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)

Diacereine (DAR) is a new anti-arthrosis drug with an unusual action mechanism. Once it was found that, unlike existing FANS, DAR has no effect on prostaglandin synthesis, it was thought interesting to assess its clinical tolerability on two groups of patients. The first was a group of high risk patients with arthrosis or arthritis. The second consisted of patients with a history of duodenal ulcer or cirrhotics in the ascitic phase. In the first group the DAR was given (100 mg per diem per os) for 30 days after oesophagogastroduodenoscopy that was repeated at the end of treatment. DAR treatment of patients with ulcers in the clinical remission phase was reliable in the sense that no recurring ulceration or major endoscopic lesions were observed but the subjective tolerability was not excellent in about half the patients due to the appearance of dyspeptic symptoms that are, however, a notoriously common response to any drug treatment in this kind of case series. In a second group of 5 patients with various types of cirrhosis of the liver, the aim was to assess the effect of DAR treatment on kidney function and ascitic decompensation. The drug was administered orally in doses of 100 mg per diem for 10 days. On the basis of the results observed in this case series only it can be stated that the use of DAR on ascitic cirrhosis patients produces no alterations in kidney function and does not reduce the effectiveness of diuretic treatment. Indeed it may well be that DAR has a positive effect on diuresis, that increased in this series in line with earlier experimental results.
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PMID:[Influence of diacereine on the gastroduodenal mucosa of ulcer patients in remission and on the diuresis of cirrhosis ascites patients]. 377 5

The excessive storage of iron in idiopathic haemochromatosis leads to severe organic lesion up to life-threatening conditions (cardiac insufficiency, portal decompensation). The symptoms melanodermia , diabetes mellitus and other endocrine failures, liver cirrhosis, cardiac insufficiency and arthropathy appear together or in various combinations. The diagnosis is ascertained by the proof of iron storage, the multiple organic affection and by familial accumulation of the various laboratory diagnostic possibilities are particularly to be emphasized the serum iron value together with the percetal transferrin saturation (as search test), serum ferritin, the desferrioxamine test, simple ferrokinetic investigations and the quantitative determination of iron in the liver in the bioptate . For family examinations, apart from the search test, a HLA typisation is reasonable, in order to estimate the risk of the disease (particularly of brothers and sisters). The therapy of choice are blood- lettings (0.5 l once to twice a week) up to obtaining a permanent easy iron deficiency anaemia. The maintenance therapy should be performed with monthly to quarterly blood- lettings . Only in cases exception a desferal treatment is indicated. Endocrine failures and cardiac disturbances need a particular therapy.
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PMID:[Idiopathic hemochromatosis--diagnosis and therapy]. 673 May 91

In three patients arthropathy was the earliest symptom of hemochromatosis. Two of these patients had a precirrhotic stage of hemochromatosis. The liver histology of the third patient showed a beginning cirrhosis. The serum iron ranged from 212 to 260 micrograms/dl. The transferrin saturation was 95-100%. Serum iron and transferrin should be determined in all patients with arthralgias, since arthropathy may be the first clinical sign of hemochromatosis.
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PMID:[Joint diseases as the early clinical symptom of hemochromatosis]. 721 95

We identified 35 homozygotes for hemochromatosis through pedigree studies. Thirteen were asymptomatic. Arthropathy was present in 20, hepatomegaly in 19, transaminasemia in 16, skin pigmentation in 15, splenomegaly in 14, cirrhosis in 14, hypogonadism in six, and diabetes in two. No homozygote was in congestive failure. Only one had the triad of hepatomegaly, hyperpigmentation, and diabetes. Serum iron was increased in 30 of 35, transferrin saturation was increased in all 35, serum ferritin in 23 of 32, urinary iron excretion after deferoxamine in 28 of 33, hepatic parenchymal cell stainable iron in 32 of 33, and hepatic iron in 27 of 27. Iron loading was 2.7 times greater in men than in women. No female had hepatic cirrhosis. Diagnosis of asymptomatic hemochromatosis is important because organ damage may be prevented by early therapy. Clinical diagnosis of early hemochromatosis is difficult. Persons with unexplained elevation of transferrin saturation should be studied for hemochromatosis.
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PMID:Homozygosity for hemochromatosis: clinical manifestations. 743 83

Hereditary hemochromatosis is a common disorder of iron metabolism with a prevalence as high as 8 per 1000. Affected individuals absorb excessive amounts of dietary iron and over time, tissue iron deposition results in skin discoloration, arthropathy, hepatic cirrhosis, heart failure, diabetes mellitus and impotence. Early diagnosis and institution of phlebotomy treatments will prevent these manifestations and normalize life expectancy. Once organ damage is established many of the manifestations are irreversible. Since the early manifestations of the disease are subtle, a case can be made for routine screening. This conclusion is supported by cost-effectiveness analysis based on available data. A reasonable screening strategy would start with a serum transferrin saturation. A value > or = 55% should trigger a repeat transferrin saturation in a fasting state and a serum ferritin level. If both these tests are abnormal, a liver biopsy with quantitative iron determination is the currently accepted confirmatory test.
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PMID:Management of hereditary hemochromatosis. 788 27

Hemochromatosis is a recessive disorder of iron metabolism characterized by progressive iron loading of parenchymal organs, which accounts for clinical complications such as cirrhosis, diabetes mellitus, cardiopathy, endocrine dysfunctions and arthropathy. Clinical complications, which usually develop after the third or fourth decade of life, can be fatal but may be prevented by phlebotomy if iron excess is detected at a very early stage. The hemochromatosis gene (HFE), located 4.5 megabases telomeric to the HLA-A locus, encodes an HLA class I like protein and two missense mutations, C282Y and H63D in complete disequilibrium have been identified within this gene. Due to its high frequency in the general population, the involvement of H63D in the pathogenesis of the disease remains controversial, and it might correspond to a minor mutation. Conversely, the C282Y mutation is tightly linked to the disease, as it accounts for 80 to 100% of the hemochromatosis cases in Northern Europe. The lower frequency observed, in the patients, in Italy and South of France led to imagine either the implication of other mutations or of other genes. The C282Y mutation is absent in Asia and Africa and is present in the general population with a decreasing gradient of frequency from Northern to Southern Europe. The prevalence of the disease was usually estimated to be 3% but the observed frequency of the C282Y homozygotes is 5% in our breton population raising the question of the penetrance of the disease, and consequently the use of the genotypic test for its systematic screening. As HFE encodes a membrane protein similar to HLA class I protein, its contribution to iron overload is not obvious. The normal protein is predicted to to be expressed at the cell surface in association with beta 2-microglobulin, a localization for which C282Y is critical as it disrupts this association. This protein has also been shown to form a stable complex with the transferrin receptor leading to a decreased affinity for transferrin. A better knowledge of its function will help to decipher iron and different metal-ions metabolism. Although the exact role of the HFE protein is unknown, the genotypic test allows the clinicians to ascertain their diagnosis and genetic counselling.
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PMID:[Molecular genetics of hemochromatosis]. 1052 Apr 11

Hereditary hemochromatosis (HHC) is one of the most common inherited disorders in the Caucasian population. Diagnosis usually made after an elevation in ferritin and serum transferrin saturation is noted, often accompanied by asymptomatic hepatomegaly. Diagnosis is confirmed by genetic testing or liver biopsy. Damage to organs is due to excessive intestinal iron, which is transported to and then deposited in the liver parenchyma, and the heart, skin, and endocrine organs, causing skin pigmentation, development of cirrhosis and hepatic carcinoma, diabetes and endocrine failure, and heart failure. Bony changes can be manifested by arthritis, often in non-weight-bearing joints. The treatment of HHC is phlebotomy, which depletes iron stores. When diagnosis is made before organ damage occurs, treatment can prevent manifestations of the disease. Skin pigmentation and some cardiac damage may reverse on depletion of iron stores, but liver and endocrine damage is rarely reversible. Arthropathy is also not reversible, and often continues to progress even with effective treatment. When hemochromatosis is diagnosed, all first degree relatives of the patient should undergo genetic testing. With early detection and treatment this can be a manageable chronic disease. If undetected, it is potentially fatal.
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PMID:Hereditary hemochromatosis: diagnosis and treatment in primary care. 1054 25

We studied peripheral blood erythrocyte parameters and HFE genotypes in 94 hemochromatosis probands and 132 white, normal control subjects. Mean red blood cell counts in probands and control subjects were not significantly different. However, mean values of hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were significantly higher in C282Y/C282Y probands (n = 60) than in wild-type control subjects (n = 65). Probands with other HFE genotypes also had increased mean erythrocyte parameters (other than red blood cell count). Peripheral blood smears prepared before therapeutic phlebotomy revealed that erythrocytes in many probands had increased diameters and were well filled with hemoglobin. Erythrocyte parameters were similar in C282Y/C282Y probands with and without hepatomegaly, elevated serum concentrations of hepatic enzymes, hepatic cirrhosis, diabetes mellitus, arthropathy, or hypogonadism. Among C282Y/C282Y probands, significantly greater values of MCV (but not other erythrocyte parameters) occurred among those who had transferrin saturation values of 75% or greater or iron overload at diagnosis. After iron depletion, the mean MCV, MCH, and MCHC values of C282Y/C282Y probands decreased but remained significantly greater than values in wild-type control subjects. Mean values of prephlebotomy MCH and MCHC concentrations were lower in HLA-A3-positive than in HLA-A3-negative C282Y/C282Y probands. We conclude that increased values of mean hemoglobin, hematocrit, MCV, MCH, and MCHC in hemochromatosis probands are caused primarily by increased iron uptake and hemoglobin synthesis by immature erythroid cells. Mechanisms of iron uptake by erythrocytes that could explain these results are discussed.
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PMID:Peripheral blood erythrocyte parameters in hemochromatosis: evidence for increased erythrocyte hemoglobin content. 1063

Hereditary hemochromatosis is the most commonly inherited autosomal recessive disorder. Hemochromatosis is a current or potential progression of abnormally high accumulations of iron in the liver. If left untreated, the condition can lead to chronic or irreversible hepatic fibrosis, cirrhosis, hepatocellular carcinoma, arthritis, and organ failure. Common signs and symptoms seen in the primary care setting include fatigue, weakness, abdominal pain, palpitations, skin pigmentation changes, and arthropathy, but any symptom associated with organ damage may be reported. Because prompt intervention can cease or reverse the debilitating effects of iron overload, prompt disease diagnosis and treatments are imperative.
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PMID:Detecting hereditary hemochromatosis. 1091 30

Arthropathy is one of the leading clinical manifestations of hereditary hemochromatosis (HH). Although cirrhosis of the liver is crucial for mortality in patients with HH, arthropathy has the greatest impact on the quality of life. Several mutations in the HFE and other genes have recently been identified, and the prevalence of some of these mutations has already been investigated in population studies in greater detail. Even though cofactors other than genetic predisposition may play a role in the establishment of the disease, the new understanding of the genetic background of this iron storage disorder may help in identifying patients before the onset of clinical symptoms. Early initiation of iron depletion therapy, not effective in established arthropathy of HH, might prevent the manifestation of arthropathy or reduce its severity.
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PMID:Arthropathy in hereditary hemochromatosis. 1114 20


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