Search PubMed⌕ Search

Biomedical subjects

G I Snell

Publications and source records attributed to G I Snell.

49 records · Page 3Linked to original sources
PubMed1997

Scar collagen deposition in the airways of allografts of lung transplant recipients.

Collagen subtype deposition has not been studied in the airways of transplanted lungs. As part of rejection, a series of immunologic insults results in a remodeling of the allograft. In chronic rejection, changes in the airway leading to obliterative bronchiolitis syndrome (OBS) are particularly important. To better understand the mechanism of OBS occurring in chronic lung rejection, we investigated deposition of three fibrillar collagens (type I, III, V) in airway biopsies of lung allografts taken from 10 clinically well lung transplant recipients (wLTR) and eight lung transplant recipients (LTR) with OBS (OBLTR) using an immunoperoxidase method. Collagen III deposition and the ratio of collagen type III to type I were found to be significantly increased in OBLTR compared with wLTR (p < 0.05), and the latter correlated inversely with both FEF(25-75) (r = -0.69; p < 0.05) and FEV1 (r = 0.62; p = 0.05) in OBLTR. This suggests that an increased proportion of collagen III in the airway walls of transplanted lungs might be an early signal of the progression to terminal chronic lung allograft dysfunction. The changes in the ratio of type III to type I collagen in the airways of lung allografts may provide important insights into the process of airway remodeling in chronic lung rejection.

Adult↗
PubMed1997

Quantitative detection of human cytomegalovirus DNA in lung transplant recipients.

Human cytomegalovirus (HCMV) disease remains a major cause of morbidity and mortality after lung transplantation. Currently, routine diagnostic tests for HCMV are inefficient and insensitive or nonspecific for HCMV disease. We describe an efficient, highly sensitive, quantitative polymerase chain reaction (PCR) assay for HCMV using competitive PCR and fluorescently labeled primers, and we have used this to measure HCMV DNA load in donor and recipient tissues of six lung transplant recipients at the time of transplantation, and 2 wk after transplantation when clinically stable. Total DNA yield was adequate for analysis in transbronchial biopsy, bronchoalveolar lavage, and peripheral blood leukocytes, but the endobronchial biopsy specimens did not consistently produce sufficient DNA for analysis. There was a large intersubject and intrasubject variability between tissues in HCMV DNA load, with a tendency for greater levels in lung tissue compared with BAL or peripheral blood cells. All six HCMV IgG seronegative donors or recipients were found to have HCMV DNA present. One of the three seronegative matched transplant recipients developed histopathologically proven HCMV disease, and HCMV DNA levels were shown to increase at that time point and subsequently decrease with ganciclovir treatment. This assay will allow prospective studies to confirm the predictive value of HCMV DNA load in donor and recipient tissues for HCMV disease.

Antibodies, Viral↗
PubMed1997

Airway versus transbronchial biopsy and BAL in lung transplant recipients: different but complementary.

Lung transplantation is now an established therapeutic intervention for end-stage cardiopulmonary disease in humans. Chronic rejection, in the form of bronchiolitis obliterans syndrome (BOS), remains the commonest cause of morbidity and mortality in those surviving more than 3 months. The pathology of BOS involves airway changes. We have evaluated the potential for endobronchial biopsies (EBB) to complement existing sampling methods used in allograft monitoring and have compared the results of EBB findings with those of bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) in 18 clinically stable patients. We found that all the EBB had inflammatory cells present but that only five TBB specimens had evidence of inflammation, with airway material being present in 78% of the TBB. Paired BAL and EBB yielded different results, with no correlations between total macrophages, lymphocytes, CD4+ cells or CD8+ cells. We conclude that endobronchial biopsies are potentially useful as an additional sample for the monitoring of inflammation in lung allografts, since they yield different, and potentially complimentary, information to bronchoalveolar lavage and transbronchial biopsy.

Adult↗
PubMed1996

Cytolytic therapy for the bronchiolitis obliterans syndrome complicating lung transplantation.

UNLABELLED: The bronchiolitis obliterans syndrome (BOS) is the major cause of late morbidity and mortality after lung transplant (LTx). Previous studies suggest cytolytic therapy may be effective for the BOS but this therapy has not been proved effective or safe. METHOD: A retrospective study of a predetermined treatment regimen to determine if the rate of fall in FEV1 can be reduced by corticosteroids and cytolytic therapy. Since August 1992, 10 to 65 long-term survivors of LTx (5 men, 5 women; mean age 36 +/- 10 years) developed BOS. All had previously had lymphocyte immune globulin, antithymocyte globulin (equine) (ATGAM sterile solution; Upjohn Pty Ltd; Sydney, Australia) induction therapy and corticosteroid avoidance for the first 7 to 10 days post-LTx. Therapy for the BOS was initiated with pulse methylprednisolone and ATGAM (aiming for an absolute CD3 count of < or - 100 cells per microliter for 5 days). ATGAM therapy was initiated at a mean 657 +/- 323 days post-LTx. Subsequent follow-up has been for 310 +/- 110 days (range, 163 to 530 days). RESULTS: Nine of ten patients had a response with tolerable side effects. Preintervention, there was a linear fall in FEV1 of 0.22 +/- 0.15% predicted FEV1 per day (mean +/- SD) (range, 0.06 to 0.56%) compared with a postintervention linear fall of 0.036 +/- 0.019% predicted per day (range, 0 to 0.13%) (paired t test; p<0.005). This effect is sustained over the follow-up period. CONCLUSION: The fall off in FEV1 that characterizes the BOS may be altered usefully by augmented immunotherapy. This effect can be rapid and sustained although it is neither completely arrested nor ever reversed. These data are preliminary but encourage a randomized control trial in the BOS.

Adult↗
PubMed1996

Pulmonary allograft ischemic time: an important predictor of survival after lung transplantation.

BACKGROUND: Traditionally organ availability in human lung transplantation has been limited by aiming to keep the graft ischemic time under 6 hours. To maximize organ supply in a country with a widely spread population, we have routinely procured organs beyond this time. Our experience outlines the clinical consequences of a prolonged allograft ischemic time. METHODS: Between 1990 and 1994 we performed 106 lung or heart-lung transplantations. The average graft ischemic time was 323 +/- 93 minutes. Lung preservation included a prostacyclin infusion (40 to 80 ng/kg/min for 10 minutes) and cold modified Euro-Collins solution flush. Organs were stored and transported on ice at 6 degrees to 10 degrees C. Graft ischemic time, transplant type, age, gender, cytomegalovirus status, and anesthetic time were subject to multivariate Cox regression analysis. RESULTS: Survival and graft ischemic times for heart-lung (n = 38), single lung (n = 33), and bilateral lung transplantation (n = 35) were not significantly different. Graft ischemic time was an independent predictor of survival (p < 0.01). Subgroup analysis notes the effect to be most pronounced beyond 5 hours (p = 0.02, hazard ratio 3.44, confidence interval 1.12 to 9.8). CONCLUSIONS: Pulmonary allograft ischemic time beyond 5 hours does not result in acceptable outcomes although survival is reduced. Attempts should be made to minimize graft ischemic times with careful coordination of transport and personnel.

Adult↗
PubMed1996

Reverse telescope anastomotic technique reduces the incidence of bronchial stricture.

BACKGROUND: Bronchial stricture remains a major problem after lung transplantation. We hypothesized that a "reverse" telescope anastomosis, where the donor bronchus is sleeved external to the recipient bronchus, would be associated with a lower incidence of anastomotic stricture. METHODS: Over a 12-month period our Unit performed 35 consecutive single and bilateral sequential lung transplantations. The 56 bronchial anastomoses were constructed as a conventional (n = 27) or as a reverse (n = 29) telescope. RESULTS: Bronchial strictures developed in 48% of the conventional anastomoses but in only 7% of the reverse anastomoses (p < or = 0.05). Furthermore, the reverse telescope anastomosis eliminated the need for stenting. CONCLUSIONS: This technique greatly reduced the need for dilatation, debridement, and stent placement and may reduce the morbidity and mortality associated with anastomotic complications.

Adult↗
PubMed1995

Inhaled nitric oxide used as a bridge to heart-lung transplantation in a patient with end-stage pulmonary hypertension.

We describe a 40-yr-old woman who received inhaled nitric oxide (NO) as a therapeutic bridge to heart-lung transplantation for end-stage primary pulmonary hypertension. After 10 yr of increasing disability, the patient presented in October 1993 with severe dyspnea, right ventricular angina, and syncope. As predicted by a prior vasodilator trial, prostacyclin produced as initial favorable clinical and hemodynamic response. With the recurrence of severe symptoms and hemodynamic compromise, inhaled NO was successfully tried at 40 ppm, initially via a face mask and later via a transtracheal Scoop catheter. The patient was "bridged" to heart-lung transplant after 68 d of therapy (mean dose of NO, 50.4 +/- 23 ppm). The explanted lungs revealed no evidence of significant NO toxicity, and the explanted heart was successfully transplanted into another patient. Inhalation of NO via a transtracheal catheter is a useful and practical treatment of refractory pulmonary hypertension. The limits of NO therapy in terms of duration and dosage have not been determined.

Administration, Inhalation↗
PubMed1994

Techniques and results in bilateral sequential single lung transplantation. The National Heart & Lung Replacement Service.

Lung transplantation continues to evolve as a therapeutic option for patients with end-stage lung disease. Bilateral sequential single lung transplantation (BSSLTx) is a recent addition to the lung transplant surgeon's armamentarium that incorporates the benefits of single lung transplantation in patients who require double lung replacement while avoiding the morbidity inherent in the en bloc double lung transplant procedure. Between November 1992 and October 1993, 17 recipients underwent 18 bilateral BSSLTx procedures for a variety of indications. In 53% of patients, the procedure was completed without the requirement for cardiopulmonary bypass. Telescoping of the bronchial anastomosis has proved satisfactory. Induction cytolytic therapy has not been utilized. Patients received methyl prednisolone from day 1 and as maintenance prednisolone therapy. Actuarial 1-year survival is 87%; 12 of the 15 survivors are in Functional Class I. BSSLTx is an evolving transplant option for patients who require double lung replacement. Definitive clinical diffusion of the procedure will depend upon intermediate and long-term outcomes for specific recipient pathologies.

Adult↗
PubMed1994

Exercise, potassium, and muscle deconditioning post-thoracic organ transplantation.

Although muscle deconditioning appears to significantly limit peak exercise performance post-thoracic organ transplantation, few confirmatory data exist. Potassium (K+) regulation during exercise may reflect muscle deconditioning, since both peak plasma K+ concentration ([K+]) and the increase in plasma [K+] relative to energy expenditure (delta [K+]/W) are reduced in healthy individuals after training. This study compares delta [K+]/W during graded exercise and the change in [K+] (delta [K+]) during both exercise and recovery in 12 heart transplant (HT) recipients, 14 lung transplant (LT) recipients, and 7 healthy subjects. Plasma [K+] was determined from arterial blood sampled at rest; during the final 15 s of each power output; and at 1, 2, and 5 min postexercise. Peak oxygen consumption was significantly lower (P < 0.0001), whereas delta [K+]/W was significantly higher (P < 0.002) among the HT and LT groups. When delta [K+] during recovery was expressed relative to delta [K+] detected during activity, no difference at 1, 2, or 5 min postexercise was detected, although the absolute fall in plasma [K+] was greater among the healthy subjects in the 1st min (P < 0.0001). The rate of delta [K+] during recovery appears to reflect the rise seen during activity in all groups. These results suggest that [K+] regulation is altered during exercise in both HT and LT recipients and may reflect muscle deconditioning.

Adult↗
PubMed1993

Lung transplantation in patients over the age of 50.

It is common to assign an upper age limit for potential lung transplant recipients. The influence of age on LTX outcome is, however not, documented. A review of our first 103 LTXs, 51 single LTXs and 52 double LTXs, includes 31 recipients aged 50-63 years (mean 55.3 +/- 3.9); 19 received single LTX, and 12 received double LTX. Indications for LTX in those aged greater than 50 included proportionately more patients with emphysema and interstitial lung disease. Actuarial survivals in those aged less than 50 at 12, 36, and 60 months were 68%, 60%, and 55%, and in those aged greater than 50 was 70%, 61%, and 61%, respectively. The causes of death reflect a tendency of younger patients to die from graft rejection and older patients to die from sepsis. Acute rejection more than 6 weeks posttransplant and chronic rejection were less frequent in older patients (P < 0.05). The 6-minute walk and modified Bruce protocol tests, the incidence of CMV pneumonitis, and the late post-LTX renal function were not related to age. In conclusion, in carefully selected candidates in their sixth and seventh decades, LTX is an acceptable operation for end-stage lung disease. The tendency of older patients to a lower incidence of late allograft rejection (acute or chronic) may reflect decreased immunological responsiveness with age.

Actuarial Analysis↗
PubMed1993

Pseudomonas cepacia in lung transplant recipients with cystic fibrosis.

Twenty-four isolated double lung transplants (LTXs) have been performed in 22 patients with cystic fibrosis, with a follow-up of 4 to 47 months. Prior to LTX, all patients were colonized with Pseudomonas aeruginosa, and ten patients were also colonized with Pseudomonas cepacia. Both organisms were specifically sought before LTX. All patients who grew P cepacia before LTX did so after LTX. Five additional patients only grew this bacterium after LTX. There was no difference between those who grew P cepacia and those who did not in terms of data before LTX for age, weight, pulmonary function, and 6-min walk. After LTX, 7 of the 15 patients who had ever grown P cepacia died. No patient who grew only P aeruginosa died. The median survival in the subgroup with P cepacia was 28 days. Five of the seven died as a direct result of P cepacia pneumonia and sepsis. One died of cyclosporin A (cyclosporine) neurotoxicity with concurrent P cepacia pneumonia, and one died at the time of a retransplant for graft failure (associated with three bouts of P cepacia pneumonia and cytomegalovirus). Four of seven had not grown this bacterium before LTX. There were no perioperative factors, including antibiotic choices, that distinguished survivors and nonsurvivors. Overall 1-year survival is about 70 percent (15/22). Fourteen bouts of P cepacia pneumonia occurred in 12 patients. Four empyemas, one lung abscess, one suppurative pericarditis, and five cases of sinusitis were also due to this bacterium. In conclusion, P cepacia is responsible for excess morbidity and mortality after LTX. This organism is particularly lethal if isolated for the first time after LTX. Factors predicting its acquisition in this setting are unknown. While it is possible that the facial sinuses may act as an unrecognized reservoir or that patients or equipment provide a source, further study into the epidemiology of this organism is necessary to improve the survival of colonized patients undergoing LTX.

Adult↗