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Biomedical subjects

Nicolas Dupin

Publications and source records attributed to Nicolas Dupin.

At least 19 recordsLinked to original sources

Low T cell responses to human herpesvirus 8 in patients with AIDS-related and classic Kaposi sarcoma.

BACKGROUND: Kaposi sarcoma (KS) occurs mainly in immunocompromised patients and is strongly associated with infection with human herpesvirus 8 (HHV-8; also known as "KS-associated herpesvirus"). We hypothesized that KS is linked to deficiencies in specific anti-HHV-8 T cell immunity. METHODS: We studied asymptomatic HHV-8 carriers coinfected with human immunodeficiency virus (HIV; n = 23) and patients with HIV-related or classic KS (n = 29). We used an interferon- gamma enzyme-linked immunospot assay with 56 specific peptides distributed on 6 HHV-8 proteins (glycoprotein [gp] B, gpH, gp35/37, latent nuclear antigen 1 [LANA-1], K12, and K15) to detect HHV-8-specific T cell responses. RESULTS: We found that patients with KS responded to these peptides less often and had much lower HHV-8-specific T cells counts than did asymptomatic HHV-8 carriers (P = .001 and P = .0004, respectively), regardless of CD4 T cell count or HHV-8 load. The frequency of Epstein-Barr virus-specific T cells was similar in both groups. CONCLUSIONS: Our results suggest that HIV-related and classic KS are associated with a lack of HHV-8-specific T cells. Also, we have described 8 new HHV-8 T cell epitopes in LANA-1, K12, and K15, including 2 CD4 T cell epitopes. These data provide new insight into HHV-8 cellular immunity.

AIDS-Related Opportunistic Infections↗

MC1R and PTCH gene polymorphism in French patients with basal cell carcinomas.

In this study, we assessed the role of melanocortin 1 receptor (MC1R) variants and of two patched (PTCH) polymorphisms (c.3944C>T (P1315L), insertion 18 bp IVS1-83) as risk factors for basal cell carcinoma (BCC) in the French population. The population investigated comprised 126 BCC patients who were enrolled on the basis of specific criteria (multiple and/or familial BCC and/or onset before the age of 40 years and/or association with another tumor)--and 151 controls matched for ethnicity, age, and sex. MC1R variants appeared as a moderate risk factor for BCC (odds ratio (OR) for one and two variants, 2.17 [1.28-3.68] and 7.72 [3.42-17.38], respectively), independently of pigmentation characteristics (OR = 2.53 [1.34-4.8]). Interestingly, in addition to the predictable red hair color (RHC) alleles, two non-RHC alleles (V60L and V92M) were also closely associated with BCC risk (OR 3.21 [1.91-5.38] and 2.87 [1.5-5.48], respectively), which differs from the situation in the Celtic population. In addition, the PTCH c.3944C/C genotype was also associated with BCC risk (OR 1.94 [1.2-3.1]), especially in the subgroup of patients with multiple tumors (OR 2.16 [1.3-3.6]). Thus, our data show that MC1R and PTCH variants are associated with BCC risk in the French population. We further suggest that assessing MC1R and PTCH status could be useful, combined with the assessment of clinical risk factors, in identifying high-risk patients to be targeted for prevention or more rigorous surveillance.

Adult↗

Scurvy in liver transplant patients.

We report on scurvy in 3 liver transplant recipients. Clinical presentation was limited to ecchymotic purpura and mild follicular keratosis with no mucosal involvement. Skin biopsies suggest vitamin C deficiency, which was confirmed by a low level of vitamin C in both sera and leukocyte specimens. Skin lesions dramatically improved within a few weeks after supplementation with ascorbic acid.

Aged↗

[Localized scleroderma (morphea)].

DEFINITION AND FREQUENCY: Localized scleroderma, also known as morphea, is a sclerotic condition limited to the skin. The specific clinical entity depends on the extent, linear disposition and depth of the lesions. Morphea is ten times more prevalent than systemic sclerosis, and its prognosis is generally good: superficial forms resolve within 3 years. NO SYSTEMIC INVOLVEMENT: In the absence of symptoms, examinations to detect systemic involvement are purposeless. Plaque morphea is the most frequent clinical presentation. Serious manifestations include extensive morphea that may involve the entire skin or linear forms, especially in children, where they may be severe, especially on the face. There are no immunological markers clearly associated with morphea and no causative agents have been implicated in its pathogenesis, although sclerodermiform dermatitis is reported to be associated with some drugs and toxic agents. TREATMENT: There is no consensual treatment for morphea. Treatment should be decided according to severity and extent of lesions. Limited lesions may be treated with local steroids such as class IV corticosteroids. Systemic treatment (methotrexate) should be discussed in extensive and linear forms when there is a risk of functional or esthetic complications.

Administration, Topical↗

Looking for the target cell of Kaposi's sarcoma-associated herpesvirus.

The level of Kaposi's sarcoma-associated herpesvirus (KSHV) cellular viremia in patients with Kaposi's sarcoma could be related to both the tumor burden and its progression. The origin of the spindle cell, the hallmark cell of Kaposi's sarcoma, is still debated. Two hypotheses may be formulated, favoring a lymphatic endothelial cell or an endothelial-cell precursor evolving into a lymphatic phenotype, both preferentially targeted by KSHV.

Disease Progression↗

[An outbreak of lymphogranuloma venereum in Western Europe].

Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by Chlamydia trachomatis serotypes L1, L2, and L3. It is endemic in tropical areas, while seldom in industrialised countries. Since 2002, an outbreak of rectal LGV has been observed among men having sex with men, in Netherlands, France, and other countries of Western Europe. After an incubation period of 2 days to 2 months, LGV develops in three stages: ulcerated papule; inflammatory satellite lymph node and/or proctitis; chronic inflammatory complications (fistulas and sclerosis). Chlamydia trachomatis infection is confirmed by PCR and serovars is identified by RFLP of omp1 gene amplified by PCR. Recommended first line treatment is doxycycline for at least 21 days.

Adult↗

HIV-1 intermittent viraemia in patients treated by non-nucleoside reverse transcriptase inhibitor-based regimen.

BACKGROUND: It has been demonstrated that, in patients treated by protease-inhibitor-based regimen, intermittent viraemia occurred frequently and was associated with higher concentrations of residual replication but not with virological failure. Risk factors associated with intermittent viraemia and its impact in patients treated by non-nucleoside-reverse-transcriptase-inhibitor-based (NNRTI) regimen need to be evaluated. METHODS: We analyzed the occurrence of blips (one HIV-1 RNA > 50 copies/ml with a subsequent value < 50 copies/ml), the level of these blips (between 3 and 50 copies/ml) and their effect on CD4 cell count and the occurrence of virological failure in 43 patients with stable suppression of HIV-1 plasma viraemia (< 50 copies/ml) under NNRTI-based therapy. RESULTS: Eight out of 43 patients had one episode of blips during the follow-up (median = 350 copies/ml). Comparing patients with and without blips, the median level of HIV-1 RNA at baseline was 7.5 versus 3 copies/ml (P = 0.008), respectively. Patients with blips had a significantly lower CD4 cell count after 12 and 18 months than the others. Plasma concentrations of NNRTI before, during, and after the blips were adequate. In addition, the occurrence of blips was not associated with virological failure. CONCLUSION: These results suggest that blips may reflect ongoing viraemia of below 50 copies/ml and can impair the CD4 cell count recovery under an NNRTI regimen. The impairment of CD4 cell count recovery seems to be affected more by the occurrence of blips than by the level of viraemia (< 50 copies/ml) itself. Nevertheless, despite a tight genetic barrier for resistance with NNRTI drugs, no virologic failure occurred during the follow-up.

Adult↗

Evaluation of Coleman lipostructure for treatment of facial lipoatrophy in patients with human immunodeficiency virus and parameters associated with the efficiency of this technique.

OBJECTIVE: To evaluate the efficiency of Coleman lipostructure in patients infected with human immunodeficiency virus (HIV). DESIGN: Open-label study and survey. SETTING: Ambulatory dermatosurgery department of a university hospital. PATIENTS: Thirty-three consecutive HIV-infected patients undergoing Coleman lipostructure between 2000 and 2001. INTERVENTIONS: Clinical examination, blood tests, and standardized photographs at baseline and 1 year after the lipostructure. MEAN OUTCOME MEASURES: Efficiency was assessed by the agreement of 3 independent medical specialists on facial lipodystrophy improvement after surgery and by patient satisfaction. RESULTS: Facial lipoatrophy was improved in 12 patients (36%; 95% confidence interval, 20%-52%) as judged by all 3 evaluators. Quantity of fat injected (P = .01) and a low serum triglyceride level before surgery (P = .03) were significantly associated with improvement of facial lipoatrophy. Of the 33 patients, 14 (43%) were very satisfied, 17 (50%) were partly satisfied, and 27 (81%) had a better quality of life. The most common comment was that the patient looked better and appeared less ill. CONCLUSION: Our 1-year evaluation of Coleman lipostructure for correction of facial lipoatrophy in HIV-infected patients proved the efficiency of this treatment when measured conservatively by agreement on improvement by 3 independent specialists and demonstrated a patient satisfaction rate of 93%.

Adipose Tissue↗

Mycosis fungoides-type cutaneous T-cell lymphoma and neutrophilic dermatosis.

BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL). Patients with limited patch and/or plaque disease have a normal life expectancy. Neutrophilic dermatosis (ND) may be associated with various hematologic disorders. However, its association with CTCL is exceptional and has been reported only twice with leukemic forms of CTCL. OBSERVATIONS: Three patients with MF developed ND resistant to conventional therapies and responsible for an impaired quality of life due to constitutional symptoms and painful cutaneous lesions. All patients underwent an aggressive treatment course despite their varying initial clinical stages of MF, and all experienced a fatal outcome less than 18 months after the onset of ND. CONCLUSIONS: The association of MF with ND is exceptional and carries a poor prognosis, but the pathophysiologic nature of this association remains unclear. It may involve neutrophil chemoattractant cytokine production by tumor cells. A triggering role of interferon alfa is also possible.

Adult↗

Cutaneous Waldenstrom's macroglobulinemia with "deck-chair" sign treated with cyclophosphamide.

Specific skin lesions are rare in Waldenstrom's macroglobulinemia (WM). We report a case of a 58-year-old man who presented macules, papules, and an erythema of the trunk with the "deck-chair" sign revealing the relapse of WM. Histologic and immunohistochemical examinations confirmed that cutaneous lesions were related to specific infiltration with neoplastic cells. Remission of both skin lesions and immunological abnormalities was obtained with oral cyclophosphamide.

Antineoplastic Agents, Alkylating↗

Mitochondrial DNA depletion in adipose tissue of HIV-infected patients with peripheral lipoatrophy.

BACKGROUND: NRTI-induced host toxicity is proposed to involve cellular mitochondrial DNA (mtDNA) depletion. Determinants of cellular mtDNA copy number from HIV-infected patients receiving HAART and HIV-seronegative controls were investigated from subcutaneous fat samples, and relation with antiretroviral regimen was studied. STUDY DESIGN: HIV-infected patients receiving HAART (n = 50), HIV-infected patients not currently under HAART regimen (n = 2) and HIV-seronegative controls (n = 9) of similar age and BMI were enrolled prospectively when undergoing Coleman's lipostructure for correction of facial lipoatrophy or plastic surgery, respectively. After centrifugation, abdominal fat tissue was collected and stored at -80 degrees C. MtDNA analysis was blindly performed after a total DNA extraction from adipose tissue, followed by a real-time PCR quantification. The log of mtDNA copies/cell in adipose tissue [log(DNA)] was compared between groups by means of analysis of variance. RESULTS: The log(DNA) in adipose tissue of HIV-infected patients was significantly lower than in the HIV-seronegative control group (P < 0.0001). In HIV-infected patients, log(DNA) was significantly reduced in the 50 NRTI-treated patients (P < 0.01), but not when considering mtDNA level according to the use of PI or NNRTI in current HAART regimen. In NRTI-treated patients, only stavudine (n = 20) and didanosine (n=14) were significantly and independently associated with reduced mtDNA level (P < 0.0001 and <0.05, respectively). Currently stavudine or didanosine-treated patients had a significant reduced mtDNA level compared to past users (P < 0.0001 and <0.05, respectively). Other clinical, biological, and immuno-virological variables than NRTI did not correlate significantly to adipocyte mtDNA level. CONCLUSION: This study supports that current treatment by NRTI is a main determinant of mtDNA depletion in adipose tissue of HIV-seropositive patients with peripheral fat wasting. Stavudine or didanosine current intake is significantly associated with mtDNA depletion in vivo, that could be reversible after the discontinuation of these molecules, when considering mtDNA level according to current use versus past use of these molecules.

Adipose Tissue↗

Salivary lactoferrin is recognized by the human herpesvirus-8.

Human herpesvirus-8 (HHV-8) is commonly detected in all epidemiologic forms of Kaposi's sarcoma. Despite the broad cellular tropism of HHV-8, studies on mucosal shedding of HHV-8 have shown that infectious particles are restricted to saliva isolated from the oropharynx. We used biotinylated purified HHV-8 particles in a direct binding assay to whole clarified human salivary samples isolated from HHV-8-infected and uninfected individuals. We found that the major binding activity was carried out by a protein of 78-kDa size, which was further characterized as human lactoferrin (hLf) using 2-D electrophoresis and MALDI-ToF analysis. Preliminary comparison of HHV-8 binding activity of 76 salivary samples from HHV-8-infected and uninfected individuals showed that 7.8% of the uninfected population exhibited a form of Lf not recognized by HHV-8. Deglycosylation of hLf by PNGase F did not reduce HHV-8 binding activity, whereas endoproteinase cleavage of native hLf generated a non-glycosylated 8-kDa peptide recognized by HHV-8 particles and was located at the position Ala606-Tyr679 in the native hLf amino acid sequence, corresponding to the C-terminal region of the glycoprotein. This work identify the lactoferrin in saliva as a ligand for HHV-8 and suggests that this glycoprotein could be used as a carrier for the viral particles.

Adult↗

Population pharmacokinetics of tenofovir in human immunodeficiency virus-infected patients taking highly active antiretroviral therapy.

The influence of renal function on tenofovir pharmacokinetics was investigated in 193 human immunodeficiency virus (HIV)-infected patients by the use of a population approach performed with the nonlinear mixed effects modeling program NONMEM. Tenofovir pharmacokinetics was well described by a two-compartment open model in which the absorption and the distribution rate constants are equal. Typical population estimates of apparent central distribution volume (V(c)/F), peripheral distribution volume (V(p)/F), intercompartmental clearance (Q/F), and plasma clearance (CL/F) were 297 +/- 28.5 [corrected] liters, 848 +/- 209 [corrected] liters, 80 +/- 15 [corrected] liters/h and 50.5 +/- 3.1 [corrected] liters/h, respectively. Apparent plasma clearance was related to body weight/serum creatinine ratio (BW/S(CR)) and to the existence of a tubular dysfunction. Concomitant treatment with lopinavir/ritonavir was found to decrease tenofovir clearance. Individual Bayesian estimates of CL/F were used to calculate the tenofovir area under the concentration-time curve from time zero to 24 h (AUC(0-24)). In patients without tubular dysfunction, AUC(0-24) values markedly decreased from 6.7 to 1.4 mg . h/liter for BW/S(CR) increasing from 0.44 to 1.73. The relevance of a dosage adjustment based on BW/S(CR) should be further evaluated.

Adenine↗