Inflammatory cytokines in the pathogenesis of periventricular leukomalacia.

BACKGROUND: Periventricular leukomalacia (PVL) affects the developing white matter of neonatal brain. Inflammatory and infectious conditions are implicated in the cause of PVL. METHODS: The authors investigated the in situ expression of proinflammatory cytokines (interleukin-1beta and -6, tumor necrosis factor alpha [TNFalpha]), adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1) and inflammatory cell markers (CD68, leukocyte common antigen, human leukocyte antigen II) in 19 neonatal brains with PVL. The authors compared the findings with matched non-PVL brains. RESULTS: The inflammatory reaction detected at the early stage of PVL extends until the latest phase of cystic cavitation, though at an attenuated level. There is high expression of TNFalpha and to a lesser extent interleukin-1beta; interleukin-6 remains undetectable. Cytokine immunoreactivity is detected in PVL cases both with and without infection. However, cytokine production was higher with infection. A different pattern of cytokine expression was observed in anoxic brains without PVL: TNFalpha immunoreactivity was significantly lower than the PVL group. CONCLUSIONS: An immune-mediated inflammatory process may play a role in PVL. TNFalpha, a myelinotoxic factor, may be the major mediator.

Dietary composition and macronutrient storage in preterm infants.

A comparison has been made of the influence of feeding own mother's milk and formula on the oxidation and accretion of energy and macronutrients in the growing preterm infant of very low birth weight (less than 1,300 g) by using the combined techniques of nutrient balance and computerized indirect calorimetry. There were 22 studies in formula-fed infants and 15 studies in premature infants fed own mother's milk. Despite their lower metabolizable energy intake, the infants fed own mother's milk grew in weight, length, and head circumference at a rate approximating those of the formula-fed group. The metabolic rate was significantly lower in the infants fed own mother's milk (56.0 +/- 0.9 v 62.6 +/- 0.8 kcal/kg/d; P less than .001). The protein intake, oxidation, and accretion were similar in the two groups. The infants fed own mother's milk had a significantly lower fat intake (P less than .001), higher fat oxidation (P less than .025) and consequently lower fat accretion (P less than .001) than the formula-fed infants. The proportional fat content of the daily weight gain was lower in the infants fed own mother's milk (16% v 33%; P less than .001) but protein content was similar (13% v 12%). The accretion of energy, fat, and protein correlated with the respective metabolizable intakes in both groups (r = .81 to .98; P less than .001), suggesting that accretion rates and hence composition of weight gain are dependent on levels of energy and macronutrient intake.

Partition of energy metabolism and energy cost of growth in the very low-birth-weight infant.

Energy requirements are partitioned between needs for maintenance (including resting metabolism, thermoregulation, and muscular activity) and needs for synthesis and storage of new tissue. The partition of energy utilization was evaluated by 22 metabolic and nutritional balance studies in 13 formula-fed (SMA 20/24), growing, appropriate-for-gestational age, very low-birth-weight infants (mean +/- SE birth weight, 1,155 +/- 39 gm; study weight, 1,271 +/- 60 gm; age at study, 21 +/- 2 days; weight gain, 16.8 +/- 1 gm/kg/day). Continuous open-circuit, indirect calorimetry was performed for periods of 6 +/- 0.25 hours in a thermoneutral environment. Results expressed as mean kilocalories per kilogram per day (+/- SE) were: energy intake, 148.6 (+/- 3.9); stool and urine losses, 18.2 (+/- 1.5); metabolizable energy, 130.4 (+/- 3.5); "basal" metabolic rate, 47.0 (+/- 0.75); energy cost of activity, 4.3 (+/- 0.9); thermic effect of food, 11.3 (+/- 0.65); energy stored in new tissue, 67.8 (+/- 3.0). These results provide a partition of energy utilization in very low-birth-weight infants under thermoneutral conditions. Increased activity and a thermal environment outside the neutral range will augment maintenance energy requirements, thus decreasing the amount of energy available for growth if metabolizable energy intake remains constant. The energy cost of growth (ie, for synthesis of, and storage in, new tissue) was determined as 4.9 kcal/gm of weight gain. To attain the equivalent rate of intrauterine weight gain, a metabolizable energy intake of approximately 60 kcal/kg/day in excess of maintenance requirements of 51.3 kcal/dk/day must be provided.

The challenge of upper airway obstruction in pediatric intensive care.

Over a 5-year period, 75 patients were admitted to a pediatric intensive care unit because of acute upper airway obstruction (AUAO). Congenital abnormalities were demonstrated in 25 children; 9 of them died secondary to severe combined malformations or major central nervous system dysfunction. Acquired AUAOs were seen in 50 patients; 1 died in brain death secondary to anoxia. Obstructions were observed at all levels of the airways from the nose to the carina. In 28% of the patients, AUAO had remained undiagnosed until admission for complications such as acute respiratory failure, cardiac arrest, coma, seizures. With early diagnosis and prompt release of the obstruction the prognosis is good unless severe congenital abnormalities or major central nervous system damage are associated.

Diverticulum formation after circular myotomy for esophageal atresia.

Out of our last 70 cases of esophageal atresia, a circular myotomy of the upper pouch (Livaditis technique) was required in six patients to achieve an end-to-end anastomosis: all had a lower tracheoesophageal fistula. They were operated on between 15 and 96 hours after birth, without any preoperative attempt of elongation of the upper pouch. Follow-up ranged from 14 to 77 months. Three patients had an uneventful postoperative course and late outcome, despite a moderate ballooning at the myotomy site in one. Three babies developed a mild stricture which responded easily to a few dilatations. Asymptomatic ballooning at the myotomy site was observed in one baby; the other two developed a diverticulum responsible for acute respiratory distress in one case and severe dysphagia in the other. both required esophageal replacement. These observations call attention to the fact that patients treated by myotomy should be followed very carefully early and late, especially if an anastomotic stricture develops or in case of associated tracheomalacia.

[Choanal atresia: a retrospective study of 39 cases]. / Les atrésies choanales: à propos d'une série rétrospective de 39 cas.

The purpose of this study was to investigate the clinical characteristics and the surgical management in patients with choanal atresia. We performed a retrospective study at the Saint-Luc University hospital, Brussels, between January 1988 and June 2000. Surgical corrections were performed using different approach (transnasal endoscopic, transpalatal) and different instrumentations (urethral sounds, laser nd-YAG, laser CO2, microdebrider). Portex endotracheal tubes were inserted as nasal stents in the vast majority of the patients with bilateral choanal atresia. Thirty-nine children with choanal atresia (22 unilateral and 17 bilateral) (9: M, 30: F) were studied. 38 of them were surgically managed. Based on clinical inspection and On CT-Scan, choanal atresia was defined as membranous for 4 patients, osseous for 6 and mixte for 29. Associated congenital anomalies were found in 22.7% of unilateral and in 70.5% of bilateral choanal atresia (Total: 43.5%). Of those children with bilateral choanal atresia, 75% were asymptomatic after four surgical procedures. In children with unilateral choanal atresia, 45% were asymptomatic after one surgical correction and 100% after three surgical corrections. Four patients were managed using an endoscopic endonasal approach with the microdebrider and showed no evidence of recurrence. Outcome analyses of factors that may influence the results of surgery are difficult to establish since many different surgical options were taken during this period. However, it seems that bilateral choanal atresia is associated with more surgical corrections before achieving a normal nasal breathing than unilateral choanal atresia. After this review, our current strategy regarding the choanal atresia will be to begin with the endoscopic endonasal approach using the microdebrider (stents if bilateral) and to propose the transpalatal approach in case of recurrence.

[Medical treatment of juvenile hemangiomas]. / Traitement médical des hémangiomes immatures.

Infantile hemangioma always involute in 5 to 7 years. However, 10% of proliferating hemangiomas will necessitate a therapeutic approach, often medical, in order to avoid life or organ threatening, fonctional or esthetic sequelae. "Which hemangioma need to be treated, when and how" are important questions for the optimal management of infantile hemangiomas. Corticotherapy is still the treatment of choice for these lesions. Other anti-angiogenic molecules have also been successfully used such as interferon alfa-2a and vincristine. This chapter tries to answer these questions and detail the different medical modalities for the treatment of infantile hemangioma.

Clostridium difficile in neonates: serogrouping and epidemiology.

A typing scheme for Clostridium difficile based on serogrouping, toxigenicity and sorbitol fermentation was applied to 270 strains isolated in one neonatal ward during a 6-month prospective study. Two hundred and twenty-three strains were isolated from 377 faecal samples of 114 neonates and 47 from 92 environmental specimens. The isolates were distributed among five different types; 87% of the faecal and 85% of the environmental isolates belonged to two of these types (toxigenic, sorbitol negative, serogroup F and nontoxigenic, sorbitol positive, serogroup A). Nosocomial spread was clearly demonstrated and the environment appeared to be the main source of contamination: most of the neonates were colonized after admission by strains found in their environment; clusters of colonization with unusual isolates were observed following referral of patients from the intensive care unit or from other hospitals. No relation was found between the acquisition or the carriage of C. difficile and any intestinal symptoms. All the strains belonged to types different from those usually found in cases of antibiotic associated colitis (AAC) suggesting differences of pathogenicity among the different types.

Lysophosphatidylcholine-induced Ca(2+)-overload in isolated cardiomyocytes and effect of cytoprotective drugs.

It has been previously demonstrated that lysophosphatides accumulate rapidly in ischaemic tissue, and may play a key role in the genesis of ischaemia-reperfusion injury. The present study investigated the effects of exogenously added lysophosphatidylcholine (1-20 microM) on single isolated cardiomyocytes from adult rabbit hearts. Quiescent cells exposed to > or = 8 microM lysophosphatidylcholine dose-dependently displayed irreversible hypercontraction, whereas after 60 min at 3 microM lysophosphatidylcholine, most cells remained rod-shaped (87.2 +/- 2.0%, mean +/- S.E.M.). However, when combined with electrical field stimulation (1 Hz), exposure to 3 microM lysophosphatidylcholine resulted in irreversible hypercontracture of most cells after 60 min: only 27.5 +/- 7.5% of the cells remained rod-shaped. Contracture depended upon the presence of extracellular Ca2+, and coincided with a significant rise in the median intracellular free Ca2+ level from 72.2 to 352.1 nM (P = 0.0001), suggesting intracellular Ca(2+)-overload. Pretreatment with 10(-6) M flunarizine or R 56865 significantly reduced the fraction of damaged cells when exposed to 3 microM lysophosphatidylcholine and electrical stimulation: 78.3 +/- 12.2% and 56.3 +/- 13.1% respectively of the cells remained rod-shaped. No protection was observed when quiescent cells were exposed to 10 microM lysophosphatidylcholine. Cytochemical localization of Ca2+ showed that lysophosphatidylcholine induced a loss of sarcolemma-bound Ca2+ precipitate and an accumulation of Ca2+ clusters in mitochondria of damaged cells in a dose and time dependent way. These results suggest that lysophosphatidylcholine induces functional and structural damage (Ca(2+)-overload) in isolated cardiomyocytes and that this can be prevented by cytoprotective drugs.

Periventricular leukomalacia: ultrasonic and neuropathological correlations.

Ultrasound scans of a preterm neonate (27 weeks gestation) at seven weeks of age showed periventricular echo-free cavities, but these were no longer visible at 15 weeks, three weeks before the infant died. At autopsy, a linear glial scar, extending from the periventricular white-matter into the white axis of the parasagittal gyrus, was found in the area occupied by the periventricular cysts. The larger cavity was reduced to a slit-like excavation in the midst of glial tissue. Unsuspected focal infarcts in the cerebral cortex were also found. This observation demonstrates that transient echo-free cavities represent foci of cystic necrosis, which are subject to secondary collapse. In the authors' experience, the linear extension of periventricular leukomalacia (PVL) into the core of parasagittal gyri is a frequent feature of PVL, and one which cannot easily be accounted for by the usual explanations of border-zone ischaemic softening.

[Congenital paralysis due to compression. Apropos of 4 cases]. / Paralysies congénitales par compression. A propos de quatre observations.

Four cases of congenital dysfunction of major peripheral nerves are reported and discussed. The first patient was a girl born by spontaneous delivery with an area of skin and muscle necrosis on the dorsal aspect of the forearm and a palsy of the three major nerves of the upper limb. The second patient was a boy born by caesarean section with the same necrotic lesions and a palsy of the ulnar and median nerve. The third patient was a boy born uneventfully with a truncal lesion of the sciatic nerve at the thigh. The fourth who was delivered by caesarean section for alteration of the monitoring presented a severe strangulation of the arm by the umbilical cord with palsy of the radial and ulnar nerve. The palsies recovered spontaneously and the sequelae are mostly due to the muscle necrosis. Congenital dysfunction of major peripheral nerves have been described as a complication of congenital constriction band syndrome, in association with subcutaneous fat necrosis, neonatal gangrene or aplasia cutis congenita. Intrauterine compression of a limb may be favoured by decreased foetal activity, by spontaneous rupture of the amniotic sac, particularly if there is a delay in delivery and by abnormal uterine activity during labour. Our three first cases confirm that the compression may arise before the labour. The fourth demonstrates that umbilical cord strangulation may lead to anoxia of the foetus together with compression of the limb.

High CTG repeat number in nodular thyroid tissue from a myotonic dystrophy patient.

CTG triplet expansion was studied in lymphocytes and thyroid tissue in a patient with myotonic dystrophy (DM) and associated thyroid nodular disease. An approximately 7 fold larger amplification was found in abnormal thyroid tissue compared to lymphocytes, suggesting that anomalies in the putative DM kinase gene might contribute to thyroid dysfunction.

Class IV Ca2+ antagonists do not affect lipid peroxidation in singlet oxygen challenged cardiomyocytes.

The effects of various Ca2+ antagonists on lipid peroxidation in singlet O2-challenged isolated cardiomyocytes from adult rat heart were investigated. Singlet O2-challenged untreated cells all hypercontracted as a consequence of Ca2+ overload and produced 463.6 +/- 143.6 nM malondialdehyde (MDA; mean +/- SD, n = 8). Protective Ca2+ antagonists reduced the amount of damaged cells, but did generally not affect MDA production. On the other hand, free radical scavengers and antioxidants displayed a good correlation between number of protected cells and MDA produced. It is concluded that flunarizine-like Ca2+ antagonists protect cells against Ca2+ overload without, however, interfering with peroxidative processes.

Anaesthetic management of a child with Marshall-Smith syndrome.

PURPOSE: The Marshall-Smith Syndrome (MSS) is a rare disease characterized by orofacial dysmorphism, failure to thrive, accelerated osseous maturation and mental retardation. It has anaesthetic implications due to upper airway problems and possible atlanto-axial instability. We present the perioperative problems (difficult intubation, airway obstruction) encountered in a child with MSS who underwent several anaesthetics during his first two years of life. CLINICAL FEATURES: At birth, the child presented with asphyxia due to obstructive apnoea. His trachea was, therefore, intubated immediately. The morphological diagnosis of MSS was confirmed by the pathognomonic radiological appearance of the bones (bone age was eight months at the age of four days). Upper airway difficulty was caused by functional problems at the level of the hypopharynx (inspiratory collapse at the level of the velum palatinum), and was solved by the use of a nasopharyngeal airway (NPA) during the induction of anaesthesia and early postoperative period. CONCLUSION: The use of an NPA during both induction and recovery of anaesthesia may be particularly useful to prevent upper airway problems in children with MSS.

Association of bilateral renal agenesis and Di George syndrome in an infant of a diabetic mother.

We found at postmortem examination the association of bilateral renal agenesis and of apparently complete Di George syndrome in an infant whose mother was diabetic. Vertebral abnormalities and hallux duplication were present as well. There is a correlation between maternal diabetes and the bilateral renal agenesis-caudal dysplasia complex on one hand, and maternal diabetes and cardiac malformations on the other hand. Moreover, it has been suggested that the absence of thymus and parathyroids in Di George syndrome is causally linked to the cardiac malformation. Therefore we suggest that the association in our case is not coincidental; both sets of malformations may be due to the maternal diabetes.

Giant congenital melanocytic nevus with placental involvement: long-term follow-up of a case and review of the literature.

We describe a case of giant congenital melanocytic nevus with placental villous involvement in an otherwise uncomplicated pregnancy. Only four similar cases have been reported in the world literature. Nevomelanocytes were found in both villous stoma and fetal capillaries. No neonatal or maternal adverse effects were observed 5 years after diagnosis in the present case.

Considerations about the cloverleaf skull.

The study of four cloverleaf skulls (two fetuses, one infant, and a young adult) concerns two Pfeiffer syndromes, a thanatophoric dysplasia and an isolated case. Clinical and radiologic examinations showed malformations at the level of the calvarium, the base, orbital cavities, and, sometimes, limb abnormalities. Correlations between these findings and the microradiographic analysis of nondemineralized sections elucidate this trilobular appearance of the skull. Premature temporoparietal suture closure terminates at a constricted surface of the lateral sides of the skull during the fetal life. Extension of the synostosis to coronal and frontal sutures and thickening of the occipital bone squama block lengthening of the skull. The consecutive reduction in skull volume is compensated by the maintenance of the permeability during the neonatal period of the sagittal and lambdoid sutures. Microradiographic examination shows that this anomaly may be of vascular origin and associated with abnormal osteoclastic resorption.

Quality of growth in premature infants fed their own mothers' milk.

With the renewed interest in the feeding of human milk to preterm infants, we have evaluated the partition of energy metabolism and of macronutrient utilization and accretion in growing very low birth weight infants fed their own mother's milk. Fifteen studies combining macronutrient balance, computerized continuous open-circuit indirect calorimetry, and anthropometric measurements were performed in 11 growing, very low birth weight (less than 1.300 gm) preterm infants. The mean milk intake of 172 ml/kg/day provided a gross energy intake of 111 kcal/kg/day. Energy losses in excreta were 11 kcal/kg/day, and the metabolic energy expenditure was 56 kcal/kg/day. The remainder (44 kcal/kg/day) represented the energy stored in the components of new tissue. The infants were gaining weight (15.3 g/kg/day), length (0.98 cm/wk), and head circumference (0.76 cm/wk) at rates approximating intrauterine growth rates. The metabolic energy expenditure was derived from the oxidation (mean +/- SE) of carbohydrate, 9.5 +/- 0.7 gm/kg/day; fat, 1.63 +/- 0.34 gm/kg/day; and protein, 0.68 +/- 0.07 gm/kg/day. The stored energy comprised 2.98 +/- 0.86 gm/kg/day as carbohydrate, 2.25 +/- 0.54 gm/kg/day as fat, and 1.97 +/- 0.1 gm/kg/day as protein. The accretion rates of fat and protein, as well as the composition of the weight gain (fat, 16.6 +/- 4.1%; protein, 13.4 +/- 0.5%), were similar to those reported for the fetus of comparable gestational age.