La Revue de médecine interne
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To present and discuss the rationale and the results of clinical trials using supplementation with physiologic anticoagulants (Tissue Factor Pathway Inhibitor (TFPI), AntiThrombin (AT), and Protein C (PC) in patients with severe sepsis. ⋯ Randomized controlled studies were recently completed. No effect on the mortality rate could be documented after treatment with recombinant TFPI. AT concentrates neither improve mortality, but a biological interaction with heparin therapy could have biased the study results. Treatment with recombinant activated PC (alpha-drotrecogin) was associated with a significant reduction in the mortality rate of severely ill patients and received recently the approval from FDA and EC authorities in this indication. An increase in the rate of hemorrhagic adverse effects has been observed with these compounds, justifying a strict observance of contraindications and of patients selection. PROSPECTIVE: Additional studies are needed to give confirmation of the positive effects of activated PC supplementation in less severely ill patients, children and specific clinical situations. The effects of new anticoagulant compounds are currently evaluated in preclinical studies.
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The knowledge of systemic necrotizing vasculitides improved since new classifications have been established along with a better understanding of pathogenesis of the diseases. The major vasculitides are described herein. ⋯ Despite the good results obtained with and demonstrated in prospective trials, the vasculitides remain severe and deserve new studies testing new drugs but also strategies based on prognostic factors and scores which should play a major role in treatments decision.
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Sleep-wake rhythm disturbances observed in Alzheimer's disease are correlated with the severity of cognitive impairment and often result in institutionalization. These disturbances are also a major cause of psychotropic medication misuse. We report age-related physiologic and disease related pathologic changes in sleep-wake rhythms and propose chronobiological treatment approaches in patients with Alzheimer's disease. ⋯ In Alzheimer patients, controlling sleep-wake disturbances with sedative drugs often increases both sleep disturbance and cognitive dysfunction. A chronobiological approach with bright-light therapy, melatonin administration, restricted time in bed, and diurnal activity may be an interesting therapeutic alternative in the management of sleep-wake disorders in Alzheimer patients. The aim of these therapeutics is to improve sleep and diurnal activity and consequently to increase the quality of life in Alzheimer patients.
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IFN alpha are cytokines used for a number of years in the treatment of certain hemopathies, i.e. of a myeloid and lymphoid etiology. IFN alpha are a family of polypeptides produced by eukaryote cells in response to various stimulant agents. The first trials using this cytokine in humans were carried out by H. Strander in the years 1965-1970. IFN alpha contain anti-viral, anti-proliferative and immunomodulatory properties. The access of clinicians to IFN alpha molecules, in addition to elements produced by genetic engineering for approximately the past 20 years, has permitted a number of therapeutic trials to be carried out. In hematology the clinical interest of IFN alpha was primarily in chronic myeloid and lymphoid proliferating syndromes. Certain indications have to date been well demonstrated. However, the impact of IFN alpha on therapeutic care of certain hemopathies as compared to conventional treatment remains controversial. At the same time, the frequency of side effects from treatment with IFN alpha and its cost should be taken into consideration. ⋯ The future of IFN alpha use in the treatment of hemopathies appears to be linked to its association with new treatments, an association, however, where its efficacy and superiority should be demonstrated. This is the case in chronic myeloid leukemia where IFN alpha could be associated with aracytine or the inhibitors of tyrosine kinase. Also, in the treatment of malignant non-Hodgkin's lymphomas as well as the studies concerning the association between IFN alpha and monoclonal antibodies, in particular antibody anti-CD 20.
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Since the discovery of hepatitis C (HCV), the efficacy of treatment has significantly progressed using standard mono-therapy: with Interferon alpha (IFN) during six months we obtained approximately 10% sustained response and currently with the association of pegylated IFN and Ribavirin a 55% sustained response was achieved. ⋯ Despite the considerable and rapid progress obtained in the therapeutic treatment of infection due to HCV and HBV a number of unknown factors remain, which warrants further trials, in particular to evaluate the efficacy as well as the tolerance of the antiviral agent association.