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Gregory I Snell

Publications and source records attributed to Gregory I Snell.

28 records · Page 2Linked to original sources
PubMed2004

A donor history of smoking affects early but not late outcome in lung transplantation.

BACKGROUND: Liberalization of tobacco exposure history as an exclusion to lung donation has recently occurred to increase donor organ availability. This study investigated the effect of donor smoking status and current and cumulative cigarette dose on early and late outcomes in lung transplantation. METHODS: From 1995 to 2002, 173 heart-lung and bilateral single-lung transplant recipients were retrospectively reviewed. Seventy-seven (45%) of 173 donors were ever-smokers and 64 of those 77 were current smokers. These were divided into subgroups by current number of cigarettes smoked to investigate acute dose effects and by pack-year to investigate cumulative dose effects. Risks of smoking were assessed by univariate and multivariate hazard regression models. RESULTS: Univariate analysis revealed that there were significant differences between current and cumulative dose subgroups in early postoperative variables, including Pao2/Fio2 ratio, ventilation time, and intensive care unit stay. Additionally, these variables were dose dependent. There was no significant difference in 3-year survival between never-smokers and ever-smokers (73% versus 64%, P = 0.27), and a rate of decline of survival was similar. There was a trend for the percentage of patients dying of bronchiolitis obliterans syndrome to be lower in the ever-smokers group compared with the never-smokers group (6% versus 11%, respectively). Multivariate analysis revealed current and cumulative smoking as a risk factor for early but not late outcomes. CONCLUSIONS: Donor smoking history had a significant effect on early outcomes in lung transplantation in a current and cumulative dose-dependent fashion. However, no significant effect on late outcomes, including bronchiolitis obliterans syndrome, was seen.

Adult↗
PubMed2004

Epstein-Barr virus primary mismatching and HLA matching: key risk factors for post lung transplant lymphoproliferative disease.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) in lung transplant recipients (LTRs) is potentially lethal with considerable morbidity. The role of donor (D)/recipient (R) HLA matching is unknown. METHOD: We reviewed our LTRs from January 1994, when routine D/R Epstein-Barr virus (EBV) serologic screening was begun, through to January 2000. We examined whether D/R HLA match status influenced the risk of PTLD in EBV D+/R- mismatched LTRs. RESULTS: There were 16 D+/R- EBV-mismatched LTRs, 5 (31%) of whom developed PTLD (from a total of 237 LTRs; 218 survived >30 days). There were only two other cases of PTLD among the non-EBV primary mismatched patients. All patients received baseline immunosuppression of cyclosporine, azathioprine, and prednisolone without cytolytics and ganciclovir prophylaxis if "at risk" from cytomegalovirus. The five PTLD cases were diagnosed 81 to 734 (median 116) days from transplantation; three involved the lung allograft and two others involved lymph nodes. All PTLD patients seroconverted for EBV, whereas 7 of the 11 remaining EBV-mismatched patients who did not develop PTLD did not seroconvert. In the 16 EBV primary mismatched patients, there were 4 of 66 HLA allele matches in the 11 PTLD-free patients versus 15 of 30 matches in the 5 PTLD patients (P<0.001). This resulted in 2 or more HLA (A/B/DR) matches in 4 of 5 patients with PTLD versus 0 of 11 in the PTLD-free group (P=0.003). All PTLD patients were treated with reduced immunosuppression and antiviral therapy. Only two of the five LTRs who developed PTLD died, one with progressive disease despite chemotherapy and the other from chronic allograft rejection. CONCLUSION: A high degree of HLA matching in D/R EBV-mismatched LTRs significantly increases the risk of PTLD.

Graft Rejection↗
PubMed2004

Donor history of asthma is not a contraindication to lung transplantation: 12-year single-center experience.

BACKGROUND: Donor asthma has been regarded as a contraindication to lung transplantation (LTx) because of concerns that pre-existing airway inflammation will predispose to early and late graft dysfunction. The aim of this study was to describe LTx outcomes in which lungs had been transplanted from donors with a history of asthma. METHODS: A retrospective chart review was undertaken of 743 consecutive donor lung referrals to the Alfred Hospital between 1990 and September 2002. Seventy-four were noted to have a history of asthma, including 18 in whom asthma was the cause of death. Twenty-seven patients became lung donors, of whom 16 were on asthma treatment (on-treatment group) and 11 were not (no-treatment group). RESULTS: From 27 lung donors, 35 LTx procedures were performed (16 double LTx [DLTx], 19 single LTx [SLTx]). Five recipients died at <30 days (including 3 of early graft failure in the no-treatment group), and 7 died at >30 days (only 1 due to BOS). The 30-day, 1-year and 5-year survival rates in the on- and no-treatment donor groups were 90% vs 76%, 74% vs 69% and 74% vs 60%, respectively, and were not significantly different from our overall LTx survival rates. There were no significant differences in percent predicted forced expiratory volume in 1 second, ICU stay or hospital stay overall, or when analyzed according to on treatment vs no treatment and SLTx vs DLTx. Only 2 procedures LTx were performed from fatal asthma donors, both of whom had subsequent graft dysfunction and died on Days 73 and 484, respectively. CONCLUSIONS: The use of lungs from carefully selected lung donors with a history of asthma may increase the donor pool with acceptable long-term outcomes. The use of fatal asthma donors remains problematic.

Adult↗
PubMed2003

Impaired muscle Ca2+ and K+ regulation contribute to poor exercise performance post-lung transplantation.

Lung transplant recipients (LTx) exhibit marked peripheral limitations to exercise. We investigated whether skeletal muscle Ca2+ and K+ regulation might be abnormal in eight LTx and eight healthy controls. Peak oxygen consumption and arterialized venous plasma [K+] (where brackets denote concentration) were measured during incremental exercise. Vastus lateralis muscle was biopsied at rest and analyzed for sarcoplasmic reticulum Ca2+ release, Ca2+ uptake, and Ca2+-ATPase activity rates; fiber composition; Na+-K+-ATPase (K+-stimulated 3-O-methylfluorescein phosphatase) activity and content ([3H]ouabain binding sites); as well as for [H+] and H+-buffering capacity. Peak oxygen consumption was 47% less in LTx (P < 0.05). LTx had lower Ca2+ release (34%), Ca2+ uptake (31%), and Ca2+-ATPase activity (25%) than controls (P < 0.05), despite their higher type II fiber proportion (LTx, 75.0 +/- 5.8%; controls, 43.5 +/- 2.1%). Muscle [H+] was elevated in LTx (P < 0.01), but buffering capacity was similar to controls. Muscle 3-O-methylfluorescein phosphatase activity was 31% higher in LTx (P < 0.05), but [3H]ouabain binding content did not differ significantly. However, during exercise, the rise in plasma [K+]-to-work ratio was 2.6-fold greater in LTx (P < 0.05), indicating impaired K+ regulation. Thus grossly subnormal muscle calcium regulation, with impaired potassium regulation, may contribute to poor muscular performance in LTx.

Adult↗
PubMed2003

Microangiopathic haemolytic anaemia and thrombocytopenia following lung volume reduction surgery in a single lung transplant recipient on maintenance tacrolimus (FK506) therapy.

Microangiopathic haemolytic anaemia (MAHA) describes intravascular haemolysis due to mechanical destruction of red cells as a result of pathological changes in small blood vessels. It is well recognized as a complication of cyclosporin A therapy in solid organ transplantation but has been uncommonly reported in association with tacrolimus therapy and never before in the setting of lung transplantation. Discussed is a 54-year-old female recipient of a left single lung transplant who developed anaemia, thrombocytopenia and red blood cell fragmentation consistent with MAHA following lung volume reduction surgery (VRS) of the native right lung in the setting of high serum tacrolimus levels. Treatment with fresh frozen plasma and plasmapharesis plus supportive therapy with blood and platelet transfusions resulted in successful resolution of the haemolytic process. Cyclosporin A was substituted for tacrolimus and 18 months later there has been no evidence of recurrence. Tacrolimus therapy is a rare cause of MAHA in solid organ transplants but the diagnosis should be considered if there is an unexplained fall in haemoglobin and/or platelet count in the context of high serum tacrolimus levels.

Anemia, Hemolytic↗
PubMed2003

The potential for bronchoscopic lung volume reduction using bronchial prostheses: a pilot study.

STUDY OBJECTIVES: Significant morbidity and mortality offset the benefits of lung volume reduction surgery (LVRS) for emphysema. By contributing to distal lung collapse, bronchoscopic placement of valved prostheses has the potential to noninvasively replicate the beneficial effects of LVRS. The purpose of this study was to investigate the safety and feasibility of placing valves in segmental airways of patients with emphysema. DESIGN: Case series. SETTING: Tertiary hospital, severe airways disease clinic. PATIENTS: Ten patients aged 51 to 69 years with apical emphysema and hyperinflation, otherwise suitable for standard LVRS. Mean preoperative FEV(1) was 0.72 L (19 to 46% predicted), and 6-min walk distance was 340 m (range, 245 to 425 m). INTERVENTION: Apical, bronchoscopic, segmental airway placement of one-way valves (silicone-based Nitinol bronchial stent; Emphasys Medical; Redwood City, CA) under general anesthesia. Placement was over a guidewire under bronchoscopic and fluoroscopic control. RESULTS: Four to 11 prostheses per patient took 52 to 137 min to obstruct upper-lobe segments bilaterally. Inpatient stay was 1 to 8 days. No major complications were seen in the 30-day study period. Minor complications included exacerbation of COPD (n = 3), asymptomatic localized pneumothorax (n = 1), and lower-lobe pneumonia (day 37; n = 1). Symptomatic improvement was noted in four patients. No major change in radiologic findings, lung function, or 6-min walk distance was evident at 1 month, although gas transfer improved from 7.47 +/- 2.0 to 8.26 +/- 2.6 mL/min/mm Hg (p = 0.04) and nuclear upper-lobe perfusion fell from 32 +/- 10 to 27 +/- 9% (mean +/- SD) [p = 0.02]. CONCLUSION: Bronchoscopic prostheses can be safely and reliably placed into the human lung. Further study is needed to explore patient characteristics that determine symptomatic efficacy in a larger patient cohort.

Aged↗
PubMed2002

Sirolimus allows renal recovery in lung and heart transplant recipients with chronic renal impairment.

BACKGROUND: Until recently, there has been no practical alternative to the use of calcineurin inhibitors (CIs) as primary immunosuppressants in lung transplantation (LTx) and heart transplantation (HTx). Sirolimus (SRL) is a novel powerful immunosuppressant without renal toxicity, a common post-transplant problem associated with CI therapy. METHODS: SRL was used in 20 LTx and 5 HTx recipients >90 days post-transplant, where serious renal impairment was limiting CI dosing. Patients started on 2 to 5 mg/day orally at a median of 1,185 days post-transplant. Dosage adjustments were made according to trough levels, toxicity and perceived efficacy. With SRL initiation, 48% ceased CI therapy and the remainder decreased their dose substantively. RESULTS: After 30 days, 4 of 5 dialyzed patients ceased dialysis and 15 of 20 patients with an elevated serum creatinine (Cr) (mean Cr 0.29 mmol/liter) improved their Cr. The direction of change in Cr at 30 days predicted longer term Cr. The starting Cr did not predict the 30-day or long-term value. There were two bouts of acute and one bout of chronic rejection. There were 35 infectious complications in 16 patients and 24 episodes of potential SRL-related toxicity in 17 patients. These events generally responded to dose reduction or temporary cessation and were level-related. Fifteen recipients presently remain on the drug. None of the 7 deaths could be directly related to toxicity. CONCLUSION: SRL is a useful alternative immunosuppressant, allowing significant CI withdrawal in transplant recipients with renal impairment. Whether the resulting improvement in Cr can be maintained in the long term probably depends on the balance between the extent of acute and chronic renal damage.

Adult↗