Biomedical subjects

Donald Campbell

Publications and source records attributed to Donald Campbell.

5 recordsLinked to original sources

PubMed2003

Epstein-Barr virus nuclear antigen-1 and Myc cooperate in lymphomagenesis.

The lymphomagenic action of myc genes in conjunction with Epstein-Barr virus nuclear antigen-1 (EBNA-1) have been examined using transgenic mice in several separate tests. Synergy between Myc and EBNA-1 in lymphomagenesis was revealed in a cross breed study where co-expression of transgenic myc and EBNA-1 led to a tumor latency period reduced significantly in some crosses. In the resulting bitransgenic tumors, expression of the Emu-myc genes was not affected by EBNA-1 expression. MoMLV was utilized as a transposon tag to activate cellular oncogenes by infection of EmuEBNA-1 mice. Rearrangement at the c-myc locus in B cell tumors from these mice again suggests a cooperative action between myc and EBNA-1. Tumors arising in EmuEBNA-1 mice typically showed a trisomy of chromosome 15, upon which the c-myc locus resides. Bitransgenic tumors (EBNA-1/c-myc) did not show trisomy 15. This raises the possibility that amplification of c-myc is factorial in the selection of trisomy 15 in these tumors. These data indicate that myc and EBNA-1 act cooperatively and are not redundant in lymphomagenesis. Expression of EBNA-1 by EBV may provide a selection pressure in addition to translocation of the c-myc locus in the genesis of endemic Burkitt's lymphoma (BL).

Animals↗

PubMed2003

Clustering effects of chronic obstructive pulmonary disease specific quality of life in hospitalized patients.

OBJECTIVES: The primary aim of treatments for COPD is to improve health-related quality of life. However, little is known of the clustering effects related to health-related quality of life as an outcome measure. If clustering effects are observed, these have important implications for sample size estimates when cluster randomization is used in interventional studies. This study aimed to determine the intracluster correlation coefficient (ICC) of the quality of life, between hospitals for COPD patients. METHODOLOGY: The Dyspnoea Impact and Symptoms Questionnaire was administered to 100 COPD inpatients from four public hospitals (25 from each) around metropolitan Melbourne, selected on the basis that they had not had any major programs implemented within the last 2 years that aimed to improve the management of COPD. Data were collected concerning demographic and socioeconomic variables and comorbidities. RESULTS: The highest ICC value for a health-related quality of life subscale was 0.02 (psychological score), while the highest for a symptom-based subscale was 0.04. CONCLUSIONS: There is minimal clustering effect of quality of life in COPD patients between the hospitals studied. Despite this, when using a cluster randomised design the sample size needed to detect the same effect as a study using simple randomisation could be inflated by up to 183%. If cluster randomization is required, the average cluster size should be kept as small as possible to negate this effect.

Aged↗

PubMed2003

Decannulation and survival following tracheostomy in an intensive care unit.

We investigated the long-term outcome of patients requiring tracheostomy in an intensive care unit (ICU) in an attempt to identify risk factors that would indicate a low probability of early decannulation. A retrospective study was conducted of a consecutive series of 106 patients who underwent tracheostomy in the period between January 1, 2001, and December 31, 2001, during their admission to the ICU at the Royal Melbourne Hospital, Melbourne, Australia. There were 61 male and 39 female patients with a median age of 65 years. The indications for tracheostomy were prolonged mechanical ventilation (47), tracheobronchial toilet or risk of aspiration (45), and an unstable or obstructed airway (8). Thirty-seven patients died during the study period. All surviving patients were successfully decannulated (median cannulation time, 25 days). Patients with tracheostomies inserted for an unstable or obstructed airway had a significantly shorter cannulation time (median time of 13 days) as compared to the other two indications (mechanical ventilation, 25 days; risk of aspiration, 33 days; log-rank test, chi2(2) = 14.62 and p = .0007). Multivariate analysis showed that the effect of an unstable or obstructed airway was independent of the remaining group variables. We conclude that ICU patients who need a tracheostomy have a high mortality rate. Only the indication for tracheostomy insertion predicts early decannulation, and other patient variables are not significant predictors.

Adolescent↗

PubMed2002

T lymphocyte-mediated changes in airway smooth muscle responsiveness are attributed to induced autocrine release and actions of IL-5 and IL-1beta.

BACKGROUND: Bidirectional stimulatory cross-talk was recently found to exist between activated T cells and airway smooth muscle (ASM) cells, a process that involves coligation of specific cellular adhesion-costimulatory molecules that results in the induction of proasthmatic-like changes in ASM responsiveness. OBJECTIVE: The present study examined whether the cooperative intercellular signaling between activated T cells and ASM cells is coupled to the induced expression and actions of IL-5 and IL-1beta. METHODS: Agonist-induced constrictor and relaxant responses were examined in rabbit ASM segments exposed to resting and anti-CD3-activated T cells in the absence and presence of either an anti-IL-5 receptor mAb or the recombinant human IL-1 receptor antagonist. In addition, mRNA and protein expression of IL-5 and IL-1beta were assayed under control and anti-CD3-stimulated conditions. RESULTS: Relative to inactive T cells, incubation of ASM tissues with anti-CD3-activated T cells induced proasthmatic-like changes in agonist-mediated ASM responsiveness. This T cell-induced perturbation in ASM responsiveness was ablated by pretreating the tissues with either an anti-IL-5 receptor mAb or IL-1 receptor antagonist. Moreover, exposure of ASM cells to anti-CD3-activated T cells elicited an initial increased mRNA expression and release of IL-5, followed by an enhanced expression and release of IL-1beta, and the induced release of these cytokines was prevented in ASM cells that were pretreated with an anti-IL-5 receptor mAb. CONCLUSION: Collectively, these observations provide new evidence demonstrating that exposure of naive ASM cells to activated T cells induces the sequential release of IL-5 and IL-1beta from the ASM cells and that the latter cytokines act in an autocrine manner to elicit the proasthmatic phenotype of altered ASM responsiveness.

Adult↗

PubMed2002

Managing access block.

There is pessimism regarding the ability of the Acute Health Sector to manage access block for emergency and elective patients. Melbourne Health suffered an acute bed crisis in 2001 resulting in record ambulance diversions and emergency department (ED) delays. We conducted an observational study to reduce access block for emergency patients whilst maintaining elective throughput at Melbourne Health. This involved a clinician-led taskforce using previously proven principles for organisational change to implement 51 actions to improve patient access over a three-month period. The primary outcome measures were ambulance diversion, emergency patients waiting more than 12 hours for an inpatient bed, elective throughput and theatre cancellations. Despite a reduction in multi-day bed numbers all primary objectives were met, ambulance diversion decreased to minimal levels, 12-hour waits decreased by 40% and elective throughput was maintained. Theatre cancellations were also minimised. We conclude that access block can be improved by clinician-led implementation of proven process improvements over a short time frame. The ability to sustain change over the longer term requires further study.

Admitting Department, Hospital↗