Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercalcemia has not previously been recognized as a complication of advanced chronic liver disease without hepatoma. During a five-year period, 16 patients evaluated in the liver transplantation program at the University of Pittsburgh developed hypercalcemia. All had advanced chronic liver disease with mean total bilirubin concentration of 29.5 +/- 4.6 mg/dL (50.1 +/- 78.2 mumol/L) (mean +/- SEM) and prothrombin time 16.8 +/- 0.8s. The highest serum calcium level was 17.2 mg/dL (4.3 mmol/L). The mean serum calcium level was 11.7 +/- 0.3 mg/dL (2.93 +/- 0.075 mmol/L) with an ionized calcium level of 5.41 +/- 0.35 mg/dL (1.35 +/- 0.088 mmol/L) and a phosphorus level of 4.2 +/- 0.4 mg/dL (1.4 +/- 0.1 nmol/L). Mild to moderate renal insufficiency was present in 14 (87%) patients; the mean serum creatinine level was 2.8 +/- 0.4 mg/dL (247 +/- 35 mumol/L). In five (38%) patients parathyroid hormone was completely suppressed and in an additional five (38%) patients, it was in a range most compatible with nonhyperparathyroid hypercalcemia. The 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D levels were normal or low in the 11 patients in whom determinations were made. Hypercalcemia that is not due to hyperparathyroidism or hypervitaminosis D is a potential complication of advanced chronic liver disease.
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PMID:Hypercalcemia. A complication of advanced chronic liver disease. 381 45

Serum levels of the potent inhibitory neurotransmitter gamma aminobutyric acid (GABA) were measured in 10 patients with chronic liver disease and hepatic encephalopathy, 11 patients with chronic liver disease and no evidence of hepatic encephalopathy, 7 patients with end-stage renal disease and 11 healthy volunteers. Serum GABA levels were elevated in all 10 patients with hepatic encephalopathy, 5/11 with liver disease and no encephalopathy and 4/7 renal disease patients. The mean serum GABA level for the encephalopathic patients (0.92 +/- 0.13 microM, mean +/- SEM) was significantly greater than the mean for liver disease patients without encephalopathy (0.48 +/- 0.05 microM, p less than 0.05), renal disease patients (0.46 +/- 0.04 microM, p less than 0.05) and healthy volunteers (0.39 +/- 0.03 microM, p less than 0.001). These results would tend to support the hypothesis that GABA may play a role in the pathogenesis of hepatic encephalopathy.
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PMID:Serum gamma-aminobutyric acid (GABA) levels in patients with hepatic encephalopathy. 405 11

Using a sensitive fluoroimmunoassay, anti-actin antibodies (AA) of the IgM and IgG classes were measured in 240 patients with various chronic liver diseases and in 211 patients with non-hepatic autoimmune muscle, heart, malignant and inflammatory bowel diseases. Thirty-two out of 40 patients (80%) with autoimmune chronic active hepatitis (CAH) had AA only of the IgG class (geom. mean X = 1.78, SEM +/- 0.07) and only three patients (8%) had both IgG and IgM AA, the latter in lower titres. In patients with primary biliary cirrhosis (PBC) and AMA-positive cholestatic CAH, AA of both IgM and IgG classes were equally represented (60% IgG and 64% IgM AA in PBC, 73% IgG and 51% IgM AA in cholestatic CAH) but the titres were very low (geom. mean IgG AA in PBC 1.035, SEM +/- 0.03, in cholestatic CAH 1.18, SEM +/- 0.02). In contrast to autoimmune (lupoid) CAH, AA were rare in HBsAg positive CAH (9/43, 21%) and only present in low titres. However, in six out of 21 patients with anti-HBs and anti-HBc-positive chronic active hepatitis, high AA of IgG class were found, suggesting the autoimmune type of liver disease. In NANB virus-induced chronic liver disease after blood transfusion, AA were only occasionally found (IgG antibodies 1/19, IgM antibodies 3/19) and none were found in the eight patients with sporadic NANB hepatitis. They were also rare in 30 patients with alcoholic liver disease (3/30, 10%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anti-actin antibodies of IgM and IgG class in chronic liver diseases detected by fluorometric immunoassay. 636 21

Of 30 patients with chronic liver disease 16 showed some degree of impairment of glucose tolerance, and 16 patients had lack of suppression of raised fasting growth hormone levels or showed an anomalous rise after oral glucose. No relationship, however, existed between the state of glucose tolerance and the presence of abnormal growth hormone levels. Plasma glucose in those with normal growth hormone response at 0, 1/2, 1, 1-1/2, and 2 hours, after 50 g glucose were 5.55 +/- 0.41 mmol/l, 8.71 +/- 0.59, 10.66 +/- 0.99, 10.28 +/- 1.37, 8.90 +/- 1.40 (mean +/- SEM; n = 14). Under the same conditions those with abnormal growth hormone responses showed values of 5.32 +/- 0.59, 7.83 +/- 0.81, 9.41 +/- 0.95, 9.46 +/- 0.99, 8.69 +/- 0.98. At no time were the differences significantly different as judged by Student's t test. Measurement of serum insulin indicated a relative deficiency in patients with impaired tolerance. It is concluded that the abnormal growth hormone is not directly responsible for the impaired glucose tolerance.
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PMID:Impaired glucose tolerance and growth hormone in chronic liver disease. 701 88

The apparent plasms clearances of tracer amounts of radiolabelled cholic acid given orally or intravenously were compared in 14 control subjects and 20 patients with chronic liver disease. The clearance after oral administration was the more sensitive in detecting chronic liver disease and correlated better with the fasting levels of endogenous serum bile acid. This agrees with the predicted effects on clearance of hepatocellular damage and portal-systemic shunting of blood after the two routes of administration. The estimated hepatic extraction ratio, calculated from the ratio of the oral and intravenous clearances, was 0.77+/-0.02 (mean+/-SEM) in control subjects, 0.64+/-0.03 in patients with anicteric chronic liver disease, and 0.46+/-0.05 in those with icteric chronic liver disease.
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PMID:Plasma clearance of oral and intravenous cholic acid in subjects with and without chronic liver disease. 738 Mar 33

This study was performed to define the amounts of methadone and metabolites excreted in urine in otherwise healthy maintenance patients, and to determine whether the metabolism and elimination of methadone, as assessed by analyses of urines, is altered in patients with liver disease. A method was developed for the simultaneous quantitation of methadone and six of its major and minor metabolites using chemical ionization mass spectrometry with direct probe introduction to increase sensitivity for analyses of the minor metabolites. Analyses of urine from unmedicated volunteers showed that the interferences at the mass range of interest (264-326) were usually small and therefore would not introduce significant error into analysis. Nineteen patients well-stabilized in chronic long-term methadone treatment were studied, five otherwise healthy males and fourteen patients with chronic liver disease (nine males and four females). Twenty-four hour urine collections were made and analyzed following extraction procedures. The concentrations of methadone and the major pyrrolidine metabolite exceeded 1 microgram ml-1 in all cases; the concentration (listed in descending order) of pyrrolidone, pyrroline, hydroxymethadone, hydroxypyrroline, methadol and hydroxypyrrolidine were all less than 1 microgram ml-1. The total 24 hour urinary excretion of methadone and its metabolites was 48.3% (+/- 1.71 SEM) in otherwise healthy patients but was significantly lower, 32.6% (+/- 3.19 SEM) in patients with liver disease (p less than 0.05). The total 24 hour excretion of the pyrrolidone metabolite, the end product of two pathways of methadone metabolism, was also significantly reduced in patients with liver disease (p less than 0.05). Females with liver disease had significantly higher ratios of pyrrolidine to methadone than did males with liver disease (p less than 0.05).
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PMID:Effects of liver disease on urinary excretion of methadone and metabolites in maintenance patients: quantitation by direct probe chemical ionization mass spectrometry. 747 May 91

11 beta-Hydroxysteroid dehydrogenase (11 beta HSD), found predominantly in liver and kidney, is responsible for the shuttling of active cortisol to cortisone. A defect in this shuttle mechanism, e.g. after liquorice ingestion, results in an increase in the ratio of urinary cortisol [tetrahydrocortisol (THF)] to cortisone [tetrahydrocortisone (THE)] metabolites. The plasma cortisol half-life is prolonged, but concentrations remain normal because of a concomitant fall in cortisol production. Alcohol-induced pseudo-Cushing's syndrome is an ill defined cause of Cushing's syndrome. Because many of the documented cases have abnormal liver function tests, we have investigated whether abnormal hepatic 11 beta HSD activity may play a role in the pathogenesis of the condition. Fourteen patients with alcoholic (ALD) and 14 patients with non-alcoholic (CLD) chronic liver disease had marked deficiency of 11 beta HSD [5 alpha-THF + THF/THE: ALD, 1.94 +/- 0.38 (+/- SEM); CLD, 1.82 +/- 0.20] compared to controls (0.94 +/- 0.04; P < 0.01 and 0.001, respectively). In the CLD group, the daily cortisol production rate (as assessed by summation of principal cortisol metabolites) was reduced appropriately [median, 3,510; range, 1,101-8,940 micrograms/24 h; controls, 5,492 (range, 3,818-14,996) micrograms/24 h; P < 0.001], and normal 0900 h plasma cortisol and urinary free cortisol levels were maintained. However, in the ALD group, there was no concomitant fall in the cortisol production rate (sum of cortisol metabolites, 5,043 micrograms/24 h; range, 520-27,344). As a consequence, 0900 h plasma cortisol in the ALD group was significantly elevated (633 +/- 52 nmol/L) compared to values in the CLD group (487 +/- 48 nmol/L; P < 0.05) and controls (432 +/- 27 nmol/L; P < 0.001). Our findings of glucocorticoid excess in patients with chronic ALD may indicate that alcohol-induced pseudo-Cushing's syndrome develops as a result of continuing normal cortisol secretion in the face of impaired cortisol metabolism. The latter is mediated by defective hepatic 11 beta HSD activity; the former by either abnormal glucocorticoid feedback or stimulation of cortisol secretion at the level of the hypothalamus/pituitary.
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PMID:11 beta-Hydroxysteroid dehydrogenase deficiency and glucocorticoid status in patients with alcoholic and non-alcoholic chronic liver disease. 844 34

We developed an assay system for measuring free follistatin by using an anti-follistatin mouse monoclonal antibody and [125I]activin A. The sensitivity of this assay was 0.5 microgram/l and cross-reactivities with inhibin, luteinizing hormone, follicle-stimulating hormone and growth hormone were all less than 0.5%. The dose-response curves of human sera and follicular fluid were parallel to the standard curve, and the follicular fluid contained a large amount of follistatin (6.4 +/- 0.5 mg/l, mean +/- SEM; N = 13). The within- and between-assay coefficients of variation calculated from the analysis of serum samples of four different concentrations were 3.3-7.8% and 3.9-11.0%, respectively. The recovery rates of free follistatin at five different doses were 86.4 - 102.4%. When activin A was added to the same sample, free follistatin recovery rate declined dose-dependently. Gel filtration analyses of human serum and follicular fluid resulted in a single peak corresponding to authentic follistatin. Using this assay, free follistatin concentrations in sera were measured in normal, pregnant and diseased subjects. The free follistatin level in serum of normal adults was 3.5 +/- 0.2 micrograms/l (N = 60), which was significantly elevated in pregnant women (16.7 +/- 1.3 micrograms/l, N = 56), and in patients with chronic liver disease (8.1 +/- 1.1 micrograms/l, N = 20), chronic renal failure (6.7 +/- 0.9 micrograms/l, N = 42), advanced solid cancer (8.5 +/- 1.0 micrograms/l, N = 39) and hematological malignancies (6.8 +/- 1.0 micrograms/l, N = 18). These data indicated that the free follistatin concentration in serum is detectable and varies during pregnancy and in various diseased states.
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PMID:Determination of free follistatin levels in sera of normal subjects and patients with various diseases. 889 Jul 27

Our aim was to evaluate gastric emptying and orocecal transit in patients with end-stage liver disease and portal hypertension undergoing evaluation for liver transplantation. Although gastric emptying half-times for both liquid and solid emptying were similar in patients with chronic liver disease and control subjects, orocecal transit, as measured by a scintigraphic technique, was significantly prolonged in the patients with liver disease (transit time, minutes, mean +/- SEM, patients versus controls: 127 +/- 10.5 versus 80 +/- 9.5, P < .003). Serum levels of progesterone and estradiol were similar in patients and controls. We conclude that small intestinal transit is delayed in patients with advanced liver disease and portal hypertension and may contribute to gastrointestinal symptoms and promote sepsis of enteric origin in this patient population.
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PMID:Gastric emptying and orocecal transit in portal hypertension and end-stage chronic liver disease. 937 56

Body retinoids are stored in the lipid droplets of hepatic stellate (Ito) cells. In chronic liver disease, the stellate cells differentiate into myofibroblast-like cells, a process whereby they lose their retinoid-containing lipid droplets. We studied the relation between liver retinoid content, the number of lipid droplets per stellate cell, and the number of stellate cells per mm2 in human alcoholic liver disease. Semithin sections of liver biopsies from normal subjects and patients with early (steatosis, inflammation, and mild fibrosis) and late (cirrhosis and cirrhosis with acute alcoholic hepatitis) alcoholic liver disease were morphometrically evaluated. Liver retinoid content was determined by HPLC. In normal patients, liver retinoid content was 901 +/- 213 IU/g of liver (mean +/- SEM). There was a decrease in liver retinoid content in early alcoholic liver disease (409 +/- 50 IU/g) and a further reduction in cirrhosis (153 +/- 50 IU/g). In patients with acute alcoholic hepatitis, retinoid content was strikingly low (5.2 +/- 1.8 IU/g). There was a progressive decrease in the number of stellate cells per mm2 associated with progressive liver damage. We found a fair correlation between the number of stellate cells per mm2 and liver retinoid content in all patient groups (overall correlation: 0.71). In normal subjects, the mean number of lipid droplets per stellate cell was 7.4 +/- 0.7. In patients with early alcoholic liver disease and in patients with alcoholic cirrhosis, this value was increased to 13.6 +/- 0.8 and 10.4 +/- 2.0, respectively. In patients with acute alcoholic hepatitis, only a few lipid droplets were present (4.2 +/- 0.5). There was a good correlation between liver retinoid content and mean number of lipid droplets in normal patients (r = 0.58). In alcoholic cirrhosis, however, correlation was poor (r = 0.34). In early alcoholic liver disease, the correlation was absent (r = 0.004). In conclusion, the major finding of our study is that the correlation between the mean number of lipid droplets per stellate cell and liver retinoid content varies according to the hepatic pathology considered. Marked lipid droplet accumulation occurs in stellate cells in early alcoholic liver disease and, to a lesser extent, in alcoholic cirrhosis, but there is no correlation between the mean number of lipid droplets per stellate cell and liver retinoid content. Therefore, not retinoids but probably lipids are responsible for the accumulation of lipid droplets. We also find that there is a fair correlation between the number of stellate cells per mm2 and liver retinoid content in all patient groups. Finally, we confirm the decrease in hepatic retinoid content that occurs in alcoholic liver disease in humans, even at the early stages of the disease.
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PMID:Hepatic stellate cells and liver retinoid content in alcoholic liver disease in humans. 958 58


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