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Biomedical subjects

V Meignin

Publications and source records attributed to V Meignin.

At least 19 recordsLinked to original sources

Human herpesvirus 8-associated hemophagocytic lymphohistiocytosis in human immunodeficiency virus-infected patients.

We retrospectively reviewed 5 cases of hemophagocytic lymphohistiocytosis (HL) associated with human herpesvirus 8 (HHV-8) reactivation in human immunodeficiency virus (HIV)-infected patients. All patients had clinical and biological features characteristic of HL. Pulmonary symptoms were present in all patients and were frequently life threatening. The mean number of HL episodes was 6. Four patients had HL-associated Kaposi sarcoma, and 3 had multicentric Castleman disease. The mean CD4 cell count was 200 cells/mm(3). HIV loads were stable in all patients. All patients had high levels of HHV-8 in peripheral blood mononuclear cells during attacks, and a significant increase in this parameter before the attacks was seen in 3 patients. Although 2 patients died of HL, 3 are still alive and receiving etoposide therapy (mean follow-up, 3 years). HHV-8-related HL is associated with life-threatening symptoms and biological HHV-8 reactivation, and it may be controlled in the long term by etoposide therapy combined with highly active antiretroviral therapy.

AIDS-Related Opportunistic Infections↗

p53 gene mutations are associated with poor survival in low and low-intermediate risk diffuse large B-cell lymphomas.

BACKGROUND: p53 alterations have been associated with a poor prognosis in aggressive B-cell lymphoma. We investigated the clinical relevance of p53 status in diffuse large B-cell lymphoma (DLBCL), focusing on patients who belong to lower risk groups of the international prognostic index and were uniformly treated. We aimed to determine whether this biological marker could identify among such patients those with a pejorative outcome who could benefit from a distinct therapeutic approach. PATIENTS AND METHODS: We studied 69 patients presenting with no, one (low-risk, n = 40) or two (low-intermediate risk, n = 29) risk factors treated with an anthracyclin-containing induction regimen. p53 exons 5-8 mutations were screened for using denaturing gradient gel electrophoresis and confirmed by direct sequencing. Immunohistochemical detection of p53 protein and of its downstream target p21 were also evaluated in 60 of 69 cases. RESULTS: p53 mutations were detected in 16 of 69 (23%) lymphoma samples. The presence of a p53 gene mutation affected survival (P = 0.01), with a 6-year survival rate estimated to be 44% in mutated patients, compared with 79% in non-mutated ones. Using a stepwise Cox model, p53 mutation constituted the only parameter affecting survival (relative risk = 2.7, P = 0.03). A p53+/p21- immunohistochemical pattern (n = 15), suggestive of a disrupted p53 function, strongly correlated with p53 gene status and was associated with a lower 6-year survival rate when compared with a p53(-) or p53+/p21+ phenotype (47% versus 74%, P = 0.05). CONCLUSIONS: p53 alterations constitute a pejorative biological indicator able to discriminate among clinically defined lower risk patients with DLBCL.

Adult↗

A new defensive mechanism to prevent apoptosis in salivary ductal cells from patients with Sjögren's syndrome: over-expression of p53 and p21.

OBJECTIVE: In Sjögren's syndrome (SS), salivary acinar cells are destroyed even though ductal cells are frequently spared from destruction and can sometimes proliferate. We made the hypothesis that abnormalities of the tumour suppressor protein p53, either by mutations leading to proliferation or by activation of the functional wild-type p53, explain this phenomenon. METHODS: Immunohistochemistry to detect p53 and its transcription target p21, which is expressed only if p53 is functional and not mutated, was performed on labial salivary glands (LSG) from 10 patients with primary SS, all of whom had a Chisholm grade 4 LSG biopsy, and from 10 control patients with sicca symptoms or systemic diseases and a normal LSG biopsy (grade 0 or 1). RESULTS: The p53 antigen could be detected in ductal cells of nine of 10 LSG from SS patients and only one of 10 LSG from controls. The p21 antigen was detected in ductal cells of eight of 10 LSG from SS patients and two of 10 LSG from controls. The p53 and p21 antigens were localized in the same ductal cells in SS patients, and the positive ducts were those located around lymphoid foci. CONCLUSION: The colocalization of p53 and its transcription factor p21 in salivary ductal cells surrounding lymphoid foci demonstrated that p53 was functional and not mutated. Its expression may be a defensive mechanism that provides ductal cells with time to repair DNA damage and prevents apoptosis. The lack of over-expression of p53 and p21 in acinar cells could be one of the key mechanisms of acinus destruction by apoptosis in SS and could be a target for new therapeutic strategies.

Apoptosis↗

Toxoplasmic pneumonitis leading to fatal acute respiratory distress syndrome after engraftment in three bone marrow transplant recipients.

Toxoplasmosis is a rare but severe complication of bone marrow transplantation. Here, we report three patients in whom toxoplasmic pneumonitis developed, leading to fatal acute respiratory distress syndrome (ARDS). All patients had positive pretransplantation tests for Toxoplasma gondii and were therefore at risk to develop toxoplasmosis reactivation. They all recovered from aplasia, but soon after they died from brutal and severe ARDS. The possible role of an immunopathologic response to T gondii in the lungs in triggering ARDS is discussed.Early screening of parasitemia using highly sensitive polymerase chain reaction methods in seropositive patients with unexplained fever may be needed.

Acute Disease↗

Kaposi sarcoma-associated herpesvirus infects monotypic (IgM lambda) but polyclonal naive B cells in Castleman disease and associated lymphoproliferative disorders.

In a previous study, it was shown that the Kaposi sarcoma-associated herpesvirus (KSHV) was specifically associated with monotypic (IgMlambda) plasmablasts in multicentric Castleman disease (MCD). The plasmablasts occur as isolated cells in the mantle zone of B-cell follicles but may form microlymphoma or frank plasmablastic lymphoma. To determine the clonality and cellular origin of the monotypic plasmablasts, the rearranged Ig genes in 13 patients with KSHV-related MCD, including 8 cases with microlymphomas and 2 with frank lymphomas, were studied. To investigate the role of the interleukin 6 (IL-6) receptor signaling in the pathogenesis of MCD and associated lymphoproliferative disorders, viral IL-6 and human IL-6 receptor expression was examined. KSHV-positive plasmablasts were polyclonal in MCD-involved lymphoid tissues in all cases and microlymphomas in 6 of 8 cases. Monoclonal KSHV-positive plasmablasts were seen in microlymphomas of 2 cases and in both frank lymphomas. Despite their mature phenotype, KSHV-positive plasmablasts did not harbor somatic mutations in the rearranged Ig genes, indicating origination from naive B cells. Viral IL-6 was expressed in 10% to 15% of KSHV-positive plasmablasts, whereas the human IL-6 receptor was expressed in most KSHV-positive cells. Thus, KSHV infects monotypic but polyclonal naive B cells and is associated with a range of lymphoproliferative disorders from polyclonal isolated plasmablasts and microlymphomas to monoclonal microlymphoma and frank plasmablastic lymphomas in MCD patients. Activation of the IL-6 receptor signaling pathway may play a role in differentiation of KSHV-infected naive B cells into plasmablasts and development of lymphoproliferative lesions. (Blood. 2001;97:2130-2136)

Antigens, Viral↗

Diffuse large B-cell non-Hodgkin's lymphoma in a patient with autoimmune lymphoproliferative syndrome.

Mutations of Fas or Fas ligand genes result in the autoimmune lymphoproliferative syndrome (ALPS) in humans. We report here a diffuse large B-cell non-Hodgkin's lymphoma occurring in a man with ALPS. Fas-mediated lymphocyte apoptosis was defective in vitro, owing to a mutation within the death domain of the Fas molecule. High-dose methotrexate and doxorubicin-based chemotherapy led to complete remission of lymphoma.

Adult↗

[Resin polymerizing at low temperatures: II. Histochemistry, electron microscopy and immunomarkers].

For pathologists, tissu processing and analysis require good preservation of both the shape (morphology) and the content of the cells (antigens, nucleic acids). Low temperature embedding resins are the only inclusion substrate which allows both a fine morphological analysis and good preservation of antigens and nucleic acids. Automatic the technical processes and simplified protocols now allow the introduction of low temperature embedding resins in diagnostic procedures.

Biomarkers↗

Image-guided core-needle biopsy in patients with suspected or recurrent lymphomas.

BACKGROUND: It is now commonly admitted that the diagnosis of recurrence of lymphoma can be assessed by image-guided needle biopsy (IGNB). However, the means of obtaining tissue for the original diagnosis of lymphoma is often surgery. The aim of this study was to compare the accuracy of IGNB at the time of diagnosis and at the time of recurrence or progression. METHODS: The authors performed 212 IGNBs on 194 patients who eventually had a diagnosis of lymphoma. One hundred three IGNBs were obtained at original diagnosis and 109 at recurrence or progression. Large-cutting core-biopsy needles, ranging in size from 20 gauge to 14 gauge, were used. Immunohistochemistry studies were performed in all lymphoma cases. RESULTS: A diagnosis of lymphoma with subtyping was obtained in 88% of all cases, in 85% at initial diagnosis, and in 89% at follow-up. Therapy was initiated on the basis of IGNB in 93% of all cases, in 91% at initial diagnosis, and in 94% at follow-up. Benign complications occurred in 7.5% of cases and did not require specific treatment. IGNB was equally effective for making a specific diagnosis of lymphoma and initiating therapy at the time of original diagnosis and at follow-up. CONCLUSIONS: The authors recommend that IGNB be performed as the initial procedure for the diagnosis of lymphoma in the absence of peripheral lymph nodes, either at presentation or at recurrence.

Adolescent↗

Prognostic significance of serum p53 antibodies in patients with limited-stage small cell lung cancer.

p53 tumour suppressor gene alterations are one of the most frequent genetic events in lung cancer. A subset of patients with p53 mutation and cancer exhibited circulating serum anti-p53 self-antibodies (p53-Ab). The prevalence of these antibodies in lung cancer is currently being analysed in a multicentric study. In a group of homogeneous SCLC patients, p53-Ab were detected in 20/97 (20.6%) individuals. In this group of patients, Cox's multivariate analysis identified disease extent (p = 0.022), WHO initial performance status greater than 0 (p = 0.005), and the absence of a complete response after 6 months of treatment (p < 0.0001) as independent prognostic variables, with p53-Ab being of borderline significance (p = 0.051). In the subset of limited-stage SCLC patients, Cox's multivariate analysis found p53-Ab (p = 0.033), WHO initial performance status greater than 0 (p = 0.028), and absence of a complete response (p < 0.001) to be independent prognostic variables. Thus, actuarial analysis showed that patients with limited-stage SCLC and p53-Ab had a median survival time of 10 months, whereas limited-stage SCLC patients without p53-Ab had a 17-month median survival time (p = 0.014).Therefore, serum assay of p53-Ab could help to identify a population of SCLC patients with an especially poor prognosis. This population could represent patients with tumours harboring aggressive p53 mutations.

Biomarkers↗

Restaging with gallium scan identifies chemosensitive patients and predicts survival of poor-prognosis mediastinal Hodgkin's disease patients.

UNLABELLED: Following treatment of mediastinal Hodgkin's disease (HD), residual masses are frequent and gallium scanning has proven to be of value in the evaluation of their specificity (fibrosis or active disease). This study assessed, for relapse and survival, the predictive value of restaging gallium scan of patients with a residual mass on computed tomography scan after induction chemotherapy. Between 1/89 and 12/97, in 53 newly diagnosed HD patients with a residual mediastinal mass, a gallium scan was performed after chemotherapy (3 or 4 courses) and always before consolidative radiotherapy. Characteristics at diagnosis were: nodular sclerosis histology, 89%; bulky mediastinal disease, 79%; B-symptoms, 51%. RESULTS: gallium scan was positive in 16 patients (30%) and negative in 37 (70%). At median follow-up period of 36 months, freedom-from-progression rate was 86% versus 19% (P<0.0001) for patients with negative vs positive gallium scans, respectively. The 5-year overall survival (OS) rate was 68% and differed significantly (P<0.0001) between negative (91%) and positive (25%) gallium scanning groups. The specificity of gallium scanning was 91% and the sensitivity 72% with a positive predictive value of 81% and a negative predictive value of 86%. Evaluation with gallium scan after induction chemotherapy identifies chemosensitive patients among those with poor-prognosis mediastinal HD. Although relapse may occur in patients with negative gallium scan, a postive gallium scan is highly predictive of failure and poor outcome, and treatment should thus be modified.

Adult↗

[Techniques to improve the accuracy of CT-guided abdominal biopsy].

STUDY AIM: The aim of this paper is to present an overview of the various technical progresses made in the field of CT-guided abdominal biopsies. Recent improvements allowed to markedly increase the efficiency of biopsies and to decrease the number of complications. The main innovations concern the guidance technique itself with the availability of ultra-fast CT systems, the development of automated biopsy systems, which allow to improve the size and quality of tissue samples and numerous technical tricks, allowing an easier access to target lesions, either in patient positioning or in displacement of anatomical structures. A better management of tissue samples favored by a close collaboration with pathologists is also mandatory. The last section of the paper is an overview of the rare complications of CT-guided biopsies.

Abdomen↗

[Hodgkin disease with nodular lymphocytic predominance or type I (paragranuloma of Poppema-Lennert): a clinico-pathological entity. Study of 21 cases and review of the literature].

We have studied clinical and pathological features of a series of 21 patients followed at the hospital Saint-Louis for a nodal nodular lymphocytic predominant Hodgkin's disease or paragranuloma of Poppema-Lennert. Histopathologically, all these lymph nodes were involved by a nodular proliferation of atypical cells, called pop corn cells with a B cell phenotype, admixed with small lymphocytes. Clinically, most patients were young males. The disease was localized except in one case and the prognosis good (only one death). However, one patient relapsed and another developped an aggressive lymphoma. These results were in keeping with different studies in the literature and confirmed that the paragranuloma is a clinicopathological entity, distinct from the classical Hodgkin's disease. Nowadays, it's strongly suggested that the pop corn cell is of centroblastic origin. Treatment remains controversial, however, according to most of the authors, patients with localized disease could be followed without treatment after surgical excision.

Adult↗

[Resins polymerizing at low temperatures. I. Different families and principle technics].

For pathologists, tissue processing and analysis require good preservation of both the shape (morphology) and the content of the cells (antigens, nucleic acids). Low temperature embedding resins are the only inclusion substrate which allows both a fine morphological analysis and good preservation of antigens and nucleic acids. Automatic the technical processes and simplified protocols now allow the introduction of low temperature embedding resins in diagnostic procedures.

Cold Temperature↗