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

A 21 y/o female presented with fulminant hepatic failure and hemolysis. On the basis of the clinical presentation, levels of ceruloplasmin and serum copper a presumptive diagnosis of Wilson's disease was made. In spite of supportive measures and hemodialysis, the patient died one week after admission. Postmortem examination showed cirrhosis and increased copper stores in the liver, corroborating the clinical diagnosis of Wilson's disease. Study of the four siblings revealed that two are carriers, one is healthy and one may have the disease. Wilson's disease is a rare cause of fulminant hepatic failure that must be suspected specially when hemolysis is associated to the clinical picture. This mode of presentation is virtually fatal and early liver transplantation is the best form of therapy.
 ...
PMID:Fulminant Wilson's disease: a report. 222 83

Authors examined the effect of D-penicillamin (Pw) on liver cirrhosis induced by chronic CCl4 and phenobarbital (Pb) treatment in Fischer 344 rats. Morphometric analysis of quantity of connective tissue fibres did not show decrease on the effect of Pe treatment. Quantity of hydroxiproline, which is one of the parameters of coll ahen decrease, did not change significantly on effect of drug, but only compared to CCl4 and Pb treated control. Quantity of glycosaminoglycan showed increase following Pe treatment. Lymphocyte stimulation by Con-A was different in CCl4 and Pb and Pe treated groups, respectively. According to our examinations in case of liver fibrosis cirrhosis induced by CCL4-PB treatment in rats the Pe treatment proved to be unsuccessful. It seems that Pe is effective only in forms of cirrhosis accompanied by significant copper accumulation, by decrease of toxic effects of copper.
 ...
PMID:[The effect of D-penicillamine on experimental liver cirrhosis induced by CCl4]. 223 69

Hepatolenticular degeneration (Wilson's disease) is a hereditary disease in which metabolic disorder of copper leads to its accumulation in the liver, brain, cornea and kidneys with consequent pathologic changes in those organs. Hereditary mechanism of the disease is autosomal recessive with prevalence of 30-100 per 1,000,000 inhabitants. Etiology of this disease is not yet explained. There are two hypotheses. The first one is that it is the disorder of ceruloplasmine metabolism caused by insufficient synthesis of normal ceruloplasmine, or synthesis of functionally abnormal ceruloplasmine. The second one is: the block of copper biliar excretion which is the consequence of the liver lysosomes functional defect. Pathogenetic mechanism of disease is firstly long-term accumulation of copper in the liver, and later, when the liver depo is full, its releasing in circulation and accumulation in the brain, cornea, kidneys and bones, which causes adequate pathologic changes. Toxic activity of copper is the consequence of its activity on enzymes, particularly on those with -SH group. There are two basic clinical forms of the disease: liver disease or neurologic disease. Before puberty the liver damage is more frequent, while in adolescents and young adults neurologic form of the disease is usual. The liver disease is nonspecific and characterized by symptoms of cirrhosis and chronic aggressive hepatitis. The only specificity is hemolytic anemia which, in combination with previous symptoms, is important for diagnosis of the disease. Neurologic symptoms are the most frequent consequence of pathologic changes in the basal ganglia. In our patients the most frequent symptoms were tremor (63%); dysarthria, choreoathetosis and rigor (38%); ataxia and mental disorders (31%); dysphagia and dystonia (12%), diplopia, hypersalivation, nystagmus and Babinski's sign (6%). Among pathologic changes in other tissues and organs the most important is the finding of Kayser-Fleischer ring in the cornea as a result of copper accumulation. Its importance for precise diagnosis is great. The diagnosis of the disease is based on anamnesis, clinical examination, specific and nonspecific laboratory tests. The therapy of choice is penicillamine. If we use it early, the result will be good remission in the majority of patients. Late diagnosis or delay in treatment cause death which is the result of bleeding from esophageal varices or basal ganglia disease. Immunologic damages caused by penicillamine demand interruption of therapy and substitution by three-ethyl-tetra-amine (TETA). We also use zinc salts and tetratiomolibdate in therapy of this disease. Pathogenesis, clinical picture and therapy of the disease are based on our own results.
 ...
PMID:[Hepatolenticular degeneration]. 226 49

Diagnosis of Wilson's Disease in the early stages may be elusive in patients presenting without neurological symptoms. A case history is presented which demonstrates the pitfalls in making the diagnosis. Presenting psychiatric symptoms were nonspecific. Ceruloplasmin level was initially elevated to normal range. Liver biopsy showed early nonspecific cirrhosis; staining for copper did not show the dramatic effects expected with Wilson's Disease. Neurological examination, including NMR, was within normal limits. Kayser-Fleischer rings are no longer considered pathognomic. Urinary copper excretion helped to establish the diagnosis.
 ...
PMID:Pitfalls of diagnosis in the early stages of Wilson's disease. 200 54

Copper granules in hepatocytes were examined by the p-dimethylaminobenzylidene rhodanine method in 965 liver biopsy specimens obtained from patients with various liver abnormalities other than Wilson's disease and biliary diseases. The granules were found in chronic active hepatitis (incidence of positive cases: 17.2%) and alcoholic fibrosis (22%) with lobular disarray and fibrosis, nonbiliary liver cirrhosis (28%), and drug-induced cholestasis (15%). Copper granules were present in the periportal or periseptal hepatocytes where the granules were mainly found in the perinuclear cytoplasm. These intracellular and intralobular distribution patterns of copper granules resembled those of primary biliary cirrhosis. These data suggest that hepatic fibrosis and lobular disarray with fibrosis in these chronic liver disease may lead to distortion or interruption of small biliary branches followed by disturbance of bile flow and deposition of copper granules. Copper stain seems to provide a valuable information for assessment of progression of these chronic liver diseases. Impaired biliary excretion seems important in deposition of copper granules in drug-induced cholestasis.
 ...
PMID:Survey of copper granules in liver biopsy specimens from various liver abnormalities other than Wilson's disease and biliary diseases. 246 23

The ultrastructural localization of copper, zinc-superoxide dismutase (Cu, Zn-SOD) in the liver of patients with acute hepatitis, chronic hepatitis, liver cirrhosis and alcoholic fatty liver was studied by means of the indirect immunoperoxidase technique. In hepatocytes Cu, Zn-SOD was found to be localized in perinuclear cisternae, rough endoplasmic reticulum (rER), vesicles and Golgi apparatus. The Cu, Zn-SOD was also detected around the lipid droplets in hepatocytes as well as on the cytoplasmic membrane in cases of liver cirrhosis. These findings suggest that Cu, Zn-SOD is produced in the rER in hepatocytes and protects the cells from cellular injury caused by superoxide anion radical in various disorders of the liver.
 ...
PMID:Ultrastructural localization of Cu, Zn-SOD in hepatocytes of patients with various liver diseases. 248 85

To evaluate the prognostic value of serum copper (S-Cu) and ceruloplasmin and their pathophysiologic significance in human hepatocellular carcinoma (HCC), we studied 49 patients with HCC (20 of which were submitted to partial hepatectomy) compared with 110 patients with liver cirrhosis. In HCC both S-Cu and ceruloplasmin were higher than in cirrhosis; moreover, S-Cu was correlated with the extension of HCC, evaluated by instrumental data and by surgical inspection. In cirrhotic patients, mean S-Cu was 122.9 micrograms/dl (SD, 29.3), in early HCC, 153.0 micrograms/dl (SD, 34.5), and in advanced HCC, 193.1 micrograms/dl (SD, 37.7). Variance analysis gave F = 59.4. In HCC patients S-Cu was positively correlated with ceruloplasmin and with fibrinogen. Survival, evaluated by Mantel's test stratified for surgical therapy, was longer in patients with S-Cu levels lower than 175 micrograms/dl and in those at an earlier stage. We therefore conclude that S-Cu has a relevant diagnostic value in detecting HCC also in early stage and allows prognostic evaluation as regards survival.
 ...
PMID:Serum copper and ceruloplasmin in early and in advanced hepatocellular carcinoma: diagnostic and prognostic relevance. 255 94

Eleven patients with newly diagnosed Wilson's disease were treated with zinc acetate as their sole anticopper therapy. Treatment duration was 8 to 37 months. Three of the patients had symptoms; in eight who were presymptomatic, diagnosis was made because of affected siblings who had symptoms. All patients did well clinically. Copper absorption was suppressed, as reflected by blockade of absorption of orally administered copper 64. Values for 24-hour urine copper and nonceruloplasmin plasma copper (freely available copper) were reduced. Values for liver-derived serum enzymes were also generally reduced in patients who had pretreatment elevations. Percutaneous liver biopsies were done initially and repeated in seven of the patients after 12 to 35 months of zinc therapy. In five of these patients a second biopsy specimen showed higher levels of copper than the first. In three of these five a third biopsy 6 to 23 months after the second revealed liver copper values that either had returned to the baseline value or were lower. One patient's initial biopsy specimen showed active inflammation, which subsided with therapy. All of the biopsies revealed histologic scarring typical of cirrhosis, and this did not appear to change over the course of therapy. We conclude that hepatic copper may increase temporarily during early zinc therapy but that the accumulated copper is sequestered in a nontoxic form. On the basis of animal studies we postulate that this sequestered copper is primarily bound to the high levels of hepatic metallothionein induced by zinc. Zinc appears to be a reasonable option for the initial treatment of patients with Wilson's disease, particularly those with presymptomatic disease.
 ...
PMID:Treatment of Wilson's disease with zinc. VI. Initial treatment studies. 259 53

Pathohistological findings are playing an important role in the advice of toxic organ damages. After presentation of some details about the frequency of toxic organ damages, the pathways of toxic agents in the organism are discussed. In cells toxic damage may induce cell necrosis, functional disturbance, inhibition of cell proliferation or malignant transformation; in extracellular structures it may lead to degradation phenomena in the connective tissue matrix. As demonstrated in example of calciphylaxis, a combination of different noxes may not only add but even potentiate the effects of the single noxes. In intracellular reparation processes the lysosomal system is involved. In case of necrosis regeneration is possible in most kinds of tissues, if connective tissue rails are preserved. Otherwise an irreversible reparative fibrotic alteration of organ structure is induced which develops according to particular general and schematic rules. As mostly character and course of the tissue reaction is unspecific, pathohistological findings do not enable conclusions on the type of inducing toxic agent. The following presentation of some examples of toxic damages with pathognomonic histological appearance deals with asbestosis, silicosis, chloroquine-induced cardiomyopathy, aluminum-induced osteopathy and a recently described liver cirrhosis in early childhood induced by copper-containing drinking water. Some limits of traditional pathohistological evaluation of toxic organ damages have been overcome by application of new morphological techniques. Own investigations revealed that the immunocytochemical demonstration of the C5b-9-complement complex enables a better and earlier detection of irreversibly damaged cells. Discrimination of toxic and virus-induced tissue damage is facilitated by the technique of in-situ-hybridization. Sometimes a specific recognition and localization of toxic agents is achieved by X-ray microanalysis, electron-spectroscopic imaging (= ESI) resp. laser microprobe mass spectrometry (= LAMMA); comparing these techniques X-Ray microanalysis and ESI, both, enable specific identification of chemical elements, while LAMMA, in addition, offers some information about the involved molecules and isotopes.
 ...
PMID:[Toxic organic damage]. 265 Apr 56

We treated a sixteen-year old Japanese girl with fulminant hepatic failure in Wilson's disease. The diagnosis of Wilson's disease was made immediately after the admission because of low serum copper and ceruloplasmin levels with high urinary copper excretion. Her hepatic failure was accompanied by bouts of hemolytic crisis. In spite of the administration of D-penicillamine and repeated plasmapheresis, she died of hepatic failure four months later. At autopsy, the surface of the liver was smooth. The histology of the liver showed massive necrosis. There were only a few remaining scattered hepatocytes, in which copper was revealed by Rhodanine staining. There was no evidence of cirrhosis. The livers of the previously reported cases of Wilson's disease accompanied by fulminant hepatic failure were all cirrhotic. Our case indicated that Wilson's disease could occur as true fulminant hepatic failure without preceeding neurological and hepatological signs and the evidence of cirrhosis.
 ...
PMID:Fulminant hepatic failure without evidence of cirrhosis in a case of Wilson's disease. 265 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>