Early weight measures and long-term neuropsychological outcome of critically ill neonates and infants: a secondary analysis of the PEPaNIC trial.

Neonates and infants surviving critical illness show impaired growth during critical illness and are at risk for later neuropsychological impairments. Early identification of individuals most at risk is needed to provide tailored long-term follow-up and care. The research question is whether early growth during hospitalization is associated with growth and neuropsychological outcomes in neonates and infants after pediatric intensive care unit admission (PICU). This is a secondary analysis of the PEPaNIC trial. Weight measurements upon PICU admission, at PICU discharge, at hospital discharge, at 2- and 4-year follow-up, and of different subgroups were compared using (paired) t-tests. Multiple linear regression analyses were performed to investigate the association between early growth in weight measures and neuropsychological outcomes at 4-year follow-up. One hundred twenty-one infants were included, and median age upon admission was 21 days. Growth in weight per week was less than the age-appropriate norm, resulting in a decrease in weight-for-age Z-score during hospitalization. Weight is normalized at 2- and 4-year follow-up. Weight gain in kilograms per week and change in weight Z-score were not associated with neurodevelopmental outcome measures at 4-year follow-up. Lower weight-for-age Z-score at PICU admission and at hospital discharge was associated only with lower weight and height Z-scores at 4-year follow-up. CONCLUSION: Growth in weight during hospital stay of young survivors of critical illness is impaired. Worse early growth in weight is associated with lower weight and height but not with neuropsychological outcomes at 4-year follow-up. WHAT IS KNOWN: • Critically ill neonates and infants show impaired early growth during admission and are at risk for later neuropsychological impairments. • Unraveling the association between early growth and later neuropsychological impairments is crucial since the first year of life is critical for brain development. WHAT IS NEW: • Critically ill neonates and infants had age appropriate weight measures at 4-year follow-up. • Poor growth in weight during hospital stay was not associated with poorer cognitive, emotional, or behavioral functioning four years after critical illness.

A ratiometric imaging method for mapping ion flux densities.

A heterogeneous distribution of ion channels on the cell surface is a prerequisite for several cellular functions. Thus, there has been considerable interest in methods allowing the mapping of ion channel distributions. Here we report on a novel ratiometric imaging technique appropriate to measure spatially resolved ion flux signals by using ion sensitive dyes. However, given that certain relevant cell properties like the surface to volume ratio may exhibit significant spatial heterogeneities, the local influx signal cannot be interpreted as a measure of the local open channel concentration or flux density. To overcome this problem, we suggest an internal normalization procedure, which, in analogy to, but clearly distinct from, well-established ratioing techniques, eliminates effects which would otherwise obscure the desired result. Ratioing is performed on flux signals from a given cell, triggered by two different, subsequent stimuli. If the two stimuli address different ion channels, the flux density distribution caused by two channel types can be determined relative to each other. In cases where one of the stimuli triggers a spatially homogeneous flux signal, ratioing yields an ion flux density map for a given channel type. Thus distribution patterns of ion channels active during a given stimulus may be derived.

Fallacy in direct cystourethrography.

Voiding cystourethrography is widely used in children to detect vesicoureteral reflux disease. A case of radionuclide voiding cystourethrography is reported, where the initial location of the catheter tip in an open ureter ostium might have lead to erroneous interpretation. Recommendations for catheter technique and control of imaging in voiding cystourethrography are given.

[Attitudes of parents towards treatment of extremely premature infants]. / Foraeldreholdninger til behandling af ekstremt tidligt fødte børn.

The aim of this study was to evaluate the attitude among parents of extremely premature newborn children towards fixed lower limits for treatment and towards parent involvement in decisions about the treatment of their child. All parents with extremely premature newborns admitted from January 1, 1992 to June 30, 1994 to the Neonatal Department, Hvidovre Hospital, Copenhagen, Denmark, were asked to fill in questionnaires. The study population comprised the parents of 58 children. The parents of 14 children did not want to participate. Of the remaining 44, 36 children were alive and eight had died at the time of the study. Almost all parents stated that neither birth weight nor gestational age were acceptable as criteria for treatment or non-treatment of premature newborns. This attitude contrasted with the recommendation in 1994 from The Danish Council of Ethics. Half of the parents expressed a wish to be involved in the decisions about the treatment of their newborn child. This attitude agreed with the recommendation from the Danish Council of Ethics.

Purification and characterization of the sesquiterpene cyclase patchoulol synthase from Pogostemon cablin.

The sesquiterpene cyclase, patchoulol synthase, from Pogostemon cablin (patchouli) leaves was purified to apparent homogeneity by chromatofocusing, anion exchange, gel permeation, and hydroxylapatite chromatography. The enzyme showed a maximum specific activity of about 20 nmol/min/mg protein, and a native molecular weight of 80,000 as determined by gel permeation chromatography. The protein was very hydrophobic, as judged by chromatographic behavior on several matrices, and possessed a pI value of about 5.0, as determined by isoelectric and chromatofocusing. SDS-PAGE showed the enzyme to be composed of two apparently identical subunits of Mr approximately 40,000. Maximum activity was observed at pH 6.7 in the presence of Mg2+ (Km approximately 1.7 mM); other divalent metal ions were ineffective in promoting catalysis. The Km value for the substrate, farnesyl pyrophosphate, was 6.8 microM. Patchoulol synthase copurified with the ability to transform farnesyl pyrophosphate to cyclic olefins (alpha- and beta-patchoulene, alpha-bulnesene, and alpha-guiaene) and this observation, plus evidence based on differential inhibition and inactivation studies, suggested that these structurally related products are synthesized by the same cyclase enzyme. In general properties, the patchoulol synthase from patchouli leaves resembles fungal sesquiterpene olefin cyclases except for the ability to synthesize multiple products, a property more typical of monoterpene cyclases of higher plant origin.

Inhaled budesonide for treatment of recurrent wheezing in early childhood.

77 children, aged 11 to 36 months (mean 24) with moderately severe recurrent wheezing, were treated with budesonide pressurised aerosol 400 micrograms twice daily or placebo for 12 weeks in a double-blind, parallel-group trial. Aerosols were inhaled from a spacer with a facemask. Budesonide significantly improved symptom scores of wheezing, sleep disturbance, and patient happiness. The frequency of severe exacerbations that required a course of oral prednisolone was also significantly reduced. The treatment effect appeared to be fully established after 6-8 weeks and no side-effects could be ascribed to the active treatment. The findings indicate that young children below 3 years of age can inhale a pressurised aerosol from a spacer with a facemask. Use of topically active glucocorticosteroids with this simple device may reduce symptoms and distress in young children with moderately severe recurrent wheeze and dyspnoea, and possibly reduce their requirement for oral steroids.

Biosynthesis of the sesquiterpene patchoulol from farnesyl pyrophosphate in leaf extracts of Pogostemon cablin (patchouli): mechanistic considerations.

Several mechanistic alternatives have been proposed for the enzyme-catalyzed, electrophilic cyclization of farnesyl pyrophosphate to the tricyclic sesquiterpene alcohol patchoulol, which is the characteristic component of the essential oil of Pogostemon cablin (patchouli). These alternatives include schemes involving deprotonation-reprotonation steps and the intermediacy of the monocyclic and bicyclic olefins germacrene and bulnesene, respectively, and involving a 1,3-hydride shift with only tertiary cationic intermediates and without any deprotonation-reprotonation steps. Analytical studies, based on analyses of P. cablin leaf oil at different stages of plant development, and in vivo time-course investigations, using 14CO2 and [14C]sucrose, gave no indication that germacrene and bulnesene were intermediates in patchoulol biosynthesis. A soluble enzyme system from P. cablin leaves was prepared, which was capable of converting farnesyl pyrophosphate to patchoulol, and isotopic dilution experiments with both labeled and unlabeled olefins were carried out with this system to confirm that sesquiterpene olefins did not participate as fre intermediates in the transformation of the acyclic precursor to patchoulol. Patchoulol derived biosynthetically from [12,13-14C;1-3H]farnesyl pyrophosphate was chemically degraded to establish the overall construction pattern of the product. Similar studies with [12,13-14C;6-3H]farnesyl pyrophosphate as a precursor eliminated deprotonation steps to form bound olefinic intermediates in the biosynthesis of patchoulol, while providing supporting evidence for the hydride shift mechanism.