The development of allergy in high-risk children

BACKGROUND: It is uncertain as to what extent the development of allergic disease in childhood is predictable during early infancy. A number of environmental factors have been suspected of increasing the risk of acquiring allergy, but the evidence is conflicting. OBJECTIVE: To observe the development of atopy and allergic disease in a cohort of high-risk children so as to determine the importance of certain environmental factors and to study the relationship between early and later manifestations. METHODS: A cohort of infants, all at high risk of allergy, was followed up from birth to the age of 7 years. In half, selected at random, cow's milk protein was avoided for 4 months. Skin-prick tests were performed and serum IgE measured in infancy and at 7 years, when an AlaTOP test was also performed. RESULTS: Skin sensitivity to egg in the first year of life was strongly associated with eczema, asthma, mite sensitivity and serum IgE at the age of 7 years, when mother's atopic history was associated with AlaTOP status, father's atopic history with skin sensitivity, and male sex with both. Maternal smoking during pregnancy was associated positively with IgE at 3 months and negatively with skin sensitivity at 7 years. The development of allergy was unrelated to infant feeding method or number of older siblings. CONCLUSION: Allergic disease in childhood is to a large degree determined before birth or during infancy.     

Primary gastrointestinal lymphoma--disease spectrum and management: a 15-year review from north India

The anthropometric measurements of face were taken in 21 infants of 6-9 months (15 boys, 6 girls) with bilateral cleft lip, alveolus and palate, prior to surgery. The control group consisted of 30 normal infants, without facial defects. In each child 9 measurements were performed. The comparative analysis revealed an underdevelopment of maxilla and mandible and an increase in nasal width in children with bilateral cleft lip and palate.     

Application of the polymerase chain reaction to the diagnosis and management of neonatal herpes simplex virus disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group

Cerebrospinal fluid (CSF) specimens from 77 neonates with herpes simplex virus (HSV) disease were evaluated retrospectively by polymerase chain reaction (PCR). Samples were collected from 202 infants enrolled in a National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial that compared vidarabine with acyclovir for the treatment of neonatal HSV infection. HSV DNA was detected in the CSF of 26 (76%) of 34 infants with CNS disease, in 13 (93%) of 14 infants with disseminated infection, and in 7 (24%) of 29 with skin, eye, or mouth (SEM) involvement. One of the 7 PCR-positive SEM patients subsequently developed severe neurologic impairment. Eighteen (95%) of 19 infants with positive CSF PCR results after the completion of 10 days of antiviral therapy experienced significant morbidity or mortality. Application of PCR to neonatal HSV disease may provide additional information on which clinical decisions may be based, although its diagnostic utility outside the research setting is unproven.     

Replication of the multidimensionality of activities of daily living

We attempted to replicate the three-dimensional factor structure of a previously proposed ADL scale and demonstrate an association between the advanced ADL dimension and cognitive function. Data used in these analyses were baseline assessments of health and functional status of hospitalized patients enrolled in a randomized controlled trial of case managers as a means of reducing health care utilization. We submitted 14 items from the OARS to a two-stage process of principal components factor analysis. Four significant dimensions emerged that were remarkably similar to the advanced, basic, and household ADL dimensions reported by Wolinsky and Johnson (1991). In this sample of hospitalized patients, however, incontinence emerged as a weak fourth dimension. Multiple regression of SPMSQ mental status examination scores on these ADL dimensions demonstrates the association between cognitive function and the advanced ADL dimension. These data confirm that the underlying structure of ADLs consists of at least three separate dimensions, one of which is aligned with cognitive capacity.     

Prenatal application of somatic gene therapy

Somatic gene therapy in the fetus or neonate represents an exciting new approach for the management of some congenital or inherited diseases. It is likely that clinical trials of these methods will take place in the future. In contrast, despite the potential for manipulation of embryos and inherited genetic material, the clinical applicability of these methods is uncertain.     

Rifampin, a useful drug for nonmycobacterial infections

Hexokinase I, the pacemaker of glycolysis in brain tissue and red blood cells, is comprised of two similar domains fused into a single polypeptide chain. The C-terminal half of hexokinase I is catalytically active, whereas the N-terminal half is necessary for the relief of product inhibition by phosphate. A crystalline complex of recombinant human hexokinase I with glucose and phosphate (2.8 A resolution) reveals a single binding site for phosphate and glucose at the N-terminal half of the enzyme. Glucose and phosphate stabilize the N-terminal half in a closed conformation. Unexpectedly, glucose binds weakly to the C-terminal half of the enzyme and does not by itself stabilize a closed conformation. Evidently a stable, closed C-terminal half requires either ATP or glucose 6-phosphate along with glucose. The crystal structure here, in conjunction with other studies in crystallography and directed mutation, puts the phosphate regulatory site at the N-terminal half, the site of potent product inhibition at the C-terminal half, and a secondary site for the weak interaction of glucose 6-phosphate at the N-terminal half of the enzyme. The relevance of crystal structures of hexokinase I to the properties of monomeric hexokinase I and oligomers of hexokinase I bound to the surface of mitochondria is discussed.     

Neonatal morbidity and mortality associated with triplet pregnancy

OBJECTIVE: To compare neonatal morbidity and mortality in a large cohort of triplet pregnancies with singleton and twin neonates managed at a single tertiary center over a short time. METHODS: Records from all triplet pregnancies managed and delivered from 1992 to 1996 were reviewed for neonatal outcome data. Pregnancies delivered before 20 weeks' gestation and neonates with lethal congenital anomalies were excluded. The comparison group comprised all singleton and twin neonates managed in the same neonatal intensive care unit (NICU) during the same period. RESULTS: During the 5-year period, 55 triplet pregnancies and their resulting 165 neonates were managed and delivered at this center. Their outcomes were compared with those of 959 singleton and 357 twin neonates born at similar gestational ages. The median gestational age at delivery for triplets was 32.1 weeks, and 149 of the 165 infants were admitted. Sixteen triplet neonates were not admitted to our neonatal intensive care unit, 12 because of previable gestational age, three because of stillbirth, and one because of a lethal congenital anomaly. The crude perinatal mortality rate in triplets was 121 per 1000 births, and there was no significant difference in outcome based on triplet birth order. There were no significant differences in survival rates between singleton, twin, and triplet neonates, with an overall neonatal survival of 95%, 95%, and 97%, respectively. The only significant differences in morbidity were an increased incidence of mild intraventricular hemorrhage (relative risk [RR] 6.20; 95% confidence interval [CI] 2.64, 14.61), mild retinopathy of prematurity (RR 20.05; 95% CI 3.59, 111.79), and severe retinopathy of prematurity (RR 46.69; 95% CI 6.25, 348.85) in triplets compared with singletons, and severe retinopathy of prematurity (RR 6.83; 95% CI 1.24, 37.56) in triplets compared with twins. CONCLUSION: When stratified by gestational age, triplet neonates delivered at 24-34 weeks' gestation have similar outcomes as singleton and twin neonates, with the only clinically significant difference being an increased incidence of retinopathy of prematurity in triplets.     

Gene therapy of neoplastic meningosis

Gene therapy of neoplastic meningosis is a promising new approach that relies on introduction of 'suicide' genes into cancer cells. The most commonly used gene has been the herpes virus thymidine kinase gene (HSV-tk) which has been delivered to cancer cells via retroviral or adenoviral vectors. A bystander cytocidal effect to non-transduced tumor cells has been documented and is dependent upon intercellular communication via gap junctions. A variety of gene therapy approaches using the HSV-tk system have been used in experimental models of neoplastic meningosis with promising results. Optimizing vector design and bystander cytotoxicity is a prerequisite for successful gene therapy in patients with neoplastic meningosis.