Emergency response to the Canberra bushfires

On 18 January 2003, Canberra experienced major bushfires. Over 6 hours, The Canberra Hospital Emergency Department treated 139 patients, 105 with fire-related problems (mostly ophthalmological and respiratory), representing an additional workload of one patient every 4 minutes above average. Only 15% required hospital admission. We believe this is the largest single emergency department response to a disaster since Cyclone Tracy devastated Darwin in 1974, although the total severity of injury was relatively low. Major issues were communication difficulties and transport, with most patients (including the two most critically ill) arriving by private vehicle. Overall, medical outcomes were excellent, and the hospital system coped well.     

Role of xanthine oxidase in conduit artery endothelial dysfunction in cigarette smokers

Xanthine oxidase contributes to oxidant stress and has been proposed as a risk factor for endothelial dysfunction. We studied the role of xanthine oxidase in conduit artery endothelial dysfunction in 12 smokers and 12 controls. Conduit artery vasodilation was impaired in smokers (4.3%) compared with controls (7.9%) (p = 0.006) and improved with xanthine oxidase inhibition in smokers (9.2%, p <0.001).     

Infantile choriocarcinoma: a case report with MRI,angiography and bone scintigraphy

Infantile and maternal choriocarcinoma is a very rare disease. We report a case with the characteristic clinical features of infantile choriocarcinoma: developing anemia, hemorrhagic liver tumors, rapid progression to death and matemal choriocarcinoma. Bone scintigraphy showed increased uptake by the liver tumors. In this case there were two possible primary sites: the placenta of this pregnancy and a hydatidiform mole that had been present 2 years previously.     

Bancroftian filariasis in Nepal: a survey for circulating antigenemia of Wuchereria bancrofti and urinary IgG4 antibody in two rural areas of Nepal

Serum and urine samples were randomly collected from residents in two rural areas at different altitudes in Nepal, and were examined for Wuchereria bancrofti antigens and antibodies (IgG4) to filarial antigens, respectively. In Judigaun, located at 900 m in altitude, 25.2% of 238 serum samples were positive for antigen, and 50.8% of 244 urine samples were positive for antibody. The level of IgG4 antibodies was higher among antigen positive individuals than among the antigen negatives. In Kotyang, located at 1100-1300 m, the prevalence of antigenemia was 15.4% of 117 serum samples.     

Enzyme therapy in Gaucher disease type 2: an autopsy case

A Japanese patient with Gaucher disease type 2 was treated with enzyme therapy, alglucerase, from 7 to 22 months of age. Whereas hematologic parameters were normalized and hepatosplenomegaly was alleviated, no improvement in neurologic symptoms occurred, and the patient died of respiratory failure at age 22 months. Postmortem examination revealed massive intra-alveolar infiltration of Gaucher cells in lungs and in the central nervous system, i.e., the presence of Gaucher cells in the perivascular Virchow-Robins spaces in the cortex and deep white matter and extensive lamilar necrosis with reactive proliferation of blood vessels and macrophage infiltration of the cerebral cortex. It is suggested that enzyme therapy, with thus far recommended dose, does not prevent long-term respiratory and central nervous system involvement in severe varients of Gaucher disease.     

The pathobiology of amyotrophic lateral sclerosis: a proteinopathy?

Amyotrophic lateral sclerosis (ALS) is increasingly considered to be a disorder of multiple etiologies that have in common progressive degeneration of both upper and lower motor neurons, ultimately giving rise to a relentless loss of muscle function. This progressive degeneration is associated with heightened levels of oxidative injury, excitotoxicity, and mitochondrial dysfunction--all occurring concurrently. In this article, we review the evidence that suggests, in common with other age-dependent neurodegenerative disorders, that ALS can be considered a disorder of protein aggregation. Morphologically, this is evident as Bunina bodies, ubiquitin-immunoreactive fibrils or aggregates, neurofilamentous aggregates, mutant copper/zinc superoxide dismutase (SOD1) aggregates in familial ALS variants harboring mutations in SOD1, peripherin-immunoreactive aggregates within spinal motor neurons and as neuroaxonal spheroids, and in an increasingly greater population of patients with ALS with cognitive impairment, both intra- and extraneuronal tau aggregates. We review the evidence that somatotopically specific patterns of altered kinase and phosphatase activity are associated with alterations in the phosphorylation state of these proteins, altering either solubility or assembly characteristics. The role of nonneuronal cells in mediating motor neuronal injury is discussed in the context of alterations in tyrosine kinase activity and enhanced protein phosphorylation.     

Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability

Several mutations in PTEN-induced putative kinase 1 (PINK1) gene have been reported to be associated with recessive parkinsonism. The encoded protein is predicted to be a Ser/Thr protein kinase targeted to mitochondria. In this study, we have investigated the effects of mutations on PINK1 kinase activity in vitro and on expression levels and localization in mammalian cells. We chose to examine two point mutations: G309D, which was originally reported to be stable and properly localized in cells and L347P, which is of interest because it is present at an appreciable carrier frequency in the Philippines. We were able to confirm kinase activity and produce artificial "kinase-dead" mutants that are stable but lack activity. The L347P mutation grossly destabilizes PINK1 and drastically reduces kinase activity, whereas G309D has much more modest effects on these parameters in vitro. This finding is in line with predictions based on homology modeling. We also examined the localization of PINK1 in transfected mammalian cells by using constructs that were tagged with myc or GFP at either end of the protein. These results show that PINK1 is processed at the N terminus in a manner consistent with mitochondrial import, but the mature protein also exists in the cytosol. The physiological relevance of this observation is not yet clear, but it implies that a portion of PINK1 may be exported after processing in the mitochondria.