Upper airway obstruction in infants and children: evaluation with ultrafast CT

The diagnostic accuracy of ultrafast computed tomography (CT) was evaluated prospectively in 25 infants and children with suspected airway obstruction. All examinations were conducted in spontaneously breathing, nonsedated children. Scan acquisition times were 0.05 or 0.1 second. CT examinations, completed in an average of 10 minutes, routinely included localizing, contiguous sections through the trachea followed by serial images obtained at a rate of 17 per second through regions of interest. Imaging results were correct in 24 of 25 examinations as judged from clinical and surgical data. Ultrafast CT data permitted diagnosis of dynamic changes in airway caliber, small intraluminal polyps, focal tracheal atresia, compressive mediastinal masses, and foreign body obstructions of the major bronchi. Dose measurements showed a maximum skin exposure of 245 mR (0.06 mC/kg) per 0.05-second image. Ultrafast CT provides an accurate, minimally invasive method for dynamic imaging of the airway in nonsedated children.     

Iron and non-alcoholic fatty liver disease

The mechanisms that promote liver injury in non-alcoholic fatty liver disease(NAFLD) are yet to be thoroughly elucidated. As such, effective treatment strategies are lacking and novel therapeutic targets are required. Iron has been widely implicated in the pathogenesis of NAFLD and represents a potential target for treatment. Relationships between serum ferritin concentration and NAFLD are noted in a majority of studies, although serum ferritin is an imprecise measure of iron loading. Numerous mechanisms for a pathogenic role of hepatic iron in NAFLD have been demonstrated in animal and cell culture models. However, the human data linking hepatic iron to liver injury in NAFLD is less clear, with seemingly conflicting evidence, supporting either an effect of iron in hepatocytes or within reticulo-endothelial cells. Adipose tissue has emerged as a key site at which iron may have a pathogenic role in NAFLD. Evidence for this comes indirectly from studies that have evaluated the role of adipose tissue iron with respect to insulin resistance. Adding further complexity, multiple strands of evidence support an effect of NAFLD itself on iron metabolism. In this review, we summarise the human and basic science data that has evaluated the role of iron in NAFLD pathogenesis.     

CHD7 mutations in patients initially diagnosed with Kallmann syndrome – the clinical overlap with CHARGE syndrome

Kallmann syndrome (KS) is the combination of hypogonadotropic hypogonadism and anosmia or hyposmia, two features that are also frequently present in CHARGE syndrome. CHARGE syndrome is caused by mutations in the CHD7 gene. We performed analysis of CHD7 in 36 patients with KS and 20 patients with normosmic idiopathic hypogonadotropic hypogonadism (nIHH) in whom mutations in KAL1 , FGFR1 , PROK2 and PROKR2 genes were excluded. Three of 56 KS/nIHH patients had de novo mutations in CHD7 . In retrospect, these three CHD7 -positive patients showed additional features that are seen in CHARGE syndrome. CHD7 mutations can be present in KS patients who have additional features that are part of the CHARGE syndrome phenotype. We did not find mutations in patients with isolated KS. These findings imply that patients diagnosed with hypogonadotropic hypogonadism and anosmia should be screened for clinical features consistent with CHARGE syndrome. If such features are present, particularly deafness, dysmorphic ears and/or hypoplasia or aplasia of the semicircular canals, CHD7 sequencing is recommended.     

Bacterial contamination of bone marrow grafts intended for autologous and allogeneic bone marrow transplantation. Incidence and clinical significance

In a series of 100 bone marrow harvests, the incidence of bacterial contamination of the bone marrow graft was 17 percent. Ex vivo manipulation of some of the grafts prior to infusion may have caused additional bacterial contamination. All isolated bacteria were common skin flora, and no serious sequelae were observed in the patients receiving the culture-positive bone marrow grafts. Samples of harvested bone marrows purposely contaminated with an isolate of Staphylococcus epidermidis demonstrated a bactericidal property that was maximal early after bone marrow collection. Bone marrow collection and ex vivo manipulation may result in considerable bacterial contamination. Procedures must be developed to assure that marrow collection and processing do not result in clinically significant contamination.     

Deficiency of non-suppressible insulin-like activity in thalassaemia major

The commonly occurring short stature in the condition of thalassaemia major was investigated with respect to the possible role of the somatomedin growth factor low molecular weight non-suppressible insulin-like activity (NSILAs). Nineteen affected patients (12 boys, 7 girls) aged between 2 and 21 years were studied. Twelve of them were on or below the 10th centile for height of whom 7 were on or below the 3rd centile for height. Serum immunoreactive growth hormone responses to exercise were normal in 9 of 11 subjects tested. Using an isolated fat cell bioassay NSILAs was undetectable in 10 and was more than 2 SD below the normal mean value in the other 9 subjects. High molecular weight NSILA (not a growth factor) was very low or undetectable in all 9 subjects tested. Low molecular weight NSILAs did not show the normal correlation with age in childhood, nor was there any correlation with height, height velocity, or bone age. The 2 children above the 50th centile for height had undetectable NSILAs. There was no evidence of iron or ferritin interfering in the bioassay, and mixing experiments showed no evidence of inhibitory activity towards NSILAs in thalassaemic sera. Low circulating levels of the somatomedin NSILAs may contribute to the short stature in thalassaemia major, but other factors may permit normal growth in some affected children.     

Lactose malabsorption during gastroenteritis, assessed by the hydrogen breath test

Thirty-eight infants and young children with gastroenteritis were investigated for lactose malabsorption. Each of them was given an oral lactose load of either 0.5 g/kg or 2 g/kg after which breath hydrogen excretion was measured, and each was observed to see if he had clinical symptoms of lactose intolerance. Only one patient, given 2 g/kg lactose, had clinical intolerance. His breath hydrogen excretion however was negative. Three of 18 patients given 0.5 g/kg lactose had positive breath hydrogen tests. None of these was symptomatic. Lactose intolerance in gastroenteritis was rare in our study, and the hydrogen breath test was not an appropriate technique for detecting it.     

Health and safety problems and lack of information among international visitors backpacking through North Queensland

BACKGROUND: International visitors to tropical Australia may be exposed to health and safety problems. Because they are younger, stay longer and participate in more activities, backpackers have a greater exposure to such problems than other visitors. METHOD: The study's aim was to determine how many backpackers experience problems and lack health and safety information. Four hundred and thirty-one international visitors staying in a random sample of youth hostels and backpacker accommodation in Townsville were surveyed over the summer. RESULTS: Sixty two percent experienced a health and safety problem, commonly, insect bites, sunburn, headaches, lacerations, coral cuts, ear infections and diarrhea. Seventeen percent resolved only with professional help. Only 54% of backpackers had been offered health and safety information prior to departure, mainly vaccination advice. CONCLUSION: The proportion of backpackers offered health and safety information about tropical Australia, and the breadth of that information, needs to be increased.     

Idiotype-specific CD4+CD25+ T suppressor cells prevent,by limiting antibody diversity,the occurrence of anti-dextran antibodies crossreacting with histone H3

CD25(+) suppressor T cells regulate the immune response against the type-2 "thymus independent" bacterial polysaccharide antigen alpha(1-->3)dextran (Dex) in BALB/c mice. These T cells, represented by the clone 178-4 Ts, restrict the Dex-specific IgG antibody repertoire such that the J558 idiotype dominates. Antibodies with other structures in the heavy-chain variable region (V(H) region), predominantly within the CDR3 domain, occur when the T cell control fails. This increase of antibody diversity caused by a lack of CD25(+) Ts cells, e.g. in nude mice, does not result in the appearance of antibodies with enhanced affinity to the antigen Dex, but often leads to a crossreactivity with autologous proteins. Twenty-two out of sixty Dex-specific hybridomas from nude mice, but no hybridomas from euthymic mice, crossreact with a nuclear protein, as tested by ELISA. This nuclear protein was identified as histone H3. Ten of the sixty hybridomas from nude mice were sequenced and show V(H) sequences that deviate from the original J558 sequence. Three of these ten hybridomas crossreact with the histone H3. Adoptive transfer of CD25(+) Ts cells to nude mice leads to a marked increase of antibodies carrying the original J558 idiotype within the IgG pool after immunization with Dex. Our data demonstrate a CD25(+) Ts cell-mediated restriction of V(H) usage, which prevents the appearance of crossreactive autoantibodies.