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A Sharma

Publications and source records attributed to A Sharma.

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

Oral immunization with recombinant Streptococcus gordonii expressing porphyromonas gingivalis FimA domains.

Porphyromonas gingivalis, a gram-negative anaerobe, is implicated in the etiology of adult periodontitis. P. gingivalis fimbriae are one of several critical surface virulence factors involved in both bacterial adherence and inflammation. P. gingivalis fimbrillin (FimA), the major subunit protein of fimbriae, is considered an important antigen for vaccine development against P. gingivalis-associated periodontitis. We have previously shown that biologically active domains of P. gingivalis fimbrillin can be expressed on the surface of the human commensal bacterium Streptococcus gordonii. In this study, we examined the effects of oral coimmunization of germfree rats with two S. gordonii recombinants expressing N (residues 55 to 145)- and C (residues 226 to 337)-terminal epitopes of P. gingivalis FimA to elicit FimA-specific immune responses. The effectiveness of immunization in protecting against alveolar bone loss following P. gingivalis infection was also evaluated. The results of this study show that the oral delivery of P. gingivalis FimA epitopes via S. gordonii vectors resulted in the induction of FimA-specific serum (immunoglobulin G [IgG] and IgA) and salivary (IgA) antibody responses and that the immune responses were protective against subsequent P. gingivalis-induced alveolar bone loss. These results support the potential usefulness of the S. gordonii vectors expressing P. gingivalis fimbrillin as a mucosal vaccine against adult periodontitis.

Administration, Oral↗
PubMed2001

Development of a gene inactivation system for Bacteroides forsythus: construction and characterization of a BspA mutant.

Bacteroides forsythus is a gram-negative anaerobic bacterium associated with periodontitis. The bspA gene encoding a cell surface associated leucine-rich repeat protein (BspA) involved in adhesion to fibronectin and fibrinogen was recently cloned from this bacterium in our laboratory. We now describe the construction of a BspA-defective mutant of B. forsythus. This is the first report describing the generation of a specific gene knockout mutant of B. forsythus, and this procedure should be useful in establishing the identity of virulence-associated factors in these organisms.

Antigens, Bacterial↗
PubMed2001

Identification of Enterococcus, Streptococcus, and Staphylococcus by multivariate analysis of proton magnetic resonance spectroscopic data from plate cultures.

A new fingerprinting technique with the potential for rapid identification of bacteria was developed by combining proton magnetic resonance spectroscopy ((1)H MRS) with multivariate statistical analysis. This resulted in an objective identification strategy for common clinical isolates belonging to the bacterial species Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, and the Streptococcus milleri group. Duplicate cultures of 104 different isolates were examined one or more times using (1)H MRS. A total of 312 cultures were examined. An optimized classifier was developed using a bootstrapping process and a seven-group linear discriminant analysis to provide objective classification of the spectra. Identification of isolates was based on consistent high-probability classification of spectra from duplicate cultures and achieved 92% agreement with conventional methods of identification. Fewer than 1% of isolates were identified incorrectly. Identification of the remaining 7% of isolates was defined as indeterminate.

Culture Media↗
PubMed2001

Is glucose/amino acid supplementation after exercise an aid to strength training?

BACKGROUND: The precise timing of carbohydrate and amino acid ingestion relative to a bout of resistance exercise may modulate the training effect of the resistance exercise. OBJECTIVE: To assess whether regular glucose/amino acid supplementation immediately after resistance exercise could enhance the gain in muscle strength brought about by resistance training. METHODS: Seven untrained participants with a median age of 23 years and mean (SD) body mass 68.9 (13.5) kg resistance trained on a leg extension machine for five days a week for 10 weeks, using four sets of 10 repetitions. Alternate legs were trained on successive days, one leg each day. Subjects ingested either a supplement including 0.8 g glucose/kg and 0.2 g amino acids/kg, or placebo, on alternate training days immediately after training. Therefore the supplement was always ingested after training the same leg (supplement leg). Isometric, isokinetic, and 1 repetition maximum (RM) strength were measured before, during, and after training. Blood samples were analysed to determine the acute responses of insulin and glucose to resistance exercise and supplementation or placebo. RESULTS: Serum insulin concentration peaked 20 minutes after supplement ingestion at ninefold the placebo level, and remained significantly elevated for at least 80 minutes (p<0.01). Isometric, isokinetic, and 1 RM strength improved on both supplement and placebo legs (p<0.05). There were no significant differences in the gain in strength between the supplement leg and the placebo leg (p>0.05). CONCLUSION: Regular glucose/amino acid supplementation immediately after resistance exercise is unlikely to enhance the gain in muscle strength brought about by resistance training.

Adult↗
PubMed2001

Factors influencing pneumothorax rate at lung biopsy: are dwell time and angle of pleural puncture contributing factors?

PURPOSE: To study factors that may influence pneumothorax and chest tube placement rate, especially needle dwell time and pleural puncture angle. MATERIALS AND METHODS: In 159 patients, 160 coaxial computed tomography (CT)-guided lung biopsies were performed. Dwell time, the time between pleural puncture and needle removal, was calculated. The smallest angle of the needle with the pleura ("needle-pleural angle") was measured. These and other variables were correlated with pneumothorax and chest tube rates. RESULTS: One hundred fifty biopsies were included. There were 58 (39%) pneumothoraces (14 noted only at CT), with eight (5%) biopsies resulting in chest tube placement. Longer dwell times (mean, 29 minutes; range, 12-66 minutes) did not correlate with pneumothoraces (P =.81). Smaller needle-pleural angles (< 80 degrees) [corrected], decreased forced expiratory volume in 1 second to vital capacity ratio (<50%), lateral pleural puncture, and lesions along fissures were associated with higher [corrected] pneumothorax rates (P <.05). Emphysema along the needle path, pulmonary function tests showing ventilatory obstruction, and lesions along fissures predisposed patients to chest tube placement (P <.05). Pleural thickening and prior surgery were associated with lower pneumothorax rates (P <.05). CONCLUSION: Longer dwell times do not correlate with pneumothorax and should not influence the decision to obtain more biopsy samples. A shallow pleural puncture angle may increase the pneumothorax rate.

Aged↗
PubMed2001

Adaptation of beta-cell mass to substrate oversupply: enhanced function with normal gene expression.

Although type 2 diabetes mellitus is associated with insulin resistance, many individuals compensate by increasing insulin secretion. Putative mechanisms underlying this compensation were assessed in the present study by use of 4-day glucose (GLC; 35% Glc, 2 ml/h) and lipid (LIH; 10% Intralipid + 20 U/ml heparin; 2 ml/h) infusions to rats. Within 2 days of beginning the infusion of either lipid or glucose, plasma glucose profiles were normalized (relative to saline-infused control rats; SAL; 0.45% 2 ml/h). During glucose infusion, plasma glucose was maintained in the normal range by an approximately twofold increase in plasma insulin and an approximately 80% increase in beta-cell mass. During LIH infusion, glucose profiles were also maintained in the normal range. Plasma insulin responses during feeding were doubled, and beta-cell mass increased 54%. For both groups, the increase in beta-cell mass was associated with increased beta-cell proliferation (98% increase during GLC and 125% increase during LIH). At the end of the 4-day infusions, no significant changes were observed in islet-specific gene transcription (i.e., the expression of islet hormone genes, glucose metabolism genes, and insulin transcription factors were unaffected). Two days after termination of the infusions, the glucose-stimulated plasma insulin response was increased approximately 67% in glucose-infused animals. No sustained effect on insulin secretory capacity was observed in the LIH animals. The increase in plasma insulin response after glucose infusion was achieved in the absence of any change in insulin clearance. We conclude that, in rats, an increase in insulin demand after an increase in glucose appearance or free fatty acid leads to an increase in beta-cell mass, mediated in part by an increase in beta-cell proliferation, and that these compensatory changes lead to increased insulin secretion, normal plasma glucose levels, and the maintenance of normal islet gene expression.

Adaptation, Physiological↗
PubMed2001

Clinical benefit and approach of ultrafiltration in acute heart failure.

Because of the increasing incidence of acute heart failure admissions to critical care units, nephrologists have been asked to become more involved in the management of these patients. Renal dysfunction is a major element in impeding clinical recovery. In acute heart failure, renal function is often abnormal. The judicious application of ultrafiltration techniques may represent an efficacious adjunct to present conventional practice. In patients with refractory congestive heart failure, the ability to provide continuous, daily, large volume removal not only improves volume status but also the clinical symptoms of the decompensated patient. A thorough literature review supports the premise that starting hemofiltration is an appropriate alternative for difficult and unstable cardiac patients. An optimal strategy utilizing continuous renal replacement therapy can dramatically improve the patient's clinical condition, mitigate the neurohumoral stimulation, increase urinary output and promote absorption of excessive extravascular fluid.

Aged↗
PubMed2001

Tolerability of the low-affinity, use-dependent NMDA antagonist AR-R15896AR in stroke patients: a dose-ranging study.

BACKGROUND AND PURPOSE: AR-R15896AR is a use-dependent, low-affinity blocker of the NMDA ion channel with neuroprotective effects in animal models of focal cerebral ischemia. This study aimed to establish the highest safe and tolerated loading and maintenance dosing regimen of AR-R15896AR in acute ischemic stroke patients and to determine the associated plasma concentrations of AR-R15896AR. METHODS: This was a 4-part, multicenter, randomized, double-blind, placebo-controlled study in 175 patients (mean age, 69 years) within 24 hours of acute stroke symptom recognition. Ascending 60-minute intravenous infusion loading doses of AR-R15896AR were initially examined (100, 150, 200, 250, or 300 mg or placebo in 3:1 randomization, n=36 treated); in part 2, 250, 275, or 300 mg was compared with placebo (n=33). In part 3, a 250-mg loading dose was followed by 9 maintenance doses of 60, 75, 90, 105, or 120 mg every 8 hours versus placebo in 3:1 randomization (n=59); subsequently, in part 4, maintenance doses of 90, 105, and 120 mg after the 250-mg loading dose were directly randomized against placebo (n=42). Safety, tolerability, and pharmacokinetics were the primary end points; NIHSS at 1 week and Barthel and modified Rankin scores at 1 month were also recorded, but the study was neither designed nor powered to assess efficacy. RESULTS: Rates for mortality and serious adverse events (SAE) were similar in active and placebo groups (9% mortality and 23% SAE for all active combined versus 11% mortality and 33% SAE for placebo). Adverse events associated with AR-R15896AR were dizziness, vomiting, nausea, stupor, and some agitation/hallucination. Withdrawal from treatment occurred only in response to loading doses with AR-R15896AR: placebo, 3 of 46 (7%); 250 mg, 11 of 89 (12%); 275 mg, 1 of 8 (12.5%); and 300 mg, 3 of 15 (20%). No significant difference in outcome was observed between groups. Plasma concentrations of AR-R15896AR were 1524+/-536 ng/mL at the end of the 250-mg loading infusion and were 1847+/-478 ng/mL at steady state after the 9 maintenance doses of 120 mg. CONCLUSIONS: The maximum tolerated loading infusion of AR-R15896AR in this study was 250 mg over a period of 1 hour. Subsequent maintenance infusions of 120 mg every 8 hours were well tolerated. With these doses, putative neuroprotective concentrations of 1240 ng/mL are attained by the loading dose and are satisfactorily maintained thereafter. The loading dose may be improved further by adjustment on an individual patient basis, but tolerability issues remain.

Aged↗