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)

The glycogen storage diseases are caused by inherited deficiencies of enzymes that regulate the synthesis or degradation of glycogen. In the past decade, considerable progress has been made in identifying the precise genetic abnormalities that cause the specific impairments of enzyme function. Likewise, improved understanding of the pathophysiologic derangements resulting from individual enzyme defects has led to the development of effective nutritional therapies for each of these disorders. Meticulous adherence to dietary therapy prevents hypoglycemia, ameliorates the biochemical abnormalities, decreases the size of the liver, and results in normal or nearly normal physical growth and development. Nevertheless, serious long-term complications, including nephropathy that can cause renal failure and hepatic adenomata that can become malignant, are a major concern in GSD-I. In GSD-III, the risk for hypoglycemia diminishes with age, and the liver decreases in size during puberty. Cirrhosis develops in some adult patients, and progressive myopathy and cardiomyopathy occur in patients with absent GDE activity in muscle. It remains unclear whether these complications of glycogen storage disease can be prevented by dietary therapy. Glycogen storage diseases caused by lack of phosphorylase activity are milder disorders with a good prognosis. The liver decreases in size, and biochemical abnormalities disappear by puberty.
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PMID:Glycogen storage diseases. Phenotypic, genetic, and biochemical characteristics, and therapy. 1060 21

Myocardial contractility in cirrhosis is impaired, particularly under stressful situations, in a phenomenon termed cirrhotic cardiomyopathy. Impairment of the cardiac beta-adrenergic receptor and its signaling function appears to be involved in the pathogenesis of this disorder. Additional mechanisms that may have a role include alterations in the physicochemical properties of the cardiomyocyte plasma membrane and abnormalities in circulating humoral factors, such as nitric oxide, carbon monoxide, and catecholamines. The widespread use of orthotopic liver transplantation (OLT) and its associated stresses on the cardiovascular system have highlighted this condition. Cardiac failure has emerged as an important cause of morbidity and mortality in the liver transplant recipient. Unfortunately, pre-OLT recognition of cirrhotic cardiomyopathy is suboptimal because of a lack of sensitive, noninvasive diagnostic tests. Similarly, the management of cirrhotic cardiomyopathy is largely empirical because of a paucity of existing literature. Although evidence suggests that cirrhotic cardiomyopathy may be reversible after OLT, the natural history of this condition warrants further investigation.
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PMID:Cirrhotic cardiomyopathy and liver transplantation. 1091 91

To outline the recent features of methamphetamine-related fatalities from the medico-legal point of view, a retrospective investigation of forensic autopsy cases involving methamphetamine during a 5-year period (1994-1998) in the southern half of Osaka city and surrounding areas (about 1.57 million population) was undertaken. Among 646 autopsy cases, methamphetamine was detected in 15 victims (nine males, six females; 16-71 years of age; most frequently in males in their thirties). Primary scenes of fatal events were concentrated in the middle of the city. About half of them were transferred from emergency medical centers (survival time, up to 30 h). The cause and manner of death were: methamphetamine poisoning (n=4), homicide (n=4), accidental falls and aspiration from drug abuse (n=4), fire death (n=1), myocardial infarction (n=1), and cerebral hemorrhage (n=1) under drug influence. Usually injection scars and fresh puncture sites were found. Blood methamphetamine concentrations were 2.29-17.05 micromol/dl in the fatal poisoning, 0. 44-3.80 micromol/dl in deaths from other extrinsic causes (trauma), and 1.35-2.17 micromol/dl in cardio- and cerebrovascular strokes. Common complications were cardiomyopathy, cerebral perivasculitis and liver cirrhosis/interstitial hepatitis. Fatal and nonfatal methamphetamine poisonings are separately dealt with by the administrative medical examiner's office and in emergency medical centers. Tightly cooperative approaches of clinical and medico-legal experts are required for the effective social and medical management of drug abuse.
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PMID:Methamphetamine-related fatalities in forensic autopsy during 5 years in the southern half of Osaka city and surrounding areas. 1097 60

Primary care physicians will be providing longitudinal health care for long-term survivors of childhood acute lymphoblastic leukemia (ALL) with increasing frequency. Late effects (sequelae) secondary to treatment with radiation or chemotherapeutic agents are frequent and may be serious. Depending on treatment exposures, this at-risk population may experience life-threatening late effects, such as cirrhosis secondary to hepatitis C or late-onset anthracycline-induced cardiomyopathy, or life-changing late effects, such as cognitive dysfunction. Many survivors of childhood ALL will develop problems such as obesity and osteopenia at a young age, which will significantly affect their risk for serious health outcomes as they grow older. The goal of our review is to assist primary care physicians in providing longitudinal health care for long-term survivors of childhood ALL. We also highlight areas needing further investigation, including the prevalence of different late effects, determination of risk factors associated with a late effect, a better understanding of the potential impact of late effects on the premature development of common adult health problems, and the value and timing of different tests for screening asymptomatic survivors.
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PMID:Providing primary care for long-term survivors of childhood acute lymphoblastic leukemia. 1113 63

Hereditary hemochromatosis (HHC) is an inherited disorder of iron metabolism affecting approximately 1 in 200-300 individuals of Northern European descent. Over time, the continued deposition of iron in parenchymal cells of many organs can eventually lead to diabetes mellitus, cardiomyopathy, and hepatic cirrhosis, the last of which is frequently followed by hepatocellular carcinoma. Although the complications of HHC can be devastating, its clinical management is simple and effective if the disease is identified early in its progression. The recent elucidation of the HFE gene has provided insight into the pathogenesis of HHC and provided a means for the early identification of individuals in whom HHC may develop. Two mutations have been implicated in HHC: C282Y and H63D. The former occurs in a homozygous state seen in 75-100% of patients with HHC. The high correlation of HFE to HHC has caused it to be considered as a candidate gene for population-based genetic testing for diagnosis and detection of predisposition to HHC. In addition, mechanisms of iron transport and metabolism are unfolding and are providing clues to the enigma of iron homeostasis and the pathophysiology of iron overload.
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PMID:What's new in hemochromatosis. 1122 84

Patients with cirrhosis and portal hypertension exhibit characteristic hemodynamic changes with hyperkinetic systemic circulation, abnormal distribution of blood volume and neurohumoral dysregulation. Their plasma and noncentral blood volumes are increased. Splanchnic vasodilation is of pathogenic significance to the low systemic vascular resistance and abnormal volume distribution of blood, which are important elements in the development of the concomitant cardiac dysfunction, recently termed 'cirrhotic cardiomyopathy'. Systolic and diastolic functions are impaired with direct relation to the degree of liver dysfunction. Significant pathophysiological mechanisms are reduced beta-adrenergic receptor signal transduction, defective cardiac excitation-contraction coupling and conductance abnormalities. Vasodilators such as nitric oxide and calcitonin gene-related peptide are among the candidates in vasodilation and increased arterial compliance. Reflex-induced, enhanced sympathetic nervous system activity, activation of the renin-angiotensin aldosterone system, and elevated circulation vasopressin and endothelin-1 are implicated in hemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the hemodynamic and neurohumoral abnormalities in cirrhosis are part of a general cardiovascular dysfunction, influencing the course of the disease with the reduction of organ function, with sodium and water retention as the outcome. These aspects are relevant to therapy.
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PMID:Splanchnic and systemic hemodynamic derangement in decompensated cirrhosis. 1124 Mar 79

Like most essential nutrients, Fe needs to be maintained in the body at a defined level for optimal health, with appropriate adaptation to varying Fe needs and supply. The primary mechanism for controlling Fe level is the regulation of Fe absorption. Several different proteins have been identified as contributors to the process. Despite a complex regulatory system, Fe disorders (both Fe deficiency and Fe overload) occur. Fe deficiency is a common problem worldwide, resulting from inadequate dietary Fe and blood loss. Complications include pre-term labour, developmental delay, and impaired work efficiency. No specific genetic syndromes causing isolated Fe deficiency have been described, but animal studies and clinical observations suggest that such a relationship may be a possibility. Conversely, the known causes of Fe overload are genetic. Fe overload is less common than Fe deficiency, but can result in serious medical complications, including cirrhosis, primary liver cancer, diabetes, cardiomyopathy and arthritis. The most common and best characterized syndrome of Fe overload is hereditary haemochromatosis (HHC), an autosomal recessive disorder. Mutations in the HFE protein cause HHC, but the clinical presentation is variable. Of particular interest is the factor that some FIFE genotypes appear to be associated with protection from Fe deficiency. Other genetic variants in the regulatory pathway may influence the likelihood of Fe deficiency and Fe overload. Studies of genetic variants in HFE and other regulatory proteins provide important tools for studying the biological processes in Fe regulation. This work is likely to lead to new insights into Fe disorders and potentially to new therapeutic approaches. It will not be complete, however, until coordinated study of both genetic and nutritional factors is undertaken.
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PMID:Iron deficiency and iron overload: effects of diet and genes. 1131 Apr 26

Hereditary hemochromatosis (HHC) is an autosomal recessive disorder of iron metabolism characterized by increased iron absorption and deposition in the liver, pancreas, heart, joints, and pituitary gland. Without treatment, death may occur from cirrhosis, primary liver cancer, diabetes, or cardiomyopathy. In 1996, HFE, the gene for HHC, was mapped on the short arm of chromosome 6 (6p21.3). Two of the 37 allelic variants of HFE described to date (C282Y and H63D) are significantly correlated with HHC. Homozygosity for the C282Y mutation was found in 52-100% of previous studies on clinically diagnosed probands. In this review, 5% of HHC probands were found to be compound heterozygotes (C282Y/H63D), and 1.5% were homozygous for the H63D mutation; 3.6% were C282Y heterozygotes, and 5.2% were H63D heterozygotes. In 7% of cases, C282Y and H63D mutations were not present. In the general population, the frequency of the C282Y/C282Y genotype is 0.4%. C282Y heterozygosity ranges from 9.2% in Europeans to nil in Asian, Indian subcontinent, African/Middle Eastern, and Australasian populations. The H63D carrier frequency is 22% in European populations. Accurate data on the penetrance of the different HFE genotypes are not available. Extrapolating from limited clinical observations in screening studies, an estimated 40--70% of persons with the C282Y homozygous genotype will develop clinical evidence of iron overload. A smaller proportion will die from complications of iron overload. To date, population screening for HHC is not recommended because of uncertainties about optimal screening strategies, optimal care for susceptible persons, laboratory standardization, and the potential for stigmatization or discrimination.
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PMID:HFE gene and hereditary hemochromatosis: a HuGE review. Human Genome Epidemiology. 1147 83

Patients with cirrhosis and portal hypertension exhibit characteristic haemodynamic changes with a hyperkinetic systemic circulation, abnormal distribution of the blood volume, and neurohumoral dysregulation. Moreover, the circulating levels of several vasoactive substances may be elevated. Splanchnic vasodilatation is of pathogenic significance for the low systemic vascular resistance and abnormal volume distribution, which are important elements in the development of the concomitant cardiac dysfunction, recently termed cirrhotic cardiomyopathy. The systolic and diastolic functions are impaired with direct relation to the degree of liver dysfunction. Significant pathophysiological mechanisms seem to include a reduced beta-adrenergic receptor signal transduction, defective cardiac excitation-contraction coupling, and conductance abnormalities. Various vasodilators. such as nitric oxide and calcitonin gene-related peptide, are among candidates in the vasodilatation and the increased arterial compliance recently described in advanced cirrhosis. Reflex-induced enhanced sympatho-adrenal activity, activation of the renin-angiotensin-aldosterone system, and elevated circulating vasopressin and endothelin-1 are implicated in the haemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the haemodynamic and neurohumoral abnormalities in cirrhosis are part of a general cardiovascular dysfunction influencing the course of the disease, with reduction of organ function and sodium-water retention as the outcome. These aspects are relevant to therapy.
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PMID:Vasoactive substances in the circulatory dysfunction of cirrhosis. 1168 31

Subtle cardiac abnormalities have been described in patients with cirrhosis. Natriuretic peptide hormones have been reported to be sensitive markers of early cardiac disease. We postulate that plasma levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide could be used as markers of cardiac dysfunction in cirrhosis. The aim of the study was to evaluate the levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide and their relationship with cardiac structure and function in patients with cirrhosis. The study population comprised 36 patients with cirrhosis of mixed aetiologies, but with no cardiac symptoms; 19 of the patients had ascites and 17 did not. The subjects underwent (i) trans-thoracic two-dimensional echocardiography, and (ii) radionuclide angiography for measurements of cardiac structural parameters, diastolic and systolic function. Levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide were also measured. The results were compared with those from eight age- and sex-matched healthy volunteers. Compared with the controls, the baseline mean ejection fraction was increased significantly in both patient groups (P=0.02), together with prolonged deceleration times (P=0.03), left atrial enlargement (P=0.03) and interventricular septal thickening (P=0.02), findings that are compatible with diastolic dysfunction. Levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide were significantly higher in all patients with cirrhosis with ascites (P=0.01 and P=0.05 respectively), but in only some of the pre-ascitic cirrhotic patients, compared with controls. All high levels of brain natriuretic peptide were correlated significantly with septal thickness (P<0.01), left ventricular diameter at the end of diastole (P=0.02) and deceleration time (P<0.01). We conclude that elevated levels of brain natriuretic peptide are related to interventricular septal thickness and the impairment of diastolic function in asymptomatic patients with cirrhosis. Levels of brain natriuretic peptide may prove to be useful as a marker for screening patients with cirrhosis for the presence of cirrhotic cardiomyopathy, and thereby identifying such patients for further investigations.
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PMID:Brain natriuretic peptide: is it a predictor of cardiomyopathy in cirrhosis? 1172 49


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