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Biomedical subjects

S Keiding

Publications and source records attributed to S Keiding.

At least 55 records · Page 3Linked to original sources
PubMed1991

CCl4 cirrhosis in rats: irreversible histological changes and differentiated functional impairment.

Cirrhosis of the rat liver was induced by a 12 week individualized CCl4/phenobarbital treatment. After treatment, all surviving animals (81%) showed cirrhosis of the liver. The cirrhosis induced was irreversible when evaluated 24 weeks after cessation of treatment. Quantitative liver function measurements were reduced in a differentiated manner. Ranked according to the most pronounced changes they are: capacity of urea-N synthesis (CUNS), galactose elimination capacity (GEC) and antipyrine clearance (APC). Hepatic glutathione concentrations were only slightly decreased after the CCl4 treatment. It is possible to produce a high incidence of irreversible cirrhosis with differentiated functional impairment in the rat.

Animals↗
PubMed1990

Galactose removal kinetics during hypoxia in perfused pig liver: reduction of Vmax, but not of intrinsic clearance Vmax/Km.

The galactose elimination kinetics was examined in five perfused pig livers of 1.2 kg during hypoxia induced by administration of 2, 4 or 7% oxygen in the oxygenator instead of 20% as used in nine control experiments, previously published. Galactose was given as four to five successive constant infusion rates so that successive steady-state period with galactose concentrations from 0.04 to 5 mmol l-1 were obtained in each experiment. From the relationship between the calculated elimination rate and the perfusate galactose concentration, values of the maximal elimination rate Vmax and the half saturation concentration Km were calculated. Both Vmax and Km were reduced by hypoxia: the lower the oxygen supply, the greater the reduction. Vmax was about 0.08 mmol min-1 kg-1 liver at 2% oxygen and about 0.18 mmol min-1 kg-1 liver at 4-7% oxygen; both being significantly lower than the value of 0.43 mmol min-1 kg-1 liver at 20% oxygen. Km was about 0.07 mmol l-1 at 2% oxygen and 0.13 mmol l-1 at 7% oxygen; both significantly lower than the value of 0.23 mmol l-1 at 20% oxygen. A nearly parallel reduction of liver ATP concentration and galactose Vmax indicates that the galactose Vmax may reflect the phosphorylation capacity of the liver cells. The Vmax/Km ratio (intrinsic hepatic clearance) was unchanged during hypoxia.

Animals↗
PubMed1990

Survival after liver transplantation of patients with primary biliary cirrhosis in the Nordic countries. Comparison with expected survival in another series of transplantations and in an international trial of medical treatment.

Until December 1988, 38 patients with primary biliary cirrhosis (PBC) had been transplanted in the Nordic countries. The observed survival probability in accordance with Kaplan-Meier analysis was around 75% 2-3 months after surgery, with few deaths during the next 3 years. The observed survival curve was compared with the expected survival calculated from the experience of a recent English PBC transplant series; the patterns are very similar. Secondly, the observed survival was compared with the expected survival curve, calculated from the survival experience of an international trial of medical treatment--that is, the expected survival had the patients not been transplanted; after the first 2-3 months the observed survival stayed better than the expected survival. Finally, the merits of transplantation for each particular patient was evaluated by means of the ratio of probability of survival when transplanted to probability of survival when medically treated 3, 6, and 8 months after surgery. The ratio increased with time, indicating a relative increase in the benefit of transplantation with time after surgery.

Denmark↗
PubMed1989

[Liver transplantation undertaken on Danes abroad].

The indication for liver transplantation is the end stage of liver disease. Liver transplantations are not carried out in Denmark at present, one of the reasons being that it requires introduction of the brain death criterion, because the donor liver must be removed during maintained circulation. To date (November 1988), liver transplantations have been carried out abroad on seven Danes. One of these died after operation, one has chronic rejection and is to have retransplantation while the remaining five patients are well. In Europe (including Sweden, Norway and Finland) and USA, more than 5,000 patients have been liver transplanted. The one-year survival is approximately 75%. After this, only few liver-related deaths occur and the majority of patients can resume their previous activities. A total of 18 Danes have been assessed in transplantation centres abroad: Two are waiting for transplantation in the near future and seven have been accepted for transplantation at a later date, depending on the course of the disease. In a number of Danes, liver transplantation has been considered indicated but has not been effectuated because the disease was so advanced at the time of referral, that the patient died before transfer or the patient did not desire operation abroad.

Adolescent↗
PubMed1989

Age dependence of rat liver function measurements.

Changes in the galactose elimination capacity, the capacity of urea-N synthesis and antipyrine clearance were studied in male Wistar rats at the age of 8, 20 and 44 weeks. Further, liver tissue concentrations of microsomal cytochrome P-450, microsomal protein and glutathione were measured. All liver function measurements increased from the age of 8 to 44 weeks when expressed in absolute values. In relation to body weight, these function measurements were unchanged or reduced from week 8 to week 20. At week 44, galactose elimination capacity and capacity of urea-N synthesis related to body weight were increased by 10% and 36%, respectively, and antipyrine plasma clearance was reduced to 50%. Liver tissue concentrations of microsomal cytochrome P-450 and microsomal protein increased with age when expressed in absolute values, but were unchanged per g liver, i.e., closely related to liver weight in the age range studied. Glutathione showed an increase of 35% from 8 to 44 weeks of age expressed per g liver. Careful age matching of control animals is important for experimental rat studies.

Aging↗
PubMed1988

Galactose clearance measurements and liver blood flow.

Galactose clearance, measured during low galactose infusion and calculated as infusion rate divided by peripheral galactose concentration (systemic clearance), has been proposed as a measure of liver blood flow. This requires nearly complete hepatic extraction as well as negligible extrahepatic elimination. The purpose of the study was to examine if these assumptions are fulfilled in subjects with no liver disease, and to compare the galactose clearance measurement with an independent measurement of liver blood flow. Liver blood flow was measured in 6 subjects by means of a constant indocyanine green infusion, indocyanine green concentration measurements in a peripheral artery and a hepatic vein, and calculation according to Fick's principle. The mean (+/- SEM) blood flow rate was 1.2 +/- 0.1 L/min. Galactose was given at a constant infusion rate of 142 +/- 10 mumol/min, and steady-state concentrations were measured in the peripheral artery (A) and the hepatic vein (V). The hepatic extraction fraction [(A - V)/A] was 0.91 +/- 0.03. The hepatic galactose elimination rate [(A - V) X flow] was 101 +/- 12 mumol/min; this is about two-thirds of the total elimination rate (viz., infusion rate). Urinary excretion was negligible. This indicates an extrahepatic galactose elimination of approximately 41 mumol/min. Systemic galactose clearance, calculated as mentioned above, was 1.5 +/- 0.1 L blood/min. It was significantly higher than the liver blood flow in each subject (paired t-test, each p less than 0.02), on average 133% of the flow. Thus the systemic galactose clearance value overestimates liver blood flow, probably due to a small, but in this context quantitatively important, extrahepatic galactose elimination.

Galactose↗
PubMed1988

Methodological limitations of the use of intrinsic hepatic clearance of ICG as a measure of liver cell function.

Negligible extra-hepatic elimination of indocyanine green (ICG) makes it well suited as a liver test substance. The liver blood flow rate (Q) is estimated from concentration measurements in peripheral (A) and hepatic venous (V) blood during a constant ICG infusion rate (Inf), as Q = Inf/(A-V). Intrinsic hepatic clearance of ICG, Cli = Inf/((A-V)/ln(A/V)), is interesting because it should give a flow-independent quantitative estimate of liver cell function, utilizing the same concentration measurements. The present study was aimed to investigate possible limitations involved in the estimation and use of Cli of ICG in 41 liver patients and 20 controls. Time-dependence was studied by means of two successive 40-min infusion periods (with no significant change in Q). Cli of ICG decreased 6% per hour +/- 3% (mean +/- SD, n = 6, P less than 0.01) due to a small but significant increase of the concentrations during the infusion period. Flow-dependence was studied by measurements before and after an increment of flow of on average 51%, induced by the intake of a meal. This caused no significant change in Cli of ICG (P greater than 0.5, n = 5, Student's paired t-test). The intrinsic hepatic clearance of ICG was on average 0.75 +/- 0.26 l plasma min-1 (+/- SD, n = 20) in controls and 0.39 +/- 0.18 l plasma min-1 in liver patients (n = 41), P less than 0.001. It was positively correlated to the galactose elimination capacity, although the scatter was large (P less than 0.05, n = 56).(ABSTRACT TRUNCATED AT 250 WORDS)

Galactose↗
PubMed1988

Muscle capillary permeability for [14C]inulin and [51Cr]EDTA in human forearm.

Capillary permeability of [14C]inulin and [51Cr]EDTA was examined in human forearm in five healthy, subjects by indicator diffusion technique. Injections of, initially [125I]albumin and [14C]inulin, and after 30 min resting, of [125I]albumin and [51Cr]EDTA, were given in a brachial artery. During light exercise of the forearm, blood was sampled in 2-s periods from a deep cubital vein primarily draining muscles. The plasma flow rate, calculated as the dose of [125I]albumin in the injectate divided by the area under the curve for the venous concentration of 125I, was, on average, 8.5 ml min-1 100 g-1 forearm. Assuming [125I]albumin is a partially permeable tracer, a correction for extraction of albumin was performed. This gave extraction fractions of 0.107 +/- 0.015 (mean +/- SEM) for [14C]inulin and 0.377 +/- 0.033 for [51Cr]EDTA, respectively. The capillary permeability surface area product per 100 g tissue (CDC) was for [14C]inulin 0.90 +/- 0.19, and for [51Cr]EDTA 3.31 +/- 0.38 ml min-1 100 g-1 forearm. The average of the ratios of the CDC values of [51Cr]EDTA to those of [14C]inulin, 4.0 +/- 0.5, is significantly higher than the corresponding ratio between the measured free diffusion coefficients in water at 37 degrees C, 3.07 +/- 0.002 (N = 36 and 17, respectively). This indicates that there is some degree of restriction for [14C]inulin (MW 5200) relative to [51Cr]EDTA (MW 340.2) and it points to an 'equivalent pore radius estimate' of about 160 A in human muscle capillaries.

Adult↗
PubMed1987

Methodological problems in the use of indocyanine green to estimate hepatic blood flow and ICG clearance in man.

Liver blood flow (Q) is often measured by constant infusion of ICG (i), concentration measurements in an artery (A) and a hepatic vein (V): Q = (A-V)/A. Some authors use ICG clearance, Cl = i/A, as a measure of Q assuming complete hepatic extraction. During the infusion, the ICG concentration often increases. The importance of this for calculated values of Q and Cl was examined, and the use of Cl as a measure of Q was reevaluated. ICG was given as 0.06-0.20 mumol/min to 52 subjects with liver disease, and about 0.20 mumol/min to 86 subjects with no liver disease. ICG concentration increased steeply during the first 90 min after start of the infusion; thereafter the increment was constant as evaluated in successive 40-min periods in eleven 320-min studies (analysis of variance P greater than 0.5); on average, 6 +/- 1% per hour (+/- SD). Q was not time-dependent (P greater than 0.5). ICG clearance decreased significantly, on average 5 +/- 2% per hour (+/- SD). Hepatic extraction fraction, (A-V)/A, (measurement period 90-130 min) was 0.34 +/- 0.21 in liver patients (+/- SD) and 0.61 +/- 0.80 in controls. Cl and Q were positively correlated in both groups but with substantial scatter. Thus, not only is the calculated ICG clearance time-dependent but the extraction fraction is further so low and variable, that any use of ICG clearance as a measure of liver flow is not justified.

Humans↗
PubMed1986

Effect of short lasting hypoxia on the metabolic function of the perfused pig liver. Comparison of ischaemic and hypoxaemic hypoxia.

The effects of hypoxaemia and ischaemia were compared in the perfused pig liver. Decreased hepatic oxygen uptake, galactose elimination, ATP phosphorylation and increased lactate output occurred when the oxygen supply was diminished below 55% of the mean of controls. Below the control limits for oxygen uptake and oxidative phosphorylation, the change in the above variables were correlated to the degree of hypoxia, with no quantitative differences regarding ischaemic or hypoxaemic hypoxia. Galactose elimination was correlated to the ATP concentration (r = 0.81). After 80 min of hypoxia almost complete recovery was seen. It can be inferred from the data that other factors than oxygen diffusion into the liver cells may limit oxidative metabolism. Long and severe hypoxia may be required before irreversible cellular damage occurs in the liver.

Animals↗
PubMed1986

The effect of physiological temperature changes on the galactose elimination capacity of the isolated perfused pig liver.

The effect of temperature changes (36-40 degrees C) on the liver function was studied in the isolated perfused pig liver. When compared with control studies no effect was observed on lactate, glucose, bile flow, ATP and energy charge, and the recovery after the changes in temperature was complete. The only significant changes observed regarded the hepatic oxygen uptake and galactose elimination capacity. The increase of 1 degree C resulted in an increase in galactose elimination of 6%, corresponding to a Q10 of 1.98 (SEM 0.12) with an energy of activation of 48 kJ/mol (SEM 4.7). Oxygen uptake was linearly related to galactose elimination (1.75 mol for 1 mole change in galactose elimination). These results indicate that circulatory changes are unimportant within physiological temperature changes. It is concluded that temperature effects on galactose elimination are too small to warrant a correction when used as a clinical test of quantitative liver function.

Adenosine Diphosphate↗