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Biomedical subjects

N Dupin

Publications and source records attributed to N Dupin.

At least 19 recordsLinked to original sources

[Epidemiology of sexually transmitted infections in France].

BACKGROUND: Sexually transmitted infections (STI) in France are reported on a voluntary basis through several sentinel surveillance systems. METHODS: To monitor STI, sentinel laboratory- or clinician-based surveillance systems were set up by the Institut de Veille Sanitaire: gonorrhea surveillance (Renago) in 1986, Chlamydia infections surveillance (Renachla) in 1989, and more recently, syphilis surveillance in 2000 and rectal lymphogranuloma venereum (LGV) in 2004. RESULTS: From 2000 to 2003, 1,089 syphilis infections were reported. Most of the cases were diagnosed in men having sex with men (MSM) and were mainly reported by STI clinics located in the Paris area. From 1997 to 2000, an increase of gonorrhea was observed each year. After two years of stable trend, the prevalence of gonorrhea increased again in 2003. From 2002 to 2004, 123 LGV cases were diagnosed in France and were observed only in MSM. Since 2001, Chlamydia infections have steadily increased, particularly in women. COMMENTS: Because STI surveillance is based on a voluntary basis, the number of reported cases is probably lower than the number of STI diagnosed in France. However, the data provided by the different surveillance systems reveals that STI have been increasing in France since 1997. Moreover, the resurgence of syphilis in 2000 and the emergence of rectal LGV in 2004 indicate that these STI occur mainly in MSM. Trends on incidence and patients characteristics observed in France are similar to those of several Europeans countries. European Public Health interventions are becoming necessary to prevent and control STI.

Chlamydia Infections↗

Weight related differences in the pharmacokinetics of abacavir in HIV-infected patients.

AIM: To study the possible influence of patient characteristics on abacavir pharmacokinetics. METHODS: A population pharmacokinetic model for abacavir was developed using data from 188 adult patients by the use of a nonlinear mixed effects modelling method performed with NONMEM. RESULTS: Abacavir pharmacokinetics was well described by a two-compartment open model with linear absorption and elimination. Typical population estimates for the absorption rate constant (Ka), the apparent central distribution volume (Vc/F), the apparent peripheral distribution volume (Vp/F), the apparent intercompartmental clearance (Q/F) and the apparent plasma clearance (CL/F) were 1.8 h(-1), 75 l, 23.6 l, 10 l h(-1) and 47.5 l h(-1), respectively. Apparent plasma clearance was positively related to bodyweight. Individual Bayesian estimates of CL/F were used to calculate abacavir AUC. The latter decreased from 10.7 +/- 5.0 to 5.7 +/- 1.6 mgh l(-1) when bodyweight increased from 36 to 102 kg. This drop in abacavir exposure could lead to suboptimal treatment for the heaviest patients, as antiviral efficacy of abacavir is known to be related to its AUC. A 400 mg abacavir dose would be necessary to achieve adequate exposure to abacavir in patients weighing more than 60 kg. CONCLUSIONS: The apparent plasma clearance of abacavir was positively related to bodyweight. The efficacy of the current recommended abacavir dosage for patients with high bodyweight should be evaluated in further studies.

Administration, Oral↗

[Epstein-Barr virus-associated cutaneous plasmacytoma post-solid organ transplantation].

BACKGROUND: Post-transplantation lymphoproliferative disorders develop in 1 to 10p. 100 of organ transplant recipients and are frequently associated with Epstein-Barr virus (EBV). Among post-transplantation lymphoproliferative disorders, plasmacytoma with cutaneous involvement is exceptional. Association with EBV has been rarely reported in post-transplantation plasmacytomas and the latency type of EBV has never been characterized. We report 2 new cases of cutaneous monotype EBV-related plasmacytomas. CASE-REPORTS: Clinical presentation was a sub-cutaneous tumor on the thigh in the first case and an ulcerated nodule of the leg in the second case, occurring respectively 7 and 8 years after organ transplantation (liver transplantation and heart transplantation). In both lesions, tumor cells exhibited lambda light chain restriction and the association with EBV was confirmed using immunohistochemistry and in situ hybridization. The expression of EBV genes in tumor cells demonstrated type III latency. DISCUSSION: The classification of post-transplantation lymphoproliferative disorders is not well defined and some authors retain 3 categories. Among the latter, plasmacytomas have been rarely described. Cutaneous involvement is reported in 4 cases and an association with EBV in only 2 cases without description of viral latency. Clinical and histological features of post-transplantation plasmacytomas appear polymorphic. We report EBV-association in both cases, with a type III latency clearly demonstrated in one case, as has been reported in other lymphoproliferative diseases in patients with congenital or acquired immunodeficiency. We also discuss various possible therapeutic strategies for post-transplantation lymphoproliferative disorders.

Epstein-Barr Virus Infections↗

Syphilis surveillance in France, 2000-2003.

This article describes syphilis trends, characteristics of patients from 2000 to 2003 in France and trends of the benzylpenicillin benzathine 2.4 million UI sales from 2001 to 2003. The ongoing surveillance system for syphilis case reporting since 2001 has been set up in volunteer settings, mostly public settings where STI treatment is offered. Clinical case reporting is complemented by sexual behavioural data based on a self-administered questionnaire. From 2000 to 2003, 1089 syphilis cases were reported in France, increasing from 37 cases in 2000 to 428 in 2003. Overall, 96% of syphilis cases were in men with a mean age of 36.5 years and 70% of whom were born in France. The proportion of syphilis cases with HIV co-infection decreased over time from 60% in 2000 to 33% in 2003. The most affected area by the syphilis epidemic is the Ile-de-France region, mainly the city of Paris. The greatest proportion of syphilis cases diagnosed in men who have sex with men (MSM) were in the Ile-de-France region, where they made up 87% of cases, compared with 75% in other regions. Among the patients who completed the self-administered questionnaire on sexual behaviour, 83% reported having casual sex partners in the 3 months prior to their syphilis diagnosis. Trends in the sales of benzylpenicillin benzathine 2.4 million UI in private pharmacies are similar to those observed in the surveillance system, and increased between 2001 and 2003. In conclusion, syphilis transmission is still ongoing in France in 2003 and the role of unprotected oral sex in the transmission of syphilis should be emphasised.

Adolescent↗

Quantitative analysis of human mitochondrial DNA using a real-time PCR assay.

OBJECTIVES: Known for their ability to inhibit the human DNA polymerase-gamma, nucleoside analogues induce toxic effects on mitochondria ranging from increased serum lactate levels to fatal lactic acidosis. DNA polymerase-gamma ensures the mitochondrial DNA (mtDNA) replication and, thus, its inhibition leads to the decrease of the mtDNA. We describe a real-time PCR assay for mtDNA quantification associating DNA extraction procedures applied on peripheral blood mononuclear cells (PBMCs) and subcutaneous adipose tissues and to study the antiretroviral effect on mitochondria. METHODS: Total DNA was extracted from PBMCs and subcutaneous adipose tissues. Nuclear and mitochondrial genes were amplified to determine the number of copies of mtDNA per cell using a cyt-b recombinant plasmid as standard control. We analysed eight HIV-infected asymptomatic patients never treated, four patients who had been treated for 6 months with highly active antiretroviral therapy (HAART) and six non-infected donors. RESULTS: The mtDNA quantification gave rise to reproducible results as the mean coefficients of variation were 1.09% for replicates of samples undertaken 10 times within the same run, and 5.78% and 3.7% for replicates tested in five different runs at 1:100 and 1:1000 dilutions, respectively. Median levels of mtDNA in PBMCs of healthy donors, naive and treated HIV-infected patients were 2.94, 2.78 and 1.93 log HIV-1 RNA copies/mL, respectively. Whereas DNA from PBMCs was shown to be devoid of inhibitors, subcutaneous adipose tissues needed an extra treatment as they were found to be highly inhibited. CONCLUSIONS: The method generated consistent and reproducible results and was successfully applied to DNAs extracted from PBMCs and subcutaneous adipose tissues with adapted extraction. The mtDNA changes in PBMCs were found to be fast as they fall off after 6 months' therapy, decreasing from 2.78 to 1.93 log copies/mL.

Adipose Tissue↗

Current treatments for scabies.

Scabies is a frequent interhuman ectoparasitic infection. Several treatments are available worldwide. There are local treatments: synthetic pyrethrins, benzyl benzoate, lindane, crotamiton. Recently a few studies were published concerning ivermectin, systemic antiparasitic agent use in onchocercosis treatment. We reviewed the literature with an evidence-based medicine method. We attempt to answer two questions in particular: what is the treatment of choice for common scabies in a patient otherwise in good health? What is the role of systemic ivermectin? We also report specific situations. Among local treatments, studies are heterogeneous according to products, countries, group of treated patients, with or without contact subjects, and the method of treatment application. There are very few high proof-level controlled studies. In France, a combination of benzyl benzoate 10% and sulfiram 2% is used most, according to professional consensus. The most studied product is the cream permethrin 5%, available in the USA and UK. Its efficacy seems slightly superior to lindane and less toxic. It is more efficient than crotamiton. There is no study comparing benzyl benzoate and permethrin. Concerning systemic ivermectin, five controlled studies showed its efficiency in common scabies. But its relative efficiency over local treatment has not been established. A few open studies showed its efficacy in institutional epidemic, profuse scabies and in HIV-positive patients. Local treatment of choice in common scabies remains to be determined among the four principal molecules. There is no study comparing permethrin or esdepallethrin to benzyl benzoate. In what cases should we prescribe crotamiton or lindane? Indication of ivermectin seems proved in common scabies and probably for HIV-positive patients. It remains to be determined if it should be prescribed in the first instance, be double or triple, be associated or not with local treatment. In case of keratotic scabies, ivermectin seems interesting with two applications within 1 week, and should be associated with local treatment (duration remains to be defined). Ivermectin is probably useful in institutional epidemic, and therapeutic attitude remains to be defined. Ivermectin seems to have little or no risk. Treatment must be adapted case-by-case, according to feasibility. It is still important to treat contacts, and modality of this treatment remains to be specified.

Administration, Oral↗

Effects of cyclosporine and hydrocortisone on Kaposi's sarcoma-associated herpesvirus genome replication and cell apoptosis induction.

BACKGROUND: Iatrogenic immunosuppressed patients are at increased risk for development of various cancers that comprise Kaposi's sarcoma (KS). METHODS: To investigate the direct impact of immunosuppressive agents on Kaposi's sarcoma-associated herpesvirus (KSHV) and KS development, we quantified the effects of cyclosporine (CsA) and hydrocortisone (HC) on KSHV genome replication and the consequences on the cell survival. RESULTS: In the presence of phorbol ester 12-O-tetradecanoyl phorbol-13-acetate, we observed an increase of intracellular and extracellular KSHV DNA concomitantly with an increase of gp (glycoprotein) K8.1 expression, indicating KSHV genome replication. This replication was accompanied by cell apoptosis. In comparison, in the presence of CsA, HC, or both, we did not observe any effect on KSHV replication or gp K8.1 expression. CONCLUSION: Our results suggest that immunosuppressive agents such as HC and CsA do not activate the lytic cycle of KSHV and do not modify the cell survival thus promoting cancer progression by a direct cellular effect.

Apoptosis↗

Human herpesvirus-8 seroconversions after renal transplantation.

BACKGROUND: Human herpesvirus-8 (HHV-8) is a new human herpesvirus that is clearly associated with Kaposi's sarcoma (KS). A previous study has reported that the prevalence of KS in a cohort of renal transplant recipients with previous HHV-8 infection was 28% and two other studies have shown that KS can be linked to HHV-8 seroconversion after graft. The aim of this study was to evaluate the HHV-8 seroconversion rate in a cohort of renal allograft recipients in Paris. METHODS: Two hundred eighty-seven patients who were HHV-8 seronegative before renal transplantation were tested for HHV-8 antibodies by an immunofluorescence assay 12 months after transplantation. RESULTS: Of the 287 patients, 6 (2.09%) seroconverted after renal transplantation. None of these 6 patients developed KS within 3 years of the first HHV-8 positive serum. None of the clinical manifestations that could be associated with HHV-8 primary infection were observed during the seroconversion. CONCLUSIONS: Our results demonstrated that HHV-8 seroconversion can be observed even in a low HHV-8 prevalence area and confirmed the need to perform systematic screening for HHV-8 antibodies in renal graft donors and recipients.

Adult↗

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↗

Seroepidemiology and molecular epidemiology of Kaposi's sarcoma-associated herpesvirus among Jewish population groups in Israel.

BACKGROUND: The incidence of classic Kaposi's sarcoma among Jews in Israel is among the highest in the developed world. Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) is causally linked to Kaposi's sarcoma. Very little is known about the prevalence of KSHV in the Middle East or about the modes of transmission in Mediterranean countries. METHODS: From 1992 through 1995, sera were obtained from 1648 adults who had tested positive for hepatitis B virus (HBV) surface antigen 20 years earlier at blood donations; sera were also obtained from 2403 of their family members. All sera were tested for anti-KSHV antibodies with the use of an indirect immunofluorescence assay. To analyze the effects of various factors on the risk of KSHV infection for both the HBV-positive cohort and their families, logistic regression for cluster data and generalized estimating equations were used. All statistical tests were two-sided. RESULTS: Among family members, the seroprevalence of antibodies against KSHV was 9.9% (95% confidence interval [CI] = 8.7% to 11.1%); among the former blood donors who had tested positive for hepatitis B, it was 22% (95% CI = 19.9% to 24.1%). Overall, the best predictor of KSHV status was the place of birth. The most important risk factors found for both husband and wife to test KSHV positive were their own places of birth and their spouse's seropositivity. For a child to test positive, the most important risk factor was maternal seropositivity. CONCLUSIONS: The crude prevalence rate of KSHV among the Jewish population in Israel is 9.9%. Important routes of KSHV transmission in the families studied are spouse to spouse and mother to child. The presence of KSHV in Jews in Israel of all ethnic origins and their high incidence of reported Kaposi's sarcoma suggest that KSHV was introduced into the Jewish population prior to the major Diaspora.

Adolescent↗

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↗

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↗