Cobalamin and Folic Acid Status in Relation to the Etiopathogenesis of Pancytopenia in Adults at a Tertiary Care Centre in North India

Background. Pancytopenia has multiple etiologies like megaloblastic anemia, aplastic anemia, leukemia, and various infections. We investigated the clinical, etiological and hematological profile including bone marrow morphology of patients with pancytopenia in relation to their vitamin B12 and folic acid status at a tertiary care referral hospital in north India. Methods. A total of 140 consecutive patients with pancytopenia were selected from June 2007 to December 2008. Bone marrow examination and other tests were carried out as warranted, including serum cobalamin and folate assays using liquid chromatography mass spectroscopy (LC MS/MS). Results. The study population consisted of 92 males and 48 females with a mean age of 32.8 years. Megaloblastic anemia 60.7%, aplastic anemia (7.8%), and leukemia (9.2%) were common causes. Infectious causes (16.4% of all cases) included leishmaniasis, HIV–AIDS, malaria and tuberculosis. Severe cobalamin deficiency (B12 < 100 pg/mL) was seen in 81% of all patients including 91.6% of patients with MA. In contrast, only 7.14% of all pancytopenic patients were folate deficient. Folate deficiency (<5 ng/mL) was seen in just 5% MA patients. Combined cobalamin and folate deficiency was seen in 5 patients (3.51%). Conclusion. Cobalamin deficiency was found to be more common in our setting and is largely underdiagnosed in the age of folate supplementation. Infectious diseases like tuberculosis, leishmaniasis, and increasingly HIV are important and treatable causes of pancytopenia. This is in contrast with the developed nations where the bulk of disease is due to malignancy or marrow aplasia

Safety profile of imatinib in Indian chronic myeloid leukemia patients

Introduction: Imatinib mesylate has become the choice of drug in the treatment of chronic myeloid leukemia. Objective: To study safety profile of Imatinib (specific inhibitor or bcrabl tryosne kinase protein) in Philadelphia chromosome t {(9:22), bcr-abl} positive chronic myeloid leukemia (CML) chronic phase patients. Materials and Methods: After IEC clearance, 36, BCR-ABL positive CML patients in the chronic phase of the disease were recruited. Imatinib mesylate (Gleevec, Novartis), was started (400mg daily) and followed up weekly in first month, two weekly till three months &amp; monthly thereafter. Safety profile data, recorded in pre-designed proforma, were analyzed for time of onset, duration and severity of adverse effects. Causality relationship of recorded adverse events was established with imatinib therapy using WHO-UMC criteria. Results: A total of 222 adverse events were reported in 36 CML-CP patients over 12 months of follow up. Thrombocytopenia was the most commonly reported in 60% of the patients followed by musculoskeletal (17%), dermatological (16%), gastrointestinal disturbances (13%), body weight changes (11%), superficial edema (8%) and liver enzyme rise (4%). More than 80% events reported within months of therapy which persisted for less than 3 months in most of the cases. No treatment was needed in 68% of cases while therapy alteration was not needed in 88% of cases. Most of the reactions (60%) had probable relationship with the therapy. Conclusion: Imatinib was well tolerated, having only mild to moderate grade of toxicities, mostly within 3 months of therapy and most of them persisted for less than 3 months of duration, requiring only symptomatic treatment and drug withhold or dose decrement in only few cases

The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

Abstract Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART) when co-administered with rifampicin-containing antituberculosis treatment (ATT) and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1%) patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD) Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10), 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08), 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10) respectively and 3.04 μg/ml (in cases). Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in antiretroviral effectiveness. Larger sample sized studies and longer follow-up are required to identify populations of individuals where the reduction in nevirapine concentration may result in lower ART response or shorter response duration

Transconjunctival penetration of mitomycin C

<b>Aims:</b> The study was performed to estimate transconjunctival penetration of mitomycin C (MMC) to Tenon&#x2032;s tissue following application over the intact conjunctiva before routine trabeculectomy. <b> Settings and Design:</b> Institution-based case series. <b> Materials and Methods:</b> In 41 eyes of 41 patients, MMC (0.4 mg/ml for 3 min) was applied over the intact conjunctiva before beginning trabeculectomy. Tenon&#x2032;s capsule directly beneath the site of application was excised during trabeculectomy and was homogenized, centrifuged and MMC concentrations were analyzed using high-performance liquid chromatography (HPLC). <b> Statistical Analysis Used:</b> Statistical analysis was performed using stata0 8.0 version software (STATA Corporation, Houston, TX, USA). In this study, <i> P</i> -values less than 0.05 were considered as statistically significant. <b> Results:</b> The average weight of the sample of Tenon&#x2032;s tissue excised was 5.51 &#x00B1; 4.42 mg (range: 0.9-17.1) and the average estimated MMC concentration found to be present in Tenon&#x2032;s tissue using HPLC was 18.67 &#x00B1; 32.36 x 10^&#8722;6 moles/kg of the tissue (range: 0.38-197.05 x 10^&#8722;6 ). In 36 of the 41 patients (87.80&#x0025;), the MMC concentration reached above 2 x 10^&#8722;6 moles/kg of the tissue concentration required to inhibit human conjunctival fibroblasts. <b> Conclusions:</b> Mitomycin C does permeate into the subconjunctival tissue after supraconjunctival application for 3 min. Application of MMC over the conjunctiva may be a useful alternative to subconjunctival or subscleral application during routine trabeculectomy and as an adjunct for failing blebs

Comprehensive evaluation of formulation factors for ocular penetration of fluoroquinolones in rabbits using cassette dosing technique

Charu Sharma,1,2 Nihar R Biswas,1 Shreesh Ojha,3 Thirumurthy Velpandian1 1Department of Ocular Pharmacology and Pharmacy, All India Institute of Medical Sciences, New Delhi, India; 2Department of Internal Medicine, 3Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al&nbsp;Ain, UAE Objective: Corneal permeability of drugs is an important factor used to assess the efficacy of topical preparations. Transcorneal penetration of drugs from aqueous formulation is governed by various physiological, physiochemical, and formulation factors. In the present study, we investigated the effect of formulation factors like concentration, pH, and volume of instillation across the cornea using cassette dosing technique for ophthalmic fluoroquinolones (FQs). Materials and methods: Sterile cocktail formulations were prepared using four congeneric ophthalmic FQs (ofloxacin, sparfloxacin, pefloxacin mesylate, and gatifloxacin) at concentrations of 0.025%, 0.5%, and 0.1%. Each formulation was adjusted to different pH ranges (4.5, 7.0, and 8.0) and assessed for transcorneal penetration in vivo in rabbit&rsquo;s cornea (n=4 eyes) at three different volumes (12.5, 25, and 50&nbsp;&micro;L). Aqueous humor was aspirated through paracentesis after applying local anesthesia at 0, 5, 15, 30, 60, 120, and 240&nbsp;minutes postdosing. The biosamples collected from a total of 27 groups were analyzed using liquid chromatography&ndash;tandem mass spectroscopy to determine transcorneal permeability of all four FQs individually. Results: Increase in concentration showed an increase in penetration up to 0.05%; thereafter, the effect of concentration was found to be dependent on volume of instillation as we observed a decrease in transcorneal penetration. The highest transcorneal penetration of all FQs was observed at pH 7.0 at concentration 0.05% followed by 0.025% at pH 4.5. Lastly, increasing the volume of instillation from 12.5 to 50&nbsp;&micro;L showed a significant fall in transcorneal penetration. Conclusion: The study concludes that formulation factors showed discernible effect on transcorneal permeation; therefore, due emphasis should be given on drug development and design of ophthalmic formulation. Keywords: transcorneal penetration, ophthalmic, in vivo, antibacteria