Respiratory symptoms in preterm infants: burden of disease in the first year of life.

OBJECTIVE: While respiratory symptoms in the first year of life are relatively well described for term infants, data for preterm infants are scarce. We aimed to describe the burden of respiratory disease in a group of preterm infants with and without bronchopulmonary dysplasia (BPD) and to assess the association of respiratory symptoms with perinatal, genetic and environmental risk factors. METHODS: Single centre birth cohort study: prospective recording of perinatal risk factors and retrospective assessment of respiratory symptoms during the first year of life by standardised questionnaires. MAIN OUTCOME MEASURES: Cough and wheeze (common symptoms), re-hospitalisation and need for inhalation therapy (severe outcomes). PATIENTS: 126 preterms (median gestational age 28.7 weeks; 78 with, 48 without BPD) hospitalised at the University Children's Hospital of Bern, Switzerland 1999-2006. RESULTS: Cough occurred in 80%, wheeze in 44%, re-hospitalisation in 25% and long term inhalation therapy in wheezers in 13% of the preterm infants. Using logistic regression, the main risk factor for common symptoms was frequent contact with other children. Severe outcomes were associated with maximal peak inspiratory pressure, arterial cord blood pH, APGAR- and CRIB-Score. CONCLUSIONS: Cough in preterm infants is as common as in term infants, whereas wheeze, inhalation therapy and re-hospitalisations occur more often. Severe outcomes are associated with perinatal risk factors. Preterm infants who did not qualify for BPD according to latest guidelines also showed a significant burden of respiratory disease in the first year of life.

The distribution of congenital anomalies within the VACTERL association among tumor necrosis factor antagonist-exposed pregnancies is similar to the general population.

OBJECTIVE: To compare the distribution of congenital anomalies within the VACTERL association (vertebral defects, anal atresia, cardiac, tracheoesophageal, renal, and limb abnormalities) between patients exposed to tumor necrosis factor-α (TNF-α) antagonist and the general population. METHODS: Analysis for comparison of proportional differences to a previous publication between anomaly subgroups, according to subgroup definitions of the European Surveillance of Congenital Anomalies (EUROCAT), a population-based database. RESULTS: Most EUROCAT subgroups belonging to the VACTERL association contained only one or 2 records of TNF-α antagonist exposure, so comparison of proportions was imprecise. Only the category "limb abnormalities" showed a significantly higher proportion in the general population. CONCLUSION: The high number of congenital anomalies belonging to the VACTERL association from a report of pregnancies exposed to TNF-α antagonists could not be confirmed using a population-based congenital anomaly database.

Recombinant erythropoietin in acute chemotherapy-induced anemia of children with cancer.

Chemotherapy-induced anemia in children with cancer is usually of acute onset. To investigate an alternate treatment to transfusion (Tx), we undertook a phase I-II clinical trial of daily administrations of recombinant erythropoietin (rHuEPO). Patients with a hemoglobin (Hgb) value < 75 g/l were treated for 14 days in cohorts of 3 at escalating daily doses of 25, 50, 70, 80, 90, and 100 U/kg respectively. The maximum-tolerated dose was not encountered. Of 18 courses given to 15 children aged 0.5-18 years, 7 (39%) were associated with increased or stable Hgb levels (courses without Tx), while 11 (61%) were terminated by a Tx, without evidence of a dose-response relationship. Changes in mean Hgb levels and absolute reticulocyte counts were paralleled by those of mean white blood cell, platelet, and absolute neutrophil counts during the first 7 days and when the end-points of the study were reached. Numbers of circulating burst-forming units-erythroid remained low throughout courses without Tx. No cumulative increase of serially determined serum EPO levels was observed and serum ferritin levels were elevated in both groups of courses. We conclude that daily administration of rHuEPO were safe but ineffective in our trial. Recovery of chemotherapy-induced myelosuppression appeared to be the rate-limiting factor for the outcome, without evidence of an enhanced stimulation of erythropoiesis. The lack of a proliferative response of specific progenitor cells suggested a mechanism of transient primary resistance to rHuEPO.

Interim analysis of the Reitan Catheter Pump (RCP) heart failure efficacy study: RCP improves cardiovascular and renal function in acute decompensated heart failure (ADHF)

Background: The RCP is a 14 French collapsable percutaneous cardiovascular support device positioned in the descending part of the thoracic aorta via the femoral artery. A 10 patient first in man study demonstrated device safety and significant improvement in renal function among high risk PCI patients. We now report haemodynamic and renal efficacy in patients with ADHF.Methods: Prospective non randomised study seeking to recruit 20 patients with ADHF with a need for inotropic or mechanical circulatory support with: i) EF < 30% ii)Cardiac index(CI) < 2.2 L / min / m2 Outcome measures included: 1) Cardiac index (CI) 2) Pulmonary Capillary Wedge Pressure (PCWP) 3) Urine output / serum creatinine 4) Vascular / device complications 5) 30 day mortalityResults: INTERIM ANALYSIS (n=12) The mean age of the study group was 64 years, with a mean baseline creatinine of 193 umol/L, eGFR 38 ml/min. The intended RCP treatment period was 24 hours. During RCP treatment there was a significant mean reduction of PCWP at 4 hours of 17% (25 to 21 mmHg p=0.04). Mean CI increased at 12 hours by 11%, though not reaching significance (1.78 to 1.96 L/min/m2 p=0.08). RCP insertion prompted substantial diuresis. Urine output tripled over the first 12 hours compared to baseline (55 ml/hr vs 213 ml/hr p=0.03). This was associated with significantly improved renal function, a 28% reduction in serum creatinine at 12 hours (193 to 151 umol/L p=0.003), and a increase in eGFR from 38 ml/min to 50 ml/min (p=0.0007). 2 patients previously refused cardiac transplantation were reassessed and successfully transplanted within 9 months of RCP treatment on the basis of demonstrable renal reversibility. There were no vascular or device complications. There were 2 deaths at 30 days, one from multi-organ failure and sepsis, and one from intractable heart failure - neither were device related.Conclusion: RCP support in ADHF patients was associated with improved haemodynamics, and an improvement in renal function. The Reitan Catheter Pump may have a role in providing percutaneous cardiovascular and renal support in the acutely decompensated cardiac patient, and may have a role in suggesting renal reversibility in potential cardiac transplant patients. Further data will be reported at recruitment completion.

Effects of corticosterone pellets on baseline and stress-induced corticosterone and corticosteroid-binding-globulin.

Exogenous administration of glucocorticoids is a widely used and efficient tool to investigate the effects of elevated concentrations of these hormones in field studies. Because the effects of corticosterone are dose and duration-dependent, the exact course of plasma corticosterone levels after exogenous administration needs to be known. We tested the performance of self-degradable corticosterone pellets (implanted under the skin) in elevating plasma corticosterone levels. We monitored baseline (sampled within 3min after capture) total corticosterone levels and investigated potential interactions with corticosteroid-binding-globulin (CBG) capacity and the endogenous corticosterone response to handling in Eurasian kestrel Falco tinnunculus and barn owl Tyto alba nestlings. Corticosterone pellets designed for a 7-day-release in rodents elevated circulating baseline total corticosterone during only 2-3 days compared to placebo-nestlings. Highest levels occurred 1-2days after implantation and levels decreased strongly thereafter. CBG capacity was also increased, resulting in a smaller, but still significant, increase in baseline free corticosterone levels. The release of endogenous corticosterone as a response to handling was strong in placebo-nestlings, but absent 2 and 8 days after corticosterone pellet implantation. This indicates a potential shut-down of the hypothalamo-pituitary-adrenal axis after the 2-3 days of elevated baseline corticosterone levels. 20 days after pellet implantation, the endogenous corticosterone response to handling of nestlings implanted with corticosterone pellets attained similar levels as in placebo-nestlings. Self-degradable pellets proved to be an efficient tool to artificially elevate circulating baseline corticosterone especially in field studies, requiring only one intervention. The resulting peak-like elevation of circulating corticosterone, the concomitant elevation of CBG capacity, and the absence of an endogenous corticosterone response to an acute stressor have to be taken into account.

Naissances vaudoises 1993-1994: caractéristiques et facteurs de risque pour une affection chronique: rapport EDEN no 1

Une cohorte de 6477 nouveau-nés de mères résidant dans le Canton du Vaud a été recrutée pendant une année (1993-1994) dans les 18 maternités vaudoises et celle de Châtel-St-Denis. L'objectif de l'étude EDEN (Etude du DEveloppement des Nouveau-nés) est de calculer l'incidence et la prévalence des affections chroniques de toute étiologie et pour toutes les catégories de poids de naissance, à 18 mois et à 4 ans. Ce rapport présente la méthode de l'étude et l'état de santé à la naissance. Cinq critères de sélection non exclusifs ont permis de cibler un groupe de nouveau-nés à haut risque de développer une affection chronique (12% des nouveau-nés, n=760): (1) le petit poids de naissance (n=408, 6.5% des naissances vivantes); (2) une malformation congénitale ou une maladie génétique (n=157, 2.4% des naissances vivantes); (3) une affection susceptible de devenir chronique liée à une utilisation importante des services de soins au cours de la petite enfance (n=61, 0.9% des naissances vivantes); (4) le transfert aux soins intensifs (n=287, 4.4% des naissances vivantes); (5) des difficultés sociales importantes (n=105, 1.6% des naissances vivantes). Le taux d'acceptation de l'étude par les parents est bon (90%). En tout 5.9% des enfants étaient prématurés et 2.2 pour mille sont décédés à < ou = à 7 jours de vie. Selon les indicateurs à disposition, le réseau vaudois répond efficacement aux besoins en soins obstétricaux et néonatals La durée moyenne du séjour hospitalier était de 7 jours, avec des variations importantes. L'influence néfaste du tabagisme pendant la grossesse se manifeste par un doublement du risque de poids de naissance < ou = à 2500g chez les fumeuses; 24% des femmes ont fumé pendant leur grossesse, pour les trois quarts jusqu'à l'accouchement. Un grand potentiel de prévention subsiste dans ce domaine. L'examen des enfants à 18 mois, terminé fin mai 1996, ainsi que celui des 4 ans, permettront de valider les critères de sélection à la naissance comme indicateurs précoces de problèmes de santé chroniques dans la petite enfance. Les nouveaux cas d'affection chronique seront alors signalés par les pédiatres et les médecins spécialistes. [Auteurs, p. 9]

Caracterització i conservació d’una població de tortuga de rierol (Mauremys Leprosa) a l’ein del riu Llobregat al terme d’Abrera

S'ha estudiat una població de tortuga de rierol (Mauremys leprosa) present al curs principal del riu Llobregat, al seu pas pel municipi d'Abrera (Baix Llobregat). El tram té una longitud de 4.140 metres de recorregut sinuós, inclòs a l'EIN Riu Llobregat, amb predomini d'albaredes i pollancredes. S'ha caracteritzat el tram de riu segons el tipus de secció que presenta al llarg de l'àrea d'estudi. L'activitat de les tortugues comprèn de mitjans de febrer a mitjans de novembre, sense que s'hagi detectat una disminució a l'estiu. L'ús de l'espai no és uniforme amb una marcada preferència per trams del riu amb una certa fondària i velocitat de l'aigua alentida. S’han capturat 68 tortugues de rierol mitjançant nanses de pesca adaptades i, un cop marcades, s'han alliberat al mateix lloc. Per a cada animal es van obtenir les dades biomètriques i es va determinar el sexe. Mitjançant el mètode de captura-recaptura s'ha estimat la mida de la població en 100 ± 11 individus. La ràtio de sexes de la població és de 2:1 a favor dels mascles. La distribució de classes d'edats permet comprovar que la població està ben estructurada. No s'ha comprovat la reproducció, tot i que el nombre de femelles reproductores és elevat. La falta de captures de nounats i d’individus d'un hivern d’edat, i el baix nombre de juvenils capturats fa pensar que la taxa de reclutament és baixa. La mobilitat dels animals aigües amunt està limitada per la presència de dos assuts a l'àrea d'estudi, la qual cosa compromet la connectivitat de la població dins i fora de l'àrea d'estudi. També s'ha detectat la presència de tortuga de Florida (Trachemys scripta spp.) sense que s'hagi observat cap interacció entre ambdues espècies. Es proposen un seguit de mesures per afavorir la conservació de la tortuga de rierol.

Neonatal dexamethasone induces premature microvascular maturation of the alveolar capillary network.

Postnatal glucocorticoid treatment of preterm infants was mimicked by treating newborn rats with dexamethasone (0.1-0.01 microg/g, days 1-4). This regimen has been shown to cause delayed alveolarization. Knowing that microvascular maturation (transformation of double- to single-layered capillary networks in alveolar septa) and septal thinning prevent further alveolarization, we measured septal maturation on electron photomicrographs in treated and control animals. In treated rats and before day 10, we observed a premature nonreversing microvascular maturation and a transient septal thinning, which both appeared focally. In vascular casts of both groups, we observed contacts between the two capillary layers of immature alveolar septa, which were predictive for capillary fusions. Studying serial electron microscopic sections of human lungs, we were able to confirm the postulated fusion process for the first time. We conclude that alveolar microvascular maturation indeed occurs by capillary fusion and that the dexamethasone-induced impairment of alveolarization is associated with focal premature capillary fusion.

Prospective evaluation of three point of care devices for glycemia measurement in a neonatal intensive care unit.

Hypoglycemia, if recurrent, may have severe consequences on cognitive and psychomotor development of neonates. Therefore, screening for hypoglycemia is a daily routine in every facility taking care of newborn infants. Point-of-care-testing (POCT) devices are interesting for neonatal use, as their handling is easy, measurements can be performed at bedside, demanded blood volume is small and results are readily available. However, such whole blood measurements are challenged by a wide variation of hematocrit in neonates and a spectrum of normal glucose concentration at the lower end of the test range. We conducted a prospective trial to check precision and accuracy of the best suitable POCT device for neonatal use from three leading companies in Europe. Of the three devices tested (Precision Xceed, Abbott; Elite XL, Bayer; Aviva Nano, Roche), Aviva Nano exhibited the best precision. None completely fulfilled the ISO-accuracy-criteria 15197: 2003 or 2011. Aviva Nano fulfilled these criteria in 92% of cases while the others were <87%. Precision Xceed reached the 95% limit of the 2003 ISO-criteria for values ≤4.2 mmol/L, but not for the higher range (71%). Although validated for adults, new POCT devices need to be specifically evaluated on newborn infants before adopting their routine use in neonatology.

Cell Adhesion Peptide RGDSP and Laminin Support Proliferation and Migration of Postnatal Retinal Stem Cells in a 3D Hydrogel Culture System

Purpose: Retinal stem cells (RSCs) can be isolated from radial glia population of the newborn mouse retina (Angénieux et al., 2006). These RSCs have great capacity to renew and generate neurons including cells differentiated towards the photoreceptor lineage (Mehri-Soussi et al., 2006). However, our published results showed poor integration and survival rate after cell grafting into the retina. The uncontrollable environment of retina seems to be the problem. To bypass this, we are trying to generate hemi-retinal tissue in vitro that can be used for transplantation. Methods: Expanded RSCs were seeded in a mixture of poly-ethylene-glycol (PEG)-polymer-based hydrogels crosslinked by peptides that also serve as substrates for matrix metalloproteinases. Different doses of crosslinker peptides were tested. Several growth factors were studied to stimulate cell proliferation and differentiation. Results: Cells were trapped in hydrogels and cultured in the presence of FGF2 and EGF. Spherical cell clusters indicating proliferation appeared within several days, but there was no cell migration within the gel. We then added cell adhesion molecules integrin ligand RGDSP, or laminin, or a combination of both, into the gel. Cells grown with laminin showed the best proliferation. Cells grown with RGDSP proliferated a few times and then started to spread out. Cells grown with the combination of RGDSP and laminin showed better proliferation than with RGDSP alone and larger spread-outs than with laminin alone. After stimulations with first FGF2 and EGF, and then only FGF2, some cells showed neuronal morphology after 2 weeks. The neuronal population was assessed by the presence of neuronal marker b-tubulin-III. Glial cells were also present. Further characterizations are undergoing. Conclusions: RSC can grow and migrate in 3D hydrogel with the addition of FGF2, EGF, RGDSP and laminin. Further developments are necessary to form a homogenous tissue containing retinal cells.

Number of X-ray examinations performed on paediatric and geriatric patients compared with adult patients.

The age of the patient is of prime importance when assessing the radiological risk to patients due to medical X-ray exposures and the total detriment to the population due to radiodiagnostics. In order to take into account the age-specific radiosensitivity, three age groups are considered: children, adults and the elderly. In this work, the relative number of examinations carried out on paediatric and geriatric patients is established, compared with adult patients, for radiodiagnostics as a whole, for dental and medical radiology, for 8 radiological modalities as well as for 40 types of X-ray examinations. The relative numbers of X-ray examinations are determined based on the corresponding age distributions of patients and that of the general population. Two broad groups of X-ray examinations may be defined. Group A comprises conventional radiography, fluoroscopy and computed tomography; for this group a paediatric patient undergoes half the number of examinations as that of an adult, and a geriatric patient undergoes 2.5 times more. Group B comprises angiography and interventional procedures; for this group a paediatric patient undergoes a one-fourth of the number of examinations carried out on an adult, and a geriatric patient undergoes five times more.