Cyclosporine A induces endothelin-converting enzyme-1: Studies in vivo and in vitro.

AIM: Cyclosporine A (CsA) induces renal vasoconstriction and hypoxia and enhances the expression of endothelin-1 (ET-1) pro-hormone (pre-pro-ET-1), plausibly leading to a feed-forward loop of renal vasoconstriction, hypoxia and enhanced synthesis of the potent vasoconstrictor ET-1. Endothelin-converting enzyme (ECE)-1 cleaves big endothelin to generate endothelin (ET)-1 and is upregulated by hypoxia via hypoxia-inducible factor (HIF). We hypothesized that in addition to the direct induction of ET-1 synthesis, CsA might also intensify renal ECE-1 expression, thus contributing to enhanced ET-1 synthesis following CsA. METHODS: CsA was administered to Sprague Dawley rats (120 mg/kg/SC) for 4 days, and renal HIF and ECE-1 expression were assessed with Western blots and immunostaining. Human umbilical vein endothelial cells (HUVEC) and proximal tubular cell line (HK-2) were subjected to CsA, and ECE-1 induction was evaluated using real-time mRNA PCR and Western blots. RESULTS: Cyclosporine A intensified renal parenchymal ECE-1 expression in the rat kidney, particularly in distal nephron segments, along with renal hypoxia (detected by pimonidazole adducts) and HIF expression, in line with our recent observations showing episodic hypoxia in mice subjected to CsA. Furthermore, in cultured normoxic HUVEC and HK-2 cells, CsA dose-dependently induced both pre-pro-ET-1 and ECE-1 mRNA and protein expression, with enhanced ET-1 generation. CONCLUSION: CsA induces ECE-1 via both hypoxic and non-hypoxic pathways. ECE-1 may contribute to increased renal ET-1 generation following CsA, participating in a feed-forward loop of renal parenchymal hypoxia and ET synthesis.

Early dexamethasone treatment in preterm infants treated with surfactant: a double blind controlled trial.

The objective of the study was to test the hypothesis that early postnatal dexamethasone administration (days 1-5) in preterm infants with respiratory distress syndrome would improve acute respiratory status and therefore decrease long-term neonatal morbidity. This was a prospective, blind randomized controlled trial. Eligible neonates were preterm infants with birthweight < or = 1500 g who developed respiratory distress syndrome requiring mechanical ventilation and surfactant. A 5-day course of dexamethasone or placebo was initiated within the first 6 h after birth. The starting dose of dexamethasone was 0.5 mg/kg/day and it was tapered progressively. Results were analysed with t-test chi 2, Wilcoxon test, and ANOVA. Twenty-nine infants (n = 15 of early dexamethasone and n = 14 of placebo group) fulfilled the inclusion criteria. The dexamethasone group exhibited a significant improvement in arterial to alveolar oxygen ratio only between postnatal days 2 and 5 (p = 0.02). This initial improvement was not associated with long-term benefits. Infants who received dexamethasone had increased systolic blood pressure (p = 0.0001), diastolic blood pressure (p = 0.001), blood sugar (p = 0.02, serum urea (p = 0.03), and creatinine level (p = 0.02). All these side-effects were resolved by postnatal day 7. We concluded that a 5-day course of early postnatal dexamethasone was associated with only a transient improvement in oxygenation with no long-term benefits. Side-effects were more common in the dexamethasone group.

Predictive factors and incidence of complications in apparently healthy full term infants of diabetic mothers.

AIM: To determine the incidence of different complications of the apparently healthy full-term infants of diabetic mothers (IDMs) and whether these complications could be predicted early. METHODS: A prospective study was performed in the Nursery Unit of King Fahd Hospital of the University in Al-Khobar over an 18-month period. Eligible neonates were those full-term IDMs who were asymptomatic at birth, with birth weight ≥ 2000 g and whose mothers had gestational or pregestational diabetes. AUDMs were routinely observed for at least 2 days. A complete blood count, glucose, bilirubin and calcium serum levels were monitored. The morbidity study group included all IDMs who experienced complications requiring treatment or observation for > 48 hours. RESULTS: One hundred and eighty eight infants with a birth-weight of 3411 ± 616 g and with gestational age of 38.5 ± 1.2 weeks were enrolled in the study. Asymptomatic hypoglycemia (31%) was mostly mild and transient. The rate of other complications such as hypocalcemia (4%), polycythemia (13%), hyperbilirubinemia (18%), intrauterine growth retardation (2%) with 30% rate for large gestational age. Using a logistic regression model; maternal insulin therapy, poor diabetic control, birth asphyxia, early neonatal hypoglycemia and polycythemia were found to be highly predictive of morbidity with an odd ratio of 2.41, 2.91, 9.65, 3.88 and 3.74 respectively. CONCLUSION: Complications of apparently healthy IDMs appear to be very mild and transient. These were found to be strongly associated with specific perinatal events.

[Hydroelectrolytic requirements during the first week of life in premature infants weighing less than 1000 g. Physiopathology and recommendations]. / Besoins hydroélectrolytiques pendant la première semaine de vie chez les prématurés de moins de 1,000 g. Physiopathologie et recommandations.

Fluid and electrolyte maintenance in very low birth weight infants during the first week of life must be adapted to their physiological characteristics and to pathological events. Insensible water losses are elevated and may reach 100 mL/kg/24 h depending upon many factors, such as type of incubator, phototherapy, presence of respiratory distress syndrome, changes in transepidermal water losses and renal water and electrolyte regulation (prediuretic, diuretic and postdiuretic phases); there is also a major risk of hypernatremia and hyperkaliema. In cases of insufficient fluid intake the main complication is dehydration with hypernatremia. Excessive fluid intake results in increased incidence of bronchopulmonary dysplasia, patent ductus arteriosus and necrotizing enterocolitis. Hypernatremia is a major risk factor of intracranial hemorrhage. A careful management of water and electrolyte requirements is therefore mandatory in very low birth weight infants. Guidelines on daily maintenance and management are presented.

Cost-effectiveness of surfactant replacement therapy in a developing country.

A comparison study was conducted to evaluate the cost effectiveness of surfactant replacement therapy in the treatment of hyaline membrane disease (HMD). Study population included neonates admitted because of HMD severe enough to require assisted ventilation with FiO2 greater that 0.4 per cent. This group (n = 44) was compared with the outcome for neonates treated in the same centre 1 year before surfactant became available (n = 39). Comparison between the two groups was made in relation to cost of care depending on the duration of hospitalization. The duration of hospitalization in the survivors of the treated group was shorter (P = 0.06); accordingly, the cost of care was less. A savings of US $11,880 per patient survived in the treated group was expected, the nationwide financial impact of this treatment modality is discussed.

Effects of early indomethacin administration on oxygenation and surfactant requirement in low birth weight infants.

A previous study found that early intravenous indomethacin administration prolonged respiratory support in very low birth weight infants. We have, therefore, designed a randomized, double blind controlled study to evaluate the oxygenation, and surfactant requirements in preterm low birth weight infants receiving early indomethacin administration. Premature neonates who received surfactant therapy and on mechanical ventilation were prospectively randomized to receive either placebo or indomethacin (0.2 mg/kg intravenously at 12 postnatal hours and every 24 h for two more doses). Oxygenation was assessed by FiO2 required and arterial/alveolar oxygen (a/A O2) ratio during the first 48 h of life. The doses of surfactant were compared between the two groups. Twenty-seven infants (n = 14 of early indomethacin and n = 13 of placebo group) fulfilled inclusion criteria. At admission to the study, there were no differences in the birth weight, gestational age, sex, Apgar scores, a/A O2 ratio, and FiO2. The control group exhibited a significant improvement in oxygenation (FiO2 requirement and a/A O2 compared with the early indomethacin group at 24 (P = 0.026 and 0.02, respectively) and 48 h of life (P = 0.037 and 0.026, respectively). The requirement of surfactant was significantly larger in the early indomethacin group (P = 0.029). Early indomethacin administration increases oxygen and surfactant requirement.

[A severe form of vitamin D deficiency with hypocalcemic cardiomyopathy]. / Une forme sévère de carence en vitamine D avec cardiomyopathie hypocalcémique.

The authors report on a case of cardiomyopathy with congestive heart failure in an infant with severe hypocalcemia related to vitamin D deficient rickets. The heart failure was successfully treated with calcium gluconate and vitamin D, associated with dobutamide.

[Trial of initial non surgical treatment of subdural empyema]. / Tentative de traitement non chirurgical d'emblée d'un empyème sous-dural.

The authors report on an 8-year-old girl who experienced bilateral subdural frontoparietal and interhemispheric empyema following sinusitis. The child improved after initial treatment with a 3 weeks course of parenteral antibiotics. Surgical drainage was further required because of clinical aggravation; however, this evolution was related to bilateral frontoparietal brain edema and abscesses fluid was sterile.

[Cerebral arteriovenous malformations in a probable familial form of Rendu-Osler disease]. / Malformations artério-veineuses cérébrales dans une probable forme familiale de maladie de Rendu-Osler.

Cerebral arteriovenous malformations with neonatal manifestations are infrequent and virtually always fatal. Heart failure with an intracranial bruit is the most common presentation. Exceptionally, the aneurysm is a manifestation of Rendu-Osler-Weber syndrome which is inherited on an autosomal dominant basis. Development of cerebral arteriovenous malformations occurs very early as demonstrated by the discovery of two aneurysms with major repercussions on the cerebral parenchyma in a female with severe prematurity. Pregnant women with suspected Rendu-Osler-Weber syndrome should undergo ultrasound studies targeted at identifying untreatable cerebral lesions antenatally.

Maturation of peripheral nerves in preterm infants. Motor and proprioceptive nerve conduction.

The peripheral nerve maturation (proprioceptive and motor nerve conduction velocities (PNCV and MNCV] was studied in 3 groups of newborn babies. Two groups of premature babies (PT), studied when they reached the expected date of birth (group I, gestational age (GA) at birth 27-31 weeks, n = 13, group II, GA at birth 32-35 weeks, n = 9), were compared to 10 normal full-term newborns (FT). The MNCV of PT babies was similar to that of FT babies: group I 22.8 +/- 3.3 m/sec (X +/- S.D.), group II 24.9 +/- 4.3 m/sec, FT 25.7 +/- 3.9 m/sec. PNCV was significantly lower in group I (18.1 +/- 5.9 m/sec) than in group II (28.3 +/- 6.4 m/sec) and in FT babies (32.0 +/- 7.4 m/sec) (P less than 0.001). Such a delay in maturation could be partly responsible for the neurological impairment often observed in PT babies.