The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis

To determine whether MDR1 reversal by the addition of the P-glycoprotein (P-gp) inhibitor PSC-833 to standard induction chemotherapy would improve event-free survival (EFS), 419 untreated patients with acute myeloid leukemia (AML) aged 60 years and older were randomized to receive 2 induction cycles of daunorubicin and cytarabine with or without PSC-833. Patients in complete remission were then given 1 consolidation cycle without PSC-833. Neither complete response (CR) rate (54% versus 48%; P = .22), 5-year EFS (7% versus 8%; P = .53), disease-free survival (DFS; 13% versus 17%; P = .06) nor overall survival (OS; 10% in both arms; P = .52) were significantly improved in the PSC-833 arm. An integrated P-gp score (IPS) was determined based on P-gp function and P-gp expression in AML cells obtained prior to treatment. A higher IPS was associated with a significantly lower CR rate and worse EFS and OS. There was no significant interaction between IPS and treatment arm with respect to CR rate and survival, indicating also a lack of benefit of PSC-833 in P-gp-positive patients. The role of strategies aimed at inhibitory P-gp and other drug-resistance mechanisms continues to be defined in the treatment of patients with AML.     

高位腰椎间盘突出症

目的：通过147例高位腰椎间盘突出症的回顾性研究,旨在提高对本症的认识,减少漏诊,误诊,方法：回顾性分析报告147例高位腰椎间盘突出,结果：治疗腰1,210例,腰2。3 32例,腰3,4 105例,其中双间隙突出34例,跳跃性突出27例,伴椎管狭窄31例。瘫痪3例,非手术治疗34例,手术113例,优47例,良8例,差92例,重点讨论了高位腰椎及椎间盘和神经根的解剖特点和临床三大特征及诊断治疗,提出对不同程度的病人用不同治疗方式以及手术中需要注意的六个问题。     

Association of Piebaldism,Multiple Café‐au‐lait Macules,and Intertriginous Freckling: Clinical Evidence of a Common Pathway between KIT and Sprouty‐Related,Ena/Vasodilator‐Stimulated Phosphoprotein Homology‐1 Domain Containing Protein 1 (SPRED1)

Abstract: Piebaldism is a rare genodermatosis caused by KIT mutations. We report the case of a 5‐year‐old boy who had the white forelock and leukoderma of piebaldism, but the presence of many café‐au‐lait macules and axillary and inguinal freckling complicated the diagnosis. Patients with similar cutaneous findings have been previously reported, and their disorder has been attributed to an overlap of piebaldism and neurofibromatosis type 1. Legius syndrome is a recently described syndrome caused by Sprouty‐related, Ena/vasodilator‐stimulated phosphoprotein homology‐1 domain containing protein 1 (SPRED1) mutations that also has multiple café‐au‐lait macules and intertriginous freckling. Based on our current understanding of KIT and SPRED1 protein interactions, we propose that café‐au‐lait macules and freckling may be seen in some patients with piebaldism and does not necessarily represent coexistence of neurofibromatosis type 1.     

UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia.

Nilotinib is a novel BCR-ABL inhibitor with significantly improved potency and selectivity over imatinib. In Phase I and Phase II clinical studies of nilotinib in patients with a variety of leukemias, infrequent instances of reversible, benign elevation of bilirubin were observed. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) glucuronidates bilirubin in humans, and a polymorphism in the promoter of the gene that encodes it has been associated with hyperbilirubinemia during treatment with a number of drugs. Pharmacogenetic analysis of that TA-repeat polymorphism found an association between the (TA)7/(TA)7 genotype and risk of hyperbilirubinemia in Phase I patients with imatinib-resistant/intolerant chronic myeloid leukemia (CML) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL); this result was replicated in two separate analyses of the chronic phase (CP) and accelerated phase (AP) CML arms of a Phase II study. As nilotinib is not known to be glucuronidated by UGT1A1, the combined impact of inhibition of UGT1A1 activity by nilotinib and genetic polymorphism is the most likely cause of the increased rate of hyperbilirubinemia.     

蒙药如达溃疡散对大鼠乙酸性胃溃疡及其血清促胃液素的影响

目的:探讨如达溃疡散对大鼠乙酸性胃溃疡的作用及对其血清促胃液素(gastrin)含量的影响.方法:采用乙酸法复制胃溃疡模型,将大鼠随机分为对照组、如达溃疡散组、雷尼替丁组,观察如达溃疡散对大鼠胃溃疡的作用,并检测其对大鼠血清中促胃液素含量的影响.结果:与对照组相比,如达溃疡散能明显抑制溃疡的发生,抑制血清促胃液素含量.结论:如达溃疡散具有抗胃溃疡的作用,其作用机理可能是通过抑制促胃液素释放,进一步减少胃酸分泌来实现的.     

Hospitals do not inform GPs about medication that should be monitored

BACKGROUND: General practitioners are now asked to prescribe drugs that, due to possible risks and side effects, had previously been prescribed almost exclusively at hospital. OBJECTIVE: To assess the quality of hospital letters as the key communication between hospitals and GPs. METHOD: Hospital letters examined using a predetermined protocol. RESULTS: Of 224 patients identified who were taking drugs that required regular monitoring, 173 were commenced in hospital. Fewer than one in five (30; 17%) hospital letters indicated that there was a risk associated with the drug or that it should be routinely monitored. Monitoring frequency was identified on only 14 occasions and the majority of letters (129; 74. 6%) did not state who was to be responsible for ongoing monitoring (either GP or hospital). Information was slow to arrive at the practice and, in 12% of cases, the hospital letter had not arrived within 14 days of commencement of medication. CONCLUSION: The information provided in hospital letters is insufficient to allow GPs to put structures in place to monitor drug therapy.