PubMed Health⌕ Search

Biomedical subjects

F Moulin

Publications and source records attributed to F Moulin.

At least 37 records · Page 2Linked to original sources
PubMed2001

Hepatic and extrahepatic factors critical for liver injury during lipopolysaccharide exposure.

Bacterial endotoxin [lipopolysaccharide (LPS)] causes liver injury in vivo that is dependent on platelets, neutrophils [polymorphonuclear leukocytes (PMNs)], and several inflammatory mediators, including thrombin. We tested the hypothesis that thrombin contributes to LPS-induced hepatocellular injury through direct interactions with platelets and/or PMNs in vitro. Perfusion of isolated livers from LPS-treated rats with buffer containing thrombin resulted in a significant increase in alanine aminotransferase (ALT) activity in the perfusion medium, indicating hepatocellular damage. This effect was completely abolished by prior depletion of PMNs from the LPS-treated donor rats but not by depletion of platelets, suggesting interaction between thrombin and PMNs in the pathogenesis. Thrombin did not, however, enhance degranulation of rat PMNs in vitro, and it was not directly toxic to isolated rat hepatocytes in the presence of PMNs even after LPS exposure, suggesting that hepatocellular killing by the PMN-thrombin combination requires the intervention of an additional factor(s) within the liver. In livers from naive donors perfused with buffer containing PMNs and LPS, no injury occurred in the absence of thrombin. Addition of thrombin (10 nM) to the medium caused pronounced ALT release. These results indicate that thrombin and PMNs are sufficient extrahepatic requirements for LPS-induced hepatocellular damage in intact liver.

Alanine Transaminase↗
PubMed2001

Association of the apolipoprotein E epsilon4 allele with late-onset depression.

Apolipoprotein E (ApoE) phenotyping was determined in 42 subjects with Alzheimer's disease (AD), 49 with depression, including 26 with early-onset depression (EOD) and 23 with late-onset depression (LOD), and 49 controls. In the EOD group, the frequency of the ApoE epsilon4 allele was not different from the control frequency (p = 0.532) but was significantly lower than in AD (p < 0.001). In the LOD group, the ApoE epsilon4 frequency was significantly higher than in the controls (p = 0.034) but was not different from that in the AD group (p = 0.229). Individuals with ApoE epsilon4 were at greater risk of getting AD (odds ratio, OR = 5.5, 95% confidence interval, CI, 2.0-14.0) or LOD (OR = 6.1, 95% CI, 1.9-19.0) than of EOD (OR = 0.7, 95% CI, 0.2-2.5). These results suggest an association between the ApoE epsilon4 allele frequency and LOD. Patients with LOD could be at risk of developing AD by an epsilon4-dependent pathway.

Age of Onset↗
PubMed2001

Fluoroquinolones in paediatrics.

The fluoroquinolones are an important group of antibiotics, which are widely used in adult patients because of their high penetration in tissues and bactericidal activity. However, they are not licensed for paediatric use (except the limited indication of Pseudomonas infection in cystic fibrosis) because of their potential to cause joint toxicity (observed in experiments using juvenile animal models). In recent years, there has been a change in the susceptibility of pathogens to widely used antibiotics; however, many of these pathogens remain sensitive to the fluoroquinolones (agents which can often be administered orally to treat severe infections). Fluoroquinolones have a number of potential indications in children: cystic fibrosis, intestinal infections due to resistant strains of Salmonella spp. and Shigella spp., severe infections due to Enterobacteriaceae (including the neonatal period), complicated urinary tract infections, the immunocompromised host, and some mycobacterial infections. The third generation fluoroquinolones have improved activity against Gram-positive bacteria and could be useful in respiratory tract, and ear, nose and throat infections in adult patients. Their potential role in routine use for paediatric patients will remain limited because of potential joint complications and the availability of other treatment options. However, available clinical data does indicate that the incidence of arthrotoxicity in children treated with ciprofloxacin appears to be the same as that in adult patients. The use of other fluoroquinolones is too rare to obtain meaningful information on their toxicity in children. For future fluoroquinolones, pneumococcal meningitis will probably be a potential indication. Despite their important activity, fluoroquinolones remain a second-line treatment in children, for use following the failure of a well established antibiotic treatment, to avoid potential adverse effects and the emergence of resistant strains.

Anti-Infective Agents↗
PubMed2000

Sequential colonization by Streptococcus pneumoniae of healthy children living in an orphanage.

A prospective study of nasopharyngeal colonization by Streptococcus pneumoniae in the exceptional conditions of a closed community of abandoned children was done over a 1-year period; 71 children (age <24 months) were studied monthly. S. pneumoniae was isolated from 58 (81.7%), and 94.5% of the 111 isolates were resistant to penicillin. The mean rate of carriage was estimated at 57.4%, ranging from 42.8% to 70.4%. Children were sequentially colonized by a mean of 3 different isolates. The mean duration of carriage for a given isolate was approximately 2.2 months. Serotyping and molecular typing by pulsed-field gel electrophoresis showed that children were colonized by a limited number of clones belonging to only 4 serotypes and 4 pulsotypes. These clones rapidly spread in the community and colonized the children in waves, with a rapid turnover of S. pneumoniae isolates, facilitated by close contact between children.

Electrophoresis, Gel, Pulsed-Field↗
PubMed2000

[Procalcitonin in pediatric emergencies: comparison with C-reactive protein, interleukin-6 and interferon alpha in the differentiation between bacterial and viral infections].

OBJECTIVE: Procalcitonin concentration increases in bacterial infections but remains low in viral infections and inflammatory diseases. The change is rapid and the molecule is stable making it a potentially useful marker for distinguishing between bacterial and viral infections. PATIENTS AND METHODS: Procalcitonin (PCT) was determined with an immunoluminometric assay on plasma collected at admission in 436 infants and children hospitalized for bacterial or viral infection. It was compared with C reactive protein, interleukin-6 and interferon-alpha measured on the same sample. RESULTS: PCT was 41.3 +/- 77.4 micrograms/l in children with septicemia or bacterial meningitis (n = 53), 0.39 +/- 0.57 microgram/l in children with viral infection (n = 274) and 3.9 +/- 5.9 micrograms/l in children with a localized bacterial infection who had a negative blood culture (n = 109). PCT was > 1 microgram/l in 126 children with a localized or systemic bacterial infection (sensitivity 78%). PCT was < 1 microgram/l in 258 children with a viral infection (specificity 94%). For differenciation between viral and bacterial infections, CRP value > or = 20 mg/l, IL-6 > 100 pg/ml and interferon-alpha > 0 Ul/ml have 85, 48 and 76% sensitivity and 73, 85 and 92% specificity respectively. CONCLUSIONS: In this study, a PCT value of 1 microgram/l or greater had better specificity, sensitivity and predictive value than CRP, IL-6 and interferon-alpha in children for distinguishing between viral and bacterial infections. PCT may be useful in pediatric emergency room for making decision about antibiotic treatments.

Adolescent↗
PubMed2000

The apolipoprotein E epsilon4 allele and the response to tacrine therapy in Alzheimer's disease.

The objective of our study was to evaluate the effects of the apolipoprotein E (ApoE) phenotype and gender on the response to tacrine treatment in Alzheimer's disease (AD). ApoE phenotyping was performed on 76 patients treated with tacrine for AD. This group comprised 33 ApoE epsilon4 allele carriers (epsilon4+) and 43 non-epsilon4 carriers (epsilon4-). Patients were treated blindly in relation to the ApoE phenotype, with incremental tacrine dosages ranging from 40 mg/day up to the highest dosage (160 mg) tolerated without side-effects. At least 6 weeks elapsed between each increase. Changes in the scores for the Alzheimer Disease Assessment Scale-Cognitive Component (ADAS-Cog) between baseline and each increment in dosage were assessed in the epsilon4- and epsilon4+ groups. The cut-off point for being considered as responsive to tacrine treatment was a 4-point decrease in the ADAS-Cog score. There was no tendency for the epsilon4- carriers to respond better than the epsilon4+ carriers. When patients were stratified by gender, no differences were found between the effects of the treatment on men and women. Consequently, these results do not support the hypothesis that the ApoE phenotype and gender are predictors of the response to tacrine in AD patients.

Aged↗
PubMed2000

Reduced lung diffusion capacity after Mycoplasma pneumoniae pneumonia.

BACKGROUND: Mycoplasma pneumoniae is a frequent but underdiagnosed cause of community-acquired pneumonia (CAP) in children, and appropriate macrolide treatment is often given late. The aim of this work was to estimate the frequency of pulmonary involvement in children 6 months after a clinical episode of Mycoplasma CAP. METHODS: We measured carbon monoxide diffusion capacity (TLCO) and conducted spirometric tests in 35 children without asthma or chronic lung disease (ages 4.5 to 15 years), 6 months and 1 year after acute CAP caused by M. pneumoniae (23 children), pneumococci (5 children) or viruses (7 children). Only 11 of 23 patients with M. pneumoniae CAP required hospitalization, whereas all the patients with pneumococcal or viral pneumonia were admitted to hospital. RESULTS: Lung volumes and spirometric tests were normal for all children. TLCO was normal 6 months after pneumococcal or viral pneumonia (87 to 112% of expected values for height and sex). After acute M. pneumoniae CAP, 11 of 23 patients (48%) had TLCO values <80% of the expected value. The extent of change in lung diffusion capacity was correlated with the delay to diagnosis and treatment: TLCO was low in 8 of 11 patients given macrolide treatment 10 days or more after the onset of acute symptoms vs. only 3 of 10 patients given appropriate treatment in the first 10 days. TLCO was low in 7 of 7 who received macrolide therapy for <2 weeks. TLCO had increased slightly after 1 year in the 5 patients retested after a new course of macrolide treatment. TLCO reached the lower normal range in 2 patients controlled after 3 years. CONCLUSIONS: The abnormal TLCO values suggest that some children with Mycoplasma pneumonia have reduced pulmonary gas diffusion after recovery from the illness. The reduction is related to delay and short macrolide therapy.

Adolescent↗
PubMed1999

[Coincidental outbreaks of rotavirus and respiratory syncytial virus in Paris: a survey from 1993 to 1998].

PATIENTS AND METHODS: In a pediatric hospital of Paris, from 1993 to 1998, respiratory secretions were positive for respiratory syncytial virus (RSV) in 26.3% of 4,738 children (0-5 years) examined or hospitalized for lower respiratory tract infections. Rotavirus detection was positive in stools of 23.7% of the 8,537 children of the same age with acute diarrhea. RESULTS: The RSV epidemic peak occurred annually in Paris in December and the rotavirus outbreak peaks were observed in December/January. The winter seasonal peaks remained constant for both pathogens and the temporal appearance of these peaks was constant from 1993 to 1998. Fifty to sixty-one percent of rotavirus and 77 to 92% of RSV infections were observed in November, December or January. These simultaneous outbreaks provoked important problems in hospital organization and prevention of nosocomial infections. CONCLUSION: The coincidence of RSV and rotavirus peaks is not found in all countries. The epidemic patterns have to be checked in other parts of France and Europe because this could be important when active immunization programs will be available for these two pathogens.

Child, Preschool↗
PubMed1999

Interferon-alpha in viral and bacterial gastroenteritis: a comparison with C-reactive protein and interleukin-6.

The aim of the study was to identify serum markers able to differentiate bacterial and viral origin in acute diarrhoea. Interferon-alpha (INF-alpha), C-reactive protein (CRP) and interleukin-6 were determined on admission in the sera of 119 children aged between 1 mo and 14 y who were hospitalized for rotavirus (n = 60) or bacterial diarrhoea (Salmonella spp. 39 cases, Shigella spp. 15 cases, Campylobacter jejuni 5 cases). CRP concentration was >10 mg/l in 48.3% of children with viral gastroenteritis and 86.4% of children with bacterial gastroenteritis. IL6 concentration was >100 pg/ml in 11.7% and 26.3% of cases, respectively. INF-alpha was detected in 79.1% of children with rotavirus (sens 79%) and in 3.5% (spec 93%) with bacterial gastroenteritis. However the INF-alpha assay takes 48 h and pathogens are often identified from stools before interferon results are available. We found that serum markers are not discriminating enough to differentiate between viral and bacterial gastroenteritis in emergency cases.

Acute Disease↗
PubMed1999

Comparison of procalcitonin with C-reactive protein, interleukin 6 and interferon-alpha for differentiation of bacterial vs. viral infections.

BACKGROUND: Procalcitonin (PCT) concentration increases in bacterial infections but remains low in viral infections and inflammatory diseases. The change is rapid and the molecule is stable, making it a potentially useful marker for distinguishing between bacterial and viral infections. METHODS: PCT concentration was determined with an immunoluminometric assay on plasma collected at admission in 360 infants and children hospitalized for bacterial or viral infection. It was compared with C-reactive protein (CRP), interleukin 6 and interferon-alpha measured on the same sample. RESULTS: The mean PCT concentration was 46 microg/l (median, 17.8) in 46 children with septicemia or bacterial meningitis. PCT concentration was > 1 microg/l in 44 of 46 in this group and in 59 of 78 children with a localized bacterial infection who had a negative blood culture (sensitivity, 83%). PCT concentration was > 1 microg/l in 16 of 236 children with a viral infection (specificity, 93%). PCT concentration was low in 9 of 10 patients with inflammatory disease and fever. A CRP value > or =20 mg/l was observed in 61 of 236 patients (26%) with viral infection and in 105 of 124 patients (86%) with bacterial infection. IL-6 was > 100 pg/ml in 14% of patients infected with virus and in 53% with bacteria. A secretion of interferon-alpha was found in serum in 77% of viral infected patients and in 8.6% of bacterial infected patients. CONCLUSIONS: In this study a PCT value of 1 microg/l or greater had better specificity, sensitivity and predictive value than CRP, interleukin 6 and interferon-alpha in children for distinguishing between viral and bacterial infections. PCT values are higher in invasive bacterial infections, but the cutoff value of 1 microg/l indicates the severity of the disease in localized bacterial infection and helps to decide antibiotic treatment in emergency room. PCT may be useful in an emergency room for differentiation of bacterial vs. viral infections in children and for making decisions about antibiotic treatments.

Adolescent↗
PubMed1998

[Procalcitonin, C-reactive protein and interleukin 6 in bacterial and viral meningitis in children].

OBJECTIVES: In young children with meningitis, blood or cerebrospinal fluid (CSF) analysis cannot differentiate all cases of viral meningitis (VM) from bacterial meningitis (BM). Empirical antibiotic therapy is often given. As new markers are needed, we compared serum proCalcitonin (PCT) with CSF analysis for C-reactive protein (CRP) and interleukin-6 (IL6). PATIENTS AND METHODS: PCT was measured with a chemoluminescent assay in the sera of 23 children (aged 3 months to 14 years) hospitalized for BM and in 51 patients with VM. RESULTS: Initial CRP (mean 143.3 mg/l, range 28-351 and mean 13.9, range 1-48), CSF proteins (mean 2.2, range 0.4-4.74 and mean 0.57, range 0.12-2.72) and white blood cell count in CSF (range 240-17500 and 20-3200) in BM and VM respectively, were not sufficiently discriminative to distinguish between BM and VM. Twenty-four of the 51 patients with VM were given antibiotics. IL6 values at admission showed an overlap zone (> 100 pg/ml in 7/19 patients with VM and < 100 pg/ml in 1/8 patients with BM. PCT was discriminative in all cases: mean PCT in BM was 61 micrograms/l (range 4.8-335) and 0.33 in VM (range 0-1.7; p < 0.001). No production of PCT was detected in CSF. After antibiotic therapy, PCT decreased and reached undetectable levels after recovery. CONCLUSION: PCT is a sensitive and specific marker for early diagnosis of viral meningitis versus bacterial meningitis in children.

Adolescent↗
PubMed1998

[Nosocomial urinary tract infections: retrospective study in a pediatric hospital].

Urinary tract infections (UTI) are the most frequent nosocomial infection in the adult, yet very few data are available concerning these infections in children. In a retrospective 1-year study in a paediatric hospital, we analysed the incidence of nosocomial UTI and the characteristics of the affected children. The incidence was of 1.97/1,000 admissions which represented 6.8% of all UTI diagnosed by the microbiology laboratory. Most cases were in surgery and neurology wards. The frequency was inversely proportional to the age, with 50% of children being less than 2 years old. Pathogens most frequently isolated were E coli (39%), Pseudomonas sp (12.1%) and Enterococcus sp (12.1%). When compared with the organisms found in all the urine cultures during the same period, two organisms were more frequently found in nosocomial urinary tract infections: Pseudomonas sp and Candida sp. Most patients presented one or more risk factors, mainly:bladder catheterisation (41.4%), prior antibiotic therapy (62%), cerebral palsy (6.9%). No bacteriema was observed. The diagnosis of nosocomial UTI must be interpreted with caution and needs close collaboration between microbiologists and paediatricians. These infections increase the cost of hospitalisation, but only exceptionally do they present with complications. Some risk factors are inherent in hospital conditions, but others can be reduced by improving hand washing or by changing catheterisation practices.

Adolescent↗
PubMed1997

Etiology and response to antibiotic therapy of community-acquired pneumonia in French children.

The aim of this study was to determine the etiologic agents associated with community-acquired pneumonia in 104 French children ages 18 months to 13 years. Potential respiratory pathogens were identified in 87 (85%) cases; these included respiratory syncytial virus in ten, other viruses in 20, Streptococcus pneumoniae in 14 and Mycoplasma pneumoniae (diagnosed by serologic procedures) in 43. Of 32 patients with Mycoplasma pneumoniae infection who were initially treated with beta-lactam antibiotics, 30 failed treatment. Recovery from mycoplasma infection occurred rapidly in patients treated with macrolide antibiotics (which included spiramycin in 31 patients, josamycin in 7, and erythromycin in 3); however, cough persisted in 12 patients for one month. The high frequency of Mycoplasma pneumoniae in children over 18 months of age must be considered when selecting an antibiotic for initial therapy.

Adolescent↗
PubMed1997

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↗
PubMed1996

[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↗
PubMed1996

Thrombin is a distal mediator of lipopolysaccharide-induced liver injury in the rat.

Previous results demonstrated that rats given Escherichia coli lipopolysaccharide (LPS; 4 mg/kg, i.v.) experience hepatocellular necrosis that begins within 4 hr and that prior treatment with anticoagulants (e.g., heparin) which target thrombin prevents the liver injury. In this study, hepatocellular injury, as marked by increased plasma alanine aminotransferase (ALT) activity and histologic changes, was prevented when heparin or hirudin was administered to rats shortly before the onset of injury. These results suggest that thrombin is a critical mediator that acts distally in the series of inflammatory events that culminates in hepatocellular damage. To explore further this hypothesis, livers isolated from rats 2 hr after LPS administration were perfused with various media. Perfusion of livers with medium comprising diluted blood from heparin-treated donors resulted in no release of ALT activity. By contrast, perfusion with similar medium anticoagulated with ancrod, which prevents clotting by depleting fibrinogen but does not inhibit thrombin, resulted in hepatocellular injury evidenced as a time-dependent appearance of ALT activity in the medium. Moreover, when livers from rats treated 2 hr previously with LPS were perfused with buffer to which thrombin had been added, injury resulted. No injury resulted when thrombin was omitted from the buffer or when livers from saline-treated rats were used. These results indicate that thrombin is a critical and distal mediator of LPS-induced liver damage and contributes to hepatocellular injury through a mechanism that is independent of clot formation. Furthermore, inflammatory events triggered by LPS exposure are a prerequisite for thrombin-induced injury.

Alanine Transaminase↗