Ranolazine for the treatment of refractory angina in a veterans population

BackgroundPivotal ranolazine trials did not require optimization of conventional medical therapy including coronary revascularization and antianginal drug therapy prior to ranolazine use. This case series describes the use of ranolazine for the treatment of chronic stable angina refractory to maximal medical treatment in a veterans population.ResultsA total of 18 patients with a median age of 66 years were identified. All patients had prior percutaneous coronary intervention and/or coronary artery bypass graft surgery; 83% had three-vessel coronary artery disease, with left main disease present in 39% of patients. Prior to initiating ranolazine, antianginal use consisted of beta blockers (94%), long-acting nitrates (83%) and calcium channel blockers (61%). Median blood pressure (116.2/61.8 mmHg) and pulse (65 beats per min) were controlled. Median preranolazine angina episodes and sublingual nitroglycerin (SLNTG) doses per week were 14 and 10, respectively, with a Canadian Cardiovascular Society (CCS) angina grade of III–IV in 67% of patients. After initiation of ranolazine, median angina episodes per week and SLNTG doses used per week decreased to 0.7 and 0, respectively, with CCS grade of III–IV declining to 17%. Of the 18 subjects enrolled, 44% had complete resolution of angina episodes.ConclusionThe addition of ranolazine to maximally tolerated conventional antianginal drug therapy post coronary revascularization was associated with decreases in angina episodes and SLNTG utilization and improvement in CCS angina grades. Ranolazine may provide an effective treatment option for revascularized patients with refractory angina.     

Comparative study of efficacy and tolerability of flupirtine versus tramadol in non-steroidal anti-inflammatory drug intolerant mechanical low back pain

BackgroundMechanical low back pain (MLBP) is a commonly encountered entity in clinical practice. Pain relief and restoration of functional capacity are management goals.Aims and objectivesTo compare the efficacy and tolerability of flupirtine, a selective neuronal potassium channel-opener (SNEPCO), with tramadol, a widely-used opioid analgesic, in MLBP.MethodsThis randomized, single-blinded, intention to treat (ITT) trial started with 240 non-steroidal anti-inflammatory drug (NSAID) intolerant patients who were prescribed either tablet flupirtine (100 mg twice daily) or capsule tramadol (50 mg twice daily), for 4 weeks. Follow-up was done on days 14, 28 and 4 weeks after treatment completion. Assessment of improvements in Indian Health Assessment Questionnaire Disability Index (Indian HAQ-DI), Visual Analogue Scale (VAS), Numerical Rating Scale (NRS) and measurement of Pain Relief Rate (PRR) were performed. Adverse events were recorded.ResultsOne hundred and seven patients receiving flupirtine and 103 receiving tramadol were analyzed on an ITT basis. Scores in Indian HAQ-DI, VAS and NRS improved significantly in both groups in the last visit, but more so with flupirtine. PRR was reasonably higher with flupirtine, [59 (55.14%)] patients experiencing significant to complete pain relief at the end of the study, compared to tramadol [41 (39.81%)]. Adverse effects were less with flupirtine [26 (24.30%) versus 41 (39.81%), p < 0.05], minimizing drop-outs.ConclusionFlupirtine has better sustained efficacy and tolerability than tramadol in MLBP.     

Protein Folding Activity of the Ribosome (PFAR) –– A Target for Antiprion Compounds

Prion diseases are fatal neurodegenerative diseases affecting mammals. Prions are misfolded amyloid aggregates of the prion protein (PrP), which form when the alpha helical, soluble form of PrP converts to an aggregation-prone, beta sheet form. Thus, prions originate as protein folding problems. The discovery of yeast prion(s) and the development of a red-/white-colony based assay facilitated safe and high-throughput screening of antiprion compounds. With this assay three antiprion compounds; 6-aminophenanthridine (6AP), guanabenz acetate (GA), and imiquimod (IQ) have been identified. Biochemical and genetic studies reveal that these compounds target ribosomal RNA (rRNA) and inhibit specifically the protein folding activity of the ribosome (PFAR). The domain V of the 23S/25S/28S rRNA of the large ribosomal subunit constitutes the active site for PFAR. 6AP and GA inhibit PFAR by competition with the protein substrates for the common binding sites on the domain V rRNA. PFAR inhibition by these antiprion compounds opens up new possibilities for understanding prion formation, propagation and the role of the ribosome therein. In this review, we summarize and analyze the correlation between PFAR and prion processes using the antiprion compounds as tools.     

“It’s Not JUST Skin Cancer”: Understanding Their Cancer Experience From Melanoma Survivor Narratives Shared Online

Cancer survivors narrate their experiences in unique ways, articulating different aspects of the cancer journey. The purpose of this study was to analyze the content of cancer narratives that melanoma survivors share online in order to present the ways that survivors narrate their cancer experience, to identify survivors’ motivations for sharing, and to better understand the ways in which survivors are impacted by and cope with the diagnosis and treatment of cancer. The sample consisted of 95 unique melanoma survivor narratives, accessed from the Melanoma Research Foundation in November 2015, that were inductively and deductively coded for key themes and subthemes. Emergent themes described different aspects of the melanoma experience during prediagnosis (identification of self-phenotype, searching for causes, suspicious findings, delay in diagnosis), diagnosis (communication of diagnosis, emotional responses), transition from diagnosis to beginning treatment (second opinion), treatment (positive reframing of attitude, proactive cancer management, side effects), and posttreatment phases (social support, vigilance behaviors posttreatment). Two themes that cut across all phases of the cancer journey included recognizing and dealing with uncertainty and survivors’ motive for sharing narrative. These findings have implications for understanding how melanoma survivors may benefit personally from sharing their cancer experience online and for the potential for survivor narratives to motivate behavior change and facilitate coping among readers.     

Absence of Mycobacterium avium ss paratuberculosis-specific IS900 sequence in intestinal biopsy tissues of Indian patients with Crohn’s disease

Background and Objective  

The role of Mycobacterium avium ss paratuberculosis (MAP) in the etiopathology of Crohn’s disease (CD) remains controversial, because of conflicting reports demonstrating the presence of MAP-specific insertion sequence from intestinal biopsy tissues of patients clinically diagnosed for the disease. The present study was carried out to investigate the presence of MAP DNA in the intestinal tissues of CD patients to ascertain the relevance of MAP in Indian patients with CD.     

Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.