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Biomedical subjects

S Keiding

Publications and source records attributed to S Keiding.

At least 19 recordsLinked to original sources
PubMed2004

Combined liver vein and spleen pulp pressure measurements in patients with portal or splenic vein thrombosis.

BACKGROUND: Patients with thrombosis of the portal or splenic vein may develop portal hypertension with bleeding from oesophageal or gastric varices. The relevant portal pressure cannot be measured by liver vein catheterization or transhepatic puncture of the portal vein because the obstruction is peripheral to the accessible part of the portal system. METHODS: Liver vein catheterization was combined with percutaneous splenic pressure measurement in 10 patients with portal or splenic vein thrombosis and no cirrhosis, and 10 cirrhotic patients without thrombosis. The splenic pressure was measured by percutaneous puncture below the curvature of the ribs with an angle of the needle to skin of 30 degrees in order to minimize the risk of cutting the spleen if the patient took a deep breath. RESULTS: None of the patients in whom the described procedure was followed had complications. Pressure measurements in the spleen pulp and splenic vein were concordant. The pressure gradient across the portal venous system (splenic-to-wedged hepatic vein pressure) was -1.3 to 8.5 mmHg (median, 2.8 mmHg) in cirrhosis patients and 0-44 mmHg (median, 18 mmHg) in thrombosis patients, the variation reflecting various degrees of obstruction to flow in the portal venous system. Peripheral portal pressure (splenic-to-free liver vein pressure gradient) was 1.1-28 mmHg (median, 17 mmHg) in cirrhotic patients and 11-52 mmHg (median, 23 mmHg) in thrombosis patients. CONCLUSIONS: Liver vein catheterization combined with percutaneous splenic pressure measurement is feasible in quantifying pressure gradient across a thrombosis of the portal/splenic vein and in quantifying portal pressure peripheral to this kind of thrombosis.

Adult↗
PubMed2004

Budd-Chiari and inferior caval vein syndromes due to membranous obstruction of the liver veins: successful treatment with angioplasty and transcaval transjugular intrahepatic porto-systemic shunt.

The case is presented of a 25-year-old Caucasian patient with Budd-Chiari syndrome due to membranous obstruction of the liver veins and inferior caval vein syndrome as a result of secondary hyperplasia of the caudate lobe of the liver, obstructing the caval vein. Diagnosis was established by intravascular pressure measurements, ultrasound examinations and caval and liver vein angiograms. Treatment consisting of stent placement in the outlet of a hepatic vein and subsequent transjugular intrahepatic porto-systemic shunt (TIPS) insertion via the caval vein was successful. After 34 months of follow-up the stents remain open and the patient is symptom free. This successful combination of stent placement and TIPS has not been described before. The case report is followed by a review of the literature on the use of angioplasty in short hepatic vein stenosis and TIPS in Budd-Chiari syndrome. It is concluded that angioplasty and TIPS are safe and efficient procedures to reduce liver engorgement and complications of portal hypertension in selected patients with Budd-Chiari syndrome.

Adult↗
PubMed2002

Intrahepatic heterogeneity of hepatic venous pressure gradient in human cirrhosis.

BACKGROUND: The hepatic venous pressure gradient (HVPG) is used to evaluate portal hypertension. METHODS: We measured HVPG in two separate liver veins in 169 liver vein catheterizations in 102 cirrhosis patients and in 27 patients with no liver disease (controls). RESULTS: In the controls, the two measurements differed by 0.0 +/- 1.8 mmHg (mean +/- s, n = 27), upper 95% confidence limit 3.6 mmHg (mean + 2 s). HVPG ranged from -0.1 to 8.3 mmHg, upper 95% confidence limit 6.7 mmHg. In cirrhosis, the two measurements agreed within +/- 3.6 mmHg in 39%. In 61%, the measurements differed by 4-34 mmHg. In 35%, fluoroscopy demonstrated hepatic vein-to-hepatic-vein shunting in veins with low HVPG values. In some patients with HVPG measurements above 30 mmHg, Doppler ultrasound examination showed arterialization of the hepatic vasculature. DISCUSSION: Our results demonstrate a hitherto unrecognized notable heterogeneity of the intrahepatic vasculature and HVPG measurements in cirrhosis. The presumption of interposition of non-flowing blood between the catheter tip and the portal system for the measurement of HVPG may thus be violated in about one-third of the cirrhosis cases because of abnormal outlet into hepatic venous shunts and in a minor fraction because of abnormal arterial inlet. In 26%, one measurement was below 12 mmHg, the other measurement above. If the HVPG had been measured in only one liver vein, 13% of the cases would have been classified in a lower risk group than appropriate according to the 12 mmHg concept of risk of bleeding from oesophageal varices.

Adult↗
PubMed2001

Positron emission tomography of hepatic first-pass metabolism of ammonia in pig.

Hepatic first-pass metabolism plays a key role in metabolic regulation and drug metabolism. Metabolic processes can be quantified in vivo by positron emission tomography scanning (PET). We wished to develop a PET technique to measure hepatic first-pass metabolism of ammonia. Seven anaesthetised pigs were given positron-labelled ammonia, (13)NH(3), into the portal vein and into the vena cava as successive 2-min infusions followed by 22-min dynamic liver scanning. Vena cava infusion data were used to account for recirculation of tracer and metabolites following the portal vein infusion. The scan data were analysed by a model of sinusoidal zonation of ammonia metabolism with periportal urea formation and perivenous formation of glutamine. The hepatic extraction fraction of (13)NH(3) was 0.73+/-0.16 (mean+/-SD, n=7 pigs). Values of clearance of ammonia to urea and to glutamine were obtained, as were rate constants for washout of these two metabolites. Overall, the modelling showed half of the ammonia uptake to be converted to urea and half to glutamine. The washout rate constant for glutamine was about one-tenth of that for urea. We conclude that hepatic first-pass metabolism of ammonia was successfully assessed by PET.

Ammonia↗
PubMed2001

Liver kinetics of glucose analogs measured in pigs by PET: importance of dual-input blood sampling.

UNLABELLED: Metabolic processes studied by PET are quantified traditionally using compartmental models, which relate the time course of the tracer concentration in tissue to that in arterial blood. For liver studies, the use of arterial input may, however, cause systematic errors to the estimated kinetic parameters, because of ignorance of the dual blood supply from the hepatic artery and the portal vein to the liver. METHODS: Six pigs underwent PET after [15O]carbon monoxide inhalation, 3-O-[11C]methylglucose (MG) injection, and [18F]FDG injection. For the glucose scans, PET data were acquired for 90 min. Hepatic arterial and portal venous blood samples and flows were measured during the scan. The dual-input function was calculated as the flow-weighted input. RESULTS: For both MG and FDG, the compartmental analysis using arterial input led to systematic underestimation of the rate constants for rapid blood-tissue exchange. Furthermore, the arterial input led to absurdly low estimates for the extracellular volume compared with the independently measured hepatic blood volume of 0.25 +/- 0.01 mL/mL (milliliter blood per milliliter liver tissue). In contrast, the use of a dual-input function provided parameter estimates that were in agreement with liver physiology. Using the dual-input function, the clearances into the liver cells (K1 = 1.11 +/- 0.11 mL/min/mL for MG; K1 = 1.07 +/- 0.19 mL/min/mL for FDG) were comparable with the liver blood flow (F = 1.02 +/- 0.05 mL/min/mL). As required physiologically, the extracellular volumes estimated using the dual-input function were larger than the hepatic blood volume. The linear Gjedde-Patlak analysis produced parameter estimates that were unaffected by the choice of input function, because this analysis was confined to time scales for which the arterial-input and dual-input functions were very similar. CONCLUSION: Compartmental analysis of MG and FDG kinetics using dynamic PET data requires measurements of dual-input activity concentrations. Using the dual-input function, physiologically reasonable parameter estimates of K1, k2, and Vp were obtained, whereas the use of conventional arterial sampling underestimated these parameters compared with independent measurements of hepatic flow and hepatic blood volume. In contrast, the linear Gjedde-Patlak analysis, being less informative but more robust, gave similar parameter estimates (K, V) with both input functions.

3-O-Methylglucose↗
PubMed2001

Metabolites of (18)F-FDG and 3-O-(11)C-methylglucose in pig liver.

UNLABELLED: PET uses (18)F-FDG widely to estimate glucose metabolism in vivo. Dynamic PET data are evaluated by kinetic models of the metabolic pathways. Knowledge of the metabolites of FDG is of critical importance for the interpretation of kinetic PET studies. The purpose of this study was to determine the metabolic pathways of FDG and 3-O-(11)C-methylglucose (MG) in liver tissue in vivo. It is usually assumed that MG is not metabolized and FDG is converted to (18)F-FDG-6-phosphate (FDG-6-P). METHODS: The study was performed on 6 anesthetized 40-kg pigs that were given the 2 tracers intravenously. The content of metabolites was determined in successive liver tissue biopsies. Freeze-clamped liver tissue samples were subjected to extraction by acetonitrile at -5 degrees C to -10 degrees C, and extracts were analyzed by radio-high-performance liquid chromatography (radio-HPLC). The findings were identified by means of radio-HLPC measurements of the products of in vitro enzymatic reactions. RESULTS: The applied extraction technique provided almost quantitative recovery of the radioactivity from tissue. After MG injection, only MG was detectable in the liver tissue; no labeled metabolites were found. After FDG injection, 2 metabolites were identified, FDG-6-P and 2-(18)F-fluoro-2-deoxy-6-phosphogluconate (FD-6-PG1). The tissue content of FDG increased rapidly, and, after 5 min, only FDG was identified; hereafter, the fraction of FDG decreased to approximately 40% of the tissue radioactivity after 180 min. After 20 min, FDG-6-P was found in each of the pigs and it increased throughout the measurement period of 180 min, with a somewhat slower rise at late time points. FD-6-PG1 began to appear in the liver tissue after 45 min and increased throughout the 180-min experiment, with the increase somewhat slower than that of FDG-6-P. After 180 min, approximately 40% of the metabolites was attributed to FD-6-PG1. The content of other metabolites was <2%, even after 180 min. CONCLUSION: After the FDG injection, not only FDG-6-P but also FD-6-PG1 were formed in the liver. Any possible incorporation of FDG into glycogen was of minor importance.

3-O-Methylglucose↗
PubMed2000

[Detection of cholangiocarcinoma in primary sclerosing cholangitis by positron emission tomography].

Primary sclerosing cholangitis (PSC) predisposes to cholangiocarcinoma (CC). PET scanning can assess metabolism in vivo. The glucose analogue [18 F]fluoro-2-deoxy-D-glucose (FDG) accumulates in malignant tumours because of high glucose metabolism. PET scanning of the liver was performed after intravenous FDG in nine patients with PSC, six with PSC + CC, and five controls. "Hot spots" with radioactivity accumulation were seen in each PSC + CC patient, but not in the two other groups. Values of net metabolic clearance of FDG, K (ml min-1 100 ml-1 tissue), was in CC hot spots 1.59 to 4.17 (median, 2.34; n = 6); in reference liver tissues of these patients 0.40 to 0.69 (0.49); in PSC 0.23 to 0.53 (0.36); in controls 0.20 to 0.34 (0.31). The difference between K in CC hot spots and the other groups was statistically significant (P < 0.001). FDG-PET may detect small CC tumours and be useful in therapeutic management of PSC.

Bile Duct Neoplasms↗
PubMed2000

Liver transplantation in patients over 60 years of age.

Liver transplantation was previously only offered to patients under 60 years of age. We have analyzed the outcome after acceptance on the waiting list and after liver transplantation of patients over 60 years old. A total of 150 patients over 60 years old were listed for a first liver transplantation during 1990-1998. The annual number increased throughout the period. Primary biliary cirrhosis, primary sclerosing cholangitis, and acute hepatic failure were the most frequent diagnoses. A total of 119 patients received a first liver allograft. The patient 1-year survival was 75% and 3-year survival 62%, which was not significantly lower (P = 0.21) than that of the younger patients. When correcting for year of transplantation, the survival was, however, moderately but significantly lower than among the younger patients. Survival among those > 65 years (n = 38) did not differ from that of patients 60-65 years of age (n = 81). We conclude that an increasing number of patients over 60 years old can be listed for liver transplantation and receive a liver allograft with highly satisfying results.

Age Distribution↗
PubMed2000

Dynamic 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography of liver tumours without blood sampling.

Positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) is a useful diagnostic tool for the detection of tumours. Using dynamic FDG PET, net metabolic clearance of FDG, K, can be calculated by Gjedde-Patlak analysis of the time course of the radioactivity concentrations in tissue and arterial blood. We examined whether time-activity curves (TACs) based on arterial blood sampling could be replaced by TACs obtained from the descending aorta in dynamic PET scans of patients with liver tumours. The study was performed in two parts, using data from dynamic liver scans with arterial blood sampling in human subjects: First, data from four patients with no liver tumours and five patients with liver tumours were used as a training group. Volumes of interest were defined in the descending aorta (aorta VOIs) by four different methods. K values were calculated based on the corresponding TACs and compared with those based on TACs of the arterial blood sample radioactivity concentrations. The aorta VOI which gave K values that were in best agreement with the K values based on the arterial blood sample measurements was called the AORTA-VOI. Use of the AORTA-VOI was subsequently tested in a test group of 19 tumour patients by comparing the K values from the AORTA-VOI with the K values based on the arterial blood sample measurements. The AORTA-VOI consisted of the sum of small regions of interest (ROIs) drawn in the centre of the aorta (approximately six pixels of 2.4x2.4 mm per transaxial slice of 3.1 mm thickness) in as many transaxial slices as possible (30-40 slices). There were no statistically significant differences between the two sets of K values. The ratio of K values in tumour tissue to K values in reference tissue was 2.1-9.7:1 (mean, 5.4:1) based on the AORTA TACs, and 2.1-8.4:1 (mean, 4.6:1) based on blood sample TACs (P>0.3). We conclude that arterial blood sampling can be replaced by the present AORTA-VOI in the calculation of the net metabolic clearance of FDG in dynamic PET studies of liver tumours in human subjects.

Adenocarcinoma↗
PubMed2000

Interpretation of simultaneous measurements of hepatic extraction fractions of indocyanine green and sorbitol: evidence of hepatic shunts and capillarization?

Sorbitol and indocyanine green (ICG) have high hepatic extraction fractions (E(sorb) and E(ICG)) in normal subjects. A curved relationship has been observed between E(sorb) and E(ICG) in liver disease. According to one interpretation, the decrease of E(sorb) is a result of intrahepatic shunting and 1 - E(sorb) is the fraction of shunted flow (the shunt hypothesis). Under the further assumption that capillarization of functioning sinusoids prevents hepatic uptake of plasma protein-bound ICG and allows uptake of water-soluble sorbitol, the difference E(sorb) - E(ICG) has been suggested as a measure of capillarization. We propose an alternative hypothesis: that the sinusoidal permeability-surface area products for sorbitol and ICG are reduced in proportion by liver disease (proportional reduction hypothesis). Based on the sinusoidal perfusion model, predictions were produced from both hypotheses for the relation between E(sorb) and E(ICG) and the additional effects of capillarization were described. By use of liver vein catheterization, E(sorb) and E(ICG) were simultaneously measured during continuous infusions in 53 human subjects with varying degrees of liver disease. The data were in better agreement with the predictions of the proportional reduction hypothesis than with the shunt hypothesis. Even though both intrahepatic portosystemic shunts and sinusoidal capillarization are known to occur in cirrhosis and also may have influenced our data, they appeared to be of minor importance from a kinetic point of view. These findings favor the proportional reduction hypothesis and do not support the use of systemic nonrenal clearance of sorbitol as a measure of "functional liver blood flow."

Acute Disease↗
PubMed2000

Feasibility of detecting hypoxia in experimental mouse tumours with 18F-fluorinated tracers and positron emission tomography--a study evaluating [18F]Fluoro-2-deoxy-D-glucose.

The study was designed to investigate the binding of [18F]Fluoromisonidazole ([18F]FMISO) and [18F]Fluoro-2-deoxy-D-glucose ([18F]FDG) in a C3H mouse mammary carcinoma. Non-anaesthetized tumour-bearing animals breathing either normal air or carbogen (to reduce tumour hypoxia) were examined by PET after tracer injection. Tumours were identified by radioactive labelling and methods of defining regions of interest (ROI) in the tumours were investigated. Reference tissue was selected elsewhere in the mice and the ratio between mean radioactivity in tumour and reference tissue was compared. The results showed a correlation between the methods of identifying ROIs and a significantly lower tumour to reference tissue ratio for carbogen-treated mice compared with controls when using [18F]FMISO. Only one of the methods showed a significant difference in the tumour labelling between treatment groups using [18F]FDG. The study supports the contention that [18F]FMISO may be able to identify hypoxia in tumours, whereas a similar role for [18F]FDG is more doubtful.

Animals↗
PubMed1999

Liver transplantation in the Nordic countries, 1982-1998: changes of indications and improving results.

BACKGROUND: Liver transplantation has become an established therapeutic option for patients with life-threatening liver disease. The aim of the present study was to analyse the results of and developments in liver transplantation in the Nordic countries during a 15-year period. METHODS: Data on all patients receiving a liver allograft in the Nordic countries during 1982-98 and waiting list data for all patients listed for a liver transplantation after 1989 were obtained from the Nordic Liver Transplantation Registry. RESULTS: A total of 1485 first liver transplantations were performed during 1982-98. The annual number of first liver transplantations increased steadily up to 1993, thereafter remaining around 150-170 per year. There are major differences between countries both in the number of transplants adjusted to populations performed per year, with more than twice as many performed in Sweden as in Norway, and in the relative distribution of patients in accordance with diagnosis. The number of patients more than 60 years old increased and comprised 13%-14% of the total patient population during 1996-98. Primary biliary cirrhosis, primary sclerosing cholangitis, acute hepatic failure, malignant liver disease, and alcoholic cirrhosis are the five most frequent diagnoses. The over-all 1-year patient survival probability has increased from 66% among patients receiving a transplant in 1982-89 to 83% in 1995-1998. The waiting time remains stable, with a median waiting time of 35 days during 1990-98. The mortality of patients while on the waiting list is 7.4% and is not increasing. CONCLUSION: Results of liver transplantation in the Nordic countries are very similar to those obtained in other countries. Waiting time and mortality remain low. There are, however, major differences between the countries both as to the number of transplantations performed and as to distribution of diagnoses.

Adolescent↗
PubMed1998

Sorbitol as a test substance for measurement of liver plasma flow in humans.

The objective of this study was to evaluate whole-body removal kinetics of sorbitol, the use of extrarenal sorbitol clearance to estimate hepatic plasma flow in humans, and to compare measurements of liver flow by Fick's principle using either indocyanine green (ICG) or sorbitol. A sorbitol bolus (5 mmol/kg) was given intravenously to 6 controls for determination of sorbitol elimination capacity (SEC) and distribution volume, V(sorb)d. Sorbitol infusion (287 micromol/ min) was given to 17 liver patients and 11 controls. Extrarenal sorbitol clearance (V(sorb)x was calculated as infusion rate (corrected for renal excretion and accumulation in V(sorb)d) divided by arterial concentration. Liver flow (Q(ICG)) was calculated from the ICG infusion and arterial and hepatic venous ICG concentrations by Fick's principle. Average SEC was 73 micromol/min/kg, V(sorb)d was 0.16 L plasma per kilogram, and in vivo V(sorb)d was 3 mmol/L. Renal sorbitol excretion rate was 0.03 to 0.31 of infusion rate. Extrahepatic extrarenal removal was not significantly different from zero but varied considerably. Hepatic extraction fraction of sorbitol, (E(sorb)), measured by liver vein catheterization, was 0.35 to 1.04 (median, 0.86) in cirrhotic patients and 0.90 to 0.98 (0.86) in controls. The requirements for using Cl(sorb)x as an estimate of Q(ICG) was not violated by the data in controls, Cl(sorb)x/Q(ICG) 0.70 to 1.55 [median, 1.08]), whereas there was a systematic underestimation in cirrhotic patients (0.72-1.08 [0.85]). Liver flow calculated by Fick's principle using either sorbitol or ICG agreed well. E(sorb) > E(ICG) in each individual except one. Curvilinear relationship between E(sorb) and E(ICG) was in agreement with different kinetic parameters for sorbitol and ICG, and did not require additional assumption of intrahepatic shunts.

Adult↗
PubMed1998

Detection of cholangiocarcinoma in primary sclerosing cholangitis by positron emission tomography.

Primary sclerosing cholangitis (PSC) predisposes to cholangiocarcinoma (CC), which usually is widespread in the liver at the time of the diagnosis and which has a median survival of approximately 6 months. Positron emission tomography (PET) is a noninvasive scanning method that allows the assessment of metabolism in vivo by means of positron-emitting radiolabeled tracers. [18F]Fluoro-2-deoxy-D-glucose (FDG) is a glucose analogue that accumulates in various malignant tumors because of their high glucose metabolic rates. The purpose of the study was to develop a PET method to detect small CC tumors in patients with PSC. PET scanning of the liver was performed after intravenous injection of 200 MBq FDG in 9 patients with PSC, 6 patients with PSC + CC, and 5 controls. The scanning was performed at successive time intervals for a total of 90 minutes with simultaneous successive arterial blood sampling for radioactivity concentration determination. In each of the PSC + CC patients, 2 to 7 "hot spots" were seen, with volumes of 1.0 to 45 mL (median, 4.4 mL). There were no hot spots in the two other patient groups. The localization of hot spots was confirmed by single-blind evaluation. Data were analyzed by the Gjedde-Patlak plot, yielding values of the net metabolic clearance of FDG, K [mL min(-1) 100 mL(-1) tissue]. In the CC hot spots, maximum K values were 1.59 to 4.17 (median, 2.34; n = 6); in the reference liver tissues of these patients, K values were 0.40 to 0.69 (median, 0.49); in PSC patients, they were 0.23 to 0.53 (median, 0.36); and in controls, they were 0.20 to 0.34 (median, 0.31). The difference between K in CC hot spots and the other groups was statistically significant (P < .001). We conclude that FDG-PET seems to be able to detect small CC tumors and may be useful in the therapeutic management of PSC.

Adult↗