Vancomycin Pharmacokinetics Throughout Life: Results from a Pooled Population Analysis and Evaluation of Current Dosing Recommendations.

Background And Objectives: Uncertainty exists regarding the optimal dosing regimen for vancomycin in different patient populations, leading to a plethora of subgroup-specific pharmacokinetic models and derived dosing regimens. We aimed to investigate whether a single model for vancomycin could be developed based on a broad dataset covering the extremes of patient characteristics. Furthermore, as a benchmark for current dosing recommendations, we evaluated and optimised the expected vancomycin exposure throughout life and for specific patient subgroups.

Asthma therapy for children under 5 years of age.

Purpose Of Review: The evidence for effectiveness of currently used asthma medication for wheeze in young children is reviewed.

Recent Findings: The management of the infant and preschool child with wheezing is complicated by the uncertainty with respect to the aetiology. Difficulties in defining phenotypes and objective outcome parameters combined with the transient nature of symptoms which often resolve spontaneously have confounded many therapeutic studies.

Surrogate markers of airway inflammation: inflammometry in paediatric respiratory medicine.

Until recently, there has not been any practical way to assess airway inflammation non-invasively in paediatrics. Surrogate markers of airway inflammation are potentially of great importance in the diagnosis and monitoring of inflammatory airways disease in children. A large number of substances in blood, urine and exhaled air or induced sputum are currently under study to evaluate their possible usefulness as markers of airway inflammation.

Immunological effects of environmental exposure to polychlorinated biphenyls and dioxins in Dutch school children.

Perinatal exposure to PCBs and dioxins is associated with immune changes in healthy Dutch preschool children. To examine whether such effects persist into later childhood, we here report on the immunological effects of perinatal exposure to PCBs and dioxins in 167 Dutch children at school age. A higher postnatal PCB exposure was associated with a higher prevalence of recurrent middle ear infections and a higher prenatal PCB exposure with less shortness of breath with wheeze, as assessed by parent questionnaire.

Fetus with an unusual form of nonrhizomelic chondrodysplasia punctata: case report and review.

Chondrodysplasia punctata (CDP) is a heterogeneous condition mainly characterized by premature and ectopic calcification of cartilage. Many genetic and nongenetic causes have been described leading to a preliminar etiological classification into defects of peroxisomal metabolism, defects in cholesterol metabolism, and vitamin K (vit K) metabolism. However, numerous cases of CDP still remain unclassified.

Effectiveness of pharmacotherapy in asthmatic preschool children.

The term "effectiveness" relates to the question of whether or not a certain treatment works in practice. Usually, such a treatment was first evaluated under tightly controlled conditions in selected patient populations, and the potential benefits were shown. There is, however, a great difference between the efficacy of a given treatment, indicating its optimal therapeutic action in controlled trials, and its effectiveness when applied to a less well-defined population of patients in daily practice.

A pilot case control follow-up study on hearing in children treated with tobramycin in the newborn period.

Objective: To assess the occurrence of hearing loss in children due to neonatal exposure to long courses of tobramycin and/or high tobramycin serum concentrations.

Methods: This was a pilot case-control study in 3-4-year old children. Data on tobramycin administration were abstracted from the patient files of an earlier study.

CD40 ligation-induced cytokine production in human skin explants is partly mediated via IL-1.

CD40 ligation by CD40 ligand(+) CD4(+) T cells has been claimed to be involved in inflammatory responses in human skin. However, these data are derived from in vitro cell culture systems and immunohistochemistry, and the mechanisms involved have not been fully elucidated. We previously observed that cells in intact normal human skin secrete high levels of IL-6 and IL-8 upon stimulation with IL-1 beta.

NONMEM and NPEM2 population modeling: a comparison using tobramycin data in neonates.

Nonlinear mixed effects modeling (NONMEM) and nonparametric expectation maximization (NPEM2) have both been used in population modeling of tobramycin. We compared both methods for differences in population pharmacokinetic parameters in relation to error models used. Predictive performance was compared between models.

Extended-interval dosing of tobramycin in neonates: implications for therapeutic drug monitoring.

Objective: Our objective was to individualize tobramycin dosing regimens in neonates of various gestational ages with use of early therapeutic drug monitoring.

Methods: This study was performed in neonatal patients with suspected septicemia in the first week of life. All patients received tobramycin, 4 mg/kg per dose, as a 30-minute intravenous infusion, with a gestational age-related initial interval of 48 hours (<32 weeks), 36 hours (32-36 weeks), and 24 hours (> or =37 weeks).

A model system for optimising the selection of membrane antigen-specific human antibodies on intact cells using phage antibody display technology.

The functional expression of human antibody fragments on the surface of filamentous bacteriophage, and selection of phage antibodies (PhAbs) with antigens, has provided a powerful tool for generating novel antibodies. Applications of phage antibody display technology have increased over the past decade. Successful isolation of phage antibodies has been reported mostly using purified antigens.

Inhibition of septic shock in mice by an oligopeptide from the beta-chain of human chorionic gonadotrophin hormone.

Human chorionic gonadotrophin (hCG) is a heterodimeric placental glycoprotein hormone required in pregnancy. In human pregnancy urine and in commercial hCG preparations (c-hCG) it occurs in a variety of forms, including breakdown products. Several reports have suggested modulation of the immune system by intact hormone, but such effects of breakdown products have not been reported.

Effects of prenatal PCB and dioxin background exposure on cognitive and motor abilities in Dutch children at school age.

Objective: Our purpose was to evaluate whether effects of exposure to environmental levels of PCBs and dioxins on development in the Dutch cohort persist until school age.

Study Design: In the Dutch PCB/dioxin study, cognitive and motor abilities were assessed with the McCarthy Scales of Children's Abilities in children at school age. During infancy, half of this population was fully breast-fed for at least > or = 6 weeks and the other half formula fed.

Inhibition of diabetes in NOD mice by human pregnancy factor.

Clinical symptoms of Th1 mediated autoimmune diseases regress in many patients during pregnancy. A prominent feature of pregnancy is the presence of human chorionic gonadotrophin hormone (hCG) in blood and urine. In this report we tested the effect of clinical grade hCG (c-hCG) on the development of diabetes, a Th1 mediated autoimmune disease, in nonobese diabetic (NOD) mice.

Significantly higher number of fetal cells in the maternal circulation of women with pre-eclampsia.

Although the pathophysiology of pre-eclampsia is unknown, several studies have indicated that abnormal placentation early in pregnancy might play a key role. It has recently been suggested that this abnormal placentation may result in transfusion of fetal cells (feto-maternal transfusion) in women with pre-eclampsia. In the present study, fetal nucleated red blood cells were isolated from 20 women with pre-eclampsia and 20 controls using a very efficient magnetic activated cell sorting (MACS) protocol.

Nerve outgrowth and neuropeptide expression during the remodeling of human burn wound scars. A 7-month follow-up study of 22 patients.

Unlabelled: Increasing data suggest that the skin nerve system is involved in wound healing. The objective of this study was to investigate the outgrowth of nerve fibers during the burn wound remodeling process and to analyze possible differences between normotrophic and hypertrophic burn wounds. In a prospective study, biopsies were taken from 22 patients with spontaneously healed partial-thickness burns at 1, 4 and 7-month post-burn.

Off-line sampling of exhaled air for nitric oxide measurement in children: methodological aspects.

Measurement of nitric oxide in exhaled air is a noninvasive method to assess airway inflammation in asthma. This study was undertaken to establish the reference range of exhaled NO in healthy school-aged children and to determine the influence of ambient NO, noseclip and breath-holding on exhaled NO, using an off-line balloon sampling method. All children attending a primary school (age range 8-13 yrs) underwent NO measurements on two occasions with high and low ambient NO.

Definition of respiratory symptoms and disease in early childhood in large prospective birth cohort studies that predict the development of asthma.

We have reviewed the prospective value of early respiratory symptoms for determining the risk of development of asthma later in life by using data from studies based on the general population, hospital population, and general practices. Although "wheezing" in infancy generally has a good prognosis, it is an important risk factor for the development of asthma later in life. The prognostic value of "coughing" and "shortness of breath" in infancy for the later development of asthma is less clear.

Bacterial peptidoglycan and immune reactivity in the central nervous system in multiple sclerosis.

Multiple sclerosis is believed to result from a CD4+ T-cell response against myelin antigens. Peptidoglycan, a major component of the Gram-positive bacterial cell wall, is a functional lipopolysaccharide analogue with potent proinflammatory properties and is conceivably a mediator of sterile inflammation. Here we demonstrate that peptidoglycan is present within antigen-presenting cells in the brain of multiple sclerosis patients.

Differential ultraviolet-B-induced immunomodulation in XPA, XPC, and CSB DNA repair-deficient mice.

Ultraviolet B irradiation has serious consequences for cellular immunity and can suppress the rejection of skin tumors and the resistance to infectious diseases. DNA damage plays a crucial role in these immunomodulatory effects of ultraviolet B, as impaired repair of ultraviolet-B-induced DNA damage has been shown to cause suppression of cellular immunity. Ultraviolet-B-induced DNA damage is repaired by the nucleotide excision repair mechanism very efficiently.

Interrupter resistance in preschool children: measurement characteristics and reference values.

There is a need for quick, reliable, and noninvasive lung function tests to assess airway obstruction in preschool children both for pediatric pulmonary care as well as for research purposes. We studied feasibility, reproducibility, and validity of measurements of the respiratory system using the interrupter technique (interrupter resistance [Rint]) and obtained reference values in children from a general population, 2 to 7 yr of age. Accuracy was studied by comparisons of Rint with plethysmographic airway resistance (Raw) in 20 patients (7 to 14 yr) with mild to severe chronic airways obstruction and was satisfactory in patients with FEV(1) > 60% predicted.