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Biomedical subjects

G I Snell

Publications and source records attributed to G I Snell.

At least 19 recordsLinked to original sources
PubMed2006

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↗
PubMed2006

Outcomes of patients with interstitial lung disease referred for lung transplant assessment.

BACKGROUND: Patients with interstitial lung disease (ILD) very frequently die before the opportunity to receive lung transplantation (LTx). This retrospective study describes the clinical course of 86 patients with ILD referred for LTx assessment between January 1999 and December 2002. AIMS: (i) To describe the outcomes, (ii) to identify reasons of delay to transplantation, (iii) to describe the causes of death/complications and (iv) to assess the pathological diagnosis and concordance with explanted lung pathology. METHODS: Data were collected from the case notes of all patients with ILD referred to the Alfred Hospital over a 4-year period. RESULTS: Twenty women and 66 men, mean age of 55 +/- 8 years, were referred for LTx assessment. Forty-five patients were deemed not suitable for LTx and 41 were listed. Twenty-two patients underwent transplantation, 16 died on the waiting list and 7 are still on the waiting list. Complications were frequent (e.g. pulmonary embolism, malignancy and infection) and carried high mortality. Patients dying on the waiting list appeared generally to be in accelerated decline, dying shortly after listing, with no evidence in their lung function test assessment predicting them as a poor prognosis group. CONCLUSIONS: Serious complications and death on the waiting list of patients with idiopathic pulmonary fibrosis are high, not apparently because of delayed referral but usually in patients undergoing very rapid decline.

Female↗
PubMed2006

Everolimus versus azathioprine in maintenance lung transplant recipients: an international, randomized, double-blind clinical trial.

Everolimus is a proliferation signal inhibitor with immunosuppressive activity that may reduce the rate of progression of chronic rejection, bronchiolitis obliterans syndrome (BOS), after lung transplantation. In a randomized, double-blind clinical trial, 213 BOS-free maintenance patients received everolimus (3 mg/day) or azathioprine (AZA, 1-3 mg/kg/day) in combination with cyclosporine and corticosteroids. The prospectively defined primary endpoint was the incidence of efficacy failure (decline in FEV1 >15%[deltaFEV1 >15%], graft loss, death or loss to follow-up) at 12 months. Incidence of efficacy failure at 12 months was significantly lower in the everolimus group than AZA (21.8% vs. 33.9%; p = 0.046); at 24 months, rates of efficacy failure became similar between the groups. At 12 months, the everolimus group had significantly reduced incidences of deltaFEV1 >15%, deltaFEV1 >15% with BOS, and acute rejection. At 24 months, only incidence of acute rejection remained significantly less in the everolimus group. Treatment discontinuations (particularly due to adverse events), serious adverse events and high serum creatinine values were more common with everolimus. For the first time, a drug has demonstrated significant slowing of loss in lung function, suggesting that patients kept on prolonged maintenance treatment with everolimus may benefit from replacing AZA with everolimus 3 months after lung transplantation.

Adrenal Cortex Hormones↗
PubMed2006

The dynamics and associations of airway neutrophilia post lung transplantation.

UNLABELLED: Bronchoalveolar lavage (BAL) neutrophilia has been repeatedly observed in lung transplant recipients with established bronchiolitis obliterans syndrome (BOS). Little is known of the fluctuations in BAL and airway neutrophilic inflammation post-transplant. This prospective longitudinal study aimed to evaluate the dynamic changes of lung allograft neutrophils with time, immunosuppression, infection and BOS. A total of 28, initially healthy, BOS 0, lung transplant recipients underwent 134 bronchoscopic assessments, including BAL and endobronchial biopsies (EBB) (with immunohistochemistry) over 3-year follow up. Subsequently, 21 developed BOS 0p and 16 ultimately BOS. Compared to controls, there was early and persistent BAL neutrophilia (p < 0.05), contrasting with an initially normal EBB that shows a progressive increased airway wall neutrophil infiltrate. BAL neutrophilia (but not airway wall neutrophilia) was most striking when there was concomitant bronchopulmonary infection, particularly in the patients with BOS. Univariate and multivariate analyses suggested that BAL neutrophilia was linked to markers of infection while EBB neutrophilia was linked with coexistent inflammation with macrophages and lymphocytes. IN CONCLUSION: (i) BAL neutrophilia is predominantly associated with infection; (ii) Airway wall neutrophilia (as monitored by EBB) increases with time post-transplant and is not associated with infection; (iii) By itself, BOS is not the major contributor to BAL and EBB neutrophilia.

Adult↗
PubMed2005

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↗
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

Non-heart beating organ donation.

Increasing the levels of non-heart beating organ donation (NHBOD) is a potential means of improving the supply of transplantable organs. NHBOD may provide a mechanism to enable a patient's prior wishes to be realised and to provide comfort to a family in grief. There is an overriding ethical principle to strictly divide the responsibility for the care of the dying patient and the potential transplant recipient. Medical protocols need to be written, and institutional ethics committees and our national organ procurement system need to be involved if we are to protect public confidence and see NHBOD realise its full potential.

Cadaver↗
PubMed2002

Increased soluble CD14 in bronchoalveolar lavage fluid of stable lung transplant recipients.

Macrophages, neutrophils and infection have been implicated in the genesis of the bronchiolitis obliterans syndrome (BOS) post lung transplantation. sCD14 is a soluble form of a shed-cell surface protein. It is capable of promoting cytokine-induced inflammation and it's presence in clinically stable lung transplant recipients (LTR) might be important as an early marker of BOS. Bronchalveolar lavage (BAL) and blood samples were taken from 26 stable LTR, at or near their best forced expiratory volume in one second who were free from infection. sCD14 levels were measured via enzyme-linked immunosorbent assay. Cell counts were performed on unfiltered BAL. LTR neutrophil count, BAL sCD14 and serum sCD14 levels were higher than controls (median 3.8% versus 1.3%, p<0.05; 11.5 ng x mL(-1) versus 6 ng x mL(-1), p<0.001; 6.2 microg x mL(-1) versus 2.4 microg x mL(-1), p<0.05, respectively). BAL albumin and sCD14 correlated (regression coefficient: 0.77, p<0.001). In this hypothesis-generating, cross-sectional study, the authors have described for the first time soluble CD14 levels in the bronchoalveolar lavage and serum of stable lung transplant recipients, and show that these are elevated compared to controls. This is a practicable candidate marker system, which can be tested for a predictive role in bronchiolitis obliterans syndrome following lung transplantation. The origin of this cellular protein and its temporal relationship to the development of the bronchiolitis obliterans syndrome remains to be elucidated in more definitive longitudinal studies, which should include other measurements potentially relevant to the innate immune system, such as bronchoalveolar lavage endotoxin levels.

Adult↗
PubMed2001

Increased human cytomegalovirus (HCMV) DNA load in peripheral blood leukocytes after lung transplantation correlates with HCMV pneumonitis.

BACKGROUND: Human cytomegalovirus (HCMV) reactivation and disease remain relatively common in lung transplant recipients (LTR) despite the use of ganciclovir prophylaxis protocols for all HCMV at-risk patients. The specific aims of this study were to (1) describe the HCMV DNA viral load in the peripheral blood leukocytes (PBL) of a cohort of LTR during the first 6 months after lung transplantation; (2) prospectively determine whether HCMV DNA viral load predicts episodes of HCMV pneumonitis in LTR; and (3) study the effect of ganciclovir on HCMV viral load. METHODS: Competitive polymerase chain reaction using an internal standard and fluorometric detection were used to quantitate HCMV DNA in the PBL of a cohort of 26 LTR monthly for the first 6 months after transplantation (145 samples). All patients were treated with standard triple immunosuppression, and ganciclovir prophylaxis was given to all at-risk LTR (donor or recipient HCMV seropositive) for at least 8 weeks after transplantation. RESULTS: Thirteen episodes of histopathologically proven HCMV pneumonitis in nine subjects occurred during follow-up with a wide intra- and intersubject variation in the HCMV DNA PBL levels. HCMV detection had a sensitivity of 92% and specificity of 76% for HCMV pneumonitis (negative likelihood ratio, 9.5), whereas greater than 10-fold increases in HCMV DNA load had a specificity of 93% and sensitivity of 67% (positive likelihood ratio, 11). HCMV DNA detection had an adjusted odds ratio for HCMV pneumonitis of 107 (95% confidence interval, 14-821; P<0.005). In those with detectable HCMV DNA in PBL (n=44), HCMV DNA levels were 4.4 (95% confidence interval, 1.2-16.8) times higher in those with HCMV pneumonitis than in those without HCMV pneumonitis. Although ganciclovir treatment was very effective in treating HCMV pneumonitis and suppressing HCMV DNA levels, thrice weekly ganciclovir prophylaxis only partially controlled HCMV DNA levels and did not eliminate HCMV pneumonitis risk as three patients developed HCMV pneumonitis while on this regimen. CONCLUSIONS: HCMV DNA detection, absolute levels, and relative change from baseline in the PBL of LTR correlate with HCMV pneumonitis episodes and may be a useful intermediate outcome measure of the efficacy of ganciclovir prophylaxis and treatment strategies.

Adult↗
PubMed2001

Idiopathic pulmonary fibrosis: in need of focused and systematic management.

Idiopathic pulmonary fibrosis (IPF) is an increasingly recognised, serious lung disease. A recent International Consensus Statement has redefined the term "idiopathic pulmonary fibrosis", restricting its use to the entity previously described as "usual interstitial pneumonia" and reclassifying some of the more benign inerstitial lung diseases formerly included under IPF. There is insufficient quality evidence for the effectiveness of current medical therapies for IPF. Lung transplantation provides a potential surgical therapeutic option for selected individuals with IPF, but referral for transplant needs to be made as early as possible. Multidisciplinary clinics specialising in interstitial lung disease have a potential role in determining which patients may benefit from novel and existing medical therapies and which patients should be referred for lung transplantation.

Adult↗
PubMed2001

Lung volume reduction surgery in emphysema: a systematic review.

The aim of this study was to systematically review the literature regarding the safety and efficacy of lung volume reduction surgery (LVRS) in patients with emphysema. Studies on LVRS to August 2000 were identified using MEDLINE, Embase, Current Contents, and the Cochrane Library. Human studies of patients with upper, lower or diffuse distributions of emphysema were included. All types of bullous emphysema were excluded. A surgeon and researcher independently assessed the retrieved articles for their inclusion in the review. When LVRS was compared with medical management, at 2 years LVRS was associated with a higher FEV1 and at least equivalent survival. The use of staple excision of selected areas of lung appeared to be more efficacious than laser ablation. There is insufficient evidence to show preference for median sternotomy or videoscopically assisted thoracotomy, as the more safe and efficacious procedure. In highly selected patients with emphysema LVRS is deemed an acceptable treatment. To fully evaluate the safety and efficacy of LVRS, outcomes beyond 2 years must be included. The results of prospective randomized trials between medical management and LVRS, now in progress, are essential before a final assessment can be made.

Hospital Mortality↗
PubMed2001

Organ procurement--strategies to optimize donor availability.

Increasing donor availability for organ transplantation requires attention to factors that are potentially modifiable. The potential pool of available organs can theoretically be enlarged by considering new sources of organs, including non-beating heart donors, live donor lobar transplants, xenotransplants, and in vitro organ culture. Increased utilization of the current pool of organs can be achieved by creating a system that identifies, considers, and optimizes all possible donors. Although protocols have been drawn up regarding general and specifically lung donor acceptance criteria, many of these can be now recognized as unduly conservative and without a proven clinical basis. Careful reanalysis of these acceptance criteria and active donor management can be balanced against the particular circumstance of an individual potential recipient to increase lung transplantation rates.

Journal Article↗
PubMed2001

Lung volume reduction surgery: the Thoracic Society of Australia and New Zealand.

Lung volume reduction surgery involves the removal of emphysematous lung tissue with the aim of palliating symptoms in selected patients with severe emphysema. This form of surgery is being practised in Australia with favourable short-term outcomes, similar to those reported in the literature. Large multicentre trials are currently underway in North America and the United Kingdom to clarify issues of safety and long-term efficacy. As a result, it is too early to apply an evidence-based approach to this procedure. In the meantime, local audits of practice need to be undertaken to define patient subgroups at higher risk of morbidity and mortality.

Humans↗
PubMed2000

Predictors of perioperative morbidity and mortality in lung volume reduction surgery.

BACKGROUND: Selection criteria for lung volume reduction surgery are still being refined. We sought to determine whether preoperative features could be used to predict early morbidity or mortality. METHODS: We reviewed preoperative characteristics of the first 89 patients who underwent lung volume reduction surgery at the Alfred Hospital. Data included arterial blood gases, prednisolone use, pulmonary function tests, 6-minute walk test, and anesthetic time. Length of stay and reintubation for respiratory failure were used as markers of morbidity. RESULTS: Findings included PaCO2 of 43 +/- 0.7 mm Hg, PaO2 70 +/- 1.1 mm Hg, percent predicted values for forced expiratory volume in 1 second 29.6% +/- 0.8%, TLCO% predicted 35.2 +/- 1.4%, and 6-minute walk test of 315 +/- 10.6 m (mean +/- SEM). Mean length of stay was 19 +/- 2 days, with 17 (19%) patients reintubated for respiratory failure. Mortality rate was 5.6% at 1 year post surgery, with no deaths in patients less than 65 years old. Multivariate analysis revealed that length of stay, reintubation and mortality were predicted by age and surgical time (p < 0.05), with no correlation with any other variables tested. Age greater than 70 years was associated with a significant risk of mortality (OR 9.0; p = 0.04). CONCLUSIONS: Age greater than 70 years and anesthetic time greater than 210 minutes predict both perioperative morbidity and mortality.

Adult↗
PubMed2000

Bilateral sequential single lung transplantation for pulmonary hypertension and Eisenmenger's syndrome.

BACKGROUND: Lung transplantation, with and without intracardiac repair for pulmonary hypertension (PH) and Eisenmenger's syndrome (EIS), has become an alternative transplant strategy to combined heart and lung transplantation (HLT). METHODS: Thirty-five patients with PH or EIS underwent either bilateral sequential single lung transplantation (BSSLT, group I, n = 13) or HLT (group II, n = 22). Another 74 patients, who underwent BSSLT for other indications, served as controls (group III). Immediate allograft function, early and medium-term outcomes, lung function, and 2-year survival were compared between the groups. RESULTS: Comparisons between groups I and II showed no significant difference in any variables except percent predicted forced vital capacity. Immediate allograft function was significantly inferior (p < 0.05) and the blood loss was greater (p < 0.01) in group I when compared with those in group III. However, this resulted in no significant difference in early and medium-term outcomes, and 2-year survival between the 2 groups. CONCLUSIONS: BSSLT for PH and EIS can be performed as an alternative procedure to HLT without an increase in early and medium-term morbidity and mortality. Results are comparable with BSSLT performed for other indications.

Adult↗
PubMed2000

Maximizing thoracic organ transplant opportunities: the importance of efficient coordination.

BACKGROUND: In Australia, despite large distances and one of the world's lowest multiorgan donor rates (11.4/million population/year), the thoracic organ transplant (TOTx) rate of 9.6/million population/year is one of the world's highest. METHODS: As an example of the Australian approach, a system of transplant coordination and organ allocation has evolved at the Alfred Hospital. Donor organs are assigned locally, or between the 4 major TOTx units on rotation. The recipient team then selects appropriate recipients, matching by blood group, size, cytomegalovirus (CMV) status, prospective cross matching and clinical status. An experienced recipient coordinator takes responsibility for organization of the retrieval and transplant process, including all operating room staff, all medical personnel, and transport for the donor team and the potential TOTx recipients. RESULTS: Between February 1989 and February 1999, 307 hearts, 48 heart/ lung, 124 single and 116 bilateral lung transplants were performed from 452 donor offers (52% beyond 500 miles). This represents 1.74 organs transplanted/thoracic donor and compares favourably to American United Network for Organ Sharing (1.43) and European (1.3) figures. CONCLUSIONS: The Australia TOTx model has enabled high transplant rates by efficiently using the available donor organs. This has been achieved through an enlarged, experience TOTx team, the optimizing of donor acceptance criteria and improving coordination logistics to allow multiple thoracic procedures simultaneously.

Australia↗