Prevalence of bronchial hyperresponsiveness in children: the relationship between asthma and skin reactivity to allergens in two communities

A coastal population mainly reactive to house dust mite was compared with an inland population mainly reactive to other allergens to investigate whether exposure to house dust mite plays a part in initiating childhood asthma. Respiratory symptoms, asthma, bronchial hyperresponsiveness, hay fever and atopy were all more common in the dry inland area than in the humid coastal area. In both areas 38% of children were atopic. Coastal children had more skin reactivity to house dust mites and inland children were more reactive to grass pollen extracts. The findings suggest that the clinical presentation of asthma may be related more to the total burden of aeroallergens than to exposure to a particular allergen.     

The need for leadership in global health

Globalisation has brought with it many advances in health, but also a new range of challenges. There is a need to move from "nation-focused" (international) public health to global public health--and the terminology we use here matters. Global public health leadership requires that respect be shown to evidence, especially that about the changing nature of disease worldwide. The Australian medical and research communities have a significant opportunity to provide global public health leadership.     

A pathway to a stronger research culture in health policy

Background

There are currently limited pathways into a career in health policy research in Australia, due in part to a serious absence of health policy research capability in Australian universities.

Discussion

We define what we consider health policy research and education should comprise. We then examine what is currently on offer and propose ways to strengthen health policy research in Australia.

Summary

This paper, which is part analysis and part commentary, is offered to provoke wider debate about how health policy research can be nurtured in Australia.

     

High-pressure liquid chromatographic analysis of ceftazidime in serum and urine.

A rapid and sensitive high-pressure liquid chromatographic procedure was developed for quantitative analysis of a new semisynthetic cephalosporin, ceftazidime, in serum and urine. A good linear relationship was established between peak height and the amount of ceftazidime injected over a concentration range of 1.9 to 30 micrograms/ml. Recovery was approximately 90% at concentrations of 3, 15, and 30 micrograms/ml. The method is specific for ceftazidime, with no interference noted from 11 other beta-lactam antibiotics tested. The assay is accurate, reproducible, and useful for pharmacokinetic studies in humans as demonstrated in two subjects.     

Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis

BACKGROUND: Platelet activating factor (PAF) is believed to amplify the activity of key mediators of the systemic inflammatory response syndrome (SIRS) in acute pancreatitis, resulting in multiorgan dysfunction syndrome. We tested the hypothesis that a potent PAF antagonist, lexipafant, could dampen SIRS and reduce organ failure in severe acute pancreatitis. METHODS: We conducted a randomised, double blind, placebo controlled, multicentre trial of lexipafant (100 mg/24 hours intravenously for seven days commenced within 72 hours of the onset of symptoms) involving 290 patients with an APACHE II score >6. Power calculations assumed that complications would be reduced from 40% to 24%. Secondary end points studied included severity of organ failure, markers of the inflammatory response, and mortality rate. FINDINGS: Overall, 80/138 (58%) patients in the placebo group and 85/148 (57%) in the lexipafant group developed one or more organ failures. The primary hypothesis was invalidated by the unexpected finding that 44% of patients had organ failure on entry into the study; only 39 (14%) developed new organ failure. Organ failure scores were reduced in the lexipafant group only on day 3: median change -1 (range -4 to +8) versus 0 (-4 to +10) in the placebo group (p=0.04). Systemic sepsis affected fewer patients in the lexipafant group (13/138 v 4/148; p=0.023). Local complications occurred in 41/138 (30%) patients in the placebo group and in 30/148 (20%) in the lexipafant group (20%; p=0.065); pseudocysts developed in 19 (14%) and eight (5%) patients, respectively (p=0.025). Deaths attributable to acute pancreatitis were not significantly different. Interleukin 8, a marker of neutrophil activation, and E-selectin, a marker of endothelial damage, decreased more rapidly in the lexipafant group (both p<0.05); however, absolute values were not different between the two groups. INTERPRETATION: The high incidence of organ failure within 72 hours of the onset of symptoms undermined the primary hypothesis, and power calculations for future studies in severe acute pancreatitis will need to allow for this. Lexipafant had no effect on new organ failure during treatment. This adequately powered study has shown that antagonism of PAF activity on its own is not sufficient to ameliorate SIRS in severe acute pancreatitis     

An endogenous glycosylphosphatidylinositol-specific phospholipase D releases basic fibroblast growth factor-heparan sulfate proteoglycan complexes from human bone marrow cultures

Basic fibroblast growth factor (bFGF) is a hematopoietic cytokine that stimulates stromal and stem cell growth. It binds to a glycosylphosphatidylinositol (GPI)-anchored heparan sulfate proteoglycan on human bone marrow (BM) stromal cells. The bFGF- proteoglycan complex is biologically active and is released by addition of exogenous phosphatidylinositol-specific phospholipase C. In this study, we show the presence of an endogenous GPI-specific phospholipase D (GPI-PLD) that releases the bFGF-binding heparan sulfate proteoglycan and the variant surface glycoprotein (a model GPI-anchored protein) from BM cultures. An involvement of proteases in this process is unlikely, because released proteoglycan contained the GPI anchor component, ethanol-amine, and protease inhibitors did not diminish the release. The mechanism of release is likely to involve a GPI-PLD and not a GPI-specific phospholipase C, because the release of variant surface glycoprotein did not reveal an epitope called the cross- reacting determinant that is exposed by phospholipase C-catalyzed GPI anchor cleavage. In addition, phosphatidic acid (which is specifically a product of GPI-PLD-catalyzed anchor cleavage) was generated during the spontaneous release of the GPI-anchored variant surface glycoprotein. We also detected GPI-PLD-specific enzyme activity and mRNA in BM cells. Therefore, we conclude that an endogenous GPI-PLD releases bFGF-heparan sulfate proteoglycan complexes from human BM cultures. This mechanism of GPI anchor cleavage could be relevant for mobilizing biologically active bFGF in BM. An endogenous GPI-PLD could also release other GPI-anchored proteins important for hematopoiesis and other physiologic processes.     

A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis

We have examined the prothrombin gene as a candidate gene for venous thrombosis in selected patients with a documented familial history of venous thrombophilia. All the exons and the 5'- and 3'-UT region of the prothrombin gene were analyzed by polymerase chain reaction and direct sequencing in 28 probands. Except for known polymorphic sites, no deviations were found in the coding regions and the 5'-UT region. Only one nucleotide change (a G to A transition) at position 20210 was identified in the sequence of the 3'-UT region. Eighteen percent of the patients had the 20210 AG genotype, as compared with 1% of a group of healthy controls (100 subjects). In a population-based case-control study, the 20210 A allele was identified as a common allele (allele frequency, 1.2%; 95% confidence interval, 0.5% to 1.8%), which increased the risk of venous thrombosis almost threefold odds ratio, 2.8; 95% confidence interval, 1.4 to 5.6. The risk of thrombosis increased for all ages and both sexes. An association was found between the presence of the 20210 A allele and elevated prothrombin levels. Most individuals (87%) with the 20210 A allele are in the highest quartile of plasma prothrombin levels (> 1.15 U/mL). Elevated prothrombin itself also was found to be a risk factor for venous thrombosis.     

Blastomycosis in a young African man presenting with a pleural effusion

Blastomyces dermatitidis is a dimorphic fungus endemic to northwestern Ontario, Manitoba and some parts of the United States. The fungus is also endemic to parts of Africa. Pulmonary and extrapulmonary findings of a 24-year-old African man who presented with weight loss, dry cough and chronic pneumonia not resolving with antibiotic treatment are presented. The unusual occurrence of pulmonary blastomycosis associated with skin lesions and a moderate pleural effusion is reported.