Jonas Boberg

Development, implementation and pilot evaluation of a Web-based Virtual Patient Case Simulation environment – Web-SP

BackgroundThe Web-based Simulation of Patients (Web-SP) project was initiated in order to facilitate the use of realistic and interactive virtual patients (VP) in medicine and healthcare education. Web-SP focuses on moving beyond the technology savvy teachers, when integrating simulation-based education into health sciences curricula, by making the creation and use of virtual patients easier. The project strives to provide a common generic platform for design/creation, management, evaluation and sharing of web-based virtual patients. The aim of this study was to evaluate if it was possible to develop a web-based virtual patient case simulation environment where the entire case authoring process might be handled by teachers and which would be flexible enough to be used in different healthcare disciplines.ResultsThe Web-SP system was constructed to support easy authoring, management and presentation of virtual patient cases. The case authoring environment was found to facilitate for teachers to create full-fledged patient cases without the assistance of computer specialists. Web-SP was successfully implemented at several universities by taking into account key factors such as cost, access, security, scalability and flexibility. Pilot evaluations in medical, dentistry and pharmacy courses shows that students regarded Web-SP as easy to use, engaging and to be of educational value. Cases adapted for all three disciplines were judged to be of significant educational value by the course leaders.ConclusionThe Web-SP system seems to fulfil the aim of providing a common generic platform for creation, management and evaluation of web-based virtual patient cases. The responses regarding the authoring environment indicated that the system might be user-friendly enough to appeal to a majority of the academic staff. In terms of implementation strengths, Web-SP seems to fulfil most needs from course directors and teachers from various educational institutions and disciplines. The system is currently in use or under implementation in several healthcare disciplines at more than ten universities worldwide. Future aims include structuring the exchange of cases between teachers and academic institutions by building a VP library function. We intend to follow up the positive results presented in this paper with other studies looking at the learning outcomes, critical thinking and patient management. Studying the potential of Web-SP as an assessment tool will also be performed.More information about Web-SP: http://websp.lime.ki.se

Lipoprotein-lipase activity in human skeletal muscle and adipose tissue in the fasting and the fed states☆

Sixteen healthy subjects, 7 females and 9 males, with a mean age of 25 years (range 22--29 years), were studied in the fasting state in the morning and 8 h later after partaking of breakfast, lunch and two small meals. The lipoprotein-lipase activity in the adipose tissue increased significantly from 80 +/- 32 to 117 +/- 61 nmol fatty acid released per gram and minute (nmol FA/g/min), whereas in skeletal-muscle tissue it decreased significantly from 25 +/- 11 to 17 +/- 9 nmol FA/g/min. The concentration of serum triglycerides increased significantly from 0.93 +/- 0.18 mmol/l (mean +/- SD) in the fasting state to 1.57 +/- 0.64 mmol/l in the fed state. In the fasting state the lipoprotein-lipase activity of skeletal muscle was inversely related to the ratio between the concentrations of insulin and glucagon.

Reduction of high density lipoprotein cholesterol and apolipoprotein a-i concentrations by a lipid-lowering diet

Nine hyperlipoproteinaemic patients were treated with a serum lipid-lowering diet during 4 weeks in a metabolic ward. The diet contained 35% energy from fat and the ratio between polyunsaturated and saturated fats (the P/S ratio) was 2.0. This treatment caused a reduction of the serum concentrations of the low density lipoprotein cholesterol (Chol) by 17% (P less than 0.01), of the apolipoprotein (apo) B by 27% (P less than 0.01), of high density lipoprotein (HDL) Chol by 15% (P less than 0.05) and of the apo A-I by 9% (P less than 0.02). The apo B/apo A-I ratio decreased by 19% (P less than 0.01). It is suggested that the reduced HLD Chol and apo A-I concentrations may be due to both the qualitative change to more polyunsaturated fats in the diet and to the reduction of the total dietary fat intake.

Splanchnic Secretion Rates of Plasma Triglycerides and Total and Splanchnic Turnover of Plasma Free Fatty Acids in Men with Normo‐ and Hypertriglyceridaemia

Abstract. Plasma triglyceride (TG) “turnover rates” were estimated in the fasting state in three different ways: splanchnic chemical TG secretion, splanchnic isotope TG secretion and plasma TG clearance. Forty‐two men with a wide range of fasting plasma TG concentrations, from 0.53 to 16.50 mmol/l were investigated. A constant intravenous infusion of albumin‐bound 3H‐labelled palmitate was given and blood was simultaneously sampled from the hepatic vein and an artery for determination of hepatic venous‐arterial differences of labelled and unlabelled plasma TG. In addition total and splanchnic turnovers of plasma FFA were measured. Similar values were obtained for plasma TG “turnover rate” by the splanchnic chemical TG secretion and the plasma TG clearance method. The values for these two methods varied between 3 and 74 μmol/min. and m2 body surface area, except for two cases who had considerably higher values. The splanchnic isotope TG secretion method gave lower values varying from 1 to 34 μmol/min. and m2 body surface area. This method probably measures only that fraction of the splanchnic TG secretion which is derived from plasma FFA. No correlations were found among normotriglyceridaemic subjects between plasma total TG or VLDL‐TG concentrations and plasma TG “turnover rates” measured by any of the three methods. For patients with hypertriglyceridaemia significant positive correlations were found between plasma VLDL‐TG concentrations and plasma “turnover rates”. The “fractional turnover rate” decreased with increasing TG levels in an apparently hyperbolic fashion. The results suggest an impaired plasma TG removal capacity in patients with hypertriglyceridaemia. In 7 out of 14 patients the plasma TG “turnover rates” were in the upper part of the normal range and seemed to have contributed to the hypertriglyceridaemia in these patients. Plasma FFA turnover rate ranged between 102 and 439 μmol/min. and m2 body surface area. On the average splanchnic FFA mobilization and uptake were about 30 and 60 per cent respectively of total FFA turnover rate. Significant positive correlations were found for the interrelationships between the three plasma FFA total and splanchnic transport parameters. Significant positive correlations were found between the three plasma TG “turnover rates” and total and splanchnic turnover of plasma FFA in subjects with normal plasma TG concentrations. Some patients with hypertriglyceridaemia fell outside the intervals of 99 per cent confidence of the regression analyses for the normo‐triglyceridaemic subjects. This group had higher TG “turnover rates” than “expected” from plasma FFA turnover rates and may represent a distinctive group of hypertriglyceridaemia from the point of view of pathogenesis. It was concluded that all patients with hypertriglyceridaemia who were investigated had decreased “fractional turnover rates” of plasma TG indicating a decreased removal capacity which might be a primary cause of the hypertriglyceridaemia although inflow of plasma TG seemed to be an essential contributing factor in half the number of patients.

Comparison between Fractional Turnover Rate of Endogenous Plasma Triglycerides and of Intralipid® (Intravenous Fat Tolerance Test) in Man*

Abstract. The validity of the intravenous fat tolerance test (IVFTT) as a tracer for the fractional turnover rate of endogenous plasma triglycerides (TG) has been studied in 32 fasting men with either normal or elevated plasma TG concentrations. The endogenous plasma TG turnover was determined by sampling arterial and hepatic vein blood, determination of splanchnic net secretion of plasma TG and calculation of fractional TG turnover rate. Later the fractional elimination rate of exogenous TG was determined following a single IV injection of Intralipid® (IVFTT). The TG fractional removal rate constants derived from these two tests were significantly correlated (r= 0. & ‐0.7) but IVFTT gave higher absolute values. A statistical evaluation showed that the error for the determination of the fractional turnover rate of endogenous TG and the IVFTT were about 30–50% and 10% respectively. It is probable that the correlation would have been still better if the error for the estimation of endogenous plasma TG turnover had been lower. A significant negative correlation was found between very low density lipoprotein‐TG concentration and fractional removal rate of both endogenous and exogenous plasma TG (r=−0.7–0.8).

Determination of lipoprotein-lipase activity in human skeletal muscle tissue.

An in vitro assay system was developed for the determination of lipoprotein-lipase activity in 10--30-mg specimens of human skeletal muscle tissue. The reaction medium of the assay was based on a glycine buffer of pH 8.3 (at 37 degrees C) with a heparin concentration of 1.5 g/l (about 180 IU/ml). The enzyme activity was measured as the release of [3H]oleic acid from a serum-activated, triglyceride emulsion, in which [3H]trioleate was used as trace substance. The enzyme activity studied had the characteristic properties of lipoprotein-lipase activity, i.e. it was activated by the addition of serum or apolipoprotein C-II and inhibited in the presence of high ionic strength, protamine sulphate or apolipoprotein C-III. A mean Km of 0.40 +/- 0.13 (S.D.) mmol/l for triglyceride substrate was found in tissue samples that had very different concentrations of lipoprotein-lipase activity. This Km was similar to the low fasting concentrations of very low density lipoprotein triglycerides often found in healthy individuals. The lipoprotein-lipase activity was not decreased freezing and storing the tissue specimens in liquid nitrogen. The within-day variation of the method was 16 percent and the between-day variation 8 percent. Muscle tissue from the vastus lateralis muscle had, on the average, a 60 percent higher concentration of lipoprotein-lipase activity than the rectus abdominis muscle in the same subject.

Determination of Splanchnic Secretion Rate of Plasma Triglycerides and of Total and Splanchnic Turnover of Plasma Free Fatty Acids in Man

Abstract. A method has been developed whereby the splanchnic secretion rate of plasma triglycerides (TG) and the splanchnic uptake and mobilization of plasma free fatty acids (FFA) can be measured in man. The method includes constant intravenous infusion of albumin‐bound 3H‐labelled palmitate, and simultaneous sampling of blood from the hepatic vein and an artery.

Determination of the intravenous fat tolerance test with intralipid by nephelometry.

Abstract The estimation of intravenous fat tolerance by a nephelometric method has been studied. The value for the fat tolerance, K 2 , obtained with this method compared to simultaneously estimated K 2 by the original PVP gradient method showed good agreement between the two methods, the coefficient of correlation being r = 0.92. The nephelometric method for the intravenous fat tolerance test is quite simple and suitable for routine clinical diagnosis.

Increase of the lipoprotein‐lipase activity in human skeletal muscle during clof ibrate administration

Abstract. Lipoprotein‐lipase activity was determined in tissue from the skeletal muscle of the leg and the subcutaneous adipose tissue of the abdomen in fourteen patients before and after 1 month of clofibrate administration. The concentrations of serum triglycerides decreased by, on the average, 37% in a group of thirteen patients which mainly consisted of subjects with type‐IV hyperlipoproteinaemia. Clofibrate administration was associated with an average increase of the skeletal muscle‐tissue lipoprotein‐lipase activity of 50% (P< 0.005). There was a significant correlation between the percentage changes in skeletal muscle‐tissue lipoprotein‐lipase activity and those of the triglycerides concentrations and the K2‐values in an intravenous fat tolerance test during clofibrate treatment. Adipose‐tissue lipoprotein‐lipase activity did not change significantly. One patient with type‐I hyperlipoproteinaemia had very low values of skeletal muscle‐tissue lipoprotein‐lipase activity and moderately low adipose‐tissue lipoprotein‐lipase activity. In this patient, neither the tissue lipoprotein‐lipase activity nor the triglycerides concentration changed during clofibrate therapy. Fasting serum insulin concentrations decreased significantly during clofibrate administration and the percentage decrease was significantly correlated to the percentage increase of skeletal‐muscle lipoprotein‐lipase activity. It is suggested that the lowering of insulin levels is a possible mechanism through which glucagon activity is enhanced and this may increase skeletal muscle‐tissue lipoprotein‐lipase activity.

A method of determining lipoprotein-lipase activity in human adipose tissue

A method of determining lipoprotein-lipase activity (LPLA) in human adipose tissue specimens (weighting 5-50 mg) is described. The specimens were incubated at 37 degrees C in a reaction medium based on a glycine buffer (pH 8.3, ionic strength 0.08), in which the enzyme was stablized and the velocity of release of fatty acids was constant during the incubation. The enzyme activity was increased, as is characteristic of lipoprotein-lipase (LPL), three to four-fold by the addition of serum. The inhibitions by NaCl, protamine sulphate and apolipoprotein C-III were as for LPL, when analysed in both a serum-activated and non-activated reaction medium. The apparent LPLA was about six times greater when analysed in a reaction medium based on a glycine buffer in the presence of heparin (1 g/l) than when analysed in a reaction medium based on a Tris buffer. An analysis of the influence of a high (1 g/l) and a low (0.05 g/l) concentration of heparin on the properties of the enzyme activity was carried out, using LPL of bovine skim milk as a reference enzyme. A phospholipid/soybean-oil emulsion was used as substrate, with [3H]triolein as a trace substance. The emulsion was stable for 5 months. The adipose tissue specimens were stored in liquid nitrogen. The analytical error was 15%, which was reduced to 11% (=within-day variation) when intra-individual comparisons were made.