儿童造血干细胞移植抗胸腺细胞球蛋白预处理期间降钙素原和C反应蛋白的变化

目的 探讨重型β-地中海贫血儿童异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)预处理期间使用抗胸腺细胞球蛋白(anti-thymocyte globulin,ATG)后降钙素原(procalcitonin,PCT)及C反应蛋白(C-reactive protein,CRP)升高的临床价值.方法 25例重型β-地中海贫血患儿纳入本前瞻性研究组,allo-HSCT前予以ATG预处理,使用前监测体温、PCT、CRP、肝功能及血常规,以后每天监测CRP及血常规,隔天监测PCT及肝功能,至少持续1周.结果 ATG使用前,PCT、CRP、体温等均在正常范围内;第1天PCT、CRP及体温较基础水平显著增高(P<0.01),其后持续下降,平均4～6 d降至正常水平.移植前血清铁蛋白水平及肝功能优劣与CRP及PCT变化无显著相关性(P>0.05).结论 使用ATG会引发发热反应,同时炎症指标PCT、CRP快速增高.ATG使用期间的CRP及PCT这些常用的炎症指标的升高不能说明存在感染,对判断有无感染价值有限.PCT及CRP升高与使用ATG前的肝功能、血清铁蛋白、白细胞水平等无显著相关.     

The utility of the Edmonton Symptom Assessment System in screening for anxiety and depression

BAGHA S.M., MACEDO A., JACKS L.M., LO C., ZIMMERMANN C., RODIN G. & LI M. (2013) European Journal of Cancer Care 22 , 60–69 The utility of the Edmonton Symptom Assessment System in screening for anxiety and depression The Edmonton Symptom Assessment System (ESAS) is a common screening tool in cancer, although its validity for distress screening is unproven. Here, screening performance of the ESAS anxiety (ESAS-A) and depression (ESAS-D) items were validated against the anxiety [Generalised Anxiety Disorder-7 (GAD-7)] and depression [Patient Health Questionnaire-9 (PHQ-9)] subscales of the PHQ. A total of 1215 cancer patients completed the Distress Assessment and Response Tool (DART), a computerised distress screening instrument. Spearman's rank correlation coefficients and receiver operating characteristic curve analyses were used to evaluate the ability of ESAS-A and ESAS-D to identify moderate distress (GAD-7/PHQ-9 ≥ 10). Spearman's rank correlation coefficients comparing ESAS-A and ESAS-D with GAD-7 and PHQ-9 were 0.74 and 0.72 respectively. Areas under the receiver operating characteristic curves were 0.89 and 0.88 for anxiety and depression respectively. A cut-off of ≥3 on ESAS-A demonstrated a sensitivity of 0.91, specificity of 0.68, positive predictive value of 0.34 and negative predictive value of 0.97. A cut-off of ≥2 on the ESAS-D demonstrated a sensitivity of 0.86, specificity of 0.72, positive predictive value of 0.46 and negative predictive value of 0.95. High sensitivities of ESAS-A and ESAS-D at certain cut-offs suggest they have use in ruling-out distress. However, their low specificities indicate secondary screening is needed to rule-in anxiety or depression for case-finding.     

Multigenetic lesions in infant acute leukaemias: correlations with ALL-1 gene status

The large majority of childhood B-precursor cell acute lymphoblastic leukaemia cases present IgH and TCRδ gene rearrangements. These rearrangements have been widely used as specific markers for monitoring minimal residual disease. However, their prognostic value still remains unclear. In order to determine whether IgH and TCRδ gene rearrangements have any influence on relapse and event-free survival (EFS), we analysed the clinical impact of these genetic characteristics in 51 B-precursor acute lymphoblastic leukaemia patients. 46/51 patients (90.2%) showed IgH gene rearrangements by Southern blot and/or polymerase chain reaction (PCR) analysis. No statistically significant associations were found between IgH gene rearrangement pattern and age, sex, WBC count, immunophenotype, risk factor, relapse or EFS. 27/41 patients (66%) showed Vδ₂Dδ₃ recombination by Southern blot and/or PCR analysis. At a median follow-up of 53 months the estimated 5-year EFS probability was 78 ± 3% for the whole group. The EFS probability among patients with a Vδ₂Dδ₃ recombination pattern in the TCRδ locus was 90 ± 3%, whereas for patients without Vδ₂Dδ₃ recombination was 39 ± 13% ( P  < 0.005).
IgH rearrangement patterns do not appear to influence relapse or EFS probability. However, TCRδ gene rearrangement patterns have a relevant impact on the relapse rate and the EFS probability. Patients with Vδ₂Dδ₃ recombination have better clinical outcome than patients without this recombination, independent of any other prognostic factors.     

Clinical value of tumour markers and serum-ascites albumin gradient in the diagnosis of malignancy-related ascites

Abstract To determine the clinical value of tumour markers in the diagnosis of malignancy-related ascites (not including hepatocellular carcinoma), serum and ascitic fluid levels of carcinoembryonic antigen, cancer antigen 125, carbohydrate antigen 19–9, tissue polypeptide antigen and serum-ascites albumin gradient were determined in 66 patients with cirrhotic ascites, 28 patients with hepatocellular carcinoma and ascites, and 29 patients with malignancy-related ascites. Three tumour markers and serum-ascites albumin gradient showed significant difference between patients with malignancy-related ascites and those without: serum carcinoembryonic antigen (26.4 ± 31.5 vs 4.8 ± 4.6 ng/mL, P < 0.01), ascitic fluid carcinoembryonic antigen (118.4 ± 196.5 vs 2.0 ± 1.4 ng/mL, P < 0.01), ascitic fluid carbohydrate antigen 19–9 (12 933 ± 25 496 vs 23 ± 67 U/mL, P < 0.01), and serum-ascites albumin gradient (1.1 ± 0.4 vs 2.0 ± 0.4 g/dL, P < 0.01). At the best cut-off levels chosen from near 95% of the data in those without malignancy-related ascites, the sensitivity, specificity and accuracy to diagnose malignancy-related ascites were, respectively, 65.5%, 93.6%, 87.0% using serum carcinoembryonic antigen 10 ng/mL; 69.0%, 94.7%, 88.6% using ascitic fluid carcinoembryonic antigen 5 ng/mL; 65.5%, 93.6%, 87.0% using ascitic fluid carbohydrate antigen 19–9 50 U/mL; 62.1%, 98.9%, 90.2% using serum-ascites albumin gradient < 1.1 g/dL. Although serum-ascites albumin gradient offered the best diagnostic accuracy and specificity, its sensitivity was not good enough. Our study indicates that serum-ascites albumin gradient and tumour markers are not sensitive parameters in the diagnosis of malignancy-related ascites.     

Immunophenotype of adult and childhood acute promyelocytic leukaemia: correlation with morphology, type of PML gene breakpoint and clinical outcome. A cooperative Italian study on 196 cases

Acute promyelocytic leukaemia (APL), characterized by a specific PML-RARα fusion gene resulting from translocation t(15;17) and by a high response rate to differentiation therapy with all- trans retinoic acid, presents clinical (varying WBC counts, age and treatment outcome), morphological (hypergranular M3 and hypogranular M3V) and molecular (three isoforms of PML breakpoint) heterogeneity.
We correlated leukaemic immunophenotype with these aspects in 196 molecularly confirmed APLs (63 children and 133 adults) in Italy. The bcr3 isoform ( P  = 0.05) and FAB M3V ( P  = 0.05) were more frequent in children. We confirmed in APL an immunophenotype characterized by frequent expression of CD13, CD33 and CD9 and rare expression of HLA-DR, CD10, CD7 and CD11b. However, we recognized CD2 in 28%, CD34 in 23% and CD19 in 11% of cases and demonstrated by double labelling that CD34 and CD2 may be co-expressed. CD2, CD34 and CD19 were significantly intercorrelated, and variably associated to other features: CD2 and CD34 with PML bcr3 ( P  < 0.001 and P  < 0.001, respectively) and with M3V ( P  < 0.001 and P  = 0.002), whereas only CD19 was directly correlated with WBC counts and only CD2 positively influenced CR rate (logistic model) and event-free survival (Cox model). We conclude that immunophenotype plays a role in the determination of the biological and clinical heterogeneity of childhood and adult APL.     

Anti-nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A1 adenosine receptors

Background and purpose

Allopurinol is a potent inhibitor of the enzyme xanthine oxidase, used primarily in the treatment of hyperuricemia and gout. It is well known that purines exert multiple effects on pain transmission. We hypothesized that the inhibition of xanthine oxidase by allopurinol, thereby reducing purine degradation, could be a valid strategy to enhance purinergic activity. The aim of this study was to investigate the anti-nociceptive profile of allopurinol on chemical and thermal pain models in mice.

Experimental approach

Mice received an intraperitoneal (i.p.) injection of vehicle (Tween 10%) or allopurinol (10–400 mg kg⁻¹). Anti-nociceptive effects were measured with intraplantar capsaicin, intraplantar glutamate, tail-flick or hot-plate tests.

Key results

Allopurinol presented dose-dependent anti-nociceptive effects in all models. The opioid antagonist naloxone did not affect these anti-nociceptive effects. The non-selective adenosine-receptor antagonist caffeine and the selective A₁ adenosine-receptor antagonist, DPCPX, but not the selective A_2A adenosine-receptor antagonist, {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304","term_text":"SCH58261"}}SCH58261, completely prevented allopurinol-induced anti-nociception. No obvious motor deficits were produced by allopurinol, at doses up to 200 mg kg⁻¹. Allopurinol also caused an increase in cerebrospinal fluid levels of purines, including the nucleosides adenosine and guanosine, and decreased cerebrospinal fluid concentration of uric acid.

Conclusions and implications

Allopurinol-induced anti-nociception may be related to adenosine accumulation. Allopurinol is an old and extensively used compound and seems to be well tolerated with no obvious central nervous system toxic effects at high doses. This drug may be useful to treat pain syndromes in humans.