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)

Recent advances in techniques to determine free drug concentrations have lead to a substantial increase in the monitoring of this parameter in clinical practice. The majority of drug binding to macromolecules in serum can be accounted for by association with albumin and alpha 1-acid glycoprotein. Albumin is the primary binding protein for acidic drugs, while binding to alpha 1-acid glycoprotein is more commonly observed with basic lipophilic agents. Alterations in the concentrations of either of these macromolecules can result in significant changes in free fraction. Diseases such as cirrhosis, nephrotic syndrome and malnourishment can result in hypoalbuminaemia. Burn injury, cancer, chronic pain syndrome, myocardial infarction, inflammatory diseases and trauma are all associated with elevations in the concentration of alpha 1-acid glycoprotein. Treatment with a number of drugs has also been shown to increase alpha 1-acid glycoprotein serum concentrations. A wide variety of biological fluids have been examined for their ability to provide an estimation of free drug concentration at receptor sites. The most useful fluid for estimating free drug concentrations appears to be plasma or serum, with subsequent treatment of the sample to separate free and bound drug by an appropriate technique. The two most widely used methods are equilibrium dialysis and ultrafiltration. Of these two, ultrafiltration has the greatest utility clinically because it is rapid and relatively simple. The major difficulty associated with this method involves the binding of drug to the ultrafilters, but significant progress has been made in solving this problem. Several authors have endorsed the routine use of free drug concentration monitoring. Data examining the clinical usefulness of free drug concentration monitoring for phenytoin, carbamazepine, valproic acid, disopyramide and lignocaine (lidocaine) are reviewed. While available evidence suggests that free concentrations may correlate with clinical effects better than total drug concentrations, there are insufficient data to justify the recommendation of the routine use of free drug concentration monitoring for any of these agents at present.
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PMID:Free drug concentration monitoring in clinical practice. Rationale and current status. 354 37

A method for the simultaneous measurement of gastrointestinal protein loss and total albumin turnover entailing the use of a combination of (125)iodine- and (51)chromium-labeled albumin is described. Albumin turnover was calculated by the measurement of albumin-(125)I plasma decay and cumulative urinary excretion, and the results obtained agreed closely with previous studies utilizing albumin-(131)I. Gastrointestinal catabolism was calculated from the rate of fecal excretion of (51)Cr and the specific activity of plasma albumin-(51)Cr, and these data were related to the calculated albumin turnover results. During the period of 6-14 days after administration, the ratio of specific activties of albumin-(125)I and -(51)Cr in plasma and in extravascular spaces or gastric and biliary secretions remained almost identical. Fecal excretion of (51)Cr was also quite stable at this time. In six normal subjects gastrointestinal catabolism accounted for less than 10% of total albumin catabolism. Excessive gastrointestinal protein losses did not contribute to the low serum albumin in three patients with cirrhosis or in two adults with the nephrotic syndrome. Multiple mechanisms leading to hypoalbuminemia were demonstrated in other subjects with a variety of gastrointestinal disorders.
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PMID:Use of 125-I- and 51-Cr-labeled albumin for the measurement of gastrointestinal and total albumin catabolism. 563 Apr 19

Problems raised by major hepatobiliary surgery affect the total economy of the human body. The liver is implicated in all body metabolism processes and possible problems during partial or total hepatectomy can only be solved by a knowledge of liver physiology. The liver plays a major role in the metabolism of products of digestion, whether these are carbohydrates or amino acids arriving in the portal blood. The most important activity of the liver is the preservation of a constant level of glucose by ensuring a fixed and predictable concentration to extrahepatic tissues. It ensures a very precise control of plasma and tissue flow of amino acids and thus protein synthesis and neoglycogenesis. Synthesis and degradation of non-esterified fatty acids, ketogenesis, cholesterol synthesis and triglyceride production result from the action of the liver on lipid metabolism. Free cholesterol is the precursor of bile acids and steroid hormones, but esterified cholesterol is not synthetized in the liver. Apart from its role in bilirubin metabolism, it has a key role to play in correct functioning of most endocrine systems: many are catabolized in the liver. But one of the most interesting properties of the hepatic tissue, as far as the surgeon is concerned, is liver regeneration, which combines hypertrophy with hyperplasia. This is dependent on age, hepatotrophic factors of portal blood, and extraportal factors. A study of hepatic metabolic processes allows assessment of the consequences of partial hepatectomy. Postoperative hypoglycemia, in the absence of a continuous infusion of glucose, is easily explained by the weakness of hepatic reserves in glycogen. Albumin levels fall during the first 7-10 days after liver resection, but this hypo-albuminemia is often marked by the need to infuse large quantities of frozen fresh plasma to try to avoid lesions of the other specific proteins, which are coagulation factors. Lipid metabolism disorders are of little clinical consequence. Hepatic resection is being alarming when it involves 80 to 90% of the hepatic mass and menaces the life of the patient. The existence of a previous liver alteration worsens the consequences of major hepatobiliary surgery. Indications for hepatic resection must be weighed carefully in patients with cirrhosis, liver regeneration being totally absent after resection. Metabolic consequences of total hepatectomy followed by transplantation are identical in kind to those of partial hepatectomy but are increased in frequency and start during operation. Postoperative surveillance must be strict to avoid marked variations in glycemia with the risk of hypoglycemia, and variations in kaliemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Hepatic insufficiency and nutritional problems after major hepatobiliary surgery]. 643 25

This study was undertaken to investigate permselectivity of the liver blood-lymph (ascitic fluid) barrier to endogeneous marcomolecules in patients with decompensated cirrhosis. Albumin (mol wt 69,000), immunoglobulin-G (mol wt 160,000) and immunoglobulin-M (mol wt 900,000) were determined in plasma and ascitic fluid from 13 cirrhotic patients. As previously substantiated in patients with cirrhosis, the ascitic fluid/plasma concentration ratio (R) of a protein is proportional to the transport rate from blood to lymph (ascitic fluid). Mean Ralb = 0.28 and RIgG = 0.29 were identical, but significantly higher than, RIgM = 0.18 (P less than 0.01). Ralb was directly correlated to RIgG (r = 0.97, P less than 0.001) and to RIgM (r = 0.78, P less than 0.005). Mean RIgG/Ralb = 1.03, which expresses the relative flux rates between IgG and albumin, was significantly above the ratio between the free diffusion coefficients (DIgG/Dalb = 0.64, P less than 0.01). Mean RIgM/Ralb = 0.61 was significantly above DIgM/Dalb = 0.39 (P less than 0.05) and significantly below unity (P less than 0.01). The results are best explained by filtration as the dominant mechanism of the liver blood-lymph (ascitic fluid) exchange of endogeneous macromolecules. A significant 'sieving' is present in this barrier to the largest macromolecule (IgM). Calculations of pore-size equivalent to the observed permselectivity of macromolecules suggest microvascular gaps (or channels) with an average radius about 300 A, i.e. in the lower end of the range of gaps in normal liver sinusoids (from 200 to 5000 A).
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PMID:Permselectivity of the liver blood-lymph (ascitic fluid) barrier to macromolecules in decompensated cirrhosis: relation to calculated pore-size. 668 37

Albumin-kinetics and haemodynamic studies were performed in 20 patients with decompensated liver cirrhosis in order to improve the knowledge on genesis and perpetuation of hepatic ascites, especially with respect to determinants of intraperitoneal protein. A positive relationship was found between the plasma-to-peritoneal transport rate of albumin (index of 'lymph-imbalance') and the mass of intraperitoneal albumin (rlog = 0.82, P less than 0.001), indicating a significant role of 'lymph-imbalance' to sequestration of protein in the peritoneal cavity. Ascitic fluid albumin concentration was on the average 0.22 of that of plasma and directly correlated to the plasma concentration (rlin = 0.68, P less than 0.01). The hydrostatic pressure difference across the splanchnic microvasculature (assessed as wedged hepatic vein minus inferior vena caval pressure) was directly correlated to the effective (plasma minus ascitic fluid) oncotic pressure (rlin = 0.74, P less than 0.001) but significantly higher than that (P less than 0.005), indicating a 'non-equilibrium' in the splanchnic Starling forces. The results point to a multivariate genesis and perpetuation of cirrhotic ascites as laid down in the 'lymph-imbalance' theory of ascites formation, whereas a 'fluid equilibrium' theory seems to be too simple, especially with respect to explain protein sequestration in the peritoneal cavity.
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PMID:Plasma-to-ascitic fluid transport rate of albumin in patients with decompensated cirrhosis. Relation to intraperitoneal albumin. 668 94

Although elevated gamma globulin is known to produce hypoalbuminemia both experimentally and in disease, a low albumin concentration in chronic liver disease often is assumed to reflect impaired liver synthetic function. Albumin and gamma globulin measurements in a series of 200 patients with a variety of chronic diseases (including cirrhosis, connective tissue disease, chronic inflammation, and malignancy) associated with diffuse hypergammaglobulinemia were combined with similar measurements from a previous study (Am J Med 1959; 29:596-616). The mean serum albumin concentration correlated inversely with mean gamma globulin, irrespective of disease category. Double reciprocal plot analysis showed that the relationship fits a rectangular hyperbola (r = -0.915, P less than 0.001), with the mean albumin concentration approaching 2.31 g/dL at infinite gamma globulin. This suggests that serum albumin decreases to a similar extent in various chronic diseases and that hypoalbuminemia has no diagnostic implications, except to the extent that it reflects the severity of hypergammaglobulinemia.
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PMID:Hypoalbuminemia associated with diffuse hypergammaglobulinemia in chronic diseases: lack of diagnostic specificity. 670 48

A close correlation between the presence of hepatitis B surface antigen and albumin in the cytoplasm of hepatocytes infected with hepatitis B virus was established by immunofluorescence and immunoelectron microscopy in 52 liver biopsy specimens of various forms of hepatitis and liver cirrhosis. Albumin deposits usually accompanied cytoplasmic content of hepatitis B surface antigen, but were less frequently observed together with hepatitis B antigen localized in or on the membranes. Ultrastructural observations demonstrated albumin on the tubular and spherical forms of hepatitis B surface antigen in the endoplasmic reticulum. The hepatocytes with the content of hepatitis B surface antigen and albumin showed the ability of binding with the fluorescein-labeled preparation of polymerized human serum albumin. The affinity of polymerized albumin to hepatitis B surface antigen was considerably increased after preincubuation of liver sections with 2-mercaptoethanol that removed most of the originally present albumin. This may be indicative for the role of disulfide bonds in the formation of hepatitis B surface antigen-albumin complexes. These results justify the hypothesis that albumin may be incorporated into the viral coat protein during its synthesis in the cytoplasm of infected hepatocytes.
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PMID:Hepatitis B surface antigen and albumin in human hepatocytes. An immunofluorescent and immunoelectron microscopic study. 700 3

We attempted to detect circulating hepatocellular carcinoma by demonstrating hepatocyte-associated mRNA in the nuclear cell component of peripheral blood using nested reverse transcription-polymerase chain reaction because of the extremely small number of tumor cells in the circulation. Albumin mRNA was demonstrated not only in the liver tissue (hepatocytes) and HepG2 cells but also in nuclear cells of the blood from normal healthy volunteers (neutrophils and lymphocytes) by reverse transcription-polymerase chain reaction. In contrast, alpha-fetoprotein mRNA was demonstrated in the liver tissue, as well as in HepG2 cells, but not in peripheral blood of normal healthy volunteers, indicating the possibility of using alpha-fetoprotein mRNA for detection of benign and malignant hepatocytes among the population of neutrophils and lymphocytes. alpha-Fetoprotein mRNA in peripheral blood was detected in 17 of 33 cases of hepatocellular carcinoma (52%), 2 of 13 cases of cirrhosis (15%) and 2 of 17 cases of chronic hepatitis (12%). alpha-Fetoprotein mRNA was not demonstrated in 26 cases of normal healthy volunteers (0%). Among the patients with hepatocellular carcinoma, total volume of tumor tissue, maximum size of tumor and serum alpha-fetoprotein level were markedly increased in the patients with alpha-fetoprotein mRNA in blood. In addition, alpha-fetoprotein mRNA was detected in the blood of all 6 patients showing metastasis at extrahepatic organs (100%), in contrast to 11 of 27 cases without metastasis (41%). From these results, we conclude that the presence of alpha-fetoprotein mRNA in peripheral blood may be an indicator of circulating malignant or benign hepatocytes, which might predict hematogenous spreading metastasis of tumor cells in patients with hepatocellular carcinoma.
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PMID:Detection of alpha-fetoprotein mRNA, an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation: a possible predictor of metastatic hepatocellular carcinoma. 752 2

The fasting concentration of free fatty acids (FFA) in the ascitic fluid was determined in 14 patients with malignant ascites and in 19 patients with liver cirrhosis. In malignant ascites FFA levels were increased more than three times when compared with the levels in cirrhotic ascites (5.241 +/- 0.493 vs. 1.558 +/- 0.170 mumol/ml; P < 0.0001). Palmitic acid was the most representative saturated FFA (which together accounted for 2.499 +/- 0.323 vs. 0.833 +/- 0.064 mumol/ml; P < 0.0001), while unsaturated FFA (2.741 +/- 0.298 vs. 0.725 +/- 0.111 mumol/ml; P < 0.001) were represented, in decreasing order, by oleic, linoleic and arachidonic acids. The ratio of unsaturated to saturated FFA was higher in neoplastic patients (1.35 +/- 0.29 vs. 0.826 +/- 0.065 P < 0.05). Albumin concentration in ascitic fluid of neoplastic patients was 22.44 +/- 1.35 g/l, while that of cirrhotic patients was 8.19 +/- 0.32 g/l, P < 0.0001. A close relationship (R2 = 95.14%) between albumin concentration in ascitic fluid and levels of total FFA was found. These data support the hypothesis that the elevation of FFA in ascitic fluid allows discrimination between malignant and non-malignant ascites.
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PMID:Free fatty acid analysis in ascitic fluid improves diagnosis in malignant abdominal tumors. 758 83

A large percentage of patients with advanced-stage hepatocellular carcinoma (HCC) have a recurrence of tumor in the liver or lung after primary resection and even after orthotopic liver transplantation. One reason for this may be the presence of small numbers of tumor cells circulating in the blood before surgery or the liberation of tumor cells into circulation during surgical manipulation. We tested this hypothesis by measuring messenger RNA (mRNA) for human albumin gene as a liver cell marker with the highly sensitive reverse transcriptase polymerase chain reaction (RT-PCR) technique. Albumin mRNA was not found in peripheral blood from normal humans (0 of 6), from patients with liver cirrhosis (0 of 10), from other tumors metastatic to liver (0 of 10), or during liver transplant surgery for cirrhosis (0 of 10). In patients with advanced-stage HCC (TNM stages III and IV), albumin mRNA was detected (16 of 17) in peripheral blood. After liver transplantation in the HCC patients, the level of mRNA decreased below the detectable limit (0 of 9). Three of these patients again had detectable mRNA levels when they had recurrence of HCC after liver transplantation. Patients with stage I HCC did not have detectable expression. These results suggest that circulating tumor cells are present in patients with advanced-stage HCC, which may be one of the reasons why these patients have a high incidence of tumor recurrence after apparently definitive surgical resection and even after liver transplantation.
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PMID:Detection of liver cells in peripheral blood of patients with advanced-stage hepatocellular carcinoma. 784 13


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