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.

scholarly journals Quantitative aspects of bilirubin metabolism for hematologists

Blood ◽  
1981 ◽  
Vol 57 (6) ◽  
pp. 983-999 ◽  
Author(s):  
NI Berlin ◽  
PD Berk
Keyword(s):  
Hemoglobin Concentration ◽  
Unconjugated Bilirubin ◽  
Cell Physiology ◽  
Mean Corpuscular Hemoglobin ◽  
Red Cell ◽  
Bilirubin Concentration ◽  
Bilirubin Metabolism ◽  
Red Cell Survival ◽  
The Mean ◽  
Kinetics Of

Abstract Techniques now available for the study of plasma disappearance kinetics of isotopically labeled unconjugated bilirubin have led to new insights into the factors that determine the plasma unconjugated bilirubin concentration (BR). This variable can be shown to depend in turn on five other parameters: the total circulating red cell volume (TRVC), the mean corpuscular hemoglobin concentration (MCHC), the mean red cell lifespan (RBCLS), plasma volume (PV), and the hepatic extraction coefficient for unconjugated bilirubin (ke). Of these, three clearly relect varying aspects of erythrokinetics and red cell physiology, while only one is reflective of liver function. It is not surprising, therefore, that knowledgeable interpretations of measurements of the plasma unconjugated bilirubin concentration can provide substantial information of value to the clinical hematologist. In particular, such interpretations can increase the sensitivity of these measurements as a screening test for the presence of hemolysis and provide the earliest indication of changes in red cell survival, as may occur during the therapy of various acquired hemolytic anemias. Furthermore, an understanding of the physiology of bilirubin in plasma substantially enhances the ability of the physician to categorize individual cases of hyperbilirubinemia as being due to hepatic dysfunction, hemolysis, or some combination of both.

scholarly journals Quantitative aspects of bilirubin metabolism for hematologists

Blood ◽  
1981 ◽  
Vol 57 (6) ◽  
pp. 983-999
Author(s):  
NI Berlin ◽  
PD Berk
Keyword(s):  
Hemoglobin Concentration ◽  
Unconjugated Bilirubin ◽  
Cell Physiology ◽  
Mean Corpuscular Hemoglobin ◽  
Red Cell ◽  
Bilirubin Concentration ◽  
Bilirubin Metabolism ◽  
Red Cell Survival ◽  
The Mean ◽  
Kinetics Of

Techniques now available for the study of plasma disappearance kinetics of isotopically labeled unconjugated bilirubin have led to new insights into the factors that determine the plasma unconjugated bilirubin concentration (BR). This variable can be shown to depend in turn on five other parameters: the total circulating red cell volume (TRVC), the mean corpuscular hemoglobin concentration (MCHC), the mean red cell lifespan (RBCLS), plasma volume (PV), and the hepatic extraction coefficient for unconjugated bilirubin (ke). Of these, three clearly relect varying aspects of erythrokinetics and red cell physiology, while only one is reflective of liver function. It is not surprising, therefore, that knowledgeable interpretations of measurements of the plasma unconjugated bilirubin concentration can provide substantial information of value to the clinical hematologist. In particular, such interpretations can increase the sensitivity of these measurements as a screening test for the presence of hemolysis and provide the earliest indication of changes in red cell survival, as may occur during the therapy of various acquired hemolytic anemias. Furthermore, an understanding of the physiology of bilirubin in plasma substantially enhances the ability of the physician to categorize individual cases of hyperbilirubinemia as being due to hepatic dysfunction, hemolysis, or some combination of both.

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.

scholarly journals Granulocyte colony-stimulating factor recruitment of CD34+ progenitors to peripheral blood: impaired mobilization in chronic granulomatous disease and adenosine deaminase--deficient severe combined immunodeficiency disease patients

Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 1104-1112 ◽  
Author(s):  
S Sekhsaria ◽  
TA Fleisher ◽  
S Vowells ◽  
M Brown ◽  
J Miller ◽  
...  
Keyword(s):  
Severe Combined Immunodeficiency ◽  
Normal Subjects ◽  
Cell Counts ◽  
Cd34 Cells ◽  
The Mean ◽  
Cell Mobilization ◽  
Immunodeficiency Disease ◽  
Severe Combined Immunodeficiency Disease ◽  
Kinetics Of ◽  
Stimulating Factor

Peripheral blood (PB) CD34+ cells mobilized by granulocyte colony- stimulating factor (G-CSF) administration are potentially useful for transplantation and as a target of gene transfer for therapy of hematopoietic disorders. Efficient harvest and planning for clinical use of PB CD34+ cells ideally requires foreknowledge of the expected mobilization kinetics and yield. We developed a sensitive flow cytometric assay for accurately enumerating CD34+ cells throughout the range seen at baseline to peak mobilization. We used this assay to assess the kinetics of G-CSF-mediated mobilization of CD34+ cells to PB in normal volunteers and in patients with chronic granulomatous disease (CGD) or adenosine deaminase (ADA)-deficient severe combined immunodeficiency disease (SCID). Two dose levels of G-CSF were examined (5 and 10 micrograms/kg/d for 7 days). Both doses were well tolerated. For normal subjects and patients an increase in PB CD34+ cells was first detected only preceding the third dose of G-CSF (day 3), peaked transiently on day 5 or 6, and then decreased thereafter despite additional doses of G-CSF. With 32 normal volunteers mean peak CD34+ cell counts were 57 and 76 cells/mm2 of blood (5 and 10 micrograms doses, respectively), whereas for 18 CGD patients the mean peaks were 31 and 40 cells/mm2 of blood. For 2 ADA-deficient SCID patients studied at a G-CSF dose of 5 micrograms/kg/d, the average peak was 16 cells/mm2 of blood. For both of these patient groups mobilization of CD34+ cells to PB was impaired compared with similarly treated normal subjects (P < .05). By contrast to the kinetics of the CD34+ cell mobilization, the absolute neutrophil count (ANC) increased markedly by 6 hours after the first dose of G-CSF and then increased steadily through day 8. At days 5 and 6 (peak mobilization of CD34+ cells) the mean ANC of CGD and ADA patients was only slightly lower ( < or = 15%) than that seen with normal subjects, whereas the difference in CD34+ cell mobilization was > 48%. Thus, ANC is not a reliable surrogate to predict peak PB CD34+ cell counts and direct enumeration of PB CD34+ counts should be undertaken in decisions regarding timing and duration of apheresis to harvest a specific number of these cells. Finally, unexpected, but significant differences in the PB CD34+ cell mobilization between normal subjects and patients with inherited disorders can occur and underscores the importance of establishing the expected mobilization of PB CD34+ cells in the planning of treatment approaches using these cells.

scholarly journals Blood kinetics and in vivo chemotaxis of transfused neutrophils: effect of colllection method, donor corticosteroid treatment, and short-term storage

Blood ◽  
1979 ◽  
Vol 54 (5) ◽  
pp. 977-986
Author(s):  
TH Price ◽  
DC Dale
Keyword(s):  
Cell Function ◽  
Cell Damage ◽  
Corticosteroid Treatment ◽  
Normal Subjects ◽  
Intermittent Flow ◽  
Short Term ◽  
Short Term Storage ◽  
Kinetics Of ◽  
Term Storage

To evaluate effect of collection technique and short-term storage on in vivo cell function, neutrophils were collected from 53 normal subjects by phlebotomy (PB), intermittent flow centrifugation (IFC), or filtration leukopheresis (FL), stored 0 or 1 day, labeled with 32P- diisopropylfluorophosphate, reinfused into the donor, and blood kinetics and/or skin chamber accumulation of labeled cells measured. The blood kinetics of unstored PB and IFC cells were similar; the kinetics of unstored FL cells were markedly abnormal. The percent of infused neutrophils localizing to the skin chamber was 0.1, 0.06, and 0.006 for unstored PB, IFC, and FL cells, respectively. One-day storage substantially decreased chamber accumulation of infused neutrophils. Donor steroid pretreatment had no effect on chamber results. Thus, in vivo chemotactic ability of IFC neutrophils is slightly impaired, whereas that of FL cells is severely impaired. One-day storage of either cell concentrate causes further cell damage.

Kinetics of gas exchange and ventilation in transitions from rest or prior exercise

1977 ◽  
Vol 43 (4) ◽  
pp. 704-708 ◽  
Author(s):  
L. B. Diamond ◽  
R. Casaburi ◽  
K. Wasserman ◽  
B. J. Whipp
Keyword(s):  
Normal Subjects ◽  
Cycle Ergometer ◽  
Work Rate ◽  
Prior Exercise ◽  
Exercise Hyperpnea ◽  
The Mean ◽  
Highly Correlated ◽  
Co2 Flow ◽  
Kinetics Of ◽  
High Work

Seven normal subjects each performed three transitions to a subanaerobic threshold work rate on a cycle ergometer: 1) from rest, 2) from a low work rate (both at 60 rpm), and 3) from a low work rate at 40 rpm to the high work rate at 80 rpm. Oxygen uptake (VO2), carbon dioxide output (VCO2), and ventilation (VE) were computed breath-by-breath and response kinetics extracted. The mean half-times of VO2, VCO2, and VE were 32, 44, and 49 s, respectively, and were not appreciably affected by the prior exercise or by variation of pedal rate. The kinetics of VE was highly correlated with VCO2 (r = 0.94), with VCO2 leading VE, providing further description of the relation of the exercise hyperpnea to CO2 flow to the lungs.

Effect of sodium-restricted diet and posture on norepinephrine kinetics in humans

1988 ◽  
Vol 254 (2) ◽  
pp. E222-E230 ◽  
Author(s):  
O. A. Linares ◽  
L. A. Zech ◽  
J. A. Jacquez ◽  
S. G. Rosen ◽  
J. A. Sanfield ◽  
...  
Keyword(s):  
Compartmental Analysis ◽  
Volume Of Distribution ◽  
Plasma Norepinephrine ◽  
Metabolic Clearance ◽  
Upright Posture ◽  
Norepinephrine Concentration ◽  
The Mean ◽  
Young Subjects ◽  
Kinetics Of ◽  
Vascular Compartment

We used compartmental analysis to analyze the kinetics of distribution and metabolism of norepinephrine (NE) and to determine whether the increase in plasma norepinephrine concentration (PNE) during sodium restriction in humans is due to sympathetic nervous system (SNS) activation. [3H]-NE infusion and postinfusion decay were measured in young subjects in the supine position and during 60 min of standing during normal sodium (NS) diet and after 7 days of 10 meq/day sodium-restricted (SR) diet. The mean supine PNE was greater during SR diet compared with NS diet (154 +/- 9 vs. 185 +/- 12 pg/ml, P = 0.02, n = 10). During both NS and SR diets, upright PNE increased (163 +/- 4 vs. 359 +/- 38 pg/ml and 182 +/- 8 vs. 401 +/- 26 pg/ml, respectively, multivariate one-way analysis of variance, P less than 0.001, alpha = 0.05). The increases of PNE with both SR diet and upright posture were accompanied by a fall in NE metabolic clearance rate (MCR1). During SR diet this was due to a fall in the volume of distribution of NE (6.1 +/- 0.4 vs. 5.0 +/- 0.4 liters, P = 0.003, n = 10). In contrast to the effect of upright posture to increase NE release into the extra-vascular compartment (NE2), during SR diet there was no change in NE2 (1.63 +/- 0.09 vs. 1.62 +/- 0.1 micrograms.min-1.m-2, P = 0.97, n = 10). Thus the increase in PNE during SR diet in humans can be explained by a fall in the volume of distribution of NE, resulting in a decrease in MCR1.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased endothelin-1 production in patients with chronic heart failure

2004 ◽  
Vol 286 (3) ◽  
pp. H1141-H1145 ◽  
Author(s):  
John D. Parker ◽  
Jake J. Thiessen
Keyword(s):  
Heart Failure ◽  
Compartment Model ◽  
Normal Subjects ◽  
Volume Of Distribution ◽  
Endothelin 1 ◽  
Normal Individuals ◽  
Three Compartment Model ◽  
Total Body ◽  
Body Production ◽  
Kinetics Of

Endothelin-1 (ET-1) concentrations are elevated in patients with congestive heart failure (CHF), although the cause of this increase remains uncertain. We hypothesized that abnormalities in ET-1 production, clearance, or a combination of these may be the cause of elevated ET-1 concentrations in chronic CHF. The kinetics of clearance of ET-1 were measured with 125I-labeled ET-1 in eight patients with CHF and five age-matched normal individuals. In both normal subjects and the CHF group, the kinetics of ET-1 clearance were best described by a three-compartment model. The steady-state volume of distribution of ET-1 was significantly greater in the CHF group compared with normal subjects (25.2 ± 3.9 vs. 13.8 ± 2.1 l/kg; P < 0.05). The total clearance rate from plasma was greater in the CHF group (0.119 ± 0.018 vs. 0.047 ± 0.013 l·kg–1·min–1; P = 0.05). The total body production rate of ET-1 was also significantly higher in patients with CHF (0.21 ± 0.03. vs. 0.06 ± 0.02 ng·kg–1·min–1; P < 0.05). It appears that increased ET-1 production rather than decreased clearance is the cause of elevated ET-1 concentrations in patients with chronic CHF.

scholarly journals Granulocyte colony-stimulating factor recruitment of CD34+ progenitors to peripheral blood: impaired mobilization in chronic granulomatous disease and adenosine deaminase--deficient severe combined immunodeficiency disease patients

Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 1104-1112 ◽  
Author(s):  
S Sekhsaria ◽  
TA Fleisher ◽  
S Vowells ◽  
M Brown ◽  
J Miller ◽  
...  
Keyword(s):  
Severe Combined Immunodeficiency ◽  
Normal Subjects ◽  
Cell Counts ◽  
Cd34 Cells ◽  
The Mean ◽  
Cell Mobilization ◽  
Immunodeficiency Disease ◽  
Severe Combined Immunodeficiency Disease ◽  
Kinetics Of ◽  
Stimulating Factor

Abstract Peripheral blood (PB) CD34+ cells mobilized by granulocyte colony- stimulating factor (G-CSF) administration are potentially useful for transplantation and as a target of gene transfer for therapy of hematopoietic disorders. Efficient harvest and planning for clinical use of PB CD34+ cells ideally requires foreknowledge of the expected mobilization kinetics and yield. We developed a sensitive flow cytometric assay for accurately enumerating CD34+ cells throughout the range seen at baseline to peak mobilization. We used this assay to assess the kinetics of G-CSF-mediated mobilization of CD34+ cells to PB in normal volunteers and in patients with chronic granulomatous disease (CGD) or adenosine deaminase (ADA)-deficient severe combined immunodeficiency disease (SCID). Two dose levels of G-CSF were examined (5 and 10 micrograms/kg/d for 7 days). Both doses were well tolerated. For normal subjects and patients an increase in PB CD34+ cells was first detected only preceding the third dose of G-CSF (day 3), peaked transiently on day 5 or 6, and then decreased thereafter despite additional doses of G-CSF. With 32 normal volunteers mean peak CD34+ cell counts were 57 and 76 cells/mm2 of blood (5 and 10 micrograms doses, respectively), whereas for 18 CGD patients the mean peaks were 31 and 40 cells/mm2 of blood. For 2 ADA-deficient SCID patients studied at a G-CSF dose of 5 micrograms/kg/d, the average peak was 16 cells/mm2 of blood. For both of these patient groups mobilization of CD34+ cells to PB was impaired compared with similarly treated normal subjects (P < .05). By contrast to the kinetics of the CD34+ cell mobilization, the absolute neutrophil count (ANC) increased markedly by 6 hours after the first dose of G-CSF and then increased steadily through day 8. At days 5 and 6 (peak mobilization of CD34+ cells) the mean ANC of CGD and ADA patients was only slightly lower ( < or = 15%) than that seen with normal subjects, whereas the difference in CD34+ cell mobilization was > 48%. Thus, ANC is not a reliable surrogate to predict peak PB CD34+ cell counts and direct enumeration of PB CD34+ counts should be undertaken in decisions regarding timing and duration of apheresis to harvest a specific number of these cells. Finally, unexpected, but significant differences in the PB CD34+ cell mobilization between normal subjects and patients with inherited disorders can occur and underscores the importance of establishing the expected mobilization of PB CD34+ cells in the planning of treatment approaches using these cells.

Origin and disposal of 1,5-anhydroglucitol, a major polyol in the human body

1992 ◽  
Vol 263 (2) ◽  
pp. E268-E273 ◽  
Author(s):  
T. Yamanouchi ◽  
Y. Tachibana ◽  
H. Akanuma ◽  
S. Minoda ◽  
T. Shinohara ◽  
...  
Keyword(s):  
Human Body ◽  
De Novo ◽  
Normal Subjects ◽  
The Body ◽  
Diabetic Patients ◽  
Food Ingestion ◽  
De Novo Synthesis ◽  
The Mean ◽  
Kinetics Of ◽  
Oral Supplement

The origin and disposal of 1,5-anhydro-D-glucitol (AG), one of the main polyols found in the human body, was studied in normal subjects and diabetic patients. AG was detected in various kinds of foods. The mean AG supplement through foods was estimated to be approximately 4.38 mg/day, which was compatible with that calculated in a food analysis (average 0.22 mg AG/100 kcal in Japanese foods) on eight healthy subjects. The mean AG excretion in urine was approximately 4.76 mg/day in these subjects. Excretion into stools was negligible. From observations on the patients without oral supplement of AG, 0.4 mg of daily de novo synthesis of AG was strongly suggested. It was also implied that urinary AG excretion occurred soon after food ingestion and that its amount was closely correlated with daily supplement through foods. Thus the fundamental kinetics of AG were recognized as follows: 1) AG in the body originates mainly from foods and is well absorbed in the intestine, 2) AG is little degraded and metabolized in the body, and 3) an equilibrium exists between oral supplement plus a small but steady amount of de novo synthesis and excretion in urine.

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