Forskolin is the first pharmaceutical drug and product derived from a plant to be approved in India by the DCGI in 2006. Forskolin (7beta-acetoxy-8, 13-epoxy-1a, 6β, 9a-trihydroxy-labd-14-en-11-one) is a diterpenoid isolated from plant Coleus forskohlii (Lamiaceae). It is a lipid-soluble compound that can penetrate cell membranes and stimulates the enzyme adenylate cyclase which, in turn, stimulates ciliary epithelium to activate cyclic adenosine monophosphate, which decreases intraocular pressure (IOP) by reducing aqueous humor inflow. The topical application of forskolin is capable of reducing IOP in rabbits, monkeys, and humans. In its drug interactions, forskolin may act synergistically with epinephrine, ephedrine and pseudoephedrine. Whereas the effects of anti-clotting medications like warfarin, clopidogre, aspirin, anoxaparin, etc., may be enhanced by forskolin. Forskolin is contraindicated in the medications for people with ulcers as forskolin may increase acid level. Forskolin has a very good shelf-life of five years. Recently, its Ophthalmic inserts and in situ gels for sustained and delayed-release drug delivery systems were tested in New Zealand Albino Rabbits for its antiglaucoma efficacy. This drug review explains Forskolin as a drug, its antiglaucoma potential and recent findings of forskolin as an antiglaucoma agent. The literature search method used for this review was different databases and search engines like PubMed, International Pharmaceutical Abstracts, Google, Medicinal and Aromatic Plants (MAPA).

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Background: Drug-resistant tuberculosis is one of major current challenges to global public health. The transmission of resistant strains is increasing as a burden of multidrug-resistant tuberculosis (MDR-TB) patients in extra pulmonary tuberculosis (EPTB) cases in India. Aim and Objectives: The aim was to study trends of anti-tuberculosis drug resistance pattern in new cases and previously treated cases of EPTB in referral hospitals in northern India. Study Design and Setting: A prospectively observational study and referral medical institutions in northern India. Materials and Methods: All EPTB specimens were processed for Ziehl Neelsen staining, BACTEC culture and BACTEC NAP test for Mycobacterium tuberculosis complex. All M. tuberculosis complex isolates were performed for radiometric-based drug susceptibility pattern against streptomycin, isoniazid, rifampicin and ethambutol using the 1% proportion method. Results: We found that 165/756 (20.5%) isolates were identified as M. tuberculosis complex by the NAP test. We observed that 39.9% were resistant to first-line antitubercular drugs. The resistance rate was higher in previously treated patients: H (30.3%), R (16.3%), E (15.7%) and S (16.3%). MDR-TB was observed in 13.4%, but, in new cases, this was 11.4% and 19.1% of the previously treated patients (P<0.05). Conclusion: MDR-TB is gradually increased in EPTB cases and predominant resistance to previous treated cases of EPTB. The molecular drug sensitivity test (DST) method can be an early decision for chemotherapy in MDR-TB patients. The International Standards of TB Care need to be used by the RNTCP and professional medical associations as a tool to improve TB care in the country.

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Over the last 20 years, the prevalence of healthcare-associated Clostridium difficile (C. diff) disease has increased. While multiple tests are available for the diagnosis of C. diff infection, enzyme immunoassay (EIA) testing for toxin is the most used. Repeat EIA testing, although of limited utility, is common in medical practice. To assess the utility of repeat EIA testing to diagnose C. diff infections. Systematic literature review. Eligible studies performed >1 EIA test for C. diff toxin and were published in English. Electronic searches of MEDLINE and EMBASE were performed and bibliographies of review articles and conference abstracts were hand searched. Of 805 citations identified, 32 were reviewed in detail and nine were included in the final review. All studies except one were retrospective chart reviews. Seven studies had data on number of participants (32,526), and the overall reporting of test setting and patient characteristics was poor. The prevalence of C. diff infection ranged from 9.1% to 18.5%. The yield of the first EIA test ranged from 8.4% to 16.6%, dropping to 1.5-4.7% with a second test. The utility of repeat testing was evident in outbreak settings, where the yield of repeat testing was 5%. Repeat C. diff testing for hospitalized patients has low clinical utility and may be considered in outbreak settings or when the pre-test probability of disease is high. Future studies should aim to identify patients with a likelihood of disease and determine the utility of repeat testing compared with empiric treatment.

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Hidradenitis suppurativa (HS), a painful and chronic condition, commonly occurs in women and coincides with post-pubertal increase in sex hormones. A 13-year-old pre-pubertal HIV-infected male child presented to our clinic with a discharging right axillary lymph node swelling. The biopsy of the lesion showed features of HS. The patient was treated with oral antibiotics, oral steroids, and local antibiotic wash. Though the patient responded to this treatment, the clinical response was not adequate and the lesion recurred. Subsequently, the child was started on antiretroviral therapy (zidovudine, lamivudine, and nevirapine). Following these medications, the lesions healed and had not recurred till we last examined the child. Thus, this is a rare presentation of a known condition in an HIV-infected pre-pubertal male child, which did not respond to usual modalities of treatment and had to be treated with antiretroviral therapy.

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Background : Chronic damage to the central nervous system resulting in cognitive impairment has been shown with repeated, low doses of organophosphorus (OP) exposure over month or years. Aim: The study aimed to find out whether there is any cognitive impairment following acute OP exposure that could be detected by a simple screening instrument, the Mini Mental State Examination (MMSE), in clinical settings. Settings and Design: A cohort study. Materials and Methods: The study was conducted with matched controls. Consecutive patients admitted to the hospital with acute ingestion of OP were recruited. Cognitive function was assessed with the MMSE, digit span test, test of long-term memory function and concentration. Patients were assessed twice: at 1 and 6 weeks of exposure. Statistical Analysis: Continuous variables were analyzed with the paired and unpaired T-tests. Non-normally distributed data were analyzed with the Mann-Whitney U test and Wilcoxon Signed Rank test. Discrete variables were analyzed with the Chi-square test. Results: There were 60 patients and 61 controls. The mean age (SD) of the patients and controls was 31.5 (11.6) and 31.3 (11.8) years, respectively. Forty-two patients turned up for the second assessment. Significant impairment of cognitive function was seen in the total score of MMSE (95% CI -2.5 to -0.3), orientation (95% CI -1 to -0.2) and language (95% CI -0.9 to -0.1) domains of MMSE, digit span test (95% CI 0.1-1.7) and test of long-term memory function (95% CI 0.3-2.3) in the first assessment compared with the controls. When the results of the second assessment were compared with the controls, no significant differences were seen. Conclusion: Although there was a slight transient cognitive impairment detected with the screening tests following acute OP ingestion, no long-term cognitive defects was detected.

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Background: Diagnosis of visceral leishmaniasis (VL) is a major obstacle in the control of this disease. The rK39 strip-test using patient's blood is a breakthrough; however, it still requires a blood sample, which is a concern for safety in the field. We tried to simplify the test using the patient's urine instead of blood. Aims: To observe the sensitivity and specificity of the urine test in comparison with the blood test. Materials and Methods: We tested active and post-treatment VL patients, Post Kala azar dermal leishmaniasis (PKDL), VL/HIV and control subjects (healthy, disease suspects and diseased other than VL) with the rK39 strip-test using blood and urine samples. Statistical Analysis: The level of agreement between the urine and blood testing was calculated by inter-rater agreement (kappa) statistics. Results: Forty-two active VL, 40 treated VL, six PKDL, three VL/HIV and 139 controls (54 healthy, 21 disease suspects and 64 diseased other than VL) were tested. All VL-related cases showed positive results with urine as well as blood samples (100%). The urine testing was found to have 100% sensitivity and 86.33% specificity for the diagnosis of VL. Kappa statistic between the two methods was 0.916 (P<0.001). Urine testing had more false-positive results in comparison with blood testing (13.67% vs. 9.45%), but the test subjects were from VL-endemic areas and they might be exposed to Leishmania donovani infection. Conclusions: The present study has the potentiality of providing a new, yet simplest non-invasive screening tool for VL in remote rural areas.

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Background: Out of a panel of 37 candidate genes tested for linkage with polycystic ovary syndrome (PCOS), the strongest evidence of linkage was reported in the follistatin (FST) gene region. Subsequently, a couple of studies outside India investigated the FST gene for the presence of any mutations and its association with PCOS and the results were found to be largely inconsistent probably due to differences in the ethnic backgrounds and small sample sizes. Aims: To screen the FST gene for mutations and to establish their association pattern with PCOS among a large cohort of South Indian women. Settings and Design: Case-control study. Materials and Methods: PCOS cases were recruited according to the 2003 Rotterdam diagnostic criteria. All the exons of the FST gene were amplified and analyzed in all the cases and controls for the presence of mutations using polymerase chain reaction (PCR) and direct DNA sequencing. Results: A total of 549 women consisting of 250 PCOS cases and 299 controls were recruited for the study. No mutations were found in any of the exons of the FST gene in our Indian sample which is consistent with an earlier finding among the Asian women from Singapore. Although three of the four cohorts of Caucasian background studied earlier reported variants, none of them could establish a strong association with PCOS. Conclusions: The occurrence of the exonic variants of FST gene seems to be dependent on the ethnic background of the subjects under study and its role in the PCOS pathophysiology cannot be established with hitherto available evidence.

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Androgen-deprivation therapy is the mainstay of treatment for the management of advanced prostate carcinoma till transition to castration-resistant prostate carcinoma (CRPC). Recently, adrenal and intratumoral synthesis of androgens has been found to be the major cause for CRPC. Abiraterone acetate is an orally active, potent and selective inhibitor of 17 a hydroxylase and c 17, 20 lyase, which acts by decreasing the de novo production of androgens with no rise in steroids downstream. Multiple randomized trials have shown significant improvement of >50% decline in prostate-specific antigen (PSA) and time to PSA progression (TTPP) with abiraterone acetate 1000 mg per day in chemotherapy/ketoconazole treated and naive CRPC patients producing reversible and manageable adverse effects due to mineralocorticoid excess. This article reviews the available evidence on efficacy and safety of this drug in CRPC. Searches of Pubmed, Cochrane database, Medscape, Google and clinicaltrial.org were made for terms like CRPC and abiraterone.

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This case describes a 42-year-old female with longstanding history of rheumatoid arthritis (RA) and Felty syndrome (FS). She presented with acute renal kidney failure, skin rash and hemoptysis. A clinical suspicion of small vessel vasculitis (SVV) was thought, serology was also positive for various markers of SVV. However, these serology markers could be false-positive in a patient of rheumatoid arthritis. A renal biopsy was performed that led to the final diagnosis of cryoglobulinemic vasculitis. Patient was managed according to the standard guidelines for therapy (plasmafiltration and immunosuppression). It is challenging to manage a patient of RA, in the presence of Felty syndrome-related granulocytopenia and thrombocytopenia. Patient initially showed signs of improvement, but finally succumbed to complications of therapy. The case provides insight into the diagnosis and management of such cases.

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A 69-year-old man presented with multiple spontaneous bruises in the past 2 weeks. Several large-sized hematomas were found on examination. The initial investigation revealed a prolonged activated partial thromboplastin time (aPTT) with normal platelet count and international normalized ratio. Further investigation revealed a low factor VIII activity secondary to presence of factor VIII inhibitor, making the diagnosis of acquired hemophilia A. Further work-up revealed that pernicious anemia was present and acted as an associated disease. After steroids therapy, his aPTT was normalized and the factor VIII inhibitor titer became undetectable. 2 months later, a relapse occurred and new hematomas appeared at his retropharyngeal space and left arm. His bleeding was controlled by administration of recombinant factor VIIa, and a combined therapy of intravenous steroids and rituximab was given to eradicate the inhibitor. The approach to workup of bleeding disorders as well as treatment of acquired hemophilia A are herein discussed.

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Background: CD4 counts are a standard laboratory measure of disease progression in HIV-infected children. However, CD4 counting is done by flow cytometry and may not always be possible in every centre treating HIV-infected children in resource-limited countries. Absolute Lymphocyte Count (ALC) can be derived easily by performing a routine white blood cell count. The World Health Organization (WHO) in 2006 had recommended ALC to identify HIV-infected children in need of ART in resource-limited settings, when CD4 cell count is not available. Aims: This study aims to assess the reliability of using ALC as a marker for starting antiretroviral therapy (ART) in HIV-infected children in a tertiary hospital setting. Settings and Design: Retrospective analysis of 46 HIV-infected children who presented at a pediatric HIV clinic at a tertiary referral centre from 2002-2005. Materials and Methods: Using WHO 2006 guidelines for cutoff values of ALC and 2008 guidelines for CD4% as a comparative standard, a retrospective analysis was done on ART-naοve HIV-infected children who underwent baseline CD4% and ALC, and sensitivity and specificity of ALC was calculated. Statistical Analysis: Fischer exact two-tailed analysis was used to correlate ALC and CD4 and need for starting ART. Results: Sensitivity of ALC was 27.6% (72.4% were false negatives), specificity was 70.6%, with positive predictive value of 61.5%. On comparison across all clinical stages of disease, only 13/46 children (28.2%) would have been started on ART according to ALC cutoffs versus 29/46 children (63.04%) using CD4 criteria (P value=0.0015). In children with WHO clinical Stage 1 or 2 of disease, only 1/11 (9.1%) children were identified by ALC as requiring ART as opposed to 6/11 (54.5%) children by CD4% (P=0.0635). Conclusions: ALC is an unreliable marker to determine the need for starting ART in HIV-infected children.

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