Biomedical subjects
J F Duhamel
Publications and source records attributed to J F Duhamel.
[Respiratory allergy and the viruses].
Viral respiratory tract infections are a major cause of wheezing in infants. Investigators determined that 80% to 85% of school-aged children with wheezing episodes were tested positive for virus. To more fully understand how viral respiratory tract infections influence asthma, investigators have evaluated the effect of respiratory tract infections on airway symptoms, function, and inflammation. Although the mechanisms by which respiratory viruses enhance lower airway inflammation are not established, cytokines may play a key role in this process. The respiratory epithelial cell is a principal host for respiratory virus replication and is likely to be the first source of cytokines during an acute infection. T cells orchestrate immune responses to both allergens and viruses, and regulate effector cells with virucidal and proinflammatory effects. Although studies demonstrate that virus-specific T cells may contribute to virus-induced lung disease, evidence to define the role of virus-specific T lymphocytes in asthma has not been fully established. Some infections early in life may also have an important immunoregulary role in the subsequent development of allergy and asthma. Atopy is characterised by exaggerated Th-2 cell responses to common allergens with secretion of cytokines such as IL-4 and IL-5 that promote IgE production and eosinophil activation. In contrast, childhood infections typically induce a Th-1 cell response, characterised by secretion of interferon-gamma, which enhances the antiviral activities of effector cells. These two types of T cell responses are mutually antagonistic.
Detection of viral, Chlamydia pneumoniae and Mycoplasma pneumoniae infections in exacerbations of asthma in children.
BACKGROUND: A high frequency of virus infections has been recently pointed out in the exacerbations of asthma in children. OBJECTIVES: To confirm this, using conventional and molecular detection methods, and expanding the study to younger children. STUDY DESIGN: One hundred and thirty-two nasal aspirates from 75 children hospitalized for a severe attack of asthma were studied (32 infants, mean age 9.1 months; and 43 children, mean age 5.6 years). According to the virus, a viral isolation technique, immunofluorescence assays (IFA) or both were used for the detection of rhinovirus, enterovirus, respiratory syncytial (RS) virus, adenovirus, coronavirus 229E, influenza and parainfluenza virus. Polymerase chain reaction (PCR) assays were used for the detection of rhinovirus, enterovirus, RS virus, adenovirus, coronavirus 229E and OC43, Chlamydia pneumoniae and Mycoplasma pneumoniae. RESULTS: Using IFA and viral isolation techniques, viruses were detected in 33.3% of cases, and by PCR techniques, nucleic acid sequences of virus, Chlamydia pneumoniae and Mycoplasma pneumoniae were obtained in 71.9% of cases. The combination of conventional and molecular techniques detects 81.8% of positive samples. Two organisms were identified in the same nasal sample in 20.4% of the cases. The percentage of detections was higher (85.9%) in the younger group than in the other (77%). The most frequently detected agents were rhinovirus (46.9%) and RS virus (21.2%). Using PCR rather than conventional techniques, the detection rates were increased 5.8- and 1.6-fold in rhinovirus and RS virus infections, respectively. The detection levels of the other organisms are as follows: 9.8, 5.1, 4.5, 4.5, 4.5, 3.7, and 2.2% for enterovirus, influenza virus, Chlamydia pneumoniae, adenovirus, coronavirus, parainfluenza virus, and Mycoplasma pneumoniae, respectively. CONCLUSION: These results confirm the previously reported high frequency of rhinovirus detection in asthmatic exacerbations in children. They also point out the frequency of RS virus detection, and emphasize the fact that PCR assays may be necessary to diagnose respiratory infections in asthma.
[Fever in children less than 3 months old].
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[Virus bacteria interactions in acute viral pneumonia in infancy: clinical and therapeutic consequences].
Although signs and symptoms may become severe, most viral respiratory infections of infancy are self-limited and improvement usually occurs within several days. Patients hospitalized with viral pneumonia usually require supportive therapy, including oxygen and fluids, and eventually mechanical ventilation. Bacterial superinfection can occur, accompanied by purulent sputum production and isolation of pathogenic bacteria from sputum. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus are the most common secondary invaders. Appropriate antibiotherapy must be administrated after cultures. There is no evidence that prophylactic antibiotherapy is of any use to prevent bacterial superinfection in viral pneumonia.
Relationship between bone mineralization and aluminium in the healthy infant.
OBJECTIVE: This prospective study was designed to assess the relationship between variations of serum Aluminium levels and bone mineralization, which is one of its target tissues, in healthy premature (PT) and fullterm (FT) infants. STUDY DESIGN: Lumbar spine bone mineral density (BMD) and content (BMC) studied by dual energy X-ray absorptiometry were compared to serum aluminium (S-Al), Ca (S-Ca), P (S-P), osteocalcin, alkaline phosphatase activity (S-AP), and 25 OH Vitamin D (25 OH D) by simple and multiple regressions in healthy PT (n = 44) following their hospital discharge and FT (n = 82). PT (gestational age at birth (mean +/- 1 s.d.) 32 +/- 2 weeks) and FT were 43 +/- 39 and 36 +/- 32 weeks old respectively. RESULTS: In PT multiple stepwise regression analysis including gestational age at birth, postconceptional age and postnatal age displayed only a significant correlation between BMD or BMC and postnatal age and a negative one with S-Al. In FT correlations were found between BMD or BMC and age and S-Ca. CONCLUSIONS: In PT, variations in blood Al are associated with developmental delays. Care should be taken to lessen Al levels, even in healthy PT babies.
The triangular test to assess the efficacy of metoclopramide in gastroesophageal reflux.
BACKGROUND: Sequential methods are particularly interesting when recruitment is difficult because they may allow a study to be stopped early while maintaining type I and II error rates. METHODS: This placebo-controlled, randomized double-blind study was aimed at assessing the efficacy of metoclopramide (0.2 mg/kg three times daily during 14 days) on gastroesophageal reflux in infancy. The main end point was the relative variation of the percentage of time at pH < 4 between inclusion (day 0) and evaluation (day 14) assessed on two 24-hour esophageal pH recordings. Statistical analysis was performed with use of a sequential method, the triangular test. RESULTS: The study was stopped after the seventh analysis (39 infants evaluated: 20 placebo and 19 metoclopramide) without showing the expected benefit. Improvement on the main end point was 30% +/- 48% (mean +/- SD). Corresponding unbiased median estimates were 22% for placebo and 39% for metoclopramide (p = 0.28, sequential analysis). On day 14, the percentage of time at pH < 4 was 8.1% +/- 11.7% for placebo and 6.7% +/- 9.2% for metoclopramide (p = 0.68, t test), and the number of reflux episodes > 5 minutes was 3.0 +/- 3.5 for placebo and 1.9 +/- 3.0 for metoclopramide (p = 0.33, t test). CONCLUSION: If a tendency for a superior improvement with metoclopramide than with placebo was observed on the main end point, it was lower than expected and the difference was not significant. Compared with the corresponding single-stage design, the triangular test allowed to stop the study with a 15% reduction in sample size.
Detection of respiratory syncytial virus, parainfluenzavirus 3, adenovirus and rhinovirus sequences in respiratory tract of infants by polymerase chain reaction and hybridization.
BACKGROUND: Immunofluorescence assay (IFA) of viral antigens in nasal aspirates is largely used for the diagnosis of respiratory syncytial virus (RSV), parainfluenzavirus (PIV) type 3 and adenovirus (AdV) infections, whilst rhinovirus (RV) are detected by virus isolation technique (VIT) only. Using the two techniques, IFA and VIT, a significant number of specimens remain negative in spite of clinical and epidemiological presumptions of viral infection. OBJECTIVES AND STUDY DESIGN: The polymerase chain reaction (PCR) should improve the sensitivity of viral detection in clinical specimens. From October 1995 to March 1996, 277 nasal aspirates from hospitalized infants were tested simultaneously by IFA, VIT, polymerase chain reaction and hybridization with a DNA enzyme immunoassay (PCR-EIA) for RSV, PIV-3, AdV and RV. RESULTS: RSV were detected in 177 (64%) samples, PIV-3 in 23 (8%), RV in 40 (14%), and AdV in 30 (10%). PCR-EIA detected RSV in more samples 173 (62%) than IFA/VIT: 109 (39%) (P < 10(-7)). In most cases (79%), RSV-infected infants had lower respiratory tract disease, and routine and PCR techniques were positive. Out of the 23 PIV-3 infections, 12 were IFA/VIT- and PCR-EIA-positive, and 11 IFA/VIT-negative and PCR-EIA-positive. For RV, 35 (87%) specimens were PCR EIA-positive and 11 (27%) culture-positive; for AdV 30 samples were PCR-EIA-positive and four were culture-positive. Simultaneous viral infections were revealed in a significantly higher proportion than in conventional techniques: 18% (50/277) versus 2.5% (7/277); P < 10(-7). One RSV infection in four was associated with the presence of another virus, mainly PIV-3 (16 cases) and AdV (13 cases). CONCLUSIONS: PCR-EIA detects more positive-specimens than IFA/VIT, 1.5 times more for RSV, 1.9 for PIV-3, 4 for RV and 10 for AdV, respectively. This increased sensitivity of viral detection by PCR-EIA compared to the IFA/VIT could suggest that samples containing low levels of virus are missed by routine methods IFA/VIT, and consequently, RSV or PIV-3, and above all RV or AdV are overlooked as agents of respiratory diseases. However, apart from the fact that the economic and convenient aspects of virus diagnostic cannot be missed, it is difficult to answer the following questions: what is the meaning of the detection of a viral sequences in nasal aspirates of infants, or may PCR have detected virus in patients who would not developed disease?
A randomized, double-blind, multicentre controlled trial of ibuprofen versus acetaminophen and placebo for symptoms of acute otitis media in children.
Two hundred and nineteen children (boys: 56%, girls: 44%) were included in a randomized, double-blind, multicentre (4 centres) controlled trial designed to assess the efficacy and safety of ibuprofen (IBU) in the treatment of 1 to 6 year-old children with otoscopically proven acute otitis media (AOM), either unilateral or bilateral. They randomly received 10 mg/kg IBU (n = 71), or acetaminophen (PARA) (n = 73) or placebo (PLA) (n = 75), orally, tid, for 48 hours. All received oral cefaclor (Alfatil, Lilly, France) for seven days. They were evaluated before (D0) and at the end of treatment (D2). The main criterion of response was the aspect (landmarks and color) of the tympanic membrane assessed on a semi-quantitative scale from 0 to 6. Other criteria, assessed on semi-quantitative scales, included relief of pain (0 or 1), rectal temperature (0 to 2), and overall evaluation by parents of the improvement of quality of life on three items: appetite (0 to 2), sleep (0 to 2), and playing activity (0 to 2). The results at D2 were as follows: there was no significant difference between treatment groups as to the main criterion, but only a trend for IBU and PARA to do better than PLA but not for IBU to do better than PARA. From these data there is no argument to emphasize the utility of non-steroidal anti-inflammatory drugs (NSAIDs) in treating the inflammatory signs of the tympanic membrane in otitis. There was a statistically significant difference between treatment groups at D2 for pain, IBU being superior to PLA (P < 0.01): 7%, 10% and 25% of the children were still suffering at D2 in the IBU, PARA and PLA treatment groups, respectively. The difference between PARA and PLA for pain was not statistically significant. There was no significant difference between treatment groups for the other criteria. All treatments were well and equally tolerated. Although no significant difference was found between the treatment groups on the aspect of the tympanic membrane, the efficacy of IBU was evidenced on the relief of pain, the symptom that most disturbs the child.
[Outcome of cystic fibrosis children screened at birth].
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Virological diagnosis of cytomegalovirus in renal transplantation: comparison of three diagnostic methods: DNA in plasma by PCR, PP65 leukocytic antigenemia, and viremia.
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[Must the perspective of the gene therapy modify the screening strategy of cystic fibrosis?].
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Detection of respiratory syncytial virus by reverse transcription-PCR and hybridization with a DNA enzyme immunoassay.
Nasal aspirates from 238 infants hospitalized with acute respiratory infections during the winter of 1994 and 1995 were tested for respiratory syncytial virus (RSV) by immunofluorescence assay (IFA) and the viral isolation technique (VIT) and by two PCR and hybridization methods: reverse transcription PCR 1 (RT-PCR1), which amplifies the RNAs of all RSV strains, and RT-PCR-2, which allows subgroup classification of RSV. RT-PCR-1 and RT-PCR-2 detected viral sequences in 56.7% (135 of 238) and 48.3% (115 of 238) of the samples, respectively, while only 80 (33.6%) samples were found to be positive by IFA and VIT. Of the PCR-positive specimens, 57 were missed by these routine techniques in RT-PCR-1 and 45 were missed in RT-PCR-2. Although the RSV-PCR-1 and RSV-PCR-2 techniques amplified two different sequences of the RSV genome, they gave similar results for 218 (91.6%) nasal aspirates. Compared with conventional methods, the sensitivity, specificity, and agreement were 97.5, 63.9, and 75.2%, respectively, for RT-PCR-1 and 89.7, 71.9, and 77.7%, respectively, for RT-PCR-2, and for these two RT-PCR assays, the positive predictive value (PPV) and the index of agreement (kappa) were comparable and moderate, respectively: PPV was 57.8% and kappa was 0.52 in RT-PCR-1, and PPV was 60.9% and kappa was 0.54 in RT-PCR-2. However, there was a perfect correlation between the two RT-PCRs, with a PPV of 100% and an excellent index of agreement (kappa = 0.88). Therefore, most RT-PCR results were really true positive, and VIT and IFA, which missed some of them, appeared to be less sensitive.
[Virological diagnosis and treatment of respiratory syncytial virus infections].
Respiratory syncytial virus infections occur frequently in children, often localized in the upper respiratory tract. Outcome is usually quite satisfactory, but in nearly one half of the infants lower tract involvement may cause severe respiratory insufficiency leading to hospitalization in about 1% of the cases. Its frequency has been estimated at 20 to 30% of the viral infections in hospitalized infants, 10 times the frequency of the other respiratory virus. Respiratory syncytial epidemias last about 4 to 5 months with a seasonal peak in december and january. The direct detection of respiratory syncytial antigens in nasal specimens by immunofluorescence or enzymatic immunoassay is the key to rapid diagnosis. They appear as performant and more convenient than specific IgM antibodies or nucleic acid detections, and than virus isolation on cell culture, which is justified to evaluate strain sensitivity to ribavirin. Immunofluorescence has also been used to identify the subgroups A and B from 1981 to 1993, and respiratory syncytial subgroup A seems to signify more severe disease. Symptomatic assistance may require hydratation, oxygenotherapy and respiratory physical therapy. Antibiotics should not be given as a routine treatment since bacterial superinfection is infrequent, but may be indicated in cases with associated signs of complications. Indications for bronchodilators and corticosteroids are still under debate. Significant results have been obtained with ribavirin and specific anti respiratory syncytial immunoglobulins but further evaluations are still required to precise their use in clinical practice.
Chromium and parenteral nutrition in children.
Chromium (Cr) dosage was assayed in i.v. nutrition, serum, and losses of five children on total parenteral nutrition for > or = 4 weeks. The Cr supply (4.7 +/- 1.2 micrograms/kg/day) was above recommended levels (0.5 microgram/kg/day). Serum (18.2 +/- 1.8 micrograms/L) and urine (37.4 +/- 10.5 micrograms/L) were also higher than control values (0.7-0.9 microgram/L and 0.2-0.8 microgram/L, respectively). Serum and urine Cr concentrations displayed a positive correlation. Serum Cr and Fe showed a negative correlation. These results confirm the potential toxicity of Cr previously reported in animals. Cr levels of i.v. nutrition solutes should be checked thoroughly.
Pharmacokinetics of fusidic acid after a single dose of a new paediatric suspension.
The pharmacokinetics of fusidic acid (Fucidine, Leo Laboratories) were studied in 10 children after single oral dosing with 20 mg/kg of a new banana-flavoured paediatric suspension (titrating at 50 mg/ml). Nine blood samples were drawn from each child at 0, 1, 2, 3, 6, 8, 12, 24 and 48 h following dosing with the antibiotic. Serum fusidic acid levels were measured by high-performance liquid chromatography (HPLC). A model-independent method was used for the pharmacokinetic analysis. Results were compared with those obtained after dosing eight healthy adult volunteers with 500 mg of sodium fusidate by parenteral administration (infusion) then per os. The acceptability of the single dose was good. The terminal elimination half-life t1/2 (h) and the mean residence time (MRT, h) of fusidate were similar to those determined in healthy adults after oral dosing, i.e. 16.0 +/- 14.5 versus 16.0 +/- 3.5 and 17.7 +/- 12.1 versus 17.7 +/- 2.5, respectively. In contrast, the oral bioavailability of the suspension (Fapprox., %) was relatively low: of the order of 22.5 versus 91.0% for tablets in the healthy adult, which justifies the use of a relatively higher dose in the child. This led to the calculation of an estimated total clearance (Clest., ml/min) significantly less than that in the healthy adults, while the estimated apparent volume of distribution (Vd, litre/kg) was significantly increased (10.4 +/- 9.1 versus 21.8 +/- 2.1 and 0.73 +/- 0.53 versus 0.30 +/- 0.04, respectively). Fusidic acid is normally excreted in metabolized form (98%). The decrease in clearance could be attributed to the almost immediate saturation of liver enzymes in immature infants.(ABSTRACT TRUNCATED AT 250 WORDS)
Dose-response study of metoclopramide in gastroesophageal reflux in infancy.
Twenty-four infants, 1 to 18 months-old, who were referred to four centers for suspected gastroesophageal reflux and whose esophageal pH after a standard formula meal given at 9 to 10 am (Ho-day 1) fulfilled the criterion of being < 4 for more than 5% of the time between H1 and H6, entered a double-blind placebo-controlled dose-response trial of metoclopramide (M). Twenty-four hours later (day 2), patients were randomly assigned to receive either placebo or a single 0.1, 0.2, or 0.4 mg/kg dose of metoclopramide, 30 min before the formula meal (n = 6/group) and the procedure was repeated. Metoclopramide plasma concentration was measured 1 h after dosing (C1h). On day 1, the time during which the esophageal pH was < 4 (time pH < 4), and five other parameters, were not significantly different in the treatment groups. On day 2, time pH < 4 (m(SD)) decreased from 33(13) to 30(33), 39(27), to 36(47), 42(15) to 18(13) and 48(25) to 31(46) min in the placebo, 0.1, 0.2, and 0.4 mg/kg metoclopramide groups, respectively. Possibly due to the large interindividual variability, no significant differences in parameters were observed between the different groups. None of the parameters correlated with the metoclopramide dose. Time pH < 4 expressed as the difference between day 1 and day 2, relative to day 1, decreased significantly as a function of C1h. No side effects were observed. A similar study should be performed after repeated dosing regimen.
[Prevalence and clinical aspects of A and B subgroups of respiratory syncytial virus infection. Observation of 8 consecutive epidemics between 1982 and 1990].
BACKGROUND: Infants suffering from respiratory syncytial virus (RSV) infection can have severe responses that require intensive care. This study compares the epidemiologic patterns and the severity of respiratory diseases produced by RSV strain subtypes A and B. POPULATION AND METHODS: The prevalence of RSV subgroups was studied over 8 consecutive outbreaks from 1982 to 1990. The files of 73 infants aged from 1 to 24 months admitted because of RSV infection between October 1987 and March 1990 were studied. The criteria of severity were tachypnea and/or the use of the accessory muscles for respiration, apnea and/or cyanosis, hospitalization for > 8 days, hypercapnia and/or acidosis, oxygen therapy, use of corticosteroids and/or bronchodilators, nutritional difficulties. RESULTS: A total of 374 RSV strains were isolated: 142 were group A and were 232 group B. Subtype A predominated during the winter 1987-1988 and subtype B during 1983-1984, 1984-1985 and 1989-1990. Some indicators of severity, such as degree of respiratory distress, duration of hospitalization and levels of oxygen saturation, were correlated with A subgroup infections, but the difference in the severity index for the two subtypes was not statistically significant. CONCLUSIONS: The results are not consistent with other previous reports, perhaps because different indicators of severity were used in this study and infants less than one month old or having other underlying diseases were excluded.