Effect of in utero growth retardation on lung function at follow-up of prematurely born infants.

The aim of the study was to determine if prematurely born children who had suffered intra-uterine growth retardation (IUGR) had more severe lung function abnormalities than those born an appropriate weight for gestational age (AGA). Analysis of the lung function results of 119 infants (median (range) gestational age of 30 (23-35) weeks) was undertaken. In total, 31 of the infants had suffered IUGR and were born small for gestational age (SGA). Functional residual capacity and airways resistance (Raw) were measured at a median post-natal age of 10 (6-24) months. Specific airway conductance (sGaw) was calculated from thoracic gas volume and Raw. The SGA children were born at a greater gestational age and had a lower body weight at testing than the AGA children. Raw and sGaw differed between the SGA and AGA children. Regression analysis demonstrated that lung volumes were significantly related to body weight at testing, Raw was related to IUGR, maternal smoking and bronchopulmonary dysplasia, and sGaw to maternal smoking. In conclusion, these results suggest that prematurely born infants who have suffered intra-uterine growth retardation may be at increased risk of impaired lung function at follow-up.     

Wilson's disease in children: 37-year experience and revised King's score for liver transplantation.

Wilson's disease (WD) is a rare liver-based disorder of copper metabolism. Prognostic criteria described by our group in 1986 to predict death without transplantation have not been universally validated. The clinical features of 88 children were reviewed, retrospectively in 74 and prospectively in 14. Data from the retrospectively recruited patients that died or survived on long-term chelation were used to evaluate the validity of our old scoring system and to devise a new prognostic index, then assessed in the 14 prospectively recruited patients. Using the old scoring system, 5 children scoring > or = 7, the cutoff value for death without transplantation, survived, whereas 4 scoring < or = 7 died (sensitivity 87% and specificity 90%). A new index based on serum bilirubin, international normalized ratio, aspartate aminotransferase (AST), and white cell count (WCC) at presentation identified a cutoff score of 11 for death and proved to be 93% sensitive and 98% specific, with a positive predictive value of 88%. When the new index was evaluated prospectively in 14 patients, it predicted the need for transplantation in only the 4 who required it, although 1 child with a score of 11 survived on medical treatment. In conclusion, the new Wilson Index is more sensitive and specific in predicting mortality without transplantation than the old scoring system, but needs to be validated in a larger number of patients.     

Synthesis, corticotropin-releasing factor receptor binding affinity, and pharmacokinetic properties of triazolo-, imidazo-, and pyrrolopyrimidines and -pyridines

The synthesis and CRF receptor binding affinities of several new series of N-aryltriazolo- and -imidazopyrimidines and -pyridines are described. These cyclized systems were prepared from appropriately substituted diaminopyrimidines or -pyridines by nitrous acid, orthoester, or acyl halide treatment. Variations of amino (ether) pendants and aromatic substituents have defined the structure-activity relationships of these series and resulted in the identification of a variety of high-affinity agents (Ki's < 10 nM). On the basis of this property and lipophilicity differences, six of these compounds (4d,i,n,x, 8k, 9a) were initially chosen for rat pharmacokinetic (PK) studies. Good oral bioavailability, high plasma levels, and duration of four of these compounds (4d,i,n,x) prompted further PK studies in the dog following both iv and oral routes of administration. Results from this work indicated 4i,x had properties we believe necessary for a potential therapeutic agent, and 4i1 has been selected for further pharmacological studies that will be reported in due course.     

Invasive antenatal procedures and requirement for neonatal intensive care unit admission

Neonatal respiratory difficulties are increased following second trimester amniocentesis. In preterm, prolonged rupture of the membranes, respiratory outcome is particularly poor when rupture occurs in the first trimester. It therefore seems likely that first trimester/early amniocentesis (EA) would be associated with severe respiratory problems necessitating a high neonatal intensive care unit (NICU) admission rate. To test that hypothesis, the requirement for admission to the NICU of 278 infants whose mothers had undergone EA, 262 whose mothers had undergone chorion villus sampling (CVS group) and 264 controls whose mothers had undergone no invasive procedures were reviewed as were their diagnoses if they needed admission. There was no significant difference in the mode of delivery, gestational age or gender distribution of the three groups and the median maternal age of the EA and CVS groups was similar. Nineteen EA, eight CVS and five control infants required admission to the NICU (EA versus controls, P < 0.01; EA versus CVS plus controls, P < 0.005). Nine EA, one CVS and four control infants had suffered respiratory problems (EA versus CVS P < 0.05). Logistic regression analysis demonstrated that immaturity and EA were significantly associated with a requirement for NICU admission. We conclude infants whose mothers have undergone EA may be at increased risk for NICU admission, this is partly due to respiratory problems but the association is uncommon. Received: 1 August 1996 / Accepted: 12 December 1996     

Birth characteristics and the risk of childhood leukaemias and lymphomas in New Zealand: a case-control study

Background  

Some studies have found that lower parity and higher or lower social class (depending on the study) are associated with increased risks of childhood acute lymphoblastic leukaemia (ALL). Such findings have led to suggestions that infection could play a role in the causation of this disease. An earlier New Zealand study found a protective effect of parental marriage on the risk of childhood ALL, and studies elsewhere have reported increased risks in relation to older parental ages. This study aimed to assess whether lower parity, lower social class, unmarried status and older parental ages increase the risk of childhood ALL (primarily). These variables were also assessed in relation to the risks of childhood acute non-lymphoblastic leukaemia, non-Hodgkin's lymphomas and Hodgkin's disease.