Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied maximal aerobic work capacity in 24 cirrhotic patients whose clinical condition was well compensated. Nineteen of our patients had no heart or lung disease, and five had mild mechanical ventilatory impairment. The patients performed incremental exercise on a treadmill until subjective exhaustion. The maximal exercise levels reached by all were relatively low and led to a lower observed maximal oxygen uptake (VO2 max), than predicted uptake (19.6 +/- 0.5 vs. 37.9 +/- 0.6 ml/kg; p less than 0.001). Observed VO2 max values correlated strongly with the Pugh score, which reflects the degree of liver failure (r = -0.571; p less than 0.01). Since there were no clear cardiac or pulmonary causes to explain the decrease in work capacity, these observations suggest that liver cirrhosis might induce or be accompanied by muscular impairment. VO2 max, which seems to decline with the functional severity of the disease, may be a useful index for evaluating the capacity of patients for physical rehabilitation.
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PMID:Submaximal oxygen consumption in liver cirrhosis. Evidence of severe functional aerobic impairment. 233 86

Alpha 1-protease inhibitor can exist as over seventy different biochemical variants (the Pi system) which are inherited as autosomal codominant alleles. The majority of these variants are of no clinical significance. Epidemiologically, the most abundant are Pi types M, S and Z. Homozygotes of type Z have only 10 to 20% of the normal serum concentration of the inhibitor and have an increased risk of developing pulmonary emphysema. Cigarette smoking is the most important risk factor. A minority of Pi Z homozygotes (10 to 20%) develop a form of neonatal hepatitis and a proportion of these suffer from cirrhosis in adult life. Heterozygotes of Pi type SZ have about one third of the normal serum alpha 1-protease inhibitor concentration but this phenotype does not in itself appear to be a significant emphysema risk factor. Heterozygotes of Pi type MZ are thought to have a moderately increased risk of developing emphysema but only if they smoke; there is also evidence for an increased risk of cirrhosis among subjects of type MZ. No excessive risk appears to be attached to the MS phenotype. Cumulative survival curves have suggested that type Z homozygotes have a poor prognosis but such estimates are based on clinic or hospital patients who already have respiratory symptoms. Calculations based on population frequencies however, suggest that about 90% of the total number of type Z subjects are not accounted for in such surveys. Their whereabouts remains unclear at present; some will undoubtedly have died of liver or lung disease but it is possible that the majority escape and live undetected among the general population.
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PMID:Epidemiology of alpha 1-protease inhibitor deficiency. 234 48

Patients with cirrhosis may show ventilation-perfusion (VA/Q) inequality in the absence of any intrinsic heart or lung disease. However, the high cardiac output of cirrhosis generally prevents or minimizes the appearance of a severe degree of arterial hypoxemia. Propranolol has been used to reduce cardiac output and portal pressure in these patients. We wondered whether it might alter arterial oxygenation and reduce O2 transport to tissues. We studied eight patients (three women) 54 +/- 3 (SEM) yr of age before and after intravenous propranolol (0.1 mg/kg followed by 2 mg/h). Cardiac output (QT) fell from 7.8 +/- 0.7 to 6.0 +/- 0.7 L/min (p less than 0.05), and portal pressure was reduced (22 +/- 2 to 19 +/- 2 mm Hg, p less than 0.01). Arterial PO2 did not change (88 +/- 4 to 89 +/- 5 mm Hg) because the fall in mixed venous PO2 (43 +/- 1 to 40 +/- 1 mm Hg, p less than 0.01) that followed the lower QT was counterbalanced by a lower intrapulmonary shunt (multiple inert gas technique) (4 +/- 2 to 2 +/- 1%, p less than 0.05) and a shift of the VA/Q distributions toward a higher VA/Q ratio. Paralleling the fall in QT, oxygen transport to tissues (QO2) was reduced (19 +/- 2 to 14 +/- 1 ml/min/kg, p less than 0.01). However, O2 uptake (VO2) remained constant (3.4 +/- 0.2 to 3.6 +/- 0.2 ml/min/kg) because O2 extraction by the tissues increased appropriately (22 +/- 2 to 28 +/- 1%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of propranolol on arterial oxygenation and oxygen transport to tissues in patients with cirrhosis. 238 94

Alpha-1-antitrypsin (AAT) is the predominant protease inhibitor in human sera. The major physiological role of this inhibitor is to protect elastin fibers in the alveolar structure of the lung from excessive degradation by neutrophil elastase. AAT is synthesized predominantly by hepatocytes, although the AAT gene is expressed to a small degree in the epithelial cells of various tissues. Recent studies have shown that the enhanced liver-specific expression of the AAT gene is controlled by the binding of hepatic nuclear proteins to specific DNA sequences upstream from the structural gene. A variety of mutations within the AAT gene have been identified that result in a partial deficiency or total absence of the inhibitor in sera. Inheritance of a particular combination of these alleles can result in a predisposition towards the development of destructive lung disease. Interestingly, the most common AAT deficiency variant, designated PiZ, causes the mutant protein to accumulate as an insoluble aggregate within the lumen of the hepatic rough endoplasmic reticulum, which is an etiological agent for the development of liver disease. Overall, investigation into the genetic control of AAT has led to an increased understanding of the factors that control hepatic gene expression, as well as mechanisms involved in the pathophysiology of emphysema and liver cirrhosis.
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PMID:Genetic control of human alpha-1-antitrypsin. 269 88

Sulfasalazine has been associated with bronchopulmonary complications of inflammatory bowel disease (IBD) in adults. We describe a 12-year-old boy who developed desquamative interstitial pneumonitis and hepatic cirrhosis several years following the onset of ulcerative colitis. The restrictive lung disease progressed despite cessation of sulfasalazine and initiation of corticosteroid therapy. We discuss a variety of bronchopulmonary complications of IBD and their association with sulfasalazine.
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PMID:Desquamative interstitial pneumonitis complicating inflammatory bowel disease of childhood. 286 42

Alpha 1 antitrypsin deficiency is one of the most common metabolic disorders, frequently associated with obstructive lung disease and occasionally with childhood liver cirrhosis. Prenatal diagnosis of this deficiency has been accomplished using a DNA polymorphism detected by the restriction enzyme AvaII. A unique haplotype of DNA fragments is observed in deficient (PI type ZZ) subjects. Diagnosis is therefore possible directly from fetal tissue, unlike other prenatal diagnoses using linkage of a DNA polymorphism within a specific family. This approach must be modified for rare deficiency alleles of alpha 1 antitrypsin (PI* Mmalton, PI* Mdurate, and PI*QO or null). Knowledge of risk of severe disease in the fetus is important for the application of prenatal diagnosis. From the limited data available to date, the risk for a given PI ZZ fetus to develop severe liver disease has been estimated at 13% where a previous PI ZZ sib had no liver disease or liver disease which resolved during early childhood, and a risk of 40% where a previous PI ZZ sib had developed severe liver disease.
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PMID:Prenatal diagnosis of alpha 1 antitrypsin deficiency and estimates of fetal risk for disease. 287 35

13 patients with severe lung disease and cor pulmonale from cystic fibrosis were accepted for heart-lung transplantation (HLT). 6 have had the operation, of whom 5 are well, with normal lung function, 3-29 months after operation. 1 patient died from adult respiratory distress syndrome after reoperation to control persistent chest-wall bleeding: at necropsy, this patient proved to have cirrhosis. Respiratory tract infections and acute lung rejection after HLT for cystic fibrosis were no more common than in other HLT patients. Of the 7 patients for whom suitable donor organs were not found, 3 died within 3 months of assessment. Initial severity of disease had been similar to that in the transplant group. The cost of assessment, operation, and 1 year's treatment after HLT is similar to that of medical treatment for such patients.
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PMID:Heart-lung transplantation for cystic fibrosis. 289 64

The cirrhosis and hepatocellular carcinoma associated with alpha 1-antitrypsin deficiency has been exclusively reported with the PI Z allele. We present a 63-yr-old white man with emphysema, cirrhosis, and hepatocellular carcinoma. The latter occurred on a background of diffusely distributed hepatocellular dysplasia. Serum protein electrophoresis suggested a deficiency of alpha 1-antitrypsin quantitated at 13% of normal. PI phenotyping showed that he had only the rare PI Mmalton allele, previously associated only with severe lung disease. Family studies demonstrated the distribution of this rare allele. The liver at autopsy displayed well-differentiated hepatocellular carcinoma in addition to alpha 1-antitrypsin deposits in normal, dysplastic, and malignant cells.
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PMID:Diffuse hepatocellular dysplasia and carcinoma associated with the Mmalton variant of alpha 1-antitrypsin. 303 14

The present review concentrates on environmental factors which influence the outcome of peptic ulcer disease by acting from the outside. Endogenous risk factors, such as acid output, pepsin secretion and serum pepsinogen, gastritis and mucosal defense, blood group, and secretor status, are only dealt with when they help to explain the mechanism by which exogenous risk factors affect the upper gastrointestinal mucosa. After outlining the wax and wane of peptic ulcer, it is concluded that these changes resulted from similar temporal patterns of occupational workload in the general population. Cross sectional studies also support the contention of occupational workload being a risk factor in peptic ulcer, explaining several characteristic features of peptic ulcer, such as its sex, race, and social class distribution, increased incidence in immigrant workers, seasonal variation, healing by bed rest, and urban versus rural distribution. Susceptible subjects may react to a rise in occupational workload and acute exposure to stressful life events by increased gastric secretion which, in turn, leads to ulceration and symptoms. Cigarette smoking, intake of aspirin and related drugs, dietary salt, and alcohol abuse represent additional environmental risk factors, which form the etiologic link of the association of peptic ulcer with chronic lung disease, rheumatoid arthritis, hypertensive disease, and liver cirrhosis, respectively.
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PMID:Factors which influence the incidence and course of peptic ulcer. 307 62

Epidemiologic evidence shows a strong relationship between gastric cancer and cerebrovascular disease. It was speculated that salt intake might be the linking factor causing hypertension and vascular damage as well as damage to the gastric mucosa. This study tested whether hypertensive diseases, such as ischemic heart disease and cerebrovascular disease, occurred more frequently in patients with gastric cancer and gastric ulcer than expected by chance alone. In addition, it was studied whether gastric and duodenal ulcer coincided more frequently with other diseases that in the past have been associated with peptic ulcer, such as liver cirrhosis, chronic lung disease, and rheumatoid arthritis. The German statistics of rehabilitation were used to assess the frequency of coincidences. The statistics include a description of the primary, secondary, and tertiary diagnoses leading to rehabilitation. This study confirms the presence of a high coincidence of both ulcer types with liver cirrhosis. In patients with rheumatoid arthritis, both ulcer types also occurred more frequently than expected from their general distribution. Gastric but not duodenal ulcer coincided more frequently with ischemic heart disease than expected. Gastric cancer occurred more frequently in patients who had concomitant ischemic heart disease or cerebrovascular disease. Duodenal ulcer was not associated with an increased risk for any disease related to hypertension. The results of the study support the contention that gastric diseases and diseases related to hypertension share a common etiologic factor.
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PMID:Concordant occurrence of gastric and hypertensive diseases. 337 23


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