Lactoferrin and desferrioxamine are ineffective in the treatment of Helicobacter pylori infection and may enhance H. pylori growth and gastric inflammation in mice.

AIMS: To evaluate the efficacy of bovine lactoferrin (BLf), recombinant human lactoferrin (rHLf) and desferrioxamine against Helicobacter pylori in vitro and in mice and also to determine whether BLf or rHLf alter gastric inflammation. METHODS AND RESULTS: In vitro: Broth dilution susceptibility tests were performed using different concentrations of desferrioxamine, BLf and rHLf. Murine trials: In the prevention trial, C57BL/6 female mice were treated with BLf or rHLF, and then infected with the SS1 strain of H. pylori. In the treatment trial, mice were gavaged with either BLf, rHLf or desferrioxamine. In addition, gastric myeloperoxidase activity (MPO) was measured to assess gastric inflammation. Desferoxamine was found to have a direct bactericidal effect, while BLf and rHLf only partially suppressed H. pylori growth in vitro. However, in both prevention and treatment trials all three forms of treatment failed to reduce H. pylori load in mice. Gastric MPO activity and H. pylori load were noted to be higher with lactoferrin treatments. CONCLUSIONS: Our study does not support the use of BLf or rHLF in the treatment of human H. pylori infection. Interestingly, H. pylori growth and gastric inflammation appear to be enhanced by lactoferrin treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: The mouse model is ideal for testing novel H. pylori eradicating agents.

Passive exposure to tobacco smoke and bacterial meningitis in children.

OBJECTIVE: To determine whether an association exists between passive exposure to tobacco smoke and bacterial meningitis in childhood, in an Australian population. METHODOLOGY: A retrospective, case-controlled telephone survey of the parents of 71 children admitted to the Women's and Children's Hospital, North Adelaide, with bacterial meningitis between 1990 and 1999. RESULTS: The annual incidence of Haemophilus influenzae type b (Hib) meningitis decreased significantly during the study period (11.0 cases per year 1991-93 and 1.5 cases per year 1994-99, Fisher's exact test; P < 0.001) whilst pneumococcal cases significantly increased (2.3 cases per year 1991-93 and 4.9 cases per year 1994-99, Fisher's exact test; P < 0.001). Although comparable numbers of cases and controls came from smoking families (41% vs 45%), more cases came from bi-parental smoking households (17% vs 8%; odds ratio (OR) = 2.20, 95% confidence interval (CI) 0.77-6.24) and cases were more likely to live in households where parents smoked inside (27% vs 13%; OR 2.51, 95% CI 1.05-6.03). In households where parents smoked, children who had had meningitis were significantly more likely to have parents who smoked inside the house, than children who had not had meningitis (66% vs 28%, Fisher's exact test; P = 0.005). CONCLUSION: This study suggests there may be an association between high levels of passive exposure to tobacco smoke and bacterial meningitis in Australian children. A study with larger numbers of affected children which quantifies passive exposure to tobacco smoke is needed to determine the strength of this association.

Indomethacin treatment of infantile cortical periostosis in twins.

Twin girls presented with infantile cortical periostosis (Caffey's disease) at 2 and 3 weeks of age, respectively. This disorder initially involved their upper and lower limbs and resulted in fever, irritability and tenderness. X-rays showed extensive periosteal new bone formation. Multiple relapses occurred in the first year of life and during some of these relapses mandibular and clavicular involvement was noted. Prednisolone, 1 mg/kg per day, was used to treat relapses until 9 months of age. Indomethacin therapy at this age at a dose of 3 mg/kg per day allowed the cessation of prednisolone therapy and disease flares were thereafter infrequent and responsive to indomethacin.

Gastric distension, cerebral palsy and unexpected death.

Two cases of unexpected death from massive gastric dilatation in individuals with severe spastic quadraparesis aged 14 and 20 years, respectively, are reported. Spontaneous rupture of the stomach occurred in one case. Predisposing factors to gastric dilatation associated with cerebral palsy include autonomic neuropathy, neuromuscular incoordination, air swallowing and malposition of the stomach. Death may be due to compromise of respiratory function caused by lung compression by the dilated stomach, or to peritonitis with sepsis. Acute gastric dilatation, with or without rupture, should be considered a potential cause of unexpected death in individuals with severe mental and physical disabilities.

Methaemoglobinaemia secondary to topical lignocaine/ prilocaine in a circumcised neonate.

The use of topical lignocaine/prilocaine (EMLA, Astra Pharmaceuticals, North Ryde, NSW, Australia) for pain relief for neonatal circumcision is becoming more prevalent. Because of immaturity of the methaemoglobin reductase pathway, the neonate is vulnerable to methaemoglobinaemia which is a recognized complication of prilocaine therapy. This is the second report of methaemoglobinaemia due to the use of EMLA in association with circumcision during the newborn period.

Hepatocyte growth factor in human semen and its association with semen parameters.

Hepatocyte growth factor (HGF) is a structurally unique growth factor with potent motogenic (motility inducing) effects. Studies in the murine male genital tract have suggested important associations between HGF and the acquisition of sperm motility during epididymal maturation. The aim of this study was, therefore, to determine the concentration of HGF in human semen and assess its correlation, if any, with sperm motility and other semen parameters. Semen samples were collected by masturbation and analysed using standard procedures. HGF concentrations were measured in duplicate using an enzyme-linked immunoassay technique. Total protein estimations were also made in a subset of samples. The 95 subjects were divided into three groups for analysis: normozoospermic, subnormal semen and azoospermic. HGF was detected in all samples (median 0.456, 25th centile 0.388, 75th centile 0.556 ng/ml). No significant correlations were found between semen HGF concentrations and sperm concentration, motility, total sperm count or total motile count. There were no significant differences in mean HGF concentrations between the three subgroups. In conclusion HGF is present in human semen in significant quantities. The data do not suggest HGF concentrations are correlated with parameters of sperm motility.

Non-alcoholic steatohepatitis in children and adolescents.

We describe 17 children with non-alcoholic steatohepatitis. All had elevated levels of serum liver enzymes and 16 were morbidly obese. Liver biopsy showed variable steatosis and fibrosis in nine patients. At follow-up, 12 of 14 patients had persistent morbid obesity and 11 had elevated liver enzyme levels.

Cloning of rat betacellulin and characterization of its expression in the gastrointestinal tract.

Betacellulin (BTC) is relatively a more recently discovered member of the EGF family of growth factors. As a prelude to its expression and functional studies in rat models of gut damage/repair, we have cloned rat BTC and examined its expression in the gastrointestinal tract. Rat BTC was found to be nearly identical to mouse betacellulin. A single 3 kb mRNA species was detected by Northern blotting, and ribonuclease protection analysis showed that its expression was ubiquitous but low in abundance throughout the gut. BTC mRNA and protein were found expressed in the gastric surface and upper pit epithelium as well as in some cells of gastric glands. In the jejunum, BTC mRNA and protein were localised to the crypt epithelium and in villous goblet cells. In the colon, BTC mRNA and protein were found produced in crypt and surface epithelium as well as in goblet cells. Taken together, the wide spread expression in the gut epithelium and in mucous cells in particular suggests an important and unique role for BTC in the gastrointestinal tract.

The sugar permeability test reflects disease activity in children and adolescents with inflammatory bowel disease.

OBJECTIVES: To investigate the relationship of intestinal permeability in children and adolescents with inflammatory bowel disease (IBD) to disease activity, disease extent, and response to therapy. STUDY DESIGN: Patients with new and established diagnoses of IBD (12 Crohn's disease [CD] and 18 ulcerative colitis [UC]) were studied. Intestinal permeability was evaluated by measuring with high-performance liquid chromatography 5-hour urinary excretion ratio of lactulose/L-rhamnose (L/Rh). RESULTS: In 8 of 9 patients with active CD, the L/Rh ratio was higher than the reference range (0.006 to 0.074, n = 36). In inactive CD (n = 3) the L/Rh ratio was within the reference range. In 6 of 7 patients with active extensive UC, the L/Rh ratio was elevated. In inactive extensive UC (n = 6) the normal permeability ratio was shown. In both active CD and active extensive UC, the frequency of elevated intestinal permeability was significantly greater than values in both inactive forms. The permeability ratio was normal in 4 of 5 patients with active left-sided colitis. In 5 of 7 patients (3 CD, 4 UC), repeat permeability values entered the reference range after acute phase therapy. Two patients with persistently elevated intestinal permeability (1 CD, 1 UC) had a disease flare-up within 6 months. CONCLUSIONS: Intestinal permeability is a marker of disease activity in CD and extensive UC. Serial permeability test may be useful in monitoring disease activity.

Digoxin-like immunoreactivity in early infantile death.

The aim of this study was to determine if the level of digoxin-like immunoreactivity in post-mortem sera obtained from infants differs according to the cause of death and if the level is related to age, post-mortem interval, cardiac pathology or adrenal weight. Twelve infants whose deaths were attributed to sudden infant death syndrome (SIDS), and 11 infants who died from other causes, had blood sampled between 3 to 53 hours post-mortem from their right atrial cavity. Digoxin-like immunoreactivity was measured, using a specific and sensitive digoxin radioimmunoassay, and was detected in 7 of the infants who died of SIDS and 7 of those who died from other causes. The highest levels were seen in two patients who died from meningococcal sepsis and haemorrhage, hyperpyrexia and encephalopathy syndrome, respectively. No correlation was detected between the digoxin-like immunoreactivity level, gender, age at death, post-mortem interval or cardiac pathology. Digoxin-like immunoreactivity levels correlated with adrenal weight. It is concluded that digoxin-like immunoreactivity is frequently found in infant sera, but levels are not specific to and are no higher in SIDS infants than infants dying of other conditions.

Novel approaches to the diagnosis of pancreatic disease in childhood.

The diagnosis of pancreatic disease is difficult. Most tests of pancreatic function need to be interpreted in the context of the patient's presenting history and clinical examination. In childhood, classical signs of hemorrhagic pancreatitis are seldom useful because they rarely occur. A careful history is particularly useful in conditions with an autosomal dominant inheritance such as hereditary pancreatitis. Pedigree construction should be undertaken in all cases of pancreatitis. Assessment of exocrine pancreatic function is made easier by a thorough appreciation of the constellation of signs, both pancreatic and extrapancreatic, of various pancreatic disease. The purpose of this review is to explore novel means of diagnosing pancreatic disease, including pancreatic function testing, organ imaging and, more recently, molecular biology techniques. Most of the potentially novel techniques surround organ imaging or molecular biology.

Oncocytic cardiomyopathy: a rare cause of unexpected early childhood death associated with fitting.

A 15-month-old girl died unexpectedly in hospital following a five-day history of intermittent cardiac arrhythmias and convulsions preceded by several weeks of occasional vomiting. Autopsy revealed subendocardial nodules in the left ventricle, and tricuspid and mitral valves that were composed of aggregated large cells with foamy, pale pink cytoplasm characteristic of oncocytic cardiomyopathy. Fat stains were positive for neutral lipid and phospholipid and electron microscopic examination revealed numerous irregular mitochondria within affected cells. Examination of the brain revealed no structural or histologic abnormalities, anoxic damage or thromboembolic material. Oncocytic cardiomyopathy, though rare, may cause unexpected death in previously well young children with quite variable preceding clinical symptoms and signs which include fitting. Although the aetiology is unknown there is evidence that mitochondrial dysfunction may be involved.

Dehydration deaths in infants and young children.

Dehydration in developed countries is an uncommon but important mechanism resulting in the death of infants and children. The clinicopathological features of a series of 37 fatal dehydration cases autopsied at the Adelaide Children's Hospital over a 33-year period (1961-1993) are presented. Causative factors for dehydration included gastroenteritis (21 cases), gastroenteritis with high environmental temperature (one case), high environmental temperatures (six cases), neglect/failure to thrive (four cases), mental retardation/chromosomal abnormality (three cases), congenital adrenal hyperplasia (one case), and unsuspected cystic fibrosis (one case). The mean age at death was 11.4 months (range 2 weeks to 6.25 years; median 6 months; 95% confidence interval 6 months to 1 year and 4 months; male-to-female ratio, 19:18). Sixteen of the 22 cases of fatal gastroenteritis (73%) occurred during the fall/winter months (March to August). There were a total of seven aboriginal or part aboriginal children in the group (19%). Children with mental retardation were at higher risk of dehydration, and previously unsuspected cases of child abuse/neglect also presented with lethal dehydration. Vitreous humor electrolyte levels and immunoassay for rotavirus were useful diagnostic adjuncts.