[Better methods and improved competence is needed within the medical audit].
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Clinical Competence↗
Biomedical subjects
M Bergström
Publications and source records attributed to M Bergström.
[Step by step administrative education for physicians in Norway].
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Education, Medical, Continuing↗
The effect of one night without sleep on problem-solving and immediate recall.
The aim of the study was to investigate the effect of spending one night without sleep on the performance of complex cognitive tasks, such as problem-solving, in comparison with a purely short-term memory task. One type of task investigated was immediate free recall, assumed to reflect the holding capacity of the working memory. The other type of task investigated was represented by syntactical reasoning and problem-solving tasks, assumed to reflect the processing (the mental transformation of input) and monitoring capacity of the working memory. Two experiments with a repeated-measures design were performed. Experiment 1 showed a significant decline in performance as a function of sleep loss on Raven's progressive matrices, a problem-solving task. No other main effect of sleep loss was found. Experiment 2 had a different order between tasks than Experiment 1 and the time without sleep was increased. A number-series induction task was also used in Experiment 2. A significant, negative effect of sleep loss in performance on Raven's progressive matrices was found in Experiment 2. The effects of sleep loss on the other tasks were nonsignificant. It is suggested that Raven's progressive-matrices task reflects the ability to monitor encoding operations (selective attention) and to monitor mental "computations".
Adult↗
Differentiation of pituitary adenoma and meningioma: visualization with positron emission tomography and [11C]-L-deprenyl.
Seven patients with clinically nonsecreting pituitary adenoma and 5 patients with meningioma were examined with positron emission tomography using [11C]-LL-deprenyl and [11C]-LL-methionine. The dynamics of the uptake of [11C]-L-deprenyl in the pituitary adenomas demonstrated a rapid and high uptake immediately after the injection, and, later, an almost constant level was observed that was equal to or higher than that observed in normal brain tissue. In the meningiomas, however, the initially high uptake was followed by a marked decrease with time, reaching a level that was approximately half that observed in brain tissue. The study demonstrated high binding of [11C]-L-deprenyl to monoamine oxidase B in pituitary adenomas, whereas the binding in meningiomas was very low. This fact can be used in the differential diagnosis of pituitary adenoma and parasellar meningioma. Operative samples from 10 patients with meningioma and from 5 patients with pituitary adenoma were analyzed biochemically for activity of monoamine oxidase B, using [14C]-phenyl-ethylamine as substrate. The nonsecreting pituitary adenomas demonstrated high enzyme activity, the secreting adenomas about one-tenth of that of the nonsecreting, and the meningiomas one-thirtieth of that of nonsecreting adenomas.
Adenoma↗
Comparison of the proportion of unconjugated to total serum cholic acid and the [14C]-xylose breath test in patients with suspected small intestinal bacterial overgrowth.
The proportion of unconjugated to total cholic acid in fasting serum and the 1-gram [14C]-xylose breath test were determined in 36 patients with suspected bacterial overgrowth of the small intestine. Twenty-two patients had an abnormal [14C]-xylose breath test, indicating bacterial overgrowth. The proportion of unconjugated to total cholic acid was significantly higher in the patients with an abnormal breath test compared with those displaying a normal breath test (47 +/- 5% vs 16 +/- 3%). A good correlation was obtained between the proportion of unconjugated to total cholic acid and the breath test (r = 0.63, n = 36). Provided the [14C]-xylose breath test is reliable as a test of bacterial overgrowth, determination of the proportion of unconjugated to total cholic acid in fasting serum had a sensitivity of 73% and a specificity of 94%. It is suggested that determination of the proportion of unconjugated to total cholic acid in peripheral venous blood may be useful as a simple screening test for detection of bacterial contamination of the upper small intestine provided the patients do not have bile acid malabsorption.
Adult↗
Relaxation and force during fatigue and recovery of the human quadriceps muscle: relations to metabolite changes.
Force and relaxation were measured during electrical stimulation of the quadriceps muscle of 14 volunteers. Stimulation produced 51.2 s of intermittent ischaemic contractions either as 16 3.2-s tetani or as 64 0.8-s tetani. Changes during recovery were followed for 180 s. On 8 subjects muscle biopsies were taken during work and after the rest period for determination of ATP, phosphocreatine and intermediates in glucolysis. The stimulation using 0.8-s contractions gave more pronounced fatigue and slowing of relaxation. There was a good correlation between force and relaxation during work but this relation changed during recovery, indicating that no general relation exists between these two contraction characteristics. In the 0.8-s stimulation more ATP was utilized and there were more profound changes in metabolite levels. We found a correlation between estimated [H2PO4-] and relaxation covering both work and recovery and hypothesize that inorganic phosphate and its removal by phosphocreatine resynthesis during recovery might be important. Since stimulation patterns differ in force and relaxation even after the recovery period we suggest that additional factors, such as pH, are of importance in this work model.
Adenosine Triphosphate↗
Positron emission tomography applied in the study of pituitary adenomas.
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Adenoma↗
Genetic variation in Con A-induced production of interleukin 2 by porcine peripheral blood mononuclear cells.
Genetic variation in concanavalin A (Con A)-induced proliferation and interleukin 2 (IL-2) production by peripheral blood mononuclear cells (PBMC) was studied in blood collected from 96 piglets, aged 7 weeks. The piglets were the offspring of seven sires and 24 dams. Pronounced differences between litters from various dams were observed in the immune parameters measured. Also, large individual differences in the magnitudes of Con A-induced proliferation and IL-2 production were seen for PBMC collected from individual pigs within each litter. Both the time course and magnitude of IL-2 activity showed genetic variation, as results from the offspring of the seven sires differed significantly. However, only the time course, not the magnitude, of proliferation differed among the offspring groups. It was possible to establish a rank order for the sires based on the IL-2 production of PBMC by their offspring. As IL-2 has a key role in regulating the immune response, mitogen-induced IL-2 activity seems to be a good candidate as a general marker for cell-mediated immunity in pigs.
Animals↗
Inhibition of the growth of cultured human meningioma cells by recombinant interferon-alpha.
In this paper the results of investigations on the effect of interferon-alpha (IFN-alpha) on the growth of meningioma cells in culture is reported. A consecutive series of six meningiomas and one meningioma/neurofibroma derived from a patient with neurofibromatosis type 2 was investigated and it was found that the growth of all seven tumours in response to mitotic stimuli (fetal bovine serum or epidermal growth factor) is strongly inhibited by IFN-alpha. Maximal response varied between 100% and 70% inhibition of the incorporation of tritiated thymidine. In some cases an inhibitory response was obtained already at very low doses (less than or equal to 10 U of IFN-alpha per ml). These results indicate that further clinical investigation of the application of IFN-alpha to the treatment of meningioma is warranted.
Adult↗
Effects of the PAF-analog and -antagonist CV-6209 on cultured human glioma cell lines.
Cell lines of human glioma (U-343 MGa and U-251 MG) and human glia (U-533 CG) origin were cultured as monolayers and exposed to CV-6209, an alkyl-phospholipid analog and antagonist of platelet activating factor. This drug had very potent antiproliferative effects on the studied human glioma cell lines; IC50 was 0.9 microM after 48 h treatment and 0.2 microM after 2 weeks treatment. At these doses no growth inhibitory effect was noted on the normal glia cells. The effects on the glioma cells were reversible in the dose intervals, where cell proliferation, 3H-thymidine and 14C-methionine uptakes were greatly inhibited. The simultaneous administration of platelet activating factor [(R)PAF] did not influence the antiproliferative effects of CV-6209 on the cells cultured as monolayers. The structurally similar analog CV-3988 also had antiproliferative effects, although at 10 times higher concentration than CV-6209. Two other, structurally unrelated, PAF-antagonists (WEB-2086 and TCV-309) gave effects only at very high concentrations. The U-343 MGa cell line was also exposed to CV-6209 when growing as multicellular spheroids. The studies on the spheroid cultures also demonstrated good antitumoral effects with decreases of both the volume growth and the thymidine uptake. The simultaneous administration of (R)PAF reversed the inhibitory effect of CV-6209 on thymidine incorporation. This study demonstrates a strong antitumoral effect at low concentrations of CV-6209. The antiproliferative effects were probably primarily related to the ether-lipid structure and not to the PAF-antagonistic properties. The good antitumoral effect of CV-6209 on both monolayer and spheroid cultures and the possible PAF-antagonistic properties are discussed.
Cell Division↗
Application of (methyl-11C)-methionine in the multicellular spheroid system.
Human glioma (U-343 MGa) and human colon carcinoma (HT-29) cell lines were cultured as multicellular spheroids, and the accumulations of the L- and D-enantiomers of 11C-methionine were investigated. The accumulation of radioactivity in the spheroids was expressed as relative counts, by dividing the radioactivity measured in the spheroid with the radioactivity of the same volume of the incubation medium. The experiments were verified using 14C-labeled L- and D-methionine. The influence of spheroid volume, specific activity, incubation time, washing time, and the environmental temperatures were investigated. The spheroid model was used to determine the effect of the lipoxygenase inhibitors BW A4C and AA-861, the ether-phospholipid type PAF-antagonist CV-6209 and the protein synthesis inhibitor cycloheximide on methionine uptake. The results showed that 11C-L-methionine can be applied in the study of drug effects on multicellular tumor cell aggregates.
Benzeneacetamides↗
PET as a tool in the clinical evaluation of pituitary adenomas.
Positron emission tomography (PET) was used in over 400 examinations in patients with pituitary adenoma. It was demonstrated that PET with carbon-11-methionine can give valuable complementary information in the diagnosis of this tumor due to PET's ability to adequately depict viable tumor tissue in contrast to fibrosis, cysts and necrosis. Furthermore, PET with dopamine D2 receptor ligands can characterize the degree of receptor binding and thus give information as to the prerequisites for dopamine agonist treatment. Most important is the very high sensitivity given by PET with carbon-11-methionine in the evaluation of treatment effects. It is concluded that when properly used PET can be fully justified in the clinical handling of patients with pituitary adenomas and other intracranial tumors.
Adenoma↗
Contraction characteristics of the human quadriceps muscle during percutaneous electrical stimulation.
Percutaneous electrical stimulation was used to study the force response of the quadriceps muscle. The normal frequency dependence of force was investigated in muscles at rest and after fatiguing contractions. A comparison between force response during fatigue induced by electrical stimulation at different frequencies and by voluntary work suggested equal changes in contractility, irrespective of the fatigue-inducing procedure. In fresh muscle we found a linear relation between stimulation period (10-100 ms) and force. At fatigue the relation changes with maximal deviation from linearity at a 50-ms period (20 Hz). There is a rapid recovery of high frequency force whereas the low frequency response remains low even after 30 min rest. At very low frequencies there is initially unexpectedly high force in fatigued muscle. This could be a result of increased fusion of twitches with initially prolonged relaxation time. To study the twitch summation we compared experimental results in a wide frequency range with computer-simulated twitch summations and present the frequency dependence of summation processes in human quadriceps muscle.
Adult↗
Effect of iscoms and their adjuvant moiety (matrix) on the initial proliferation and IL-2 responses: comparison of spleen cells from mice inoculated with iscoms and/or matrix.
In the iscom, antigen is attached by hydrophobic interactions to a matrix which is built up by the adjuvant Quil A and lipids. Thus, the iscom presents antigen in multiple copies on a small particle with a built-in adjuvant. By studying the specific antibody response, in vitro proliferation and IL-2 secretion by splenocytes from mice following different in vivo treatments with iscoms and/or matrix, we attempted to distinguish between nonspecific stimulatory effects, caused by the matrix or iscoms, and specific responses to the antigens incorporated into iscoms. The results strongly suggest that matrix and also iscoms exert a nonspecific adjuvant activity by a transient high spontaneous proliferation of cells collected within 2 weeks after administration of iscoms or matrix. This high rate of proliferation was preceded by suppressed proliferation, 3 days after injection with matrix or iscom. The adjuvant component included in iscoms, i.e., the matrix, does not excert a mitogenic stimulation in vitro or influence the levels of specific antibodies in serum. Specific responses to the antigens included in iscoms were recorded both as increasing levels of serum antibodies and as iscom-induced proliferation of immune spleen cells in vitro. The recruitment of IL-2 was only related to the specific stimulation induced by the antigens in iscom.
Adjuvants, Immunologic↗
Effects of prostaglandin and leukotriene inhibitors on the growth of human glioma spheroids.
Established cell-lines of human glioma origin were cultured as multicellular spheroids or as monolayers. Volume growth and 3H-thymidine labelling were analysed for the spheroids after continuous exposure to drugs interfering with the release of arachidonic acid and the production of prostaglandins and leukotrienes. Comparative measurements were made on monolayer cultures. The cyclo-oxygenase inhibitor indomethacin enhanced growth at intermediate concentrations (0.5-5.0 micrograms/ml) but reduced growth at 50 micrograms/ml. The dual cyclo-oxygenase and lipoxygenase inhibitor ketoprofen had a significant inhibitory effect on growth and cell proliferation of spheroids at high concentration (50 micrograms/ml). The weak lipoxygenase inhibitor NDGA (quinone-form) decreased growth whereas the strong lipoxygenase inhibitor NDGA (hydroquinone-form) did not reduce growth rate but significantly decreased cell proliferation. Quinacrine reduced the spheroid growth rate although dexamethasone had no effects. Thus, inhibitors of the arachidonic acid cascade had growth inhibitory effects in the spheroid tumour model as well as in cells cultured as monolayers.
Arachidonic Acids↗
Effects of the 5-lipoxygenase inhibitors AA-863 and U-60,257 on human glioma cell lines.
The effects of two specific 5-lipoxygenase inhibitors AA-863 and U-60,257 (piriprost) on the growth of two human glioma cell lines, U-343 MGa and U-251 MG were investigated. Both monolayer cultured cells and spheroids were studied. The results of the monolayer studies showed potent and dose dependent inhibitory effects on the proliferation of glioma cells (IC50/one week treatment/of AA-863: 9.0 microM, IC50 of U-60,257: 40.0 microM). The experiments made on the tumor spheroids suggested an inhibitory effect on proliferation and volume growth already at lower doses (AA-863: 0.4-2.0 microM, U-60,257: 1.0-5.0 microM), a dose range where effects were not found in monolayers. At higher doses (AA-863: 10.0-30.0 microM, U-60,257: 30.0-90.0 microM) the experiments with spheroids failed to demonstrate a further inhibitory effect on spheroid volume, probably attributed to phenomena such as swelling of cells, dissociation of spheroid structure and development of necrosis. The clearly dose dependent inhibitory effect on the proliferation of human glioma cells in monolayer culture and the inhibitory effects on spheroid growth with these specific inhibitors indicate a role for lipoxygenase products in the growth of gliomas.
Arachidonate Lipoxygenases↗
Delineation of gliomas with magnetic resonance imaging using Gd-DTPA in comparison with computed tomography and positron emission tomography.
Fourteen patients with cerebral gliomas were investigated by MR imaging using Gd-DTPA (Magnevist), CT with the contrast agent iohexol (Omnipaque) and, as a reference, positron emission tomography (PET) using 11C-L-methionine. Tumour areas with disruption of the blood-brain-barrier (BBB) as seen on MR and CT were compared with areas increased accumulation of methionine in PET. There were 6 patients with high-grade astrocytoma (grade III-IV), 5 with low-grade astrocytoma (grade I-II) and 3 with oligodendroglioma. In 4 high-grade tumours, PET showed a larger tumour or tumour tissue in additional areas, compared with enhancement on MR and CT, while in 2 cases the tumour extension was similar in the three modalities. In the low grade tumour group, the findings on PET differed from those on post-contrast MR or CT in 7 cases. In 3 of these cases, no disruption of the BBB was seen either on MR or on CT. In 2 of our 14 patients CT showed larger enhancement extension than MR and in 2 cases MR was superior to CT in this respect. The enhancement intensity was higher on MR in 4 patients and on CT in 2 patients. No definite difference in the delineation of tumour tissue between the T1 weighted SE sequences was found. The gradient echo sequences FLASH and FISP gave limited information that was less than that provided by the T1 weighted SE sequences. A greater increase in signal intensity in T1 weighted images was usually seen 5 min post-contrast in the high-grade tumours than in the low-grade ones.
Adult↗
High affinity [3H]paroxetine binding to serotonin uptake sites in human brain tissue.
[3H]Paroxetine binding to human brain tissue was characterized. Competition studies in the putamen and frontal cortex revealed single-site binding models for binding sensitive to 5-hydroxytryptamine (5-HT) (Ki 1-3 microM) and citalopram (Ki 0.6 nM), which displaced the same amount of binding. However, desipramine, norzimeldine and fluoxetine displaced additional binding (10-20%) and these competitors fitted two-site binding models with high affinity components in the nanomolar range and low affinity components in the micromolar range. The high affinity components approximated the 5-HT- and citalopram-sensitive binding fraction. Most of the [3H]paroxetine binding sites were protease-sensitive, but the low-affinity (microM) sites appeared to be protease-resistant. Based on these findings, only the [3H]paroxetine binding representing the fraction sensitive to 30 microM 5-HT (or e.g. 0.3 microM norzimeldine), was regarded as specific binding. This binding fraction was saturable with an apparent binding affinity (Kd) of 0.03-0.05 nM throughout the brain. The highest binding densities were obtained in the hypothalamus and substantia nigra (Bmax 500 fmol/mg protein). The basal ganglia reached intermediate densities (Bmax 200 fmol/mg protein), whereas cortical areas had low Bmax values (less than 100 fmol/mg protein). The lowest B max value was noted in cerebellar cortex (30 fmol/mg protein). The [3H]paroxetine binding was competitively inhibited by low concentrations of 5-HT, imipramine and norzimeldine, suggesting that the substrate recognition site for 5-HT uptake was labeled. Compounds active at dopaminergic, noradrenergic, histaminergic, 5-HT1, 5-HT2 and cholinergic muscarinic sites did not affect the binding at 100 microM concentrations. It is concluded that [3H]paroxetine is a marker for the 5-HT uptake site in the human brain, provided that an adequate pharmacological definition of specific binding is performed.
Aged↗