Fluticasone furoate induced iatrogenic Cushing syndrome in a pediatric patient receiving anti-retroviral therapy.

SUMMARY: We present a case of iatrogenic Cushing's syndrome, induced by treatment with fluticasone furoate (1-2 dd, 27.5 µg in each nostril) in a pediatric patient treated for congenital HIV. The pediatric patient described in this case report is a young girl of African descent, treated for congenital HIV with a combination therapy of Lopinavir/Ritonavir (1 dd 320/80 mg), Lamivudine (1 dd 160 mg) and Abacavir (1 dd 320 mg). Our pediatric patient presented with typical Cushingoid features (i.e. striae of the upper legs, full moon face, increased body and facial hair) within weeks after starting fluticasone furoate therapy, which was exacerbated after increasing the dose to 2 dd because of complaints of unresolved rhinitis. Biochemical analysis fitted iatrogenic Cushing's syndrome, with a repeatedly low cortisol (<0.03 µM, ref 0.14-0.60 µM) and low ACTH (9 pg/mL, ref 9-52 pg/mL) without signs of adrenal insufficiency. No other biochemical abnormalities that could point to adrenal or pituitary dysfunction were detected; electrolytes, thyroid and gonadal function, and IGF-1 were within the normal range. Pharmacogenetic analysis revealed that the pediatric patient carried the CYP3A4 *1B/*1G and CYP3A5 *3/*3 genotype (associated with a partial and complete loss of enzyme activity, respectively) which is associated with the development of iatrogenic Cushing's syndrome in patients treated for HIV due to the strong inhibition of CYP3 enzymes by Ritonavir. Upon discontinuation of fluticasone treatment, the pediatric patient improved both clinically and biochemically with normalisation of cortisol and ACTH within a couple of weeks. LEARNING POINTS: Fluticasone therapy may induce iatrogenic Cushing's syndrome in a patient treated with anti-retroviral therapy.Pharmacogenetic analysis, in particular CYP3A genotyping, provides useful information in patients treated for HIV with respect to possible future steroid treatment.Fluticasone furoate is not detected in the Siemens Immulite cortisol binding assay.

[Dehydration due to "mouth broken"]. / Dehydratie door "mond kapot".

Two children were admitted to a medical centre due to dehydration after an oral injury and the extraction of a tooth. One child complained of "mouth broken". Dehydration is the most common water-electrolyte imbalance in children. Babies and young children are prone to dehydration due to their relatively large body surface area, the high percentage extracellular fluid, and the limited ability of the kidneys to conserve water. After the removal ofa tooth, after an oral trauma or in case of oral discomfort, a child is at greater risk of dehydration by reduced fluid and food intake due to oral pain and/or discomfort and anxiety to drink. In those cases, extra attention needs to be devoted to the intake of fluids.

Haemolytic disease of the newborn because of rare anti-Vel.

Routine screening for maternal immunization in a 36-year-old woman revealed an alloimmunization against the high-incidence Vel antigen during a second pregnancy. Because of the development of immunoglobulin G-type anti-Vel, the infant developed haemolytic disease of the newborn, with severe jaundice and reticulocytosis. Phototherapy was needed to reduce hyperbilirubinaemia.

[A careful course of action in a conflict regarding useful treatment of a newborn infant with severe brain damage]. / Zorgvuldige handelwijze bij een conflict over zinvol handelen bij een pasgeborene met ernstige cerebrale beschadiging.

In a newborn female infant, it was concluded that severe perinatal asphyxia had caused such extensive cerebral damage that further medical treatment was useless. Based on their religious beliefs, the parents disagreed, despite the fact that the requested second opinions supported the conclusion of the medical staff. Since the parents persisted, a period of inurement was agreed upon during which reanimation would be performed if necessary. After several months, there was no change in the attitude of the parents towards the policy not to reanimate, even though it was clear that there was no improvement whatsoever in the patient's neurological status, while everyone agreed that she showed signs of increased suffering. The decision regarding the determination of a situation in which further medical treatment was useless was re-evaluated carefully. In a legal procedure started by the parents, the judge supported the decision of the attending physicians. In order to prevent the parents from taking their child home, in which case a situation could arise in which she would be deprived of adequate sedation or analgesia, which the attending physicians were obliged to provide, the Dutch Child Protection Council was consulted and the parents were deprived of their parental authority. Ultimately, the patient died suddenly due to respiratory and circulatory arrest without another situation in which reanimation might have been indicated.

Effect of preeclampsia in the mother on the leucine metabolism in the newborn infant.

The leucine turnover in newborn infants is influenced by factors such as nutritional state and corticosteroid treatment. Little is known about maternal factors influencing the leucine turnover in the newborn. In order to approach the effect of preeclampsia in the mother on neonatal protein turnover, we studied the leucine turnover in preterm infants soon after birth and again after 7 days. Ten infants from preeclamptic mothers (birth weight 1,280 +/- 240 g, gestational age 31 +/- 2 weeks) and 15 control patients (birth weight 1,320 +/- 210 g, gestational age 30 +/- 2 weeks) were enrolled. The leucine turnover was measured using a primed constant 5-hour intravenous infusion of [1-(13)C]leucine within the first 24 h after delivery and again on day 7 of life. The turnover (leucine flux; micromol.kg(-1).h(-1)) was calculated from the enrichment in alpha-ketoisocaproic acid in plasma. The leucine turnover on day 1 was 300 +/- 65 in the preeclampsia group and 358 +/- 70 in the controls (ANOVA, p < 0.05). The values on day 7 were 474 +/- 73 in the preeclampsia group and 485 +/- 80 in the control group (n.s.). To conclude, the leucine turnover on day 1 is lower in infants of preeclamptic mothers as compared with controls. This difference has disappeared on day 7 of life after receiving the same protein and energy intake.

Leucine kinetics during simultaneously administered insulin and dexamethasone in preterm infants with severe lung disease.

The objective of this study was to determine whether insulin administration would prevent the well-documented catabolic effect of dexamethasone given to preterm infants with chronic lung disease. We studied leucine metabolism in 11 very-low-birth-weight infants before dexamethasone treatment and on d 2, 4, and 7 thereafter. During the first 4 d of dexamethasone, insulin was administered i.v. at a dose of 0.5 (n = 7) or 1.0 (n = 5) IU/kg/d. Leucine turnover was not significantly different between d 0 (337 +/- 41.3 micromol leucine/kg/h), d 2 (288 +/- 27.2 micromol leucine/kg/h), d 4 (302 +/- 22.1 micromol leucine/kg/h), and d 7 (321 +/- 21.2 micromol leucine/kg/h), and neither was leucine breakdown (272 +/- 21.9 micromol leucine/kg/h on d 0, 225 +/- 21.5 micromol leucine/kg/h on d 2, 231 +/- 21 micromol leucine/kg/h on d 4, and 242 +/- 17.6 micromol leucine/kg/h on d 7). Weight gain rates were significantly lower during the first week of dexamethasone treatment compared with the week before treatment or the second and third week. We conclude that during insulin and corticosteroid administration in very-low-birth-weight infants, no changes were observed in leucine kinetics in contrast to previous studies. The decrease in weight gain was not reversed.

Endogenous surfactant turnover in preterm infants measured with stable isotopes.

We studied surfactant synthesis and turnover in vivo in preterm infants using the stable isotope [U-13C]glucose, as a precursor for the synthesis of palmitic acid in surfactant phosphatidylcholine (PC). Six preterm infants (birth weight, 916 +/- 244 g; gestational age, 27.7 +/- 1.7 wk) received a 24-h [U-13C]glucose infusion on the first day of life. The 13C-enrichment of palmitic acid in surfactant PC, obtained from tracheal aspirates, was measured by gas chromatography-combustion interface-isotope ratio mass spectrometry. We observed a significant incorporation of carbon-13 from glucose into surfactant PC palmitate. PC palmitate became enriched after 19.4 +/- 2.3 (16.5 to 22.3) h and reached maximum enrichment at 70 +/- 18 (48 to 96) h after the start of the label infusion. The fractional synthesis rate (FSR) of surfactant PC palmitate from glucose was 2.7 +/- 1.3%/d. We calculated the absolute production rate of surfactant PC to be 4.2 mg/kg/d, and the half-life to be 113 +/- 25 (87 to 144) h. Data on endogenous surfactant production and turnover were obtained for the first time in human infants with the use of stable isotopes. This novel and safe method could be applied to address many important issues concerning surfactant metabolism in preterm infants, children, and adults.

Fibre optic versus conventional phototherapy for hyperbilirubinaemia in preterm infants.

UNLABELLED: Studies comparing efficacy of fibre optic phototherapy to conventional phototherapy are performed mostly in term infants and give conflicting results. This randomized prospective study compares efficacy of fibre optic phototherapy using the Ohmeda Biliblanket device to conventional fluorescent phototherapy in preterm infants. A total of 124 preterm infants with a nonhaemolytic hyperbilirubinaemia were evaluated. Stratification at randomisation was performed according to birth weight ( < 1000 g, 1000-1500 g or 1500-2000 g). Fifty-six infants received fibre optic and 68 conventional phototherapy. Efficacy was assessed by comparing the required duration of phototherapy. Median duration of phototherapy was 118 h and 114 h in the fibre optic and conventional groups respectively, the difference in which was not statistically significant. The median durations were also not significantly different within the separate weight groups. The number of infants requiring exchange transfusions was similar in both treatment groups. CONCLUSION: The efficacy of fibre optic phototherapy in preterm infants is comparable to conventional phototherapy.

Effect of dietary triacylglycerol fatty acid positional distribution on plasma lipid classes and their fatty acid composition in preterm infants.

Seven premature infants were each fed, for 1 wk in a crossover design. The beta formula contained triacylglycerols resembling the stereoisomeric structure of human milk fat (25.4% by wt 16:0, 76.1% of which is at the sn-2 position), whereas in the alpha formula 87.3% of total 16:0 (25.7% by wt was at the sn-1,3 positions. Plasma lipids and their fatty acid compositions were determined at the end of each 1 wk study period. Infants fed with the beta formula had higher percentages of palmitic acid in plasma sterol esters, triacylglycerols, and free fatty acids, and lower linoleic acid in triacylglycerols than with the alpha formula. Premature infants fed formulas with triacylglycerols 16:0 predominantly in the sn-2 rather than the sn-1,3 positions had alterations in their plasma fatty acids consistent with enhanced absorption of 16:0 from the sn-2 compared with the sn-1,3 positions.

Nutrition in the neonate.

Good nutrition is of great importance for all living individuals, especially for the rapidly growing newborn infant. Nutrition is needed not only for the maintenance of physiologic functions but also for growth. Despite extensive research in this field, numerous questions remain regarding the nutrition of the term as well as the preterm infant. It should be stressed that the requirements of term infants are different from those of preterm infants, and a further distinction has to be made between very low birth weight and extremely low birth weight infants. In this review, the following issues are addressed: breastfeeding versus formula feeding, the role of polyunsaturated fatty acids, nutrition of the infant with bronchopulmonary dysplasia, and parenteral nutrition.

[Focal dermal hypoplasia, or the Goltz-Gorlin syndrome]. / Focale dermale hypoplasie, ofwel het syndroom van Goltz-Gorlin.

A female newborn is reported with focal dermal hypoplasia (Goltz-Gorlin syndrome) presenting multiple skin and extremity-abnormalities. A short review of today's literature in relation to mode of inheritance and clinical manifestations is given.