Clinical presentation of young people (10–24 years old) with brain tumors: results from the international MOBI-Kids study

Journal of Neuro-Oncology - We used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in...     

Detection and identification of monoclonal components: immunoelectrophoresis on agarose gel and immunofixation on cellulose acetate compared

Immunofixation on cellulose acetate has been compared with immunoelectrophoresis on agarose gel. We studied 90 sera containing monoclonal components and 10 containing polyclonal immunoglobulins according to agarose gel screening electrophoresis. Results by the two methods agreed about 80% of the time for monoclonal components in concentrations exceeding 1-2 g/L. Immunofixation appeared more sensitive, but it is more susceptible to technical artifacts. Immunofixation may be adopted as a first-step method for easier cases, but it should be supported by immunoelectrophoresis for difficult cases, such as when there is an uncertain presence of monoclonal components at screening electrophoresis or presence of more and (or) small bands of monoclonal components.     

TAK1-regulated expression of BIRC3 predicts resistance to preoperative chemoradiotherapy in oesophageal adenocarcinoma patients

Background:

About 20% of resectable oesophageal carcinoma is resistant to preoperative chemoradiotherapy. Here we hypothesised that the expression of the antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3 induced by the transforming growth factor β activated kinase 1 (TAK1) might be responsible for the resistance to the proapoptotic effect of chemoradiotherapy in oesophageal carcinoma.

Methods:

TAK1 kinase activity was inhibited in FLO-1 and KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA expression was measured by qRT–PCR in 65 pretreatment frozen biopsies from patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were performed to determine the performance of BIRC3 expression levels in distinguishing patients with sensitive or resistant carcinoma.

Results:

In vitro, (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1 cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol resulted in a strong synergistic antiapoptotic effect. In patients, median expression of BIRC3 was significantly (P<0.0001) higher in adenocarcinoma than in the more sensitive squamous cell carcinoma subtype. The BIRC3 expression significantly discriminated patients with sensitive or resistant adenocarcinoma (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard''s tumour regression grade classifications, respectively).

Conclusions:

The BIRC3 expression might be a valid biomarker for predicting patients with oesophageal adenocarcinoma that could most likely benefit from preoperative chemoradiotherapy.     

The effect of therapy on platelet-associated autoantibody in chronic immune thrombocytopenic purpura

Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder due to autoantibody-induced destruction of platelets. Several forms of therapy have been used, including corticosteroids, splenectomy, danazol, and a variety of immunosuppressants. We studied the mechanism of action of some of these treatments by evaluating patients' platelet- associated autoantibodies (PAAb) and platelet count before and serially following therapy. Treatment with corticosteroids, splenectomy, cyclophosphamide, and combination chemotherapy resulted in a progressive decrease in PAAb associated with an improvement in the platelet count, and appeared to act by primarily affecting autoantibody production. Conversely, PAAb levels either remained stable or increased during vincristine or danazol therapy despite improvement in the platelet count, suggesting that the major effect of these agents was decreased platelet removal by the reticuloendothelial (RE) system.     

Prospective study of the meaning of indeterminate results of the Recombinant Immunoblot Assay for hepatitis C virus in blood donors

Background

The interpretation of “indeterminate” results of the recombinant immunoblot assay (RIBA) is a particularly sensitive issue for Transfusion Services, and donors with such a serological condition require long-term follow-up.

Materials and methods

In the Immunohaematology and Transfusion Medicine Division of Umberto I University Hospital (Rome, Italy), 102,979 donor blood units were screened for hepatitis C virus (HCV) antibodies by enzyme-linked immunosorbent assay (ELISA) over a 5-year period (01.01.2000 – 31.12.2004). Since 24.10.2001, HCV -RNA testing was added. All samples repeatedly reactive by ELISA were then submitted to a HCV confirmatory assay (RIBA).

Results

Among the 102,979 donors we found 271 positive to HCV ELISA testing. The results of the RIBA assay for these donors were negative in 178 (65.7%) cases, positive in 28 (10.3%) and indeterminate in 65 (24.0 %).Of the 65 subjects with an indeterminate pattern, 24 completed a sufficient follow-up (median 25 months; range, 6 – 52), during which some (n=8; 33%) converted to a negative status, some (n=16; 67%) maintained their reactivity pattern, but none became seropositive for HCV.

Conclusions

The HCV-RIBA indeterminate status may indicate either a non-specific reaction (false positive) or a real pre-existing or initial infection and does not, therefore, enable a prediction of outcome. The use of HCV genomic assays (nucleic acid amplification testing), which are more specific than antibody-based assays (ELISA, RIBA), therefore improves HCV blood donor testing by allowing an accurate interpretation of such primary assays.     

Separate impact of metabolic syndrome and altered glucose tolerance on early markers of vascular injuries

ObjectiveWe investigated the separate impact of metabolic syndrome (MS) and altered glucose tolerance on early markers of vascular injuries.MethodsIntima-media thickness (IMT) and Pulse Wave Analysis (PWA), were evaluated in 132 overweight or obese subjects, with (MS⁺) or without (MS^?) MS; subjects were further classified as normotolerant (NT) or with altered glucose tolerance (AGT) according to a 2 h oral glucose tolerance test (OGTT).ResultsIn MS⁺ patients, IMT was higher than in the MS^? group, and PWA revealed higher Augmentation Pressure (Aug, the contribution that wave reflection makes to systolic arterial pressure) and lower subendocardial viability ratio (SEVR, an estimate of myocardial perfusion). When analyzed according to glucose tolerance, IMT was higher in MS⁺NT subjects and AGT patients with and without MS, vs. MS^?NT subjects. Logistic regression modeling showed that both AGT and MS were independently associated with increased IMT. However, only MS remained associated with IMT after adjustment for age. SEVR was reduced only in MS⁺ patients, independently of glucose tolerance. In both groups, Aug and AugI were higher in the AGT group, but the correlation with 2 h-plasma glucose disappeared when corrected for age.ConclusionBoth MS and AGT altered IMT, but the effect of AGT disappears when age is added to the multiple regression model. In contrast, arterial stiffness was affected differently in the two categories: in subjects with MS, the subendocardial viability ratio (an estimate of myocardial perfusion) was impaired, while in subjects with AGT, both Aug and AugI were increased. These data suggest that applying the definition of MS might help to better characterize cardiovascular risk in subjects with altered glucose tolerance or obesity.