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Biomedical subjects

M J Bailey

Publications and source records attributed to M J Bailey.

At least 19 recordsLinked to original sources

Relation of interlobar collaterals to radiological heterogeneity in severe emphysema.

BACKGROUND: A study was undertaken to assess the prevalence of interlobar collateral ventilation in patients with severe emphysema to identify factors that may help to predict patients with significant collateral ventilation. METHODS: Between April 2002 and August 2003, ex vivo assessment of the lungs 17 consecutive patients with smoking related severe emphysema was performed. To assess collateral flow, all lobes of explanted specimens were selectively intubated using a wedged cuffed microlaryngeal intubation tube and then manually ventilated using a bagging circuit. Interlobar collateral ventilation was defined as the ability to easily inflate a non-intubated lobe at physiological pressures. Pre-transplant demographic characteristics, physiological data, radiological results, and explant histology were assessed for retrospective relationships with the degree of interlobar collateral ventilation in the explanted lung. RESULTS: A total of 23 lungs were evaluated, 15 of which (66%) had significant collateral interlobar airflow. There were no significant differences in any demographic, physiological, or pathological variables between patients with collateral ventilation and those with no collateral ventilation. However, there was a significant relationship between the presence of interlobar collateral ventilation and radiological scores (p<0.05). CONCLUSIONS: Interlobar collateral ventilation occurs to a much greater extent in patients with radiologically homogeneous emphysema than in those with heterogeneous emphysema. Heterogeneity of emphysema may predict patients with a significantly reduced risk of interlobar collateral ventilation.

Female↗

Investigation into the impact of couch sag on delivered dose.

The effect of couch sag on treatment delivery accuracy has been investigated by modelling the variation of delivered dose from planned dose due to the difference between the treatment and simulation couches. The couch sag of the Siemens (Concord, USA) Primus linac was determined relative to the couch sag of the Siemens (Germany) Sensation 4 CT Scanner. A phantom planning study was then undertaken to evaluate the likely clinical impact of the couch sag through an evaluation of changes in dose distribution, dose volume histograms and monitor units. The couch sag was simulated by altering the angle of the CT gantry when obtaining image studysets. A second investigation into the effects of couch sag was undertaken using an existing patient CT studyset. For this investigation, the couch sag was simulated by appropriate rotation of the gantry and collimator angles. The effect of couch sag on calculated monitor units (MU) was found to be statistically insignificant. The small monitor unit changes observed were likely to result from differences in the average linear attenuation coefficient along the beam path to the isocentre. The major differences seen however were in the regions away from the central axis. The dose volume histograms showed that both the bladder and rectum were further spared with increasing tilt angle whilst the PTV dose was unchanged. The only issue at South West Sydney Cancer Services (SWSCS) in terms of patient position variation arises from the angle induced by the couch sag (or more precisely, the difference in couch sag angle between the CT and Linac couches). Due to the relatively uniform structures (of PTV, bladder and rectum), and the proximity of these critical structures to the isocentre, this angular rotation about the isocentre did not cause any major variations to the DVH, MU and isodoses for realistic levels of couch sag (i.e. less than 20mm).

Artifacts↗

Focal MIBI uptake is a better indicator of active myeloma than diffuse uptake.

PURPOSE: Technetium-99m 2-methoxyisobutylisonitrile (MIBI) imaging has been proposed as a front-line investigation to detect bone disease both before and after the treatment of myeloma. In this study, we have compared the pattern of MIBI uptake (focal and diffuse) between patients with proven myeloma and a cohort of patients without myeloma, in order to identify the uptake pattern that best correlates with disease activity. METHODS: Nineteen scans were taken in 16 consecutive patients (nine males and seven females: aged 39-71 yr) with active myeloma. A further 20 scans (10 subjects having MIBI myocardial perfusion scintigraphy and 10 subjects having MIBI parathyroid adenoma localisation studies), comprised the control (non-myeloma) cohort. Scans were evaluated in a double-blinded fashion by two observers for any diffuse skeletal MIBI uptake (homogeneous uptake in spine, sternum and/or long bones), and/or abnormal focal uptake (patchy, focal or tubular uptake in the skeleton or soft tissues). RESULTS: The pattern of MIBI uptake was significantly different in the myeloma-positive subjects and the control cohort. Focal uptake was highly discriminatory, being seen in 15 of 19 (79%) scans of the myeloma-positive group as opposed to one of 20 (5%) scans of the control group (P < 0.0001). In contrast, diffuse uptake was seen in 17 of 19 (89%) scans in patients with myeloma, and in 11 of 20 (55%) of the control cohort (P = 0.02). Using multiple logistic regression analysis, any focal uptake was significantly predictive for active myeloma (P = 0.0007) but diffuse uptake was not (P = 0.15). Diffuse uptake alone, without focal uptake, was found in four of 19 scans with myeloma and in 10 of 20 without active myeloma, but was not significantly associated with absence of active myeloma (P = 0.06). Using the criteria of Pace et al. for positivity (diffuse activity >50% myocardial activity), we demonstrated improved specificity from 45% to 100%, but significantly impaired sensitivity for presence of myeloma (79% vs. 37%, P = 0.02). CONCLUSION: Our study thus illustrates that the presence of any focal uptake of MIBI is useful in indicating active myeloma whereas diffuse uptake is not.

Adolescent↗

Road traffic injuries in the elderly.

OBJECTIVE: Elderly victims of motor vehicle collisions are increasing with the aging population. This study aimed to investigate the injury pattern of elderly victims involved in motor vehicle collisions. METHODS: This was a retrospective study using data from the Victorian State Trauma Outcome Registry and Monitoring Group (VSTORM) from June 2001 to July 2003, Australian Bureau of Statistics year 2001 population estimates, and Victoria Transport Accident Commission year 2001 total road death toll. Elderly victims were defined as age 65 and above. Comparison of fatality rates and general injury patterns for the elderly and young victims was undertaken. RESULTS: The total fatality rate of the elderly group was almost double that of the younger group. The elderly victims had a higher rate of chest injuries (23.42% v 18.17%; p = 0.003). The three most common chest injuries of the elderly victims were rib fractures (23.58%), flail chest (9.55%), and sternum fractures (5.97%). Elderly chest injured patients also had longer intensive care unit stay compared with the younger group (7.96 days v 5.31 days; p = 0.048). CONCLUSIONS: Elderly victims of motor vehicle collisions have a higher risk of chest injuries, especially of chest wall injuries. Age specific injury patterns are important in determining primary and secondary prevention strategies.

Accidents, Traffic↗

Rapid prototyping to create vascular replicas from CT scan data: making tools to teach, rehearse, and choose treatment strategies.

Our goal was to develop and prove the accuracy of a system that would allow us to re-create live patient arterial pathology. Anatomically accurate replicas of blood vessels could allow physicians to teach and practice dangerous interventional techniques and might also be used to gather basic physiologic information. The preparation of replicas has, until now, depended on acquisition of fresh cadaver material. Using rapid prototyping, it should be able to replicate vascular pathology in a live patient. We obtained CT angiographic scan data from two patients with known arterial abnormalities. We took such data and, using proprietary software, created a 3D replica using a commercially available rapid prototyping machine. From the prototypes, using a lost wax technique, we created vessel replicas, placed those replicas in the CT scanner, then compared those images with the original scans. Comparison of the images made directly from the patient and from the replica showed that with each step, the relationships were maintained, remaining within 3% of the original, but some smoothing occurred in the final computer manipulation. From routinely obtainable CT angiographic data, it is possible to create accurate replicas of human vascular pathology with the aid of commercially available stereolithography equipment. Visual analysis of the images appeared to be as important as the measurements. With 64 and 128 slice detector scanners becoming available, acquisition times fall enough that we should be able to model rapidly moving structures such as the aortic root.

Angiography↗

High central venous pressure is associated with prolonged mechanical ventilation and increased mortality after lung transplantation.

BACKGROUND: Poor oxygenation might occur in transplanted lungs as a result of reperfusion injury and lack of lymphatic drainage. Low central venous and pulmonary capillary wedge pressures are advocated to reduce pulmonary edema and maximize oxygenation but might adversely affect cardiac index, circulation, and renal function. METHODS: Histories, intensive care unit charts, and donor data on 118 lung transplantations performed between 1999 and 2002 were retrospectively assessed. Multiple logistic regression analysis was performed on donor, recipient, operative, and intensive care unit parameters to determine the relationship of filling pressure (central venous and pulmonary capillary wedge pressures) to prolonged mechanical ventilation and outcome. The mean central venous pressure was used to divide patients into high and low central venous pressure groups, which were then compared to determine differences in outcome and complication rates. RESULTS: A high central venous pressure was found to be associated with prolonged mechanical ventilation (odds ratio, 1.57; 95% confidence interval, 1.13-2.20; P = .008). After removing the effect of poor myocardial function by excluding patients with low cardiac index (< 2.2 L x min -1 x m(-2) ) and high inotrope requirement (> 10 microg/min), central venous pressure remained associated with prolonged mechanical ventilation (odds ratio, 2.31; 95% confidence interval, 1.31-4.07; P = .004). Duration of ventilation (P < .001), intensive care unit mortality (P = .02), hospital mortality (P = .09), and 2-month mortality (P = .02) were higher in patients with central venous pressures of greater than 7 mm Hg. There was no evidence of complications caused by hypovolemia in the low (< or = 7 mm Hg) central venous pressure group, who had lower inotrope requirements (P = .02) and lower creatinine levels (P = .013). Conclusions A high central venous pressure was associated with adverse outcomes after lung transplantation.

Adult↗

Successful mobilization of peripheral blood stem cells using recombinant human stem cell factor in heavily pretreated patients who have failed a previous attempt with a granulocyte colony-stimulating factor-based regimen.

To assess the efficacy of recombinant human stem cell factor (rHuSCF), 48 patients who had failed to mobilize >2.0 x 10(6) CD34+ cells/kg with granulocyte colony-stimulating factor (G-CSF) (10 microg/kg twice daily) with, or without, concomitant chemotherapy (G-CSF-based regimen), were remobilized with the addition of rHuSCF (20 microg/kg/day). In all, 18/48 (38%) achieved a total of >2.0 x 10(6) CD34+ cells/kg with the second rHuSCF-based mobilisation alone and 29/48 (60%) achieved a cumulative total of >2.0 x 10(6) CD34+ cells/kg following remobilization. Inclusion of chemotherapy in the mobilization regimen resulted in a higher yield of CD34+ cells/kg for both the initial G-CSF-based and subsequent rHuSCF-based regimens (0.90 vs 0.54, P < 0.01 and 2.36 vs 1.34, P < 0.01, respectively). The total peripheral blood stem cells PBSC collected from the G-CSF-based regimen, performance status, baseline platelet count and albumin were significantly associated with successful remobilization. Patients with multiple myeloma were also more likely to successfully remobilize. There was no threshold of total collected from the failed G-CSF-based regimen below which successful remobilization with the rHuSCF-based regimen was not possible. We therefore propose a predictive model [PBSC expected = 0.6+(G-CSF-based total collection)+2 (rHuSCF-based day 1 collection)] to calculate the cumulative total of PBSC expected following a maximum of five leukaphereses. This algorithm may permit the early identification of patients who are unlikely to achieve sufficient PBSC for transplantation and allow physicians to direct the resources involved in PBSC collection in a more appropriate and economical manner.

Adult↗

Outcomes, cost and long term survival of patients referred to a regional weaning centre.

BACKGROUND: Regional weaning centres provide cost effective care for patients who have undergone prolonged mechanical ventilation. There are few published European data on outcomes in these patients. METHODS: Patients admitted for weaning to the Lane Fox Respiratory Unit (LFU) between January 1997 and December 2000 were identified. The proportion weaned from mechanical ventilation, in-hospital mortality, and subsequent survival after discharge were examined. RESULTS: A total of 153 patients had been ventilated for a median of 26 days before transfer. The daily cost per patient stay was 1350. Fifty eight patients (38%) were fully weaned, 42 (27%) died, and 53 (35%) required ventilatory support at discharge from hospital of whom 36 (24%) required only nocturnal ventilation. Univariate analysis showed increasing age (OR 1.06, p<0.001), length of ICU stay (OR 1.02, p = 0.001), APACHE II predicted risk of death score (OR 1.02, p = 0.05), and a surgical cause for admission (OR 4.04) were associated with mortality. Neuromuscular/chest wall conditions were associated with low mortality (OR 0.36) but low likelihood of weaning from ventilation (OR 0.28). Female sex (OR 2.13, p = 0.03) and COPD (OR 2.81) were associated with successful weaning. Overall survival at 3 years from admission was 47%. Long term survival was lowest in patients with COPD. CONCLUSIONS: Most patients survived to leave hospital, the majority having been liberated from ventilatory support. Survivors were younger and spent less time ventilated in the referring ICU. The underlying diagnosis determined success of weaning, hospital survival, and long term outcome.

APACHE↗

Efficient cellulase production by Trichoderma reesei in continuous cultivation on lactose medium with a computer-controlled feeding strategy.

A low-foaming hydrophobin II deletant of the Trichoderma reesei strain Rut-C30 was used for production of cellulases by continuous cultivation on lactose medium in a laboratory fermenter. The control paradigm of the addition of new medium to the continuous process was based on the growth dynamics of the fungus. A decrease in the rate of base addition to the cultivation for pH-minimum control was used as an indicator of imminent exhaustion of carbon source for growth and enzyme induction. When the amount of base added per 5 min computation cycle decreased below a given value, new medium was added to the fermenter. When base addition for pH control thereafter increased above the criterion value, due to increased growth, the medium feed was discontinued or decreased. The medium feeding protocol employed was successful in locking the fungus in the stage of imminent, but not actual, exhaustion of carbon source. According to the results of a batch cultivation of the same strain on the same medium, this is the phase of maximal enzyme productivity. The medium addition protocol used in this work resulted in a very stable continuous process, in which cellulase productivity was maintained for several hundred hours at the maximum level observed in a batch cultivation for only about 10 h. Despite a major technical disturbance after about 420 h, the process was restored to stability. When the cultivation was terminated after 650 h, the level of enzyme production was still maximal, with no signs of instability of the process.

Bioreactors↗

Structure and evolution of the luciferin-regenerating enzyme (LRE) gene from the firefly Photinus pyralis.

To study the structural features of genes for the luciferin-regenerating enzyme (LRE), the entire gene along with 524 bp of upstream sequence was determined from Photinus pyralis (Coleoptera: Lampyridae). The LRE gene revealed an open reading frame composed of five exons divided by four introns ranging in size from 47 to 904 bp. The deduced LRE amino acid sequence showed identity to senescence marker protein-30 (SMP30) from a number of insects and mammals including four putative SMP30 sequences from Anopheles gambiae. Gene structure comparisons showed some intron/exon site conservation with A. gambiae and mammalian SMP30 proteins but not Drosophila. LRE and luciferase sequence comparisons revealed two conserved putative luciferin-binding sites. The evolution of LRE was discussed in relation to its function.

Amino Acid Sequence↗

Population dynamics and gene transfer in genetically modified bacteria in a model microcosm.

The horizontal transfer and effects on host fitness of a neutral gene cassette inserted into three different genomic loci of a plant-colonizing pseudomonad was assessed in a model ecosystem. The KX reporter cassette (kanamycin resistance, aph, and catechol 2, 3, dioxygenase, xylE) was introduced on the disarmed transposon mini-Tn5 into: (I) the chromosome of a spontaneous rifampicin resistant mutant Pseudomonas fluorescens SBW25R; (II) the chromosome of SBW25R in the presence of a naturally occurring lysogenic-phage (phage Phi101); and (III) a naturally occurring plasmid pQBR11 (330 kbp, tra+, Hgr) introduced into SBW25R. These bacteria were applied to Stellaria media (chickweed) plants as seed dressings [c. 5 x 104 colony-forming units (cfu)/seed] and the seedlings planted in 16 microcosm chambers containing model plant and animal communities. Gene transfer to pseudomonads in the phyllosphere and rhizosphere was found only in the plasmid treatment (III). Bacteria in the phage treatment (II) initially declined in density and free phage was detected, but populations partly recovered as the plants matured. Surprisingly, bacteria in the chromosome insertion treatment (I) consistently achieved higher population densities than the unmanipulated control and other treatments. Plasmids were acquired from indigenous bacterial populations in the control and chromosome insertion treatments. Plasmid acquisition, plasmid transfer from inocula and selection for plasmid carrying inocula coincided with plant maturation.

Bacteriophages↗

How well do doctors know their patients with severe asthma?

BACKGROUND: Rates of asthma mortality have fallen in Australia since the commencement of the National Asthma Campaign and promotion of the Australian asthma management plan. New strategies are now needed to further reduce mortality. AIM: To examine agreement about key features between asthma patients and their general practitioners (GPs). METHODS: We interviewed: (i) the next of kin of 56 asthma deaths, (ii) 91 asthma patients presenting to emergency departments with acute severe asthma and (iii) 147 of their GPs. RESULTS: Agreement was substantial for usage of oral symptomatic medication, but poor for inhaled symptomatic and preventive medications. There was moderate agreement regarding hospital admissions within the last 12 months among the cases, but little about other markers of severity. There was moderate agreement where the presenting or fatal attack was triggered by an upper respiratory-tract infection or aspirin. The next of kin and GPs agreed about family problems, but not about other psychosocial issues. They also agreed about which cases had been given action plans or verbal instructions, but few other aspects of asthma management. There was also moderate agreement regarding the use of peak flow meters by the controls. CONCLUSIONS: Doctors often have relatively poor insights into self-management practices, social background or trigger factors, even in high-risk patients. This should be considered when planning future campaigns to improve asthma management and further reduce mortality.

Adult↗

Process technological effects of deletion and amplification of hydrophobins I and II in transformants of Trichoderma reesei.

Transformants of the Trichoderma reeseistrains QM9414 and Rut-C30 were constructed in which the genes for the two major hydrophobin proteins, hydrophobins I (HFBI) and II (HFBII), were deleted or amplified by molecular biological techniques. Growth parameters and foam production of the transformant strains were compared with the corresponding properties of the parent strains by cultivation in laboratory bioreactors under conditions of catabolite repression (glucose medium) or induction of cellulolytic enzymes and other secondary metabolites (cellulose and lactose media). All the transformed strains exhibited vegetative growth properties similar to those of their parent. The Delta hfb2 (but not the Delta hfb1) transformant showed reduced tendency to foam, whereas both strains overproducing hydrophobins foamed extensively, particularly in the case of HFBII. Enzyme production on cellulose medium was unaltered in the Delta hfb2 transformant VTT D-99676, but both the Delta hfb2 and HFBII-overproducing transformants exhibited somewhat decreased enzyme production properties on lactose medium. Production of HFBI by the multi-copy transformant VTT D-98692 was almost 3-fold that of the parent strain QM9414. Overproduction of HFBII by the transformant VTT D-99745, obtained by transformation with three additional copies of the hfb2 gene under the cbh1 promoter, was over 5-fold compared to production by the parent strain Rut-C30. The Delta hfb2transformant VTT D-99676 produced a greatly increased number of spores on lactose medium compared with the parent strain, whereas the HFBII-overproducing transformant VTT D-99745 produced fewer spores.

Base Sequence↗

Substrate-regulated cyanide hydratase (chy) gene expression in Fusarium solani: the potential of a transcription-based assay for monitoring the biotransformation of cyanide complexes.

The fungus Fusarium solani detoxifies cyanide through induction of the cyanide hydratase gene activity (chy) in the presence of either KCN or the metal-complexed cyanides, K2Ni(CN)4 or K4Fe(CN)6, at pH 7.0 and 4.0 respectively. Sequence analysis of the chy gene identified primers for reverse transcriptase-polymerase chain reaction (RT-PCR)-directed analysis of mRNA transcripts, which demonstrated that activity correlated to the substrate-specific induction of gene expression. chy transcription was initiated 30-60 min after exposure of F. solani cultures to cyanide complexes. Maximum expression was detected within 4.5 h, after which chy mRNA synthesis declined below the limits of detection within 26 h. A lag period of approximately 2 h, following initial transcription, was recorded before cyanide complexes were converted to formamide. mRNA transcripts of chy were not detected in the absence of cyanide or cyanide complexes. The presence of introns within the gene resulted in a difference in size of 100 bp for DNA compared with mRNA of the corresponding 5' region. This size difference facilitated PCR detection of gene and transcript respectively. Comparisons of the predicted amino acid sequence of the F. solani chy gene and those of Gloeocerospora sorghi, Fusarium lateritium and Leptosphaeria maculans demonstrate that cyanide hydratase genes are highly conserved and of a similar evolutionary origin. These data predict that the functional assay described here to monitor the induction of chy gene expression and, potentially, cyanide degradation would be applicable to a variety of polluted environments.

Amino Acid Sequence↗

The rate of gastroenteritis in a large city before and after chlorination.

There is conflicting evidence about the contribution of drinking water to endemic community gastroenteritis in water supplies which meet conventional microbiological standards with some studies reporting associations between drinking water and endemic disease and others finding no evidence that water is implicated in disease. This study reports the results of an ecological study investigating the effect on community gastroenteritis of chlorinating a city of over 3 million people in the mid 1970s. Prior to chlorination faecal coliforms were regularly identified in the water. Admissions for gastroenteritis and attendances to the Emergency Department of the Royal Children's Hospital, Melbourne's major children's hospital, were measured between 1974 and 1980 inclusive and the influence of chlorination on rates of gastroenteritis was examined. No statistically significant difference was found in the number of admissions or emergency department visits before and after chlorination of the water supply. The study highlights the need for caution when interpreting the relationships between drinking water and gastroenteritis. The result suggests that water was not a dominant contributor to the burden of gastrointestinal disease in the community despite faecal coliforms being present in the water supply. It indicates the need for caution when attributing significant illness to drinking water when there have been only small changes in water quality without first stringently reviewing the studies methodology and understanding their limitations.

Child, Preschool↗

beta-Actin and GAPDH housekeeping gene expression in asthmatic airways is variable and not suitable for normalising mRNA levels.

BACKGROUND: The use of reverse transcription-polymerase chain reaction (RT-PCR) to measure mRNA levels has led to the common use of beta-actin and GAPDH housekeeping genes as denominators for comparison of samples. Expression of these genes is assumed to remain constant, so normalising for variations in processing and signal quantitation. However, it is well documented that beta-actin and GAPDH expression is upregulated with proliferation, activation, and differentiation. We hypothesised that airway samples which differ in their cellular profiles and activation status have different levels of expression of GAPDH and beta-actin. METHODS: The mRNA for beta-actin, GAPDH, and interleukin (IL)-2 was measured in bronchoalveolar lavage (BAL) fluid cells and endobronchial biopsy tissue by competitive RT-PCR in a cross sectional study of 26 normal controls and 92 asthmatic subjects. RESULTS: For both BAL fluid cells and biopsy tissue, asthmatics overall had reduced expression of GAPDH and beta-actin mRNA. In asthmatic subjects not using inhaled corticosteroids (ICS), GAPDH mRNA levels in both BAL fluid and biopsy tissue, and beta-actin mRNA in BAL fluid cells were 10 times lower than samples from both normal controls and from asthmatic subjects using ICS. beta-Actin mRNA in biopsy specimens showed the same pattern of expression, but asthmatic subjects not using ICS were not significantly different from those receiving ICS treatment. IL-2 mRNA levels did not differ between the subject or treatment groups but, when expressed as a ratio with beta-actin, significant differences were seen. CONCLUSIONS: beta-Actin and GAPDH used as denominators of gene expression quantitation in asthma research can cause confounding. Housekeeping genes need careful validation before their use in such quantitative mRNA assays.

Actins↗

Reliable use of green fluorescent protein in fluorescent pseudomonads.

When fluorescent pseudomonads are cultured on standard solid media under iron limiting conditions, they produce fluorescent, pigmented iron collating agents (siderophores). Siderophores can be readily identified by strong fluorescence seen under UV/blue light. The application of the eukaryotic green fluorescent protein (GFP) as a bacterial marker in microbial ecology is increasingly being used, particularly as it is a powerful method for non-destructive monitoring in situ. As gfp expressing bacteria have to be detected under UV/blue light, the fluorescence of siderophore-producing Pseudomonas spp. masks normal levels of GFP fluorescence when colonies are viewed on standard bacterial agar. Here, we describe a simple but effective way of identifying gfp-expressing Pseudomonas fluorescens using media supplemented with 0.45 mM FeSO(4).7H(2)O. This is of relevance for the screening of insertion libraries and in the application of GFP transposons as promoter probes.

Culture Media↗