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Y Horsmans

Publications and source records attributed to Y Horsmans.

At least 37 records · Page 2Linked to original sources

Expression of presumed specific early and late factors associated with liver regeneration in different rat surgical models.

Experiments performed on the portal branch ligation (PBL) model indicate that early changes observed after surgery are not related to the regenerative process because they also occur in atrophying lobes. To further confirm the lack of specificity of the early events and to exclude the influence of circulatory factors released by proliferating lobes on their occurrence, we investigated this response after sham operation (SO) and portacaval shunt (PCS), a model characterized by liver atrophy. We also attempted to determine expression of later events associated specifically with regeneration, ie, expression of p53 or c-Ha-ras, or inhibition of proliferation, ie, interleukin-1beta (IL-1beta) and transforming growth factor-beta1 (TGF-beta1) after partial (PH) and temporary partial (TPH) hepatectomy, SO and PCS. Nuclear factor-kappaB (NF-kappaB) and signal transducer and activator of transcription 3 (STAT3) DNA binding were assessed by electrophoretic mobility shift assay (EMSA), interleukin-6 (IL-6) mRNA by reverse transcription-polymerase chain reaction (RT-PCR), c-myc and c-jun mRNAs by Northern blot analysis at 0.5 and 2 hours, p53 and c-Ha-ras mRNAs by Northern blot analysis at 8 and 24 hours, and IL-1beta and TGF-beta1 by RT-PCR at 24 hours. The early response including an increase of NF-kappaB, STAT3, IL-6, and immediate-early genes expression was present after PH, PCS, and SO. In SO, slight differences were observed in comparison with PH: no NF-kappaB p65/p50 DNA binding was observed, only three of six SO rats were positive for IL-6, and immediate-early genes induction showed differences in the intensity of the response. At later times, p53 mRNA increased at 8 hours after PH and TPH, c-Ha-ras mRNA at 24 hours after PH, and IL-1beta mRNA at 24 hours after PCS. Early events are not specifically associated with the reduction of liver mass or with the regenerative process, are not predictive of future cell fate, and are most likely related to surgical stress. p53 and c-Ha-ras induction is closely associated with cell cycle progression whereas IL-1beta, but not TGF-beta1, appears to be one of the negative growth regulators that might play an important role in atrophy.

Animals↗

Therapeutic drug monitoring of azathioprine and 6-mercaptopurine metabolites in Crohn disease.

BACKGROUND: 6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) have proven efficacy in the treatment of Crohn disease (CD). The immunosuppressive properties of AZA/6-MP are mediated by the intracellular metabolism of 6-MP into its active metabolites, 6-thioguanine nucleotides (6TGN) and 6methylmercaptopurine (6-MMP). Preliminary studies have suggested that the red blood cell concentration of 6TGN (RBC 6TGN) is a potential guide to therapy. The aims of the study were to evaluate the RBC 6TGN concentrations in adult patients with CD under long-term AZA/6-MP therapy and to correlate it with response to treatment and haematological parameters. METHODS: Twenty-eight CD patients treated for at least 3 months with AZA/6-MP were prospectively studied. Patients were separated into three main groups: group 1 (n = 19), corresponding to quiescent CD receiving AZA (dose: 2.05 +/- 0.4 mg/kg/day for a mean of 28.6 +/- 25 months) or 6-MP (dose: 1.4 +/- 01 mg/kg/day for a mean of 7.5 +/- 3.5 months) alone; group 2 (n = 6), corresponding to quiescent CD treated by AZA (dose: 2.14 +/- 0.5 mg/kg/day for a mean of 29.5 +/- 22 months) with oral steroids; and group 3 (n = 3), corresponding to active CD on AZA (dose: 1.94 +/- 0.6 mg/kg/day for a mean of 31.3 +/- 35 months) as the only treatment. An assessment was also made by merging groups 1 and 2 forming a larger group of patients (n = 25) defined by clinical remission and groups 2 and 3 forming a larger group of patients (n = 9), non-complete responders with AZA/6-MP alone. Crohn disease index activity (CDAI), blood samples for full blood count and differential white cell count and measurement of RBC 6TGN and 6-MMP concentrations were evaluated at inclusion and at 6 months (n = 17). RBC 6TGN were measured using high performance liquid chromatography (HPLC) on heparinized blood. RESULTS: The baseline characteristics of the three groups of patients were similar. There was no significant difference among the three groups of patients regarding the dose and the duration of immunosuppressive treatment. There was no significant difference between groups according to various parameters tested. Particularly, the median RBC 6TGN concentration at inclusion was similar in the three groups of patients (166 (105-688), 183 (90-261) and 160 (52-194) pmol/8 x 10(8) RBC, respectively). The majority of patients had no detectable level of 6-MMP metabolite, except for 3 patients. There was also no difference between merging groups. Furthermore, there was no significant correlation between RBC 6TGN concentrations and the various biological parameters tested except for the mean erythrocyte volume. At 6 months, all patients of group 1 remained in remission and median RBC 6TGN concentration remained stable. No side effects were observed. CONCLUSIONS: There is, contrary to preliminary studies, a broad overlap in RBC 6TGN levels as well as for haematological parameters in patients in remission or not and responders or not to AZA/6-MP therapy. This suggests, beside a variability in the metabolism of these drugs, the existence of complex mechanisms of action. Nevertheless, beside the use of RBC 6TGN determination to confirm compliance to therapy, this dosage could be useful in non-responding patients, allowing, in absence of leukopenia, to increase the dose of AZA/6-MP safely.

Adult↗

Intravenous omeprazole in critically ill patients: a randomized, crossover study comparing 40 with 80 mg plus 8 mg/hour on intragastric pH.

OBJECTIVE: To compare intravenous omeprazole 40-mg single dose with 8 mg/hr after an 80-mg bolus injection on 24-hr intragastric pH in intensive care unit (ICU) ventilated patients. DESIGN: Prospective, randomized crossover study. SETTING: A 42-bed medicosurgical ICU in a university hospital PATIENTS: Medicosurgical ventilated patients at risk of gastrointestinal bleeding. INTERVENTIONS: After baseline determination of intragastric pH, patients were randomly allocated to have a 40-mg iv omeprazole bolus injection (arm I) or 80 mg bolus, followed by 8 mg/hr continuous infusion for 24 hrs (arm II). After a 24-hr washout period, the opposite regimen was given in a crossover design. Intragastric pH was determined at regular intervals during the treatment period. RESULTS: In ten patients completing the protocol, the intragastric pH was similar for the two regimens for the first 12 hrs. The area under the pH curve was 5.51 +/- 0.48 for arm I compared with 6.02 +/- 0.33 for arm II (NS). Time to reach a pH of 4 or 6 was not significantly different for the two regimens. Time spent with a pH greater than 4 and 6 for the first 12 hrs was 10.11 +/- 1.14 and 8.31 +/- 1.16 hrs vs. 10.11 +/- 0.75 and 7.43 +/- 1.19 hrs for arm I and arm II, respectively (NS). When the first 24 hrs are considered, the area under the pH curve was 5.17 +/- 0.49 for arm I vs. 6.36 +/- 0.25 for arm II (p <.05). Time spent with a pH greater than 4 and 6 was 17.2 +/- 2.4 hrs and 12.63 +/- 2.22 vs. 23 +/- 0.41 and 19.48 +/- 1.63 in arm I and arm II, respectively (p <.05 and.01). An intragastric pH above 6 for all determinations was only observed in arm II. CONCLUSIONS: In critically ill patients, intravenous omeprazole 40 mg single dose is as effective as 8 mg/hr after an 80-mg bolus injection on mean intragastric pH, time spent with a pH greater than 4 and 6, but only for the first 12 hrs. If an intragastric pH greater than 6 has to be maintained for 24 hrs in all patients, an 80-mg bolus followed by 8 mg/hr iv omeprazole is to be given. Our data suggest that in several critically ill patients, a single 40-mg iv omeprazole bolus injection may be able to achieve stress ulcer prophylaxis and that 40 mg twice daily should be compared with 8 mg/hr after an 80-mg bolus injection in bleeding ulcers.

Adult↗

After portal branch ligation in the rat, cellular proliferation is associated with selective induction of c-Ha-ras, p53, cyclin E, and Cdk2.

BACKGROUND: In liver regeneration after portal branch ligation we previously showed that early cellular changes are observed in both the proliferating and atrophying liver lobes. They are therefore not indicative of future proliferative response. In this study we attempted to define precisely, in the same model, the time at which the cellular processes diverge between the lobes by measuring various parameters associated with cellular proliferation. We also investigated the possible role of inhibitors of cell proliferation in the absence of progression towards the S phase in the atrophying lobes. AIMS: Expression of p53, c-Ha-ras, cyclin E, cyclin dependent kinase (Cdk2), transforming growth factor (TGF)-beta, and interleukin (IL)-1alpha and IL-1beta were assessed in relation to their potential role in proliferating and atrophying cellular phenomenons. METHODS: Immunohistochemistry, northern blotting, western blotting, and reverse transcription-polymerase chain reaction were performed, mainly at time points corresponding to mid-G1/S phase progression (8-24 hours after surgery). RESULTS: The common and thus most likely non-specific response was still evident 5-8 hours after surgery and included an increase in IL-1 mRNA as well as p53 and cyclin E proteins. From 12 hours onwards, p53, c-Ha-ras, cyclin E, and Cdk2 were selectively induced in proliferating lobes whereas IL-1beta was predominantly activated in atrophying lobes. No changes in TGF-beta or IL-1alpha expression were observed at the same time points in any of the liver lobes. CONCLUSIONS: The initial response to portal branch ligation and thus probably to partial hepatectomy seems to be non-specific for at least eight hours. Thereafter, p53, c-Ha-ras, cyclin E, and Cdk2 seem to drive cellular proliferation while IL-1beta is associated with cellular atrophy. In contrast, TGF-beta and IL-1alpha do not seem to play a role in determining the commitment of cells towards atrophy or proliferation.

Animals↗

Hepatic perfusion parameters in chronic liver disease: dynamic CT measurements correlated with disease severity.

OBJECTIVE: The aim of our study was to determine if hepatic perfusion parameters measured with CT change in relation to disease severity in patients with chronic liver disease. SUBJECTS AND METHODS: Dynamic contrast-enhanced single-section CT scans of the liver were obtained in 40 individuals who included six control subjects, 16 patients with noncirrhotic chronic liver disease, and 18 patients with cirrhosis. Hepatic, aortic, and portal venous time-density curves were fitted to a dual-input one-compartment model to calculate the liver perfusion, arterial fraction, distribution volume, and mean transit time. RESULTS: Liver perfusion decreased in patients with cirrhosis (67 +/- 23 mL. min(-1). 100 mL(-1) versus 108 +/- 34 mL. min(-1). 100 mL(-1) in control subjects [p = 0.009] and 98 +/- 36 mL. min(-1). 100 mL(-1) in patients with noncirrhotic chronic liver disease [p = 0.003]), and the arterial fraction and the mean transit time increased (41 +/- 27% and 51 +/- 79 sec versus 17 +/- 16% and 16 +/- 5 sec in control subjects, and 19 +/- 6% and 17 +/- 8 sec in patients with noncirrhotic chronic liver disease [p < 0.05]). A significant correlation was seen between these three perfusion parameters and the severity of chronic liver disease based on clinical and biologic data (p < 0.001). No significant change in distribution volume was observed. CONCLUSION: Hepatic perfusion parameters measured with CT were significantly altered in cirrhosis and correlated with the severity of chronic liver disease.

Case-Control Studies↗

Midazolam and cortisol metabolism before and after CYP3A induction in humans.

INTRODUCTION: CYP3A is responsible for the metabolism of numerous endogenous and exogenous compounds. Several substrates of CYP3A have been investigated to assess the CYP3A-metabolizing capacity of an individual in an attempt to predict the rate of metabolism of other CYP3A substrates. Two such tests of CYP3A activity are the midazolam plasma clearance after its intravenous administration and the 6beta-OH cortisol urinary ratio. Possible correlations between these 2 tests were investigated before and after treatment with rifampin in a group of healthy volunteers. METHODS: Pharmacokinetic parameters of midazolam and 6beta-OH cortisol urinary ratio were evaluated in 8 volunteers before and after 6 days treatment with rifampin, a potent inducer of CYP3A, and after cessation of rifampin treatment. RESULTS: Midazolam systemic clearance and the 6beta-OH cortisol urinary ratio were significantly higher at Days 7 and 10 than at Day 0. There was a strong positive correlation between these 2 parameters (r = 0.70, p < 0.001). In contrast, no correlation was observed between the ratio of the AUCs of 1'-OH midazolam vs. midazolam (AUC0-1(1'-OH)/AUC0-t(MDZ)) or the ratio of plasma concentration of 1'-OH midazolam vs. midazolam (C30 min(1'-OH)/C30 min(MDZ)) and the 6beta-OH cortisol urinary ratio (r = 0.05, p = 0.82; r = 0.04, p = 0.88, respectively). Considering only data obtained before or after treatment with rifampin, however, no correlation was observed between midazolam systemic clearance and the 6beta-OH cortisol urinary ratio. CONCLUSIONS: These data demonstrate that there is a strong positive correlation between systemic midazolam clearance and 6beta-OH cortisol urinary ratio before and after induction. This suggests that the 6beta-OH cortisol urinary ratio test is a non-invasive alternative to the use of systemic midazolam clearance for monitoring the time-course of CYP3A induction.

Adult↗

Gadolinium-enhanced arterial-phase MR imaging of hypervascular liver tumors: comparison between tailored and fixed scanning delays in the same patients.

The purpose of this study was to compare in the same patients tailored and fixed scanning delays during gadolinium-enhanced arterial-phase magnetic resonance imaging of hypervascular liver tumors. Tailored scanning delays were obtained with automated region of interest threshold triggering. A delay of 23 seconds between the start of contrast material injection and imaging was used for fixed delay examinations. Quantitative and qualitative evaluation was performed in 21 patients with normal cardiac function referred for MR assessment of hypervascular liver tumors. In the tailored examinations, the median time delay between the start of contrast material injection and the start of magnetic resonance imaging was 21 seconds (range, 18-34 seconds). The median tumor-to-liver contrast during tailored examinations was 19.1 versus 14.7 during fixed delay examinations. This difference, however, was not significant. Similarly, the enhancement in the aorta, the portal vein, the liver, and the tumor did not differ significantly between examinations performed with tailored and fixed delays. It is concluded that in our group of patients with hypervascular liver tumors and normal cardiac function, no significant improvement in tumor-to-liver contrast and enhancement during the arterial phase was found when gadolinium-enhanced magnetic resonance imaging was performed with a tailored scanning delay rather than with a fixed delay.

Adult↗

Disposable versus reusable biopsy forceps: a prospective cost evaluation.

BACKGROUND: There is growing advocacy for the use of disposable medical accessories to reduce the risks of infection transmission. Their purchase costs can, however, be considered as prohibitive in an endoscopy unit operating under a cost-containment program. We therefore compared the costs of reusable and disposable biopsy forceps. METHODS: From October 1995 to September 1997, biopsies were obtained in 7740 sessions. The evaluation of costs included purchase prices, repairs, cleaning (chemicals, equipment, technician time) and autoclaving costs in a centralized sterilization unit. For comparison, the lowest purchase price for disposable biopsy forceps was $26.90 in 1997. RESULTS: A mean of 12 new reusable forceps were purchased every year for a total purchase price of $5460. A total of 315 biopsy sessions were performed per forceps (mean time life of 3 years per forceps, including 3 repairs). Yearly repair cost was $3308, equipment $1002, chemicals $3250, central sterilization $8333, and technician salary $4373. Total cost was $25,726 and cost per biopsy session was $6.65. CONCLUSIONS: Total purchase and reprocessing costs for reusable biopsy forceps were 25% of those of disposable devices. The use of disposable biopsy forceps would have led to a yearly extra cost of $78,377 in the operation of our endoscopy unit.

Belgium↗

The compensatory hyperplasia (liver regeneration) following ligation of a portal branch is initiated before the atrophy of the deprived lobes.

BACKGROUND/AIMS: In rats, partial ligation of portal branches produces atrophy of the deprived lobes and hypertrophy of the intact lobes. The hepatocyte proliferation observed in the nondeprived lobes is viewed as a compensatory hyperplasia, implying that the atrophy somewhat precedes the initiation of the proliferative response. As this has not been demonstrated, the time course and magnitude of those two sequences of events were investigated and compared with the well-defined response to a partial hepatectomy. METHODS: The portal branch feeding the anterior liver lobes was ligated in male Wistar rats. One-third and two-thirds partial hepatectomies were also performed. Liver weight, the aminopyrine demethylation rate, an index of the liver mass, the DNA content and various indices of cell proliferation were measured. RESULTS: Resection of the anterior lobes (PH) or ligation of their portal blood supply (PBL) induced a marked DNA synthesis in the posterior lobes (3H-thymidine incorporation) reaching its maximum 24 h after both interventions. This response can even be accelerated by performing a sham operation 6 h before the PBL. The process leading to DNA synthesis thus seems to start as early after PBL as after a PH, although the weight of the liver or the aminopyrine demethylation rate was nearly unchanged 2 h following PBL. The initiation of the proliferative response clearly precedes and is thus independent of the reduction of the liver mass. On the other hand, the progressive reduction of the liver mass seems to determine the magnitude of the proliferative response, which is, for instance, greatly increased following the excision of the deprived lobes, as late as 10 h after ligation of their portal branches. In comparison with the results obtained after a 113 PH, the peak of DNA synthesis at the 24th hour is greater than predicted by the liver weight loss, but this parameter could underestimate the reduction of the functional liver mass. CONCLUSION: The proliferative response following a PBL can be divided into an early phase occurring independently of the reduction of the liver mass and a late phase controlled by this reduction. The paradox of the proliferative response which seems to start before the atrophy to be compensated is resolved by this hypothesis.

Animals↗

Early down-regulation of cytochrome P450 3A and 2E1 in the regenerating rat liver is not related to the loss of liver mass or the process of cellular proliferation.

AIMS/BACKGROUND: Conflicting data have been reported concerning the modification of cytochrome P450 expression in the regenerating liver. Ligation of branches of the portal vein (PBL) perfusing 70% of the liver parenchyma, which produces regeneration and atrophy within the same liver, constitutes an ideal model to study the relative specificity of the early events in the regenerating liver and their relationship to the loss of liver mass. METHODS: In this PBL model and in sham models, we studied the expression and the metabolic activities of two major cytochromes, CYP3A and CYP2E1, and the expression of inducible nitric oxide synthase protein (iNOS). They were simultaneously measured in the atrophying and regenerating liver lobes following PBL using Western Blot and HPLC methods. RESULTS: The metabolic activities of both cytochromes were transiently and simultaneously down-regulated in the regenerating and atrophying lobes during the first 2-5 h after PBL. No significant modification was observed at the protein level. In contrast, iNOS protein was significantly induced in both lobes. Similar results were observed after sham operation. CONCLUSIONS: The reduction of these CYP activities in both lobes after PBL and in sham livers suggests that other mechanisms than the regenerating process itself or the reduction of the liver mass might account for such down-regulation during the early phase of liver regeneration. The activation of nitric oxide (NO) and/or pro-inflammatory cytokine production provides clues to pathways liable to affect the CYP activities in the regenerating liver.

Animals↗

Differential activities of CYP1A isozymes in hepatic and intestinal microsomes of control and 3-methylcholanthrene-induced rats.

Differences in expression of CYP1A isoforms (CYP1A1 and CYP1A2) in liver and small intestine of male Wistar rats and their inducibility by 3-methylcholanthrene as well as the effect of different CYP1A1/1A2 expression on caffeine metabolism were investigated. In rat liver, CYP1A2 is the predominant isoform and CYP1A1 protein expression in liver is significantly increased after treatment by 3-methylcholanthrene. In contrast, only CYP1A1 was detected in control and 3-methylcholanthrene induced small intestine microsomes. Treatment with 3-methylcholanthrene (40 mg/kg intraperitoneally daily during 1, 2, 3 or 4 days) demonstrated that liver CYP1A1 is more sensitive for the induction effects than CYP1A2 and also that significant induction of CYP1A1 in rat small intestine only occurred after 3 to 4 days pretreatment. Caffeine metabolism and inhibition studies by furafylline, CYP1A1 antiserum and ketoconazole revealed that the differences in the expression of CYP1A1 and CYP1A2 in the two tissues led to significant changes in the contribution of the various isoenzymes involved in the biotransformation of caffeine. Whereas in liver paraxanthine formation was almost exclusively catalyzed by CYP1A2, in rat proximal intestine it was formed by CYP1A1. In addition, other CYP enzymes (most probably CYP3A) play a significant role in theobromine and theophylline formation from caffeine in rat intestine. Overall, this study shows different expression and inducibility of CYP1A1/1A2 by 3-methylcholanthrene in rat liver and small intestine. Furthermore in rat intestine cytochrome P450 isozymes such as CYP1A1 and CYP3A replace CYP1A2 in the caffeine metabolism.

Animals↗

Relationship between red cell mean corpuscular volume and 6-thioguanine nucleotides in patients treated with azathioprine.

Azathioprine (AZA) is characterized by high interindividual differences in bioavailability and metabolization. The aim of the present study was to analyze, in patients treated with AZA for various immune system disorders, whether the variation in red blood cell mean corpuscular volume (deltaMCV) could be used as an indirect estimation of the level of the active immune modifier metabolite 6-thioguanine nucleotides (6-TGN). In 43 consecutive patients treated with a stable dose of AZA for at least 6 months who were not initially anemic, the erythrocyte 6-TGN levels with routine hematologic parameters were determined two to four times at 1-month intervals. In most patients MCV significantly increased after 3 months of therapy and stabilized after 6 months. The correlation between the daily dose of AZA and the 6-TGN level was mild (r = 0.51; P<.001). A weak correlation was also found between the dose of AZA and the deltaMCV after at least 6 months of therapy (r = 0.36; P<.05). The correlation between deltaMCV and 6-TGN level, however, was much better (r = 0.74; P<.001). The lack of a significant increase in MCV after 3 to 4 months of AZA therapy reflects low 6-TGN levels, sometimes a result of undertreatment. A determination of the 6-TGN level during the first months after AZA therapy is begun will allow more accurate adaptation of the effective dose. We observed that deltaMCV could be used as an indicator of 6-TGN levels after 6 months of AZA treatment. An increase in MCV of at least 6 fL is expected to reflect a 6-TGN level of about 175 pmol/8x10(8) red blood cells (probably being within a therapeutic value).

Adult↗

Dramatic response after an intravenous loading dose of azathioprine in one case of severe and refractory ankylosing spondylitis.

We describe a 37-yr-old Caucasian male suffering from ankylosing spondylitis (AS) with long-standing severe inflammatory lumbar pain and hip arthritis who was refractory to non-steroidal anti-inflammatory drugs, sulphasalazine and methotrexate up to 25 mg/week. In this patient, administration of an i.v. loading dose of azathioprine (AZA; 40 mg/kg for 36 h followed by 2 mg/kg oral AZA therapy) induced a dramatic response in his clinical condition. Indeed, objective and subjective clinical variables improved within 1 week and were corroborated by a decline in the levels of the inflammatory parameters; anaemia was reported at month 3 but was rapidly reversible. If confirmed, an i.v. loading dose of AZA could represent a valuable alternative in severe and refractory AS, but toxicity of this regimen should be carefully analysed.

Adult↗

Non-invasive quantification of liver perfusion with dynamic computed tomography and a dual-input one-compartmental model.

Various liver diseases lead to significant alterations of the hepatic microcirculation. Therefore, quantification of hepatic perfusion has the potential to improve the assessment and management of liver diseases. Most methods used to quantify liver perfusion are invasive or controversial. This paper describes and validates a non-invasive method for the quantification of liver perfusion using computed tomography (CT). Dynamic single-section CT of the liver was performed after intravenous bolus administration of a low-molecular-mass iodinated contrast agent. Hepatic, aortic and portal-venous time-density curves were fitted with a dual-input one-compartmental model to calculate liver perfusion. Validation studies consisted of simultaneous measurements of hepatic perfusion with CT and with radiolabelled microspheres in rabbits at rest and after adenosine infusion. The feasibility and reproducibility of the CT method in humans was assessed by three observers in 10 patients without liver disease. In rabbits, significant correlations were observed between perfusion measurements obtained with CT and with microspheres (r=0.92 for total liver perfusion, r=0.81 for arterial perfusion and r=0.85 for portal perfusion). In patients, total liver plasma perfusion measured with CT was 112+/-28 ml.min(-1).100 ml(-1), arterial plasma perfusion was 18+/-12 ml.min(-1).100 ml(-1) and portal plasma perfusion was 93+/-31 ml.min(-1).100 ml(-1). The measurements obtained by the three observers were not significantly different from each other (P>0.1). Our results indicate that dynamic CT combined with a dual-input one-compartmental model provides a valid and reliable method for the non-invasive quantification of perfusion in the normal liver.

Adult↗