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71.
OBJECTIVE: Therapeutic splenectomy in myelofibrosis with myeloid metaplasia (MMM) may result in extreme thrombocytosis and leukocytosis and accelerated hepatomegaly. We previously described initial palliative benefit from 2-chlorodeoxyadenosine (2-CdA) in such instances. The purpose of this study is to provide long-term follow-up on the durability of response in the initial cohort and in additional subsequent cases. METHODS: We retrospectively identified patients with histologically confirmed MMM who had palliative therapy with 2-CdA. Clinical characteristics and information on subsequent clinical course were abstracted at the time of diagnosis of MMM and at initiation of 2-CdA therapy until death. RESULTS: To date, we have used 2-CdA as palliative therapy in 14 patients with MMM. After a median of four cycles of therapy, responses for hepatomegaly occurred in 56% of patients, thrombocytosis 50%, leukocytosis 55%, and anemia 40%. Cytopenias were frequent but usually transient and without clinical consequence. Responses occurred usually by the second cycle; median duration of response was 6 months (range, 2-19) after completion of 2-CdA therapy. CONCLUSION: This study confirmed relevant and frequently durable palliation of symptoms in about half the patients. 2-CdA is a reasonable palliative option in postsplenectomy patients with MMM who have problematic myeloproliferation. 相似文献
72.
Dr. Ana Podesta MD Patricia Lopez MD Ruben Terg MD Federico Villamil MD Daniel Flores MD Ricardo Mastai MD Carlos B. Udaondo MD J. Perez Companc 《Digestive diseases and sciences》1991,36(2):216-220
Pruritus can be a debilitating symptom in patients with chronic cholestasis. Based on previous reports of its efficacy, we evaluated the impact of rifampin on the pruritus associated with primary biliary cirrhosis. Fourteen patients were included in a randomized, crossover study. After a 15-day washout period, subjects were followed for three weeks. During the first and third week, patients received 600 mg of rifampin or placebo; no treatment was administered during the second week. Pruritus was subjectively scored on a scale from 0 to 100. With rifampin, pruritus disappeared in 11 patients and partially improved in three; with placebo, only two had a partial response (P<0.001). Six patients with a prior poor or no response to cholestyramine improved with rifampin. No changes in biochemical tests or side effects were observed during this period. We conclude that short-term administration of rifampin relieves pruritus in primary biliary cirrhosis. When administered over a period of eight months in an open study, the relief of pruritus was maintained, while one individual developed an allergic reaction. Rifampin appears to be a safe drug in the management of the pruritus of primary biliary cirrhosis. 相似文献
73.
Bigna Lenggenhager Ruben T. Azevedo Alessandra Mancini Salvatore Maria Aglioti 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2013,224(2):233-241
Successful interaction with the external environment requires a balance between novel or exploratory and routine or exploitative behaviours. This distinction is often expressed in terms of location or orientation of the body relative to surrounding space: functions in which the vestibular system plays an important role. However, the distinction can also be applied to novel versus repetitive production of any behaviour or symbol. Here, we investigated whether vestibular inputs contribute to the balance between novel and routine behaviours, independently of their effects on spatial orienting, by assessing effects of galvanic vestibular stimulation (GVS) on a random number generation task. Right-anodal/left-cathodal GVS, which preferentially activates the left cerebral hemisphere decreased the randomness of the sequence, while left-anodal/right-cathodal GVS, which preferentially activates the right hemisphere increased it. GVS did not induce any spatial biases in locations chosen from the number line. Our results suggest that vestibular stimulation of each hemisphere has a specific effect on the balance between novel and routine actions. We found no evidence for effects of non-specific arousal due to GVS on random number generation, and no evidence for effects on number generation consistent with modulation of spatial attention due to GVS. 相似文献
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75.
Heat shock protein 90 inhibition sensitizes acute myelogenous leukemia cells to cytarabine 下载免费PDF全文
Mesa RA Loegering D Powell HL Flatten K Arlander SJ Dai NT Heldebrant MP Vroman BT Smith BD Karp JE Eyck CJ Erlichman C Kaufmann SH Karnitz LM 《Blood》2005,106(1):318-327
Previous studies demonstrated that ataxia telangiectasia mutated- and Rad3-related (ATR) kinase and its downstream target checkpoint kinase 1 (Chk1) facilitate survival of cells treated with nucleoside analogs and other replication inhibitors. Recent results also demonstrated that Chk1 is depleted when cells are treated with heat shock protein 90 (Hsp90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). The present study examined the effects of 17-AAG and its major metabolite, 17-aminogeldanamycin (17-AG), on Chk1 levels and cellular responses to cytarabine in human acute myelogenous leukemia (AML) cell lines and clinical isolates. Cytarabine, at concentrations as low as 30 nM, caused activating phosphorylation of Chk1, loss of the phosphatase Cdc25A, and S-phase slowing. Conversely, treatment with 100 to 300 nM 17-AAG for 24 hours caused Chk1 depletion that was accompanied by diminished cytarabine-induced S-phase accumulation, decreased Cdc25A degradation, and enhanced cytotoxicity as measured by inhibition of colony formation and induction of apoptosis. Additional studies demonstrated that small inhibitory RNA (siRNA) depletion of Chk1 also sensitized cells to cytarabine, whereas disruption of the phosphatidylinositol 3-kinase (PI3k) signaling pathway, which is also blocked by Hsp90 inhibition, did not. Collectively, these results suggest that treatment with 17-AAG might represent a means of reversing checkpoint-mediated cytarabine resistance in AML. 相似文献
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78.
Leversen et al. (PLoS One 7(6):e38830, 2012) emphasise the importance of understanding the principles of life-long development. In their study of motor control, they found a common tendency towards improved motor performance from childhood to adulthood and a subsequent deterioration. The aim of our study was to examine this issue further by investigating fine motor behaviour (tracing a model line) in 196 participants (age range 12–95 years old) in two sensory conditions—proprioceptive + visual (PV) and proprioceptive only—in both hands and in two types of movement, frontal and transversal. Regression analyses of line length and task performance speed in relation to age were conducted for the different test conditions. The best performance was found in middle age, and a quadratic function provided the best fit for most of the test conditions. The corresponding inflection points (the age at which graphical analysis showed a change in performance as a peak of maturation before decline due to ageing) showed earlier ages in the proprioceptive condition. For most types of movement analysed, performance speed was slower under the PV condition. Paired correlation analysis showed that the symmetry of precision performance between hands became stronger with age. The results provide information on age-dependent differences in proprioception based on fine motor performance. They may be of use in the design of preventive strategies for preserving proprioceptive function by reducing the risk of falls and accidents or diseases such as Parkinson’s. 相似文献
79.
Natalia R. Genaro M.D. Daniel D. Anselm M.D. Nahuel Cervino M.D. Ariel O. Estevez M.D. Carlos Perona M.D. Alejandro M. Villamil M.D. Ruben Kervorkian M.D. Adrian Baranchuk M.D. 《Annals of noninvasive electrocardiology》2014,19(4):387-390
Brugada phenocopies (BrP) are clinical entities that are etiologically distinct from true congenital Brugada syndrome (BrS). BrP are characterized by type 1 or type 2 Brugada electrocardiogram (ECG) patterns in precordial leads V1–V3; however, BrP are elicited by various underlying clinical conditions such as electrolyte disturbances, myocardial ischemia, or poor ECG filters. In this report, we describe the first case of clinically reproducible BrP which is important to the conceptual evolution of BrP. 相似文献
80.
Gian-Battista Chierchia Giacomo Di Giovanni Juan Sieira-Moret Carlo de Asmundis Giulio Conte Moises Rodriguez-Mañero Ruben Casado-Arroyo Giannis Baltogiannis Gaetano Paparella Giuseppe Ciconte Andrea Sarkozy Pedro Brugada 《Journal of interventional cardiac electrophysiology》2014,39(2):145-151