Anthracycline cardiotoxicity.

Anthracycline drugs have been widely used as chemotherapeuticagents against a range of cancers, including sarcomas, carcinomas,leukaemias, and lymphomas. However, cardiotoxic effects, inparticular the development of cardiomyopathy, have limited theirclinical use. The observation of dose-dependent cardiotoxicityhas resulted in a recommended empirical dose limit of 450 mg/m²of body surface area. Age, gender, pre-existing heart disease,hypertension, and mediastinal irradiation have also been implicatedas factors contributing to the development of doxorubicin-associatedcardiomyopathy. However, cardiotoxicity may still occur at relativelylow levels of drug administration, even in individuals withno additional risk factors, and the onset may be delayed bymany years.¹ More recently, the use of trastuzumab, a monoclonalantibody directed against the HER2 receptor, has been     

Characteristics of apathy in Parkinson's disease.

The objective of this study was to use the Lille Apathy Rating Scale to assess apathy in a large population of Parkinson's disease (PD) patients and identify several different apathy profiles. One hundred fifty-nine patients with probable PD and 58 healthy controls participated in the study. Apathy was assessed using the Lille Apathy Rating Scale. Motor, cognitive, and depressive symptoms were rated on standardized scales. Data were analyzed using linear regression and multivariate analyses of variance. Thirty-two percent of the PD patients were classified as apathetic. Apathy was more frequent in patients with dementia. The four apathy dimensions contributed differently to the overall severity of the apathetic condition. Action initiation and intellectual curiosity had a marked influence. Linear regression analysis revealed that the apathy level was mainly determined by cognitive impairment, not associated with the severity of motor symptoms, and only associated with the apathy subcomponent of the Montgomery and Asberg Depression Rating Scale. Apathy is highly prevalent in PD patients. Apathy profiles vary according to the clinical presentation of PD. The high prevalence of apathy in PD suggests the involvement of frontal-subcortical circuits. Although the neurochemical substrate of apathy remains poorly characterized, the strong link between apathy and cognitive impairment observed in several studies suggests the participation of nondopaminergic circuits.     

Pseudoinvasion with high-grade dysplasia in a colonic adenoma. Distinction from adenocarcinoma

High-grade dysplasia was found to extend to an area of pseudoinvasion in the submucosa of a colonic adenoma mimicking invasive carcinoma. The presence of both benign and cytologically malignant epithelium and residual foci of lamina propria among the submucosal glands distinguishes this entity from adenocarcinoma arising in an adenomatous polyp.     

Radiologic long-term results after cervical vertebral interbody fusion with Polymethyl Methacrylat (PMMA)

Long-term results of cervical interbody fusion with PMMA were evaluated in a retrospective study. X-ray films of 83 patients were obtainable. Post-operative follow-up in this series was between 15 and 20 years. The results show that PMMA is engrafted after about 2 years. Stable vertebral interbody fusion is obtained in about 90% of cases. Development of malignoma was not observed. Resorptive bone alterations, which can be seen in about 2% of cases one to two years after operation are shown not to be progressive. This process heals and stable fusion develops.     

Predominance of Th1-type T cells in synovial fluid of patients with Yersinia-induced reactive arthritis.

The pathogenetic mechanisms underlying the development of reactive arthritis and the functional capacities of synovial T cells specific for Yersinia enterocolitica are still unclear. In this study we have determined the cytokine secretion patterns of 24 CD4+ synovial fluid (SF)-derived T cell clones from 2 patients with Yersinia-induced reactive arthritis, 16 clones specific for different Yersinia antigens and 8 clones as controls. The clones specific for Yersinia antigens predominantly belong to the T helper cell 1 (Th1) subset with production of interferon (IFN)-gamma and interleukin (IL)-2, but no IL-4, whereas SF T cells not reactive with Yersinia antigens produce IL-2, IL-4 and IFN-gamma and thus belonged to the Th0 subset. Moreover, short-term T cell lines established from SF and peripheral blood showed the same pattern. To further analyze the functional relevance of these data we investigated the influence of IFN-gamma and IL-4 on the intracellular killing of Yersinia in a human glioblastoma cell line. Our data show that the Th1 cytokine IFN-gamma promotes intracellular killing of Yersinia, whereas this effect is antagonized by the Th2 cytokine IL-4. Furthermore, the Th2 cytokine IL-10 inhibited the antigen-specific proliferative response and IFN-gamma and IL-2 production by the Th1 cells. These results provide insight into the antibacterial mechanisms at work in reactive arthritis after infection with Yersinia enterocolitica and, for the first time, reveal the cross-regulatory properties of cytokines derived from Th1 and Th2 cells in a human immune response to bacterial antigens.