Colchicine

The clinical pharmacology of colchicine has been reviewed and its therapeutic use described. There is still some disagreement about its diagnostic utility; it is clearly most effective in acute gout, but benefit has been reported from its use in sarcoid arthritis and in the inflammation associated with hydroxyapatite deposition.Colchicine toxicity is largely gastrointestinal in customary doses, with a choleriform syndrome of varying severity produced in 80% of patients. Larger doses in addition produce disseminated intravascular coagulation, marrow failure, hepatocellular failure, and late central-nervous-system dysfunction, among other effects. Treatment of colchicine toxicity is supportive.Colchicine metabolic studies demonstrate that the drug leaves the blood rapidly and remains in cells for protracted periods of time. Measurable amounts were still found in leukocytes as late as 10 days after a single administration, and urinary excretion persisted for a similar length of time.A comparison of the relation between function and the structure of colchicine and its analogues in the human and in two species of rodent revealed significant variability in results. It was concluded that urate crystal-induced inflammation in the rodent was not necessarily a suitable model for human acute gout.Studies of colchicine's mechanism of action in acute gout have previously suggested that it depended on interference with microtubular subunit protein aggregation. Evidence is here summarized that colchicine may have other effects on the cell and that the benefit in gout may possibly be unrelated to the microtubular action.     

慢性乙型肝炎病人出现YMDD变异后继续长期应用拉米夫定的疗效

目的 观察慢性乙型肝炎病人出现YMDD变异后继续治疗的结果。方法 定期观察44例出现YMDD变异后继续长期应用拉米夫定的慢性乙型肝炎病人，项目包括临床表现、ALT、SB、乙型肝炎病毒血清学标志、HBV DNA及YMDD变异情况。结果 88例病人服拉米夫定3年，共有51例出现YMDD变异。48周、104周和168周YMDD变异率分别为21．7％、48％和68．4％。44例继续用药病人按变异后ALT的变化分为3组：ALT值＜1ULN（16例）、＞1－5ULN（21例）和＞5ULN（7例）；HBV DNA中位值分别为0．88、200．93和537．70mEq/ml；血清转换分别为7、1和1例。与无病毒变异组的血清转换率61．1％相比，变异后ALT正常组43．8％（P＞0．05），变异后ALT异常组为7．1％（P＜0．01）。结论 拉米夫定对大多数YMDD变异的慢性乙型肝病人仍有效，但须在严密监测下使用。     

ASCO-Update 2005--Highlights of the 41st Meeting of the American Society of Clinical Oncology/ASCO 2005

Currently, the treatment of gastrointestinal cancers is rapidly changing due to the implementation of novel chemotherapeutic agents as well as the introduction of targeted therapies into treatment protocols. The following review provides an overview of the most important clinical trials in esophageal, gastric, colorectal, pancreatic and hepatobiliary cancer that were presented at the annual meeting of the American Society of Clinical Oncology.     

Screening, diagnosis and management of early syphilis in genitourinary medicine clinics in the UK

New diagnoses of syphilis in the UK increased eight-fold between 1997 and 2002. This study, conducted in 2002, demonstrated that 31% of clinics were not confident of their expertise to obtain an adequate specimen for dark ground microscopy (DGM), and 35% were not confident of their expertise to detect treponemes on DGM. In all, 64% of clinics had observed adherence problems in HIV-positive patients treated with parenteral regimens, as against 42% with oral regimens. Also, 51% of clinics waited more than a week for the results of initial serological tests for syphilis, and 88% of clinics waited more than a week for confirmatory test results. Other concerns include the failure to perform syphilis serology consistently whenever HIV-positive patients were at risk, and the widespread use of doxycycline as a therapy for syphilis in HIV-positive patients despite concerns that this is not known to be fully treponemicidal in cerebrospinal fluid.     

Management of chronic myeloid leukaemia in relapse following donor lymphocyte infusion induced remission: a retrospective study of the Clinical Trials Committee of the British Society of Blood & Marrow Transplantation (BSBMT)

Donor lymphocyte infusion (DLI) can restore remission in a high percentage of patients with chronic myeloid leukaemia (CML) who relapse after allogeneic stem cell transplant (SCT). Subsequent relapses after a DLI-induced remission do occur and the optimal management of these patients is not defined. A retrospective study of the practice of UK transplant centres was conducted. In all, 13 patients from seven centres were identified: all were treated for relapse post allogeneic SCT with DLI and achieved either a complete cytogenetic (n=5) or molecular (n=8) remission. All patients subsequently had a second relapse, at molecular (n=7), cytogenetic (n=4) and haematological (n=2) levels. Further DLI was used in the treatment of 11 patients, imatinib mesylate in three and chemotherapy in two. The two patients with haematological relapse died of blastic disease. The remaining 11 patients achieved either a complete cytogenetic (n=2) or molecular (n=9) remission. Nine patients remain in molecular remission at a median follow-up of 29 months, seven of whom had received DLI alone as treatment for second relapse, one DLI plus imatinib and one imatinib alone. Toxicity following DLI for second relapse was low. Longer follow-up will be required to see if these second DLI-induced remissions will be durable.     

The diagnosis and management of allergic reactions in patients sensitized to non-specific lipid transfer proteins

Sensitization to one or more non-specific lipid transfer proteins (nsLTPs), initially thought to exist mainly in southern Europe, is becoming accepted as a cause of allergic reactions to plant foods across Europe and beyond. The peach nsLTP allergen Pru p 3 is a dominant sensitizing allergen and peaches a common food trigger, although multiple foods can be involved. A frequent feature of reactions is the requirement for a cofactor (exercise, alcohol, non-steroidal anti-inflammatory drugs, Cannabis sativa) to be present for a food to elicit a reaction. The variability in the food and cofactor triggers makes it essential to include an allergy-focused diet and clinical history in the diagnostic workup. Testing on suspected food triggers should also establish whether sensitization to nsLTP is present, using purified or recombinant nsLTP allergens such as Pru p 3. The avoidance of known trigger foods and advice on cofactors is currently the main management for this condition. Studies on immunotherapy are promising, but it is unknown whether such treatments will be useful in populations where Pru p 3 is not the primary sensitizing allergen. Future research should focus on the mechanisms of cofactors, improving diagnostic accuracy and establishing the efficacy of immunotherapy.     

创伤后感染致多器官功能障碍综合征患者血清β-hBD-2、OPN、pro-ADM和NPt水平的变化

目的：探讨多器官功能障碍综合征（multipleorgandysfunctionsyndrome,MODS）患者的炎症感染病理过程中炎性介质水平的变化。方法：血清人类B防御素-2（humanB．defensin-2,β—hBD-2）、骨桥蛋白（osteopontin,OPN）和新蝶呤（neoptefin,NPt）采用酶联免疫分析法（ELISA）测定,肾上腺髓质素前体（pro-adrenomeduUin,pro—ADM）检测采用化学免疫发光法。结果：四项血清标志物测定结果分别显示,对照组和确诊时组B-hBD-2、OPN、pro-ADM、NPt四种血清炎症介质标志水平均显著高于正常人组（P〈0．05,P〈0．01）,出院前组β-hBD-2、OPN水平显著高于正常人组,另两项指标均与正常人组比较无显著性差异（P均〉0．05）;同时确诊时组与对照组比较β—hBD-2、OPN、pro-ADM三项指标水平也显著升高（P〈0．05,P〈0．01）,NPt水平患者组呈略高,但无统计学意义（P〉0．05）;出院前组β-hBD-2、OPN、pro-ADM、NPt四种血清炎症介质标志水平均显著低于确诊时组（P〈0．05,P〈0．01）。结论：MODS患者的炎症感染病理过程中炎性介质水平显著升高,其测定对于临床抗感染治疗提供重要价值。     

New recurrent balanced translocations in acute myeloid leukemia and myelodysplastic syndromes: Cancer and leukemia group B 8461

Acquired chromosome abnormalities in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are among the most valuable determinants of diagnosis and prognosis. In search of new recurrent balanced translocations, we reviewed the Cancer and Leukemia Group B (CALGB) cytogenetics database containing pretreatment and relapse karyotypes of 4,701 adults with AML and 565 with MDS who were treated on CALGB trials. We identified all cases with balanced structural rearrangements occurring as a sole abnormality or in addition to one other abnormality, excluded abnormalities known to be recurrent, and then reviewed the literature to determine whether any of what we considered unique, previously unknown abnormalities had been reported. As a result, we identified seven new recurrent balanced translocations in AML or MDS: t(7;11)(q22;p15.5), t(10;11)(q23;p15), t(2;12)(p13;p13), t(12;17)(p13;q12), t(2;3)(p21;p21), t(5;21)(q31;q22), and t(8;14)(q24.1;q32.2), and additionally, t(10;12)(p11;q15), a new translocation in AML previously reported in a case of acute lymphoblastic leukemia. Herein, we report hematologic and clinical characteristics and treatment outcomes of patients with these newly recognized recurrent translocations. We also report 52 unique balanced translocations, together with the clinical data of patients harboring them, which to our knowledge have not been previously published. We hope that once the awareness of their existence is increased, some of these translocations may become recognized as novel recurring abnormalities. Identification of additional cases with both the new recurrent and the unique balanced translocations will enable determination of their prognostic significance and help to provide insights into the mechanisms of disease pathogenesis in patients with these rare abnormalities. © 2012 Wiley Periodicals, Inc.