Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Single lung transplantation (SLT) has emerged as routine therapy for selected patients with end-stage lung disease. This study examines the incidence of rejection, infection, and survival during the first posttransplant year. Twenty-one patients (12 male, 9 female; mean age 46 +/- 13 years) underwent 23 SLT procedures (12 left, 11 right lung). Indications were pulmonary fibrosis in six, emphysema in seven, primary pulmonary hypertension in three, Eisenmenger's syndrome in one, pulmonary veno-occlusive disease in one, a-1 antitrypsin deficiency in two, CREST syndrome in one, and retransplantation (graft failure and bronchiolitis obliterans) in two. All were maintained on triple immunotherapy. Survival at 1 year was 100%. The five patients with preoperative pulmonary hypertension had normal hemodynamics at follow up. Freedom from event at 1 year was rejection 23 per cent, all infections 6 per cent, viral 40 per cent, bacterial 55 per cent, fungal 74 per cent. At 1 year, cumulative incidence (events/patient-year) was rejection 1.61, all infections 2.18, viral 0.78, bacterial 1.12, fungal 0.28. Two of 21 patients have developed bronchiolitis obliterans at 1 and 2 years posttransplant. SLT provided safe, effective treatment for a wide variety of end-stage lung diseases. Rejection and infection, although common, may be safely treated with resolution.
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PMID:Single lung transplantation: a temporal look at rejection, infection, and survival. 830 52

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

The normal functional state of the vasculature and the events leading to the development of significant arterial disease involve the interaction of important vasoactive substances, which play important modulating or initiating roles in the development of hypertension and arteriosclerosis. Three endothelins have now been identified, of which ET-1 is the best characterized. ET-1 is produced by epithelial, mesangial, neuronal and glial, and liver cells, and is the most potent vasoconstrictor yet found. Each endothelin is derived from a different gene on separate chromosomes, and each binds to at least 2 types of receptor. The plasma half-life of ET-1 is about 7 min, and this provides a rapid mechanism for adjusting vascular resistance or blood pressure. The actions of endothelin are mediated through several pathways of postreceptor signaling, including activation of the mitogen-activated protein kinase cascade, which give rise to its growth-stimulating properties. Secretion of ET-1 from cultured endothelial cells is stimulated by a wide range of substances, and is inhibited by some prostaglandins. Endothelin in turn stimulates secretion of nitric oxide, arginine vasopressin and atrial natriuretic peptide, and participates in the hormonal control of salt and water balance. Hypoxia and ischemia augment ET-1 secretion, as does insulin, and this could play a role in the accelerated vascular disease of diabetes. ET-1 also causes bronchoconstriction and has been implicated in the development of acute asthma, primary pulmonary hypertension and pulmonary fibrosis. Its role in hypertension is still debatable, though most of the manifestations of congestive heart failure can theoretically be explained by the actions of ET-1. Endothelin also has extensive renovascular and parenchymal effects in the kidney. It is hoped that a fuller understanding of the role of endothelins in normal or pathologic vasculature will lead to effective therapy based on antagonism or augmentation of specific functions.
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PMID:Endothelins as cardiovascular peptides. 873 84

The expression of activin A, one of the transforming growth factor-beta supergene family, was studied in various pulmonary conditions associated with interstitial pulmonary fibrosis (3 cases with diffuse alveolar damage, 6 cases with idiopathic pulmonary fibrosis, and 1 case with pulmonary fibrosis associated with rheumatoid arthritis) using immunohistochemical techniques on paraffin-embedded sections. Controls consisted of 10 cases with normal pulmonary parenchyma, and 2 cases with primary pulmonary hypertension and 1 case with secondary pulmonary hypertension were also studied. The lung specimens from normal parenchyma weakly expressed immunoreactive activin A on the bronchiolar epithelium. In marked contrast, all of the specimens from cases with diffuse alveolar damage and interstitial pulmonary fibrosis demonstrated strong expression of activin A on metaplastic epithelium, hyperplastic smooth muscle cells, desquamated cells, and alveolar macrophages. Pulmonary arteries from patients with primary or secondary pulmonary hypertension showed abundant immunoreactive activin A on smooth muscle cells. These findings suggest a potential role for this growth factor, activin A, in the pathogenesis of pulmonary tissue remodeling associated with interstitial pulmonary fibrosis.
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PMID:Expression of immunoreactive activin A protein in remodeling lesions associated with interstitial pulmonary fibrosis. 877 26

Indications for unilateral, bilateral, heart-lung, and lobar transplant procedures for emphysema, cystic fibrosis, primary pulmonary hypertension, and pulmonary fibrosis are presented, and a brief historical perspective of the procedures is supplied.
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PMID:Indications. Unilateral, bilateral, heart-lung, and lobar transplant procedures. 918 16

On the basis of development of the immunosuppressive drugs such as cyclosporine since 1981, many successful cases have been reported on clinical lung and heart-lung transplantations. A principal disease for a single lung transplantation is pulmonary fibrosis. Obstructive lung disease and bilateral pulmonary sepsis such as cystic fibrosis and bronchiectasis are now considered to be done double lung transplantation. On the other hand, heart-lung transplantations have been performed not only on primary pulmonary hypertension and Eisenmenger's syndrome but also on restrictive and/or obstructive lung disease. Today's subjects on lung and heart-lung transplantations are as follows 1) The establishment of preservation method of transplant organs. 2) Development of an appropriate technique of monitoring for the rejected lungs. 3) Assessment and improvement of bronchial anastomotic healing. 4) Investigation of the causal factors on reimplantation response and obliterative bronchitis. Long-term survivals have been reported in both lung and heart-lung transplantation. Therefore, many attempts have been increasingly made in order to obtain the heart beating cadaver donors in Japan. But experimental study on the unsolved problems of transplantation should be continuously carried out for successful clinical lung and heart-lung transplantation.
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PMID:[Present status of lung transplantation and heart-lung transplantation]. 930 6

Overproduction and overexpression of endothelin-1 (ET-1) have been reported to contribute to the pathophysiology of pulmonary diseases, including pulmonary fibrosis, obliterative bronchiolitis, and primary pulmonary hypertension. To determine whether ET-1 contributes to the pathogenesis of pulmonary disease, we locally overexpressed ET-1 using an in vivo UV-inactivated hemagglutinating virus of Japan (HVJ) liposome-mediated gene transfer system. Plasmid DNA of ET-1 (pME18fc preproET-1) and high mobility group 1 (HMG1) protein were co-encapsulated in liposomes. Then the plasmid DNA and liposome complexes were introduced into the lung via the trachea in Wistar rats, using HVJ-mediated membrane fusion. Control animals received instillation of HVJ liposome with an empty cassette. Two weeks after in vivo transfection of the preproET-1 gene, hyperplastic connective tissue plaques were seen in the alveolar duct and small conducting airways, indicating histologically distinctive obliterative bronchiolitis. No histopathologic changes were seen in the control animals. These results suggested that local overexpression of ET-1 may play an important role in the pathogenesis of obliterative bronchiolitis.
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PMID:Pulmonary disease models induced by in vivo hemagglutinating virus of Japan liposome-mediated endothelin-1 gene transfer. 959 74

The lungs are a delicate interface between the atmosphere and our bodies across which oxygen diffuses from the air we breathe to the blood which carries oxygen to the cells and mitochondria. In healthy lungs at sea level where there is a surfeit of oxygen, this process occurs easily, whereas, in lungs with disease it becomes a task which may not be fully successful and hypoxemia may ensue or worsen. At high altitude where the barometric pressure (Pb) and thus the supply of oxygen is lower, the job of getting oxygen to the blood, even in the healthy lung is more difficult, and in the diseased lung it may be impossible. This presentation will review the lungs' responses to high altitude, with emphasis on the abnormal. Both acute and chronic responses of patients with pre-existing lung disease will be reviewed. Pulmonary diseases encountered at high altitude in previously healthy people, such as high altitude pulmonary edema and chronic mountain sickness will be touched on only as they pertain to other patients. Pre-existing lung disease (with and without hypoxemia at sea level) such as obstructive lung diseases (asthma, COPD, emphysema), and restrictive lung diseases (sarcoid, asbestosis, interstitial pulmonary fibrosis) will be discussed in terms of gas exchange, lung mechanics, and treatment at high altitude. Disorders of ventilatory control; e.g., obesity-hypoventilation syndrome and sleep apnea, may present formidable problems, and guidelines for their treatment will be discussed. Infectious lung diseases; e.g., pneumonia, cystic fibrosis, and pulmonary vascular disorders such as chronic mountain sickness, primary pulmonary hypertension, and congenital absence of the pulmonary artery are important disorders that require special attention because of the accentuated hypoxic pulmonary vascular response encountered at high altitude. The purpose therefore, is to provide the medical practitioner with the insight into prevention, recognition, and treatment of pulmonary problems encountered specifically at high altitude, as well as guidance on how best to advise patients with lung disease who want to fly in airplanes and/or ascend to high altitude for work or pleasure.
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PMID:Lung disease at high altitude. 1063 92

In scleroderma patients, isolated pulmonary hypertension (PHT) has been associated with selected HLA haplotypes, severe impairment of the diffusing capacity for carbon monoxide and the diagnosis of CREST. Most patients with CREST have a late-age onset of the disease, corresponding to the perimenopausal or postmenopausal period. We conducted a retrospective cohort study to determine the role of post-menopause and of the other known clinical and biological markers in the development of isolated pulmonary hypertension in Italian patients with systemic sclerosis. 189 female patients with scleroderma who had no ecographic signs of pulmonary hypertension (PHT) and radiographic signs of lung fibrosis at the first visit and did not develop significant pulmonary fibrosis during the observation time were included. Sixty-three out of 189 patients (33.3%) presented isolated pulmonary hypertension. A severe impairment of diffusing capacity for carbon monoxide at admission was found to be an early predictive element for its development. An increased risk was associated with postmenopausal condition (RR = 5.2, p = 0.000), CREST syndrome (RR = 2.8, p = 0.001) and haplotype HLA-B35 (RR = 2.8; p = 0.002). A significant positive interaction between postmenopausal condition and either HLA-B35 (RR = 15.2; p = 0.000) or the diagnosis of CREST (RR = 14.1; p = 0.000) was found. Postmenopausal condition alone or in combination with HLA-B35 and CREST syndrome is the main risk-factor for developing primary pulmonary hypertension in scleroderma patients. This suggests that hormonal replacement therapy could play a role in preventing isolated PHT in patients with systemic sclerosis.
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PMID:Post-menopause is the main risk factor for developing isolated pulmonary hypertension in systemic sclerosis. 1211 78

Pulmonary arterial hypertension occurs in up to 15% of patients who have systemic sclerosis (SSc) and has a high mortality. It can develop as an isolated complication or secondary to pulmonary fibrosis. There have been significant advances in assessment and therapy for this complication. Patients should be screened regularly by Doppler-echocardiography and pulmonary function tests. Right heart catheterization provides important diagnostic and prognostic information. Drawing from experience with treating primary pulmonary hypertension, treatment in the context of SSc is now possible. Patients should receive oral anticoagulation and oxygen supplementation. Calcium channel blockers are rarely effective, but parenteral prostacyclin analogs improve functional capacity and pulmonary hemodynamics. The oral endothelin-receptor blocker, bosentan, was shown to be an effective therapy for established symptomatic pulmonary hypertension in SSc. The next major challenge is to improve diagnosis and treatment of early stage or presymptomatic pulmonary hypertension with the goal of preventing this important cause of premature SSc-related mortality.
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PMID:Pulmonary hypertension in systemic sclerosis. 1284 Dec 98


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