagnosed at the Postgraduate Institute of Medical Education and Research, Chandigarh, India during 1990-99, were retrospectively analysed regarding the sites of involvement, underlying disease, species of fungi isolated and outcome of therapy. RESULTS: Higher prevalence rate (19.4%) was observed in 1999. Rhino-orbito-cerebral type (44.2%) was the commonest presentation followed by cutaneous (15.5%) and renal (14.0%) involvement. Disseminated zygomycosis was seen in 11.6% patients. Pulmonary and gastrointestinal zygomycosis were diagnosed in 10.1% and 4.7% patients, respectively. Uncontrolled diabetes mellitus (in 50% of cases) was the significant risk factor in rhino-orbito-cerebral type [odds ratio (OR), 9.3; P<or=0.001) and breach of skin (in 40% cases) in cutaneous zygomycosis (OR, 6.9; P<or=0.01). However, a considerable number of 22 (22.9%) patients were apparently healthy hosts in this series. Forty-five patients (34.9%) of this series were diagnosed only at post-mortem. Among 47 patients where culture was attempted, mucorales were isolated from 25 patients with Rhizopus arrhizus (11 patients) and Apophysomyces elegans (eight patients) as the predominant isolates. Adequate therapy could be provided in 33 patients. A combination of aggressive surgical debridement of necrotic tissue and amphotericin-B was found to be the best treatment protocol as 81.3% patients treated with surgical debridement and amphotericin-B were cured, compared with 46.7% patients treated with amphotericin-B alone. CONCLUSION: The study highlights the importance of increased awareness for early diagnosis of zygomycosis and aggressive management. The large number of cases in apparently healthy hosts and increased isolation of A. elegans in the present series are important characteristics of this disease in India and requires further evaluation.

Adolescent↗
PubMed2001

Dysembryoplastic neuroepithelial tumors: report of 10 cases from a center where epilepsy surgery is not done.

Dysembryoplastic neuroepithelial tumor (DNT) is a recently recognized tumor entity with distinctive clinicopathological features and an excellent long-term prognosis. We report 10 cases of DNT out of neurosurgical specimens sent for histopathological examination since 1994. Epilepsy surgery is not done at our center, and all the cases were sent with a clinical diagnosis of glioma. On histopathological examination, all the 10 cases contained the specific glioneuronal element. In 6 cases, glial nodules were noted in addition. This study therefore reports 4 cases of simple DNT and 6 cases of complex DNT. There was no nuclear atypia or mitosis in any of the cases. Proliferative index by PCNA varied from negative to <1%. It is very important to recognize this entity, as surgery cures the patient, and radiotherapy or chemotherapy is not required.

Adolescent↗
PubMed2001

Laparoscopic intragastric stapled cystogastrostomy for pancreatic pseudocyst.

BACKGROUND: Mature symptomatic pancreatic pseudocysts require surgical intervention for their management. In this era of minimal access surgery, several reports are now available of laparoscopic management of pancreatic pseudocysts. PATIENTS AND METHODS: We have performed this procedure in five patients over the past 2 years. Four patients developed the pseudocyst after acute alcoholic pancreatitis and one following acute biliary pancreatitis. The diameter of the pseudocyst ranged from 8 to 12 cm. The procedure was performed using five ports. The Harmonic Scalpel was used to create two ports in the anterior stomach wall through which two balloon trocars were placed into the gastric lumen. Following balloon inflation, the trocars were used to lift up the anterior gastric wall. This created the space for the cystogastrostomy to be fashioned laparoscopically through the balloon trocar. The ball probe of the Harmonic Scalpel was used to puncture the cyst through the posterior gastric wall. The cystogastrostomy was completed by firing an Endo-GIA30 stapler across the fused posterior gastric wall and anterior wall of the cyst. RESULTS: The mean operative time was 90 minutes (range 80-125 minutes). The mean postoperative stay was 3.0 days. One patient had intraoperative bleeding at the anastomotic site, which was easily controlled. CONCLUSION: Laparoscopic cystogastrostomy offers a feasible and safe therapeutic option for selected patients with large symptomatic pancreatic pseudocysts.

Acute Disease↗
PubMed2001

Osteogenesis imperfecta in pregnancy: two case reports and review of literature.

Osteogenesis imperfecta (OI) is an inherited disease where basic pathology is of defective maturation of collagen. It is more common in women, and the incidence in pregnancy is 1 in 25,000 to 30,000. A multidisciplinary approach is necessary. Ideally, genetic counseling is sought before conception. Once pregnant, prenatal diagnosis can be established by chorion villous sampling. Serial scans would identify the affected fetus with fractures. A cesarean delivery is advocated if the fetus is affected or if the mother has pelvic fractures. An experienced anesthetist should be involved. Because these women are more likely to have a postpartum hemorrhage due to uterine atony, Syntocinon infusion and close observation in the third stage is indicated.

Adolescent↗
PubMed2001

Central corneal thickness, tonometry, and ocular dimensions in glaucoma and ocular hypertension.

PURPOSE: To assess possible correlations between central corneal thickness, tonometry, and ocular dimensions. PATIENTS AND METHODS: One hundred seventeen eyes of 117 patients who were not taking any intraocular pressure-lowering medications were studied prospectively. Forty-one patients had ocular hypertension; 13 patients had primary open-angle glaucoma; and 10 patients had normal-pressure glaucoma. Twenty-three healthy eyes were included. Thirty glaucoma suspects (10 patients monitored for possible normal-pressure glaucoma and 20 patients with intermittent ocular hypertension) were included for correlation analysis. Tonometry was performed with Goldmann applanation and pneumotonometry, and central corneal thickness, anterior chamber depth, lens thickness, and axial length were measured ultrasonically. RESULTS: Central corneal thickness was lowest in eyes with normal-pressure glaucoma (538 +/- 51 microm), highest in eyes with ocular hypertension (570 +/- 32 microm), and intermediate and similar in eyes with primary open-angle glaucoma and healthy eyes (547 +/- 34 microm and 554 +/- 32 microm, respectively). These differences were significant (P = 0.028). Goldmann applanation tonometry and central corneal thickness were weakly correlated (r = 0.12, P = 0.205), with a 0.2-mm Hg change per 10-microm variation in central corneal thickness. Pneumotonometry measurements were more strongly correlated with central corneal thickness (r = 0.21, P < 0.05). Lens thickness was strongly correlated with age (r = 0.57, P < 0.001). Anterior chamber depth was negatively correlated with lens thickness and age (r = -0.29, P < 0.005 and r = -0.25, P < 0.01). Axial length was correlated with anterior chamber depth and age (r = 0.5, P < .001 and r = -0.19, P < 0.05). CONCLUSION: Eyes diagnosed as having ocular hypertension have thicker corneas and eyes labeled as having normal-pressure glaucoma have thinner corneas, when compared with healthy eyes or eyes with primary open-angle glaucoma. The effect of central corneal thickness on Goldmann applanation tonometry accuracy appears to be small and usually not clinically relevant. When corneal thickness is markedly different from normal, the clinician may need to factor this into diagnosis and management.

Aged↗
PubMed2001

Maternal mortality in rural India: a hospital based, 10 year retrospective analysis.

OBJECTIVES: To estimate the maternal mortality ratio (MMR) in Ludhiana, a city of Northern India in order to determine the causes associated with MMR and to suggest ways to reduce it. METHODS: Retrospective analysis of the mortality records of obstetrics cases in Christian Medical College, Ludhiana, India. RESULTS: The mean MMR for the 10 year period was 785 per 100,000 live births. Of the total 116 reported maternal deaths, 44 (41.9%) were due to induced septic abortion. The reasons were unwanted pregnancy in 22 (50%) and 11 (25%) were female feticide. CONCLUSIONS: In our hospital based analysis, MMR was very high. Most maternal deaths are preventable by intervention at the appropriate time and it is important for health professionals, policy makers and politicians to implement the introduction of programs for reducing maternal mortality. Special emphasis should be placed on antenatal care, the establishment of a registration system and measures to abolish illegal abortion.

Abortion, Induced↗