Sudden unexpected death in infancy: place and time of death.

In recent years, many babies who die of Sudden Unexpected Death in Infancy (SUDI) in Northern Ireland are found dead in bed--i.e. co-sleeping--with an adult. In order to assess its frequency autopsy reports between April 1996 and August 2001 were reviewed and linked to temporal factors. The day and month of death, and the place where the baby was found were compared to a reference population of infant deaths between one week of age and the second birthday. Although the rate of SUDI was lower than the UK average, 43 cases of SUDI were identified, and two additional deaths with virtually identical autopsy findings that were attributed to asphyxia caused by suffocation due to overlaying. Thirty-two of the 45 (71%) were less than four months of age. In 30 of the 45 cases (67%) the history stated that the baby was bed sharing with others; 19 died sleeping in an adult bed, and 11 on a sofa or armchair. In 16 of the 30 (53%) there were at least two other people sharing the sleeping surface, and in one case, three. SUDI was twice as frequent at weekends (found dead Saturday-Monday mornings) compared to weekdays (p<0.02), and significantly more common compared to reference deaths (p<0.002). Co-sleeping deaths were also more frequent at weekends. Almost half of all SUDI (49%) occurred in the summer months--more than twice the frequency of reference deaths. While sharing a place of sleep per se may not increase the risk of death, our findings may be linked to factors such as habitual smoking, consumption of alcohol or illicit drugs as reported in case-control studies. In advising parents on safer childcare practices, health professionals must be knowledgeable of current research and when, for example, giving advice on co-sleeping this needs to be person-specific cognisant of the risks within a household. New and better means of targeting such information needs to be researched if those with higher risk life-styles are to be positively influenced.

The mechanism of inhibition of beta-oxidation by aspirin metabolites in skin fibroblasts from Reye's syndrome patients and controls.

The effects of aspirin metabolites on beta-oxidation were studied in skin fibroblasts from eight typical Reye's syndrome (RS) patients and controls. RS patients' cells did not differ from controls in rates of palmitate oxidation or in the three component activities of the mitochondrial trifunctional enzyme (MTE), indicating no inherited beta-oxidation defect. Aspirin metabolites salicylate, hydroxyhippurate and gentisate, but not aspirin, directly inhibited palmitate oxidation in control and RS cells. RS cells were significantly more sensitive to inhibition than controls at 0.5 to 5 mM salicylate. Inhibition was concentration-dependent and reversible. Inhibition did not occur in fibroblasts lacking activity of the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activity of MTE. Salicylate was therefore inhibiting beta-oxidation at this step. Hydroxyhippurate and salicylate reversibly inhibited HAD activities in extracts of control and RS cells. Studies with pure short-chain HAD and LCHAD (MTE) showed hydroxyhippurate and salicylate were competitive inhibitors of the former but mixed (not competitive) inhibitors of the latter. Both compounds inhibited the combined, three-step, MTE reaction measured in the physiological direction. We conclude that (1) salicylate and hydroxyhippurate decrease beta-oxidation in intact cells by reversible inhibition of LCHAD activity of the MTE, and (2) beta-oxidation in RS cells is inherently more sensitive to inhibition by low concentrations of salicylate than controls.

Social deprivation and childhood injuries in North and West Belfast.

Injuries in childhood represent a major public health concern. North and West Belfast is an area in which a high rate of emergency department attendance due to injury has been observed, and in which social deprivation is widespread. We carried out a cross sectional survey of 479 injuries in children aged 0-12 years presenting to four emergency departments serving North and West Belfast. Injury rates were compared between the most deprived and least deprived areas, selected on the basis of Noble Economic Deprivation scores. A significant correlation between economic deprivation and injury rate was demonstrated (r = 2.14, p < or = 0.001). Children living within the most deprived areas were particularly likely to be involved in road traffic accidents (relative risk RR = 3.25, p = 0.002). We conclude that children living within the most deprived areas of North and West Belfast are at greater risk of injury than those in less deprived areas. Specific causes of injury, for example burns and scalds, high falls, and motor vehicle accidents are particularly associated with deprivation. Targeting should be taken into account when injury prevention strategies are being developed.

Jejunal crypt cell abnormalities associated with methotrexate treatment in children with acute lymphoblastic leukaemia.

Jejunal mucosal crypts were examined in jejunal biopsies from eight children with acute lymphoblastic leukaemia who had recently received methotrexate treatment. By comparison with biopsies from children under investigation for suspected malabsorption crypt mitosis was significantly reduced and showed a negative correlation with the dose of methotrexate given prior to biopsy. The three major cell types were studied under light and transmission electron microscopy. Gut endocrine cells were unaffected by therapy and immature crypt enterocytes showed only patchy degenerative abnormalities. By contrast a number of Paneth cells showed striking structural alterations with vacuolar dilatation of the cytoplasm. The extent of this correlated with the time since methotrexate treatment rather than its dose and may have been a functional response rather than of a toxic nature.

Small bowel enterocyte abnormalities caused by methotrexate treatment in acute lymphoblastic leukaemia of childhood.

Jejunal biopsy specimens from 10 children with acute lymphoblastic leukaemia on methotrexate treatment were compared with 10 from children being investigated for diarrhoea or failure to thrive. In association with methotrexate treatment on both light and electron microscopy, there were marked morphological abnormalities in the villus enterocytes. These consisted of a striking distention of the lateral basal intercellular spaces, cell vacuolation and patchy necrosis and was most marked when methotrexate treatment was given between 24 and 72 h before biopsy. Two mechanisms may be involved: an early direct toxic effect on the mature enterocyte coupled with interference with crypt cell generation, possibly causing ageing and loss of cells proximal to the normal extrusion zone. These pathological changes may account for the malabsorption in association with methotrexate treatment.

The "mandibular mantle"--a sign of rickets in very low birth weight infants.

Mandibular periosteal new bone formation (the "mandibular mantle") is described in very low birth weight infants with other signs of severe metabolic bone disease. In infants with onset of dyspnoea and apnoea, between two and three months of age, this mandibular change suggests that the lung disorder is of skeletal, rather than pulmonary origin and aids in differentiation therefore, from the Mikity-Wilson Syndrome (pulmonary dystmaturity).

Assay of paracetamol and its metabolites in urine, plasma and saliva of children with chronic liver disease.

A high-performance liquid chromatographic (HPLC) assay of paracetamol and its metabolites is described. The method for quantifying the metabolism of paracetamol in children with chronic liver disease and the good correlation between plasma and salivary concentrations of paracetamol is demonstrated. Despite an increasing bias between the two methods with increasing concentration of paracetamol, it is concluded that salivary assay is satisfactory for characterising paracetamol pharmacokinetics in the group of patients studied.

Hepatocellular carcinoma associated with congenital macronodular cirrhosis in a neonate.

Hepatocellular carcinoma is rare in infancy. This report describes the first documented case of congenital hepatocellular carcinoma associated with macronodular cirrhosis.

The phenylpropionic acid load test: experience with 72 children at-risk for beta-oxidation disorders.

The urinary excretion of metabolites of orally administered phenylpropionic acid (PPA) in 72 children, aged 2 days to 16 years, thought to be at-risk of medium acyl CoA dehydrogenase deficiency has been studied. Forty had presented as Reye Syndrome, 9 as a Reye-like syndrome and 24 were sibs of decreased RS, sibs of RLS cases or sibs of infants who had died suddenly and without explanation where an autopsy revealed the presence of very heavy fatty infiltration of the liver. These studies demonstrated that PPA metabolites are maximally excreted during the 3 hours following the oral load and that this urine collection should be diagnostic. PPA loading is a relatively simple, safe test which is part of the investigation of a patient suspected of having an inborn error of metabolism.

Paediatric consultation patterns in general practice and the accident and emergency department.

The age, sex, source of referral and diagnosis of children brought to a paediatric accident and emergency department by their parents were compared to those consulting their general practitioner. A simultaneous, prospective review of these consultations was carried out over a six-week period in an inner-city paediatric teaching hospital and a group practice in a socially deprived urban area. 730 children less than 13 years of age who presented for a new consultation were seen. 629 (86%) presented initially to the general practitioner, who dealt with all but 25 (4.0%) without onward referral to the accident and emergency department. 127 consultations took place at the accident and emergency department, of which 104 (82%) were parental referrals. There was no sex difference in children seen by the general practitioner. There was a decreasing trend with increasing age in the proportion of children who consulted the general practitioner, perhaps due to the higher frequency of injury in the older children. Over three quarters (77%) of injured children were brought directly to the accident and emergency department, compared with only 4% of children without injuries (p < 0.001). Of 22 children with injuries who presented to the general practitioner, only 4 (18%) required onward referral. General practitioners met the great majority of the paediatric workload generated by the practice. Audit between primary and secondary care gives a more reliable picture than data from only one source. Injured children are more likely to be taken to the accident and emergency department. Further study of the severity of injury in children is required to determine if there is potential to reduce parental referrals to accident and emergency departments.