Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The common fatal hereditary disorders, alpha 1-antitrypsin (alpha 1AT) deficiency and cystic fibrosis (CF), are clinical models for the common lung diseases, emphysema and chronic bronchitis, respectively. Both are potentially amenable to therapeutic intervention by gene therapy, in which the relevant gene is used to modify cells of the affected individual. Although the gene therapy strategies for these diseases are conceptually quite different, a promising approach for both is the in vivo administration of a recombinant replication deficient adenovirus vector containing a normal copy of the abnormal gene. If the goal is to express the normal extracellular anti-protease alpha 1 AT, the route of administration could be directly into the lung, liver or vascular endothelium. If the goal is to express the normal transmembrane protein defective in CF epithelial cells, the new gene will need to be delivered directly to the affected cells. The feasibility of these approaches has been demonstrated in vitro and in vivo in experimental animals.
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PMID:Gene therapy for pulmonary diseases. 829 Mar 11

Heart-lung transplantation and lung transplantation have become accepted techniques in adult patients with end-stage cardiopulmonary disease. We report here our experience between July 1985 and March 1993 with 34 children (< 20 years) who underwent heart-lung (n = 18) or lung transplantation (n = 17). Indications for transplantation included cystic fibrosis (n = 9), congenital heart disease with Eisenmenger complex (n = 9), primary pulmonary hypertension (n = 8), pulmonary arteriovenous malformations (n = 2), desquamative interstitial pneumonia (n = 2), Proteus syndrome with multicystic pulmonary disease (n = 1), graft-versus-host disease (n = 1), rheumatoid lung disease (n = 1), and bronchiolitis obliterans and emphysema (n = 1). Twenty-six patients (76%) have survived from 1 to 88 months after transplantation; most patients have returned to an active lifestyle. Of the eight deaths, four were due to infections, two to multiorgan failure, 1 to posttransplant lymphoproliferative disease, and one to donor organ failure. Four of the patients who died had cystic fibrosis. Despite considerable morbidity related to infection, rejection, and function of the heart-lung and lung allograft in some patients, our results with this potentially lifesaving procedure in the pediatric population have been encouraging.
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PMID:Experience with pediatric lung transplantation. 830 35

The application of lung transplantation to the pediatric population was a natural extension of the success realized in our adult transplant program, which began in 1982. Thirty-two pediatric patients (age range 1 to 18 years) have undergone heart-lung (n = 16), double-lung (n = 14), and single-lung (n = 2) transplantation procedures. The cause of end-stage lung disease was primary pulmonary hypertension (n = 7), congenital heart disease (n = 7), cystic fibrosis (n = 9), pulmonary arteriovenous malformation (n = 2), desquamative interstitial pneumonitis (n = 2), graft-versus-host disease (n = 1), emphysema (n = 1), rheumatoid lung (n = 1), cardiomyopathy (n = 1), and Proteus syndrome (n = 1). Six patients (19%) underwent pretransplantation thoracic surgical procedures. The survival rate was 78% at a mean follow-up of 1.8 years. The survival rate in the 23 recipients without cystic fibrosis was 87% (95% since 1985). The actuarial 1-year survival rate in the nine recipients with cystic fibrosis was 55%. Immunosuppression was cyclosporine (n = 9) or FK 506 (n = 23)-based therapy with azathioprine and steroids. Children were followed up by spirometry, transbronchial biopsy, and primed lymphocyte testing of bronchoalveolar lavage fluid. The mean number of treated episodes of rejection per patient in the groups treated with cyclosporine and FK 506, respectively, was 1.0 and 1.2 at 30 days, 0.67 and 0.38 at 30 to 90 days, and 2.33 and 0.46 at greater than 90 days (p < 0.001, Fisher exact test).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pediatric lung transplantation: expanding indications, 1985 to 1993. 831 44

Between February 1988 and January 1992, 61 patients have undergone bilateral lung transplantations (42 heart-lung and 19 double-lung) in Bordeaux. The underlying diseases were primary or secondary hypertension (20), emphysema (22), or other diseases including cystic fibrosis, pulmonary fibrosis, silicosis, and sarcoidosis (19). Actuarial survival for double-lung and heart-lung transplant recipients was 66% and 72% at 1 year and 57% and 53% at 3 years, respectively. Forty-two patients were still alive 6 months after operation, and we studied their pulmonary function at the short and long term. All parameters except arterial carbon dioxide tension had improved dramatically at 6 months (p < 0.0001). Vital capacity, forced expiratory volume in 1 second, and forced expiratory flow rate between 25% and 75% of vital capacity were at 79% +/- 3%, 92% +/- 5%, and 105% +/- 8% of the predicted values, respectively. Arterial oxygen tension was 88 +/- 3 mm Hg. Nine months after operation, a slight decrease in forced expiratory volume in 1 second and forced expiratory flow rate between 25% and 75% of vital capacity appeared but values remained more than 75% predicted. This was related to the occurrence of obliterative bronchiolitis in 6 patients (14%). At 9 months, flow rates and oxygen tension of these 6 patients were highly different from those of patients free of obliterative bronchiolitis (p < 0.0002 for flow rates and p < 0.01 for oxygen tension). Only 1 patient required retransplantation. The others are living an almost normal life. Our results are discussed in view of the published reports on single-lung transplantation. Short-term results of bilateral lung transplantation are thus excellent and maintained on a long-term basis. Therefore, in our opinion, bilateral lung transplantation is the therapy of choice for pulmonary hypertension and emphysema.
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PMID:Long-term functional results after bilateral lung transplantation. Bordeaux Lung and Heart-Lung Transplant Group. 832 78

Malnutrition is a documented problem in some types of endstage lung disease (ESLD). Recently, isolated lung transplants have successfully reversed the respiratory failure of patients suffering from ESLD. In this study, we compare the preoperative and postoperative nutritional states of lung transplant recipients using weight-to-height ratios, anthropometric measurements, subjective global assessment, and biochemical blood values. Patients with emphysema, cystic fibrosis, and other types of bronchiectasis, but not patients with pulmonary fibrosis or pulmonary hypertension, were malnourished preoperatively. All groups had normal biochemical profiles. Caloric intake of patients with cystic fibrosis and bronchiectasis was increased above predicted basal energy expenditure levels. By six months to one year postoperatively, all groups of malnourished patients had significantly improved their nutritional status. Emphysema patients improved nutrition by maintaining preoperative caloric intake levels--however, both cystic fibrosis and bronchiectasis patients were able to achieve the same goal with significantly decreased caloric intakes. We conclude that malnourished ESLD patients receiving isolated lung grafts are able to achieve normal nutrition within one year posttransplant. Since this occurs in all cases with a reduced, or at best maintained, caloric intake, more study is needed to elucidate the factors that contribute to ESLD malnutrition.
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PMID:A comparison of preoperative and postoperative nutritional states of lung transplant recipients. 835 88

Alpha 1-proteinase inhibitor (also known as alpha 1-antitrypsin) derived from pooled human serum (Prolastin, Miles Biologicals) has been available in the United States since 1988. Although no formal controlled prospective study has been performed to prove its efficacy, intravenous administration of Prolastin has been the accepted treatment for individuals with pulmonary emphysema due to alpha 1-antitrypsin deficiency. In addition, Prolastin has been used experimentally by inhalation for the treatment of cystic fibrosis. It has been administered with some success to treat the panniculitis associated with alpha 1-antitrypsin deficiency. As a greater number of severely impaired alpha 1-antitrypsin deficient patients receive lung transplantation, the role of Prolastin in the post-transplant therapy of these patients will need evaluation. Newer antiproteases may render Prolastin obsolete with respect to its route of administration and its pricing, however, the safety record of this drug has been impressive.
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PMID:Alpha 1-antitrypsin augmentation therapy. 835 34

The significance of cytomegalovirus (CMV) infection after lung transplantation was investigated in 20 patients (ten women and ten men; mean age 46 [21-67] years). Indications for transplantation were emphysema (n = 6), cystic fibrosis (n = 2), primary pulmonary hypertension (n = 2), pulmonary fibrosis (n = 5), obliterating bronchiolitis (n = 2), cystic lung (n = 2) and bronchiectasis (n = 1). Incidence, diagnostic parameters (serology, virus isolation and histology) and efficacy of prophylactic and therapeutic measures were recorded. 16 of the 20 patients developed a CMV infection, which in 12 was clinically significant. CMV pneumonia developed in two patients, proving fatal in one. The infection occurred a median of 47 (17-200) days after the transplantation. Administration of Ganciclovir (5 mg/kg twice daily intravenously) brought about remission of symptoms in all but one of the patients and improved the clinical parameters.--This experience demonstrates that regular monitoring of the patients for possible CMV infection and its early therapy can achieve a low death rate.
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PMID:[Cytomegalovirus infection following lung transplantation]. 838 98

Optimal timing for consideration of lung transplantation remains unknown. This study examined survival in patients with end-stage lung disease awaiting transplantation. Primary disease group and relevant indicators were evaluated. Ninety-three patients who met selection criteria for lung transplantation were included in this retrospective review. Of this total, 31% underwent transplantation, 38% remain waiting, and 31% died. Results demonstrate that the six-month actuarial survival rate was 89% for Eisenmenger's syndrome, 81% for emphysema, 74% for cystic fibrosis, 60% for primary pulmonary hypertension, and 38% for interstitial lung disease. Parameters found to be significant included a higher mean right atrial pressure in primary pulmonary hypertension patients who died awaiting transplantation, and lower forced expiratory volume in one second and forced vital capacity measurements in cystic fibrosis patients who died awaiting transplantation. We conclude that primary disease significantly affects survival in candidates awaiting transplantation. Reliable indicators predictive of survival are not available. Earlier referral for consideration of lung transplantation is recommended.
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PMID:Primary diagnosis predicts prognosis of lung transplant candidates. 849 79

The authors review the recent changes observed in the indications for lung transplantation. Several classical contra-indications have been alleviated or even cancelled. Chronic infection presenting as cystic fibrosis has become one of the first indications for lung replacement. Respirator-dependent patients are at an operative risk comparable to the overall results. Long-term corticosteroid therapy and pleural adhesions are no longer formal contraindications but should be approached with extreme caution. In recent years, single lung transplantation has been extended to diseases, such as emphysema and pulmonary hypertension, which were formerly indications for double-lung or heart-lung transplantation. The reasons for this include donor shortage and the better 1-year survival following single lung transplantation. The most recent development is paediatric lung transplantation. The legitimacy of redo transplantation is controversial.
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PMID:[Lung transplantation. Contraindications and new indications]. 851 Oct 81

Lung transplantation is becoming an acceptable mode of therapy worldwide for the end-stage lung disease. We present our initial experience with the first 10 consecutive lung transplant patients at Hadassah University Hospital. There were 5 males and 5 females with an age range 27 to 59 years. Eight patients underwent single lung transplantation, one patient had double lung transplantation and one had heart-lung transplantation. Indications were: pulmonary fibrosis in 4, emphysema in 4, cystic fibrosis in 1, and cystic bronchiectasis in 1. Two patients had primary graft failure (1 death). Nine patients had a serious infection after transplantation (1 death). Four patients developed airway complications including dehiscence of bronchial anastomosis (1 death), bronchial stenosis requiring placement of a stent in 2 patients, and pneumothorax in 1 patient. One patient required tracheostomy. One patient died of massive brain infarction secondary to pulmonary venous thrombosis and embolization. Six patients are intermediate-term survivors, with a follow-up period of 4-24 months. Four of them had at least one episode of rejection each. In all survivors pulmonary functions and quality of life improved and they do not need supplemental oxygen. We conclude that lung transplantation is a viable option for end-stage lung disease. Better selection of patients and perhaps improved immunosuppression agents will further improve outcome in lung transplantation. Shortage of donor supply is currently the limiting factor in successful lung transplantation in Israel.
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PMID:Early experience in lung transplantation. 864 73


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