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Biomedical subjects

P Merle

Publications and source records attributed to P Merle.

At least 37 records · Page 2Linked to original sources

Early detection of viral resistance by determination of hepatitis B virus polymerase mutations in patients treated by lamivudine for chronic hepatitis B.

We have analyzed the molecular dynamics of emergence of drug-resistant strains in patients receiving lamivudine therapy for chronic hepatitis B. Twenty consecutive patients with lamivudine resistance were studied (13 hepatitis B e antigen [HBeAg]-positive patients and 7 HBe antibody [anti-HBe]-positive patients). Determination of viral genotype, precore mutants, and polymerase gene mutants (L528M, M552V, M552I) was performed using the research version of Lipa-HBV. Quantitative analysis of HBV DNA was performed using both branched DNA (bDNA) and polymerase chain reaction (PCR) assays. Polymerase mutants (genotypic resistance) were found in 16 of 20 patients. Genotypic resistance was detected earlier than the phenotypic resistance (P =.004). Quantitative PCR allowed detection of viral DNA throughout the entire study period in 16 of 20 patients. Analysis of pretreatment variables showed that high alanine transaminase (ALT) levels (>3 x the upper limit of normal [ULN]) was associated with a more rapid selection of drug-resistant mutants (P =.027) and a high hepatitis B virus (HBV) DNA level (>1,497 Meq/mL, bDNA) with a more rapid occurrence of phenotypic resistance (P =.04). At the time of viral breakthrough, the mean serum HBV-DNA values were not different from the pretreatment values (P =.37). ALT levels were higher in anti-HBe-positive patients compared with pretreatment values and to HBeAg-positive patients (P =.01). In 8 patients, antiviral therapy was modified after viral breakthrough, with the introduction of famciclovir and/or interferon alfa. Viral DNA became undetectable by bDNA in 3 patients who received interferon. Our results suggest that genotypic assays for polymerase mutant detection and quantitative determination of viremia with highly sensitive assay are warranted for an optimal monitoring of antiviral therapy of chronic hepatitis B.

2-Aminopurine↗

[Hepatitis G virus in blood donors].

PURPOSE: Anti-hepatitis C virus (HCV) antibodies (Abs) screening on blood donors has been introduced in France on March 1st, 1990. During the last years, a new agent named Hepatitis G Virus (HGV) has been described. We have tested different groups of blood donors with the aim of establishing the prevalence of the HGV. METHODS: Two hundred and forty-three donors negative for anti-HCV Abs, other viral markers and with normal Alanine Amino Transferase (ALT) as control [group 1], 91 with elevated ALT [group 2], 72 with Abs directed against the hepatitis B virus core (Anti-HBc) [group 3], 3 with elevated ALT and anti-HBc Abs [group 4] and 70 positive for anti-HCV Abs [group 5] were evaluated. HCV-RNA was tested by Polymerase Chain Reaction (PCR) (Amplicor, Roche) and HGV-RNA by in house PCR and Abbott Kit. Anti-HGV Abs were tested with Boehringer and/or Abbott tests. RESULTS: Among group 1, none subject is found HCV-RNA positive. Seven (2.9%) are HGV viremic and 19 positive for anti-HGV Abs (7.8%). Four (4.4%) and 5 (6.9%) donors were HGV-RNA positive and 15 (16.5%) and 16 (22.2%) anti-HGV Abs positive in group 2 and 3 respectively. In group 4, 2 donors are anti-HGV Abs positive. Furthermore, in group 5, 52 subjects (74.3%) are HCV-RNA positive and 9 HGV-RNA positive (12.9%). Six donors are viremic for the both viruses. Lastly, 26 donors have anti-HGV Abs (37.1%). None subject of the five groups has both HGV-RNA and anti-HGV Abs. CONCLUSION: The prevalence of HGV-RNA and anti-HGV is high among control donors. In donors with one or two hepatitis surrogate markers (ALT and/or anti-HBc Abs), the prevalence of HGV viremia and anti-HGV Abs is increased as well as among donors with HCV infection.

Blood Donors↗

-Vaccination against hepatitis B-.

Although relatively uncommon among French children, hepatitis B virus infection is a major problem of public health which deserves coordinated strategies of prevention and immunization, in order to eliminate chronic carriers among groups at risk. The participation of pediatricians to these strategies is essential, knowing that transmission of hepatitis B virus from asymptomatic carrier mothers to their newborns contributes to new generation of chronic carriers who will be exposed to cirrhosis and hepatocellular carcinoma. Four hepatitis B vaccine are presently available in France with equal good efficiency and tolerance. These vaccines allow a protection against hepatitis B in 90 to 95% of the vaccinated subjects. Active search for new vaccines, particularly DNA vaccines, is in progress to extend the protection to the 5-10% non or low responders. The current recommended strategy of immunization in France associates immunizations of infants, preadolescents and groups at risk. In addition newborns from carrier mothers must receive combined passive and active immunization at birth.

Adolescent↗

Initial evaluation of cystatin C measurement by particle-enhanced immunonephelometry on the Behring nephelometer systems (BNA, BN II).

Serum cystatin C has been suggested as a new marker of glomerular filtration rate (GFR). We describe a fully automated and rapid particle-enhanced nephelometric immunoassay (PENIA) for measuring serum cystatin C on the Behring nephelometer systems (BNA, BN II). Each sample is analyzed in 6 min with as many as 75 samples per batch. The assay covers the range 0.23-7.25 mg/L, up to seven times the upper limit of normal. The intra- and interassay imprecision are < 3.3% and < 4.5%, respectively. There is absolute linearity across the assay range (r2 = 0.997), with analytical recovery by cystatin C addition between 95% and 109% (mean 102%). Hemoglobin (< or = 8.0 g/L), bilirubin (< or = 488 microL), triglycerides (< or = 23 mmol/L), rheumatoid factor (< or = 2000 kIU/L), and myeloma paraprotein (< or = 41 g/L) do not interfere with the assay. This assay agreed well with an in-house particle-enhanced turbidimetric immunoassay (PETIA) (mean difference = 1.73 +/- 2.10) and a commercial PETIA (mean difference = 1.13 +/- 0.86). This is a new assay by which cystatin C may be effectively used as a marker of GFR estimation.

Animals↗

[Efficacy of interferon alpha in primary prevention of preneoplastic lesions in a transgenic murine model of hepatocellular carcinoma related to the interaction between woodchuck hepatitis viruses and c-myc oncogene].

OBJECTIVES: C-myc oncogene overexpression by near insertion of hepatitis B virus is important in woodchuck hepatocarcinogenesis. This DNA fragment was transferred in mice who developed hepatocellular carcinoma via preneoplastic lesions. In the present study, we tested the preventive effect of alpha interferon on the incidence of hepatocyte dysplasia. METHODS: Human recombinant alpha interferon hybrid B/D was continuously administered at increasing doses (0 to 10,000 IU/g) in a transgenic mouse model. One cohort was treated from day 21 to day 80. A histological liver examination was performed and the transgene expression was assessed by hybridization with or without previous genic amplification, and by indirect immunofluorescence. RESULTS: At day 15, histological liver examination was normal. Interferon treatment decreased the expression of viral sequences, but not of c-myc. At day 80, interferon treatment resulted in a reduction of the incidence and severity of dysplasic lesions, and a marked decrease in c-myc overexpression. CONCLUSION: In this transgenic mouse model, alpha interferon treatment decreased the incidence and severity of precancerous lesions, due to a reduction in c-myc overexpression. This prophylaxis could be of interest in human hepatocarcinogenesis where c-myc overexpression is frequent.

Animals↗

Severe selective magnesium malabsorption: tests of tolerance of oral magnesium supplements.

Since his birth, we have been monitoring a 12-year-old boy suffering from selective severe magnesium malabsorption. Our essential problem is to prepare a form of galena with acceptable taste, tolerated by the digestive tract and well absorbed; also, the carrier compound must not cause short- or long-term side effects. An additional factor is the steadily increasing need for magnesium from 1 mmol/kg.d at 1 year to 14 mmol/kg.d at present age (345 mg/kg.d). The galena forms currently on sale were, with the exception of lactate and pyrollidone carboxylate, immediately rejected since they contain insufficient Mg2+. Following short trials resulting in diarrhoea, the other two preparations were also rejected. We then constituted - and also abandoned - our own galena compounds: aspartate (bitterness), aspartate + glycerophosphate (GLP) (bitterness), glutamate + GLP ('Chinese restaurant syndrome' and fear of the long term toxic effect of the glutamate), gluconate (excessive volume: 11/1 proportion with Mg2+). A recent test featuring GLP of Mg 40 g + cocoa butter 40 g + cocoa 10 g, brought about vomiting and diarrhoea, and was not adequately absorbed. The best tolerated formula is: Mg GLP 21.33 g; saccharose 6 g; aspartam 1 g; gelatin 0.5 g; citric acid, conserving agent, fruity aroma; water: qs 100 g. Such composition yields a caramel cream absorbed in five small portions, at a daily quantity of 375 g (80 g GLP Mg, 10 g Mg2+). Vitamin B6, which promotes intestinal absorption of magnesium, must be given separately in tablet form at a dose of 1 g/d, since it causes nausea if it is included in the Mg preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

[Computerized obstetrical record of the North Pas-de-Calais region].

The computerized obstetrical record of the North-Pas-de-Calais region proceeds from the desire of a number of people from the Regional Health Observatory, to dispose of a prospective epidemiologic tool in the field of perinatology. The objective is a better knowledge of the cause of perinatal death, analyzing the modalities of prenatal monitoring, delivery conditions, transfer of the newborns, as well as socio-economical conditions. The program manages the computerization of a usual obstetrical file, in the region, including approximately 200 items and allowing every possible comparison with the well-known CCIM record. The program permits local treatment of the data (statistical calculations) in each maternity hospital: rapid transmission of information between maternity and correspondents (computerized personalized mail), a base of agreement between the different protagonists: midwives, pediatricians, specialists, an easier collaboration with the protection agencies and, especially, the Regional Direction of Sanitary and Social Affairs, with automatic response to hundreds of questions of the yearly questionnaire, which saves a great deal of time and an extreme reliability of the information. This program is compatible with any IBM PC microcomputer and includes a hard disk of 10 or 20 mega-octets. The current price (microcomputer with hard disk, monitor, keyboard, letter-quality printer, management program) make all these performances available at a relatively low expense, under 25,000 francs (not including the tax).

Female↗

[Outcome of the kidney with vesico-ureteral reflux. Apropos of 129 cases].

The final status of the kidneys of 129 children suffering from vesico-ureteric reflux was studied. The growth of the kidneys was comparable in the surgically treated and in the medically treated group. However, growth was better when the kidneys had been normal initially than when they presented renal scars. New scars were more frequent in the medically treated group, and/or when scars were already present at diagnosis of vesico-ureteric reflux. Our results are in agreement with those in the literature.

Adolescent↗

[Olfactory neuroblastoma disclosed by blindness in a 9-month-old girl].

A case of olfactory neuroblastoma in a 9 month-old girl is reported. Blindness and purulent meningitis were the first symptoms. Radiological examinations including CT scan revealed a sphenoidal tumor with penetration of the meninges. Surgery revealed an ethmoido-sphenoidal tumor mass extending into the pituitary fossea which consisted of malignant cells with the histological aspect of esthesioneuroblastoma. The rarity of this tumor in early childhood and its clinical polymorphism are emphasized.

Blindness↗

A new polyvalent pseudomonas vaccine.

A new polyvalent Pseudomonas aeruginosa vaccine consisting of extracts of the 24 serotypes of the Lanyi typing scheme was developed and evaluated in mouse protection studies. The vaccine, mainly consisting of lipopolysaccharides and outer membrane proteins was protective in passive and active protection studies. A rabbit antiserum against the vaccine showed high protective capacity in the IgG-fraction and was protective against 3 out of 6 challenge strains in a leucopenic mouse model.

Animals↗

Separation of mammalian cytochrome c oxidase into 13 polypeptides by a sodium dodecyl sulfate-gel electrophoretic procedure.

A sodium dodecyl sulfate-gel electrophoretic procedure which allows the separation of isolated cytochrome c oxidase from different mammalian sources into 13 different polypeptides is described. Application of the silver-staining procedure results in the same protein pattern as obtained by Coomassie blue staining. From the correlation of the gel bands with 12 isolated polypeptides from which the complete amino acid sequence is known, it is concluded that mammalian cytochrome c oxidase consists of 13 different polypeptides which can all be separated by the described procedure.

Animals↗

[X-ray anatomy of the recto-genital pouch in the child].

Peritoneography is a simple radio-anatomic method to get informations about the depth and the orientation of the Douglas pouch in children in relation to fixed bony landmarks in the pelvis (upper part of the pubic bone-lowest sacral segment). Measurements were recorded on patients ranging from 15 days-old to 15 years-old. The older the patient, the deeper and the more posterior seemed to be the Douglas pouch.

Adolescent↗

[Value of herniography in the therapeutic management of inguinal hernias in young girls. Apropos of 148 cases].

The authors report a study on 148 female children demonstrating clinical evidence for inguinal hernias. The diagnosis was evaluated using Ducharme-Bensoussan's procedure for herniography hernia was documented in 143 cases, so which 44% revealed genital tract content. Eight cases produces unrelated pathological findings, especially crural hernia, nephro-uropathy diaphragmatic hernia. However, the main interest of the procedure is in evaluating the controlateral inguinal canal. Whereas three infants presented with bilateral symptoms, bilateral hernia was proven in 66 cases (46,2%) by herniography. In this way, the procedure is a sure way to ensure that hernia is really unilateral and to prevent any controlateral recur in the coming months.

Child↗