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Biomedical subjects

F Denis

Publications and source records attributed to F Denis.

At least 19 recordsLinked to original sources

Real-time PCR quantitation of hepatitis B virus total DNA and covalently closed circular DNA in peripheral blood mononuclear cells from hepatitis B virus-infected patients.

It remains unclear whether hepatitis B virus (HBV) replicates in extrahepatic tissues, and particularly in peripheral blood mononuclear cells (PBMCs), which may serve as a reservoir for the maintenance of infection. A real-time PCR assay for the quantitation of total and covalently closed circular (ccc) HBV DNA in serum and in PBMCs was developed. This assay was highly sensitive (detection limit: 27 IU/mL), linear over a wide range (9 log10), and was displayed high inter- and intra-assay reproducibility for the quantitation of total DNA. Genotypes A to E were detected and the results were consistent with those obtained with the COBAS Amplicor HBV Monitor Test. The specificity of the methodology was increased by prior treatment with an enzyme that digests relaxed circular DNA, and the elimination of background signals from virus adsorbed to the surface of PBMCs. HBV DNA was detected in the serum and PBMCs of 12 HBsAg-positive patients, with less than 1% in the cccDNA form. In conclusion, the quantitation of total and ccc HBV DNA in PBMCs is potentially useful as a non-invasive marker, and may help to increase our knowledge of the natural history of hepatitis B.

DNA, Circular↗

[Human papillomavirus prophylactic vaccines: stakes and perspectives].

Human Papillomavirus (HPV) infection is established as the necessary cause of cervical precancers and cancers. To date, more than 120 genotypes are known, but only high risk oncogen genotypes could induce a cancer. HPV 16 and 18 are implied in nearly 70% of cervical cancer around the world. Although some persistent HPV infections progress to cervical cancer, host immunity is generally able to clear most HPV infections providing an opportunity for cervical cancer prevention through vaccination. Candidate prophylactic vaccines based on papillomavirus L1 virus-like particles (VLPs) are currently on human clinical trials: one targeting cervical cancer with a bivalent VLP L1 vaccine containing the two genotypes most frequently involved in cervical cancer (type 16 and 18) and the other, protecting against warts as well as cervical cancer, with a quadrivalent HPV VLP L1 vaccine containing genotypes 6, 11, 16 and 18. The first clinical trials revealed the satisfactory tolerance and excellent immunogenicity of these vaccines inducing high serum antibody titers with minimal side effects. After more than three years, both clinical trials on women 15 to 25 years old have shown that vaccines are able to type specifically protect against nearly 90% of infection and all cervical intra-epithelial neoplasia. The vaccinal strategy defined to date targets preadolescents and adolescent young females (11-13 years) before the first sexual course but some questions are still not resolved concerning the prescriber, the actors of the vaccination and the duration of the protection. Nevertheless cervical cancer screening should be carried on for many years, even if a large vaccinal strategy is decided. Such a vaccine would save lives and reduce the need for costly medical procedures and the psychological stress induced by this cancer.

Adolescent↗

Mass vaccination against hepatitis B: the French example.

Mainland France is considered as a low endemicity area for hepatitis B, but the French Caribbean and Pacific territories are classified into areas of intermediate and high endemicity. In France vaccination programmes aimed at high-risk groups were started in 1982 (including health care workers and patients receiving blood products) and the immunization of babies born of hepatitis B virus surface antigen (HBsAg)-positive mothers was reinforced in 1992. Considering the drawbacks and limited effect of targeted vaccination policies, universal vaccination targeted particularly to the preadolescent and adolescent population was initiated in 1994. In 1995, hepatitis B virus (HBV) vaccination was included in the infant immunization schedule. However, the emotion generated by the claim that HBV vaccination could have led to the development of central nervous system demyelinating disorders resulted in a marked decline of HBV vaccine use, both in the pediatric (23.3% vaccination coverage in children less than 13 years old) and in the adult population. The current coverage rates are likely to be insufficient to bring about a significant reduction in the control of hepatitis B in France. The success of universal immunization is highly dependent on reinstating the confidence of the public and health care professionals in the safety and efficacy of hepatitis B vaccines.

France↗

[Herpesviruses serologic survey of corneal allograft recipients].

AIMS: Herpesviruses are ubiquitous viruses, providing circulating antibodies in a wide range of patients. Donor-to-host transmission of Herpes simplex virus via corneal graft has been proven, leading to primary graft failure. However, the serological survey of the corneal recipient for Herpesviruses has not yet been investigated. METHODS: Circulating antibodies to HSV, VZV, CMV, and EBV were tested in 117 corneal recipients prior to surgery as well as 8 days and 3 months following surgery. Twenty-two patients had a history of corneal herpes. All patients were treated with local steroids, and no patient received systemic immunosuppressive therapy. RESULTS: No seroconversion was encountered, in particular, no CMV--patient was found CMV+ after grafting. The mean concentration of antibodies significantly decreased after grafting in a few patients. A serological profile of EBV reactivation was detected after surgery in four patients at day 8 and three more patients at 3 months. CONCLUSIONS: This study shows no significant seroconversion after grafting. However, it shows a postoperative decrease in antibody levels as well as a serological profile of EBV reactivation, possibly related to local steroids or graft immune processes.

Adult↗

Inhibition of apoptosis by Nur77 through NF-kappaB activity modulation.

The orphan nuclear receptor Nur77 has been described as a mediator of apoptosis and has also been associated with growth promotion and apoptotic resistance. This study aimed at evaluating the contribution of Nur77 to different apoptotic stimuli. Nur77 overexpression in the fibroblastic cell line HEK293 promoted resistance to programmed cell death induced by death receptor engagement, DNA-damaging agents and endoplasmic reticulum stress. Nur77 overexpression led to enhanced NF-kappaB activity, and DNA-binding inhibitors confirmed the contribution of NF-kappaB to Nur77 antiapoptotic activity. Nur77 overexpression leads to NF-kappaB-dependent induction of the antiapoptotic gene cIAP1. Paradoxically, while dominant-negative Nur77 expression sensitised cells to Fas ligand-induced cell death, it protected cells from endoplasmic reticulum stress apoptosis in a manner similar to wild-type Nur77. These results show that nuclear crosstalk between Nur77 and other transcription factors contribute to cell fate in response to different apoptosis-inducing agents.

Apoptosis↗

[Antiviral vaccination and respiratory mucosal immunity: still disappointing results from a seductive idea].

Mucosal surfaces of the respiratory tract represent a major portal of entry for most human viruses and a critical component of the mammalian immunologic repertoire. The major antibody isotype in external secretions is secretory immunoglobin A (S-IgA). The major effector cells in mucosal surfaces, however, are not IgA B cells, but T lymphocytes, which may account for up to 80% of the mucosal lymphoid cell population. Mucosal immunoprophylaxis is theoretically an important approach to control infections acquired through these portals. Passive antibodies can protect against mucosal viral infections, as shown for respiratory syncytial virus, but very high quantities of passive antibodies are needed to restrict virus replication on mucosal surface. Factors likely to induce mucosal antibody and cell-mediated immune responses include oral or respiratory routes of immunization and active (effectively replicating) vaccine agents. Very few antiviral vaccines have been developed to protect the mucosal surface of the respiratory tract, and only an attenuated influenza virus vaccine uses the nasal route. Other vaccines, approved for parenteral use, have been administered experimentally by the nasal route; these include active (replicating) and inactive (nonreplicating) vaccines. By this route they induce only a moderate local mucosal response. Neither the development of mucosal immunity nor the administration of vaccines via the mucosal route is essential for control or prevention of most respiratory viral infections and diseases acquired through the respiratory tract. Nonetheless, the example of the live attenuated intranasal influenza vaccine, which induces both systemic and local immune response, is promising for the future of mucosal immunization against respiratory viral infections.

Humans↗

[Hybrid Capture 2 vs HPV Consensus kit: comparison of 2 assays for human papillomavirus detection and typing].

BACKGROUND: Many laboratories use the DNA Hybrid Capture 2 HPV-high risk assay (Digene) to detect and type oncogenic HPV. The aim of this work was to compare this assay with a new HPV genotyping assay: HPV Consensus kit (Argène). Actually, this assay is not commercially available. MATERIALS AND METHODS: Ninety-four cervical samples were tested with both the routine assay Hybrid Capture 2 and the HPV Consensus kit. Discordant results were analysed by amplification with a nested PCR and sequencing of amplified products. RESULTS: Only 81 results could be analysed concerning the oncogenic risk. The overall concordance was 92,6%. But we find 13 "generic" results with the HPV Consensus kit, the generic probe including high risk and low risk genotypes. CONCLUSION: HPV Consensus kit results showed a better detection sensitivity for this assay than Hybrid Capture 2 assay. Nevertheless, "generic" results give no information about the oncogenic risk of the HPV detected in a sample.

DNA Primers↗

Double hepatitis B virus infection in a patient with HIV/hepatitis C virus coinfection and 'anti-HBc alone' as serological pattern.

Reported here is a case of double hepatitis B virus (HBV) infection in an HIV/hepatitis C virus (HCV)-coinfected patient with antibodies against hepatitis B core antigen as the only serological marker (anti-HBc alone). Two different HBV genotypes were identified in this patient. A search of the medical literature indicated this report is the first to describe a multiple silent HBV infection in an HIV/HCV-coinfected-patient. The elevated incidence of the anti-HBc alone pattern in HIV-positive patients and the increasing number of silent HBV infections detected in those patients demonstrate the need to carefully examine HIV-positive patients for occult HBV infection. In addition, it appears necessary to thoroughly study such patients in order to evaluate the impact of mixed HBV infection and triple HIV/HCV/HBV infection on morbidity.

DNA, Viral↗

Detection of ganciclovir resistance after valacyclovir-prophylaxis in renal transplant recipients with active cytomegalovirus infection.

Whether valaciclovir (VCV) prophylaxis could be responsible for ganciclovir (GCV)-resistance of Human cytomegalovirus (HCMV) in transplantation has never been documented. A multicentric retrospective pilot study was undertaken to detect GCV-resistance through mutations within the UL97 gene in renal transplant recipients who experienced active HCMV infection and received valacyclovir prophylaxis. Twenty-three patients who experienced HCMV antigenaemia or DNAemia during or at the end of prophylaxis were included. UL97 genotyping was carried out on peripheral blood samples, using a nested in-house PCR, which amplified the full-length UL97 gene. One patient has a resistance-related mutation (M460I); the major risk factor for emergence of resistance in this patient was the presence of early and persistent antigenaemia. GCV-resistance during VCV-prophylaxis was rare after renal transplantation. However, special attention must be paid to patients developing early active HCMV infection under prophylaxis.

Acyclovir↗

Contrast enhanced magnetic resonance imaging underestimates residual disease following neoadjuvant docetaxel based chemotherapy for breast cancer.

AIMS: We prospectively compared the ability of magnetic resonance imaging (MRI) to measure residual breast cancer in patients treated with different neoadjuvant chemotherapy regimen. METHODS: Forty patients with locally advanced breast carcinoma underwent neoadjuvant chemotherapy. Twelve patients received 5-fluoro-uracyl-epirubicin-cyclophosphamide (FEC-group, six cycles), 28 (DXL-group) received docetaxel-based chemotherapy (six cycles DXL-epirubicin: 13 patients, eight cycles DXL alone: 15 patients). All patients had baseline and preoperative MRI. The spread of pathologic residual disease (PRd) was compared to preoperative MRI measures according to chemotherapy regimen. RESULTS: MRI over/underestimation of the spread of residual tumour was never superior to 15mm in FEC group, whereas it appeared in 11/28 (39%, 30-48%-95% CI) patients in DXL group (p=0.017). Tumour shrinkage led to single nodular residual lesions in FEC group, whereas vast numerous microscopic nests were observed in docetaxel group in pathology. CONCLUSION: Among tumours treated with a taxane-containing regimen, residual disease was frequently underestimated by MRI because of PRd features.

Adult↗

[Evolution of strategy and coverage rates for hepatitis B vaccination in France, a country with low endemicity].

Both HBV plasma derived vaccines and HBV recombinant vaccines have proved safe and highly immunogenic. In France, exhaustive population surveys have revealed a vaccine coverage rate of over 21.7% and very low three-dose vaccine coverage among infants (19.8%), children (23.3%), and adolescents. Among hospital staff, around 80 to 90% of physicians and health care personnel in public or private hospitals were vaccinated against hepatitis B and the level of coverage was higher among personnel accidentally exposed to blood (90 to 100%). Among risk groups, the specific prevention program against mother-infant transmission was unevenly applied, and between 25 to 45% of intravenous drug abusers, prisoners, or STD patients were vaccinated. These coverage rates are inadequate to obtain a significant reduction and control of hepatitis B infections in France. The complete eradication of HBV transmission might take another 20 years to achieve unless great efforts are made to vaccinate the general population (infants especially) and high-risk groups.

Adolescent↗

[Anaemia and radiation therapy].

Anaemia is frequent in cancer and may increase tumour hypoxia that stimulates angiogenesis. However, erythropoietin is a hypoxia-inducible stimulator of erythropoiesis which seems to improve quality of life in cancer patients. Two recent phase III randomized studies showed negative results using erythropoietin in head and neck cancer patients and in metastatic breast cancer patients with impaired specific survival. In vitro and in vivo experiments have provided erythropoietin-receptor expression in endothelial cancer cells including malignant tumours of the breast, prostate, cervix, lung, head and neck, ovary, melanoma, stomach, gut, kidney etc. Biologic effect of erythropoietin and its receptor linkage induces proliferation of human breast cancer and angiogenesis and may limit anti-tumour effect of cancer treatment, in part, by tumour vascularization improvement. In addition, the use of exogenous erythropoietin could be able to favour tumour progression by improving tumour oxygenation and nutriment supply. If erythropoietin receptor were functional in human cancer, the assessment of erythropoietin receptor expression on tumour cell may help to select patients benefiting from exogenous erythropoietin. However, the relationship between erythropoietin receptor expression, tumour growth and exogenous erythropoietin, requires more studies. The results of recent clinical trials suggest that using erythropoietin should be avoided in non-anemic patients and discussed in patients receiving curative therapy.

Anemia↗

[Regional variations of adult population vaccinal status].

OBJECTIVE: The authors had for aim to study the regional variations of vaccination coverage in adult population. METHODS: Cross-sectional epidemiological study, including a representative sample of 2122 general practitioners and analyzed according to eight French regions. RESULTS: Six thousand two hundred sixty-nine patients, 44 +/- 15 old, were included in the study. 90.5% of the patients were vaccinated against diphtheria, 94.4% against tetanus, and 92.6% against poliomyelitis. No difference between regions was noted but the rate of patients with up to date vaccination strongly differed, ranging from 54.8% (Paris/Ile de France) to 64.3% (South West) for diphtheria, from 60.4% (Paris/Ile de France) to 73% (South West) for tetanus, and from 58.8% (Paris/Ile de France) to 69.8% (South West) for poliomyelitis. Vaccination coverage against measles, parotiditis, hepatitis A and B, typhoid fever, yellow fever also significantly differed between regions and the only ones evenly distributed were vaccination against tuberculosis, meningococcus, and pneumococcus. CONCLUSION: These results show insufficient vaccination coverage against diphtheria, tetanus, and poliomyelitis in all regions and show other important variations in vaccination coverage between regions, especially for hepatitis A and B.

Adult↗

[Infectious complications after surgery for hypopharyngeal and laryngeal carcinomas].

OBJECTIVE: The objective of this study was to analyze the infectious complications of procedures for carcinoma of the hypopharynx and the larynx to optimize the prevention of septic risks. MATERIAL AND METHODS: This retrospective study included 608 patients who underwent total (n=270) or partial (n=338) laryngectomy between 1984 and 1999. The procedures were performed under rigorous conditions of surgical asepsis and with prolonged antibiotic chemotherapy depending on the type of laryngectomy and past history of external radiotherapy. Twenty factors were studied. Univariate analysis, including 9 factors, and multivariate analysis were performed. RESULTS: The global rate of infectious complications was 11.1%. The percentages of salivary leaks, other wound infections and non-wound infections were respectively 11.9%; 1.5%; 1.5% for total laryngectomy and 1.8%; 2.4%; 3.8% for partial laryngectomy. Statistically significant factors were tumor stage, postoperative hematoma, postoperative lymphorrhea and, to a lesser degree, pharyngeal localization. CONCLUSION: Our rate of infectious complications in oncologic pharyngeal and laryngeal surgery, which is low compared with data in the literature, emphasizes the importance of strict measures of surgical asepsis and prolonged antibiotic chemotherapy as is recommended for so-called contaminated surgery.

Anti-Bacterial Agents↗

[Hepatitis viruses: mother to child transmission].

The infection by the hepatitis viruses, when appearing during the pregnancy, could result in damages for the infant. However, risks differ according to the implicated virus. Hepatitis B virus infection, for which prevalence varies according to areas, is injurious when the mother is chronic HBsAg carrier. Risk consists of neonate's contamination during the labour, and if contaminated, the neonate becomes a chronic carrier himself in 80 to 90% of cases. When the mother is positive for viral DNA in her serum, transmission rate is estimated at 90%. In the opposite, if the mother is negative for viral DNA in the serum, transmission rate is about 10 to 30%. HBsAg screening is obligatory in France during the sixth month of pregnancy: in case of positivity, serovaccination of the neonate is systematically carried out. Protection rate is 100% if the mother had a low viral load (<150 pg/ml) at the end of pregnancy, and weaker (about 70%) if the mother had a higher level of viral DNA. Transmission risk of hepatitis C virus (HCV) is much lesser, since it is about 5% for a woman who is positive for viral RNA at the end of her pregnancy, and at least 10% if the woman is moreover positive for the HIV. Risk is more important if the woman had an important plasmatic viral load (> 10(5) copies/ml) and if the duration between membrane rupture and delivery is long. Vaginal delivery and breast-feeding are not advised. Neonates from mothers who replicate the HCV at the end of pregnancy are serologically evaluated until 12-15 months of age, in order to determine their possible contamination.Delta virus transmission from mother to infant is exceptional and could be avoided by the HBV serovaccination of the new-born.Intra-utero transmission of hepatitis A virus is very rare, but perinatal transmission could occur. Materno-fetal transmission of hepatitis E virus has been reported, but the virus is essentially dangerous for the mother, resulting in a mortality rate of 15 to 25% if the acute infection occurs during the third trimester of the pregnancy.

DNA, Viral↗