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S Sharma

Publications and source records attributed to S Sharma.

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

Immunobiology of CD28 expression on human neutrophils. I. CD28 regulates neutrophil migration by modulating CXCR-1 expression.

CD28, described as a T cell costimulatory molecule so far, is expressed on human peripheral blood neutrophils, as shown by cell surface staining and immunoprecipitation with anti-CD28 monoclonal antibody, and by reverse transcription PCR. The phorbol 12-myristate 13-acetate-augmented expression of CD28 on these cells can be blocked by actinomycin D, an RNA transcription inhibitor, and staurosporin, a protein kinase inhibitor. Cross-linking of CD28 results in an early increase in IL-8 receptor A (IL-8RA or CXCR-1) expression and a concurrent increase in IL-8-induced chemotaxis. The expression of CXCR-1 is down-regulated by receptor internalization 3 h after CD28 cross-linking with concurrent decrease in IL-8-induced chemotactic migration. Thus, our results demonstrate for the first time that CD28 is expressed on human peripheral blood neutrophils and that CD28 may play an important role in the regulation of IL-8RA expression and migration of neutrophils in response to IL-8.

Adult↗
PubMed2001

Morbidity and mortality in rheumatoid arthritis patients with prolonged and profound therapy-induced lymphopenia.

OBJECTIVE: Therapies that deplete lymphocytes often improve symptoms in patients with otherwise refractory autoimmune disease but may result in long-term lymphopenia, the consequences of which are uncertain. To assess the impact of prolonged lymphopenia on morbidity and mortality, we studied patients who had previously received lymphocytotoxic monoclonal antibody (mAb) therapy for rheumatoid arthritis (RA). METHODS: Fifty-three patients who received the lymphocytotoxic mAb CAMPATH-1H between 1991 and 1994 in the United Kingdom were assessed for mortality and infectious and malignant morbidity, by interview and case-note review. In addition, patients were monitored via the National Health Service Central Registry, to verify notification of death. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. A retrospective, matched-cohort study of mortality was also performed with 102 control subjects selected from the European League Against Rheumatism database, which comprises patients with rheumatic disorders who have received immunosuppressive drugs. RESULTS: There was profound and persistent peripheral blood lymphopenia in the mAb-treated patients, affecting predominantly the CD4+ subset. Median CD4+, CD8+, and CD19+ peripheral blood lymphocyte counts at 73-84 months after therapy were 185 cells/microl, 95 cells/microl, and 115 cells/microl, respectively. At a median followup of 71 months (range 14-90), 13 patients had died (24.5%), compared with 18% of the matched controls, providing a mortality rate ratio of 1.45 (95% confidence interval 0.65-3.13). During 283 patient-years of followup, there were 36 infections classified as major (12.7 per 100 patient-years). The causes of death and the spectrum of infections documented were similar to those expected in a hospital-based RA cohort. Patients who received more than 1 course of therapy had more severe lymphopenia than did patients who received a single course, but this did not have an impact on mortality or morbidity. CONCLUSION: Despite the occurrence of profound and long-lasting lymphopenia following treatment with antilymphocyte mAb therapy for RA, this therapy is not associated with a large excess of mortality nor with an unusual spectrum of infections, at least during a medium-term period of followup. These data are also relevant to patients receiving lymphocytotoxic mAb therapy for other indications, and to patients receiving other lymphodepleting therapies such as autologous stem cell transplantation.

Aged↗
PubMed2001

Clinical relevance of benign endometrial cells in postmenopausal women.

Our objective was to determine if the finding of benign endometrial cells on a Papanicolaou (Pap) smear of a postmenopausal woman is associated with endometrial/uterine pathology, independent of symptomatology and hormone replacement therapy (HRT) status. The medical records of 146 postmenopausal patients who had a Pap smear showing normal-appearing endometrial cells between January 9, 1997 and January 12, 2000 were reviewed. Uterine pathology for each patient was determined by reviewing the results of endometrial sampling (endometrial biopsy or dilatation and curettage), hysterectomy, or pelvic sonogram, which were performed within 24 mo of the cytologic smear. The results were then correlated with clinical symptomatology and HRT status of each patient at the time the cytologic smear was obtained. Of the 146 Pap smears coded with "endometrial cells in a postmenopausal woman," 50 were excluded due to prior hysterectomy, perimenopausal status, and absence of further follow-up. Of the remaining 96 women, 27 (28%) had benign pathologic findings including polyps, leiomyomata, and simple hyperplasia without atypia, whereas 11 (12%) had significant pathologic findings including hyperplasia with atypia, adenocarcinoma, mixed Mullerian tumor, and leiomyosarcoma. Of the 11 patients with significant pathology, only one patient did not have abnormal vaginal bleeding but instead had a 30-wk-size irregular uterus on examination, and only 2 patients received hormone replacement therapy. In conclusion, Reporting endometrial cells on Pap smears in postmenopausal women did not lead to the diagnosis of any cases of significant pathology that would have gone unsuspected clinically. Moreover, HRT status did not affect the incidence of normal endometrial cells on Pap smears in postmenopausal women, nor did it aid in distinguishing which postmenopausal women had endometrial/uterine pathology. This calls into question the usefulness of the current Bethesda guideline to report "benign endometrial cells in a postmenopausal woman."

Aged↗
PubMed2001

Purification of phospholipase D from Dacus carota by three-phase partitioning and its characterization.

Phospholipase D from Dacus carota (carrot) was purified by subjecting it to three-phase partitioning. The single step of three phase partitioning led to 13-fold purification with an activity recovery of 72%. SDS-PAGE analysis showed a single band with minimum molecular weight corresponding to nearly 60 kDa. The purified enzyme had a pH optimum in the range of 6.0--6.5 and was unstable above 30 degrees C. Kinetic studies showed a K(m) value of 9.5 mM and a V(max) of 0.35 mL min(-1). The enzyme purified by three-phase partitioning was found to resolve into two isoenzymes on a DEAE-cellulose column.

Ammonium Sulfate↗
PubMed2001

DNA as the intracellular secondary target for antibacterial action of human neutrophil peptide-I against Mycobacterium tuberculosis H37Ra.

The secondary intracellular target of human neutrophil peptide-1 has been examined in M. tuberculosis H37Ra. Binding studies with radioiodinated HNP-1 revealed biphasic equilibrium binding kinetics with respect to time. The major site of HNP-1 binding was found to be plasma membrane/cell wall whereas the cytosol appears to be a secondary site. Among the different macromolecules examined, maximum inhibition (75%) was observed in DNA biosynthesis during treatment with HNP-1. The interaction of HNP-1 with mycobacterial genomic DNA on the basis of gel retardation assay revealed HNP-1 binding to DNA. These results indicate that HNP-1 has DNA as the secondary intracellular target for antibacterial action against mycobacteria.

Anti-Bacterial Agents↗
PubMed2001

Surgical debulking and intraperitoneal chemotherapy for established peritoneal metastases from colon and appendix cancer.

BACKGROUND: Aggressive treatment of peritoneal metastases from colon cancer by surgical cytoreduction and infusional intraperitoneal (IP) chemotherapy may benefit selected patients. We reviewed our institutional experience to assess patient selection, complications, and outcome. METHODS: Patients having surgical debulking and IP 5-fluoro-2'-deoxyuridine (FUDR) plus leucovorin (LV) for peritoneal metastases from 1987 to 1999 were evaluated retrospectively. RESULTS: There were 64 patients with a mean age of 50 years. Primary tumor sites were 47 in the colon and 17 in the appendix. Peritoneal metastases were synchronous in 48 patients and metachronous in 16 patients. Patients received IP FUDR (1000 mg/m2 daily for 3 days) and IP leucovorin (240 mg/m2) with a median cycle number of 4 (range, 1-28). The median number of complications was 1 (range, 0-5), with no treatment related mortality. Only six patients (9%) required termination of IP chemotherapy because of complications. The median follow-up was 17 months (range, 0-132 months). The median survival was 34 months (range, 2-132); 5-year survival was 28%. Lymph node status, tumor grade, and interval to peritoneal metastasis were not statistically significant prognostic factors for survival. Complete tumor resection was significant on multivariate analysis (P = .04), with a 5-year survival of 54% for complete (n = 19) and 16% for incomplete (n = 45) resection. CONCLUSIONS: Surgical debulking and IP FUDR for peritoneal metastases from colon cancer can be accomplished safely and has yielded an overall 5-year survival of 28%. Complete resection is associated with improved survival (54% at 5 years) and is the most important prognostic indicator.

Adenocarcinoma↗
PubMed2001

The role of exercise testing in the evaluation of the patient with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic disease of the sarcomeric contractile proteins that is characterized by left ventricular hypertrophy and myocyte disarray. The majority of patients are limited in terms of functional capacity and a minority die suddenly. The main aims of management are symptom alleviation and prevention of sudden cardiac death. In patients with HCM, cardiopulmonary exercise testing provides a more accurate index of functional capacity than New York Heart Association classification status and is useful in assessing symptoms following various therapeutic interventions. Cardiopulmonary exercise testing plays an important role in differentiating HCM from other conditions associated with left ventricular hypertrophy. Cardiopulmonary exercise testing is also valuable in identifying individuals at high risk of sudden cardiac death and is an integral part of the algorithm in risk stratification and delivery of prophylactic therapy. Over the past few years, cardiopulmonary exercise testing has provided insight into the determinants and mechanisms of exercise limitation. This understanding helps in targeting therapy and the development of new treatment modalities.

Cardiomyopathy, Hypertrophic↗
PubMed2001

Epithelial infectious crystalline keratopathy.

PURPOSE: To report 2 cases of epithelial infectious crystalline keratopathy. METHODS: Two patients (2 eyes) with significant meibomitis presented with minimal inflammation and plaque-like lesions on the corneal surface made of fine crystalline structures. Corneal scrapings of these lesions were performed for microbiological evaluation. The patients were treated with topical ciprofloxacin and artificial tears. RESULTS: Smear examination of the corneal scrapings revealed numerous bacteria and keratinized epithelial cells with no inflammatory cells. Culture showed a significant growth of Staphylococcus epidermidis and Corynebacterium species in the first case and Pseudomonas aeroginosa in the second case. The response to treatment was poor, with recurrence of the crystalline lesion. CONCLUSION: Infectious crystalline keratopathy lesions may involve the epithelium and occur on the corneal surface.

Adult↗
PubMed2001

In vivo flow dynamics of the total cavopulmonary connection from three-dimensional multislice magnetic resonance imaging.

BACKGROUND: The total cavopulmonary connection (TCPC) design continues to be refined on the basis of flow analysis at the connection site. These refinements are of importance for myocardial energy conservation in the univentricular supported circulation. In vivo magnetic resonance phase contrast imaging provides semiquantitative flow visualization information. The purpose of this study was to understand the in vivo TCPC flow characteristics obtained by magnetic resonance phase contrast imaging and compare the results with our previous in vitro TCPC flow experiments in an effort to further refine TCPC surgical design. METHODS: Twelve patients with TCPC underwent sedated three-dimensional, multislice magnetic resonance phase contrast imaging. Seven patients had intraatrial lateral tunnel TCPC and 5 had extracardiac TCPC. RESULTS: In all patients in both groups a disordered flow pattern was observed in the inferior caval portion of the TCPC. Flow at the TCPC site appeared to be determined by connection geometry, being streamlined at the superior vena cava-pulmonary junction when the superior vena cava was offset and flared toward the left pulmonary artery. Without caval offset, intense swirling and dominance of superior vena caval flow was observed. In TCPC with bilateral superior vena cavae, the flow patterns observed included secondary vortices, a central stagnation point, and influx of the superior vena cava flow into the inferior caval conduit. A comparative analysis of in vivo flow and our previous in vitro flow data from glass model prototypes of TCPC demonstrated significant similarities in flow disturbances. Three-dimensional magnetic resonance phase contrast imaging in multiple coronal planes enabled a comprehensive semiquantitative flow analysis. The data are presented in traditional instantaneous images and in animated format for interactive display of the flow dynamics. CONCLUSIONS: Flow in the inferior caval portion of the TCPC is disordered, and the TCPC geometry determines flow characteristics.

Adolescent↗
PubMed2001

De Vega tricuspid annuloplasty for tricuspid regurgitation in children.

BACKGROUND: Significant tricuspid valve regurgitation (TR) occurs with other congenital heart defects, typically after repair of right-sided obstructive lesions. Since 1991, we applied the De Vega tricuspid annuloplasty technique for TR in children. METHODS: Forty-one children, aged 5 months to 22.7 years (mean, 9.9 years) underwent 42 De Vega tricuspid annuloplasties for moderate or severe TR during correction of other heart defects. One child had a De Vega during primary ventricular septal defect repair. The remaining patients had prior repair of tetralogy of Fallot or pulmonary atresia, or both (19 patients), double-outlet right ventricle (6 patients), pulmonary stenosis (4 patients), pulmonary atresia and intact ventricular septum (3 patients), complete atrioventricular septal defect (3 patients), and other diagnoses (6 patients). At the time of the De Vega, 37 patients (88%) had pulmonary valve replacement or right ventricular to pulmonary artery conduit replacement. Other procedures included aortic or mitral repair or replacement (6 patients), atrial septal defect and ventricular septal defect closure (5 patients), pulmonary arterioplasty (6 patients), and tracheoplasty (1 patient). RESULTS: There were no deaths at follow-up of 3.4 +/- 2.1 years; 1 child required cardiac transplantation 17 months postoperatively. Early postrepair echocardiography quantified TR as absent or mild (34 patients; 81%), mild-to-moderate (4 patients), moderate (3 patients), and severe (1 patient). The most recent echocardiogram showed moderate TR in 11 patients and severe TR in 2 patients (both with recurrent right ventricular hypertension). One child required tricuspid valve replacement 3 years later and 1 child had redo De Vega at the time of conduit re-replacement. No other child has symptomatic TR, significant tricuspid stenosis, or De Vega-related pacemaker implantation. CONCLUSIONS: The De Vega tricuspid annuloplasty safely provides excellent relief of TR, usually in children undergoing pulmonary valve replacement or conduit replacement. Although echocardiographic TR tends to increase with time (especially with right ventricular hypertension), it rarely requires reintervention or causes symptoms.

Adolescent↗
PubMed2001

Tubercular pseudoaneurysms of aorta.

BACKGROUND: Tubercular pseudoaneurysm of aorta is a rare but important complication of tuberculosis. With worldwide resurgence of tuberculosis due to increasing incidence of drug-resistant tuberculosis and its association with acquired immunodeficiency syndrome, the tubercular pseudoaneurysm has become a real clinical entity. METHODS: In the past 3 years, 5 young patients (22 to 40 years) presented with tubercular pseudoaneurysm. Site of involvement included ascending aorta, distal aortic arch, proximal descending thoracic aorta, distal descending thoracic aorta, and infrarenal abdominal aorta. Two patients had macroscopic focus of tuberculosis in the nearby vicinity, and all 5 patients had evidence of active/treated pulmonary pericardial tuberculosis. All patients either had received antitubercular therapy previously or were receiving it at the time of presentation. Rapid deterioration in the clinical status was the most marked clinical feature. All patients underwent operation. Graft interposition was performed in 2, patch repair in 2, and direct closure of the rent was performed in 1 patient. All 5 patients received antitubercular therapy in the postoperative period. RESULTS: All patients survived the operation and were discharged from the hospital. One patient developed recurrence at the original site after 8 months and died at reoperation. The remaining patients are symptom free at 18 to 36 months postoperatively. CONCLUSIONS: A combination of chemotherapy and operation yields gratifying results for the treatment of tubercular pseudoaneurysm.

Adult↗
PubMed2001

Reliability of the time trade-off technique of utility assessment in patients with retinal disease.

BACKGROUND: Studies in medical fields other than ophthalmology have given conflicting results regarding the reliability of the time trade-off technique of utility assessment. We performed a study to determine the test-retest reliability of the time trade-off technique for assessing utilities in patients with ocular diseases of the retina and to investigate possible factors associated with differences in utility over time. METHODS: Patients referred to the retina service of a tertiary care hospital in eastern Canada were eligible for the initial interview if they had best corrected vision of 20/30 or worse in at least one eye and were deemed competent to answer the required questions. Patients were interviewed prospectively between December 1999 and March 2000 during a normal 30-minute period needed for pharmacologic mydriasis to occur. Demographic, clinical (including Snellen visual acuity) and time trade-off utility information was collected through chart review and standardized interview. Patients who completed the interview successfully were called back 28 days later for follow-up. RESULTS: Of the 138 eligible patients 112 (81.2%) completed the initial interview. Of the 112, 96 (85.7%) completed the second interview. Half of the respondents were women, and all but one respondent were white. The mean age was 65.3 years. The primary reasons for visual loss included diabetic retinopathy (59 patients [61.4%]) and age-related macular degeneration (14 patients [14.6%]). The intraclass correlation coefficient between the initial and follow-up visual utilities was 0.7634 (95% confidence interval 0.6655-0.8355). INTERPRETATION: Our results show excellent reliability of the time trade-off technique of utility assessment in patients with ocular diseases of the retina.

Adult↗
PubMed2001

Improvement in quality of life from photodynamic therapy: a Canadian perspective.

BACKGROUND: The Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study showed that at 1 year, photodynamic therapy significantly reduced the chances of severe visual loss (15 letters or greater) compared with placebo treatment in patients with "predominantly classic" subfoveal choroidal neovascularization (CNV). We performed a study to determine the expected gain in quality of life associated with photodynamic therapy for the treatment of subfoveal CNV in a Canadian cohort of patients with age-related macular degeneration. METHODS: We created a decision analysis model to determine the incremental gain in quality-adjusted life years (QALYs) associated with photodynamic therapy over placebo over a 2-year period. The analysis was conducted using efficacy data derived from the TAP Study and patient-based utilities collected by means of the time trade-off technique. We conducted one-way and two-way sensitivity analyses to determine the robustness of our model. A Monte Carlo simulation was used to determine whether the observed gain in QALYs with photodynamic therapy was significant. RESULTS: Photodynamic therapy was associated with a relative increase in QALYs of 11.3% compared with placebo. In one-way and two-way sensitivity analyses, the relative increase in quality of life associated with photodynamic therapy ranged from 4.2% to 25.7%. The Monte Carlo simulation showed that the gain in QALYs conferred from photodynamic therapy was statistically significant (p < 0.001). INTERPRETATION: Photodynamic therapy improves the quality of life of Canadians with predominantly classic subfoveal CNV secondary to age-related macular degeneration.

Canada↗
PubMed2001

Oxidation of unsaturated fatty acids by human fibroblasts with very-long-chain acyl-CoA dehydrogenase deficiency: aspects of substrate specificity and correlation with clinical phenotype.

The degradation of unsaturated fatty acids was examined in fibroblasts from 16 patients with very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Analysis of acylcarnitine intermediates following incubation of intact human cells with these compounds revealed that the milder clinical phenotypes could be distinguished from the severe cardiomyopathic phenotype. These findings may reflect more effective contributions of alternate pathways in the milder forms of the disease. Incubation of VLCAD-deficient cells with cis-9 or trans-9 unsaturated fatty acids indicate that VLCAD is largely responsible for the 2,3-dehydrogenation of cis-5 or trans-5 intermediates in fibroblasts. The first two cycles of beta-oxidation with oleic and linoleic acids occur in the absence of VLCAD activity suggesting the presence of an additional acyl-CoA dehydrogenase or alternate pathway for the oxidation of these unsaturated fatty acids. These observations have clinical relevance for determining diagnosis, prognosis and strategies for dietary treatment of these patients.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed2001

Process development for the removal of lead and chromium from aqueous solutions using red mud--an aluminium industry waste.

Red mud, an aluminium industry waste, has been converted into an inexpensive and efficient adsorbent and used for the removal of lead and chromium from aqueous solutions. Effect of various factors on the removal of these metal ions from water (e.g. pH, adsorbent dose, adsorbate concentration, temperature, particle size, etc.) has been studied and discussed. The effect of presence of other metal ions/surfactants on the removal of Pb2+ and Cr6+ has also been studied. The material exhibits good adsorption capacity and the data follow both Freundlich and Langmuir models. Thermodynamic parameters indicate the feasibility of the process. Kinetic studies have been performed to understand the mechanism of adsorption. Dynamic modelling of lead and chromium removal on red mud has been undertaken and found to follow first-order kinetics. The rate constant and mass transfer coefficient have also been evaluated under optimum conditions of removal in order to understand the mechanism. Column studies have been carried out to compare these with batch capacities. The recovery of Pb2+ and Cr6+ and chemical regeneration of the spent column have also been tried.

Aluminum↗
PubMed2001

Clp ATPases and their role in protein unfolding and degradation.

Although much has been learned about the structure and function of Clp chaperones and their role in proteolysis, the mechanism of protein unfolding catalyzed by Clp ATPases and the mechanism of translocation of the unfolded proteins from Clp ATPases to partner proteases remain unsolved puzzles. However, models in which mechanical force is used to destabilize the structure of the substrate in a processive and directional manner are probable. It also seems likely that when ClpA ATPases are associated with proteases, unfolding is coupled to extrusion of the unfolded protein into the proteolytic cavity. In summary, it is anticipated that the large family of Clp ATPases will accomplish their many important cellular functions by similar mechanisms and what has been learned by studying the prokaryotic members reviewed here will shed a great deal of light on all members of the family.

Adenosine Triphosphatases↗
PubMed2001

Radiographic versus pathologic size of renal tumors: implications for partial nephrectomy.

OBJECTIVES: To compare the radiographic size with the pathologic size of renal tumors to determine whether these two measurements vary significantly and to evaluate whether any differences in tumor size could have an impact on the decisions regarding partial nephrectomy. METHODS: In 87 renal tumors excised by partial nephrectomy, the maximum transaxial tumor size on computed tomography (CT) was compared with its corresponding pathologic transverse size. Tumors were locally excised after vascular occlusion and hypothermia. The average size of the tumors selected for partial nephrectomy by preoperative CT scan was 3.4 cm (range 1.9 to 9.3). The difference between the CT size and pathologic size was correlated with the histologic type of the renal tumors. RESULTS: Of the 87 tumors, 52 (60%) were classified as clear cell carcinoma and 35 (40%) as other histologic types (papillary, chromophobe, oncocytoma, and angiomyolipoma). Clear cell carcinomas decreased an average of 0.97 cm versus 0.39 cm for the other tumor types. Of 62 tumors greater than 3 cm on CT, 43 averaged 0.87 cm smaller at pathologic evaluation (36 clear cell and 7 other types) and 19 showed no significant (less than 0.5 cm) decrease in size (2 clear cell and 17 other histologic types). Of 30 tumors greater than 4 cm on CT, 22 clear cell carcinomas shrank more than 1 cm and 8 tumors displaying other histologic features showed no decrease in size. CONCLUSIONS: For renal tumors measuring greater than 4 cm, a decrease in tumor size may help facilitate partial nephrectomy, especially for clear cell carcinomas that do not extensively involve major vascular structures or the collecting system.

Adenocarcinoma, Clear Cell↗