Arterial oxygen tension and response to oxygen breathing in differential diagnosis of congenital heart disease in infancy

Arterial oxygen tension was measured from radial artery samples in 276 infants referred for cardiological investigation. Values obtained during air breathing in infants with congenital heart disease showed considerable overlap between 'cyanotic' and 'acyanotic' groups, and are of limited diagnostic use. By contrast, values obtained while breathing oxygen in concentrations of over 80%, measured in 182 infants, allowed clear differentiation between these groups. All infants with acyanotic, but only 2 of 109 with cyanotic lesions, achieved an arterial oxygen tension of more than 150 mmHg. In the cyanotic group the response to oxygen breathing was significantly greater in common mixing situations and in the hypoplastic left heart syndrome than with either pulmonary outflow tract obstruction or transposition of the great arteries. Infants with transposition had a significantly lower mean arterial oxygen tension in air than infants with other forms of cyanotic congenital heart disease. Of 23 infants whose final diagnosis was primary lung disease but in whom cyanotic congenital heart disease had been suspected, 7 achieved arterial oxygen tensions of more than 150 mmHg during oxygen breathing, and on this basis cardiac catheterization was not performed. We therefore conclude that measurement of the arterial oxygen tension while breathing high concentrations of oxygen should be routinely performed in the initial assessment of sick infants with suspected congenital heart disease.     

Gender and the sudden infant death syndrome

Abstract A nationwide case-control study compared the prevalence and magnitude of risk factors for sudden infant death syndrome (SIDS) in male and female infants. The risk factors of SIDS and their magnitude for males and females are very similar. After adjustment for potential confounders male infants had a 1.42-fold (95% CI = 1.04, 1.94) increased risk of SIDS compared with females. Risk factors identified in most epidemiological studies are not the reason for the increased SIDS mortality seen in male infants.     

Respiratory syncytial virus immune globulin treatment of RSV lower respiratory tract infection in previously healthy children

OBJECTIVE: To evaluate the efficacy of high titer respiratory syncytial virus (RSV) immune globulin (RSVIG) in the treatment of previously healthy children hospitalized with proven RSV lower tract infection (LRI). METHOD: Infants and young children /=2. 5 were enrolled. RESULTS: One hundred and one previously healthy children hospitalized with RSV LRI received either 1500 mg/kg of RSVIG (RespiGam, MedImmune Inc, Gaithersburg, MD) or albumin placebo in a randomized, double-blind, placebo-controlled trial. Forty-six RSVIG and 52 recipients of placebo met all eligibility criteria. Demographic characteristics of the two groups were similar. More RSVIG recipients (46% vs 29%) had an SaO2 /=3.0) had 1.6 fewer hospital days and 2.7 days less ICU stays. CONCLUSION: RSVIG infusions seemed safe and generally well tolerated. Although some beneficial effect trends were seen for those with more severe disease who were treated there was no evidence that treatment with RSVIG resulted in reduced hospitalization and reduced ICU stays in all children with RSV disease.     

SIDS, illness, and acute medical care. New Zealand Cot Death Study Group

One component of the Back to Sleep campaign to reduce the risk of sudden infant death syndrome (SIDS) is the recommendation that parents seek medical attention if their infant is unwell. The aim of this study was to investigate of SIDS could in part be explained by sick infants not getting appropriate medical care. Data on symptoms of illness and on acute medical contacts made for infants dying from SIDS (n = 390) within two weeks of their death were compared with those from a randomly selected group of control infants (n = 1592). SIDS cases had more severe illness than controls (odds ratio (OR) = 3.43; 95% confidence interval (CI) = 1.69 to 5.38), and were more likely to have seen a general practitioner (OR = 1.37; 95% CI = 1.09 to 1.73) or attended hospital (OR = 3.43, 95% CI = 1.09 to 1.73). Only 1.3% of all SIDS cases had symptoms suggesting severe illness and had not seen a general practitioner. A lack of medical contacts in the two weeks before death does not contribute to the risk of SIDS.     

Evaluation of tamoxifen and alpha-hydroxytamoxifen 32P-post-labelled DNA adducts by the development of a novel automated on-line solid-phase extraction HPLC method

A novel HPLC system has been developed that has allowed the separation of tamoxifen DNA adducts formed in the livers of rats and mice treated with this drug. At least 13 different peaks have been separated from 32P-post-labelled DNA, with two major peaks jointly accounting for >60% of the total adducts formed by tamoxifen in the livers of treated rats and mice. This is a great improvement on the resolution obtained by thin layer chromatography, which separates the adducts into one main product consisting of a group of major adduct spots eluting together, plus several other minor spots. Identification of the nature of some of the peaks has been investigated. Comparisons of the products formed when alpha-acetoxytamoxifen is reacted with DNA in vitro with 32P-post- labelled liver DNA adducts from rats treated with tamoxifen or alpha- hydroxytamoxifen in vivo, appear to confirm that a major route of activation of tamoxifen in vivo is via alpha-hydroxylation. The resolving power of this HPLC system has further extended this result to show that six of the peaks, including the two major peaks, are formed by the reaction of an activated alpha-hydroxytamoxifen with DNA. Activation of 4-hydroxytamoxifen by the peroxidase/H2O2 system in vitro gives a more polar DNA adduct seen only at trace levels in liver DNA from tamoxifen-treated rats and mice.      

Contemporary results of balloon valvuloplasty and surgical valvotomy for congenital aortic stenosis

The purpose of this study was to compare contemporary results of balloon dilatation and surgery for valvar aortic stenosis in infants and children in the five years between August 1988 and October 1993. Thirty four children underwent attempted balloon valvuloplasty (age 1 day-16 years, weight 1720 g-68 kg) (group 1), eight of whom were neonates with critical aortic stenosis. During the same period, 17 children underwent direct surgical valvotomy (group 2) (seven neonates). Successful balloon valvuloplasty was achieved in 33 (97%) with immediate reduction in the instantaneous systolic pressure gradient from 82 to 34 mm Hg (mean). There were two deaths in this group (both neonates), the second in a preterm neonate from necrotising enterocolitis. Complications requiring intervention in group 1 were aortic regurgitation in one and femoral artery injury in two. Follow up from four months to five years showed sustained results in most cases. There were two neonatal deaths in the surgical group. When the two groups were compared there was no significant difference in mortality, morbidity, or need for reintervention within 12 months. Deaths from both groups were attributed to small left ventricles. Hospital stay was significantly shorter in group 1. It is concluded that balloon dilatation for valvar aortic stenosis is effective and safe for the entire paediatric population. The results compare favourably with those of surgery.     

A novel heteroplasmic tRNAleu(CUN) mtDNA point mutation in a sporadic patient with mitochondrial encephalomyopathy segregates rapidly in skeletal muscle and suggests an approach to therapy

A novel mtDNA point mutation was detected in the tRNAleu(CUN) gene (G to A at position 12315) in a sporadic patient with chronic progressive external ophthalmoplegia, ptosis, limb weakness, sensorineural hearing loss and a pigmentary retinopathy. The mutation disrupts base pairing in the T psi C stem at a site which has been conserved throughout evolution. Although the other mtDNA tRNAleu gene (UUR) is a hotspot for mutation, this is the first pathogenic mutation to be reported in the gene coding for tRNAleu(CUN). MtDNAs carrying the mutation constituted 94% of total mtDNAs in two separate muscle biopsies. Single fibre analysis showed that skeletal muscle fibres without detectable cytochrome c oxidase activity (COX-ve fibres) contained predominantly mutant mtDNAs (93-98%) while fibres with apparently normal COX activity had up to 90% mutant mtDNAs, demonstrating that the G12315A mutation is functionally recessive. Immunofluorescence studies with specific antibodies to mtDNA- or nuclear-encoded subunits of COX were consistent with a defect in mitochondrial protein translation. The mutation was not present in blood cells or cultured fibroblasts and surprisingly, it could not be detected in satellite cells cultured from the patient's muscle. This pattern, which may by typical of patients who have inherited new germline pathogenic mtDNA mutations, possibly reflects loss of the mutation by random genetic drift in mitotic tissues and proliferation of mitochondria containing the mutant mtDNA in post- mitotic cells. The absence of mtDNA carrying the mutation in satellite cells suggests that regeneration of skeletal muscle fibres from satellite cells could restore a wild-type mtDNA genotype and normal muscle function.      

Complete restoration of a wild-type mtDNA genotype in regenerating muscle fibres in a patient with a tRNA point mutation and mitochondrial encephalomyopathy

Replicative segregation of mitochondrial DNA (mtDNA) can produce large differences in the proportions of wild-type and mutant mtDNAs in different cell types of patients with mitochondrial encephalomyopathy. This is particularly striking in the skeletal muscle of patients with Kearns-Sayre syndrome (KSS), a sporadic disease associated with large- scale mtDNA deletions, and in sporadic patients with tRNA point mutations. Although the skeletal muscle fibres of these patients invariably contain a large proportion of mutant mtDNAs, mutant mtDNAs are rare or undetectable in satellite cells cultured from the same muscle biopsy specimens. Since satellite cells are responsible for muscle fibre regeneration, restoration of the wild-type mtDNA genotype might be achieved in these patients by encouraging muscle regeneration. To test this concept, we re-biopsied a patient with a KSS phenotype and a mtDNA point mutation in the tRNAleu(CUN)gene and analysed muscle fibres regenerating at the site of the original muscle biopsy. Regenerating fibres were identified by morphological criteria and by expression of neural cell adhesion molecule (NCAM). All such fibers were positive for cytochrome c oxidase (COX) activity by cytochemistry and essentially homoplasmic for wild-type mtDNA, while the majority of non-regenerating fibres were COX-negative and contained predominantly mutant mtDNAs. These results demonstrate that it may be possible to improve muscle function in similar patients by methods that promote satellite cell incorporation into existing myofibres.