Case report: Febrile infection-related epilepsy syndrome in a 14-year-old girl with multiple organ failure and lethal outcome.

We report a case of an otherwise healthy 14-year-old girl with febrile infection-related epilepsy syndrome (FIRES), multiple organ failure (MOF), and ultimately a lethal outcome. This is a rare case of FIRES with MOF and consecutive death. Only a few cases have been described in the literature. The adolescent girl was initially admitted to our pediatric emergency department with a first episode of generalized tonic-clonic seizures after a short history of fever a week before admission. Seizures progressed rapidly into refractory status epilepticus without any evidence of the underlying cause, and treatment subsequently had to be escalated to thiopental anesthesia. Since the initial diagnostics showed no promising leads, the rare syndrome of FIRES was suspected, representing a catastrophic epileptic encephalopathy linked to a prior benign febrile infection. Methylprednisolone, intravenous immunoglobulins, and a ketogenic diet were initiated. Respiratory, circulatory, kidney, and liver failure developed during treatment, requiring increasing intensive care. Multiple attempts to deescalate antiepileptic treatment resulted in recurrent status epilepticus. A cranial MRI on the 10th day of treatment revealed diffuse brain edema and no cerebral perfusion. The patient was declared dead on the 11th day of treatment. FIRES should be taken into account in previously healthy children with a new onset of difficult-to-treat seizures after a short febrile infection when no other cause is apparent. First-line treatment, besides seizure control, is the early initiation of immunomodulatory therapy and the start of a ketogenic diet. As treatment is difficult and MOF may develop, patients should be transferred to a specialized children's hospital providing full intensive care.

Successful implementation of a rater training program for medical students to evaluate simulated pediatric emergencies.

Introduction: Simulation-based training is increasingly used in pediatrics to teach technical skills, teamwork, and team communication, and to improve potential deficiencies in pediatric emergency care. Team performance must be observed, analyzed, and evaluated by trained raters. The structured training of medical students for the assessment of simulated pediatric emergencies has not yet been investigated. Methods: We developed a rater training program for medical students to assess guideline adherence, teamwork, and team communication in simulated pediatric emergencies. Interrater reliability was measured at each training stage using Kendall tau coefficients. Results: In 10 out of 15 pairs of raters interrater reliability was moderate to high (tau>0.4), whereas it was low in the remaining 5 pairs of raters. Discussion: The interrater reliability showed good agreement between medical students and expert raters at the end of the rater training program. Medical students can be successfully involved in the assessment of guideline adherence as well as teamwork and team communication in simulated pediatric emergencies.

[Resuscitation of newborn infants]. / Geburtshilfliche Anästhesie--Erstversorgung und Reanimation von Neugeborenen.

Successful resuscitation of newborn infants depends on adequate preparation, exact evaluation and prompt initiation of support according to the recently updated recommendations by trained personnel. The key step in postnatal adaptation is the initiation of breathing with a subsequent increase in pulmonary blood flow and pulmonary gas exchange. Therefore, in compromised newborn infants, adequate ventilation is the most important step in cardiopulmonary resuscitation. Ventilation should be initiated with room air in term infants and with low concentrations of supplemental oxygen in preterm infants. Subsequently, oxygen supplementation should always be guided by pulse oximetry. Chest compressions are only effective if adequate ventilation has been ensured. The compression ventilation ratio remains 3:1. The prevention of heat loss and maintaining a normal body temperature by adequate measures is an essential part of the care for healthy as well as asphyxiated infants. Therapeutic hypothermia should only be initiated after successful resuscitation and consultation with the regional neonatal intensive care unit.

Lacticacidosis after short-term infusion of propofol for anaesthesia in a child with osteogenesis imperfecta.

We describe the case of a 7-year-old boy with osteogenesis imperfecta, who underwent anaesthesia with propofol-fentanyl-nitrous oxide-suxamethonium for orthopaedic surgery of a distal femur fracture. He developed lacticacidosis after short-term propofol infusion (150 min, mean infusion rate 13.5 mg.kg-1.h-1) associated with a prolonged recovery time without serious haemodynamic changes. The highest lactate concentration was 9.2 mmol.l-1 at 160 min after discontinuation of propofol. There was no significant increase in body temperature. The boy fully recovered.

Expression of prostanoid receptors in human lower segment pregnant myometrium.

Prostanoids, especially prostaglandin (PG) E(2), are important mediators of uterine relaxation and contractions during gestation and parturition. Inhibitors of PG formation as well as PG analogues are used to modulate uterine tonus. So far, only limited data are available regarding the expression of prostanoid receptors in human pregnant myometrium. In the present study, the expression of the receptors for PGE(2) (EP1, EP2, EP3, EP4), PGF(2alpha) (FP), prostacyclin (IP), and thromboxane A(2) (TP) in human pregnant myometrium was studied by RT-PCR, in situ hybridization and immunohistochemistry. Myometrial tissue was obtained from five women at term and not in labour and from two women who delivered preterm. Tissue specimens were excised from the upper edge of the transverse lower uterine segment incision. In all tissues analysed, EP1, EP2, EP3, EP4, FP, TP and IP receptor mRNA and protein was detected. mRNA expression for PGD(2) (DP) receptor was not detected in the majority of tissue specimens. EP1, EP2, EP4, IP, TP and FP receptor protein was detected on myometrial smooth muscle cells, whereas EP3 receptor protein was only expressed by stromal and endothelial cells. In situ hybridization experiments yielded similar results. The expression of the EP2 receptor mRNA was inversely related to gestational age. We suggest that the contractile effect of PGE(2) at term is probably mediated directly by the EP1 receptor expressed in myometrial smooth muscle cells and indirectly by the EP3 receptor expressed in stromal cells and a decrease in EP2 receptor expression.

Preschool development of very low birth weight children born 1994-1995.

UNLABELLED: This study reports on the developmental outcome of a sample of pre-term children with a birth weight < or =1500 g born in 1994 and 1995 studied at the age of 5 to 6 years. The sample included 60 out of 81 surviving pre-term children (74.1%) of a German neonatal intensive care unit which was matched to a control group of 60 kindergarten children of the same region. The results show significant differences between term and pre-term children with regard to their intellectual development, language comprehension, attentiveness, and hyperactivity. Moreover, the pre-term children required more early intervention to compensate for developmental problems. The developmental deficits were intensified by the presence of biological risk factors like increasingly low birth weight, bronchopulmonary dysplasia and intraventricular haemorrhage. CONCLUSION: differences between term and pre-term children still exist, although the early 1990s witnessed fundamental changes in the treatment of pre-term children. The persistence of these differences is explained mainly by the increase in the survival rate of children with high biological risk factors.

Expression of prostanoid receptors in human ductus arteriosus.

1. Prostaglandins play a major role in maintaining ductal patency in utero. Ductal tone is regulated by both locally released and circulating vasodilatory prostaglandins. In infants with ductus arteriosus-dependent congenital heart disease, ductal patency is maintained by intravenous administration of prostaglandin (PG) E(1). Little information is available regarding the expression of prostaglandin receptors in man. 2. By means of RT-PCR and immunohistochemistry we studied the expression of the PGI(2) receptor (IP), the four different PGE(2) receptors (EP1, EP2, EP3 and EP4), and the receptors for thromboxane (Tx) A(2) (TP), PGD(2) (DP) and PGF(2alpha) (FP) in the ductus arteriosus of three newborn infants with ductus arteriosus-dependent congenital heart disease and intravenous infusion of PGE(1) and of one 8 month old child with a patent ductus arteriosus. 3. The EP3, EP4, FP, IP and TP receptor were markedly expressed at the mRNA and protein level, whereas the EP2 receptor was weakly expressed and the EP1 receptor was detected in two out of four tissue specimens only. The DP receptor was not detected in any of the samples. The most pronounced expression, which was located in the media of the ductus arteriosus, was observed for the EP4 and TP receptors followed by IP and FP receptor protein. 4. These data indicate that ductal patency during the infusion of PGE(1) in infants with ductus arteriosus-dependent congenital heart disease might be mediated by the EP4 and IP receptor. The data further suggest that a heterogeneous population of prostanoid receptors may contribute to the regulation of ductus arteriosus tone in humans.

Low-dose aspirin in pregnancy: maternal and neonatal aspirin concentrations and neonatal prostanoid formation.

OBJECTIVE: To evaluate maternal and neonatal plasma concentrations of acetylsalicylic acid and salicylic acid and the neonatal endogenous prostanoid formation during low-dose aspirin prophylaxis (LDA; 100 mg daily) in pregnant women. METHODS: Concentrations of acetylsalicylic acid and salicylic acid in maternal plasma after at least 4 weeks of LDA (n = 14) and in umbilical cord plasma of newborns after maternal LDA (n = 7) were determined by gas chromatography-mass spectrometry. Platelet and renal formation of thromboxane A2 and the formation of prostaglandin E2 and prostacyclin were evaluated in vivo by quantification of index metabolites in plasma and urine by gas chromatography-mass spectrometry in neonates after maternal LDA (n = 14) and in a control group. RESULTS: In the pregnant women, acetylsalicylic acid and salicylic acid concentrations rapidly increased after ingestion of LDA. Acetylsalicylic acid was completely eliminated within 4 hours, whereas salicylic acid was detected with low concentrations at 18 and 21 hours after dosing. In the neonates, acetylsalicylic acid was not detected. Salicylic acid was detected in 1 infant only. Platelet thromboxane A2 formation in the newborn infants was significantly suppressed but recovered within 2 to 3 days after discontinuation of LDA. Renal thromboxane A2 formation and the formation of prostaglandin E2 and prostacyclin were not affected by LDA. CONCLUSION: In pregnant women who are treated with LDA, acetylsalicylic acid is not completely inactivated in the portal circulation but reaches the uteroplacental circulation and exerts antiplatelet effects in the fetus and newborn.

Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies.

PURPOSE: Hypokalemic salt-losing tubulopathies (Bartter-like syndromes) comprise a set of clinically and genetically distinct inherited renal disorders. Mutations in four renal membrane proteins involved in electrolyte reabsorption have been identified in these disorders: the furosemide-sensitive sodium-potassium-chloride cotransporter NKCC2, the potassium channel ROMK, the chloride channel ClC-Kb, and the thiazide-sensitive sodium-chloride cotransporter NCCT. The aim of this study was to characterize the clinical features associated with each mutation in a large cohort of genetically defined patients. PATIENTS AND METHODS: The phenotypic characteristics of 65 patients with molecular defects in NKCC2, ROMK, ClC-Kb, or NCCT were collected retrospectively. RESULTS: ROMK and NKCC2 patients presented with polyhydramnios, nephrocalcinosis, and hypo- or isosthenuria. Hypokalemia was less severe in the ROMK patients compared with the NKCC2 patients. In contrast, NCCT patients had hypocalciuria, hypomagnesemia, and marked hypokalemia. While this dissociation of renal calcium and magnesium handling was also observed in some ClC-Kb patients, a few ClC-Kb patients presented with hypercalciuria and hypo- or isosthenuria. CONCLUSIONS: ROMK, NKCC2, and NCCT mutations usually have uniform clinical presentations, whereas mutations in ClC-Kb occasionally lead to phenotypic overlaps with the NCCT or, less commonly, with the ROMK/NKCC2 cohort. Based on these results, we propose an algorithm for the molecular diagnosis of hypokalemic salt-losing tubulopathies.