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L T Skovgaard

Publications and source records attributed to L T Skovgaard.

68 records · Page 4Linked to original sources

Kinetics of hepatic alanine uptake and urea synthesis in pigs.

The kinetics of hepatic alanine uptake and urea synthesis in relation to sinusoid alanine concentration was investigated in seven anesthetized pigs weighing 63 kg, using liver vein catheterizations. Each experiment consists of four steady-state periods of 40 min with alanine concentrations in the range of 0.4-27 mmol/l. The process rates were measured as the products of transhepatic concentration gradients and hepatic blood flow rate, determined by indocyanine green. The data suggest that both processes follow saturation kinetics, that there exists a sinusoidal concentration of alanine below which net removal is limited, and that urea synthesis consists of two components: one alanine independent and one depending on alanine concentration according to Michaelis-Menten kinetics. The kinetic parameters were estimated iteratively by the maximum likelihood method. The maximum rate of alanine uptake was 1.13 +/- 0.74 mmol.min-1.kg liver wt-1 (mean +/- SD), the alanine concentration resulting in half-maximum alanine uptake rate was 1.69 +/- 0.99 mmol/l, and the removal-limiting alanine concentration was 0.27 +/- 0.09 mmol/l. The maximum rate of urea-N synthesis was 1.49 +/- 0.87 mmol.min-1.kg liver wt-1, the alanine concentration resulting in half-maximum urea-N synthesis rate was 2.32 +/- 1.11 mmol/l, and the alanine concentration-independent urea-N synthesis rate was 0.13 +/- 0.10 mmol.min-1.kg liver wt-1.

Alanine↗

In vitro diagnosis of susceptibility to malignant hyperthermia: comparison between dynamic and static halothane and caffeine tests.

In vitro tests for the diagnosis of malignant hyperthermia susceptibility were performed in 105 patients and 20 normal controls according to the protocol of the European MH Group. Results of dynamic halothane and caffeine tests (in which muscle bundle length is cyclically changed) were compared to those of static tests (constant muscle bundle length). Overall, no significant differences between dynamic and static tests were found in threshold concentrations eliciting contractures. Identical diagnostic results with dynamic and static tests were obtained in 94.3% with halothane and in 88.9% with caffeine. The magnitude of contractures was, however, significantly greater in the dynamic than in the static halothane test for halothane concentrations less than 3%, but this did not influence diagnosis. The results indicate that dynamic tests are not superior to static tests, but several tests should be performed to enhance diagnostic safety.

Caffeine↗

In vitro diagnosis of susceptibility to malignant hyperthermia: evaluation of tests with halothane-caffeine, potassium chloride, suxamethonium and caffeine-suxamethonium.

Susceptibility to MH was determined in 77 patients according to the protocol of the European MH Group. Additional muscle bundles were used for diagnostic in vitro tests with caffeine in the presence of 1% halothane, potassium chloride, suxamethonium, and caffeine-suxamethonium. Significant differences between MH-susceptible (MHS) and MH-negative (MHN) patients were obtained with the halothane-caffeine test and the potassium chloride test, whereas no differences were found with the suxamethonium test. In the test with caffeine-suxamethonium, a different response to caffeine but not to suxamethonium was obtained. In all tests there was an overlap in results between MHS and MHN groups, and the predictive values of the tests ranged between 63 and 95%. Prior small doses of caffeine followed by a 4 mmol/l dose of caffeine elicited significantly smaller contractures than 4 mmol/l given as the first dose of caffeine. This underlines the necessity of a common protocol for performance and interpretation of diagnostic tests for MH.

Caffeine↗

The influence of fentanyl on the cardiovascular effect of suxamethonium.

The influence of fentanyl on the cardiovascular effect of a single dose of suxamethonium was evaluated during thiopentone N2O/O2 anaesthesia. Sixty adult patients were randomly allocated to three groups. In one group (control group) no fentanyl was given. In two groups fentanyl 0.002 mg/kg and 0.004 mg/kg, respectively, was given before induction of anaesthesia. Three minutes after the injection of suxamethonium 1 mg/kg, both heart rate (HR) and mean arterial pressure (MAP) in the two groups receiving fentanyl were significantly lower than in the control group. However, the absolute changes were small and no dose-related effect was seen. An estimation of the change in HR following suxamethonium was made using as predictors initial HR before induction of anaesthesia, age, sex, and the injection of fentanyl. The higher the initial HR, the greater was the chance of a decrease in HR following suxamethonium. Injection of fentanyl lowered the threshold HR above which a decrease was to be expected following injection of suxamethonium. This effect was most pronounced among the younger patients. It is concluded that injection of fentanyl potentiates the decrease in HR sometimes seen after a single dose of suxamethonium and that this effect is influenced by HR before induction of anaesthesia and by age of the patient.

Adult↗

Acetaminophen metabolism by the perfused rat liver twelve hours after acetaminophen overdose.

The effect of a toxic dose of acetaminophen on the hepatic conjugations of acetaminophen was studied in single pass perfused livers from rats given acetaminophen overdose 12 hr prior to perfusion and from control rats. Four different acetaminophen concentrations (0.1-6 mmol/1) were used in each perfusion. Glucuronidation of acetaminophen was increased and sulfation of acetaminophen occurred at an unchanged rate in acetaminophen damaged livers as compared to control livers. Hepatic glutathione concentrations declined to about 0.4 mumol/g liver during perfusion, possibly due to excretion of glutathione to perfusion medium, but in spite of this the formation of glutathione conjugates was increased with acetaminophen concentrations increasing up to about 5 mmol. We conclude that decreased sulfation, glucuronidation and glutathione conjugation in the liver is not present in the early development of acetaminophen-induced hepatic damage.

Acetaminophen↗

Dose-response curves for vecuronium during halothane and neurolept anaesthesia: single bolus versus cumulative method.

The purpose of this study was to compare the incremental, cumulative dose method and the single bolus injection technique for construction of dose-response curves for vecuronium. Dose-response curves were determined in 77 patients divided into four groups according to the anaesthetic given and the method used for construction of dose-response curves. The regression lines corresponding to the four dose-response curves were found to be parallel. For vecuronium ED50 during neurolept anaesthesia was found to be 28 micrograms kg-1 with the single bolus injection technique and 35.2 micrograms kg-1 with the incremental, cumulative dose method (P less than 0.05). During halothane anaesthesia, ED50 was found to be 25.7 micrograms kg-1 and 26.2 micrograms kg-1, respectively (P greater than 0.05). Potentiation of vecuronium by halothane was found with the cumulative method only. It is concluded that the incremental, cumulative dose method is not suitable for potency determinations of vecuronium.

Adult↗

Pancreatic islet volume distribution: direct measurement in preparations stained by perfusion in situ.

The islets of Langerhans in normal mice were analyzed and quantitated morphologically after selective in situ perfusion staining with dithizone of the isolated pancreas. Total islet area and number of islets were determined in a texture-analyzing system on projected images of each islet. Islets varied considerably in size and in shape and did not conform with ideal spheroids or ellipsoids. In order to derive methods for estimation of the total number and total volume of islets, a distributional study of the areas was carried out. The size distribution of the islets of Langerhans was not of a known simple type, and was fitted best with a (power)-generalized inverse Gaussian distribution.

Animals↗

beta-Cell function relative to islet volume and hormone content in the isolated perfused mouse pancreas.

The beta-cell function, total islet volume, and number were studied in 1- to 18-month-old mice, together with the extractable pancreatic insulin and glucagon. The beta-cell function, determined as the total amount of insulin released in response to glucose from the in vitro perfused pancreas showed an age-related increase, without any differences in the kinetics of insulin secretion between young and old mice. The total islet number and area in each individual pancreas was determined planimetrically after selective staining of the islets by perfusing the pancreas with dithizone. The islet area increased from 5.4 +/- 1.7 mm2 at 1 month to 16.3 +/- 2.1 mm2 at 18 months, whereas the number of islets remained virtually unchanged (1072 +/- 51). Pancreatic insulin increased with age by nearly 500%, in contrast to a 35% reduction in pancreatic glucagon. There was a strong relationship between body weight and total pancreatic DNA (P = 4.7 X 10(-8)), islet area (P = 3.2 X 10(-7)), insulin secretory capacity (P = 7 X 10(-4)), and total pancreatic insulin (P = 1.9 X 10(-5)), but no relationship between body weight and islet number. The insulin secretory capacity increased proportionally to the increase in islet area (P = 9.9 X 10(-3)). The islet area and total pancreatic insulin were closely related (P = 2.8 X 10(-12)), as were pancreatic insulin and the insulin secretory capacity (P = 3.3 X 10(-11)). There was a negative relationship between pancreatic glucagon and islet area (P = 0.005) and between pancreatic glucagon and insulin (P = 0.01). The close relationship between pancreatic insulin and islet area, shown to be an expression of islet volume, makes it possible to estimate the volume of the endocrine pancreas after standard RIA of pancreatic insulin. The combined morphometric and physiological analysis is unique in studying islet cell function relative to the volume of the endocrine pancreas.

Aging↗

No evidence for altered cellular immune functions in personnel deployed in the Persian Gulf during and after the Gulf War--The Danish Gulf War study.

Veterans who have participated in the Gulf War suffer from a number of symptoms, collectively referred to as the Gulf War Syndrome. It has been hypothesized that a change in the systemic cytokine balance or other changes in immunological parameters could be responsible for some of the symptoms. We analyzed the peripheral blood natural killer (NK) cell activity of 686 Gulf War personnel who had been present in the Persian Gulf area during and immediately after the Gulf War as well as 231 gender and age-matched controls. The test material included individual samples of frozen peripheral blood mononuclear cells kept at -139 degrees C for a period of 50 to 380 days prior to NK cell analysis of freshly thawed cells. Significant differences in NK-cell activity were not observed by direct comparison of the levels of natural cytotoxic activity in the two groups. However, NK-cell cytotoxicity as such decreased due to cryopreservation. Surprisingly, the NK cells obtained from control donors were significantly (p<0.0001) more sensitive to freezing conditions than cells from the Gulf War personnel, leaving the marginal comparison between the two groups untrustworthy, in particular because of the marked difference between the -139 degrees C storage times used for the two groups. Freshly thawed samples of peripheral blood T lymphocytes (CD2+ cells) from 109 randomly selected Gulf War personnel and 68 gender- and age-matched controls were stimulated for 3 days with phytohemagglutinin followed by 4 h activation by phorbol ester and ionomycin, and were stained for intracellular content of interleukin-2, -5, -10 and interferon-gamma. As with natural cytotoxicity, the length of cell storage at -139 degrees C influenced the production of cytokines. No significant differences in the cytokine production between the two groups were observed when the influence of the storage period was taken into consideration. Together, these data suggest that no overall long-term effects on NK-cell function and T-cell cytokine production are present in the Danish Gulf War personnel. Moreover, cryopreservation is a major potential source of bias when studying the physiology of thawed NK and T cells.

Adult↗

Synchronous optokinetic nystagmus. The prediction area in normal humans.

Optokinetic nystagmus was investigated in 150 normal subjects who were separated into two groups according to age (17-50 years and 65-89 years). The investigations were carried out at target speeds of 10 degrees/sec and 20 degrees/sec. Both of the test situations were within the area of synchronous response, i.e. every target gave rise to one or more nystagmic beats. The normal variation of the eye velocity of horizontal OKN was determined. It was impossible to obtain stable ENG recordings of vertical OKN. No age- or sec dependent asymmetry of the eye velocity was observed. Five of the participants from the older group were unable to produce a continuous and regular OKN. From the rest of the participants regular responses were recorded at one or both of the test situations. The eye velocity is encumbered with a considerable individual variation, which is reduced when considering the difference between clockwise and counter-clockwise OKN.

Adolescent↗