Integrated plasma cortisol concentration in children with asthma receiving long-term inhaled corticosteroids.

We assessed the effect of long-term therapy with inhaled beclomethasone dipropionate (BDP) on the pituitary-adrenal axis, by measuring the integrated concentration (IC) of plasma cortisol in eight children with asthma (age, 6-16 years) who regularly used inhaled BDP in doses ranging from 8 to 26.5 micrograms/kg (200-450 micrograms/day) for 6 months to 4 years. The control group included six children (age, 6-16 years) who had the IC of plasma cortisol measured as part of an endocrinological evaluation and were found to be healthy. Cortisol concentration was measured in blood samples collected continuously over a 24-hr period. Mean IC of plasma cortisol in the study group was significantly lower than in the healthy controls (mean +/- SD, 4.9 +/- 3.3 vs 9.1 +/- 1.9 micrograms/mL; P less than 0.02). Cortisol response to 0.25 mg ACTH (iv) was abnormal in one of the eight BDP-treated patients. No correlation was found between IC of plasma cortisol and the BDP dose, severity of asthma, height percentile, or the Tanner stage. We conclude that long-term therapy, even with relatively conventional doses of inhaled BDP may cause reduction in the normal physiological secretion of cortisol. The clinical relevance of low IC of plasma cortisol is not clear, but it may reflect partial suppression of the pituitary-adrenal axis.     

Neonatal RBC transfusions: Do benefits outweigh risks?

Preterm neonates represent one of the most transfused categories of patients. Their target hematocrits, however, are mainly based on expert opinion. The risk of transfusions are very high in the smallest preterm baby with a weak immune response, immature antioxidant ability, fragile germinal matrix and impaired cerebral autoregulation, yet red cell transfusions remain the only life saving measure in the baby with symptomatic anemia.Minimizing phlebotomy losses, following a restrictive transfusion policy and using screened, leukocyte depleted, irradiated, single donor blood remain the best means of avoiding the possible risks while maximizing the benefits of red cell transfusions in the preterm newborn.     

Three monthly doses of palivizumab are not adequate for 5-month protection: A population pharmacokinetic analysis

Recent guidelines in British Columbia, Canada have suggested that the use of a maximum of 3 monthly doses of palivizumab 15 mg/kg intramuscularly for RSV immunoprophylaxis of high risk infants born prior to the RSV season is adequate to provide protection against severe RSV disease for a 5-month RSV season. Efficacy was established, however, with 2 large, randomized controlled clinical studies using 5 monthly doses of immunoprophylaxis. To evaluate the differences in expected palivizumab exposures between the 2 dosing regimens (3 vs 5 monthly doses across a 5-month period), we used a population pharmacokinetic (PK) model that was developed using palivizumab PK data collected from 22 clinical studies with a total of 1800 subjects. This model adequately described observed palivizumab concentrations from the different pediatric studies and was subsequently used to simulate expected palivizumab serum concentrations for 3 monthly doses compared with 5 monthly doses in children younger than 24 months with chronic lung disease of prematurity and infants younger than 6 months postnatal age who were born at ≤35 weeks gestational age. Results from the population PK model indicated lower serum concentrations of palivizumab during the fourth and fifth months, after an abbreviated 3-monthly–dose regimen when compared with the mean trough concentrations seen with the 5-monthly–dose regimen studied in the pivotal clinical trials in premature infants. Specifically, during the fourth and fifth months, 52% and 85%, respectively, would have levels below the lowest concentration (fifth percentile) in those receiving the 5-monthly-dose regimen. Simulations using this model did not support a 3-monthly–dose regimen to protect against severe RSV disease during the typical 5-month season.     

Effect of sleep state on chest wall movements and gas exchange in infants with resolving bronchopulmonary dysplasia

During active sleep, neonates exhibit asynchronous chest wall movements, which have been associated with a small but significant decrease in oxygenation. To determine the effects of maturation and residual chronic lung disease on both these phenomena, we studied 11 preterm infants with resolving bronchopulmonary dysplasia (BPD) and compared these infants to ten healthy preterm infants all at time of discharge. Synchrony of chest wall (upper rib cage and abdominal) movements, sleep state, O2 saturation, and transcutaneous CO2 (TcPCO2) were recorded during both active (AS) and quiet sleep (QS). Sleep state was determined by electroencephalographic and behavioral criteria. Normal preterm infants displayed asynchronous chest wall movements only in AS, whereas, in infants with BPD, asynchrony predominated in both sleep states, although O2 saturation and TcPCO2 did not differ between sleep states in either group. The O2 saturation during AS was lower in the BPD group than in the group of normal infants (92% vs 96%; P less than 0.02), whereas TcPCO2 was higher in the BPD group unrelated to sleep state. We conclude that infants with resolving BPD exhibit asynchronous chest wall movements in both AS and QS, and that change in sleep state from QS to AS is not associated with a detrimental fall in oxygenation in these infants.     

Metabolic Surgery: Weight Loss,Diabetes, and Beyond

The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity. Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further examines their potential effects on cardiovascular outcomes and mortality and discusses future perspectives.     

Laparoscopic Adjustable Pyloric Band with Fundoplication in Bariatric Surgery: Technique and Preliminary Results

Background Laparoscopic biliopancreatic diversion according to Scopinaro is an extremely effective operation for weight loss, but carries significant morbidity in terms of metabolic deficiencies. Methods A study was conducted as to the feasibility, safety and efficiency of a novel procedure, accomplishing a ‘reversible Scopinaro BPD’, performed in two stages: first the placement of an adjustable band in a juxtapyloric position, aiming at maintaining postprandial satiety, and second, the construction of a transmesocolic Roux-en-Y gastro-enterostomy with a 2.5-m long distal jejunal limb, reanastomosed 50 cm proximal to the ileocecal valve. Results 15 patients, mean BMI 38.9, 8 males and 7 females, underwent the first stage of pyloric adjustable banding. All benefited at the same time from a Nissen fundoplication, to avoid gastroesophageal reflux. 1 patient was withdrawn from the study at this stage because of peritonitis of unknown cause and removal of the band. 3 patients benefited from the second stage of the operation because of insufficient weight loss, and/or symptoms of gastric stasis. 1 patient developed diarrhea and was treated by peroral cholestyramine.Weight loss was similar to the regular BPD figures. Conclusion The placement of an adjustable gastric band in a juxtapyloric position, combined with a Nissen fundoplication, appears to be a safe and efficient satiety-inducing operation. In case of insufficient weight loss, and/or exaggerated gastric stasis, a Scopinaro BPD construction can be added to the otherwise unharmed stomach, hereby constituting an instantly reversible malabsorptive component.