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Biomedical subjects

D Gendrel

Publications and source records attributed to D Gendrel.

At least 73 records · Page 4Linked to original sources

Isoniazid acetylation metabolic ratio during maturation in children.

Isoniazid acetylation metabolic ratio (MR) was studied in 61 children with tuberculosis after administration of isoniazid. MR was calculated as the molar acetylisoniazid to isoniazid concentration ratio. MR was used as a probe for N-acetyltransferase activity and to determine the acetylation phenotype. MR had a bimodal distribution with an antimode between 0.48 and 0.77. MR and the percentage of fast acetylators increased significantly with age. The cumulative frequency of fast acetylators increased with age, with a plateau reached around 4 years. MR value was checked during treatment in 44 children. All children but one who initially appeared as fast acetylators remained in this group after repeated testing. Among the 30 slow acetylators, 12 became fast acetylators, and 10 showed a variable phenotyping at different ages. A bimodal distribution of the isoniazid acetylation MR was shown in children, with an antimode close to that described in the literature and a maturation of isoniazid acetylation during the first 4 years.

Acetylation↗

Measurement of procalcitonin levels in children with bacterial or viral meningitis.

We measured the plasma procalcitonin levels in 59 children who were admitted to the hospital because of bacterial or viral meningitis. Eighteen children with acute bacterial meningitis had elevated procalcitonin levels (mean level, 54.5 micrograms/L; range, 4.8-110 micrograms/L). The procalcitonin levels in 41 children with viral meningitis were low (mean level, 0.32 micrograms/L; range, 0-1.7 micrograms/L; P < .0001). Assay of cerebrospinal fluid (CSF) cells and proteins and serum C-reactive protein showed a zone of overlapping values between the two groups. Procalcitonin was not produced in CSF. Plasma procalcitonin levels decreased rapidly during antibiotic therapy. These data suggest that the measurement of plasma procalcitonin might be of value in the differential diagnosis of meningitis due to either bacteria or viruses.

Adolescent↗

[Antibiotic strategy in lower respiratory infections in children].

Antibiotic treatment of community-acquired lower respiratory tract infections in children remains widely empiric since the determination of the causative agent is difficult and rarely done. Antibiotic therapy is not necessary in all cases since viral infections are frequent. Antibiotic choice must take in account the possibility of pneumococcal infections. Pneumococci are not the most frequent causative agent but always provoke severe infections with a risk of death and amoxicillin is the first-line choice, with high doses (100 mg/kg/d) because of the emergence of strains with a reduced sensitivity to penicillin. In younger children, Haemophilus influenzae infections are frequent and clavulanic acid must be associated. When intravenous route is required, 3rd generation cephalosporins are useful. The clinical failure of beta-lactams antibiotics is widely due, after the age of two years, to a Mycoplasma pneumoniae infection and a macrolide is required as second-line choice. Markers specific of viral infection are needed in children to reduce antibiotic prescription.

Adolescent↗

[Community-acquired pneumonia in children: importance of Mycoplasma pneumoniae infections and efficacy of antibiotics].

OBJECTIVES: Define a therapeutic management schema adapted to children with community-acquired pneumonia. METHODS: A prospective survey was conducted in 104 children over 18 months of age with community-acquired pneumonia. The pathogen was isolated in 85% of the cases. RESULTS: Viral infection alone was proven in 30 children (respiratory syncytial virus in 10). Pneumococci pneumonia was found in 12 patients; the isolated strains were sensitive to penicillin. Apyrexia was obtained in 11/12 cases with amoxicillin. Mycoplasma infections occurred in 42% of the cases (41 alone and in association with pneumococci in 2 cases). Pneumococci and mycoplasma infections could not be differentiated with standard radiography and laboratory tests. Initial treatment with beta lactamines was always unsuccessful in children with mycoplasma infections. Apyrexia was achieved when antibiotics were changed to macrolides. CONCLUSION: Since lower respiratory tract infections due to pneumococci are much more severe than those due to mycoplasma, beta lactamines should be given as first intention treatment for children over 18 months with pneumonia. Macrolides should be given in case of failure because mycoplasma would then be the most probable infectious agent.

Adolescent↗

Evaluation of a serological test for diagnosis of Helicobacter pylori infection in children.

A serological test for the diagnosis of Helicobacter pylori infection (Cobas Core Roche, IgG, 2nd Generation; Roche, France) was compared with the examination of biopsy samples (culture and histology) obtained after endoscopy in 115 children to assess its value. In 94 children (42 positive and 52 negative), results were concordant. In 10 children a positive serological test was associated with an absence of Helicobacter pylori, while in 11 others a negative serological test was associated with a positive culture. Sensitivity of the test was 79.2% and specificity 83.9%. A relationship between IgG titers and age (r = 0.31, p < 0.05) was found. Serological tests could be useful for the diagnosis of Helicobacter pylori infection, but a negative test result does not rule out infection, particularly in children under 10 years of age.

Adolescent↗

Procalcitonin as a marker for the early diagnosis of neonatal infection.

Serum procalcitonin was determined in newborn infants at the time of admission to the pediatrics or obstetrics unit. Increased levels were found in all neonates with bacterial sepsis. Neonates with viral infection, bacterial colonization, or neonatal distress had normal or slightly increased levels. These data suggest that procalcitonin might be of value in diagnosing neonatal sepsis.

Bacterial Infections↗

[Pneumococcal meningitis resistant to penicillin and nosocomial transmission in pediatric hospitals confirmed by genomic analysis].

BACKGROUND: Careful epidemiological studies and sophisticated diagnostic procedures are necessary to prove that bacterial infection is nosocomial in origin. DNA finger printing method can be useful with this aim in view. CASE REPORTS: A 11 month-old girl suffered from a febrile pneumonia. She developed acute meningitis 15 days later; culture of CSF grew Streptococcus pneumoniae, serotype 23 F, resistant to beta-lactamines, erythromycin and cotrimoxazole. She died 24 hours later. Five days after this death, a 5 month-old infant hospitalized in the next bed developed an acute pulmonary infection due to the same strain with the same bacterial characteristics; this patient was cured with cefotaxime plus vancomycin and gentamicin. Randomly amplified polymorphic DNA analysis showed an identical profile of both strains. CONCLUSION: This is the first case of meningitis due to penicillin-resistant Streptococcus pneumoniae (PRSP) associated with nosocomial spread between two children in adjacent beds. This case suggests that it is necessary to isolate patients with PRSP infection during hospitalization.

Cross Infection↗

Serum alpha-interferon in lower respiratory tract infections of children.

BACKGROUND: Serum alpha-interferon (IFN-alpha) concentrations are high in some children with viral meningitis and other viral infections. We have tried to assess the utility of determining serum IFN-alpha concentrations as a marker of acute viral respiratory infections. METHODS: Measurement of IFN-alpha via a biologic assay on Madin-Darby bovine kidney cells was performed in 138 patients with lower respiratory tract infection in whom a pathogen was identified. RESULTS: Serum IFN-alpha was detectable at the early stage of respiratory infections in the era of 59 of 75 (78.7%) of patients with a viral infection and in 4 of 63 (6.3%) of those with bacterial infection (P < 0.001). In the 4 patients with positive IFN-alpha and bacterial infection, a concomitant viral infection was found. The production of IFN-alpha is independent of age, and detectable levels are found in young infants, including the first 3 months of life, and in children with an acute viral disease. CONCLUSION: This test could be useful in distinguishing between bacterial and viral origins in lower respiratory tract infection (the specificity was 94% and the sensitivity was 79%) and could help guide the use of antibiotics, but more rapid techniques, available in a matter of hours, are required.

Acute Disease↗

Alteration of lung diffusion capacity in IgA nephropathy.

OBJECTIVE: To establish whether changes of lung transfer for carbon monoxide (TLCO) are related to the phase of IgA nephropathy. METHODS: Respiratory function was tested in 12 children with IgA nephropathy assessed by percutaneous renal biopsy. This was done during acute exacerbations or haematuria-free phases of the disease. RESULTS: TLCO was low in 12/13 measurements made in the haematuric phase of IgA nephropathy or during the month following gross haematuria (mean TLCO 64% of expected values). Lung volumes and blood gas values were normal and only minor radiological signs of interstial lung involvement were observed in 11/12 patients. When respiratory tests were performed more than three months after gross haematuria, TLCO was low in 4/9 patients, with no relation to the significance of residual proteinuria or severity of findings at renal biopsy. There was a significant difference between tests performed when haematuria was present or recent and those performed more than three months after an episode of gross haematuria (p < 0.01). CONCLUSIONS: The decrease of TLCO in the acute phases of the disease is probably related to alterations of the lung alveolarcapillary membrane by immune complexes containing IgA. This non-invasive technique, easy to perform and repeat, could be of value in the diagnosis of IgA nephropathy in haematuric children.

Acute Disease↗

Growth hormone-binding proteins and insulin-like growth factor-binding proteins in protein-energy malnutrition, before and after nutritional rehabilitation.

To clarify the influence of nutrition on the GH-IGF axis in protein-energy malnutrition (PEM), we determined the serum levels of GH, GH-binding proteins (BP) (GHBPs), IGF-I, and IGFBPs in nine children with kwashiorkor and 13 with marasmus, before and after nutritional rehabilitation. In a basal condition, the GH level was significantly higher in the two malnourished groups than in controls (p < 0.01); in contrast, the second fraction of GHBP was lower and seemed to be related to the high GH and to a reduction in GH receptors. After refeeding, the GH level increased and the second fraction of GHBP decreased. The IGF-I basal level was higher in kwashiorkor than in marasmus subjects (p < 0.05), but in both groups it was significantly lower than in controls (p < 0.01); after refeeding it increased. IG-FBP-3, measured by RIA and Western blotting techniques, was in the control range in the kwashiorkor group but in the marasmic group it was significantly lower than in controls; after refeeding it decreased in kwashiorkor (p < 0.01 versus basal values) and increased in marasmus (p < 0.05 versus prerefeeding level). When sera of malnourished patients were mixed with adult control sera, incubated for 5 h at 37 degrees C, and assessed by ligand blotting, a low IGFBP-3 level in marasmus was found to be due to increased adaptive proteolysis of IGFBP-3; in contrast, in kwashiorkor the IGFBP-3 proteolytic activity was very low, probably because of inhibition by aflatoxins. These findings confirm that malnutrition affects the GH-IGF axis.

Adult↗

A new mutation in the gene for lysosomal acid lipase leads to Wolman disease in an African kindred.

Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both autosomal recessive disorders associated with reduced activity and genetic defects of lysosomal acid lipase (LAL). The strikingly more severe course of WD is caused by genetic defects of LAL that leave no residual enzymatic activity. Mutations at the exon 8/intron 8 transition of the LAL gene have been identified in several CESD and WD patients and are responsible for the manifestation of the disease. We have determined the genetic defect in a 3-month-old boy of African origin affected by WD. No enzymatic activity of the lysosomal acid lipase was detectable in white blood cells and cultured fibroblasts. Analysis of his LAL cDNA and genomic DNA revealed that he was homozygous for a mutation at position -3 of the exon 8 splice donor site. A C-->T transition leads to a nonsense codon and to a premature termination of the LAL protein at amino acid 277. Due to this mutation, a shorter LAL mRNA species was also generated that lacked exon 8 and was deficient of the nonsense codon. As a consequence, the protein synthesis proceeded to the natural termination codon, but the enzyme generated had an internal deletion of 24 amino acids (254-277) and was also inactive. These findings, together with our previous observations when analyzing the mutations in WD and CESD patients lead to the conclusion that the more severe WD is due to mutations that absolutely abolish lysosomal acid lipase (LAL) enzyme activity and the cholesteryl ester storage disease phenotype is due to mutations that allow some residual LAL activity to be manifested.

Alternative Splicing↗

Neonatal infection with Streptococcus milleri.

Streptococcus milleri is a known commensal of the female genitourinary tract, but its pathogenicity in neonates has been reported in only a few cases. During a period of one year in an obstetrical unit, Streptococcus milleri was isolated from nine neonates and from one foetus after a spontaneous abortion. In seven of the nine newborns, neonatal infection was assessed and Streptococcus milleri was the lone pathogen involved, associated with positive blood or vaginal cultures in four mothers. Because Streptococcus milleri requires special conditions for identification, it is probably underestimated as a cause of neonatal infection and septic abortion.

Female↗

[Failure of the treatment with antibiotics in severe Salmonella infections in children and use of quinolones].

BACKGROUND: Quinolone antibiotics are effective in the treatment of Salmonella infections in adults. Their use in children is limited by their side-effects. POPULATION AND METHODS: Forty-two patients (21 girls and 21 boys), aged 1 month to 12 years (mean 3.3 yrs) were admitted from September 1991 to June 1993 for severe Salmonella infections. Criteria of severity were persistent diarrhea and fever for more than 3 days. Thirty-one of these patients were less than 5 years of age. Blood culture was positive in 7 out of 35 patients: culture of the stools was positive in all patients. Five of the 42 patients had presented an acute episode of Salmonella infection a few weeks earlier and had remained asymptomatic carriers until the new acute and severe episode of diarrhea. All patients were given usual antibiotics, mainly ampicillin, amoxicillin, trimethoprime-sulfamethoxazole. Twenty-five of these patients were then given pefloxacin, 12 mg/kg/day, since the 5th day, for 7 days, because persistence of diarrhea and fever. RESULTS: Diarrhea and fever disappeared within less than 2 days in the group of patients given pefloxacin, even though in 6 patients the infecting Salmonella was in vitro resistant to beta-lactamins. Twenty % of patients remained asymptomatic carriers of Salmonella in the group treated by pefloxacin vs 47% in the group without it. There was no difference in species of Salmonella between both groups. None of the patients treated by pefloxacin developed side-effects during the six months following its administration. CONCLUSIONS: Short treatment by pefloxacin may be an alternative choice for treating severe Salmonella infections in children.

Amoxicillin↗

[Measurement of peak expiratory flow in young children: comparison of four portable equipments].

BACKGROUND: Peak expiratory flow (PEF) monitoring is seldom used in young children because peak flow meter normal values are needed for children less than 7 years old. POPULATION AND METHODS: PEF was measured in 152 non asthmatic school children, aged 2.9 to 14.5 years with four peak flow meters (Assess, DHS, Vitalograph, MiniWright). Calibration of these peak flow meters were performed with flows ranging from 100 to 700 l/min with a calibration syringe. RESULTS: Calibration demonstrated the excellent linearity of each device but there was a slight overestimation by DHS and MiniWright, and a slight underestimation by Vitalograph and Assess. PEF measured with the four devices was better linearly correlated with height (r = 0.72 to 0.77) than with age. Differences similar to calibration have been found between the four linear regressions. CONCLUSION: These results indicate that PEF can be used in young children less than 7 years old. It is necessary to always use the same peak flow meter for a child.

Adolescent↗

[Eradication of asymptomatic carrier state of non-typhoid Salmonella with two doses of pefloxacin].

BACKGROUND: The carrier state of Salmonella may represent a source of contamination for other people. Its treatment is unsatisfactory so that a carrier may shed organisms for numerous months. POPULATION AND METHODS: From 1990 to 1993, 17 children aged 1.5 months to 8 years were seen because they were asymptomatic carriers of non-typhoid Salmonella, confirmed by three successive stool cultures. All had presented earlier acute severe infection having required treatment with amoxicillin (13 cases) and ceftriaxone or cefotaxime (four cases). They were given one dose of pefloxacin, 12 mg/kg, 4 to 8 weeks after the initial episode. This unique dose was administered again 4 days later. Stool cultures were performed before the first administration and 10, 30, 45 and 60 days after, with a last control 3 to 4 months later. RESULTS: Eradication of the Salmonella was obtained by the 10th day in 13 patients and within the 3 following weeks in 2 others. Those children who excreted a few number of organisms were early eradicated while the 2 patients who did not respond to pefloxacin shed larger number of bacteria. There was no side-effects of treatment. CONCLUSION: A short treatment with pefloxacin appears to be effective and safe in eradicating the carrier state when stool excretion of Salmonella is moderate.

Carrier State↗