Biomedical subjects
Publications and source records attributed to René Gérolami.
We report a case of Budd-Chiari syndrome caused by protein C deficiency. The association of thrombosis of the the inferior vein cava of the hepatic vein resulted in the development of epidural varices and a central and peripheral neurological syndrome. These symptoms, which are atypical in this disease, resolved after surgical treatment of the Budd-Chiari syndrome (cavoatrial and mesocaval stenting).
A 25-year-old woman had a high serum level of alkaline phosphatase activity (2571 UI/L). Serum levels of transaminases, gamma glutamyl transferase and bilirubin were normal. Abdominal ultrasonography revealed a tumor nodule in the right liver lobe. There was no evidence of biliary obstruction. The serum activity of alkaline phosphatase returned to normal after surgical removal of the liver tumor. Histologic examination showed that the tumor was a liver adenoma with no evidence of degeneration. The adenoma cells reacted strongly positive to alkaline phosphatase by histochemical staining. The production of hepatic and biliary type alkaline phosphatase by the tumor is the most likely mechanism for the high serum levels observed in this patient.
Progressive multifocal leucoencephalopathy due to JC virus is a rare complication of liver transplantation. Only four cases have already been described in the literature. This disease is difficult to differentiate from leucoencephalopathy associated with immunosuppressive drugs such as cyclosporin or tacrolimus. Positive diagnosis of progressive multifocal leucoencephalopathy no longer requires cerebral biopsy. It must be confirmed by positive JC virus RNA amplification in the cerebrospinal fluid. We report a case of progressive multifocal leucoencephalopathy occurring 18 months after liver transplantation for hepatitis C-related cirrhosis.
We report a case of hepatitis B virus reactivation that occurred after immunosuppressive treatment in a hepatitis B surface antigen-negative patient with detectable antibodies to hepatitis B core antigen and hepatitis B surface antigen. Sequence analysis revealed an 11-bp insertion in the core promoter region of hepatitis virus DNA, creating a novel hepatocyte nuclear factor-1 binding site. This led to enhanced viral replication and fulminant hepatitis.
Radioiodine therapy of nonthyroid cancers after sodium iodide symporter (NIS) gene delivery has been proposed as a potential application of gene therapy. However, it seems to be precluded by the rapid efflux of taken up iodine from most transduced xenografted tumors. We present an in vivo kinetic study of NIS-related hepatic iodine uptake in an aggressive model of hepatocarcinoma induced by diethylnitrosamine in immunocompetent Wistar rats. We followed the whole-body iodine distribution by repeated imaging of live animals. We constructed a rat NIS (rNIS) adenoviral vector, Ad-CMV-rNIS, using the cytomegalovirus (CMV) as a promoter. Injected in the portal vein in 5 healthy and 25 hepatocarcinoma-bearing rats and liver tumors in 9 hepatocarcinoma-bearing rats, Ad-CMV-rNIS drove expression of a functional NIS protein by hepatocytes and allowed marked (from 20 to 30% of the injected dose) and sustained (>11 days) iodine uptake. This contrasts with the massive iodine efflux found in vitro in human hepatic tumor cell lines. In vivo specific inhibition of NIS by sodium perchlorate led to a rapid iodine efflux from the liver, indicating that the sustained uptake was not attributable to an active retention mechanism but to permanent recycling of the effluent radioiodine via the high hepatic blood flow. Radioiodine therapy after Ad-CMV-rNIS administration achieved a strong inhibition of tumor growth, the complete regression of small nodules, and prolonged survival of hepatocarcinoma-bearing rats. This demonstrates for the first time the efficacy of NIS-based radiotherapy in a relevant preclinical model of nonthyroid human carcinogenesis.
We tested 53 fixed duodenal biopsy samples from 25 patients with Whipple disease for the presence Giardia and 6 fresh duodenal biopsy samples for Giardia duodenalis DNA by polymerase chain reaction (PCR). We also used histological examination and PCR assay to determine the prevalence of G. duodenalis in duodenal biopsy samples from 150 control patients without Whipple disease. Three of 25 patients with Whipple disease had histological evidence of giardiasis, whereas only 1 of 150 control patients was affected (P<.001). By PCR, we found Giardia in 2 of 6 patients with Whipple disease whom we tested, but in only 2 of 150 control patients (P<.001). In a literature review, we identified 15 other cases of coinfection. The occurrence of these diseases may be promoted by a common immune defect or a common source of infection, or infection with one may predispose to infection with the other.
Hepatocellular carcinoma (HCC), the most prevalent histological form of primary liver cancer is one of the most frequent cancer worldwide. This pathology still requires the development of new therapeutical approaches. Gene therapy strategies focusing on the genetic manipulation of accessory cells involved in the immune reaction against cancer cells, or on the direct transduction of tumor cells with transgenes able to "suicide" cancer cells have been largely developed for more than ten years.
Suicide gene therapy combining herpes simplex virus thymidine kinase gene transfer and ganciclovir administration can be envisioned as a powerful therapeutical approach in the treatment of hepatocellular carcinoma; however, safety issues regarding transgene expression in parenchyma cells have to be addressed. In this study, we constructed LATKW, a lentiviral vector expressing the HSV-TkEGFP gene placed under the control of the promoter elements that control the expression of the rat alpha-fetoprotein, and assayed its specific expression in vitro in hepatocarcinoma and nonhepatocarcinoma human cell lines, and in epidermal growth factor stimulated human primary hepatocytes. Using LATKW, a strong expression of the transgene was found in transduced hepatocarcinoma cells compared to a very low expression in nonhepatocarcinoma human cell lines, as assessed by Northern blot, RT-PCR, FACS analysis and ganciclovir-mediated toxicity assay, and no expression was found in lentivirally transduced normal human hepatocytes. Altogether, these results demonstrate the possibility to use a lentivirally transduced expression unit containing the rat alpha-fetoprotein promoter to restrict the HSV-TK-mediated induced GCV sensitivity to human hepatocarcinoma cells.