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Biomedical subjects

Michael Bailey

Publications and source records attributed to Michael Bailey.

At least 37 records · Page 2Linked to original sources
PubMed2005

Total leukocyte control for elective coronary bypass surgery does not improve short-term outcome.

BACKGROUND: Despite early promise as a means of reducing the inflammatory response to surgery and subsequent organ damage, the evidence of the clinical value of leukocyte filtration remains equivocal. METHODS: Three hundred patients presenting for routine coronary artery bypass surgery were randomized to a total leukocyte filtration group (filters in five different locations) and a control group with a standard 40-mum filter in the bypass return line only. Data on efficacy and safety of leukocyte filtration were collected by research and postoperative care staff who were blinded to the mode of filtration. RESULTS: Leukofiltration achieved a transient fall in white cells immediately after surgery (p = 0.07) and a sustained fall in platelets, which was still significant on the second postoperative day (p = 0.0001). However, there were no significant differences in postoperative hospital stay, the primary outcome variable (p = 0.35), in ICU stay (p = 0.92), or mortality (p = 1.0). There were no differences in postoperative cardiac status including cardiac output (p = 0.16), inotrope (p = 0.93) or balloon pump (p = 0.48) requirement, or 24-hour troponin (p = 0.60). Similarly there were no differences in pulmonary or renal function (intubation time (p = 0.83), respiratory index (p = 0.19) rise in creatinine (p = 0.13) or hemofiltration (1.0)). Leukofitration was not associated with a statistically significant increase in bleeding or requirement for blood or blood products. It was associated with a decrease approaching significance (p = 0.1) in number and severity of postoperative wound infections. Three filters were blocked during use but were changed without incident or compromise to patient safety. CONCLUSIONS: Leukocyte filtration is safe but not efficacious in improving short-term outcome.

Aged↗
PubMed2005

Development of the palatine tonsil in conventional and germ-free piglets.

Palatine tonsils, like the Peyer's patches, are considered to be major inductive sites for the mucosa-associated lymphoid tissue (MALT), providing sampling and effector functions for the upper respiratory tract. Consistent with this, they have the architecture required of a classic inductive site (B-cell follicles, immunoglobulin class switching and the presence of naïve and memory T-cells). Here we show that much of this architecture develops after birth in the neonatal piglet, the numbers of T-cells, B-cells and accessory cells increasing with age. Conventional piglets also had higher levels of activated and memory T-cell subsets than germ-free piglets, consistent with development occurring as a result of microbial stimulus. The results suggest that the microbial environment influences the development of the tonsil immunological architecture. Given the role of the tonsil in induction of mucosal responses, this raises questions as to the effectiveness of the tonsil in dealing with colonising organisms in the neonate.

Age Factors↗
PubMed2005

Airway vascular changes after lung transplant: potential contribution to the pathophysiology of bronchiolitis obliterans syndrome.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) remains the primary factor limiting successful lung transplantation. In asthma and lung transplantation BOS-increased sub-mucosal vascularity has been shown to contribute to airflow limitation. Vascularity has 2 components: sprouting angiogenesis (more vessels) and microvascular enlargement (larger vessels). We hypothesized that the lack of a reanastomosed bronchial arterial blood supply at the time of transplant might stimulate angiogenesis and be a risk factor for subsequent BOS. METHODS: Twenty-seven initially stable lung transplant recipients (BOS 0) were recruited at 148 +/- 80 days post-transplant and underwent clinical and bronchoscopic longitudinal follow-up for at least 3 years. Eight remained stable and BOS developed in 19. Nine normal controls were also recruited. Airway vasculature was examined immunohistochemically in endobronchial biopsy (EBB) specimens with collagen IV antibody, quantified by computer image analysis, and expressed as average vessel size, vessel number, and overall vascularity. The effects of demographic, clinical, bronchoalveolar lavage (BAL), and EBB variables on airway vasculature were analyzed in a multivariate model. RESULTS: No significant differences in airway vascularity were found between stable and BOS lung transplant recipients cross-sectionally or longitudinally. However, both lung transplant groups at baseline showed significantly greater airway vascularity compared with normal controls (p < .05). Multivariate analysis suggested that the percentage of BAL CD3+ cells and acute rejection are the most influential variables on airway vasculature. CONCLUSIONS: This study suggests early and persistent airway vasculature changes occur in lung transplant recipients, mainly manifested as microvascular enlargement. Potentially this baseline change contributes to airway obstruction and also puts all lung transplant recipients at risk for further exponential loss of airway caliber with any subsequent airway inflammatory insult.

Adult↗
PubMed2005

Gastroesophageal reflux (symptomatic and silent): a potentially significant problem in patients with cystic fibrosis before and after lung transplantation.

BACKGROUND: The significance of gastroesophageal reflux (GER) and aspiration are unclear in cystic fibrosis (CF) and may contribute to declining lung function before and after lung transplantation (LTx). METHODS: We sought to establish whether GER occurs in patients with CF on the LTx waiting list and after LTx. We then investigated whether GER correlates with patients' symptoms. Adults with CF on the waiting list and after LTx were prospectively recruited. Completion of a valid, structured symptom questionnaire was followed by ambulatory, dual-probe, 24-hour esophageal pH monitoring. RESULTS: Twenty-four patients were studied, including 11 (6 males) in the pre-LTx group and 13 (9 males) in the post-LTx group. The pre-LTx group was 29.3 +/- 8.2 years of age, and the post-LTx group was 32.7 +/- 8.2 years of age. DeMeester score (normal value <14.7) was 36.6 +/- 22.3 for the pre-LTx group and 40.0 +/- 37.3 for the post-LTx group. Proximal esophageal acid exposure was significantly higher in both CF groups compared with normal. Symptom scores (normal <4, range -2 to 18) were: pre-LTx group, 5.8 +/- 6.5; post-LTx group, 7.7 +/- 5.4. Percent forced expiratory volume in 1 second (FEV1%) predicted was: pre-LTx group, 31.3 +/- 7.8; post-LTx group, 65.2 +/- 29.3. In the pre-LTx group, 10 of 11 (90.9%) patients had significant GER on monitoring, including 4 (40%) with symptomatic GER and 6 (60%) with silent GER. In the post-LTx group, 11 of 13 (84.6%) had significant GER on monitoring, including 9 (82%) with symptomatic GER and 2 (18%) with silent GER. CONCLUSIONS: GER, symptomatic and silent, is a significant problem in CF. This condition should be aggressively treated and surgery should be considered if GER persists on re-testing.

Adolescent↗
PubMed2005

Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue.

OBJECTIVES: Previous clinical trials suggest that coenzyme Q(10) might afford myocardial protection during cardiac surgery. We sought to measure the effect of coenzyme Q(10) therapy on coenzyme Q(10) levels in serum, atrial trabeculae, and mitochondria; to assess the effect of coenzyme Q(10) on mitochondrial function; to test the effect of coenzyme Q(10) in protecting cardiac myocardium against a standard hypoxia-reoxygentation stress in vitro; and to determine whether coenzyme Q(10) therapy improves recovery of the heart after cardiac surgery. METHODS: Patients undergoing elective cardiac surgery were randomized to receive oral coenzyme Q(10) (300 mg/d) or placebo for 2 weeks preoperatively. Pectinate trabeculae from right atrial appendages were excised, and mitochondria were isolated and studied. Trabeculae were subjected to 30 minutes of hypoxia, and contractile recovery was measured. Postoperative cardiac function and troponin I release were assessed. RESULTS: Patients receiving coenzyme Q(10) (n = 62) had increased coenzyme Q(10) levels in serum (P = .001), atrial trabeculae (P = .0001), and isolated mitochondria (P = .0002) compared with levels seen in patients receiving placebo (n = 59). Mitochondrial respiration (adenosine diphosphate/oxygen ratio) was more efficient (P = .012), and mitochondrial malondialdehyde content was lower (P = .002) with coenzyme Q(10) than with placebo. After 30 minutes of hypoxia in vitro, pectinate trabeculae isolated from patients receiving coenzyme Q(10) exhibited a greater recovery of developed force compared with those in patients receiving placebo (46.3% +/- 4.3% vs 64.0% +/- 2.9%, P = .001). There was no between-treatment difference in preoperative or postoperative hemodynamics or in release of troponin I. CONCLUSIONS: Preoperative oral coenzyme Q(10) therapy in patients undergoing cardiac surgery increases myocardial and cardiac mitochondrial coenzyme Q(10) levels, improves mitochondrial efficiency, and increases myocardial tolerance to in vitro hypoxia-reoxygenation stress.

Administration, Oral↗
PubMed2005

In vitro inhibitory effects of atorvastatin on cardiac fibroblasts: implications for ventricular remodelling.

1. Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) reduce mortality after myocardial infarction (MI). Although this may be predominantly due to their known anti-ischaemic actions, these drugs are known to have other beneficial effects. 2. Because pathological deposition of extracellular matrix (ECM) material is a key component of remodelling after MI, we sought to determine whether atorvastatin could inhibit ECM production in vitro. 3. The addition of atorvastatin to rat cardiac fibroblasts stimulated with either transforming growth factor (TGF)-beta1 (TGF-beta1) or angiotensin (Ang) II reduced collagen synthesis in a dose-dependent manner (3.7-fold reduction (95% confidence interval (CI) 1.8-15; P < 0.01) and 5.3-fold reduction (95% CI 1.8-7.7; P < 0.01), respectively, compared with stimulant alone). Similar observations were made in human cardiac fibroblast cell culture. Atorvastatin also dose-dependently reduced TGF-beta1 and AngII-induced increases in alpha(I)-procollagen mRNA (P < 0.01 for both), as well as gene expression of the profibrotic peptide connective tissue growth factor. 4. Atorvastatin appears to directly inhibit collagen production by cardiac fibroblasts. This antifibrotic action may contribute to the antiremodelling effect of statins.

Angiotensin II↗
PubMed2005

Everolimus alters the bronchoalveolar lavage and endobronchial biopsy immunologic profile post-human lung transplantation.

Everolimus has recently shown promise in terms of short- and long-term clinical lung transplant outcomes. This study aims to determine the altered lung allograft cellular and cytokine mileau when everolimus is substituted for azathioprine (AZA). Twenty-three stable lung transplantation (LTx) recipients were randomized in a double-blinded study to receive everolimus (13) or AZA (10) plus standard cyclosporine/prednisolone. Bronchoalveolar lavage (BAL) and endobronchial biopsies (EBB) were performed on three occasions (T(0)-T(2)) to elucidate cellular and cytokine profiles via immunocytochemistry, immunohistology and enzyme-linked immunosorbent assay (ELISA) techniques. There were no group differences for demographics or clinical events throughout the study nor baseline cellular/cytokine differences. BAL lymphocyte percentage fell in the AZA group by T(2) (p = 0.05). BAL and EBB CD4 measures significantly declined in the everolimus group by T(2) (p < 0.05). EBB neutrophils rose significantly in the AZA group, with a fall in the everolimus group resulting in a significant difference at T(2) (p = 0.01). In conclusion, everolimus has contributed to potentially important differences in BAL and EBB cellular profiles.

Anti-Inflammatory Agents↗
PubMed2005

Factors that impact upon the time to hospital presentation following the onset of chest pain.

INTRODUCTION: Although morbidity and mortality associated with chest pain are related to time to intervention, many patients have delayed ED presentations. We aimed to assess the extent of and reasons for prehospital delay, and identify patient subgroups more at risk of delayed presentation. METHODS: This was an analytical, cross-sectional survey of patients with undifferentiated, potentially ischaemic chest pain, at a tertiary referral ED. Data were collected on the circumstances surrounding the chest pain incident (including components of total prehospital time) and the proportion of delayed presentations (defined as >3 h). Multiple linear regression determined variables significantly associated with prehospital time. RESULTS: One hundred and fifty patients were enrolled. Mean age was 51.9+/-15.9 years and 90 (60.0%, 95% CI 51.7-67.8) were male. The mean total prehospital time was 6.38 h (median 3.17). Seventy-nine (52.7%, 95% CI 44.4-60.8) patients had a delayed presentation (>3 h) and those most at risk of this were those at home at pain onset and those with a history of AMI. The decision time (from onset of pain to decision to present) comprised the majority (82.8%) of total prehospital time. Factors positively associated with decision time were: waiting to see if symptoms resolved (P<0.0001), seeking GP advice (P<0.0001), fluctuating symptoms (P=0.02), embarrassment (P=0.01) and attributing symptoms to muscle problems (P=0.04). Nine patients diagnosed with AMI had a mean total prehospital time of 10.2 h. CONCLUSION: Intensified efforts are required to promote awareness of the need to present directly to the ED upon the onset of chest pain. The factors associated with decision delay may help to inform revisions in public education initiatives.

Chest Pain↗
PubMed2005

Cardiac troponin I concentrations, but not electrocardiographic results, predict an extended hospital stay after coronary artery bypass graft surgery.

BACKGROUND: Cardiac damage in coronary artery graft (CABG) surgery is an important contributor to postoperative cardiac dysfunction and delayed hospital discharge. Currently, no simple method exists for its quantification. METHODS: In a prospective study of 300 patients having routine CABG surgery, we compared cardiac troponin I (cTnI) concentrations at 6 and 24 h after surgery with electrocardiographic (ECG) results as predictors of an extended postoperative stay in the intensive care unit (ICU) and in the hospital. We stratified outcome variables by tertiles of cTnI concentration and studied the significance of differences between outcome variables across tertiles. RESULTS: Multivariate analysis showed that 24-h cTnI is a significant predictor of increased postoperative ICU stay (P = 0.012) and postoperative hospital stay (P = 0.024). For 6-h cTnI, corresponding significance values were P = 0.29 and 0.9. ECG was of no value (P = 0.39 and 0.47). Differences in 24-h cTnI were highly significant, particularly for lowest vs highest tertiles, and allowed stratification of risk into "low" (<10 microg/L), "equivocal" (10-20 microg/L), and "high" (>20 microg/L). CONCLUSIONS: Use of a single 24-h cTnI value to quantify perioperative myocardial damage identifies patients who are at greater risk of extended ICU and hospital stays. This strategy could assist in allocation of patients to different management streams after CABG surgery.

Analysis of Variance↗
PubMed2004

Differential conductance switching of planar tunnel junctions mediated by oxidation/reduction of functionally protected ferrocene.

Planar tunnel junctions were fabricated by self-assembling 1,1'- ferrocenedicarboxylic acid (FDCA) onto native oxides of thermally deposited aluminum films and subsequently depositing a second aluminum film. Junctions were characterized using Reflection-Absorption Fourier Transform Infrared Spectroscopy (RAIRS) and current-voltage (I-V) spectroscopy. Before deposition of the second aluminum film, RAIRS of FDCA and ferrocenecarboxylic acid (FCA) films revealed COO(-), C=O, and Fc ring stretching modes, indicating that both types of molecules can interact strongly with the oxide and remain intact. After deposition, systems exhibited prominent COO(-) modes and weakened C=O modes, indicating further reaction with aluminum/aluminum oxide. Fc ring modes persisted in FDCA systems but disappeared in FCA systems, suggesting that the second COOH group in the FDCA molecule can act as a protecting group for the ferrocene moiety. Cyclic I-V measurements of FDCA tunnel junction systems revealed very strong ( approximately 10-fold) hysteretic differential conductance switching that was both reversible and stable. Control measurements using as prepared junctions, as well as junctions containing 1,6-hexanedioic acid, 1,9-nonanedioic acid, 1,4-dibenzoic acid, or FCA revealed only very weak ( approximately 10%) differential conductance changes. We attribute FDCA junction switching to barrier profile modifications induced by oxidation/reduction of the functionally protected ferrocene moieties.

Journal Article↗
PubMed2004

Vagal response varies with Valsalva maneuver technique: a repeated-measures clinical trial in healthy subjects.

STUDY OBJECTIVE: Variable success rates of the Valsalva maneuver in treatment of paroxysmal supraventricular tachycardia may be due to variations in performance technique. This study aimed to compare the magnitude of the vagal reflexes initiated by 5 variations of the Valsalva maneuver technique (supine, supine with epigastric pressure, supine with leg raise, semirecumbent position, and sitting position). METHODS: This was a single-blinded, repeated-measures, clinical trial of 65 subjects in sinus rhythm. Subjects performed each Valsalva maneuver technique 5 times in random order. The means of the longest ECG R-R intervals during the relaxation phase (postmaneuver R-R interval) and the postmaneuver pulse rates for each technique were compared. The mean differences between the pre- and postmaneuver R-R intervals for each technique were also compared. RESULTS: The supine with epigastric pressure and supine techniques resulted in longer mean postmaneuver R-R intervals (1.082 seconds [95% confidence interval (CI) 1.045 to 1.119 seconds] and 1.075 seconds [95% CI 1.035 to 1.114 seconds], respectively) than the leg raise, semirecumbent, and sitting position techniques (1.053 seconds [95% CI 1.019 to 1.086 seconds], 1.044 seconds [95% CI 1.006 to 1.081 seconds], and 1.024 seconds [95% CI 0.990 to 1.059 seconds], respectively), which equates to slower mean postmaneuver pulse rates for the supine with epigastric pressure and supine techniques (55.5 and 55.8 beats/min, respectively) than the leg raise, semirecumbent, and sitting position techniques (57.0, 57.5, and 58.6 beats/min, respectively). The supine with epigastric pressure and supine techniques also resulted in the largest premaneuver versus postmaneuver differences. CONCLUSION: For healthy subjects in sinus rhythm, the supine with epigastric pressure and supine techniques generated stronger vagal responses, as measured by R-R intervals and pulse rates, than the other techniques examined. However, the vagal responses of these 2 techniques were similar, and the addition of epigastric pressure may confer little advantage.

Adult↗
PubMed2004

Effect of inhaled fluticasone propionate on BAL TGF-beta(1) and bFGF concentrations in clinically stable lung transplant recipients.

BACKGROUND: Inhaled fluticasone propionate (FP) therapy decreases inflammation and sub-basement membrane thickness in asthmatic airways. Bronchiolitis obliterans syndrome (BOS) in lung transplant recipients (LTRs) involves progressive airway fibrosis and obliteration. Therefore, augmented immunosuppression may be of some benefit in treating BOS. In this study, we examined the effect of 3 months of treatment with high-dose inhaled FP on the concentrations of 2 fibrogenic factors, transforming growth factor (TGF)-beta(1) and beta fibrogenic growth factor (bFGF) in bronchoalveolar lavage (BAL) fluid from clinically stable LTRs. METHODS: We conducted a randomized, double-blind, placebo-controlled, parallel group study with inhaled FP (750 microg, twice/day for 3 months) in 28 LTRs (15 FP and 13 placebo). We recruited 23 healthy controls. We performed spirometry, bronchoscopy, and bronchoalveolar lavage procedures before treatment and after 3 months of treatment. We used commercially available enzyme-linked immunosorbent assay kits to measure BAL fluid TGF-beta(1) and bFGF concentrations. RESULTS: In LTRs before treatment, BAL TGF-beta(1) concentrations (but not bFGF concentrations), total cell counts, and neutrophil percentage increased compared with controls (p < 0.05). We found no significant differences between FP and placebo groups at baseline measurements. After treatment, BAL TGF-beta(1) concentrations significantly increased in the FP group (p = 0.03), but we found no difference between FP and placebo groups; BAL bFGF concentrations increased during treatment in both groups compared with controls (p < 0.05), but not significantly within either patient group (p > 0.05). We found a reverse correlation between forced expiratory volume in 1 second (FEV(1)) and BAL TGF-beta(1) concentration in the FP group (r = -0.53, p = 0.04), and between FEV(1) and BAL TGF-beta(1) concentration in the placebo group (r = -0.74, p = 0.004). Multivariable analysis indicated no significant independent effects of inhaled FP in either BAL TGF-beta(1) or bFGF concentrations. CONCLUSIONS: Bronchoalveolar fluid TGF-beta(1) concentrations increased in LTRs after transplantation and may correlate with the decrease in lung function. Inhaled FP added to conventional immunosuppression had no effect on TGF-beta(1) or bFGF production in BAL fluid.

Administration, Inhalation↗
PubMed2004

Expression of Melanocarpus albomyces laccase in Trichoderma reesei and characterization of the purified enzyme.

Previous studies on Melanocarpus albomyces laccase have shown that this enzyme is very interesting for both basic research purposes and industrial applications. In order to obtain a reliable and efficient source for this laccase, it was produced in the filamentous fungus Trichoderma reesei. Two approaches were used: production of a non-fused laccase and a hydrophobin-laccase fusion protein. Both proteins were expressed in T. reesei under the cbh1 promoter, and significantly higher activities were obtained with the non-fused laccase in shake-flask cultures (corresponding to about 230 mg l(-1)). Northern blot analyses showed rather similar mRNA levels from both expression constructs. Western analysis indicated intracellular accumulation and degradation of the hydrophobin-laccase fusion protein, showing that production of the fusion was limited at the post-transcriptional level. No induction of the unfolded protein response pathway by laccase production was detected in the transformants by Northern hybridization. The most promising transformant was grown in a fermenter in batch and fed-batch modes. The highest production level obtained in the fed-batch culture was 920 mg l(-1). The recombinant laccase was purified from the culture supernatant after cleaving the major contaminating protein, cellobiohydrolase I, by papain. The recombinant and wild-type laccases were compared with regard to substrate kinetics, molecular mass, pH optimum, thermostability, and processing of the N- and C-termini, and they showed very similar properties.

Cellulose 1,4-beta-Cellobiosidase↗
PubMed2004

Effects of infection with transmissible gastroenteritis virus on concomitant immune responses to dietary and injected antigens.

Normal piglets weaned onto soy- or egg-based diets generated antibody responses to fed protein. Concurrent infection with transmissible gastroenteritis virus (TGEV) did not affect the responses to dietary antigens at weaning, nor did it affect the subsequent development of tolerance. However, TGEV infection did enhance the primary immunoglobulin M (IgM) and IgG1, but not IgG2, antibody responses to injected soy in comparison to those of uninfected animals. Paradoxically, TGEV-infected animals showed an enhanced primary IgG1 antibody response to injected soy at 4 weeks of age, but they subsequently showed a reduced secondary response after an intraperitoneal challenge at 9 weeks of age in comparison to uninfected animals. The results suggest that an enteric virus, either used as a vaccine vector or present as a subclinical infection, may not have significant effects on the development of dietary allergies but may have effects both on the primary response and on the subsequent recall response to systemic antigens to which the animal is exposed concurrently with virus antigens.

Administration, Oral↗
PubMed2004

Prevalence of external auditory canal exostoses in Australian surfboard riders.

This paper assessed 300 surfboard riders, comprising 229 males and 71 females to determine the prevalence and rate of growth of exostoses in this population. A group of cold water swimmers and a control group were also examined. Significant obstruction, defined as two thirds or more occlusion of the ear canal was noted in 90 of the male surfers and 10 female surfers. This degree of occlusion was found in seven of the 32 cold water swimmers. A male surfer who has surfed regularly for 20 years or more has a one in two chance of developing significant obstruction of the external ear canal resulting from exostoses and this is a three in seven chance for females.

Adult↗
PubMed2004

Xenobiotic gene polymorphisms and susceptibility to multiple myeloma.

Genetic variations in the activity of xenobiotic enzymes may predict susceptibility to multiple myeloma (MM). In a case-control study, 90 Australian Caucasians with MM had significantly higher incidences of GST T1 null, PON1 BB and NAT2 slow acetylation genotypes, but no difference in polymorphism frequencies for GST M1, NAT1, and CYP1A1 when compared to 205 controls.

Adult↗