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)

Although the annual number of lung transplant operation performed in the United States and Europe is over 1000, five year survival rate is under 50%, mainly because of obstructive bronchiolitis that is considered chronic rejection. Lung transplantation may be difficult to justify on the ground of survival consideration alone for the certain disease, such as emphysema and pulmonary hypertension. But functional recovery after lung transplantation especially, bilateral is reported very good. Among the diseases of indication of lung transplant, Cystic Fibrosis and alpha antitrypsin deficiency are very rare disease in Japan and emphysema that is most frequently reported indication in the United States, is also rare disease in the age group of lung transplantation candidate. So, idiopathic interstitial pneumonitis, pulmonary vascular disease and other miscellaneous disease are most possible indications for lung transplantation in Japan. These disease have different prognosis, we discussed the timing of registration and operation of lung transplantation in each disease.
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PMID:[Indications for lung transplantation and its selection of the candidates in Japan]. 1049 11

1. The number of heart transplant operations performed in the US decreased by 52 procedures between 1996 (2,344) and 1997 (2,292). The number of lung transplants increased by 118 in 1997 (928). 2. The most frequently reported indication for heart transplantation in the US was coronary artery disease (44.9%). For other thoracic transplants, the most frequently reported indications included cystic fibrosis (36.8%) for double-lung, emphysema/COPD (53.8%) for single-lung and congenital disease (33.9%) for heart-lung transplants. The most frequently reported diagnoses for thoracic transplantation outside the US included cardiomyopathy (50.4%) for heart, cystic fibrosis (31.3%) for double-lung, idiopathic pulmonary fibrosis (32.4%) for single-lung and primary pulmonary hypertension (23.3%) for heart-lung transplants. 3. US heart transplant recipients were predominately male (77.4%), over age 50 (55.9%) and white (82.1%). In contrast, US lung transplant recipients were predominantly female (51.9%), between ages 35-64 (73.4%) and white (89.5%). No meaningful variance from the US recipient demographic profile was noted for the non-US recipients during the same time period. 4. Mean ischemic time showed minimal change for hearts (2 minutes), a sharp increase for heart-lungs (29.5 minutes) and a decrease for lungs (11 minutes) from 1997-1998. 5. The one-year survival rates for thoracic transplants performed in the US were 83.2% for heart, 75.7% for lung and 34.1% for heart-lung in 1997. Five-year survival rates for US thoracic transplants were 66% for heart and 46.4% for lung for transplants performed in 1993. 6. Long-term patient survival rates were: 29.5% at 14 years for heart, 19.4% at 9 years for lung and 26.2% at 11 years for heart-lung recipients. 7. The most important risk factor for mortality of US heart recipients at one month, one year and conditionally at 5 years after transplantation was receipt of a previous heart transplant. Significant short-term risk factors included recipient age and ischemic time. Substantial long-term risk factors included older donor age and donor race. 8. The factors having the most significant impact on lung mortality at all time points were related to either the patient's medical condition (e.g.x, in the ICU prior to transplant, requiring mechanical ventilation) or diagnosis. 9. Mechanical ventilation and previous transplant had the largest impact on heart-lung mortality. 10. For heart and lung recipients, the major cause of rehospitalization during the first year after transplantation was infection alone.
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PMID:Worldwide thoracic organ transplantation: a report from the UNOS/ISHLT International Registry for Thoracic Organ Transplantation. 1050 84

Proteinase-antiproteinase imbalances are recognized in several diseases including the two most common lethal hereditary disorders of white populations, alpha(1)-antitrypsin (alpha(1)-AT) deficiency and cystic fibrosis (CF). In alpha(1)-AT deficiency, the type Z variant of alpha(1)-AT forms polymers in the endoplasmic reticulum of hepatocytes resulting in liver disease in childhood. The block in alpha(1)-AT processing in hepatocytes significantly reduces levels of circulating alpha(1)-AT. This may lead in young adults to panacinar emphysema due to insufficient protection of the lower respiratory tract from neutrophil elastase, permitting progressive destruction of the alveoli. In CF, chronic bacterial lung infections due to impaired mucociliary clearance lead to a vigorous influx of neutrophils in the airways. Released levels of neutrophil serine proteinases, particularly elastase, exceed the antiproteinase capacity of endogenous serine proteinase inhibitors in the airways. Progressive proteolytic impairment of multiple defense pathways in addition to endobronchial obstruction and airway wall destruction are thought to be responsible for the reduced life expectancy in CF patients. Strategies to augment the antiproteinase defenses in the airways of patients with severe alpha(1)-AT deficiency or CF include the intravenous or aerosol administration of serine proteinase inhibitors. Studies in both patient groups using plasma-derived or transgenic alpha(1)-AT, recombinant secretory leukoprotease inhibitor or synthetic elastase inhibitors show promising results concerning drug safety and efficacy.
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PMID:Serine proteinase inhibitor therapy in alpha(1)-antitrypsin inhibitor deficiency and cystic fibrosis. 1053 68

The idea of generating transgenic livestock which secrete into their milk large quantities of proteins for therapeutic use, was pioneered in the late 1980s with the disclosure of the production of a number of transgenic sheep. One particular animal, a sheep called Tracy, produced milk where over 50% of the protein consisted of human alpha 1 anti-trypsin. Sheep-derived protein has now entered clinical trials for cystic fibrosis (UK, USA) and congenital emphysema (UK). There are many other examples where this technology is making inroads into more traditional ways of making biopharmaceuticals. However, although robust, this technology has several limitations, including an inability to allow targeted insertion/modification of the animal genome, long timelines to production flocks/herds, and the rather unpredictable expression levels seen when different transgenic founders are compared. We believe that there is now a technical solution to all of these problems. Dolly is a high profile example of a new technology comprising the generation of identical animals from cultured somatic cells. This work has many implications. In the commercial context, the real benefits of this advance will be seen when genetically engineered somatic cells are shown to be suitable nuclear donors, and particularly when the manipulations are targeted to pre-determined sites in the host cell genome. The first objective has now been achieved with the birth of Polly, a cloned sheep which contains the human gene encoding Factor IX, a protein involved in preventing haemophilia.
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PMID:Dolly, Polly and other 'ollys': likely impact of cloning technology on biomedical uses of livestock. 1059 58

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

Hyperpolarized gas- and molecular oxygen-enhanced MR imaging are two new techniques for high-resolution MR imaging of pulmonary airspaces. Both techniques produce excellent images in a safe, reproducible, and technically feasible manner. Because morphologic and functional information is obtained, and radiation is not used, these techniques may prove ideal for serially evaluating patients with a variety of lung diseases that affect pulmonary ventilation, such as cystic fibrosis, emphysema, asthma, or bronchiolitis obliterans syndrome in lung transplant recipients. At present, the greatest clinical experience is with hyperpolarized He-3-enhanced MR imaging. This technique is limited, however, by the limited availability of He-3, by its polarization requirements, and by the need to tune the MR system to the resonant frequency of the gas. There is less clinical experience with oxygen-enhanced MR imaging. Although this technique produces images with more inherent noise than hyperpolarized He-3 imaging, this problem can be overcome by signal averaging. Oxygen-enhanced imaging has the major advantages of lower cost and ready availability. For oxygen-enhanced imaging, the MR imaging system does not need to be readjusted; imaging is performed at the conventional hydrogen proton frequency.
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PMID:Novel techniques for MR imaging of pulmonary airspaces. 1073 Feb 43

Innovations in biotechnology and recombinant techniques have led to a large increase in the number of macromolecule drugs developed over the last several years. These molecules are enabling new therapies for many previously untreated or poorly treated diseases. Due to poor oral absorption, most biopharmaceuticals are delivered by injection. Medical science, health care providers and consumers have been searching for alternative methods of delivering macromolecule drugs. Animal and human clinical studies have demonstrated that pharmacological doses of bioactive peptides and proteins pass, by a natural biological process, from the lungs into the bloodstream or local tissue. New macromolecule drugs are also being developed for treatment of respiratory diseases such as cystic fibrosis, adult and infant respiratory distress syndromes, asthma and emphysema. This paper reviews formulations for delivering therapeutic aerosols to the lungs. Particular emphasis will be placed on preparing fine powders containing macromolecule drugs.
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PMID:Preparation of peptide and protein powders for inhalation. 1083 28

Cystic fibrosis (CF) is an autosomal recessive disorder that is rarely found in Asians. Only four cases of CF from four different families have been reported in Taiwan. We report two cases of CF involving two teenage siblings. Both presented with repeated airway infections, poor weight gain, clubbing of the fingers, hypoxemia, and obstructive ventilatory impairment. Multiple focal bronchiectases and emphysema were demonstrated on high-resolution computed tomography. Sweat chloride concentrations, as measured using the modified sweat chloride test in a closed space with a heater, were 327 mmol/L and 276 mmol/L, respectively. To confirm the CF diagnosis, DNA mutation analysis was performed. All 27 exons of the CF transmembrane conductance regulator (TR) gene and their flanking intron sequences were screened for nucleotide sequence alterations, and the mutations were then identified by direct DNA sequence analysis. Both siblings carried 1898 + 5G-->T; a mutation previously identified in Taiwan. In addition, the mutation analysis identified a new single-base-insertion mutation in exon 13 on the second CFTR allele of these patients. This mutation, named 2215insG, is expected to cause a significant disruption of CFTR function. The 1898 + 5G-->T/2215insG genotype is thus consistent with the CF diagnosis. A new missense mutation, S895N, in exon 15 of the CFTR gene, which cosegregated with 2215insG, was also identified in both of these patients.
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PMID:Novel cystic fibrosis mutation (2215insG) in two adolescent Taiwanese siblings. 1092 68

Neutrophil elastase has been linked to inflammatory lung diseases such as chronic obstructive pulmonary disease, adult respiratory distress syndrome, emphysema, and cystic fibrosis. In guinea pigs, aerosol challenge with human neutrophil elastase causes bronchoconstriction, but the mechanism by which this occurs is not completely understood. Our laboratory previously showed that human neutrophil elastase releases tissue kallikrein (TK) from cultured tracheal gland cells. TK has been identified as the major kininogenase of the airway and cleaves both high- and low-molecular weight kininogen to yield lysyl-bradykinin. Because inhaled bradykinin causes bronchoconstriction and airway hyperresponsiveness in asthmatic patients and allergic sheep, we hypothesized that elastase-induced bronchoconstriction could be mediated by bradykinin. To test this hypothesis, we measured lung resistance (RL) in sheep before and after inhalation of porcine pancreatic elastase (PPE) alone and after pretreatment with a bradykinin B(2) antagonist (NPC-567), the specific human elastase inhibitor ICI 200,355, the histamine H(1)-antagonist diphenhydramine hydrochloride, the cysteinyl leukotriene 1 receptor antagonist montelukast, or the cyclooxygenase inhibitor indomethacin. Inhaled PPE (125-1,000 microg) caused a dose-dependent increase in RL. Aerosol challenge with a single 500 microg dose of PPE increased RL by 132 +/- 8% over baseline. This response was blocked by pretreatment with NPC-567 and ICI-200,355 (n = 6; P < 0.001), whereas treatment with diphenhydramine hydrochloride, montelukast, or indomethacin failed to block the PPE-induced bronchoconstriction. Consistent with pharmacological data, TK activity in bronchial lavage fluid increased 134 +/- 57% over baseline (n = 5; P < 0.02). We conclude that, in sheep, PPE-induced bronchoconstriction is in part mediated by the generation of bradykinin. Our findings suggest that elastase-kinin interactions may contribute to changes in bronchial tone during inflammatory diseases of the airways.
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PMID:Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism. 1100 74

1. The number of heart transplant operations performed in the US has increased by 51 procedures between 1997 (2,294) and 1998 (2,345). The number of lung transplants decreased by 67 in 1998 (862). 2. The most frequently reported indication for heart transplantation in the US is coronary artery disease (44.6%). For other thoracic transplants, the most frequently reported indications include other/unknown (43.9%) for double lung, emphysema/COPD (53.5%) for single lung and other/unknown (53.2%) for heart-lung. The most frequently reported diagnoses for thoracic transplantation outside the US include cardiomyopathy (50.5%) for heart, cystic fibrosis (32.0%) for double lung, idiopathic pulmonary fibrosis (32.7%) for single lung and congenital heart disease (24.7%) for heart-lung. 3. US heart transplant recipients were predominately male (77%), between 50-64 years old (51.4%) and White (81.7%). In contrast, US lung transplant recipients are predominantly female (51.3%), between 50-64 years of age (44.7%) and White (89.7%). No meaningful variance from the US recipient demographic profile was noted for the non-US recipients during the same time period. 4. Pediatric recipients (< 18 years of age) received 10.9% of the reported heart transplants and 6.5% of reported lung transplants. 5. One-year survival for thoracic transplants performed in the US was 83.2% for heart, 70.6% for lung and 62.5%. Five-year survival for US thoracic transplants was 70% for heart and 49.1% for lung. 6. Long-term patient survival rates were: 22.3% at 18 years for heart, 20% at 9 years for lung and 25% at 12 years for heart-lung recipients. 7. The most important risk factor for mortality of US heart recipients at one month, one and 5 years after transplantation was receipt of a previous heart transplant. Significant short-term risk factors included donor age, recipient age and ischemic time. Substantial long-term risk factors include older donor age, donor race and recipient race. 8. The factors having the most significant impact on lung mortality at all time points were related to either the patient's medical condition (e.g., in the ICU prior to transplant, requiring mechanical ventilation) or diagnosis. 9. Mechanical ventilation and previous transplant had the largest impact on heart-lung mortality. 10. For heart and lung recipients, the major cause of hospitalization during the first posttransplant year was infection.
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PMID:Worldwide thoracic organ transplantation: a report from the UNOS/ISHLT International Registry for Thoracic Organ Transplantation. 1103 24


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