1.
The pathogenesis, diagnosis and management of congenital dyserythropoietic anaemia type I.
Roy, NBA, Babbs, C
British journal of haematology. 2019;(3):436-449
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Abstract
Congenital dyserythropoietic anaemia type I (CDA-I) is one of a heterogeneous group of inherited anaemias characterised by ineffective erythropoiesis. CDA-I is caused by bi-allelic mutations in either CDAN1 or C15orf41 and, to date, 56 causative mutations have been documented. The diagnostic pathway is reviewed and the utility of genetic testing in reducing the time taken to reach an accurate molecular diagnosis and avoiding bone marrow aspiration, where possible, is described. The management of CDA-I patients is discussed, highlighting both general and specific measures which impact on disease progression. The use of interferon alpha and careful management of iron overload are reviewed and suggest the most favourable outcomes are achieved when CDA-I patients are managed with a holistic and multidisciplinary approach. Finally, the current understanding of the molecular and cellular pathogenesis of CDA-I is presented, highlighting critical questions likely to lead to improved therapy for this disease.
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Dermatomyositis and polymyositis: new treatment targets on the horizon.
Hak, AE, de Paepe, B, de Bleecker, JL, Tak, PP, de Visser, M
The Netherlands journal of medicine. 2011;(10):410-21
Abstract
Polymyositis (PM) and dermatomyositis (DM) are rare idiopathic inflammatory myopathies (IIM) with a presumed autoimmune pathogenesis. Typical features are subacute onset, proximal, symmetric muscle weakness, elevated serum creatine kinase, and mononuclear cell infiltrates in the muscle biopsy. Strong support for an autoimmune pathogenesis comes from histopathological findings in biopsies of affected muscles. Furthermore, the association with autoantibodies supports the notion that immune-mediated inflammation is involved. PM and DM may occur in isolation or in connection with a connective tissue disease or cancer. The current treatment for IIM consists of first-line high-dose steroids and various conventional second-line treatments. Improvements in treatment for IIM are hampered by difficulties in the design of trials and the low incidence and prevalence of the disease. Cytokines and chemokines are factors involved in the inflammatory process in IIM, and are candidates for future therapeutic targets. Preliminary data with anti-tumour necrosis factor therapy are not very promising, but results of blockers of the lymphotoxin signalling pathway are to be awaited. Anti-B cell therapy may be a valuable therapeutic option for treatment of refractory IIM. The effects of anti-interferon-alpha in IIM are to be awaited, as are results of other anti-cytokine therapies and anti-chemokine therapy. Outcome measures to be used in clinical trials in II M include at present the core sets of outcome proposed by the International Myositis Assessment Clinical Study Group (IMACS).
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Novel therapies for hypereosinophilic syndromes.
Antoniu, SA
The Netherlands journal of medicine. 2010;(1):304-10
Abstract
BACKGROUND Conventional therapies (corticosteroids, cytotoxic agents or interferon-a) or newer compounds such imatinib are used specifically in subsets of hypereosinophilic syndromes (HES). However other therapies are still needed in this condition. OBJECTIVE To review the novel therapies for HES discussing their advantages and shortcomings. METHODS AND RESULTS Preclinical and clinical data on novel tyrosine kinase inhibitors, anti-IL -5 antibodies or anti-CD52 antibodies (alemtuzumab) are analysed. The former might represent appropriate options in case of imatinib resistance; the efficacy of anti-IL-5 monoclonal antibodies therapy is limited by the occurrence of rebound eosinophilia and alemtuzumab might be a promising anti-eosinophil therapy for all HES subsets. CONCLUSION Some of the novel therapies might become appropriate therapeutic options for HES.
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Metabolism and secretory function of white adipose tissue: effect of dietary fat.
Oller do Nascimento, CM, Ribeiro, EB, Oyama, LM
Anais da Academia Brasileira de Ciencias. 2009;(3):453-66
Abstract
Approximately 40% of the total energy consumed by western populations is represented by lipids, most of them being ingested as triacylglycerols and phospholipids. The focus of this review is to analyze the effect of the type of dietary fat on white adipose tissue metabolism and secretory function, particularly on haptoglobin, TNF-alpha, plasminogen activator inhibitor-1 and adiponectin secretion. Previous studies have demonstrated that the duration of the exposure to the high-fat feeding, amount of fatty acid present in the diet and the type of fatty acid may or may not have a significant effect on adipose tissue metabolism. However, the long-term or short-term high fat diets, especially rich in saturated fatty acids, probably by activation of toll-like receptors, stimulated the expression of proinflammatory adipokines and inhibited adiponectin expression. Further studies are needed to investigate the cellular mechanisms by which dietary fatty acids affect white adipose tissue metabolism and secretory functions.
5.
Interferon for acute hepatitis C.
Poynard, T, Regimbeau, C, Myers, RP, Thevenot, T, Leroy, V, Mathurin, P, Opolon, P, Zarski, JP
The Cochrane database of systematic reviews. 2002;(1):CD000369
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Abstract
BACKGROUND Acute hepatitis C virus (HCV) infection progresses to chronicity in the majority of patients. In order to prevent the progression to chronic disease, several studies have assessed interferon in patients with acute hepatitis C. OBJECTIVES The aim of this review was to assess the efficacy of interferon in acute HCV infection. SEARCH STRATEGY We searched MEDLINE, the Cochrane Controlled Trials Register, and the abstracts of the American Association for the Study of Liver Diseases (June 2001). We also contacted pharmaceutical companies to obtain unpublished trials. SELECTION CRITERIA Randomised clinical trials comparing interferon with placebo or no treatment, and published as an article, abstract, or letter were selected. No language limitations were used. DATA COLLECTION AND ANALYSIS Two reviewers independently assessed trial quality and extracted data. The following endpoints were analysed: normalization of alanine aminotransferase (ALT) activity at the end of treatment (biochemical ETR); sustained ALT normalization at the end follow-up (biochemical SR); disappearance of serum HCV RNA by polymerase chain reaction assay at the end of treatment (virologic ETR) and at the end of follow-up (virologic SR). Histologic data and adverse events were also recorded. Assessment of drug efficacy used the methods of Peto and Der Simonian and Laird. MAIN RESULTS Six randomised trials involving 206 patients with acute hepatitis C met the inclusion criteria. Four trials assessing interferon alfa-2b in 141 patients, all with transfusion-acquired acute hepatitis C, were included. They demonstrated no significant heterogeneity in the outcomes assessed. When compared with no treatment, interferon alfa-2b was associated with an increase in the rates of virologic ETR and SR by 45% (95% CI 31-59%, P < 0.00001) and 29% (95% CI 14-44%, P = 0.0002), respectively. The virologic ETR was 42% (95% CI: 30-56%) in the interferon alfa-2b group versus 4% (95% CI 0-13%, P < 0.00001) in the control group. At the end of follow-up, a virologic SR was seen in 32% (95% CI 21-46%) of interferon-treated patients versus only 4% (95% CI 0-13%, P = 0.00007) of controls. The tolerability of therapy, or the impact of interferon alfa-2b on hepatic histology, was not reported. Two trials assessed interferon beta in a total 65 patients. The efficacy of interferon beta could not be assessed, however, due to heterogeneity of these trials. REVIEWER'S CONCLUSIONS Interferon alfa is effective in improving biochemical outcomes and achieving sustained virologic clearance in patients with transfusion-acquired acute hepatitis C. The effect on long-term clinical outcomes could not be assessed due to limitations in the current data.