Presence of Increased Mast Cells in Infants and Children with Volume and Variety Limited Intake

Background: Reports indicate patients with feeding difficulties demonstrate signs of inflammation on biopsies, notably eosinophilia, but it is unknown whether mast cell density contributes to variety or volume limitation symptoms. The aim of our study was to evaluate eosinophil and mast cell density of EGD biopsies in pediatric patients with symptoms of decreased volume or variety of ingested foods. Methods: We conducted a single-center, retrospective chart review of EMRs for all new feeding clinic patients between 0 and 17 years of age. Patients were categorized by symptoms at the initial visit as well as eosinophil and mast cell densities in those with EGD biopsies. Ten patients were identified as controls. Results: We identified 30 patients each with volume and variety limitation. Antral mast cell density was increased in 32.1% of variety-limited patients, 37.5% of volume limited patients, and in no controls; Duodenal mast cell density was increased in 32.1% of variety-limited patients, 40.6% of volume-limited patients, and in no controls. Conclusions: In both variety- and volume-limited patients, antral and duodenal mast cell densities were increased. These associations warrant further investigation of the mechanism between mast cells and development of feeding difficulties, allowing more targeted pediatric therapies.

Clinical Pharmacology of Fentanyl in Infants and Children

Fentanyl is a systemic opioid related to the phenylpiperidines, it is used in anaesthetic practice and in analgesia and the analgesic effect is about 100 times higher than that of morphine. Fentanyl is highly lipid soluble, rapidly crosses the blood-brain-barrier, and fentanyl concentrations rapidly decline in plasma and cerebrospinal fluid. Fentanyl causes respiratory depression and decreases the heart rate through vagal activation. Fentanyl may be administered intravenously, orally, by transdermal, intranasal or by buccal application and the oral bioavailability is poor. In infants, fentanyl is given for short term use, sustained use, and during therapeutic hypothermia. In children, fentanyl is given intravenously, by transdermal application, or by buccal administration and the fentanyl dose varies with the child age and body-weight. Fentanyl has been found efficacy and safe in infants and children but it may induce adverse-effects and fentanyl causes different effects in infants and children. Following intravenous administration of fentanyl to infants and children, the fentanyl elimination half-life ranges from 208 to 1,266 min and the distribution volume ranges from 1.92 to 15.2 L/kg. Such variability is due to the wide variation of subject’s demographic characteristics. Fentanyl interacts with drugs, the treatment and trials with fentanyl have been studied in infants and children. Fentanyl freely crosses the human placenta and poorly migrates into the breast-milk. The aim of this study is to review fentanyl dosing, efficacy, safety, effects, adverse-effects, metabolism, pharmacokinetics, drug interaction, treatment, and trials in infants and children, and fentanyl placental transfer and migration into the breast-milk.

Clinical Pharmacology of Rocuronium in Infants and Children

The main clinical use of the neuromuscular blocking agents is an adjuvant in surgical anaesthesia to obtain relaxation of skeletal muscle, particularly of the abdominal wall, to facilitate surgical manipulations. Rocuronium can be used instead of suxamethonium to provide rapid muscle paralysis during tracheal intubation but the recovery is much slower. Rocuronium is administered intravenously to infants and children. In infants, rocuronium is administered at a dose of 450 µg/kg for providing muscle relaxation for laryngeal intubation. To provide sustained paralysis, rocuronium is given at a dose of 600 µg/kg. In children, the neuromuscular blockade is obtained with 600 µg/kg followed by an intravenous infusion of 150 µg/kg per hour. For assisted ventilation in intensive care, rocuronium is administered at a dose of 600 µg/kg followed by an intravenous infusion of 300 to 600 µg/kg per hour. The effects of rocuronium have been extensively studied in infants and children. Rocuronium is converted into 17-desacetyl rocuronium. The pharmacokinetics of rocuronium have been studied in infants and children and the mean residence time is 55.6 and 25.6 min (P-value < 0.01) in infant and children, respectively. Rocuronium interacts with drugs, the treatment of infants and children with rocuronium has been studied, and rocuronium poorly crosses the human placenta. The aim of this study is to review the published data on rocuronium dosing, pharmacokinetics, and treatment in infants and children, and rocuronium metabolism and transfer across the human placenta.

Clinical Pharmacology of Levetiracetam in Infants and Children

Levetiracetam inhibits focal and secondary generalized tonic-clonic seizures. The mechanism of levetiracetam action is not fully understood, however the correlation between binding affinity of levetiracetam and its analogues and their potency toward audiogenic seizures suggest that the synaptic vesicle glycoprotein 2A mediates the anticonvulsant effects of levetiracetam. The neural function of the synaptic vesicle 2A protein is not fully understood, but binding of levetiracetam to synaptic vesicle glycoprotein 2A might affect neuronal excitability by modifying the release of glutamate GABA through an action on vesicular function. Synaptic vesicle glycoprotein 2A may plain a role in vesicle recycling following exocytosis of neurotransmitter. In addition, levetiracetam inhibits N-type Ca2+ channels and Ca2+ release from intracellular stores. Levetiracetam may be administered intravenously or orally to infants and children and in children the levetiracetam dose varies according to the child age and body-weight. Levetiracetam is almost completed absorbed after oral administration and levetiracetam is found efficacy and safe in infants and children but it may induce adverse-effects. The levetiracetam elimination half-life is about 6 hours in infants and children, and in children the renal clearance is similar to the non-renal clearance. The prophylaxis, treatment, and trials with levetiracetam have been extensively studied in infants and children. Levetiracetam freely crosses the human placenta and freely migrates into the breast-milk. The aim of this study is to review the levetiracetam dosing, efficacy, safety, adverse-effects, pharmacokinetics, prophylaxis, treatment, and trials and transfer of levetiracetam across the human placenta and levetiracetam migration into the breast-milk.

Clinical pharmacology of lorazepam in infants and children

Lorazepam is a benzodiazepine has antiepileptic activity; it may be administered intravenously, intramuscularly, orally, by intranasal or buccal application and following oral dosing it is well absorbed. In infants, the initial intravenous dose of lorazepam is 100 µg/kg and in children the initial oral and intravenous dose is 50 to 100 µg/kg and the dose varies according to the child age. Lorazepam has been found efficacy and safe in infants and children but it may induce adverse-effects. Lorazepam is a racemate and the R and S enantiomers are conjugated with glucuronic acid in human liver microsomes and the respective Km and Vmax values are 29+8.9 and 36+10 µM and 7.4+1.9 and 10+3.8 pmol/min*mg. Lorazepam interacts with drugs and the interaction may affect the activity or metabolism of lorazepam. The pharmacokinetics of lorazepam have been studied in infants and children and in diseased children. In infants and children the elimination half-life is about 15 hours and it is about 24 hours and about 37 hours in children with severe malaria and convulsions following intravenous and intramuscular administration, respectively. The treatment and trials with lorazepam have been studied in infants and children. Lorazepam freely crosses the human placenta and poorly migrates into the breast-milk. The aim of this study is to review the published data on lorazepam dosing, efficacy and safety, adverse-effects, metabolism, interaction with drugs, pharmacokinetics, treatment and trials in infants and children and the lorazepam transfer across the human placenta and migration into the breast-milk.