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258. In vitro and in vivo evaluation of clastogenicity of second-line antitubercular drug loaded PLGA nanoparticles.

Author

Pandey, Avaneesh Kumar, Kumar, Rajendra, Shafiq, Nusrat, Kondel, Ritika, Garg, Shanky, Negi, Harish, Arora, Sunil Kumar, Varma, Neelam, and Malhotra, Samir

Subjects
ANTITUBERCULAR agents, SISTER chromatid exchange, NANOCAPSULES, CHO cell, LABORATORY mice, NANOPARTICLES
Abstract

Sustained release nanoformulations of second line antitubercular drugs levofloxacin and ethionamide had shown promise in pharmacokinetics and acute and sub-acute toxicity studies. The present study evaluated the clastogenicity potential of the nanoformulations of these antitubercular agents. Clastogenicity was evaluated by (a) in vitro micronucleus assay (b) in vivo micronucleus assay in Swiss albino mice and (c) sister chromatid exchange (SCE) in CHO cell lines. Ethionamide and levofloxacin loaded nanoparticles were 312 ± 64 nm and 245 ± 24 nm in size respectively and drug encapsulation was 35.2 ± 3.1% w/w and 45.6 ± 9.4% w/w, respectively. The frequency of MN-NCE/1000 NCE and MN-PCE/1000 PCE were significantly reduced in mice treated with ethionamide nanoparticle (3.5 ± 0.9, 13.8 ± 16.68) and levofloxacin nanoparticles (5.6 ± 2.7, 16.7 ± 12.7) compared to the mice treated with free ethionamide (11.5 ± 4.1, p = 0.23 and 45.19 ± 19.21, p = 0.38) and free levofloxacin (14.7 ± 1.88, p < 0.0001 and 54.6 ± 18.1, p = 0.0017), respectively. For in vitro, micronucleus assay frequencies of micronuclei per thousand bi-nucleated cells (MN-BN/1000 BN) was 188.3 ± 20.20 and 148 ± 20.42 for ethionamide and levofloxacin nanoparticles as compared to 232.6 ± 16.04 (p = 0.52) and 175 ± 5.56 (p = 0.45) for free ethionamide and levofloxacin, respectively. The average number of SCE per cell for nanoformulation of ethionamide were not different from that of free drug (4.9 ± 0.51 vs 4.1 ± 0.55, p = 0.86). The SCE per cells were not significant difference for nanoformulation of levofloxacin (2.33 ± 1.36 vs 5.46 ± 0.25, p = 0.88). In vitro and in vivo assays have shown relatively less clastogenic potential of equivalent dose of ethionamide nanoparticles as compared to the conventional formulation. [ABSTRACT FROM AUTHOR]

Published
2021
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259. The Spectrum of Hypereosinophilia and Associated Clonal Disorders – A Real-World Data Based on Combined Retrospective and Prospective Analysis from a Tropical Setting

Author

Sreedharanunni, Sreejesh, Varma, Neelam, Sachdeva, Man Updesh Singh, Naseem, Shano, Malhotra, Pankaj, Bansal, Deepak, Trehan, Amita, and Varma, Subhash

Subjects
lymphocytic variant of hypereosinophilia, clonal hypereosinophilia, Imatinib responsive hypereosinophilia, Hypereosinophilic syndromes, Original Article, Hypereosinophilia, FIP1L1-PDGFRA, biological phenomena, cell phenomena, and immunity, reproductive and urinary physiology
Abstract

Objective To determine the frequency, etiological spectrum and treatment outcome of hypereosinophilia (HE) and hypereosinophilic syndromes (HES) in a tropical setting. Methods A retrospective analysis of hospital data of five years (January 2009 to December 2013) and a comprehensive prospective evaluation of patients presenting with HE/HES over a period of 33 months (January 2014 to September 2016) was performed. Results HE/HES was diagnosed in a total of 125 patients during the study period with an estimated prevalence of 0.5–1 case per 100,000 population in our hospital settings. 41 patients were excluded from the final analysis due to lack of sufficient data. Infections, especially helminths were the commonest cause (34%) followed by primary/clonal HE/HES (24%) and reactive HE/HES secondary to various clonal disorders (14.3%). A lymphocytic variant of HES and FIP1L1-PDGFRA positive HES were diagnosed in 3.6% each. Imatinib-responsive BCR-ABL1 negative HE/HES constitute 7.1% in our patients. None of the clinical or routine laboratory features including the age of patients, duration of HE, presence or absence of organomegaly, hemoglobin levels, eosinophil %, absolute eosinophil count, total leukocyte count, platelet counts, serum IgE levels or presence of myelofibrosis could predict or exclude malignancy in patients with HE/HES. The absence of blasts in peripheral blood or the absence of >5% blasts in bone marrow does not exclude primary/clonal HES. Conclusions An underlying malignancy (Primary HE/HES and neoplasms leading to reactive HES; 35.7%) is diagnosed with nearly equal frequency compared to infections (34.5%) in tropical settings. There are no hematological or serological parameters, which can reliably be used to exclude an underlying malignancy, necessitating a thorough follow-up and comprehensive work-up in patients with HE/HES.

Published
2018

261. Individualized, Low Dose, Fixed Duration Lenalidomide Maintenance Is an Effective Strategy in High MRD Disease Post Chemo-Immunotherapy in CLL: Outcomes of a Randomized Controlled Trial

Author

Jindal, Nishant, primary, Sachdeva, Man Updesh Singh, additional, Jain, Arihant, additional, Prakash, Gaurav, additional, Khadwal, Alka, additional, Sreedharanunni, Sreejesh, additional, Varma, Neelam, additional, Malhotra, Pankaj, additional, and Lad, Deepesh, additional

Published
2019
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262. Spectrum of Genetic Defects and Phenotype-Genotype Correlation in Dyserythropoietic Anemias: Bench to Bedside Approach in the Indian Scenario

Author

Das, Reena, primary, Jamwal, Manu, primary, Aggarwal, Anu, primary, Sharma, Prashant, primary, Sachdeva, Man Updesh Singh, primary, Bansal, Deepak, primary, Sreedharanunni, Sreejesh, primary, Kumar, Narender, primary, Naseem, Shano, primary, Ahluwalia, Jasmina, primary, Varma, Neelam, primary, Malhotra, Pankaj, primary, and Maitra, Arindam, primary

Published
2019
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263. Screening for paroxysmal nocturnal hemoglobinuria (PNH) in patients presenting with cerebral sinovenous thrombosis (CSVT): Results of a FLAER based flowcytometry study in Indian patients

Author

Sharma, Saniya, primary, Ahluwalia, Jasmina, additional, Atreja, Charu Batra, additional, Modi, Manish, additional, Sachdeva, Manupdesh Singh, additional, Kumar, Narender, additional, Bose, Parveen, additional, Bose, Sunil Kumar, additional, Uppal, Varun, additional, Lal, Vivek, additional, and Varma, Neelam, additional

Published
2019
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264. In Ph+BCR-ABL1P210+ acute lymphoblastic leukemia the e13a2 (B2A2) transcript is prevalent

Author

Baccarani, Michele, primary, Iacobucci, Ilaria, additional, Chiaretti, Sabina, additional, Foà’, Robin, additional, Balasubramanian, Poonkuzhali, additional, Paietta, Elisabeth, additional, Foroni, Letizia, additional, Jeromin, Sabine, additional, Izzo, Barbara, additional, Spinelli, Orietta, additional, Varma, Neelam, additional, Menif, Samia, additional, Terragna, Carolina, additional, Seth, Tulika, additional, Bidet, Audrey, additional, Coriu, Daniel, additional, Lunghi, Francesca, additional, Mayer, Jiri, additional, Scappini, Barbara, additional, Langabeer, Stephen, additional, Maier, Jacqueline, additional, Burt, Emma, additional, Candoni, Anna, additional, Albano, Francesco, additional, Luppi, Mario, additional, Zupan, Irena, additional, Lion, Thomas, additional, Zadro, Renata, additional, di Raimondo, Francesco, additional, Poopak, Behzad, additional, Rege-Cambrin, Giovanna, additional, Annunziata, Mario, additional, Ayala, Ana, additional, Salinas-Viedma, Victor, additional, Ines Prado, Ana, additional, Milner, Benedict, additional, Galimberti, Sara, additional, Janssen, Jeroen, additional, Polli, Valentina, additional, Comba, Lorenzo, additional, Borsellino, Beatrice, additional, Annibali, Ombretta, additional, Crugnola, Monica, additional, and Passamonti, Francesco, additional

Published
2019
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266. Genetic basis of unexplained erythrocytosis in Indian patients

Author

Mallik, Nabhajit, primary, Sharma, Prashant, additional, Kaur Hira, Jasbir, additional, Chhabra, Sanjeev, additional, Sreedharanunni, Sreejesh, additional, Kumar, Narender, additional, Naseem, Shano, additional, Sachdeva, Man Updesh Singh, additional, Ahluwalia, Jasmina, additional, Malhotra, Pankaj, additional, Varma, Neelam, additional, Varma, Subhash, additional, and Das, Reena, additional

Published
2019
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275. Adolescent and Young Adult Chronic Myeloid Leukemia in Real-World Settings: Experience from a Tertiary Care Institute in Northern India

Author

Yanamandra, Uday, primary, Sahu, Kamal Kant, additional, Karunakaran, Parathan, additional, Katoch, Deeksha, additional, Jain, Nidhi, additional, Khadwal, Alka, additional, Prakash, Gaurav, additional, Lad, Deepesh, additional, Naseem, Shano, additional, Varma, Neelam, additional, Varma, Subhash, additional, and Malhotra, Pankaj, additional

Published
2019
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277. Treatment and outcome of chronic myeloid leukemia in children and adolescents: The Indian Pediatric Oncology Group-CML-16-01 multicentric study

Author

Totadri, Sidharth, primary, Mahajan, Amita, additional, Gupta, Vineeta, additional, Das, Anirban, additional, Meena, Jagdish Prasad, additional, Singh, Manisha, additional, Mohammed, Sajid, additional, Aggarwal, Priyanka, additional, Tuladhar, Sucharita, additional, Seth, Rachna, additional, Naseem, Shano, additional, Varma, Neelam, additional, Trehan, Amita, additional, and Bansal, Deepak, additional

Published
2019
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285. Variation in Adherence Measures to Imatinib Therapy

Author

Yanamandra, Uday, primary, Malhotra, Pankaj, additional, Sahu, K.K., additional, Sushma, Yanamandra, additional, Saini, Neha, additional, Chauhan, Pooja, additional, Gill, Jasmeen, additional, Rikhi, Deepika, additional, Khadwal, Alka, additional, Prakash, Gaurav, additional, Lad, Deepesh, additional, Suri, Vikas, additional, Kumari, Savita, additional, Varma, Neelam, additional, and Varma, Subhash, additional

Published
2018
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286. Characterization of immunophenotypic aberrancies in adult and childhood acute lymphoblastic leukemia: A study from Northern India

Author

Sharma, Manupriya, Sachdeva, Man, Varma, Neelam, Varma, Subhash, and Marwaha, R.

Subjects
Phenotypes -- Identification and classification, Gene expression -- Health aspects, Acute lymphocytic leukemia -- Genetic aspects -- Development and progression, Health
Abstract

Byline: Manupriya. Sharma, Man. Sachdeva, Neelam. Varma, Subhash. Varma, R. Marwaha Background: Identification of aberrant antigen expression is important in characterizing neoplastic population among non.neoplastic bone marrow counterparts and further [...]

Published
2016

290. Markers of Thrombin Generation and Inflammation in Patients with Paroxysmal Nocturnal Hemoglobinuria.

Author

Dhawan, Rishi, Ahluwalia, Jasmina, Malhotra, Pankaj, Mahapatra, Manoranjan, Varma, Neelam, and Varma, Subhash

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) presents with intravascular hemolysis, bone marrow failure and thrombosis. Various studies have reported geographic and ethnic variation in prevalence of thrombosis in PNH. There is limited data on thrombosis in PNH from the Indian subcontinent. In this study we describe disease burden and risk factors for thrombosis in 18 Indian PNH patients. We studied markers of thrombin generation (Thrombin-antithrombin complexes; TAT and D-Dimer), endothelium and platelet activation (soluble P-selectin) and inflammation (interleukin-6; IL-6) in PNH patients and compared their levels with healthy controls. Thrombosis was identified in 17% of PNH patients. TAT, sP-selectin and D-Dimer levels were significantly elevated in PNH patients (TAT: 5.06 ± 1.08 ng/ml; sP-selectin: 80.57 ± 19.5 ng/ml; D-Dimer mean: 936 ng/ml 95% CI 559, 1310) compared to control population (TAT: 3.39 ± 0.769 ng/ml P = 0.016; sP-selectin: 44.67 ± 5.17 ng/ml P = 0.002). Using Youden's J statistic, the cut-off values for TAT and sP-selectin in our cohort of PNH patients were 2.90 ng/ml and 58.41 ng/ml respectively. TAT, sP-selectin and D-Dimer levels were elevated beyond the cut-off values in PNH patients with thrombosis compared to those without thrombosis. A positive correlation was noted between TAT, sP-selectin and D-Dimer levels. Increased TAT, sP-selectin, and D-Dimer levels may indicate impending thrombosis in PNH. [ABSTRACT FROM AUTHOR]

Published
2021
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295. Receptor Ck-dependent signaling regulates hTERT gene transcription

Author

Varma Neelam, Kaul Deepak, and Sikand Kavleen

Subjects
Cytology, QH573-671
Abstract

Abstract Background Available evidence suggests that the regulation of telomerase activity primarily depends on the transcriptional control of the human telomerase reverse transcriptase (hTERT) gene. Although several activators and repressors of hTERT gene transcription have been identified, the exact mechanism by which hTERT transcription is repressed in normal cells and activated in cancer cells remains largely unknown. In an attempt to identify possible novel mechanisms involved in the regulation of hTERT transcription, the present study examined the role of Receptor Ck, a cell surface receptor specific for cholesterol, in the transcription of hTERT gene in normal human peripheral blood mononuclear cells. Results Activated Receptor Ck was found to down-regulate hTERT mRNA expression by repressing the transcription of c-myc gene. Receptor Ck-dependent signaling was also found to down-regulate the mRNA expression of the gene coding for the ligand inducible transcription factor, peroxisome proliferator-activated receptor γ (PPARγ). The ligand activation of PPARγ resulted in the down-regulation of c-myc and hTERT mRNA expression. By using specific activator and inhibitor of protein kinase C (PKC), it was demonstrated that Receptor Ck dependent down-regulation of hTERT gene transcription involved inhibition of PKC. In addition, 25-hydroxycholesterol was found to contribute to the transcriptional regulation of hTERT gene. Conclusion Taken together, the findings of this study present evidence for a molecular link between cholesterol-activated Receptor Ck and hTERT transcription, and provide new insights into the regulation of hTERT expression in normal human peripheral blood mononuclear cells.

Published
2006
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296. Polymerase chain reaction-restriction fragment length polymorphism method for detection of Calreticulintype-1 and type-2 mutations in myeloproliferative neoplasm

Author

Naseem, Shano, Binota, Jogeshwar, Varma, Neelam, Satyarthi, Priti, Rana, Palak, and Malhotra, Pankaj

Abstract

Calreticulin (CALR) mutations are included in the WHO diagnostic criteria of Myeloproliferative Neoplasm (MPN). Presence of CALRmutation, aids in their diagnosis by excluding reactive causes. There are several molecular techniques to detect CALRmutations; however, these require advanced equipment and technical expertise. An in-house “polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP)” method, using restriction enzymes MseI and MluCI for detection of CALRtype-1 and type-2 mutations, was developed. PCR-RFLP method was validated by comparing its results with real-time PCR (RQ-PCR) using CE-IVD marked Ipsogen® CALR RGQ PCR (Qiagen, Germany) kit. All PCR-RFLP positive CALRtype-1 and type-2 mutations samples of MPN (n=26) were confirmed positive by RQ-PCR, and all negative samples (n=21) were confirmed to be negative, showing 100% diagnostic sensitivity and specificity for CALRmutation detection by PCR-RFLP. The developed PCR-RFLP method can be used for detection of CALRtype-1 and type-2 mutations with only a PCR machine and gel electrophoresis system. It is an inexpensive and easily applicable alternative method which can be adopted even by a small molecular laboratory for detection of CALRmutations.

Published
2021
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297. Frequency of MYD88 L256P mutation and its correlation with clinico-hematological profile in mature B-cell neoplasm

Author

Shekhar, Raja, Naseem, Shano, Binota, Jogeshwar, Varma, Neelam, and Malhotra, Pankaj

Abstract

B-cell neoplasms are clonal tumors of B cells at various stages of maturation, including diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic lymphoma (CLL), Burkitt lymphoma (BL), lymphoplasmacytic lymphoma (LPL)/Waldenström’s macroglobulinemia (WM), splenic marginal zone lymphoma (SMZL), nodal marginal zone lymphoma (NMZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and hairy cell leukemia (HCL). In this study, we analyzed the frequency of MYD88L265P mutation and its correlation with clinico-hematological profile in mature B-cell neoplasms.

Published
2021
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300. Long-term outcomes of innovator versus generic melphalan formulation in autologous hematopoietic cell transplantation for multiple myeloma

Author

Lad, Deepesh P., Malhotra, Pankaj, Patil, Amol N., Nampoothiri, Ram V., Kasudhan, Kripa Shanker, Khadwal, Alka, Prakash, Gaurav, Jain, Arihant, Malhotra, Samir, Varma, Neelam, Attri, Savita Verma, and Varma, Subhash

Abstract

Most data on autologous hematopoietic cell transplantation (auto-HCT) in myeloma are based on the use of innovator formulation of melphalan. Comparative bioequivalence and efficacy studies of generic melphalan are lacking.

Published
2021
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