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)

Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) is a new liver scintigraphy agent which binds to asialoglycoprotein receptor in hepatocyte. Studies were performed in three normal volunteers and 11 patients with liver cirrhosis. Time-activity curves for the heart and liver were obtained for 60 min following an i.v. injection of 99mTc-GSA (1 mg/185 MBq). We introduced five compartments to describe 99mTc-GSA: 1) extrahepatic blood, 2) hepatic blood, 3) receptor, 4) interstitial fluid and 5) urine. The %ID of 99mTc-GSA in blood and the hepatic blood volume were obtained from the extrapolation of the biexponential fitting for the heart and liver curves. Michaelis-Menten type saturation kinetics was applied to the process of receptor-ligand binding. Numerical analysis solved the simultaneous differential equations that were introduced from the compartment model. Hepatic blood flow was 1,651 +/- 131 ml/min, maximal removal rate for the ligand was 0.547 +/- 0.069 mg/min in normal controls. Both results were significantly decreased in patients with liver cirrhosis compared with normal controls. Present study may provide a novel method for the diagnosis of liver function that allows independent quantification of the hepatic blood flow and the receptor population.
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PMID:[A compartment model of Tc-99m-DTPA-galactosyl-human serum albumin for evaluating liver function]. 156 90

Phase II study of 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA), a new radiopharmaceutical which binds to the asialoglycoprotein receptors on the hepatocytes, was performed in 81 patients with liver diseases to validate its safety and possibility for the evaluation of hepatic function. None of adverse reactions, abnormal clinical laboratory findings and anti-99mTc-GSA antibody production due to 99mTc-GSA was recognized. Immediately after the injection of 99mTc-GSA, the dynamic data and serial hepatic images were obtained for 60 min. The indices for blood clearance and liver accumulation were calculated based on the counts in the regions of interest on the hearts and livers. In 54 patients with chronic hepatic disorders such as liver cirrhosis, the blood clearance and liver accumulation of 99mTc-GSA were retarded according to the progress of the hepatic disorders. The findings of 99mTc-GSA scintigraphy also reflected the hepatic functions of the patients with large hepatic tumors, obstructive jaundice and acute hepatitis. These results suggest that 99mTc-GSA has the clinical potentials to evaluate the liver functions in the patients with hepatic disorders.
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PMID:[Phase II clinical study on 99mTc-GSA, a new agent for functional imaging of the liver]. 157 24

Functional hepatic imaging was performed using 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA), a radiolabeled ligand that reacts specifically to the asialoglycoprotein receptor that resides at the plasma membrane of hepatocytes, in 21 patients: five with chronic active hepatitis (CAH), 14 with compensative liver cirrhosis (LC), one with chronic inactive hepatitis and one with acute hepatitis. The former two diseases were mainly investigated. Serial liver images were acquired at the rates of 10 sec/frame for 0-5 min and 2 min/frame for 6-30 min after the injection of 99mTc-GSA, and the images were compared with 99mTc-phytate images in 2 patients with CAH and 11 with LC, and those with portal scintigrams using 123I-iodoamphetamine (IMP) in 3 patients with LC. The images using 99mTc-GSA were in better agreement with hepatic function than those using 99mTc-phytate, and with the findings of portal scintigraphy using 123I-IMP. LHL15 (liver/liver and heart radioactivities at 15 min after the injection of 99mTc-GSA) correlated with the hepaplastin test (r = 0.978 in CAH, and r = 0.544 in LC), indicators of hepatic reserve. These results suggest that liver scintigraphy using 99mTc-GSA might be a useful method for evaluating liver function.
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PMID:[Clinical evaluation of hepatic scintigraphy using 99mTc-GSA]. 164 14

Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) was studied in normal volunteers and in patients with impaired liver function. The extrapolation approach originated the absolute dose of 99mTc-GSA in blood and the hepatic blood volume. The heart and liver regression curves were simultaneously fractionated into the three compartments (extrahepatic blood, hepatic blood and hepatocytes). Four differential equations were integrated with the six parameters as variables, and the smallest residual sum of squares was obtained by the damping Gauss-Newton method. The result of hepatic blood flow was 1603 +/- 144 (ml/min) in normal controls, which was compatible with previously reported values. Maximal removal rate (mg/min) showed statistically significant differences between the normal volunteers and patients with chronic hepatitis or liver cirrhosis. Our kinetic model of 99mTc-GSA can be used in the evaluation of liver function.
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PMID:A quantitative model of technetium-99m-DTPA-galactosyl-HSA for the assessment of hepatic blood flow and hepatic binding receptor. 174 8

Liver scintigraphy was performed using a newly developed radiopharmaceutical, Tc-99m-DTPA-Galactosyl-Human-Serum-Albumin (Tc-99m-GSA), which binds specifically to the receptors on the hepatic cell surface, in 15 patients with chronic liver diseases. The scintigraphy was evaluated qualitatively and quantitatively, and the results were compared with those obtained from the Tc-99m-PMT or Tc-99m-sn-phytate scintigraphy, and the liver function tests. The Tc-99m-GSA scintigraphy showed clear liver images in chronic hepatitis. However, in liver cirrhosis, the liver images was not clear and the cardiac images still existed 40 minutes after administration of Tc-99m-GSA, suggesting that the image quality of the Tc-99m-GSA scintigrams may be inferior to that of Tc-99m-sn-phytate or Tc-99m-PMT in some cases of severe liver dysfunction. The time-activity curves of the heart and liver were analyzed by non-linear regression analysis. The clearance rate from plasma (Kd) were obtained from the time-activity curve of the heart, and the hepatic uptake rate (Ku), hepatic excretion rate (Ke) and peak time of hepatic uptake-excretion curve (PT) were obtained from the time-activity curve of the liver. Kd, Ku and PT values were more significantly decreased or prolonged in the patients with liver cirrhosis than those in the patients with chronic hepatitis. Kd, Ku and PT values had positive correlations with the result of the serum liver function tests, ICG-R15 and ICG-K. Ku and PT values had also correlations with the histological degrees of hepatic fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Evaluation of usefulness of Tc-99m-GSA liver scintigraphy in chronic liver diseases]. 177 Jun 48

99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA) is a newly developed liver imaging ligand which specifically binds to asialoglycoprotein receptor on the hepatic cell surface. We investigated whether 99mTc-GSA scintigraphy was able to be used as indexes for the residual functional reserve and the early regeneration of the hepatocyte after the hepatic resection. Four patients with metastatic liver cancer, 3 patients with hepatocellular carcinoma, and 1 patient with cholangiocellular carcinoma were studied. Basically, each patient was examined 4 times (before, 3, 10, 20 days after the operation). Immediately after i.v. injection of 185 MBq (3 mg) of 99mTc-GSA, serial images and dynamic data were obtained. Serial changes of HH15, as an index of blood clearance of the tracer calculated from the uptake ratio of heart at 15 minutes to that at 3 minutes, and LHL15, as an index of hepatic accumulation calculated from the uptake ratio of liver to liver plus heart at 15 minutes after the injection were analyzed before and after hepatectomy. Three out of 4 lobectomy patients which showed increased HH15, and decreased LHL15 as compared with the preoperative data were considered to be decreased residual hepatic functional reserve. The remaining one lobectomy patient showed increased HH15, but increased LHL15 inversely. One patient of two partial resections of hepatocellular carcinoma with liver cirrhosis demonstrated transiently decreased HH15, and increased LHL15. Two patients with metastatic liver cancer (one partial resection, six partial resections) showed decreased HH15, and increased LHL15. Postoperatively increased hepatic accumulation was presumed to be increased functioning hepatocyte or transiently increased asialoglycoprotein receptor on the cell surface by up-regulation. 99mTc-GSA scintigraphy might be helpful for non-invasive method to detect the residual functional reserve and the early regeneration of the hepatocyte after the hepatic resection.
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PMID:[Evaluation of the residual functional reserve and the early regeneration after the hepatic resection using asialoglycoprotein receptor imaging agent]. 773 62

To improve the results of hepatectomy in cirrhotic patients, the likely reserve function of the liver was evaluated before surgery. Asialoglycoprotein receptor (ASGP-R) is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Technetium-99m-diethylene triamine pentaacetic acid-galactosyl human serum albumin (99mTc-GSA) is a newly developed analog ligand to ASPG-R. The probable functional reserve of the remnant liver after hepatectomy was estimated preoperatively as the hepatic binding protein (HBP) concentration specific for ASGP-R on the hepatocellular membrane of the remnant liver. This estimate was based on the effective liver volume rate, obtained by the uptake of 99mTc-GSA. In all, 3 normal volunteers, 3 patients with chronic hepatitis (CH), 9 patients with liver cirrhosis (LC), 2 patients with hepatic cystadenoma, 3 patients with hepatocellular carcinoma (HCC) associated with CH, and 21 HCC patients with LC were studied. The mean value +/- SD obtained for HBP in normal volunteers (three cases) and in patients with mild (four cases), moderate (two cases), and severe liver damage (five cases) were 0.74 +/- 0.03 microM, 0.43 +/- 0.042 microM, 0.31 +/- 0.05 microM, and 0.20 +/- 0.05 microM, respectively. Most of the cases in which the preoperative HBP of the remnant liver was above 0.22 microM had a good postoperative course irrespective of the type of hepatectomy. On the other hand, in subjects with a remnant liver HBP of between 0.22 and 0.11 microM, postoperative severe liver dysfunction occurred in about 50% of cases. In all cases with a remnant liver HBP below 0.1 microM, the prognosis was very poor, indicating that hepatectomy should be avoided. The HBP concentration detected by the 99mTc-GSA study is a very sensitive indicator of changes in the hepatic functional reserve, and the HBP value for the functional reserve of the remnant liver is extremely useful for estimating the liver function before and after hepatectomy.
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PMID:Estimation of remnant liver function before hepatectomy by means of technetium-99m-diethylenetriamine-pentaacetic acid galactosyl human albumin. 813 65

Liver scintigraphy using 99mTc-GSA, which binds specifically to the asialoglycoprotein receptors on the surface of the hepatocytes, was performed in 41 patients with chronic liver disease (11 chronic hepatitis cases and 30 liver cirrhosis) to investigate the correlations between the images and the various liver function tests. Two liver functional indexes, HH15 for plasma clearance of 99mTc-GSA and LHL15 for liver accumulation of 99mTc-GSA, showed significant differences between the chronic hepatitis group and the decompensated liver cirrhosis group. These indexes also showed significant correlations with the liver function tests such as serum albumin level and prothrombin time. HH15 and LHL15 correlated with the per-rectal portal shunt index obtained in 10 patients by 99mTcO4- per-rectal portal scintigraphy. These results suggest that HH15 and LHL15 have value as new liver functional indexes.
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PMID:[Evaluation of clinical usefulness of 99mTc-GSA, a functional hepatic imaging agent--correlation with per-rectal portal scintigraphy]. 837 96

The use of numerical integration method (N. INT) was evaluated in determining parameters by two-compartment model analysis from liver scintigraphy. Among the 15 subjects, 14 had liver cirrhosis or chronic hepatitis, and one was normal. When using N.INT, the sum of two exponential functions on heart regression curve following intravenous injection of 99mTc-galactosyl human serum albumin (99mTc-GSA) was promptly calculated. The parameters obtained from N.INT, including transfer rate of 99mTc-GSA from extrahepatic blood to liver (k1), dissociation rate from liver to extrahepatic blood (k2), and excretion rate from liver to gallblader (k3), were significantly correlated with those obtained by the nonlinear least square method (NLS). k1/k2 was related with the maximum removal rate of 99mTc-GSA obtained from nonlinear five compartment model analysis (r2 = 0.705, n = 15) and also with the severity score of liver disease as classified by the First Department of Surgery, Mie University Medical School (r2 = 0.686, n = 13). In terms of the time required to obtain these parameters, including the blood retention rate of 99mTc-GSA at 15 min after injection (%ID15), N.INT was faster than the traditional method (NLS).
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PMID:[Fast two-compartment model analysis with 99mTc-GSA liver scintigraphy]. 872 38

We studied the hepatic functional reserve in the lobes of the liver in 28 patients with chronic liver disease and 13 controls using single photon emission computed tomography (SPECT) imaging with a radiolabeled asialoglycoprotein analog, Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (Tc-99m GSA). Counts of Tc-99m GSA radioactivity in the liver on SPECT images significantly correlated (P < .0001) with the serum albumin level (r = .612), log (serum cholinesterase activity) (r = .618), serum bilirubin level (r = .628), prothrombin time (r = .715), hepaplastin test (r = .637), and indocyanine green retention rate at 15 minutes (r = .771), making it possible to estimate the distribution of functional reserve in the liver based on counts. Using the intact hepatocyte theory, we estimated the number of viable hepatocytes based on the counts. With progression of hepatic functional degeneration, counts per unit hepatic volume decreased (rho = .779, P < .0001), and left lobe to right lobe ratio of this parameter increased (rho = .491, P = .0019) significantly. These findings suggest that the reduction of hepatic functional reserve per unit hepatic volume and numerical density of the hepatocytes, and the proliferation of fibrosis in patients with chronic liver disease is slower in the left lobe than in the right. We discuss a possible biological basis for these apparent lobar differences and for hepatic morphological changes seen in cirrhosis.
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PMID:Hepatic lobar differences in progression of chronic liver disease: correlation of asialoglycoprotein scintigraphy and hepatic functional reserve. 909 83


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