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Biomedical subjects

G V Brown

Publications and source records attributed to G V Brown.

At least 19 recordsLinked to original sources
PubMed2006

Energy-dependent excitation cross section measurements of the diagnostic lines of Fe XVII.

By implementing a large-area, gain-stabilized microcalorimeter array on an electron beam ion trap, the electron-impact excitation cross sections for the dominant x-ray lines in the Fe XVII spectrum have been measured as a function of electron energy establishing a benchmark for atomic calculations. The results show that the calculations consistently predict the cross section of the resonance line to be significantly larger than measured. The lower cross section accounts for several problems found when modeling solar and astrophysical Fe XVII spectra.

Journal Article↗
PubMed2006

A prospective comparison of severity scores for identifying patients with severe community acquired pneumonia: reconsidering what is meant by severe pneumonia.

BACKGROUND: Several severity scores have been proposed to predict patient outcome and to guide initial management of patients with community acquired pneumonia (CAP). Most have been derived as predictors of mortality. A study was undertaken to compare the predictive value of these tools using different clinically meaningful outcomes as constructs for "severe pneumonia". METHODS: A prospective cohort study was performed of all patients presenting to the emergency department with an admission diagnosis of CAP from March 2003 to March 2004. Clinical and laboratory features at presentation were used to calculate severity scores using the pneumonia severity index (PSI), the revised American Thoracic Society score (rATS), and the British Thoracic Society (BTS) severity scores CURB, modified BTS severity score, and CURB-65. The sensitivity, specificity, positive and negative predictive values were compared for four different outcomes (death, need for ICU admission, and combined outcomes of death and/or need for ventilatory or inotropic support). RESULTS: 392 patients were included in the analysis; 37 (9.4%) died and 26 (6.6%) required ventilatory and/or inotropic support. The modified BTS severity score performed best for all four outcomes. The PSI (classes IV+V) and CURB had a very similar performance as predictive tools for each outcome. The rATS identified the need for ICU admission well but not mortality. The CURB-65 score predicted mortality well but performed less well when requirement for ICU was included in the outcome of interest. When the combined outcome was evaluated (excluding patients aged >90 years and those from nursing homes), the best predictors were the modified BTS severity score (sensitivity 94.3%) and the PSI and CURB score (sensitivity 83.3% for both). CONCLUSIONS: Different severity scores have different strengths and weaknesses as prediction tools. Validation should be done in the most relevant clinical setting, using more appropriate constructs of "severe pneumonia" to ensure that these potentially useful tools truly deliver what clinicians expect of them.

Adolescent↗
PubMed2005

Patient knows best: blinded assessment of nonadherence with antituberculous therapy by physicians, nurses, and patients compared with urine drug levels.

BACKGROUND: Adherence with therapy is a wide spectrum of behavior rather than a categorical state. While extreme nonadherence is readily apparent, it is rare compared to lesser degrees of nonadherence, which are difficult to predict. AIMS: To compare the accuracy of doctor, nurse, and patient prediction of adherence with antituberculous therapy with urine isoniazid levels. METHODS: A prospective, blinded clinical study was conducted, comparing adherence to antituberculous therapy as reported by patients, doctors, and nurses with urine isoniazid levels. We studied 173 patients with active tuberculosis (TB) recruited over 3 years in two TB clinics in Victoria, Australia. Adherence was defined as six random urine isoniazid (INH) levels being >0. Blinded assessment of adherence was completed by doctors, nurses, and patients. Lid opening and closing of computerized pill bottles were measured in a random subsample. RESULTS: Of 173 patients, the rate of nonadherence was 24% (41/173) by urine INH, 54% (93/173) by patient self-report, 11% (19/173) by doctor assessment, and 7% (12/173) by nurse assessment. The sensitivity of prediction of nonadherence was 76% for patient self-report, 24% for doctor assessment, and 19% for nurse assessment. The 10 patients who used computerized pill bottles were all (100%) noncompliant at some stage. CONCLUSION: Nonadherence is common and poorly predicted by doctors and nurses, even those with extensive experience in treating TB. Contrary to popular belief, patient self-report is more reliable than doctor or nurse assessment of nonadherence. As clinicians, asking patients about adherence may be more valuable than attempting to judge for ourselves.

Antitubercular Agents↗
PubMed2005

Antibiotic prescribing in response to bacterial isolates in the intensive care unit.

This study aimed to identify potential knowledge-performance gaps in antibiotic prescribing for bacterial isolates in the Intensive Care Unit (ICU) in order to guide the development of interventions such as antibiotic policies, decision support, and improved systems for communication between the laboratory and the bedside. A prospective observational cohort study of all patients admitted to a mixed medical/surgical ICU was undertaken over a six-month period in an Australian adult tertiary hospital. From a cohort of 524 patients, 108 had 303 isolates that were eligible for inclusion. Overall, 14.3% and 30.8% of sterile and non-sterile isolates respectively were associated with inadequate initial antibiotic therapy after identification of the bacteria. After sensitivity results were available inadequate directed therapy was observed in 4.0% and 21.3% of sterile and non-sterile isolates respectively. Problems were most commonly associated with isolates of Pseudomonas spp., Stenotrophomonas spp., Acinetobacter spp., S. aureus, enterococci and group III Enterobacteriaceae. Inadequate antibiotic therapy was found to be independently associated with prolonged length of ICU stay. Narrower spectrum antibiotic therapy was potentially available for 30% of isolates after sensitivity results were known. We conclude that there is scope to improve antibiotic prescribing in the ICU by providing clinicians with access to information regarding local susceptibility patterns and intrinsic resistance of bacteria, and spectra of antibiotic cover. Timely notification of laboratory results at the point of care may also facilitate improved prescribing performance.

APACHE↗
PubMed2003

Determination of the charge state distribution of a highly ionized coronal Au plasma.

We present the first definitive measurement of the charge state distribution of a highly ionized gold plasma in coronal equilibrium. The experiment utilized the Livermore electron beam ion trap EBIT-II in a novel configuration to create a plasma with a Maxwellian temperature of 2.5 keV. The charge balance in the plasma was inferred from spectral line emission measurements which accounted for charge exchange effects. The measured average ionization state was 46.8+/-0.75. This differs from the predictions of two modeling codes by up to four charge states.

Journal Article↗
PubMed2003

Laboratory simulation of charge exchange-produced X-ray emission from comets.

In laboratory experiments using the engineering spare microcalorimeter detector from the ASTRO-E satellite mission, we recorded the x-ray emission of highly charged ions of carbon, nitrogen, and oxygen, which simulates charge exchange reactions between heavy ions in the solar wind and neutral gases in cometary comae. The spectra are complex and do not readily match predictions. We developed a charge exchange emission model that successfully reproduces the soft x-ray spectrum of comet Linear C/1999 S4, observed with the Chandra X-ray Observatory.

Journal Article↗
PubMed2003

A randomised controlled clinical trial of the efficacy of family-based direct observation of anti-tuberculosis treatment in an urban, developed-country setting.

SETTING: A randomised, controlled clinical trial of the effectiveness of a family-based programme of directly observed treatment (DOT) for tuberculosis. METHODS: TB patients seen in Victoria, Australia, were randomly allocated to DOT observed by a family member (FDOT), or to standard supervised but non-observed therapy (ST). The outcome measure was compliance, measured by blinded testing of isoniazid levels in urine. An intention-to-treat analysis was used. RESULTS: Of 173 patients, 87 were allocated to FDOT and 86 to ST. Only 58% in the FDOT group were able to receive FDOT, the major reason being living alone and not having a family member to observe treatment. The rate of non-compliance was 24% (41/173), with no significant difference between FDOT (22/87) and ST (19/86). No clinical or socio-demographic variable predicted compliance. CONCLUSIONS: We were unable to demonstrate a benefit of FDOT in an urban, industrialised country setting. FDOT may be more appropriate in developing countries, where extended family support is often available and the burden of TB is much higher. Poor compliance and the difficulty in predicting non-compliance shown in this study highlights the need for DOT for all TB patients.

Adolescent↗
PubMed2002

Pathogenesis of Plasmodium falciparum malaria: the roles of parasite adhesion and antigenic variation.

Malaria results in up to 2.5 million deaths annually, with young children and pregnant women at greatest risk. The great majority of severe disease is caused by Plasmodium falciparum. A characteristic feature of infection with Pfalciparum is the accumulation or sequestration of parasite-infected red blood cells (RBCs) in various organs, such as the brain, lung and placenta, and together with other factors is important in the pathogenesis of severe forms of malaria. Sequestration results from adhesive interactions between parasite-derived proteins expressed on the surface of infected RBCs and a number of host molecules on the surface of endothelial cells, placental cells and uninfected RBCs. Some receptors for parasite adhesion have been implicated in particular malaria syndromes, such as intercellular adhesion molecule 1 in cerebral malaria and chondroitin sulfate A and hyaluronic acid in placental infection. The principal parasite ligand and antigen on the RBC surface, P falciparum erythrocyte membrane protein 1 encoded by a multigene family termed var, is clonally variant, enabling evasion of specific immune responses. An understanding of these host-parasite interactions in the context of clinical disease and immunity may reveal potential targets to prevent or treat severe forms of malaria.

Animals↗
PubMed2002

Malaria--a global crisis.

The aim of this short review is to define the magnitude of the problem of malaria and the evidence that a malaria vaccine may be able to play a pivotal role in control of global malaria. Some of the challenges that would need to be faced in introducing a malaria vaccine as part of a global strategy are also discussed.

Humans↗
PubMed2001

Fever in returned travelers: review of hospital admissions for a 3-year period.

We reviewed 232 consecutive patients admitted to a tertiary-care hospital under the care of an infectious diseases unit for management of febrile illness acquired overseas. A total of 53% presented to hospital within 1 week of return and 96% within 6 months. Malaria was the most common diagnosis (27% of patients), followed by respiratory tract infection (24%), gastroenteritis (14%), dengue fever (8%), and bacterial pneumonia (6%). Pretravel vaccination may have prevented a number of admissions, including influenza (n=11), typhoid fever (n=8) and hepatitis A (n=6). Compared to those who had not traveled to Africa, those who had were 6 times more likely to present with falciparum than nonfalciparum malaria. An itinerary that included Asia was associated with a 13-fold increased risk of dengue, but a lower risk of malaria. Palpable splenomegaly was associated with an 8-fold risk of malaria and hepatomegaly with a 4-fold risk of malaria. As a cause of fever, bacterial pneumonia was > or =5 times more likely in those who were aged >40 years.

Adult↗
PubMed2001

Multiple var gene transcripts are expressed in Plasmodium falciparum infected erythrocytes selected for adhesion.

Adherence of Plasmodium falciparum-infected erythrocytes to the post-capillary endothelium is an important characteristic of malaria infection. The adhesion is mediated predominantly by P. falciparum Erythrocyte Membrane Protein-1 (PfEMP1), a clonally variant protein expressed on the surface of infected red blood cells that appears to be a target of protective immunity. A multi-membered var gene family encodes PfEMP1 and switching expression of different var genes conveys different antigenic and adhesive properties to infected red blood cells. Knowledge about transcriptional control of phenotypic expression, or the mechanisms that allow multiple binding specificities, is very limited. Here, we describe a series of phenotypic selection experiments, which resulted in the expression of different PfEMP1 and the detection of multiple full-length var gene transcripts in the mature trophozoite stage. However, a dominant form of PfEMP1 appeared to be expressed, which suggested that most var transcripts do not lead to a surface expressed PfEMP1 molecule. Parasites bound to specific receptors still expressed multiple full-length var genes and mature trophozoites selected for increased adhesion to a specific receptor retained the ability to bind to multiple receptors. Our findings suggest that a defined adhesive phenotype can be associated with expression of multiple var genes.

Alternative Splicing↗
PubMed2001

Parasite adhesion and immune evasion in placental malaria.

Parasite sequestration in the placenta is a key feature of infection by Plasmodium falciparum during pregnancy and is associated with severe adverse outcomes for both mother and baby. Here, James Beeson and colleagues draw together the findings of recent studies on parasite mechanisms that mediate this process. They review evidence for novel parasite variants that appear able to evade pre-existing immunity, for the adhesion of P. falciparum-infected erythrocytes to placental glycosaminoglycans (and the molecular basis of these parasite properties) and for the expression of var genes encoding the variant antigen and adhesive ligand P. falciparum-erythrocyte membrane protein 1 (PfEMP1).

Animals↗
PubMed2001

Risk factors for colonization with vancomycin-resistant enterococci in a Melbourne hospital.

OBJECTIVE: To determine risk factors for colonization with vancomycin-resistant enterococci (VRE) in a hospital outbreak. DESIGN: Outbreak investigation and case-control study. SETTING: A referral teaching hospital in Melbourne, Australia. PARTICIPANTS: Cases were inpatients colonized (with or without clinical disease) with VRE between July 26 and November 28, 1998; controls were hospitalized patients without VRE. METHODS: Five cases of VRE were identified between July 26 and November 8, 1998, by growth of VRE from various sites. Active case finding by cultures of rectal swabs from patients surveyed in wards was commenced on July 26, after the first isolate of VRE. RESULTS: There were 19 cases and 66 controls. All the VRE identified were vanB, and all were Enterococcus faecium. One molecular type predominated (18/19 cases). In a logistic-regression model, being on the same ward as a VRE case was the highest risk factor (odds ratio [OR], 82; 95% confidence interval [CI95], 5.7-1,176; P=.001). Having more than five antibiotics (OR, 11.9; CI95 1.1-129.6; P<.05), use of metronidazole (OR, 10.9; CI95, 1.7-69.8; P=.01), and being a medical patient (OR, 8.1; CI95, 1.4-47.6; P<.05) also were significant. Intensive care unit admission was associated with decreased risk (OR, 0.1; CI95, 0.01-0.8; P<.05). CONCLUSION: Our findings are consistent with an acute hospital outbreak. Monitoring and control of antibiotic use, particularly metronidazole, may reduce VRE in our hospital. Ongoing surveillance and staff education also are necessary.

Case-Control Studies↗
PubMed2001

Inhibition of adhesion of Plasmodium falciparum-infected erythrocytes by structurally defined hyaluronic acid dodecasaccharides.

We recently reported that Plasmodium falciparum-infected erythrocytes (IRBCs) can adhere to hyaluronic acid (HA), which appears to be a receptor, in addition to chondroitin sulfate A (CSA), for parasite sequestration in the placenta. Further investigations of the nature and specificity of this interaction indicate that HA oligosaccharide fragments competitively inhibit parasite adhesion to immobilized purified HA in a size-dependent manner, with dodecasaccharides being the minimum size for maximum inhibition. Rigorously purified and structurally defined HA dodecasaccharides, free of contamination by CSA or other glycosaminoglycans, effectively inhibited IRBC adhesion to HA but not CSA, providing compelling evidence of a specific interaction between IRBCs and HA.

Adhesiveness↗
PubMed2000

Molecular approaches to epidemiology and clinical aspects of malaria.

Malaria is a problem of global importance, responsible for 1-2 million deaths per year, mainly in African children, as well as considerable morbidity manifested as severe anaemia and encephalopathy in young children. Fundamental to the development of new tools for malaria control in humans is an increased understanding of key features of malaria infection, such as the diversity of outcome in different individuals, the understanding of different manifestations of the disease and of the mechanisms of immunity that allow clinical protection in the face of ongoing low-grade infection (concomitant immunity or premunition). Here, Graham Brown and colleagues review some of the ways in which molecular approaches might be used to increase our understanding of the epidemiology and clinical manifestations of malaria, as discussed at the Molecular Approaches to Malaria conference (MAM2000), Lorne, Australia, 2-5 February 2000.

Animals↗
PubMed2000

Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria.

Infection with Plasmodium falciparum during pregnancy leads to the accumulation of parasite-infected erythrocytes in the placenta, and is associated with excess perinatal mortality, premature delivery and intrauterine growth retardation in the infant, as well as increased maternal mortality and morbidity. P. falciparum can adhere to specific receptors on host cells, an important virulence factor enabling parasites to accumulate in various organs. We report here that most P. falciparum isolates from infected placentae can bind to hyaluronic acid, a newly discovered receptor for parasite adhesion that is present on the placental lining. In laboratory isolates selected for specific high-level adhesion, binding to hyaluronic acid could be inhibited by dodecamer or larger oligosaccharide fragments or polysaccharides, treatment of immobilized receptor with hyaluronidase, or treatment of infected erythrocytes with trypsin. In vitro flow-based assays demonstrated that high levels of adhesion occurred at low wall shear stress, conditions thought to prevail in the placenta. Our findings indicate that adhesion to hyaluronic acid is involved in mediating placental parasite accumulation, thus changing the present understanding of the mechanisms of placental infection, with implications for the development of therapeutic and preventative interventions.

Animals↗