An observational study of blood concentrations and kinetics of methyl- and propyl-parabens in neonates.

PURPOSE: Systemic exposure to parabens in the neonatal population, in particular propyl-parabens (PPB), remains a concern. Blood concentrations and kinetics of methyl-parabens (MPB) and PPB were therefore determined in neonates receiving medicines containing these excipients. METHODS: A multi-centre, non-interventional, observational study of excipient-kinetics in neonates. 'Dried Blood Spot' samples were collected opportunistically at the same time as routine samples and the observations modelled using a non-linear mixed effects approach. RESULTS: A total of 841 blood MPB and PPB concentration data were available for evaluation from 181 pre- and term-neonates. Quantifiable blood concentrations of MPB and PPB were observed in 99% and 49% of patients, and 55% and 25% of all concentrations were above limit of detection (10 ng/ml), respectively. Only MPB data was amenable to modelling. Oral bioavailability was influenced by type of formulation and disposition was best described by a two compartment model with clearance (CL) influenced by post natal age (PNA); CL PNA<21 days 0.57 versus CL PNA>21 days 0.88 L/h. CONCLUSIONS: Daily repeated administration of parabens containing medicines can result in prolonged systemic exposure to the parent compound in neonates. Animal toxicology studies of PPB that specifically address the neonatal period are required before a permitted daily exposure for this age group can be established.

Risk assessment of neonatal excipient exposure: lessons from food safety and other areas.

Newborn babies can require significant amounts of medication containing excipients intended to improve the drug formulation. Most medicines given to neonates have been developed for adults or older children and contain excipients thought to be safe in these age groups. Many excipients have been used widely in neonates without obvious adverse effects. Some excipients may be toxic in high amounts in which case they need careful risk assessment. Alternatively, it is conceivable that ill-founded fears about excipients mean that potentially useful medicines are not made available to newborn babies. Choices about excipient exposure can occur at several stages throughout the lifecycle of a medicine, from product development through to clinical use. Making these choices requires a scalable approach to analysing the overall risk. In this contribution we examine these issues.

An Experimentally Validated Numerical Modeling Technique for Perforated Plate Heat Exchangers.

Cryogenic and high-temperature systems often require compact heat exchangers with a high resistance to axial conduction in order to control the heat transfer induced by axial temperature differences. One attractive design for such applications is a perforated plate heat exchanger that utilizes high conductivity perforated plates to provide the stream-to-stream heat transfer and low conductivity spacers to prevent axial conduction between the perforated plates. This paper presents a numerical model of a perforated plate heat exchanger that accounts for axial conduction, external parasitic heat loads, variable fluid and material properties, and conduction to and from the ends of the heat exchanger. The numerical model is validated by experimentally testing several perforated plate heat exchangers that are fabricated using microelectromechanical systems based manufacturing methods. This type of heat exchanger was investigated for potential use in a cryosurgical probe. One of these heat exchangers included perforated plates with integrated platinum resistance thermometers. These plates provided in situ measurements of the internal temperature distribution in addition to the temperature, pressure, and flow rate measured at the inlet and exit ports of the device. The platinum wires were deposited between the fluid passages on the perforated plate and are used to measure the temperature at the interface between the wall material and the flowing fluid. The experimental testing demonstrates the ability of the numerical model to accurately predict both the overall performance and the internal temperature distribution of perforated plate heat exchangers over a range of geometry and operating conditions. The parameters that were varied include the axial length, temperature range, mass flow rate, and working fluid.

Surgical staple trial in accident and emergency.

A trial was undertaken at the John Radcliffe Hospital, Oxford to establish if surgical staples were a viable alternative to traditional sutures in wound closure. The trial involved a sample of trained nursing staff using staples in the closure of simple skin lacerations presented at the Accident and Emergency (A & E) department. A questionnaire collected subjective and objective information from staff and patients relating to insertion and removal of the staples. Although there was no comparative data available for sutured wounds, the results indicated that staff were satisfied with the stapler's ease and speed of use. It was concluded that stapling was a viable addition to the choice of skin closure technique, rather than an alternative.