Showing papers by "Jens Schmidt published in 2010"

Pathomechanisms of inflammatory myopathies: recent advances and implications for diagnosis and therapies.

Abstract: Importance of the field: The main subtypes of inflammatory myopathies include dermatomyositis (DM), polymyositis (PM), necrotising myopathy (NM) and sporadic inclusion body myositis (sIBM). Recent observations have helped us to understand better the unique pathomechanisms of each subset. Advances in the pathogenesis of these disorders have led to a more precise diagnosis and specific therapeutic strategies.Areas covered in this review: A critical review regarding tissue biomarkers for the diagnosis of DM, PM, NM and sIBM is provided and an outline for more effective treatment strategies is discussed, particularly in sIBM, for which there is no effective therapy.What the reader will gain: The reader will gain an objective overview of the different pathomechanisms of the major forms of myositis, the best means of arriving at the correct diagnosis, and a critical outline of the present and future therapeutic strategies.Take home message: Whereas DM is mainly mediated by humoral mechanisms, a T-cell-mediated ...

Inclusion-body myositis in the elderly: an update

Abstract: Sporadic inclusion-body myositis is a common inflammatory myopathy, which is often misdiagnosed. In contrast to other forms of myositis, no effective treatment is available. The disease leads to severe wasting of the quadriceps and long-finger flexors, so patients gradually lose ambulation and hand-grip strength. The pathology includes an intrafiber accumulation of aberrant molecules, such as β-amyloid, as well as an inflammatory cascade, with overexpression of key cytokines and chemokines, and the attack of muscle fibers by autoaggressive cytotoxic T cells. Recent data point to an early cell-stress response in muscle fibers and a unique interplay between inflammatory and degenerative pathomechanisms. Current efforts aim to improve methods for early diagnosis and design more effective targeted treatment strategies. This article will highlight recent advances in understanding the disease pathology, and how to identify promising candidate molecules for future clinical trials.

Reply: Comment on alemtuzumab and inclusion body myositis

Abstract: Sir, Dr Greenberg misinterprets several important aspects of our study, including the scope and applied methodology. Below we have addressed the points raised in his correspondence. This was a proof-of principle molecular clinicopathological study designed to investigate the effect of alemtuzumab on endomysial T cells and disease progression; it was not primarily a trial of clinical efficacy. As stated, alemtuzumab did not significantly improve patients’ strength and function but only induced short-term stability based on the difference between two time periods. Contrary to Dr Greenberg's comments, outcome was not based on any predetermined percentages that were subsequently amended. The percentages mentioned by Dr Greenberg were used only to power the sample size. As our results show, these percentages do not relate to the outcome or conclusions of the study because, regardless of whether a 10%, 13% or 15% difference is used, there is no significant improvement in the patients’ strength (as he correctly points out, only 4 of 13 patients improved, by only 4%–19%, while the mean strength for all patients declined by 1.9%). Our data and the interpretation of results have now been ratified in an independent review by the National Institutes of Health. The main finding was a significant reduction of relevant molecules seen in repeated muscle biopsies, combined with short-term clinical stability; this is encouraging and, as we stressed, warrants a controlled study. One should not read more than that from these results. The study was arguably small and uncontrolled but taught us a lot about …