Background-Enteroviruses and adenoviruses have been considered the most common causes of viral myocarditis, but parvovirus B19 (PVB19) and human herpesvirus 6 (HHV6) are increasingly found in endomyocardial biopsy samples. Methods and Results-Consequently, our aim was to evaluate the prevalence and clinical presentation of cardiac PVB19and/or HHV6 infection in a cohort of myocarditis patients and to follow its clinical course. In addition, we sought to demonstrate patterns of myocardial damage and to determine predictors for chronic heart failure. Our study design consisted of a cardiovascular magnetic resonance protocol as well as endomyocardial biopsies in the myocardial region affected as indicated by cardiovascular magnetic resonance. One hundred twenty-eight patients were enrolled by clinical criteria. In the group of myocarditis patients (nϭ87), PVB19 (nϭ49), HHV6 (nϭ16), and combined PVB19/HHV6 infections (nϭ15) were detected most frequently. The remaining patients were diagnosed with healing myocarditis (nϭ15) or did not have myocarditis (nϭ26). Patients with PVB19 presented in a manner similar to that of myocardial infarction; most had typical subepicardial late gadolinium enhancement in the lateral wall and recovered within months. Conversely, patients with HHV6 and especially with HHV6/PVB19 myocarditis presented with new onset of heart failure, had septal late gadolinium enhancement, and frequently progressed toward chronic heart failure. Conclusions-Our

Prediction of responsiveness after clopidogrel loading dose may substantially be improved by adding CYP2C19*2 genotype to nongenetic risk factors.

Purpose: The role of transforming growth factor ␤ (TGF-␤) in breast cancer is ambiguous; it can display both tumor suppressing and enhancing effects. Activation of the TGF-␤ signal transduction system is subject to hormonal regulation. This study was conducted to further analyze the role of TGF-␤ receptors in breast cancer and to evaluate their significance as prognostic markers. Experimental Design: Expression of TGF-␤ receptor I (T␤RI) and TGF␤ receptor II (T␤RII) was retrospectively analyzed by immunohistochemistry in 246 breast cancer patients.Results: Expression of T␤RI was strongly correlated with tumor size (P < 0.001) and nodal status (P ‫؍‬ 0.012) but only weakly with overall survival (P ‫؍‬ 0.056). In contrast, T␤RII was prognostic for overall survival in univariate analysis (P ‫؍‬ 0.0370). In estrogen receptor (ER) -negative patients T␤RII expression was correlated with highly reduced overall survival (P ‫؍‬ 0.0083). In multivariate analysis T␤RII proved to be an independent and highly significant prognostic marker with a hazard ratio of 6.8. Simultaneous loss of both ER and T␤RII was associated with longer overall survival times comparable with those of ER-positive patients.Conclusions: The results of this exploratory study show that T␤RII is an independent, highly significant prognostic indicator for overall survival in ER-negative patients. In addition our results are supportive of a mechanism of breast cancer progression in which a selective loss of the tumor inhibitory action of TGF␤ takes place, whereas tumorpromoting aspects remain intact.

This clinical prediction rule provides a novel and diagnostically accurate strategy for the potential prevention and improved management of kidney complications in patients with NE and, ultimately, for a possible decrease in unnecessary hospitalization in a high number of patients.

PURPOSE We started a phase II trial of induction chemotherapy and concurrent hyperfractionated chemoradiotherapy followed by either surgery or boost chemoradiotherapy in patients with advanced, stage III disease. The purpose is to achieve better survival in the surgery group with minimum morbidity and mortality. PATIENTS AND METHODS Patients treated from 1998 to 2002 with neoadjuvant chemoradiotherapy and surgical resection for stage III NSCLC were analyzed. The treatment consisted of four cycles of induction chemotherapy with carboplatin/paclitaxel followed by chemoradiotherapy with a reduced dose of carboplatin/paclitaxel and accelerated hyperfractionated radiotherapy with 1.5 Gy twice daily up to 45 Gy. After restaging, operable patients underwent thoracotomy. Inoperable patients received chemoradiotherapy up to 63 Gy. Study end points included resectability, pathologic response, and survival. Results One hundred twenty patients were enrolled; 25% patients had stage IIIA, 73% had stage IIIB, and 2% stage IV. After treatment, 47.5% had downstaging, 29.2% had stable disease, and 23.3% had progressive disease. Thirty patients (25%) were not eligible for operation because of progressive disease, stable disease, and/or functional deterioration with one treatment-related death. The 30-day mortality was 5% in patients who underwent operation. The 5-year survival rate for 120 patients was 21.7%, and it was 43.1% in patients with complete resection. In postoperative patients with stage N0 disease, 5-year survival was 53.3%; if stage N2 or N3 disease was still present, 5-year survival was 33.3%. CONCLUSION Staging and treatment with chemoradiotherapy and complete resection performed in experienced centers achieve acceptable morbidity and mortality.

BackgroundAlthough transforming growth factor β (TGF-β) typically inhibits proliferation of epithelial cells, consistent with a tumor suppressor activity, it paradoxically also exhibits pro-metastatic activity in the later stages of carcinogenesis. Since tumors often display altered TGF-β signaling, particularly involving the Smad-pathway, we investigated the role of Smad4-expression in breast cancer.MethodsSmad4 expression was investigated by immunohistochemistry in formalin-fixed, paraffin-embedded tissue from 197 samples of primary breast cancer obtained between 1986 and 1998. The prognostic value of Smad4-expression was analyzed.ResultsSmad4 expression was found to be reduced in lobular and ductal breast carcinoma as compared to surrounding uninvolved lobular and ductal breast epithelia (p < 0.001, n = 50). Smad4-expression correlated positively with expression of TGF-β-receptor I (p < 0.001, n = 197) and TGF-β-receptor II (p < 0.001, n = 197), but showed no significant correlation with tumor size, metastases, nodal status, histological grade, histological type, or estrogen receptor expression. While not achieving statistical significance, there was a trend towards longer survival times in patients with Smad4 negative tumors.ConclusionAccording to the suggested role of Smad4 as a tumor suppressor we observed that expression of Smad4 is lower in human breast cancer than in surrounding breast epithelium. However, we also observed a trend towards longer survival times in Smad4-negative patients, indicating the complex role of TGF-β signaling in tumor progression.

The consequences of associated hematuria may be long-lasting, and hantavirus IgG is detectable years after acute infection.

BackgroundThe two most relevant pathologies of long-term peritoneal dialysis (PD) are simple sclerosis and encapsulating peritoneal sclerosis (EPS). The histological differentiation of those two entities is difficult. The Aim of the study was to establish a method to standardize and facilitate the differentiation between simple sclerosis and EPSMethodsWe investigated 58 peritoneal biopsies - 31 EPS patients and 27 PD patients. Two blinded investigators analyzed 20 histological characteristics in EPS and PD patients.ResultsThe following findings were significantly more common in EPS than in patients on PD without EPS: fibroblast like cells (FLC) (p<0.0001), mesothelial denudation (p<0.0001), decreased cellularity (p = 0.008), fibrin deposits (p<0.03), Fe deposits (p = 0.05), podoplanin vascular (p<0.0001), podoplanin avascular (p<0.0001). Using all predictor variables we trained the classification method Random Forest to categorize future cases. Podoplanin vascular and avascular were taken together (p<0.0001), FLC (p<0.0001), mesothelial denudation (p = 0.0005), calcification (p = 0.0026), acellular areas (p = 0.0094), and fibrin deposits (p = 0.0336) showed up as significantly important predictor variables. Estimated misclassification error rate when classifying new cases turned out to be 14%.ConclusionThe introduced statistical method allows discriminating between simple sclerosis and EPS. The misclassification error will likely improve with every new case added to the database.