Excellent growth response to growth hormone therapy in a child with PTPN11-negative Noonan syndrome and features of growth hormone resistance.

We report a child with Noonan syndrome, referred with severe short stature (height--5.4 SD) and biochemical features of GH resistance. The Noonan syndrome phenotype was confirmed by a clinical geneticist, however analysis of the protein tyrosine phosphatase nonreceptor type 11 (PTPN11) gene showed no mutation. Baseline serum IGF-I, IGFbinding protein 3 (IGFBP-3) and acid-labile subunit (ALS) were low, and in an IGF-I generation test, IGF-I did not increase into the normal range and IGFBP-3 and ALS did not change. These results are consistent with GH resistance. Treatment with human GH (hGH) was given in a dose of 0.05 mg/kg/day and height velocity increased from 5.6 to 10.7 cm/yr during the first year, and 8.9 cm/yr during the second year of therapy. Height standard deviation score has increased by 1.85 after 2 and a half yr of therapy. Serum IGF-I, IGFBP-3 and ALS values increased well into the normal range. This case shows that the potential value of GH therapy must be evaluated in each patient individually and that an excellent response may occur in a child with a PTPN11-negative genotype.

Plasma fibronectin levels in extremely preterm infants in the first 8 weeks of life.

Fibronectin has in the past been considered to function simply as a non-specific plasma opsonin. However, recent studies have demonstrated that this molecule plays an important role in fundamental components of the immune response, for example, neutrophil adhesion, T cell activation and endothelial function. Additionally, fibronectin is important in lung homeostasis where it contributes to alveolar epithelial integrity. In this study plasma fibronectin levels were measured longitudinally in a group of extremely preterm infants, mean gestational age 27 weeks. Plasma fibronectin levels at birth were significantly lower in the preterm study group than in term controls (mean 91 +/- 33 micrograms/mL compared with 214 +/- 62 micrograms/mL in the term controls, P < 0.0001). The preterm cohort demonstrated a more than two-fold rise in plasma fibronectin on days one and two; levels fell almost to baseline values by day three with a subsequent slow rise to a plateau by day 28. No further increase was seen by day 56. This sequence of early changes in fibronectin levels mirrored closely the time course of respiratory distress syndrome. Infants of mothers with pre-eclampsia had significantly lower peak fibronectin levels than in those without (P = 0.016), and those infants with bronchopulmonary dysplasia showed a trend towards lower basal fibronectin levels (P = 0.07) and a greater difference between peak and basal levels (P = 0.05). Neonates, particularly those born preterm, have blunted immunological responses to infection. Fibronectin plays a key role in immunological responsiveness. The significant changes in fibronectin levels after birth in the preterm neonate are likely to have important pathophysiological consequences.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe thrombocytopenia in extremely low birthweight infants with systemic candidiasis.

The clinical, haematological and microbiological features of 12 extremely low birthweight (ELBW) infants with Candida infection were compared with 36 gestational-age and birthweight matched controls who experienced 42 episodes of bacterial septicaemia. Thrombocytopenia was the feature observed most commonly, occurring in 12 of 12 study infants and 23 of 42 controls (P = 0.004). Minimum platelet counts were below 50 x 10(9)/L in 11 of 12 study patients compared with seven of 42 controls (P < 0.0001). Severe thrombocytopenia may be a useful indicator of systemic Candida infection in ELBW infants.

Decreased plasma fibronectin concentrations in preterm infants with septicaemia.

Changes in plasma fibronectin concentrations were determined during bacterial septicaemia in extremely preterm infants. The study was a prospective study of fibronectin concentrations in infants of less than 30 weeks' gestation. Concentrations were determined at birth, before sepsis, and throughout the episode of sepsis. Fibronectin concentrations at birth or immediately before sepsis were not significantly different between those infants who developed septicaemia and those who did not (98 (15) v 97 (10) micrograms/ml). In the infants with septicaemia, fibronectin concentrations decreased significantly on day 1 (106 (13) v 173 (18) micrograms/ml for the controls) and remained significantly lower on day 2 (123 (26) v 201 (17) micrograms/ml). By day 5 fibronectin concentrations had increased and were no longer statistically different from controls. Fibronectin is a key modulator of the immune response, with important functions in neutrophil adhesion, bacterial opsonisation, T cell activation, and vascular integrity. Acute depletion of plasma fibronectin during sepsis in preterm neonates may further abrogate their ability to control sepsis.

Omenn's disease.

The importance of accurate pathological diagnosis is emphasised in the case of a newborn infant who presented with alopecia, a generalised erythrodermatous skin eruption, and hepatosplenomegaly. She subsequently developed generalised lymphadenopathy and recurrent septicaemia and died aged 2 months. The histological findings of widespread lymphocytic, histiocytic, and eosinophilic tissue infiltration, associated with thymic hypoplasia, were consistent with autosomal recessive Omenn's disease.

Septicaemia and adrenal haemorrhage in congenital asplenia.

Five patients developed overwhelming infection as a result of congenital asplenia, which was previously unsuspected in all cases. Each illness followed a fulminant course resulting in death within 24 hours. They illustrate the respective roles of Haemophilus influenzae infection (n = 4) and adrenal haemorrhage (n = 4) in this condition. We suggest a management protocol for screening infants with abnormalities of the atria or viscera with splenic ultrasound and examination of a blood film for Howell-Jolly bodies. Vaccination and prophylactic antibiotics should be considered for those at risk. Vigorous use of parenteral antibiotics and steroids in suspected infection is recommended.

Morphine increases synchronous ventilation in preterm infants.

OBJECTIVE: To examine the short-term cardiorespiratory effects of intravenous morphine infusion in ventilated preterm infants. METHODOLOGY: A randomized double-blind placebo-controlled trial in a neonatal intensive care unit. Twenty-six preterm infants (29-36 weeks gestation) with hyaline membrane disease requiring ventilatory assistance on the first day after birth were included in the study. A loading dose of morphine 100 micrograms/kg over 30 min followed by a continuous intravenous infusion at 10 micrograms/kg per hour was given. Primary measures were heart rate, blood pressure, respiratory rate and interaction of spontaneous respiration with mechanical ventilation. Secondary measures were durations of oxygen therapy, ventilator therapy and hospitalization as well as incidence of bronchopulmonary dysplasia, periventricular haemorrhage and pneumothorax. RESULTS: Morphine-treated infants spent a significantly greater percentage of total ventilated time breathing in synchrony with their ventilators (median [IQ] = 72[58-87] vs 31[17-51]%; P = 0.0008). Heart rate and respiratory rate, but not blood pressure, were reduced in morphine-treated infants. Duration of oxygen therapy was reduced (median [IQ] = 4.5[3-7] vs 8[4.75-12.5] days; P = 0.046). CONCLUSIONS: Intravenous morphine infusion increases synchronicity of spontaneous and ventilator-delivered breaths in preterm infants. Morphine reduces heart rate and respiratory rate without reducing blood pressure, and may help to reduce duration of oxygen therapy in preterm infants with hyaline membrane disease.

Ureaplasma urealyticum in a neonatal intensive care population.

The incidence of Ureaplasma colonization at birth and its effect on the development of chronic lung disease (CLD) and on mortality was studied in a neonatal intensive care population. Ureaplasma colonization was associated with a birthweight < 1000 g (odds ratio [OR] 3.45 confidence intervals [CI] 2.13-5.60) and a gestational age < 30 weeks (OR 2.54 CI 1.71-3.79). In a case-controlled study of 112 infants, significant associations with Ureaplasma colonization were maternal pyrexia in labour (n = 38 vs 21; P = 0.015), the requirement for antibiotics in labour (n = 39 vs 16; P = 0.0005) and vaginal delivery (n = 78 vs 58; P = 0.009). Risk factors associated with the development of CLD were birthweight < 1000 g (OR 3.77 CI 2.53-5.62) and delivery by Caesarean section (OR 1.65 CI 1.11-2.43). Within the group delivered by Caesarean section. Ureaplasma colonization was also associated with an increased risk of CLD (OR 1.97 CI 1.08-3.62). Ureaplasma colonization of infants at birth is associated with factors suggestive of maternal chorioamnionitis as well as preterm birth and low birthweight. In infants delivered by Caesarean section, Ureaplasma colonization is associated with an increased risk of chronic lung disease.