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N Dupin

Publications and source records attributed to N Dupin.

At least 37 records · Page 2Linked to original sources
PubMed2000

Outcome of kidney transplant recipients with previous human herpesvirus-8 infection.

BACKGROUND: The consequences of a prior human herpesvirus-8 (HHV-8) infection in kidney-transplant recipients are still partially unknown. The aim of this monocentric study was to determine the prevalence of HHV-8-seropositive patients at the time of transplantation and to identify the main clinical events of these HHV-8+ recipients. METHODS: From January 1, 1990 to December 31, 1996, antibodies to HHV-8 latent nuclear antigen were detected by indirect immunofluorescent method in serum samples collected just before kidney transplantation from 400 consecutive patients. Conventional double or triple immunosuppressive treatment was prescribed. For the group of HHV-8+ recipients, data including death rate, graft survival, and occurrence of Kaposi's sarcoma (KS) were retrospectively collected until December 31, 1998. Cofactors associated with KS were studied in univariate and multivariate analyses using a Cox model. RESULTS: Thirty-two patients (8%) had antibodies to HHV-8 in their sera at the time of transplantation. Among these 32, 3 years after transplantation, graft survival was 72%, and KS prevalence was 28% (KS incidence: 8.2/yr/100 HHV-8+ recipients). Multivariate analysis identified bacterial and/or Pneumocystis carinii infection (odds ratio: 8.6; P=0.019) and female gender (odds ratio: 5.34; P=0.047) as factors associated with KS. No KS was observed in patients without anti-HHV-8 antibodies at the time of transplantation. CONCLUSIONS: The low graft survival and the high prevalence of KS within the studied population of HHV-8+ transplant recipients are strong arguments for systematic screening of HHV-8 serologic features before transplantation, especially in patients of African origin. HHV-8+ transplant recipients should be closely monitored to severe infections.

Adult↗
PubMed2000

HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive plasmablastic lymphoma.

Castleman disease (CD) is a lymphoproliferative disorder of unknown etiology that is associated with the development of secondary tumors, including B-cell lymphoma. Human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated herpesvirus) sequences have been described in some cases of multicentric Castleman disease (MCD). Using a monoclonal antibody against an HHV-8-latent nuclear antigen, we show that HHV-8 is specifically associated with a variant of MCD in which HHV-8-positive plasmablasts that show lambda light-chain restriction localize in the mantle zone of B-cell follicles and coalesce to form microscopic lymphomas in some cases. Furthermore, we show that the frank plasmablastic lymphoma that develops in patients with this plasmablastic variant of MCD is also positive for HHV-8 and lambda light chain. Plasmablastic lymphoma associated with MCD is a new disease entity associated with HHV-8 infection. (Blood. 2000;95:1406-1412)

Adolescent↗
PubMed2000

Clinical features and contribution of virological findings to the management of Kaposi sarcoma in organ-allograft recipients.

OBJECTIVES: To describe the clinical features of Kaposi sarcoma (KS) in organ-allograft recipients and to determine the contribution of human herpesvirus 8 (HHV-8) investigations to the management of KS. DESIGN, SETTING, AND PATIENTS: We examined 20 organ-allograft recipients with KS at Pitié-Salpêtrière Hospital, Paris, France, between November 1, 1991, and May 31, 1999. METHODS: We detected HHV-8 antibodies using an indirect immunofluorescence assay and the HHV-8 DNA genome using nonnested polymerase chain reaction with KS-associated herpesvirus 330(233) primers in peripheral blood mononuclear cells collected at transplantation and KS diagnosis. We detected the HHV-8 genome in involved and uninvolved tissue specimens and in 10 patients' serum samples collected 1 month before the first manifestation of KS. We determined the HHV-8 double-strand DNA sequence and subtypes of open reading frame 26. INTERVENTION: Management of KS consisted of progressively tapering immunosuppressive therapy regardless of KS dissemination. Associated infections were treated when possible. Chemotherapy was prescribed only when a functional disability persisted, and polychemotherapy was prescribed for life-threatening disease. MAIN OUTCOME MEASURES: Percentage of recipients with KS remission and stabilization, organ-graft survival, and death rates. RESULTS: Remission of KS was obtained in 9 (45%) of the 20 patients independently of disease dissemination, with a mean follow-up of 35 months. The kidney graft survived in 12 (67%) of the 18 patients. Only 1 patient (5%) died of KS progression. All allograft recipients had anti-HHV-8 antibodies before transplantation. We detected HHV-8 DNA in all involved tissue samples but not in serum samples 1 month before KS onset. The most prevalent subtype was HHV-8 C (9 [53%] of 17 patients) and was not associated with extradermatological extension of KS compared with subtypes A and B'. CONCLUSIONS: Virological investigations of HHV-8 contribute poorly to KS management. Prospective studies are needed to determine the role of HHV-8 virological investigations and to identify associated cofactors so as to prevent KS in organ-allograft recipients.

Adult↗
PubMed2000

Manifestations of three HHV-8-related diseases in an HIV-negative patient: immunoblastic variant multicentric Castleman's disease, primary effusion lymphoma, and Kaposi's sarcoma.

We describe a 73-year-old HIV negative patient who presented with symptomatic hypoglycemia. Over the course of several months she was diagnosed with three human herpesvirus-8 related diseases: multicentric Castleman's disease, primary effusion lymphoma and Kaposi's sarcoma. No improvement was observed following cytotoxic therapy and she died 16 months after her initial presentation. The etiology of the hypoglycemia remained obscure over the course of this patient's disease. This case is the first report of a patient with three human herpesvirus-8 related diseases, and the first report of severe hypoglycemia as the presenting symptom of any of these diseases.

Aged↗
PubMed2000

Early peripheral lymph node involvement of human herpesvirus 8-associated, body cavity-based lymphoma in a human immunodeficiency virus-negative patient.

Human herpesvirus 8 (HHV-8), or Kaposi sarcoma-associated herpesvirus, is a gamma herpesvirus first detected in a specimen of Kaposi sarcoma from a human immunodeficiency virus (HIV)-positive patient. Human herpesvirus 8 is also found in an unusual clinicopathologic form of body cavity-based B-cell lymphoma, which has been named primary effusion lymphoma (PEL) and occurs primarily in HIV-positive patients. PEL is characterized by the formation of lymphomatous effusions, without obvious lymphadenopathy, tumor masses, or bone marrow involvement. Only a few cases of PEL in HIV-seronegative patients have been reported. We describe a case of an HHV-8-associated lymphoma, with ascites, pleural effusion, and axillary lymphadenopathy in an HIV-negative patient. The patient was a 68-year-old Jewish man of North African extraction, with a previous history of coronary bypass surgery and multiple blood transfusions. The pleural fluid contained large atypical lymphoid cells and was suggestive of lymphoma but could not provide a conclusive diagnosis of PEL. The lymph node contained groups of large anaplastic lymphoid cells. Polymerase chain reaction for HHV-8 performed on the lymph node specimen was positive, establishing the diagnosis of PEL. Polymerase chain reaction for Epstein-Barr virus was negative. Results of a gallium scan were normal. The patient did not respond to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine sulfate, and prednisone and progressively developed, massive intra-abdominal solid tumor formation. To our knowledge, this is the first report of a case of PEL that demonstrates peripheral lymph node involvement at diagnosis and the first report of PEL in an Israeli patient.

Aged↗
PubMed1999

[Human herpesvirus 8 (HHV-8)].

Human herpesvirus 8 (HHV-8) is associated with all epidemiological forms of Kaposi's sarcoma (KS), multicentric Castleman's disease and primary effusion lymphomas. HHV-8 is a gamma herpesvirus and his genome consists of an estimated 140 kb long unique coding region. Sero-epidemiologic studies support the findings that infection by HHV-8 in the occidental countries is not ubiquitous. The main routes of transmission for HHV-8 is sexual contact at least in homo-sexual men, however distribution of the prevalence of HHV-8 in Africa suggests that this virus could be transmitted by other ways such as mother to child or child to child. Analysis of the genome of HHV-8 identified an imprecedent numbers of genes implicated in cellular growth which have potentially a major role in tumorogenesis. Morphologic studies based on electron-microscopy, immunohistochemistry and in situ hybridization suggest that most of the cells in HHV-8-related tumours are latently infected. Efforts must concentrate on finding the best systems for growing the virus in cell cultures and in the strategy of treatment and (or) prevention of HHV-8-related tumours especially in organ transplant patients.

Adult↗
PubMed1999

Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma.

Human herpesvirus 8 (HHV-8, also called KSHV) is linked to the etiopathogenesis of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). The universal presence of HHV-8 in early KS has not yet been shown. We used a mAb (LN53) against latent nuclear antigen-1 (LNA-1) of HHV-8 encoded by ORF73 to study the distribution of the cell types latently infected by HHV-8 in patch, plaque, and nodular KS, MCD, and PEL. In early KS, HHV-8 is present in <10% of cells forming the walls of ectatic vessels. In nodular KS, HHV-8 is present in cells surrounding slit-like vessels and in >90% of spindle cells, but not in normal vascular endothelium. In addition, HHV-8 colocalizes with vascular endothelial growth factor receptor-3 (VEGFR-3), a marker of lymphatic and precursor endothelium. In early KS lesions, VEGFR-3 is more extensively expressed than LNA-1, indicating that HHV-8 is not inducing the proliferation of VEGFR-3-positive endothelium directly. In MCD, HHV-8 is present in mantle zone large immunoblastic B cells. No staining for LNA-1 is seen in samples from multiple myeloma, prostate cancer, and angiosarcoma, supporting the absence of any etiological link between these diseases and HHV-8.

Antigens, CD↗
PubMed1999

The influence of highly active antiretroviral therapy on AIDS-associated Kaposi's sarcoma.

To assess the clinical and biological benefit of highly active antiretroviral therapy on AIDS-associated Kaposi's sarcoma (KS), 13 patients with AIDS-associated Kaposi's sarcoma (five pulmonary KS and eight cutaneous KS) were prospectively followed for a mean duration of 12 months. Six patients were treated with specific anti-KS chemotherapy before or simultaneously with the introduction of antiretroviral therapy. Clinical response was assessed according to the AIDS Clinical Trial Group (ACTG) criteria. CD4 cell counts, plasma HIV-1 RNA and human herpesvirus 8 (HHV-8) viraemia were measured at baseline and at different points. Among patients with pulmonary KS, we observed three complete responses (CR), one partial response (PR) and one progression. The median survival time after the diagnosis of pulmonary KS was 15 months with a median duration of the response after the discontinuation of specific chemotherapy for KS of 8 months. Among patients with cutaneous KS, we observed four CR, three PR and one stable response. A complete response was significantly associated with a reversal in HHV-8 viraemia (five of six vs. one of six; P = 0.02, Mann-Whitney test).

Acquired Immunodeficiency Syndrome↗
PubMed1999

Characterization of monoclonal antibodies raised against the latent nuclear antigen of human herpesvirus 8.

Human herpesvirus 8 (HHV-8; also designated Kaposi's sarcoma-associated herpesvirus) is the likely etiological agent of Kaposi's sarcoma (KS). HHV-8 encodes a latent nuclear antigen (LNA) which is the product of the viral gene orf 73. LNA is recognized by most infected patient sera and is the basis of current immunofluorescence assays used in epidemiological studies of HHV-8 infection. Here we describe the characterization of four monoclonal antibodies raised to the C-terminal third of LNA-glutathione S-transferase fusion proteins. These monoclonal antibodies recognized discrete linear epitopes within the C terminus and repetitive region of LNA, detected antigen in primary effusion lymphoma (PEL) cells, and precipitated a 220- to 230-kDa protein doublet corresponding to LNA from HHV-8-infected PEL cell lines. In situ immunocytochemistry of KS lesions with these antibodies show that LNA is extensively expressed in KS spindle cells.

Antibodies, Monoclonal↗
PubMed1998

Prevalence of human herpesvirus 8 infection measured by antibodies to a latent nuclear antigen in patients with various dermatologic diseases.

BACKGROUND: Human herpesvirus 8 (HHV-8) has been detected in all epidemiological forms of Kaposi sarcoma (KS). The role of HHV-8 in dermatologic diseases other than KS is controversial. Some studies based on polymerase chain reaction findings suggest an association between HHV-8 and epithelial tumors of the skin, lymphoproliferative disorders, or pemphigus. OBJECTIVE: To assess the prevalence of antibodies against a latent nuclear antigen of HHV-8 in patients with various dermatologic diseases. DESIGN: An indirect immunofluorescence assay was used to search for HHV-8 antibodies. SETTING: Ambulatory or hospitalized patients from a university hospital associated with a research laboratory. PATIENTS: Eighty-three patients with various non-KS dermatologic diseases and 16 patients with KS who were seronegative for the human immunodeficiency virus. Controls were 100 healthy subjects living in the same area. RESULTS: Antibodies to HHV-8 were found in 100% (16/16) of the patients with KS and 3.6% (3/83) of the patients with non-KS dermatologic diseases: 1 patient with pemphigus vulgaris, 1 with discoid lupus erythematosus, and 1 with bullous pemphigoid. The prevalence of antibodies to HHV-8 in controls was 2% (2/100) and was not significantly different than the prevalence in patients with dermatologic diseases other than KS (P =.28). CONCLUSIONS: Our serologic study confirms the higher prevalence of HHV-8 antibodies in patients with KS and demonstrates that contrary to other human herpesviruses, HHV-8 is not a ubiquitous virus in France. We could not determine any causal association between HHV-8 and pemphigus or lymphoproliferative disorders of the skin.

Adult↗
PubMed1998

The level of human immunodeficiency virus (HIV) type 1 RNA in cerebrospinal fluid as a marker of HIV encephalitis.

We prospectively evaluated the level of human immunodeficiency virus (HIV) type 1 RNA in cerebrospinal fluid (CSF) as a marker of HIV encephalitis. Fifty-two HIV-1-infected patients (41 males and 11 females; mean age, 39 years) were tested for the presence of HIV-1 RNA in plasma and CSF. Samples of CSF were obtained by lumbar puncture to evaluate cognitive deficits, seizures, or fever among these patients. HIV encephalitis was diagnosed in 11 patients (21%), other CNS diseases were diagnosed in 12 (23%), and fever without CNS disease was diagnosed in 29 (56%). HIV-1 RNA was detectable in 92% of the plasma specimens and 75% of the CSF specimens. No significant difference was observed in CSF levels of HIV-1 RNA between patients with or without HIV encephalitis. CSF levels of HIV-1 RNA correlated with plasma levels of HIV-1 RNA (Spearman's rank correlation, +0.31; P = .02) and CSF white blood cell counts (Spearman's rank correlation, +0.4; P < .01). The absence of any significant difference between patients with or without HIV encephalitis suggests that the CSF HIV-1 RNA level is not a good marker for the diagnosis of HIV encephalitis.

AIDS Dementia Complex↗
PubMed1998

[Pruritus and the hepatitis C virus. The MULTIVIRC Unit].

OBJECTIVE: Determine the characteristics of pruritus in a selected population of patients with positive hepatitis C virus serology. PATIENTS AND METHODS: In a retrospective study, we re-examined outpatient reports for patients who consulted for pruritus from January 1993 to April 1996 and were followed in a hepatology unit for hepatitis C infection. The following data were collected: age, sex, risk factors, HIV and HBV serologies, duration of pruritus and diagnosis, ALAT, gamma GT and total bilirubin, METAVIR score, HCV RNA PCR, search for cryoglobulins, antiviral and dermatology treatments. There were 1,060 patients followed in the hepatology unit during this period, including 327 with cirrhosis. RESULTS: Twenty-seven patients were retained for study, 16 men and 11 women, mean age 53 years. None of the patients had HIV infection, 7 had a past history of hepatitis B infection (positive for anti-Hbc antibodies). Median duration of pruritus prior to consultation was 3 months (95 p. 100 CI: 3 months-2 years). Pruritus was associated with non-specific lesion in 19 cases (70 p. 100: 95 p. 100 CI: 51-85 p. 100). There were excoriated eczema-like lesions in 11 cases (41 p. 100: 95 p. 100 CI: 15-49 p. 100). Other causes were urticaria in 5 cases (18 p. 100: 95 p. 100 CI: 7-36 p. 100), including 1 case of urticarial vasculitis with cryoglobulinemia, 2 cases with atopic dermatitis, and 1 case of primary biliary cirrhosis. In four cases, lichen planus was associated. Skin biopsies were obtained in 10 patients and showed eczema-like alterations in 9 and urticarial vasculitis in 1. Mean ALAT and gamma GT levels were 2.6 N (95 p. 100 CI: 1.9 N-3.3 N) and 2.2 N (95 p. 100 CI: 1.4 N-3 N) respectively, including 11 cases without cholestasis (normal gamma Gt). PCR was positive in 13 cases out of 15. Cryoglobulinemia was found in 10 cases out of 24. At consultation, 3 patients were given ursolvan, 7 interferon, 1 ursolvan with ribavirin, and 3 an interferon-ribavirin combination. Dermatology treatment associated antihistamine agents, emollients, and corticosteroids. This population of hepatology patients referred for pruritus comprised 2.5 p. 100 of all patients (95 p. 100 CI: 1.7-3.6 p. 100). Among them, 1.8 p. 100 (95 p. 100 CI: 1.1-2.7 p. 100) had eczema-like lesions associated with cutaneous xerosis. DISCUSSION: Pruritus in our patient population was generally associated with non-specific excoriations, prurigo or xerosis in 19 cases (70 p. 100). As only ambulatory patients were retained for analysis, this is not a comprehensive population and the percentage of non-specific pruritus, evaluated at 1.8 p. 100, is probably an underestimation. Cholestasis cannot explain alone these manifestations since 11 patients had normal gamma GT levels. Several etiologies could be involved: a direct effect of HCV, interferon. A prospective study should allow an estimation of frequency, risk factors and possible impact on quality of life.

Female↗