An Evaluation of Bilirubin Kinetics with Respect to the Diagnosis of Gilbert's Syndrome

1978 ◽  
Vol 54 (5) ◽  
pp. 539-547
Author(s):  
L. Okolicsanyi ◽  
O. Ghidini ◽  
R. Orlando ◽  
S. Cortelazzo ◽  
G. Benedetti ◽  
...  
Keyword(s):  
Storage Capacity ◽  
Hepatic Clearance ◽  
Normal Subjects ◽  
Tolerance Test ◽  
Gilbert’S Syndrome ◽  
Transfer Rates ◽  
Essentially Normal ◽  
Gilbert's Syndrome ◽  
Relative Storage Capacity ◽  
Kinetics Of

1. The kinetics of the plasma disappearance of bilirubin (2 mg/kg intravenously) were studied in 106 patients with Gilbert's syndrome and in 13 normal subjects. 2. All patients had significant decreases in hepatic bilirubin clearance and transfer rates from plasma to liver, resulting in increased values for plasma retention at 4 h. The calculated value for unconjugated bilirubin production was normal in 40% of patients and increased in the remainder. 3. In 29 of the Gilbert's patients their bromosulphthalein kinetics were studied 1 week before the bilirubin test. These results were essentially normal and it was concluded that the hepatic clearance mechanisms for bilirubin and bromosulphthalein are different. 4. In 10 patients the bilirubin transport maximum (Tm) was found to be low whereas the relative storage capacity (S) was normal. Phenobarbitone treatment in four patients resulted in an increase in Tm, and S decreased in two patients and remained unchanged in the other two. 5. These results support the hypothesis that there are several variants of Gilbert's syndrome and that the bilirubin tolerance test is a useful diagnostic test.

A modeling study of the effect of fasting on bilirubin kinetics in Gilbert's syndrome

1981 ◽  
Vol 240 (5) ◽  
pp. R266-R271
Author(s):  
L. Okolicsanyi ◽  
R. Orlando ◽  
M. Venuti ◽  
G. Dal Brun ◽  
C. Cobelli ◽  
...  
Keyword(s):  
Parameter Estimation ◽  
Maximum Likelihood ◽  
Kinetic Studies ◽  
Compartment Model ◽  
Tolerance Test ◽  
Estimation Technique ◽  
Gilbert’S Syndrome ◽  
Gilbert's Syndrome ◽  
Two Compartment Model ◽  
Parameter Values

The mechanism of fasting hyperbilirubinemia (FH) is not fully understood. We investigated basal bilirubin kinetics in 20 Gilbert's patients and in 7 healthy volunteers. The study was repeated in seven of these Gilbert's patients after 48-h fasting. A two-compartment model proved to be adequate for interpreting crystalline bilirubin kinetics in these individuals. The parameters of bilirubin kinetics were estimated by employing a maximum likelihood parameter estimation technique. Consistency of the model and uniqueness of the estimated parameter values (from the covariance matrix) were shown. Our results confirmed previous observations regarding impaired bilirubin kinetics in Gilbert's patients as compared to controls. The main results obtained from kinetic studies in Gilbert's patients after fasting were i) no modification in the bilirubin clearance, and ii) a more than twice increase of bilirubin turnover. These data indicate that FH is related to an increased bilirubin production (mainly intrahepatic). Furthermore, evidence arises from this study that the bilirubin tolerance test is a useful diagnostic test for Gilbert's syndrome.

Doxorubicin Dosage Guidelines in a Patient with Hyperbilirubinemia of Gilbert's Syndrome

1998 ◽  
Vol 32 (10) ◽  
pp. 1026-1029 ◽  
Author(s):  
Melanie Johns Cupp ◽  
Gerald M Higa
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Hepatic Clearance ◽  
Large Cell ◽  
Conclusive Evidence ◽  
Hodgkin's Lymphoma ◽  
Gilbert’S Syndrome ◽  
Medline Search ◽  
Gilbert's Syndrome ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

OBJECTIVE: To reconcile dosage modification guidelines for doxorubicin in a patient with hyperbilirubinemia of Gilbert's syndrome (GS). CASE SUMMARY: A 62-year-old white man with concurrent diagnoses of large-cell non-Hodgkin's lymphoma and GS was treated with standard doses of a doxorubicin-containing chemotherapy regimen. No increase of end-organ toxicity was observed during four treatment cycles. DISCUSSION: The relative prevalence of GS coupled with the rising incidence of non-Hodgkin's lymphoma increases the probability that both disorders will be present in the same individual. A MEDLINE search (1966 through July 1997) revealed little, and often conflicting, information pertaining to drug metabolism and disposition in GS. In addition, no information has been reported regarding the metabolic fate of doxorubicin in these patients. It is important to emphasize that the lack of enhanced extramedullary toxicity in this patient is not conclusive evidence that the hepatic abnormality of GS had no effect on doxorubicin metabolism. CONCLUSIONS: Based on information regarding mechanisms for hepatic clearance, dosage modification of doxorubicin may not be necessary in hyperbilirubinemia of GS.

Definition of a Conjugation Dysfunction in Gilbert's Syndrome: Studies of the Handling of Bilirubin Loads and of the Pattern of Bilirubin Conjugates Secreted in Bile

1978 ◽  
Vol 55 (1) ◽  
pp. 63-71 ◽  
Author(s):  
C. A. Goresky ◽  
Ellen R. Gordon ◽  
E. A. Shaffer ◽  
P. Paré ◽  
D. Carassavas ◽  
...  
Keyword(s):  
Caloric Intake ◽  
Normal Subjects ◽  
Hepatic Uptake ◽  
Gilbert’S Syndrome ◽  
Pigment Pattern ◽  
Gilbert's Syndrome ◽  
Plasma Bilirubin ◽  
Average Proportion ◽  
Conjugation Process ◽  
Biliary Pigment

1. Intravenous doses of bilirubin (3.4 μmol/kg) were given to normal subjects and patients with Gilbert's syndrome. Both groups displayed an identical initial disappearance of a substantial proportion of the bilirubin but, late in time, the Gilbert's patients exhibited reduced clearance with a sustained elevation of the plasma bilirubin and no reflux into the plasma space of conjugated bilirubin. Increasing the dose in normal subjects (by factors of 3 and 6) failed to reproduce the response found in the Gilbert's patients. 2. In the bile-containing duodenal aspirates of Gilbert's patients the average proportion of bilirubin found as bilirubin diglucuronide was 68% (normal 88%) and of bilirubin monoglucuronide, 23% (normal 7%). Both differences were significant at the P < 0.001 level. In the Gilbert's patients restriction of caloric intake to 1569 kJ/day for 2 days characteristically raised the serum bilirubin with no modification of the biliary pigment pattern; phenobarbital (180 mg/day for 2 weeks) decreased the plasma bilirubin to the normal range with, concomitantly, a reversion of the biliary pigment pattern towards normal. 3. We conclude that there is no hepatic uptake defect in Gilbert's syndrome but that there is decreased activity in the conjugation process underlying the addition of the second glucuronic acid moiety to bilirubin, to form bilirubin diglucuronide.

Effect of Phenobarbitone on Plasma [14C]Bilirubin Clearance in Patients with Unconjugated Hyperbilirubinaemia

1974 ◽  
Vol 46 (1) ◽  
pp. 1-17 ◽  
Author(s):  
M. Black ◽  
J. Fevery ◽  
D. Parker ◽  
J. Jacobson ◽  
Barbara H. Billing ◽  
...  
Keyword(s):  
Plasma Clearance ◽  
Normal Subjects ◽  
Transferase Activity ◽  
Bilirubin Concentration ◽  
Gilbert’S Syndrome ◽  
Glucuronyl Transferase ◽  
Tracer Dose ◽  
Gilbert's Syndrome ◽  
Plasma Bilirubin ◽  
Relative Deficiency

1. The clearance of a tracer dose of [14C]bilirubin from the plasma was studied in patients with Gilbert's syndrome, congenital non-haemolytic jaundice, haemolytic jaundice and in normal subjects. Clearance was significantly impaired in the patients with Gilbert's syndrome and in those with congenital non-haemolytic jaundice when compared with the normal subjects, and was normal in the patient with haemolytic jaundice. 2. Treatment for 2 weeks with phenobarbitone (180 mg/day) lowered the plasma bilirubin concentration and improved all indices of plasma clearance of the isotope in patients with Gilbert's syndrome, so that they became indistinguishable from those of normal subjects. The improvement in plasma [14C]bilirubin clearance in these patients was associated with modest increases in hepatic bilirubin glucuronyl transferase in some subjects. 3. Phenobarbitone treatment improved plasma bilirubin concentrations and plasma [14C]bilirubin clearance in patients with congenital non-haemolytic jaundice, so that they resembled those seen in patients with untreated Gilbert's syndrome. Despite this improvement hepatic bilirubin glucuronyl transferase activity remained undetectable. 4. These results are compatible with the hypothesis that Gilbert's syndrome is a manifestation of a relative deficiency of hepatic bilirubin glucuronyl transferase, and differs from congenital non-haemolytic jaundice only in severity.

Studies on the Kinetics of Unconjugated [14C]Bilirubin Metabolism in Normal Subjects and Patients with Compensated Cirrhosis

1977 ◽  
Vol 52 (6) ◽  
pp. 555-570
Author(s):  
D. Owens ◽  
E. A. Jones ◽  
E. R. Carson
Keyword(s):  
Cell Function ◽  
Hepatic Clearance ◽  
Normal Subjects ◽  
Volume Of Distribution ◽  
Unconjugated Bilirubin ◽  
Group Of Seven ◽  
Compensated Cirrhosis ◽  
Bilirubin Metabolism ◽  
The Mean ◽  
Kinetics Of

1. The kinetics of unconjugated [14C]-bilirubin metabolism have been investigated and analysed in terms of a three-pool model in a group of seven normal subjects and in a group of eight cirrhotic patients who had appreciable impairment of liver cell function. 2. In the patients with cirrhosis, the plasma unconjugated bilirubin was either normal or only slightly increased but the metabolism of unconjugated bilirubin was deranged. 3. The mean volume of distribution, the mean 4 h retention, and the mean mass of the rapidly mixing pool were all significantly greater than in the normal subjects. In contrast, mean fractional clearance rate and mean estimated erythrocyte life-span were significantly less than in the normal subjects. 4. The mean fractional transfer rates and fluxes from pool 1 (rapidly mixing pool—‘plasma’) to pool 3 (‘extravascular’) and vice versa were significantly greater than the corresponding values in the normal subjects. 5. The results indicate that, in patients with compensated cirrhosis, the efficiency of the liver in extracting unconjugated bilirubin from plasma against a concentration gradient is impaired, even though the liver's capacity to conjugate bilirubin may be normal. As a consequence of the increased volume of distribution, the absolute hepatic clearance of unconjugated bilirubin is relatively well maintained.

Effect of Clofibrate on the Metabolism of Bilirubin, Bromosulphophthalein and Indocyanine Green and on the Biliary Lipid Composition in Gilbert's Syndrome

1984 ◽  
Vol 66 (4) ◽  
pp. 389-397 ◽  
Author(s):  
Klaus Kutz ◽  
Harald Kandler ◽  
Roland Gugler ◽  
Johan Fevery
Keyword(s):  
Indocyanine Green ◽  
Biliary Secretion ◽  
Total Serum ◽  
Hepatic Transport ◽  
Gilbert’S Syndrome ◽  
Gilbert's Syndrome ◽  
Initial Plasma ◽  
Relative Storage Capacity ◽  
Biliary Lipid Composition ◽  
Metabolism Of Bilirubin

1. Clofibrate (20 mg day−1 kg−1 body weight) given orally for 2 weeks to 18 subjects with Gilbert's syndrome reduced the total serum bilirubin concentration from 44.4 (22.1–71.7) μmol/l (median, range) to 15.0 (7.9–28.9) μmol/l, mainly by decreasing the ‘indirect’ fraction to 34.5% of pretreatment values. 2. In contrast to treatment with phenobarbitone, clofibrate did not change the ratio of bilirubin mono- to di-conjugates in bile. 3. The initial plasma disappearance rate of indocyanine green and of bromosulphophthalein did not show consistent changes during clofibrate treatment but the ‘apparent’ maximal biliary secretion capacity of bromosulphophthalein (Tm) decreased in most of the patients studied, whereas the relative storage capacity (S) tended to increase. 4. As expected, the cholesterol saturation of bile increased in all subjects. 5. These results suggest that clofibrate increases mainly the glucuronidation of bilirubin, promoting as such the overall hepatic transport in Gilbert's syndrome. However, it decreases the maximal biliary secretion of bromosulphophthalein, possibly by an increased hepatic retention. These phenomena might be linked to the augmented content of Z protein in the liver.

Description of a Simple Model for the Study of Bone Calcium Metabolism

1980 ◽  
Vol 19 (01) ◽  
pp. 11-15
Author(s):  
G. Roncari ◽  
L. Rapisardi ◽  
L. Conte ◽  
G. Pedroli
Keyword(s):  
Simple Model ◽  
Calcium Metabolism ◽  
Good Description ◽  
Radioactive Tracer ◽  
Normal Subjects ◽  
Bone Diseases ◽  
Compartment System ◽  
Bone Calcium ◽  
Finite Period ◽  
Kinetics Of

A simple model for the study of bone calcium metabolism is proposed. It describes the kinetics of a radioactive tracer in terms of an open single compartment system with an expanding volume for a finite period of time. In addition to the simplicity of the hypotheses introduced, the model is able to give a good description of the biological processes which regulate calcium kinetics. Moreover the functional parameters can be easily calculated, even just graphically. 15 normal subjects and 22 patients affected by various bone diseases were studied. The results were compared with those obtained by using the model proposed by Burkinshaw et al. and the method described by Reeve et al.

Abnormal Platelet Serotonin Uptake and Binding Sites in Myeloproliferative Disorders

1984 ◽  
Vol 51 (03) ◽  
pp. 349-353 ◽  
Author(s):  
C Caranobe ◽  
P Sié ◽  
F Fernandez ◽  
J Pris ◽  
S Moatti ◽  
...  
Keyword(s):  
Binding Sites ◽  
High Capacity ◽  
Specific Inhibitor ◽  
Myeloproliferative Disorders ◽  
Normal Subjects ◽  
Binding Data ◽  
Full Explanation ◽  
Number Of Binding Sites ◽  
5 Ht Uptake ◽  
Kinetics Of

SummaryA simultaneous investigation of the kinetics of serotonin (5 HT) uptake and of binding sites was carried out in the platelets of normal subjects and of 10 patients affected with various types of myeloproliferative disorders (MD). The 5 HT uptake was analysed according to the Lineweaver-Burk and the Eadie-Hofstee methods. With the two methods, the patient’s platelets exhibited a dramatic reduction of the Vi max and of the Km; in some patients the Eadie-Hofstee analysis revealed that a passive diffusion phenomenon is superimposed on the active 5 HT uptake at least for the higher concentration used. The binding data were analysed with the Scatchard method. Two classes of binding sites (high affinity - low capacity, low affinity - high capacity) were found in normal subjects and patients. Pharmacological studies with imipramine, a specific inhibitor of 5 HT uptake, suggested that both the sites are involved in 5 HT uptake. The number of both binding sites was significantly decreased in patient’s platelets while the affinity constants of these binding sites were not significantly reduced in comparison with those of the control subjects. No correlations were found between Vi max, Km and the number of binding sites. These results suggest that a reduction in the number of platelet membrane acceptors for 5 HT commonly occurs in myeloproliferative disorders but does not provide a full explanation of the uptake defect.

A familial Mediterranean fever girl due to MEFV N679H mutation with Gilbert’s syndrome

2021 ◽  
Author(s):  
Yuki Fujimaki ◽  
Takehiko Soutome ◽  
Takayuki Tanaka ◽  
Takeshi Shiba ◽  
Misa Watanabe
Keyword(s):  
Familial Mediterranean Fever ◽  
Gilbert’S Syndrome ◽  
Gilbert's Syndrome ◽  
Mediterranean Fever

KINETICS OF INSULIN DISAPPEARANCE FROM PLASMA IN CORTISONE-TREATED NORMAL SUBJECTS

1987 ◽  
Vol 26 (5) ◽  
pp. 623-628 ◽  
Author(s):  
K. ELLEMANN ◽  
B. THORSTEINSSON ◽  
S. FUGLEBERG ◽  
B. FELDT-RASMUSSEN ◽  
O. O. ANDERSEN ◽  
...  
Keyword(s):  
Normal Subjects ◽  
Kinetics Of
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