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  • 1
    ISSN: 1432-1076
    Keywords: Surfactant ; Idiopathic respiratory distress syndrome ; Clinical trial ; Randomization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We performed a multicenter prospective randomized controlled trial to determine the efficacy and safety of the surfactant preparation, Survanta (Abbott Laboratories, Chicago, USA), for 750–1750 g infants with idiopathic respiratory distress syndrome, (IRDS) receiving assisted ventilation with 40% or more oxygen. One hundred and six eligible infants from the eight participating centers were randomly assigned between March 1986 and June 1987 to receive either surfactant (100 mg phospholipid/kg, 4 ml/kg) or air (4 ml/kg) administered into the trachea within 8 h of brith (median time of treatment 6.2 h, range 3.2–9.1 h). The study was stopped before enrollment was completed at the request of the United States Food and Drug Administration when significant differences were observed in incidence of periventricular-intraventricular hemorrhage (PIH), between the surfactant treated and control infants. Surfactant treated infants had larger average increases in the arterial-alveolar oxygen ratio, (a/A ratio) (P〈0.0001), and larger average decreases in FiO2 (P〈0.0001) and mean airway pressure, (MAP) (P〈0.017) than controls over the 48 h following treatment. The magnitude of the differences between the surfactant and control groups were 0.19 (SE=0.03) for a/A ratio, −0.28 (SE=0.04) for FiO2 and −1.7 cm H2O (SE=0.70) for MAP. The clinical status on days 7 and 28 after treatment was classified using four predefined ordered categories: (1) no respiratory support; (2) supplemental O2 with or without continuous positive airway pressure (CPAP); (3) intermittent mandatory ventilation; and (4) death. There were no statistically significant differences in the status categories on days 7 or 28 between surfactant and control infants. There were no significant differences between the groups with respect to the incidence of patent ductus arteriosus, bronchopulmonary dysplasia, necrotizing entero-colitis, air leaks or death. There was a statistically significant difference between treated and control infants in the frequency and severity of periventricular-intraventricular hemorrhage (PIH) (Cochran-Mantel-Haenszelχ 2adj=6.36,P=0.01). Hemorrhages occurred in 59.6% of surfactant treated infants and 26.9% of controls. Severe hemorrhages (grades 3 or 4) occurred in 38.5% of surfactant treated infants and 15.4% of controls (χ 2adj=4.01,P=0.045). We conclude that the intratracheal administration of Survanta prior to 8 h of age to infants with IRDS receiving assisted ventilation with 40% or more oxygen results in a reduction in the severity of respiratory distress during the 48 h after therapy. Because of the difference in incidence of PIH between surfactant and control infants in this study, we recommend that future clinical trials of surfactant include more frequent prospective serial ultrasound evaluations for diagnosis of hemorrhage.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 473-477 
    ISSN: 1432-1041
    Keywords: aminophylline ; asthma ; serum theophylline ; pharmacokinetics ; prediction of serum level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 15 acutely ill asthmatics the steady-state serum theophylline concentration was predicted by the method of Chiou et al. using two serum concentration measurements obtained 1 and 5h after starting a continuous infusion of aminophylline. Two theophylline assays with different precision characteristics were compared. With a precise HPLC-assay the prediction was excellent: prediction error (predicted minus measured concentration)=−0.22±1.97 mg/l (mean ± SD); r=0.922. When the theophylline concentration was determined by a rapid enzyme immunoassay of lower precision, but convenient for clinical use, the prediction was less accurate (prediction error=0.58±3.88, r=0.852). However, it was still clearly superior to dosing recommendations based on the population average of theophylline clearance, even after taking into consideration the effect of smoking, congestive heart failure and cirrhosis (prediction error=3.62±13.36, r=0.560). As employed in this study, the method may be useful in helping the physician to choose the optimal dose in severely ill asthmatics.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. S23 
    ISSN: 1432-1041
    Keywords: Gentamicin ; Neonates ; population kinetics ; prediction of kinetic parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A population kinetic analysis was carried out on sparse plasma gentamicin (GE) concentration data from 469 neonates obtained as part of a routine therapeutic drug monitoring (TDM) programme in the hospital neonatology unit. The best predictors of the kinetic parameters of the monoexponential model, volume of distribution (Vd) and clearance (CL), were the weight (WT) and gestational age (GA). Vd of the neonates was only related to WT, whereas the half-life was only related to the GA. The clinical implications of the findings are that the initial dose per WT administered to premature infants should be larger than that for term infants, because of a larger Vd per unit WT, and the intervals between maintenance doses should extended due to the prolonged half-life. Apart from these general guidelines, specific dose recommendations are also given.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1238
    Keywords: Respiratory failure Nitric oxide High frequency ventilation ECMO Infant Neonate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective: High-frequency ventilation (HFV) and/or inhaled nitric oxide (iNO) has reduced ECMO in neonates. But, frequently, improvement with HFV/iNO is temporary and only prolongs lung injury without preventing ECMO. We tried to identify a threshold oxygenation index (OI) that predicts temporary or persistent improvement with HFV/iNO in neonatal ECMO candidates as early as possible. Design: Cohort study of all neonates with OI〉40 during intermittent positive pressure ventilation between 1992 and 1997. The first treatment was HFV; at an OI〉40 during HFV, iNO was added; at an OI〉40 during HFV+iNO, ECMO was initiated. Temporary improvement was defined as secondary need for ECMO or fatal chronic lung disease without ECMO. Setting: University hospital level III neonatal intensive care unit. Main results: Ten of the 34 neonates studied rapidly required ECMO despite HFV/iNO. Eleven neonates temporarily improved for 1–10 days before the OI was again 〉40. Nine received ECMO, two were denied ECMO after mechanical ventilation 〉14 days and died of chronic lung disease. Thirteen neonates persistently improved with HFV/iNO without ECMO. The OI before, at 24 h or 48 h of HFV/iNO did not predict temporary or persistent improvement. However, after 72 h of HFV/iNO, neonates with persistent improvement had lower OIs than those with temporary improvement [median OI 16 (4–24) vs 31 (20–40); P=0.0004]. In all neonates with an OI≥25 after 72 h, HFV/iNO eventually failed (positive predictive value 100%, sensitivity 91%, specificity 100%, positive likelihood ratio 91). Conclusion: For neonates pretreated with HFV/iNO, an OI〉40 is an inadequate ECMO indication. Based on our data we hypothesize that an OI ≥25 after 72 h of HFV/iNO is a better ECMO indication that avoids prolonged barotrauma.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1998
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ten children (age 2 months to 8 years) with a congenital cytomegalovirus (CMV) infection were studied by magnetic resonance imaging (MRI) using a 2.35 Tesla magnet. CMV infection was confirmed by serological investigations and virus culture in the neonatal period. Nine children had severe mental retardation and cerebral palsy, 1 patient suffered from microcephaly, ataxia and deafness. The cranial MRI examination showed the following abnormalities (N): dilated lateral ventricles (10) and subarachnoid space (8), oligo/pachygyria (8), delayed/pathological myelination (7), paraventricular cysts (6), intracerebral calcification (1). This lack of sensitivity for calcification is explainable by the basic principles of MRI. The paraventricular cystic lesions were adjacent to the occipital horns of the lateral ventricles and separated only by a thin membrane. This finding might represent a “new sign” for congenital CMV infection in MRI examinations, being characteristic but nevertheless nonspecific, like calcification in CT.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Kindliche Hörstörungen ; Hörscreening ; Risikofaktoren ; Prävalenz ; Keywords Childhood hearing loss ; Auditory screening ; Risk factors ; Prevalence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Objective: This prospective study reports on the prevalence of hearing impairment in an at-risk neonatal intensive care unit (NICU) population. Design: From 1990 to 1998, 1062 neonates were screened with the use of transitory evoked otoacoustic emissions (TEOAE) and brainstem evoked response audiometry (BERA). Results: 934 infants passed the primary screen for both ears, 75 for one ear, adding up to 95%. 17 infants (1.6%) were lost to follow-up. In forteen infants (1.3%), bilateral hearing impairment above 30dB was confirmed. While all children with hearing impairment belonged to the group of 862 children receiving aminoglycosides, only one of them presented no other risk factors. In twelve of the hearing impaired children other anamnestic factors, i.e. dysmorphism, prenatal rubella or cytomegaly, family history of hearing loss or severe peri- and postnatal complications seem to be more probable causes of the identified hearing loss. In one of these children, delayed onset or progression of hearing loss is suspected. Conclusions: From our data, aminoglycosides are not an important risk factor for hearing impairment, when serum levels are continuously monitored, as in our cohort. After adjustment for other risk factors, birth weight between 1000 gr and 1500 gr and a gestational age between 29 and 31 weeks were no predictive markers for hearing impairment. It might be speculated that the improved medical treatment in a NICU reduces the probability of hearing impairment for those two groups. Conductive hearing loss as a possible additional cause for hearing impairment was not studied in detail, but the high percentage of malformations detected (four out of fourteen hearing impaired infants) demands further monitoring, close follow-up, adequate treatment and counselling.
    Notes: Zusammenfassung In einer prospektiven Studie wurde die Prävalenz persistierender Hörstörungen in einer Gruppe von Neugeborenen bestimmt, die von Dezember 1990 bis Dezember 1998 in der Klinik für Neonatologie und Kinderheilkunde in Behandlung waren und von der Klinik für Audiologie und Phoniatrie des Universitätsklinikums Benjamin Franklin der FU Berlin untersucht wurden, weil sie Risikofaktoren für Hörstörungen aufwiesen. Im genannten Zeitraum wurden 1062 Kinder mit transitorisch evozierten otoakustischen Emissionen (TEOAE) bzw. mit akustisch evozierten Potentialen (BERA) untersucht. Bei 934 Kindern konnte auf beiden, bei weiteren 75 Kindern auf einem Ohr das Vorliegen einer gravierenden Hörstörung ausgeschlossen werden (zusammen 95% der untersuchten Kinder). Bei 22 Kindern (2,1%) erfolgte ein Ausschluss einer gravierenden Hörstörung durch andere Stellen, bei 17 Kindern (1,6%) erfolgte keine Abklärung. Zwei dieser Kinder sind zwischenzeitlich verstorben; 14 Kinder (1,3% der Untersuchten) erwiesen sich als vermutlich oder gesichert hörgestört (Hörverlust über 30 dB). Alle diese Kinder hatten in der Neugeborenenphase Aminoglykoside erhalten, aber nur bei einem war dies der einzige Risikofaktor. Bei 12 der 14 Kinder liegen anamnestische Risiken wie kraniofaziale Dysmorphien, pränatale Röteln- oder CMV-Infektion, familiäre Belastung oder schwere peri- und postnatale Komplikationen vor, die als wahrscheinlichste Ursache der Hörstörung gelten können. Bei einem dieser Kinder war zunächst eine gravierende Hörstörung ausgeschlossen worden (BERA-Werte 30 dB beidseits), es wird eine progrediente oder durch Einflüsse nach der Neugeborenenzeit mitverursachte Hörstörung vermutet. Nach unseren Daten scheint die Aminoglykosidgabe daher keine Rolle als Risikofaktor zu spielen, wenn die Serumspiegel überwacht werden (wie das bei den untersuchten Kindern der Fall war). Keines der hörgestörten Kinder wies als einzigen weiteren Risikofaktor ein Gestationsalter zwischen 29 und 31 SSW oder ein Geburtsgewicht zwischen 1000 und 1500 g auf. Wir vermuten daher, dass durch den Fortschritt in der intensivmedizinischen Versorgung von Frühgeborenen diese Merkmale allein kein erhöhtes Risiko für Hörstörungen mehr darstellen. Vorübergehende Schalleitungsstörungen durch Paukenerguss wurden nicht im Detail untersucht. Der relativ hohe Anteil von Hörstörungen in Verbindung mit kraniofazialen Dysmorphien (4 von 14 hörgestörten Kindern) bedeutet, dass dieser Risikogruppe hohe Aufmerksamkeit geschenkt werden sollte.
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