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)

1. In 1992, there were 2,171 heart, 48 heart-lung, and 535 lung transplants performed in the United States. The number of lung transplants increased by about 32% over 1991, whereas heart transplants only increased by about 2% over 1991. The number of heart-lung transplants decreased in 1992. 2. The number of programs performing heart and lung transplants has continued to increase: about 16% in heart and about 280% in lung, since 1988. 3. The most frequently reported primary indications for transplant were: coronary artery disease (44%) and cardiomyopathy (41%) in heart; cystic fibrosis (40%) in double lungs; emphysema/COPD (35%) in single lungs; and congenital/Eisenmenger's syndrome (36%) in heart-lung. 4. Between 1988 and 1992, the following groups showed significant increases for heart and lung transplants: pediatric transplants, non-White recipients, non-White donors, older donors, and local utilization. 5. For the entire period covered by this report, overall one-year patient survival rates were: heart 82.3%, single lung 70.1%, double lung 66.4%, and heart-lung 58.7%. There has been little change in one-year heart transplant survival rates during this time. Survival rates for lung and heart-lung transplants increased dramatically between 1988 and 1990, but have declined slightly since then.
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PMID:Thoracic organ transplants in the United States from October 1987 through December 1992: a report from the UNOS Scientific Registry for Organ Transplants. 791 70

Human leukocyte elastase (HLE) is a serine protease produced by neutrophils that has been implicated in diseases such as emphysema and cystic fibrosis. An HLE inhibitor may have therapeutic value in these diseases. An active site model of HLE bound to a tripeptidic trifluoromethyl ketone (TFMK) inhibitor, 2, was created from X-ray structures of HLE and porcine pancreatic elastase. Analysis of the model indicated a preferred binding conformation for the tripeptide and potentially important interactions between it and the enzyme. This information was used to aid in the design of a series of novel, pyridone-containing, non-peptidic HLE inhibitors such as 2-[3-[[(benzyloxy)carbonyl]amino]-2-oxo- 1,2-dihydro-1-pyridyl]-N-(3,3,3-trifluoro-1-isopropyl-2-oxopropyl)ace tam ide (5b) (Ki = 280 +/- 78 nM). Inspection of the active site model suggested that a benzyl substituent at the 5-position of the pyridone ring might improve potency by forming a lipophilic interaction with the enzyme S2 pocket. Synthesis and biological evaluation of a series of 5-benzylpyridone TFMKs provided evidence for this proposition. Further analysis of the model indicated that substitution on the 3-amino group of the pyridone ring with a hydrogen bond acceptor could potentially lead to interactions with the NH atoms of glycine-218 and/or -219. The oxalate derivative 2-[5-benzyl- 3-(carboxycarbonyl)-2-oxo-1,2-dihydro-1-pyridyl]-N-(3,3,3-trifl uor o-1- isopropyl-2-oxopropyl)acetamide (5v) was synthesized and found to have a Ki of 48 +/- 9 nM. Unfortunately, none of the compounds tested was active in an in vivo model of HLE-induced lung injury when dosed orally.
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PMID:Non-peptidic inhibitors of human leukocyte elastase. 1. The design and synthesis of pyridone-containing inhibitors. 793 32

Lung transplantation nowadays has become a therapeutic modality in the treatment of patients with a variety of end-stage lung diseases. Between July 1991 and December 1992, twelve patients received an isolated lung transplant (eight single lungs and four double lungs) at the University Hospitals of Leuven. The indication for transplantation was emphysema in five patients, pulmonary fibrosis in three, cystic fibrosis in three and primary pulmonary hypertension in one. There were four early, in-hospital deaths (30%): two from sepsis and multi-organ failure, one from anoxia following a bronchial dehiscence and another patient exsanguinated following stent insertion for a partial bronchial dehiscence. Three more patients have died during follow-up: two from chronic respiratory failure secondary to the development of obliterative bronchiolitis (one at 8 months and one at 17 months), and one from a late bronchovascular fistula 4 months following transplantation. The overall actuarial one and two year-survival was 50.0% and 41.6% respectively. All patients discharged from hospital were oxygen free with an improved lung function and exercise capacity. We conclude that lung transplantation is a viable therapeutic option for selected patients with end-stage, irreversible lung disease. In our experience, the bronchial anastomosis remains an important keystone in the early success. Lung transplantation provides a good quality of life in patients free from infection and rejection. Nevertheless, chronic rejection resulting in obliterative bronchiolitis is a major problem in long-term survivors.
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PMID:Isolated lung transplantation; initial experience at the University Hospitals Leuven. Leuven Lung Transplant Group. 797 65

We have summarized the results of international data from many institutes. In 1983 in Toronto, Canada, Cooper performed that first successful clinical case lung-transplantation. Subsequently, there have been more than 1,500 cases of lung transplantation. One reason for Cooper's success was the use of cyclosporin, the other was the performing of omentopexy. Among the total lung transplant cases, single lung transplant comprised 66%, bilateral sequential lung transplant comprised 26%, and en-blocdouble lung-transplant, (8%). Of the 1,540 recipients, the most common underlying of sease was emphysema (360 cases), followed by fibrosis (289 cases), cystic fibrosis (206 cases), alpha-1 antitripsin deficiency (210 cases) and rare diseases including pulmonary hypertension, lymphagiomyomatosis and sarcoidosis. The survival rate of all patients was 68% at 1 year, and 60% at two years.
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PMID:[Present world status and problems resolved in lung transplantation: from the surgical view]. 800 77

Human leucocyte elastase is a serine proteinase involved in phagocytosis, defence against invading micro-organisms, degradation of elastin, collagen, proteoglycans, fibrinogen and fibrin, being also responsible for the digestion of damaged tissues and of the bacterial degradation products. Lack of the enzyme regulation is at the basis of pathological states, such as pulmonary emphysema, cystic fibrosis, rheumatoid arthritis, atherosclerosis and glomerulonephritis. A detailed characterisation of the enzyme:inhibitor recognition process, based on extensive thermodynamic, kinetic and structural information, as well as on the comparative analysis with the homologous proteinase from porcine pancreas, is reported in the present review.
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PMID:Molecular bases for human leucocyte elastase inhibition. 804 99

16 patients (nine men, seven women; mean age 45 [23-62] years) with end-stage pulmonary disease underwent lung transplantation, 14 unilateral, three bilateral (one bilateral retransplantation). The diagnoses were: emphysema (n = 5), idiopathic pulmonary fibrosis (n = 5), emphysema in alpha 1-antitrypsin deficiency (n = 1), mucoviscidosis (n = 1), drug-induced fibrosis (n = 1), chronic lung rejection after heart-lung transplantation (n = 1), secondary pulmonary hypertension with persistent ductus arteriosus (n = 1), sarcoidosis (n = 1) and chronic transplant failure after unilateral transplantation (n = 1). Eleven patients survived long-term (mean follow-up period 247 [8-585] days). Ten of these patients have been independent of additional oxygen after an average of 8 months postoperatively, eight are physically active according to their age. Three patients died of reperfusion damage intraoperatively or in the early postoperative period. The two other patients died from septicaemia 5 1/2 and 7 months postoperatively. It is concluded that lung transplantation in end-stage pulmonary disease provides the only therapeutic means with any expectation of physical rehabilitation.
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PMID:[Isolated lung transplantation. Analysis of 17 consecutive operations. Munich Lung Transplant Group]. 815 68

We describe 12 patients with simultaneous bilateral spontaneous pneumothorax (SBSP). They represent 4 percent of patients with spontaneous pneumothorax seen at our hospital from 1971 to 1990. Five of the 12 had no underlying lung disease. In the seven remaining patients, SBSP was secondary to histiocytosis X, lymphangioleiomyomatosis, osteogenic sarcoma with pleural and pulmonary metastases, Hodgkin's disease, mesothelioma, cystic fibrosis, or miliary tuberculosis. Nineteen of the 56 patients with SBSP (34 percent) described in the literature (this series included) had pulmonary disease related to disorders of cells of mesenchymal origin. Emphysema and bullous lung disease were not associated with SBSP. Long-term prognosis was a function of pulmonary status. Four of the patients described herein died during the period reviewed. All suffered from severe underlying disease. In no case was SBSP the main cause of death. With timely treatment, the short-term prognosis is benign even for patients with underlying lung disease. Surgical pleurectomy should be attempted early, especially in SBSP secondary to underlying lung disease.
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PMID:Simultaneous bilateral spontaneous pneumothorax. 816 40

Lung- and heart-lung transplantation has become a serious therapeutic option for terminally ill patients with chronic pulmonary failure. Due to the still rather high risk of acute rejection, severe pulmonary or systemic infection, and the relatively demanding postoperative care, this treatment can only be considered for patients where inspite exhausted conservative options for therapy quality of life and prognosis are not acceptable. Not only due to lack of donors single-lung transplantation has developed to be the favorite treatment for patients with interstitial lung disease (idiopathic, sarcoidosis, asbestosis etc.) and even for pulmonary hypertension unless irreversible damage to the myocardium is present. Double-lung transplantation is the treatment of choice for patients with emphysema and cystic fibrosis. Heart-lung transplantation is mainly limited to patients with a high degree of right ventricular or valve dysfunction as in Eisenmenger-Syndrome. Midterm clinical results have evolved to be very satisfactory while on the longterm basis chronic transplant dysfunction not responding to any kind of therapy causes a lot of concern. One- and two-year survival rates are 85 and 82% resp. in our program and thus are in the same range as those after heart transplantation.
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PMID:[Lung and heart-lung transplantation: indications, complications and prognosis]. 818 61

Four women with a chronic respiratory illness characterized by chronic cough, dyspnea, mild to severe physiologic abnormalities, relatively normal chest radiographs, and lack of response to bronchodilators or prednisone were identified and prospectively evaluated. Constrictive bronchiolitis, defined as concentric narrowing of the bronchiolar lumen, mural scarring, smooth muscle hyperplasia, and mucus stasis, was the major histologic finding on open lung biopsy in all cases. Each presented with an illness clinically distinct from asthma, connective tissue disorders, occupational or environmental lung disease, bronchiectasis, diffuse panbronchiolitis, cystic fibrosis, and emphysema. None of the patients smoked cigarettes. None had clinical evidence of a recent viral lower respiratory tract infection. The physical examinations were normal except for rales heard on chest examination in two patients. Chest radiographs showed increased bronchovascular markings in three patients. Lung function was normal in one patient, two of the patients had a reduced diffusing capacity associated with moderate hypoxemia and an obstructive ventilatory defect, and one patient exhibited a mixture of restrictive and obstructive defects. None have experienced significant progression of their disease over 1 to 5 yr of follow-up. However, complete return to normal function did not occur. We hypothesize that patients with the constellation of findings described represent a distinct and definable clinicopathologic entity and further clarifies the spectrum of "small airways disease." Establishing the diagnosis appears important for prognostic and possibly therapeutic reasons.
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PMID:Cryptogenic constrictive bronchiolitis. A clinicopathologic study. 821 31

BACKGROUND--Bronchial epithelial function after heart-lung transplantation (HLT) for cystic fibrosis (CF) may be affected by the original disease as well as other factors such as prolonged organ ischaemic time, the interruption of bronchial arterial and lymphatic supply, infection, rejection, and cyclosporin. In vitro measurement of the bioelectric properties of the bronchial mucosal lining may be an effective means of characterising the mucosal function of the lung allografts in response to pharmacological agents. METHODS--Bronchial mucosal tissues from explanted native lungs of CF and non-CF patients at transplantation were used to assess the possible application of a mini-Ussing chamber. With this technique, the bioelectric responses of bronchial mucosal biopsies from six patients with CF, one patient with congenital heart disease, four with primary pulmonary hypertension, and one with emphysema, all after HLT, were studied. The bioelectric and pharmacological responses of biopsies of bronchial mucosa from patients after HLT were compared with biopsies from non-CF non-HLT subjects. RESULTS--The altered bioelectric properties of CF tissues could be detected by the mini-Ussing chamber technique. The basal bioelectric values and the responses to amiloride and isoprenaline in CF patients were not different from those in non-CF patients two years after HLT. No significant difference in the basal bioelectric properties and responses to amiloride and isoprenaline was found between HLT recipients and non-CF non-HLT subjects. CONCLUSIONS--The mini-Ussing chamber is an effective means of characterising the typical CF bioelectric defect which was not found in the transplanted lungs of CF patients up to two years after HLT. Furthermore, values were unaltered in comparison with non-transplanted lungs, suggesting that bronchial epithelial function is maintained after HLT.
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PMID:In vitro bioelectric properties of bronchial epithelium from transplanted lungs in recipients with cystic fibrosis. 825 29


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