In our study injection of botulinum toxin into the detrusor muscle did not lead to increased fibrotic activity within the bladder wall, on the contrary patients with previous botulinum toxin injection revealed significant less fibrosis than patients without toxin injection.

The antimalarial agents, chloroquine (CQ) and hydroxychloroquine (HCQ) are used in long-term treatment of connective tissue diseases and dermatological disorders and are generally regarded as safe. We present one case of cardiotoxicity in a 59-year-old woman treated with antimalarials during 13 years for a discoid lupus erythematosus. She progressively developed conduction disturbances and congestive heart failure (CHF). When the diagnosis of antimalarials toxicity was suspected, CQ was withdrawn. However, heart transplantation had to be performed in the following 4 months for severe CHF. Indeed, rare but severe cardiotoxicity may develop following prolonged use of antimalarials with both conduction disturbances (45 patients) and CHF (25 patients). These cardiac toxic effects have been reported with CQ and less frequently with HCQ use alone. Diagnoses are often delayed since the toxicity of the drug might be misattributed to other factors in these patients. The endomyocardial biopsy, or in some cases the muscle biopsy, are essential to confirm the antimalarials toxicity. Antimalarials have been stopped in 12 cases of CHF, leading to improvement in 8 cases (within 3 months to 5 years) and to deaths or to heart transplantation in 4 cases (within 1 week to 3 months). In the latter cases, as in our patient, the lack of improvement may have been explained by the severity of the cardiomyopathy at diagnosis and the short delay since withdrawal. As a consequence, the potential for reversibility and the severity in undiagnosed cases of these toxic cardiomyopathies emphasize the importance of recognizing early signs of toxicity in order to withdraw antimalarials before the occurrence of life-threatening CHF.

Background: End‐stage of human dilated cardiomyopathy (DCM) is characterized by myocyte loss and fibrosis, and associated with ventricular dilatation and reduced cardiac function. Matrix metalloproteinases (MMPs) and their natural tissue inhibitors (TIMPs) have been involved in the myocardial remodeling. Aims: To evaluate the potential role of matrix gelatinases (MMP‐2 and MMP‐9) in DCM, the balance between gelatinases and TIMPs and the gelatinase localization were investigated in left free wall ventricles from six normal donors and six patients with DCM at the transplantation time. Methods: TIMP‐(1, 2, 3 and 4) mRNAs were analyzed by quantitative reverse transcription‐polymerase chain reaction (RT‐PCR). TIMP‐1 and ‐2 protein content was assessed by ELISA. MMP‐2 and MMP‐9 expression were examined by zymography and immunological techniques. Results: All TIMPs were down‐regulated in DCM hearts, especially TIMP‐1 (reduced by 80%). Gel zymography revealed similar activity of MMP‐2 and MMP‐9 in both tissues. By in situ zymography and immunohistochemistry, active and immunoreactive gelatinases were pericardiomyocyte in control hearts and intracardiomyocyte in DCM hearts. Intracellular MMPs were associated with sarcomeric structure in DCM. To estimate a putative role of these gelatinases, several sarcomeric contractile proteins were digested in vitro by purified active MMP‐9. Only myosin‐heavy chain was cleaved in vitro giving 180‐, 120‐, 80‐ and 20‐kDa proteolytic fragments. In vivo, two major myosin‐heavy chain proteolytic fragments (80 and 20 kDa) were detected by specific monoclonal antibody against myosin‐heavy chain in DCM left ventricular homogenates, only. Conclusions: Taken together, these data highly suggest that MMP‐2 and MMP‐9 may be involved in the disorganization of the contractile apparatus in DCM hearts.

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P63 is a member of the p53 family, which plays a role in the differentiation of urothelium and is supposed to play a role in urothelial carcinogenesis. P53 and MIB-1 are recognised in many studies as predictive markers of progression, but few studies in the literature have examined p63. The aims of our study were to explore the expression of p63 in bladder carcinomas and to compare this expression to p53 and MIB-1, as well as to stage and grade. Tissue microarrays were performed on 158 urothelial carcinomas (56 pTa, 45 pT1 and 57>or=pT2). Immunohistochemical studies were performed with p63, p53 and MIB-1 antibodies. In our study we observed that p63 immunostaining is present in all cell layers in papillary urothelial neoplasm of low malignant potential (PUNLMP), but partially lost in non-invasive papillary urothelial carcinoma low grade (NILGC) and in pT1/>or=pT2 bladder cancers. P53 and MIB-1 displayed lower expression in PUNLMP/NILGC vs non-invasive papillary urothelial carcinoma high grade (NIHGC)/pT1, but there was no correlation between the expression of p63, p53 and MIB-1. Our study demonstrates that p63 expression distinguishes between PUNLMP/NILGC and NIHGC/pT1 (p=4.10(5)). A statistical difference disserving pTa and pT1/>or=pT2 with a statistical significance (p<10(-6)) could also be observed. P63 should be considered as an additional biomarker that might help pathologists to classify their patients.

Organ transplantation from cadaveric donors has a risk of cancer transmission. However, some reports indicate that kidneys bearing small carcinomas can be safely transplanted, as can other organs harvested from the same donor. We report herein the case of two allograft recipients (left kidney and heart with no evidence of tumor) who developed a renal carcinoma soon after transplantation. The initial tumor of the donor was a 17-mm tubulopapillary adenoma found on the right kidney, which was not transplanted. The left kidney recipient rejected all residual tumoral cells after graft removal and immunosuppression discontinuation. The heart recipient died 7 months after transplantation from metastasis of a renal carcinoma. This strongly suggests that circulating carcinoma cells were present at the time of organ retrieval and that they were not cleared by in situ perfusion. In contrast with the literature data, this report indicates that patients with small renal tubulopapillary tumors should not be considered for organ donation.

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