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Biomedical subjects

S Desai

Publications and source records attributed to S Desai.

At least 73 records · Page 4Linked to original sources
PubMed2000

Biventricular pacing diminishes the need for implantable cardioverter defibrillator therapy. Ventak CHF Investigators.

OBJECTIVES: We sought to test the postulate that biventricular pacing diminishes the need for appropriate tachycardia therapy. We reviewed the frequency of therapy in patients, serving as their own controls, who were enrolled in the Ventak CHF (congestive heart failure) biventricular pacing study. BACKGROUND: It is well established that both acute and chronic CHF contribute to the need for tachyarrhythmia therapy in recipients of an automatic implantable cardioverter defibrillator (ICD). Synchronized biventricular (BV) pacing is a new and promising therapy for symptomatic improvement of CHF in selected patients (low ejection fraction, intraventricular conduction delay). We postulate that this pacing therapy will diminish the need for tachyarrhythmia therapy. METHODS: Participants in the Ventak CHF trial received a triple-chamber biventricular ICD with a transvenous right ventricular lead and a left ventricular (LV) lead placed via thoracotomy. Of 54 patients enrolled in the Ventak CHF trial, 32 could be analyzed, with each completing three blinded months programmed to BV VDD pacing and a second randomly assigned three-month period of no pacing. RESULTS: Of the 32 patients, 13 (41%) received appropriate therapy for a ventricular tachyarrhythmia at least once in the six-month monitoring period postimplant. Five patients (16%) had at least one tachyarrhythmic episode while programmed to BV pacing, whereas 11 (34%) had at least one episode while programmed to no pacing. Three patients (9%) received therapy in both pacing periods, two with BV pacing only. The decrease in necessary tachycardia therapy during the BV pacing period was statistically significant (p = 0.035). CONCLUSIONS: In patients with standard ICD indications who also have CHF, LV dysfunction, and an intraventricular conduction delay, ICD therapy is less common with BV pacing. The mechanism for this improvement is unclear but may be related to hemodynamic improvement in CHF. Although BV pacing does not obviate the need for an ICD, it does diminish the need for appropriate tachyarrhythmia therapy in selected patients.

Cardiac Pacing, Artificial↗
PubMed2000

Relationship of cytokeratin 20 and CD44 protein expression with WHO/ISUP grade in pTa and pT1 papillary urothelial neoplasia.

The aim of this study was to assess the relationship of immunoreactivity of cytokeratin 20 (CK20) and CD44 across the spectrum of urothelial neoplasia using the WHO/ISUP consensus classification. A total of 120 papillary urothelial pTa and pT1 tumors (8 papillomas, 8 neoplasms of low malignant potential, and 42 low-grade and 62 high-grade carcinomas) were immunostained by using CK20 and CD44 antibodies. The relationships of tumor grade, pathologic stage, recurrences, and progression in stage with CK20 and CD44 immunoreactivity were assessed. WHO/ISUP grade correlated with tumor stage (P < 0.005), recurrence (P = 0.02), and progression in stage (P = 0.031). Normal urothelium showed CK20 immunoreactivity restricted to a few umbrella cells. Expression of CD44 in normal urothelium was restricted to the basal cell layer. Loss of CD44 immunoreactivity and increasing CK20 positivity were significantly associated with increasing tumor grade and stage (P < 0.005). An inverse relationship was observed in the staining patterns of CK20 and CD44 within individual cases, as well as in the aggregate data, with 79.2% of tumors with CD44 loss showing CK20 positivity (P < 0.001). In conclusion, CK20 and CD44 immunoreactivity are significantly related to the WHO/ISUP grade and to each other, and our data suggest their potential combined utility in predicting biologic behavior in patients with papillary urothelial pTa and pT1 neoplasms.

Adult↗
PubMed2000

A randomized, parallel-group study in Mumbai (Bombay), comparing chloroquine with chloroquine plus sulfadoxine-pyrimethamine in the treatment of adults with acute, uncomplicated, Plasmodium falciparum malaria.

A major problem in the control of malaria is the development of resistance, of the parasites to the existing drugs and of the vectors to insecticides. With few new drugs in the pipeline, in an era of declining resources, it is imperative to make judicious use of the existing antimalarials. In the city of Mumbai, resistance exists to chloroquine (CQ) and to sulfadoxine-pyrimethamine (SP). Use of a combination of CQ with SP would theoretically slow down the development of resistance to each of the drugs and increase their useful lives. The effectiveness of this combination in the treatment of adults from Mumbai, who had acute, uncomplicated Plasmodium falciparum malaria, was compared with that of CQ alone. The combination was found to be significantly more effective, in terms of 28- or 42-day cure rates, and to be more cost-effective.

Acute Disease↗
PubMed2000

Comparison of agonist-induced internalization of the human EP2 and EP4 prostaglandin receptors: role of the carboxyl terminus in EP4 receptor sequestration.

Prostaglandin E(2) (PGE(2)) couples to stimulation of adenylyl cyclase through two distinct G protein-coupled receptors designated EP2 and EP4. Although they have similar affinities for PGE(2), the EP(2) and EP4 receptors have distinct structural characteristics. EP2 is a 358-amino-acid protein with short third intracellular loop and C-terminal domains, whereas EP4 consists of 488 amino acids with a long third intracellular loop and a long cytoplasmic tail. The ability of the HA epitope-tagged receptors to undergo PGE(2)-induced internalization was examined by enzyme-linked immunosorbent assay and immunofluorescence microscopy after expression in human embryonic kidney 293 cells. The EP2 receptor did not internalize, whereas the EP4 receptor underwent rapid internalization. Truncation of the EP4 receptor after amino acid 350, which removes 138 residues, abolished internalization. Truncation after amino acid 369 markedly attenuated internalization, whereas truncation after amino acid 383 had little effect. Serine and threonine residues in the region 350 to 383 were mutated to determine their role in internalization. The mutants S370-382A, a full-length receptor containing six serine-to-alanine mutations in the region 370 to 382, and S354-369A, containing four serine mutations and one threonine mutation in the region 350 to 370, both internalized to the same extent as the wild-type. A further mutant, designated S354-382A, containing amino acid substitutions S354A, S359A, S364A, S366G, T369A, S370A, S371A, S374A, S377A, S379A, and S382A, also internalized to the same extent as the wild-type. We conclude that the C terminus of the EP4 receptor is involved in internalization; however, serine and threonine residues do not seem to be involved.

Amino Acid Sequence↗
PubMed2000

Outcome of pediatric thromboembolic disease: a report from the Canadian Childhood Thrombophilia Registry.

The outcome for children with deep vein thrombosis (DVT) and pulmonary embolism (PE) is unknown. An understanding of morbidity and mortality of DVT/PE is crucial to the development of rational treatment protocols. The Canadian Childhood Thrombophilia Registry has followed 405 children aged 1 mo to 18 y with DVT/PE for a mean of 2.86 y (range, 2 wk to 6 y) to assess outcome. The all-cause mortality was 65 of 405 children (16%). Mortality directly attributable to DVT/PE occurred in nine children (2.2%), all of whom had central venous line-associated thrombosis. Morbidity was substantial, with 33 children (8.1%) having recurrent thrombosis, and 50 children (12.4%) having postphlebitic syndrome. Recurrent thrombosis and postphlebitic syndrome were more common in older children, although deaths occurred equally in all age groups. The incidence of recurrent thrombosis and postphlebitic syndrome are likely underestimated because of difficulties in diagnosis, especially in younger children. The significant mortality and morbidity found in our study supports the need for international multicenter randomized clinical trials to determine optimal prophylactic and therapeutic treatment for children with DVT/PE.

Adolescent↗
PubMed2000

Burkitt lymphoma is immunophenotypically different from Burkitt-like lymphoma in young persons.

INTRODUCTION: Burkitt-like lymphoma (BLL) is a provisional category of B-cell lymphoma which is morphologically intermediate between Burkitt lymphoma (BL) and large B-cell lymphoma (LBCL). The clinical significance of this morphology is controversial. PATIENTS AND METHODS: We examined 41 cases of pediatric B-cell lymphoma by immunohistochemistry for proteins associated with proto-oncogenes c-myc, BCL-2 and BCL-6 and a subset of cases (with adequate slides) for a proliferation-associated marker (Ki-67) and for apoptosis (Apop-Tag). Sixteen cases of BLL, thirteen cases of BL and twelve cases of LBCL were examined. RESULTS: Our results showed BCL-6 expression in 16 of 16 BLL, 4 of 13 BL, and 9 of 12 LBCL; c-myc expression in 14 of 15 BLL, 9 of 13 BL, and 12 of 12 LBCL; and BCL-2 expression in 2 of 16 BLL, 9 of 13 BL, and 6 of 12 LBCL. Mean apoptotic index for BLL was 10.3% (n = 6); for BL was 17.1% (n = 5); and for LBCL was 10.9% (n = 6). Ki-67 was diffusely reactive in all cases tested. There was a significantly higher proportion of BLL than BL which expressed BCL-6 (P = 0.0001). CONCLUSIONS: Labeling for BCL-6 distinguishes BLL from BL. It is likely that in children in North America, BLL is biologically distinct from BL and more closely resembles a subset of LBCL.

Adolescent↗
PubMed2000

Relapse pattern of Plasmodium vivax in Mumbai: a study of 283 cases of vivax malaria.

OBJECTIVES: To analyze the relapse pattern of Plasmodium vivax in the city of Mumbai. METHODS: 283 cases of smear positive vivax malaria were treated with full dose (25 mg/kg) chloroquine and were asked to follow up for at least one year. None of the patients received primaquine. RESULTS: Of the 150 cases who followed up for at least one year, 19 relapsed, 17/19 relapsed within the first 6 months; indicating that the relapse pattern in the city is predominantly of the tropical or Chesson strain type. CONCLUSIONS: Vivax malaria patients should be monitored for at least six months. Those who do relapse should receive treatment with full dose chloroquine and 14 days of primaquine treatment.

Adolescent↗
PubMed1999

Follicular dendritic cell tumor of the parapharyngeal region.

BACKGROUND: Follicular dendritic cell (FDC) tumors are rare. A majority of the reported cases were confined to the lymph nodes. We report a case of FDC tumor occurring in the parapharyngeal region in a 45-year-old woman. METHODS: Characteristic histopathologic features of the excised primary and recurrent parapharyngeal tumors in conjunction with immunohistochemistry and electron microscopy helped us to arrive at a diagnosis of FDC tumor. RESULTS: Histopathology of primary excision revealed a lobulated tumor with a suggestion of ill-defined whorls. The most striking feature was regular occurrence of aggregates of lymphocytes within the tumor, especially around the blood vessels. The anatomic location together with the histology indicated the possibilities of either a meningioma, a salivary gland tumor, or a nerve sheath tumor. Immunostains for cytokeratin (CK), S-100 protein, and smooth muscle actin (SMA) were negative. However, the tumor cells showed strong immunoreactivity for epithelial membrane antigen (EMA) and vimentin. A diagnosis of parapharyngeal meningioma appeared to be the closest possibility. One year later, the patient developed a recurrence at the same site. A reexcision showed an identical tumor with an additional feature of lymphatic embolization and angioinvasion. A review of the entire case with further immunoreactivity for CD21 and CD35 confirmed the diagnosis of FDC. CONCLUSIONS: Follicular dendritic cell tumor has distinctive morphologic features and immunohistochemical profile. It is also characterized by considerable potential for recurrences.

Dendritic Cells↗
PubMed1999

Allogeneic blood stem cell and bone marrow transplantation for acute myelogenous leukemia and myelodysplasia: influence of stem cell source on outcome.

We have compared the outcomes of 87 patients with acute myelogenous leukemia (AML) and myelodysplasia (MDS) receiving matched sibling transplants with stem cells from peripheral blood (blood cell transplant, BCT) or bone marrow (BMT). In good risk patients (AML in CR1) granulocytes recovered to 0.5 x 10(9)/l a median of 14 days after BCT compared with 19 days after BMT (P < 0.0001). For patients with poor risk disease (AML beyond CR1 and MDS) corresponding figures were 16 vs 26 days (P < 0.0001). Platelet recovery to 20 x 10(9)/l was also faster after BCT (good risk 12 vs 20 days, P < 0.0001; poor risk 17 vs 22 days, P = 0.04). Red cell transfusions were unaffected by cell source, but BCT recipients required less platelet transfusions (good risk 1 vs 5, P = 0.002; poor risk 5 vs 11, P = 0.004). Blood cell transplants resulted in more chronic GVHD (86% vs 48%, P = 0.005) and a significantly higher proportion of recipients with KPS of 80% or less (48% vs 5%, P = 0.004). Disease-free survival at 4 years was 23% for both groups of poor risk patients but outcome in good risk patients was better after BCT (93% vs 62%, P = 0.047) related mainly to less relapse. While disease-free survival may be better after BCT than BMT for AML in CR1, quality of life may be relatively impaired.

Adolescent↗
PubMed1999

Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study.

This study was designed to test the hypothesis that high-dose asparaginase consolidation therapy improves survival in pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma. Five hundred and fifty-two patients (357 patients with T cell acute lymphoblastic leukemia (ALL) and 195 patients with advanced stage lymphoblastic lymphoma) were enrolled in POG study 8704 (T-3). Treatment included rotating combinations of high-dose myelosuppressive chemotherapy agents proven to be effective in T cell ALL in other POG group-wide or local institutional protocols (including vincristine, doxorubicin, cyclophosphamide, prednisone, asparaginase, teniposide, cytarabine and mercaptopurine). After achieving a complete remission (CR), patients were randomized to receive or not receive high-dose intensive asparaginase consolidation (25,000 IU/m2) given weekly for 20 weeks by intramuscular injection. Intrathecal chemotherapy (methotrexate, hydrocortisone and cytarabine) was given to prevent CNS disease, and CNS irradiation was used only for patients with leukemia and an initial WBC of >50,000/microl or patients with active CNS disease at diagnosis. CR was achieved in 96% of patients. The high-dose asparaginase regimen was significantly superior to the control regimen for both the leukemia and lymphoma subgroups. Four-year continuous complete remission rate (CCR) for the leukemia patients was 68% (s.e. 4%) with asparaginase as compared to 55% (s.e. 4%) without. For the lymphoma patients, 4-year CCR was 78% (s.e. 5%) with asparaginase and 64% (s.e. 6%) in the controls. The overall one-sided logrank test had a P value <0.001 favoring asparaginase, while corresponding values were P = 0.002 for ALL and P = 0.048 lymphoblastic lymphoma. Toxicities were tolerable, but there were 18 failures due to secondary malignancies (16 with non-lymphocytic leukemia or myelodysplasia). Neither WBC at diagnosis (leukemia patients) nor lymphoma stage were major prognostic factors. We conclude that when added to a backbone of effective rotating agents, repeated doses of asparaginase during early treatment improve the outcome for patients with T cell leukemia and advanced stage lymphoblastic lymphoma.

Adolescent↗
PubMed1999

Efficacies of 5- and 14-day primaquine regimens in the prevention of relapses in Plasmodium vivax infections.

Vivax malaria accounts for 80% of malaria cases in Mumbai (Bombay) and has high morbidity. In India, the standard treatment to prevent relapses of vivax malaria is a 5-day regimen of primaquine. However, between 1977 and 1997, the efficacy of this treatment declined from approximately 99% to 87%. The efficacy of the 5-day regimen was therefore compared with that of the 14-day regimen currently recommended by the World Health Organization, in Mumbai. The relapse rates observed, over a 6-month period of follow-up, were 0% with the 14-day regimen, 26.7% with the 5-day, and 11.7% when no primaquine treatment was given. The expenditure incurred on the door-to-door dispensing of the 5-day regimen appears to be without benefit. There is an urgent need to review the present strategy for controlling relapses in vivax malaria, at least for the city of Mumbai, and similar studies need to be carried out in other parts of India, to make all anti-relapse strategies more appropriate.

Antimalarials↗