G. Chéron

Cytochrome P-450 expression in sudden infant death syndrome.

In the human liver, the major rise of the cytochrome P-450 isoform content occurs during the first months following birth (e.g., the high vulnerability period to sudden infant death syndrome (SIDS), a syndrome frequently associated with viral infection and drug hypersensitivity. We examined the expression of individual P-450 isoforms in liver samples collected postmortem from SIDS infants and compared values with those of control adults and children of the same age suffering from various pathologies. Hepatic microsomes were prepared and examined for their content in total P-450, the level of individual isoforms (CYP1A2, CYP2E1, CYP4A, CYP3A, and CYP2C) determined with specific antibodies and for their enzymatic activities. Total RNA was extracted and probed with several CYP cDNAs and oligomers. The overall hepatic P-450 content was not modified in SIDS infants. Among cytochrome P-450 isoforms, only CYP2C was markedly increased. This rise resulted from an accumulation of RNA encoding CYP2C and was associated with a stimulation of diazepam demethylation. The precocious expression of CYP2C in SIDS could result in a higher production of epoxyeicosatrienoic acids in the neonate, believed to act as relaxant of pulmonary smooth muscles. Its consequence might be the induction of fatal apnea in SIDS.

Molecular identification of viruses in sudden infant death associated with myocarditis and pericarditis

A subset of infants dying suddenly and unexpectedly have myocarditis with or without pericarditis found at autopsy. To address whether viruses known to cause infantile myocarditis and pericarditis might be present in such infants, we examined myocardium, liver and skeletal muscle for the presence of genomic sequences from adenovirus, cytomegalovirus, enterovirus and echovirus 22/23 in infants enrolled in a comprehensive evaluation protocol. We studied eight infants who died suddenly and unexpectedly with histologic evidence of myocarditis and/or pericarditis detected at postmortem examination. One infant with myocarditis and pericarditis had adenovirus genome detected in the myocardium. In an additional infant with severe pericarditis alone, enterovirus genome was detected in the liver. Although echovirus 22/23 has been associated with myopericarditis in young infants, no previous studies have used molecular methods to search for the genomic sequences of these viruses in clinical samples. No echovirus 22/23 genome was detected in the patients reported here. The significance of enterovirus and adenovirus genome in the tissues of two patients dying suddenly and unexpectedly remains speculative but raises the possibility that pathogenic viruses may cause little or no clinical symptoms and yet be contributory to sudden death in young infants.

Randomized Trial of Oral Versus Sequential IV/Oral Antibiotic for Acute Pyelonephritis in Children

OBJECTIVE: To confirm whether oral antibiotic treatment is as efficacious as sequential intravenous/oral antibiotic treatment in the prevention of renal scarring in children with acute pyelonephritis and scintigraphy-documented acute lesions. METHODS: In a prospective multicenter trial, children aged 1 to 36 months with their first case of acute pyelonephritis, a serum procalcitonin concentration ≥0.5 ng/mL, no known uropathy, and a normal ultrasound exam were randomized into 2 treatment groups. They received either oral cefixime for 10 days or intravenous ceftriaxone for 4 days followed by oral cefixime for 6 days. Patients with acute renal lesions detected on early dimercaptosuccinic acid scintigraphy underwent a follow-up scintigraphy 6 to 8 months later. RESULTS: The study included 171 infants and children. There were no significant differences between the 2 groups in any clinical characteristic. Initial scintigraphy results were abnormal for 119 children. Ninety-six children were measured for renal scarring at the follow-up scintigraphy (per protocol analysis population). The incidence of renal scarring was 30.8% in the oral treatment group and 27.3% for children who received the sequential treatment. CONCLUSIONS: Although this trial does not statistically demonstrate the noninferiority of oral treatment compared with the sequential treatment, our study confirmed the results of previously published reports and therefore supports the use of an oral antibiotic treatment of primary episodes of acute pyelonephritis in infants and young children.

Intussusception in infants and children: feasibility of ambulatory management

Abstract To evaluate the ambulatory management of ileo-colic intussusception in infants and children, a retrospective study over 3 years of 113 children treated for ileo-colic intussusception in a paediatric emergency department was undertaken with the aim of shortening the length of stay. A total of 113 children aged 10 days to 9 years (median 12 months) were treated for intussusception between January 1993 and December 1996. None had septic shock or peritoneal aeric effusion. Barium enema reduction was attempted in all patients. Successful reduction rate was 81%. Fifty patients (44.2%) were completely ambulatory managed and 42 were hospital-supervised after successful enema reduction. Twenty-one children underwent laparotomy after failure of enema. With the ambulatory device, costs were reduced (

Neurological consequences of vitamin B12 deficiency and its treatment.

1000/case) compared with conventional in-patient treatment. Conclusion Outpatient treatment of acute ileo-colic intussusception is secure and reduces costs. It depends on the willingness of the medical team but requires simultaneous adaptation of hospital funding to promote this trend.

Can procalcitonin measurement help the diagnosis of osteomyelitis and septic arthritis? A prospective trial

In developed countries, the vitamin B12 deficiency usually occurs in children exclusively breast-fed, whose mothers are vegetarians, causing low stores of vitamin B12. Symptoms of vitamin B12 deficiency appear during the second trimester of life and include failure to thrive, lethargy, hypotonia, and arrest or regression of developmental skills. A megaloblastic anemia can be present. One half of the infants exhibit abnormal movements before the start of treatment with intramuscular cobalamin, which disappear 1 or 2 days after. More rarely, movement disorders appear a few days after treatment, whereas neurological symptoms are improving. These abnormal movements can last for 2 to 6 weeks. If not treated, vitamin B12 deficiency can cause lasting neurodisability. Therefore, efforts should be directed to preventing deficiency in pregnant and breast-feeding women on vegan diets and their infants by giving them vitamin B12 supplements. When preventive supplementation has failed, one should recognize and treat quickly an infant presenting with failure to thrive and delayed development.

Cot death and myocarditis

ObjectivesProcalcitonin (PCT) is an accurate marker for differentiating bacterial infection from non-infective causes of inflammation or viral infection. However, there is only one study in children which tested procalcitonin as a diagnostic aid in skeletal infections. With this study we sought to evaluate the sensitivity, specificity and predictive values of procalcitonin for identifying bone and joint infection in children evaluated in the emergency department for non traumatic decreased active motion of a skeletal segment.MethodsPatients aged 1 month to 14 years were prospectively included in the emergency department when suspected for osteomyelitis or septic arthritis. Procalcitonin levels, C reactiv protein, white blood cell count were measured and bacteriological samples were collected before initiation of antibiotic treatment. Patients were assigned to 3 groups according to the degree of suspected infection: group 1 confirmed infection, group 2 presumed infection and group 3 non infected patients.ResultsThree hundred thirty nine patients were included (118 girls and 221 boys). Group 1 comprised 8 patients (2 had PCT levels > 0.5 ng/ml). Two had osteomyelitis and 6 septic arthritis. Forty children were incuded in group 2 (4 had PCT levels > 0.5 ng/ml). Eighteen had presumed osteomyelitis and 22 presumed septic arthritis. Group 3 comprised 291 children (9 PCT levels > 0.5 ng/ml) who recovered without antibiotic treatment. The specificity of the PCT as a marker of bacterial infection (comparing Group 1 and Group 3) was 96.9% [95% CI, 94.2-98.6], the sensitivity 25% [95% CI, 3.2-65.1], the positive predictive value (PPV) 18.2% [95% CI, 2.3-51.8] and the negative predictive value (NPV) 97.9% [95% CI, 95.5-99.2].ConclusionPCT is not a good screening test for identifying skeletal infection in children. Larger studies are needed to evaluate still more the place of PCT measurements in the diagnosis of osteomyelitis and septic arthritis.

Ontogenesis of CYP2C-Dependent Arachidonic Acid Metabolism in the Human Liver: Relationship with Sudden Infant Death Syndrome

We have investigated the hearts from 153 infants found dead in their cots at ages ranging from one month to one year. The deaths occurred over a period of five years (January 1986 to December 1990) and were studied in a center for the study of the sudden infant death syndrome located in Paris. The epidemiological characteristics of this group are:male predominance (sex ratio 1.43), age less than four months (82%), and a predominance of winter deaths. These are the characteristic features ofthe sudden infant death syndrome. Ofthe 143 children studied with the permission of their parents, 24 (16.8%–12 girls and 12 boys) had histological lesions consistentwith myocarditis according to the Dallas criteria. The histological diagnosis of myocarditis is based on the association of cellular necrosis with a mononuclear or mixed inflammatory infiltrate. Cytoplasmic vacuolization, the presence of inflammatory cells in myocytes, and rupture of the cell walls of myocardial fibres are the equivalent histological signs of cellular necrosis. Myocarditis was diversely associated with respiratory, hepatic, muscular, gastrointestinal and/or neurological involvement. Twelve infants had previously been ill. Two died during the course of a serious illness. In only four cases was a viral association demonstrated. This incidence of myocardial involvement, similar to thatdescribed elsewhere in the literature, suggests that myocarditis could be a pathogenic explanation of some deaths thought on general autopsy investigation to be sudden and unexplained.

Cerebrospinal fluid penetration of amikacin in children with community-acquired bacterial meningitis.

A modification of the human monooxygenase system have been previously associated with the sudden infant death syndrome (SIDS): the hepatic CYP2C content was markedly enhanced and resulted from an activation of CYP2C gene transcription. To determine the possible consequence of the up-regulation of CYP2C in SIDS, we examined the metabolism of arachidonic acid (AA) an endogenous substrate of CYP2C involved in the physiologic regulation of vascular tone. The overall AA metabolism was extremely low during the fetal period and rose after birth to generate 14,15 epoxyeicosatrienoic acid (EET), 11,12 EET and the sum of 5,6 dihydroxyeicosatrienoic acid (diHETE)+ω/ω-1 hydroxy AA. In SIDS, the accumulation of CYP2C proteins was associated with a significant increase in the formation of 14,15 and 11,12 diHETE, which were shown to be supported by individually expressed CYP2C8 and 2C9 and HETE1 (presumably 15 HETE). This increase was markedly inhibited by addition of sulfaphenazole, a selective inhibitor of CYP2C9. So, we propose that the higher CYP2C content in SIDS stimulates the production of EETs and diHETEs and might have severe pathologic consequences in children.

Apport du bromure d’ipratropium dans la prise en charge des crises d’asthme aux urgences

The penetration of amikacin into the cerebrospinal fluid (CSF) was studied with 16 children (mean age, 1 year and 9 months; range, 4 months to 8 years) with community-acquired bacterial meningitis. Amikacin was given intravenously at a dose of 7.5 mg/kg of body weight twice daily. CSF was collected on day 1, at the expected peak concentration of amikacin in CSF. The mean (standard deviation) concentration of amikacin in CSF was 1.65 (1.6) mg/liter. Concentrations of amikacin in CSF correlated significantly with CSF glucose levels on admission. The mean concentrations of amikacin in CSF were 2.9, 1.1, and 0.20 mg/liter in patients with CSF glucose levels of < 1, 1 to 2, and > 2 mmol/liter, respectively. Thus, amikacin penetrates the blood-brain barrier substantially in children with bacterial meningitis and achieves particularly high concentrations when CSF glucose level is < 1 mmol/liter on admission.