Hehlmann R.,Medizinische Fakultat Mannheim |
Hehlmann R.,University of Heidelberg |
Hehlmann R.,Ludwig Maximilians University of Munich |
Hehlmann R.,Friedrich - Alexander - University, Erlangen - Nuremberg |
And 156 more authors.
Journal of Clinical Oncology | Year: 2011
Purpose Treatment of chronic-phase (CP) chronic myeloid leukemia (CML) with imatinib 400 mg/d can be unsatisfactory. Optimization of treatment is warranted. Patients and Methods In all, 1,014 newly diagnosed CP-CML patients were randomly assigned to imatinib 800 mg/d (n = 338), imatinib 400 mg/d (n = 325), or imatinib 400 mg/d plus interferon alfa (IFN-α; n = 351). Dose adaptation to avoid higher-grade toxicity was recommended. First primary end point was major molecular remission (MMR) at 12 months. Results A higher rate of MMR at 12 months occurred with tolerability-adapted imatinib 800 mg/d than with imatinib 400 mg/d (59% [95% CI, 53% to 65%] v 44% [95% CI, 37% to 50%]; P < .001) or imatinib 400 mg/d plus IFN-α (59% v 46% [95% CI, 40% to 52%]; P = .002). Median dose in the 800-mg/d arm was 628 mg/d with a maximum dose of 737 mg/d during months 4 to 6 and a maintenance dose of 600 mg/d. All three treatment approaches were well tolerated with similar grade 3 and 4 adverse events. Independent of treatment approach, MMR at 12 months showed better progression-free survival (99% v 94%; P = .0023) and overall survival (99% v 93%; P = .0011) at 3 years when compared with > 1% on the international scale or no MMR but showed no difference in 0.1% to < 1% on the international scale, which closely correlates with complete cytogenetic remission. Conclusion Treatment of early-phase CML with imatinib can be optimized. Early high-dose therapy followed by rapid adaptation to good tolerability increases the rate of MMR at 12 months. Achievement of MMR by month 12 is directly associated with improved survival. Copyright © 2011 American Society of Clinical Oncology.
Sell M.,Medizinische Fakultat Mannheim |
Kuchenhoff J.,Klinik fur Psychiatrie und Psychotherapie
Psyche (Germany) | Year: 2015
The authors explore the question of the extent to which the human body is perceived and represented by means of individual body parts and fragments. To this end, they examine the phantasm of the dismembered body («corps morcelé») in phases of psychotic disintegration and the staging of the human body and its parts in classical myths, in post-modern splatter movies, and in works of fine art. An additional section addresses bodily dismemberment as a key cognitive paradigm in medicine and its use in the field of medical transplantation. A clinical/psychopathological section offers an outline of the symptoms of the fragmented body image in schizophrenia. The study of the highly heterogeneous material concludes that the question of the wholeness of the human and his/her disintegration touches on a primordial human fear and also on an ability to oscillate between the part and the whole. The areas studied each tackle this in a very unique way. Moreover, it emerges that the psychotic experience of the dismembered body must be distinguished in particular from the metonymic phenomenon of the pars pro toto of sexual fetishism.
Schuh-Hofer S.,Medizinische Fakultat Mannheim |
Schafer-Vo S.,Medizinische Fakultat Mannheim |
Treede R.-D.,Medizinische Fakultat Mannheim
Aktuelle Neurologie | Year: 2016
Sleep, sleep deprivation and pain are closely intertwined. It is well established that sleep plays an important role in chronobiological pain disorders. Cluster and hypnic headaches are prominent examples of pain disorders with circadian rhythmicity. More recently, the impact of disturbed sleep on both spontaneous pain and pain sensitivity has been recognized. Experimental studies have shown that one night of total sleep deprivation can induce generalized, mechanical and thermal pain hypersensitivity. Sleep restriction over several days results in spontaneous pain. Several clinical studies suggest that sleep deprivation/disruption acts as an independent pain aggravating factor. Insomnia in pain patients is of therapeutic relevance since disturbed sleep is one of the most frequently reported complaints of pain patients. Clinical studies have shown that improved sleep (either by cognitive behavioral insomnia therapy or by the use of hypnotics) alleviates the (chronic) pain condition. However, the contribution of disturbed sleep to pain intensity may vary considerably and needs to be determined individually. The mechanism by which disturbed sleep affects nociception is currently unknown. There is some evidence of sleep deprivation causing imbalance of the endogenous pain modulatory system by reinforcing pro-nociceptive whilst attenuating the anti-nociceptive system. The interplay between sleep and the immune system may play an important role. Sleep deprivation induces release of pro-inflammatory cytokines. Due to their pro-nociceptive properties, they may impact on pain sensitivity, resulting in hypersensitivity to evoked pain. © 2016 Georg Thieme Verlag KG Stuttgart New York.