No description available.

The objective of this randomized, double-blind, placebo-controlled trial was to determine whether glucose enhanced memory for a repeated auditory stimulus in human newborns. Infants consumed water or glucose (2-g/kg) solution. Memory test phases were: Orientation (turning towards the stimulus); Habituation (not turning towards), indicating familiarity; Delay (100 seconds); Spontaneous Recovery (stimulus representation: not turning towards indicates remembering, while turning towards indicates forgetting), and Novelty (turning towards a different word confirms wakefulness). Decreased head-turning towards during Spontaneous Recovery indicates enhanced memory. Blood glucose levels were measured after testing. / "Glucose" infants had higher blood glucose levels than "water" infants (p < 0.001). "Glucose" infants had significantly decreased turns towards during Spontaneous Recovery compared to "water" infants (p = 0.008), indicating memory enhancement. / Therefore, glucose specifically enhances memory for a repeated auditory stimulus in newborn humans. Elevating blood glucose levels by approximately 2 mmol/L appears to be sufficient for memory enhancement in healthy newborns.

Pain behavior of neonates was compared across sleep/waking states and sex. From Gate-Control Theory (Melzack and Wall, 1982) it was hypothesized that pain behavior would vary depending on the ongoing functional state of the infant, in contrast with Specificity Theory (Mountcastle, 1980), from which one would expect neonatal pain expression to be solely a function of degree of tissue damage. The findings of facial action variation across sleep/waking state was interpreted as consistent with Gate-Control Theory. Awake alert infants responded with the most facial activity, which supported Brazelton's (1973) view that infants in this state are most receptive to environmental stimulation. Fundamental frequency of cry was not related to sleep/waking state. This suggested that findings from the cry literature on pain cry as a reflection of nervous system "stress", in unwell newborns, do not generalize directly to healthy infants under varying degrees of stress as a function of state. Sex differences were apparent in speed of response, with boys showing shorter time to cry and facial action following heel-lance. Issues raised by the study include the importance of using measurement techniques which are independent of pre-conceived categories of affective response, and the surprising degree of responsivity of the neonate to ongoing events. Exploratory analyses suggested obstetric factors were related to overall facial action. Caution was expressed in this interpretation due to the great complexity of the inter-relationships of medical, physiological and maternal variables which go far beyond the scope of this study. It was concluded that obstetric features such as mode of delivery should be considered in sample selection for neonatal pain studies, in contrast to current practise which has been to assume healthy newborns form an homogeneous population. It was clear from these findings that the issues are multifaceted, and the optimal way to proceed with research in the area of neonatal pain is with an interdisciplinary team format. / Graduate and Postdoctoral Studies / Graduate

No description available.

This study explored infants' immediate and residual responses to holding and rocking, and how these responses relate to previously proposed mechanisms to explain long term benefits found when infants are repeatedly exposed to tactile and vestibular stimulation. This form of stimulation has been proposed to increase infants' ability to control and organize l) their behavioral state, 2) their arousal and autonomic functioning, or 3) that there is no clear relationship between immediate responses and long term benefits. Behavioral state and heart rate were collected on 40 infants who were randomly assigned to either a control group where infants were briefly repositioned twice but otherwise lay undisturbed for 90 minutes or an experimental group where infants were held and rocked for 30 minutes during the middle of a 90-minute observation. Results of analyses showed that, when infants were held and rocked they 1) displayed a lower Heart Rate Mean and Standard Deviation, 2) displayed a lower Mean Heart Rate During Active Sleep, 3) spent less time in a FussCry State, 3) were less likely to cry continuously, and 4) displayed nominally Smoother State Transitions and greater Stability Within States. Following the cessation of the rocking stimulus infants in the Experimental Group l) displayed a lower Mean Heart Rate, 2) displayed a lower Mean Heart Rate while in a Quiet Alert State, 3) were more likely to spend some time in a Quiet Sleep State, and 4) were less likely to cry continuously. In addition, all infants displayed Smoother State Transitions and greater Stability Within States during the first 30 minutes than during the final 30 minutes of the observation. Finally, across the 90-minute observation, the infants who were not rocked spent progressively more time in a Quiet Alert State, whereas infants who were rocked spent less time in a Quiet Alert State. The results were the most consistent with the hypothesis that the mechanism leading to both the immediate and residual effects of the stimulation was an increase in control and organization of infants’ arousal and autonomic functioning. / Ph. D.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 5 uppsatser.

Mise en contexte : Les chémoréflexes laryngés (CRI) sont déclenchés suite au contact entre un liquide et la muqueuse laryngée. Chez un organisme mature, ces CRL sont responsables de mécanismes de protection des voies aériennes inférieures (VAI) tels que déglutitions, toux et réaction d'éveil afin d'éviter l'aspiration. Par contre, chez un organisme immature comme c'est le cas chez les nouveau-nés, ces CRL associent apnée, bradycardie, laryngospasme, hypertension et redistribution du débit sanguin. En période néonatale, ces CRL, déclenchés en réponse à un reflux gastro-oesophagien acide, sont tenus responsables d'apnées du prématuré, de malaises graves du nourrisson (ALTE) et probablement de quelques cas de mort subite du nourrisson (MSN). Malgré leur pertinence clinique évidente, la revue de la littérature permet de constater que de nombreuses questions persistent concernant les CRL, principalement parce que les conditions expérimentales des études antérieures ne reflètent pas ce qui est vu en clinique. Ainsi, les CRL ont été étudiés le plus souvent en utilisant des modèles anesthésiés, en utilisant l'eau distillée, en se servant d'une trachéotomie pour l'injection des solutions et finalement en ne prenant pas en compte les stades de conscience. Une meilleure compréhension des CRL, en particulier déclenchés par des solutions acides, est donc nécessaire. But du projet : Le but de ce travail est d'étudier les CRL chez l'agneau nouveau-né sans sédation en réponse à l'acide, en comparaison à l'eau distillée et au salin durant le sommeil calme.

Neonatal jaundice is a physiological condition which has potentially deleterious outcomes. Elevated serum bilirubin levels are well-documented antioxidants and have been shown to disrupt cellular membranes of Gram-positive organisms under specific conditions. To determine whether bilirubin had antimicrobial potential against neonatal sepsis organisms, relevant isolates were identified by clinical audit and assessed for sensitivity. 26 clinical isolates including 15 CoNS, 7 GBS, E. coli, E. faecalis, K. oxytoca and A. haemolyticum were characterised biochemically, genetically, and by MALDI Biotype. GBS isolates showed a significant reduction in growth from 100–82.0%(±6.1%), between 0–400μM bilirubin– supplemented CBA (p=0.005). A physiologically relevant liquid model with 100μM bilirubin was developed to test growth reduction. Results showed slight growth reduction in isolates at specific time points, but species specific. Transcriptomic analysis was performed on three GBS isolates to determine effect of bilirubin exposure on gene expression. 17 genes were differentially expressed between 100μM bilirubin and solvent control; 16 up-regulated and one down-regulated with bilirubin. Most significantly, a 5 gene cluster describing multiple components of the phosphotransferase system and two ABC transporter genes were up-regulated, potentially to remove bilirubin from the cell. Proteomic analysis was completed to study protein expression: 12 proteins were identified by LC-MS from 2-DGE and Progenesis SameSpots analysis. Of these, 6 were up- and 6 down-regulated with bilirubin. Up-regulated proteins included two ABC transporter components, phosphoglycerate kinase, S-ribosylhomocysteinase, and two transcription regulators: GroEL/GntR. Down-regulated was iron ABC transporter, NeuB, ornithine carbamoyltransferase and ssDNA binding proteins controlling transcription and translation. This study concluded that bilirubin may play a protective role during the neonatal period; it can be considered an antimicrobial compound which disrupts Grampositive organisms such as GBS, an important agent in early-onset sepsis. The results from this study could be used to develop novel antimicrobial treatments based on identified molecular targets.

published_or_final_version / Paediatrics / Doctoral / Doctor of Philosophy

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences