[N-methyl-D-aspartate receptor antibody encephalitis: value of immunomodulatory therapy]. / Encéphalite à anticorps anti-récepteurs N-méthyl-D-aspartate (NMDA-R) : place des immunomodulateurs.

INTRODUCTION: Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is little known to pediatricians and likely underdiagnosed. The child's vital and cognitive prognosis is at stake. The use of immunomodulatory drugs, such as rituximab has led to spectacular results, but many questions remain about its mode of action in this type of pathology. CASE REPORT: We report the case of a 6-year-old girl with no medical history, admitted for status epilepticus preceded by behavior symptoms and sleep disorders. Gradually, the child became bedridden, mute, and animated by predominantly orofacial dyskinesia. Examinations were normal (cerebrospinal fluid [CSF] analysis, brain MRI). The diagnosis was established by the presence of NMDA-R antibodies in the CSF. After exclusion of a tumor-associated syndrome, treatment was started initially by intravenous immunoglobulins, then by plasma exchange, and finally rituximab. The patient was cured with rituximab despite an unusually early recovery of the B-cell pool. DISCUSSION: Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a severe but potentially reversible neurologic disorder only recently described, even in childhood. It may be reversible without sequelae if diagnosed and treated early. The use of immunomodulatory therapy, such as rituximab seemingly improves the outcome. Immunological monitoring is needed to better understand its mechanism of action in autoimmune diseases of the nervous system in childhood.

Population pharmacokinetics and pharmacogenetics of tacrolimus in de novo pediatric kidney transplant recipients.

The aim of this study was to develop a population pharmacokinetic model of tacrolimus in pediatric kidney transplant patients, identify factors that explain variability, and determine dosage regimens. Pharmacokinetic samples were collected from 50 de novo pediatric kidney transplant patients (age 2-18 years) who were on tacrolimus treatment. Population pharmacokinetic analysis of tacrolimus was performed using NONMEM, and the impact of variables (demographic and clinical factors, and CYP3A4-A5, ABCB1, and ABCC2 polymorphisms) was tested. The pharmacokinetic data were described by a two-compartment model that incorporated first-order absorption and lag time. The apparent oral clearance (CL/F) was significantly related to body weight (allometric scaling); in addition, it was higher in patients with low hematocrit levels and lower in patients with CYP3A5*3/*3. The population pharmacokinetic-pharmacogenetic model developed in de novo pediatric kidney transplant patients demonstrated that, in children, tacrolimus dosage should be based on weight, hematocrit levels, and CYP3A5 polymorphism. Individualization of therapy will enable the optimization of tacrolimus exposure, with resultant beneficial effects on kidney function in the initial post-transplantation period.

Mortality in pediatric renal transplantation: a study of the French pediatric kidney database.

OBJECTIVE AND METHODS: To assess patient survival in pediatric renal transplantation, we retrospectively reviewed 573 transplants in 553 patients, registered from 1995 to 2005. RESULTS: Mean age at transplantation was 9.9 years. Patient survival at 1, 5 and 10 years was respectively 99%, 97% and 96%. Death occurred at a median time of 2.6 years after transplantation. Long-term patient survival was significantly lower in recipients younger than 5 years old. Seventeen patients (3.1%) died. Two deaths occurred while under maintenance dialysis. Among the remaining patients, the two main causes of death were infections (33%) and malignancies (27%). Interestingly, initial disease-related complications were a major cause of death (34%). CONCLUSION: A low mortality rate was observed, with the majority of deaths due to malignancies and infections, and with a notable participation of complications related to the initial disease. No impact of cardiovascular disease was noted with the given follow-up period. Improvements in managing immunosuppression may contribute to reducing mortality in pediatric renal transplantation.

[Study of correlations between antibiotics prescriptions and guidelines in a neonatal intensive care unit]. / Etude de la corrélation entre les prescriptions d'antibiotiques et les recommandations dans une unité de soins intensifs néonatals.

UNLABELLED: The increasing use of wide spectrum antibiotics has been reported to be associated with a greater prevalence of multi-resistant bacteria. OBJECTIVES: The aims of this study were to survey the use of antibiotics and to evaluate the correlations between patterns of prescription of antibiotics and prescription guidelines in a neonatal intensive care unit. MATERIAL AND METHODS: In this 6-month study, all newborns admitted to the NICU and treated with antibiotics were included. Data regarding criteria of antibiotic prescription, length of treatment, and criteria of withdrawing treatment were collected. The correlation between prescriptions and guidelines was evaluated a posteriori by a non-prescriber physician. One hundred and sixteen newborns were included, of whom nine had received antibiotics on more than one occasion. Mean gestational age was 33.5 weeks. In 82% of cases, the reason for hospitalisation was respiratory distress syndrome. RESULTS: Patients received systemic antibiotics for primary infection (78%), nosocomial infection (17%) and postsurgical prophylaxis (5%). Suspected foeto-maternal infections (SFMI) were the dominant features of primary infection (96%). In 49% of cases, suspected infection was not proven and justified withdrawal of treatment within 3 days. Sixty percent of nosocomial infections occurred in newborns with gestational ages of less than 28 weeks. Bacterial criteria were decision-making factors only in nosocomial infections. An absence of observance of guidelines occurred in 9% of treated newborns, and in most cases involved excessive length of treatment. CONCLUSION: These results show: (1) the majority of antibiotic prescriptions were for not proven SMFI; (2) a low rate of nosocomial infections; (3) the predominance of nosocomial infections in premature newborns; (4) less than 10% of non-observance of guidelines. It appears necessary to develop more precise guidelines to limit antibiotic use and to evaluate them regularly.

Influenza Diagnosis and Treatment : Impact of New Antivirals on Perceived Treatment Behaviours during Recent Influenza Outbreaks.

BACKGROUND: In the past patients and doctors have often underestimated the serious nature and impact of influenza outbreaks. Our aim was to determine current perceptions and behaviours among the general public and physicians regarding influenza illness and its treatment in the US, Japan and Europe during two influenza seasons (1999/2000 [99/00] and 2000/2001 [00/01]). METHODS: A survey was conducted among patients (n = 7583 in 99/00 and n = 7790 in 00/01) and physicians (n = 609 in 99/00 and n = 808 in 00/01). RESULTS: Patients recognise influenza as a severe illness, identifying it by signs and symptoms of high fever, chills and feverishness, muscle aches/pains and cough. Similarly, physicians use these signs and symptoms to clinically diagnose influenza. Physicians report that most consulting patients (53-93%) would present within 2 days of the onset of symptoms, i.e. within the time needed to receive maximum treatment benefit from the newer antivirals. However, most prescriptions or recommendations for influenza treatment in Europe were for antibiotics (30%) and analgesics or antipyretics (100%). Antivirals were recommended by only 10% of European doctors, compared with 45% of US physicians. In the past two influenza seasons the percentage of doctors using antivirals appropriately has increased from 47 to 62%. Antibiotic use in the US during the two seasons fell from 25 to 11%. CONCLUSION: Specific antiviral treatments are not yet widely used in Europe, but our survey in the US suggests that with the high and early consultation rates and prompt outbreak information they may be used effectively to reduce the influenza burden.

Prenatal diagnosis and postnatal outcome of congenital megalourethra. Report of two cases.

We present 2 cases of congenital megalourethra diagnosed by prenatal ultrasound scan during the second trimester of pregnancy. The first one was associated with features suggesting prune belly syndrome (PBS) in contrast to the other one. Fetal urine biochemistry and fetal serum beta2-microglobulin was used to rule out severe renal impairment that would have led to postnatal renal failure soon after birth. In both cases, after extensive counselling, the parents opted against termination of pregnancy and in both cases vaginal delivery of a live neonate occurred. Postnatal follow-up demonstrated that the two infants were found to have mildly altered renal function without any physical or mental development delay. Association with features of PBS didn't seem to influence the severity of renal function impairment however, but PBS may influence parents' decision regarding termination because of additional corrective surgery and further infertility.

Chronic renal failure and portal hypertension--is portosystemic shunt indicated?

We report two girls with histories of recessive polycystic kidney disease. Both were on maintenance hemodialysis. They had undergone surgical distal portocaval shunt because of portal hypertension. Later, bilateral nephrectomy was performed, and they presented with hepatic encephalopathy (HE) and evolution towards irreversible hepatic coma and death. Portosystemic shunt is the treatment of choice of portal hypertension. The kidney plays a pivotal role in ammonia disposal during portosystemic shunt. Thus, we stress the risk of HE after portosystemic shunt followed by bilateral nephrectomy in patients with end-stage renal failure and suggest that combined liver-kidney transplantation should be considered.

[Prevalence and distribution of congenital heart diseases in Indre-et-Loire. Evaluation of prenatal diagnosis (1991-1994)]. / Prévalence et répartition des cardiopathies congénitales en Indre-et-Loire. Evaluation du diagnostic anténatal (1991-1994).

UNLABELLED: Congenital heart diseases are the most frequent malformation at birth. New technologies have improved diagnosis procedures (echocardiography and Doppler). The aim of our study was to evaluate the prevalence of congenital heart diseases, their different types, and the detection rate of antenatal diagnosis. METHODS: A retrospective study was performed for all infants with congenital heart disease (CHD), born between January 1st 1991 and December 31st 1994, and for all fetuses which died after disruption of pregnancy, in Indre-et-Loire (a French country). In all cases, CHD diagnosis was confirmed with echocardiography and Doppler. RESULTS: CHD prevalence in newborns was 9.8% and 10.4% for the total population including dead fetal material. A high proportion of septal defects (64.8%) was observed with muscular, isolated and small forms (< 3 mm) in 70.2% of cases. The prevalence of great vessels transposition (0.15%), left ventricular hypoplasia (0.11%), and atrioventricular septal defect (0.11%), were lower than in previous studies. The performance of antenatal diagnosis was estimated at 40.5% for the four years; the prevalence of detectable CHD was only 1.4/1000. The atrioventricular septal defect was the most frequently detected. CONCLUSION: Relative high prevalence of congenital heart disease in this French county is due to the high level of small septal defects. Prevalence of detectable CHD remains low, which explains in part the difficulties of improving the antenatal diagnosis.

Consequences of pulmonary inflations (sighs) on cerebral haemodynamics in neonates ventilated by high-frequency oscillation.

High-frequency oscillation (HFO) is a technique frequently used in neonatal resuscitation, but which has yet to be evaluated. The use of intrathoracic pressures may have an effect on the cerebral circulation of immature neonates. The aim of this study was to examine the variations in cerebral blood velocity and oxygenation during brief pulmonary inflations (sighs), by focusing on alveolar recruitment. In this prospective study performed in 13 intubated and ventilated neonates (alpha = 5%; 1-beta = 80%), mean blood velocity and Doppler Resistance Index were measured, and variations in chromophores concentrations were evaluated by near infrared spectroscopy. Brief inflations at 4 cm H2O above the mean regulated intra-thoracic pressure did not cause any variation in the parameters measured. An explanation for this discordance with animal studies may be the level of pressure chosen, which could be more appropriate for the pulmonary compliance of neonates.

[Arterial hypertension due to mercury poisoning: diagnostic value of captopril]. / Hypertension artérielle par intoxication au mercure: intérêt diagnostique du captopril.

BACKGROUND: Mercury poisoning is a rare cause of hypertension in children. Urinary excretion sometimes remains low despite severe clinical intoxication. CASE REPORT: A 32 month-old girl was admitted with hypertension, tachycardia, apathy, irritability and excessive sweating. Erythromelalgia and neurologic symptoms permitted the diagnosis of acrodynia. Urine mercury remained normal until chelation. Captopril significantly increased urine mercury concentration but failed to improve clinical manifestations. Clinical improvement required infusions of BAL for 5 days then oral dimercaptosuccinic acid for 3 months. Metal vapors originated from the mercury which spilled from a broken thermometer onto the carpet. COMMENTS: Low basal urine mercury could be associated with real mercury poisoning. Small amounts of metal mercury held in a thermometer could produce a high level of mercury vapor leading to intoxication in young children. The binding capacity of metal ions by captopril could be used to increase urine mercury output. Nevertheless, captopril therapy fails to improve acrodynia. Total elimination of mercury requires long-term therapy with BAL or dimercaptosuccinic acid. CONCLUSIONS: An unexpected mode of intoxication and low basal urine mercury are not decisive arguments against mercury poisoning, which is the only cause of acrodynia.