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Unlabelled: Cranial irradiation in children with acute lymphatic leukaemia (ALL) decreases the risk of CNS relapse but is associated with serious long-term side-effects. We present the long-term outcome of 21 children with high-risk ALL who received prolonged intrathecal chemotherapy instead of the recommended cranial irradiation. Intrathecal triple therapy (methotrexate, hydrocortisone, and cytarabine) was administered every 2nd month throughout the maintenance phase. The average number of courses of intrathecal methotrexate was 8.7 and of triple 9.0. The 5-year event-free survival was 79%. No CNS relapses occurred. CT scan was performed at diagnosis, at cessation of therapy, and 3 years thereafter. No density abnormalities, pathological contrast enhancement, ventricular dilatation, or calcifications were found. One child showed cortical atrophy both at diagnosis and at cessation of therapy. There was a slight decrease in height SDS with time but no change in weight SDS. Delayed bone age was found in 5 children. No abnormalities of growth hormone, thyroid, adrenal, or gonadal function were observed.Conclusion: The study indicates that extended intrathecal chemotherapy in children with high-risk ALL may provide an effective protection from CNS relapses and is associated with a low risk of long-term side-effects. [ABSTRACT FROM AUTHOR]

Three distinct pharmacological corrector types (I, II, III) with different binding sites and additive behavior only partially rescue the F508del-cystic fibrosis transmembrane conductance regulator (CFTR) folding and trafficking defect observed in cystic fibrosis. We describe uniquely effective, macrocyclic CFTR correctors that were additive to the known corrector types, exerting a complementary "type IV" corrector mechanism. Macrocycles achieved wild-type-like folding efficiency of F508del-CFTR at the endoplasmic reticulum and normalized CFTR currents in reconstituted patient-derived bronchial epithelium. Using photo-activatable macrocycles, docking studies and site-directed mutagenesis a highly probable binding site and pose for type IV correctors was identified in a cavity between lasso helix-1 (Lh1) and transmembrane helix-1 of membrane spanning domain (MSD)-1, distinct from the known corrector binding sites. Since only F508del-CFTR fragments spanning from Lh1 until MSD2 responded to type IV correctors, these likely promote cotranslational assembly of Lh1, MSD1, and MSD2. Previously corrector-resistant CFTR folding mutants were also robustly rescued, suggesting substantial therapeutic potential for type IV correctors.

Background: Sleep problems and disorders are prevalent in patients with traumatic brain injury (TBI) and are associated with negative outcomes. Incidence varies because of challenges including differences in assessment methods, particularly in the acute stages of recovery when patients are cognitively impaired and unable to complete traditional self-report methods. Actigraphy (ACG) recently has been validated in the acute TBI rehabilitation setting and may serve as a superior method of assessing sleep-wake patterns at this stage of recovery. Although a few studies with small sample sizes have described the use of ACG, none have described feasibility and implementation protocols., Objective: To describe the feasibility and implementation protocol of ACG to evaluate sleep-wake patterns and white-light exposure data in patients with acute TBI during inpatient rehabilitation. Sleep-wake patterns and light exposure data are presented to characterize the sample using these methods to inform future research., Design: Retrospective study., Setting: Acute inpatient rehabilitation unit at a Veterans' Affairs Polytrauma Rehabilitation Center., Participants: Veterans (age ≥18 years) admitted to inpatient rehabilitation and enrolled in the Traumatic Brain Injury Model Systems study who were admitted and discharged in the calendar year 2013., Methods: Veterans underwent actigraph watch placement as soon as possible after admission. Records from the calendar year 2013 were reviewed to determine the number of admissions that met study criteria and what percentage of those patients had 3 days of continuous ACG data collected. The barriers to successful watch placement in this population were reviewed. Average sleep, light, and wake data from available records were collected for the study sample., Main Outcome Measurements: Percentage of patients who met study criteria and who had 72 hours of continuous ACG data collected. The barriers to successful watch placement in this population were reviewed. Average sleep, light, and wake data from available records were collected., Results: Of 22 eligible Traumatic Brain Injury Model Systems admissions, 3 consecutive nights of ACG data were successfully obtained for 86% (n = 19) of the sample. Barriers to data collection included patient access due to abbreviated lengths of stay, staff availability for ACG placement, and data collection protocols to prevent loss of data in Veterans' Affairs computing systems., Conclusions: ACG is feasible for collecting data about sleep, wake, and light exposure in patients who are in acute TBI inpatient rehabilitation settings., Level of Evidence: III., (Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Aim: To study health, well-being in daily life, educational level and socio-economic status in adulthood in moderately premature infants and the relationship to gender and socio-economic status at birth., Methods: Prospective long-term follow-up study of a cohort of infants with a gestational age between 32 and 37 weeks and term controls born between January 1972 and June 1973 in the municipality of Odense in Denmark. Information about life circumstances at 32 years was acquired by a mailed questionnaire., Results: The study comprised 373 participants aged 31-32 years (56% of the original cohort). Questionnaires were returned by 69 participants who were born moderately premature and 304 participants who were born at term (53 and 57%, respectively, of the original cohort). Multivariate analysis showed that social status and level of education at 32 years were predicted by social status and maternal educational level at birth with no demonstrable effects due to gestation or gender., Conclusion: Moderately premature infants, born before the era of intensive care, at the age of 32 years with regard to health, quality of life, education and social status proved to fare as well as their term counterparts., (©2013 Foundation Acta Paediatrica. Published by Blackwell Publishing Ltd.)

Spontaneous cerebellar hemorrhage (SCH) represents approximately 10% of all intracerebral hemorrhage (ICH) and is an important clinical problem of which little is known. This study stereotaxically infused collagenase (type VII) into the deep cerebellar paramedian white matter, which corresponds to the most common clinical injury region. Measures of hemostasis (brain water, hemoglobin assay, Evans blue, collagen-IV, ZO-1, and MMP-2 and MMP-9) and neurodeficit were quantified 24 hours later (Experiment 1). Long-term functional outcomes were measured over 30 days using the ataxia scale (modified Luciani), open field, wire suspension, beam balance, and inclined plane (Experiment 2). Neurocognitive ability was assessed on the third week using the rotarod (motor learning), T maze (working memory), and water maze (spatial learning and memory) (Experiment 3), followed by a histopathological analysis 1 week later (Experiment 4). Stereotaxic collagenase infusion caused dose-dependent elevations in brain edema, neurodeficit, hematoma volume, and blood-brain barrier rupture, while physiological variables remained stable. Most functional outcomes normalized by the third week, while neurocognitive testing showed deficits parallel to the cystic-cavitary lesion at 30 days. All animals survived until sacrifice, and obstructive hydrocephalus did not develop. These results suggest that the model can generate important translational information about this subtype of ICH and could be used for future investigations of therapeutic mechanisms after cerebellar hemorrhage., (2010 Elsevier Inc. All rights reserved.)

The present study was designed to investigate the role of matrix metalloproteinases (MMPs) in the immature brain and the long term effects of early MMPs inhibition after hypoxic-ischemic (HI) injury. HI was induced by unilateral ligation of the right carotid artery followed by hypoxia (8% O(2) for 2 h) in P7 rat pups. GM6001, a broad spectrum MMPs inhibitor, was injected (50 mg/kg or 100 mg/kg) intraperitoneally at 2 h and 24 h after HI injury. Blood-brain barrier (BBB) integrity, brain edema, MMP-2/-9 activity, TIMP-1/-2 and tight junction protein (TJP) level were evaluated using IgG staining, Evan's blue extravasation, brain water content, zymography and western blot. Doxycycline, another MMPs inhibitor, was injected (10 mg/kg or 30 mg/kg) intraperitoneally at 2 h after HI, then BBB integrity and brain edema were measured at 48 h post-HI using brain water content measurement and IgG staining. The long-term effects of early MMPs inhibition (GM6001, 100 mg/kg) were evaluated by neurobehavioral tests, body weight, and brain atrophy measurement. GM6001 attenuated brain edema and BBB disruption at the dosage of 100 mg/kg. MMP-2 activity increased at 24 h and peaked at 48 h after HI, whereas MMP-9 activity peaked at 24 h and tapered by 48 h after HI. MMP-9/-2 activities were significantly attenuated by GM6001 at 24 h and 48 h after HI. The degradation of TJPs (ZO-1 and occludin) at 48 h after HI was reversed by GM6001 treatment. Early MMPs inhibition had long-term effects that attenuated ipsilateral brain tissue loss, and improved neurobehavioral outcomes after HI. These results suggest that early MMPs inhibition with a broad-spectrum inhibitor provides both acute and long-term neuroprotection in the developing brain by reducing TJPs degradation, preserving BBB integrity, and ameliorating brain edema after neonatal HI injury.

Unlabelled: The Scandinavian approach is an effective combined treatment for respiratory distress syndrome (RDS) and prevention of bronchopulmonary dysplasia (BPD). It is composed of many individual parts. Of significant importance is the early treatment with nasal continuous positive airway pressure (nCPAP) and surfactant treatment. The approach may be supplemented with caffeine citrate and non-invasive positive pressure ventilation for apnoea. The low incidence of BPD seen as a consequence of the treatment strategy is mainly due to a reduced need for mechanical ventilation (MV)., Conclusion: Early-postnatal treatment with nCPAP and surfactant decreases the severity and mortality of RDS and BPD. This is mainly due to a diminished use of MV in the first days of life.

Introduction: The purpose of this study was to examine the efficiency of a single dose of fast-acting exogenous surfactant (Curosurf) given to premature babies with progressive respiratory insufficiency. Curosurf was given as early rescue therapy during a brief intubation (INSURE method: INtubation-SURfactant-Extubation) during treatment with nasal Continuous Positive Airway Pressure (CPAP)., Materials and Methods: Retrospective study of 115 premature infants with respiratory distress syndrome born and treated at Odense University Hospital during the years 1999 to 2004. The criterion for surfactant treatment was a decrease in the arterial/alveolar oxygen tension ratio (or corresponding values for the fraction of inspired oxygen) below 0.36 in infants with gestational age (GA) < 30 weeks and 0.22 in more mature infants., Results: The primary end point was survival during the first week of life without mechanical ventilation. This end point was reached by 51% of the infants with GA < 30 weeks. However, the effect proved to be GA-dependent, increasing from 22% in infants with a GA of 24-25 weeks to 86% in week 29. Seventy percent survived to be discharged. In infants with GA > 29 weeks the effect was 87%, and all survived., Conclusion: The effect of surfactant therapy administered per the INSURE method is GA-dependent, and the method works best after GA week 25. The question is whether earlier therapy will increase its efficiency or the method has reached its limit.

Aim: To describe physical outcome and school performance in a cohort of very-low-birthweight infants treated with early nasal continuous positive airway pressure (NCPAP)/minimal handling regimen with permissive hypercapnia, in comparison to siblings of normal birthweight., Material and Methods: Neonatal and follow-up data from 213 very-low-birthweight infants from 1983-1988 were registered and a questionnaire concerning school achievements was sent to the families of survivors and siblings attending school., Results: Mortality was 22%. Of the survivors, 4% had moderate-severe and 9% mild sequelae. Eighty-seven per cent of VLBW children and 95% of their siblings attended regular school. Average or above-average achievement was accomplished by 33 (65%) of the VLBW children and 34 (74%) of the siblings in mathematics, and 35 (69%) and 32 (68%), respectively, in reading/spelling. None of these differences reached statistical significance. However, the performance ratings correlated significantly with socio-economic conditions., Conclusion: In this study of infants treated with a regimen of early NCPAP/minimal handling, we found a relatively low incidence of handicaps and impairments. Nearly 90% attended ordinary schools, with near-average performances in mathematics and reading/spelling, which were not statistically different to their siblings. The overall results indicate that these infants fare at least as well as survivors after conventional treatment.

Authors present a case of 91 year old patient with spontaneous, neoplasmatic, external biliary fistula localized in right hypochondriac area, treated in the beginning as an abscess. The patient was operated because of the jaundice--cancer was discovered in the course of operation. Authors discussed diagnostic procedures and treatment.

Continuous positive airway pressure (CPAP) was introduced in 1971 and at that time welcomed as 'the missing link' between oxygen and ventilator treatment of premature infants. Originally CPAP was administered by tracheal tube (or head box) which because of the inherent risk of complications necessitated a cautious approach. New, more simple and less risky methods of application, such as nasal CPAP (N-CPAP), permitted earlier treatment which in randomized trials showed a reduction in inspired oxygen concentration, reduced need for mechanical ventilation and a reduction in the rate of death. Early N-CPAP/minimal handling today is an established first-line treatment in a number of centers in Denmark and Sweden, while N-CPAP outside Scandinavia apparently is used less often. However, recently the method has gained new interest as more publications have demonstrated that N-CPAP/minimal handling is both feasible and effective in most very-low-birth-weight infants. Early rescue treatment with fast-acting surfactant, given during a brief intubation, has increased the effectiveness of N-CPAP further. Descriptive studies on N-CPAP suggest that the risk of bronchopulmonary dysplasia may be lower than in conventional intensive treatment because of the relatively low need for mechanical ventilation. This question is at the present time being addressed in a randomized controlled trial in England.

The frequency of admission to neonatal intensive care units is higher in Denmark than in the UK. The organization of the paediatric departments varies from county to county in Denmark. To investigate possible differences due to the organization, the records for all hospitalized newborns in a one year period in two counties (FR and FU) were studied. The rate of prematurity was higher in county FU than in FR, but, surprisingly, the admission rate was lowest in county FU. For full term infants the highest admission rate was found in county FR, where more infants were treated with nasal continuous positive airway pressure compared to FU. Short admissions were more common in FR. The on-call paediatrician is a senior doctor in FU, whereas it is a junior doctor in FR, and this could be a possible explanation for the differences between the two counties.

Growth standards of birth weight, birth length and birth head circumference were constructed based on a population of Danish newborn boys and girls in gestational weeks twenty-five to forty-three. Study populations were residents of the municipality of Odense for later gestational ages and residents of the county of Funen for early gestational ages. Strict selection criteria were employed.

During 1988 and 1989 a regional cohort of 81 infants with birth weights of less than 1501 g were treated with oxygen (n = 11), early continuous positive airway pressure (CPAP) (n = 68) or mechanical ventilation from birth (n = 2). We used an easily applicable lightweight CPAP system with nasal prongs and a gas jet supplemented with ventilator treatment if necessary, but with conservative criteria for ventilator treatment with tolerance of high PCO2. A total of 65 infants (80%) survived to discharge, 61 of whom were supported solely with CPAP or oxygen. Nineteen infants (26%) developed periventricular-intraventricular haemorrhage, but only four survivors (6%) developed prognostically significant bleedings of grade 2-4. No survivors had bronchopulmonary dysplasia. Follow-up at 1.5-5 years of age revealed definite disabilities in seven (11%). The results suggest that treatment by early CPAP with nasal prongs with tolerance of high PCO2 may be effective and lenient in most infants of more than 25 weeks' gestation.

In the paper, the use of USG is presented in the diagnosis of breast tumours. On the basis of own material from the Breast Disease Diagnosis Unit, the authors presented the usefulness of USG examination in detection of breast diseases as easily available, non-invasive and not cumbersome for the patient.

A questionnaire on neonatal carried intensive care in Denmark was carried out in October 1990. The eighteen paediatric departments in the country with neonatal intensive care units all answered the questionnaire. The routines concerning transferral to a higher level of specialization, and the treatment procedures for children with a birthweight below 1500 grams and/or a gestational age under 32 weeks are described. Major regional variations were found in the degree of centralization of treatment, especially between the eastern and western part of Denmark. In an international perspective to neonatal intensive care Denmark seems to be modest with respect to initiation of treatment and the use of technology.

A investigation on neonatal intensive care in Denmark was carried out in October 1990 based on a questionnaire. The eighteen paediatric departments in the country with neonatal intensive care units all answered the questionnaire. The neonatal capacity and its distribution in different parts of Denmark, the level of medical qualifications, the routines for transferral to departments with higher specialization and for certain treatment procedures are described. Several variations in diagnostic and therapeutic routines were found between departments with the same level of specialization. The results are compared to the findings of a similar investigation in 1984. It was found that the neonatal bed-capacity has been reduced since 1984. It was also found that this capacity is relatively smaller in the eastern part of Denmark than in the western part, and that neonatal intensive care is centralized in the eastern part and decentralized in the western part of Denmark. Compared to 1984 better access to radiological and biochemical service has been achieved, and neonatal care is to a greater degree performed by a specialist in paediatrics.

The Authors investigated the effects of Allomin with admixture of 2% and 4% lactulose on constipation in infants aged 0-6 months reared on breast-milk substitutes. The investigation was randomized and double-blind and was carried out during the period 1.4.1987-31.7.1988 on non-hospitalized infants in the counties of Funen and North Jutland in cooperation with the health visitors in these regions. Constipation was defined as hard and difficult defaecation and the trial period lasted for 14 days. Parents of the infants who participated classified the infants' motions according to consistence and degree of difficulty in defaecation on special forms. A total of 220 children participated and these received, after randomizing, either Allomin-lactulose 2% or 4% as the only breast-milk substitute during the period of observation. The effect of treatment was defined as "no constipation" i.e. all motions during 24 hours described as easy and of normal or thin consistence. In addition, the effect was measured by the parents' general impression of what the infant thrived best on. With both of the preparations, treatment was effective in over 90% of the infants in both the groups without significant difference. The effect occurred gradually and, in some cases, up to 8-10 days after initiation of treatment without significant difference in the rate of effect between the groups. After the effect had commenced, significantly fewer thin motions occurred in the 2% group than in the 4% group. 92% of the infants in the 2% group and 91% in the 4% group wanted to continue the Allomin-lactulose preparation rather than the usual breast-milk substitute. A retrospective questionnaire to parents of 97 infants who had continued with Allomin-lactulose 2% was answered by 84.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty-four sick neonates with major duct dependent cardiac defects were given short term (1 h-408 h) intravenous infusions of prostaglandin E1 (alprostadil) in doses varying between 0.1 micrograms/kg/min (starting dose) and 0.01 micrograms/kg/min. The aim of the study was to establish an effective and safe regiment that could be initiated after clinical diagnosis of a severe duct dependent cardiac defect, whose clinical course would be adversely affected by ductus closure. After an initial dosage of 0.1 micrograms/kg/min, effective clinical improvement was achieved in 28 infants (82%). In all 28 responders, the effect was maintained at a reduced dosage of 0.05 micrograms/kg/min, and in 21 a low dosage of 0.01 micrograms/kg/min was effective. Side effects, which occurred in 21 infants (62%), were reversible and dose related, and no serious side effects were noted at a dosage of less than 0.05 micrograms/kg/min. A starting dose of 0.05 micrograms/kg/min with subsequent reduction is recommended, but in case of institution of treatment before transfer to a pediatric cardiac centre a lower starting dose of 0.01 micrograms/kg/min may be preferred.