Rebleeding from a primary brain tumor manifesting as intracerebral hemorrhage (CNN 04/077, revised version)

Symptomatic spontaneous intratumoral hemorrhage is a rare event in a patient with a brain tumor (BT). Although the treatment of choice in such a case is surgical removal of both the tumor and the hemorrhage, the optimal timing for surgical intervention has not been clearly established, particularly in those who present with minimal neurological deficits and a small hemorrhage volume. Two cases of primary BTs manifesting as an intracerebral hemorrhage (ICH) are described, in which rebleeding from the tumor occurred shortly after the initial hemorrhage. The patients each presented with the sudden onset of a headache and minimal neurological deficits, and the neuroradiological workup was consistent with a diagnosis of hemorrhagic BT. Each patient remained neurologically stable, and elective surgery had been planned within 7 days of their admission, but rebleeding occurred 5 and 6 days, respectively, after admission. A BT manifesting as an ICH may rebleed shortly after the initial bleeding, and should be treated on an emergency basis instead of an elective basis regardless of the patient's neurological status on admission or hematoma volume on the initial CT scans.     

Toxicité des antirétroviraux chez les patients co-infectés par les virus VIH et VHC

The introduction of HAART (Highly Active Antiretroviral Therapy) has deeply modified the epidemiologic data on HIV infection. Consequently, chronic hepatotoxicities, particularly those related to HCV, became a leading cause of morbidity and mortality amongst co-infected HIV-HCV patients. They became a major factor to be considered before starting and conducting a HAART regimen. Due to the epidemiology of these two infections and referring to several huge randomised prospective clinical trials recently reported, understanding the antiretroviral toxicity is a true challenge in the follow-up of co-infected patients. It includes: i) understanding the intrinsec toxicities of each antiretroviral class, particularly drugs-related hepatotoxicities; then ii) the incidences of those treatments in co-infected patients, with or without anti-HCV bitherapy; and iii) the pathogenic reciprocal interactions between HIV and HCV and between anti-HIV and anti-HCV treatments. Four mechanisms of drug-related liver toxicity have been recognized: i) direct drug toxicity; ii) immune reconstitution; iii) hypersensitivity reactions with liver involvement; and iv) mitochondrial toxicity. The benefit-risk ratio notion must be strongly evaluated and the therapeutic strategy must include, for each patient, a strict monitoring of biochemichal (liver parameters, hemogram, amylasemia, lipasemia, evaluation of liver fibrosis index) and clinical (weight, lipodystrophy) parameters. A better pharmacological knowledge, a global view and the development of new drugs with less hepatotoxicity, like fusion inhibitors, would increase the quality of life of co-infected patients. Liver transplantation could be a hope for patients with severe hepatic failure.     

Reduced graft-versus-host disease-inducing capacity of T cells after activation, culturing, and magnetic cell sorting selection in an allogeneic bone marrow transplantation model in rats.

Graft-versus-host disease (GvHD), a major complication of allogeneic bone marrow transplantation, has been ascribed to mature T cells in the graft. Because T cells play an important role in engraftment of the bone marrow and decrease the probability of relapse of leukemia, a treatment strategy was developed to preserve the benefits of T cells in the graft and to control the severe complications of GvHD. This can be accomplished by the genetic modification of donor T cells with a suicide gene that allows their selective in vivo elimination and subsequently the abrogation of GvHD. For clinical benefit the alloreactivity of herpes simplex virus thymidine kinase (HSV-TK) gene-transduced T cells should be retained. Therefore, we investigated the influence of gene transduction and the selection procedure on T cells. We demonstrated that activation and culturing of T cells reduce their capacity to induce lethal GvHD in an allogeneic rat bone marrow transplantation model. Furthermore, positive immunomagnetic selection of gene-transduced T cells resulted in loss of the GvHD-inducing capacity of HSV-TK(+) T cells directly after MACS (magnetic cell sorting) selection; this loss could be recovered by a 1-day expansion of the selected T cells. No effect on alloreactivity was observed to be caused by the gene transduction procedure. Our study resulted in the development of an optimized culture and gene transduction protocol with preservation of T cell alloreactivity. Treatment of transplanted rats with ganciclovir resulted in a rapid reduction in the number of HSV-TK(+) T cells in the peripheral blood and in increased survival of the animals.     

Comparisons of Pooled Polyclonal Rabbit Anti-Human C3d with Four Monoclonal Mouse Anti-Human C3ds

Performance characteristics of pooled rabbit IgG polyclonal anti-C3d are compared with one mouse IgM and three mouse IgG monoclonal anti-C3d antibodies (MAs). IgG MA,s employed singly or in combination, failed to precipitate C3d; by contrast, IgM MA and polyclonal anti-C3d precipitated C3d. Measurements of polyclonal anti-C3d concentration by chemical means and by 125I-C3d radioimmunoassay (RIA) agreed closely. RIA values were 50% of chemical measurement values for three of the four MAs. Use of sucrose density gradient ultracentrifugation to assess MA C3d/anti-C3d molar combining ratios for soluble anti-C3d/C3d was not possible because fast-sedimenting multimeric C3d/anti-C3d complexes did not form. Dissociation and competitive binding studies indicate that (1) two MAs had substantially lower affinities than the other anti-C3d antibodies, and (2) polyclonal anti-C3d recognizes more C3d epitopes than are recognized by individual MAs. The results demonstrate antigenic complexity of C3d fragment and illustrate the difficulties of predicting individual MA performance based on prior experience with polyclonal antibodies.