Adaptive Evolution in TRIF Leads to Discordance between Human and Mouse Innate Immune Signaling.

The TIR domain-containing adapter inducing IFN-ß (TRIF) protein is an innate immune system protein that mediates the MyD88-independent toll-like receptor response pathway in mice and humans. Previously, we identified positive selection at seven distinct residues in mouse TRIF (mTRIF), as compared with human and other mammalian orthologs, thus predicting protein functional shift in mTRIF. We reconstructed TRIF for the most recent common ancestor of mouse and human, and mutated this at the seven sites to their extant mouse/human states. We overexpressed these TRIF mutants in immortalized human and mouse cell lines and monitored TRIF-dependent cytokine production and gene expression induction. We show that optimal TRIF function in human and mouse is dependent on the identity of the positively selected sites. These data provide us with molecular data relating observed differences in response between mouse and human MyD88-independent signaling in the innate immune system with protein functional change.

Consanguineous 3-methylcrotonyl-CoA carboxylase deficiency: early-onset necrotizing encephalopathy with lethal outcome.

A patient with a severe neonatal variant of 3-methylcrotonyl-CoA carboxylase (MCC) deficiency is reported. The first child of healthy consanguineous Turkish parents presented on the second day of life with dehydration, cyanosis, no sucking, generalized muscular hypotonia, encephalopathy, respiratory depression requiring mechanic ventilation, macrocephaly, severe acidosis and hypoglycaemia. Elevated C5-OH-carnitine in dried blood spot by tandem MS and elevated urinary excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine suggested MCC deficiency, confirmed by enzyme analysis in cultured fibroblasts. Cerebral ultrasonography and cranial CT findings revealed progressive changes such as disseminated encephalomalacia, cystic changes, ventricular dilatation and cerebral atrophy. Treatment with high-dose biotin and protein-restricted diet was ineffective and the patient died at the age of 33 days with progressive neurological deterioration. Mutation analysis revealed a homozygous mutation in the splice acceptor site of intron 15 in the MCC beta-subunit. Early-onset severe necrotizing encephalopathy should be included in the differential diagnosis of isolated MCC deficiency.

An unusual complication of endotracheal intubation: ingestion of a laryngoscope bulb.

Many well described complications can result from endotracheal intubation in neonates during resuscitation. Ingestion of a laryngoscope bulb is a rare event with potentially serious consequences. We are reporting this unusual complication in a neonate during delivery room resuscitation and point to the importance of checking the integrity of the equipment prior to resuscitative efforts.

Transcutaneous measurement of hyperbilirubinaemia: comparison of the Minolta jaundice meter and the Ingram icterometer.

The effectiveness of two different non-invasive transcutaneous bilirubin measurement devices was compared with serum bilirubin levels in 96 healthy newborns. Transcutaneous measurements were obtained with the Minolta Air Shields jaundice meter and the Ingram icterometer and serum bilirubin levels were determined by a direct spectrophotometric method (Bilitron 444). A linear correlation existed between serum bilirubin values and the readings on both the Minolta jaundice meter (r = 0.83) and the Ingram icterometer (r = 0.78). The Kappa coefficient was 0.66. the sensitivity, specificity and positive and negative predictive values were 100%, 56%, 33% and 100% for the Minolta jaundice meter and 100%, 48%, 29% and 100% for the Ingram icterometer, respectively. The high sensitivity and negative predictive value of both devices render them suitable for screening neonatal hyperbilirubinaemia. However, because of its low cost, the Ingram icterometer is preferable to the more complex and expensive Minolta jaundice meter, especially in countries with a high birth rate, such as Turkey.

Breast milk beta-glucuronidase and prolonged jaundice in the neonate.

Breast milk samples from mothers of breast-fed, healthy, term newborns with unexplained prolonged jaundice were analyzed for beta-glucuronidase activity. Mean enzyme activity was 75.7 +/- 34.5 modified Sigma units/ml in the breast milk samples ingested by the study group of jaundiced babies (n = 25) and 82.2 +/- 40.1 modified Sigma units/ml in the samples ingested by the control group of non-jaundiced babies (n = 20) (p > 0.05). Enzyme activities at 2, 3 and 4 postnatal weeks were 101.0 +/- 39.9, 66.0 +/- 20.7 and 57.0 +/- 22.4 modified Sigma units/ml in the study group and 87.9 +/- 36.1, 58.5 +/- 15.0 and 88.3 +/- 49.1 modified Sigma units/ml in the controls. The differences were not statistically significant (p > 0.05). We conclude that breast milk beta-glucuronidase activity may be a contributory factor, in the presence of other variables, in hyperbilirubinemia but it is neither the main nor the only cause of prolonged jaundice in neonates.

Neonatal suppurative parotitis: a vanishing disease?

A case of neonatal suppurative parotitis due to Klebsiella pneumoniae is described. This is the first case reported in the last 20 years. Infection with unusual microorganisms should be taken into account when planning antibiotic treatment, especially in hospital acquired infections of the salivary glands in the newborn.