Positron-emission tomography as a radiological technique in neuroendocrine gastrointestinal tumors.
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5-Hydroxytryptophan↗
Biomedical subjects
M Bergström
Publications and source records attributed to M Bergström.
Non-synchronous behavior of neuronal activity, oxidative metabolism and blood supply during mental tasks in man.
In near-infrared spectroscopic studies during mental tasks such as problem solving and mental arithmetic, we found that 9 of 33 healthy volunteers showed decreases in both the regional cerebral blood flow (r-CBF) and oxygen consumption rate (CMRO2) in the frontal region of the dominant hemisphere. To confirm these unexpected observations, we performed simultaneous measurements by positron emission tomography (PET) and near-infrared spectroscopy (NIRS) in two such subjects. PET images also showed that CBF decreased within the presumptive area illuminated by near-infrared light during mental task. However, CBF decreased in almost all regions while the subject gave a correct answer. Thus, the questions arose: Are mental tasks always associated with increases in r-CBF and/or CMRO2?
Adult↗
Gadolinium-enhanced MRI and positron emission tomography in Bell's palsy: a preliminary report.
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Adult↗
Principal component analysis of dynamic positron emission tomography images.
Multivariate image analysis can be used to analyse multivariate medical images. The purpose could be to visualize or classify structures in the image. One common multivariate image analysis technique which can be used for visualization purposes is principal component analysis (PCA). The present work concerns visualization of organs and structures with different kinetics in a dynamic sequence utilizing PCA. When applying PCA on positron emission tomography (PET) images, the result is initially not satisfactory. It is illustrated that one major explanation for the behaviour of PCA when applied to PET images is that it is a data-driven technique which cannot separate signals from high noise levels. With a better understanding of the PCA, gained with a strategy of examining the image data set, the transformations, and the results using visualization tools, a surprisingly easily understood methodology can be derived. The proposed methodology can enhance clinically interesting information in a dynamic PET imaging sequence in the first few principal component images and thus should be able to aid in the identification of structures for further analysis.
Artifacts↗
Synthesis of 11C-labelled benzamide compounds as potential tracers for poly(ADP-ribose) synthetase.
Poly(ADP-ribose) synthetase catalyses the synthesis of poly(ADP-ribose) from NAD+, thereby releasing the DNA from histones to a transcriptionally and reparationally active form. In order to investigate if in vivo and in vitro studies of this enzyme are feasible to perform with PET, the poly(ADP-ribose) synthetase inhibitors benzamide, 3-aminobenzamide, 3-methoxybenzamide and nicotinamide were labelled with carbon-11 in the amide group. Starting with the corresponding aromatic halides and hydrogen [11C]cyanide, the substituted [11C]benzonitriles were prepared using a palladium promoted reaction. Conversion of the nitriles to [carboxy-11C]amides was achieved by reaction with sodium percarbonate. A one-pot procedure for the synthesis of the 11C-labelled aromatic amides was developed. The total synthesis time including reversed-phase HPLC purification was 25-35 min. Decay-corrected radiochemical yield was 45-70% and the radiochemical purity > 99%. The specific radioactivity was in the order of 2-3 Ci.mumol-1. Initial distribution and kinetic studies were performed in monkey using the tracer substance injected as a rapid bolus. These studies demonstrated that the blood-clearance was fast for [carboxy-11C]nicotinamide but considerably slower for 3-amino[carboxy-11C]benzamide and 3-methoxy[carboxy-11C]benzamide. The brain uptake was low for all substances except 3-methoxy[carboxy-11C]benzamide which initially had a high brain uptake, followed by a rapid wash-out. The 11C-labelled nicotinamide demonstrated a rapid fixation with high uptake values in the liver, kidney and lymph nodes.
Animals↗
Positron emission tomography with 11C-methionine in hyperparathyroidism.
BACKGROUND: Positron emission tomography (PET) has not been evaluated for preoperative localization and functional characterization of the parathyroid tissue in hyperparathyroidism. METHODS: Images of the neck and upper mediastinum of 23 patients with hyperparathyroidism were obtained by PET after intravenous administration of 400 to 800 MBq L-[methyl-11C]-methionine. The investigation was repeated in six patients after Na2-ethylenediamine tetraacetic acid infusion, whereby stable 65% to 157% rise in intact serum parathyroid hormone values was attained. RESULTS: Parathyroid surgical procedure revealed single (21 patients) or two enlarged parathyroid glands (two patients) that were characterized as chief cell adenoma (n = 13), hyperplasia (n = 10), or carcinoma (n = 2) and weighed 80 to 6000 mg. Twenty (80%) of these glands were localized by PET. The remaining examinations (20%) were false negative and mainly encompassed small parathyroids in juxtathyroid position. Among 15 patients undergoing parathyroid reoperation true-positive localizations were obtained for 87% of the glands. The images displayed lower tracer uptake in residual thyroid lobes (n = 40), esophagus, and cervical vertebrae. Na2-ethylenediamine tetraacetic acid infusion failed to enhance parathyroid uptake values. Ultrasonography, computed tomography, technetium-thallium scintigraphy, and venous sampling revealed 25% to 53% of the pathologic parathyroid tissues of the patients undergoing reoperation and was largely complementary to PET. CONCLUSIONS: The results suggest that PET may provide novel possibilities for the imaging of pathologic parathyroid glands in hyperparathyroidism.
Adult↗
Lipoprotein fractionation in deuterium oxide gradients: a procedure for evaluation of antioxidant binding and susceptibility to oxidation.
Oxidative modifications of lipoproteins appear to contribute to their atherogenicity. Very low and low density lipoproteins (VLDL and LDL) are protected against these modifications by antioxidants that can be incorporated in vivo or in vitro into the particles. We describe here ultracentrifugal procedures for isolation of VLDL and LDL that do not require subsequent dialysis or buffer equilibration. Lipoproteins were isolated in buffers with physiological ionic composition prepared in D2O (deuterium oxide). This allowed measurements of the content of antioxidants and of the susceptibility to oxidation of the isolated LDL without further manipulations. Conventional ultracentrifugal methods use high salt concentrations and require additional steps to eliminate them. This introduces uncertainties in the evaluation of antioxidant binding and on measurements of their effect on VLDL and LDL oxidation. With the method described, the composition of the isolated VLDL and LDL was indistinguishable from that of fractions isolated with KBr gradients. Also, the content of alpha-tocopherol was similar. LDL isolated with KBr solutions appeared to bind 20-45% more of the probucol present in serum than LDL isolated in isotonic solutions prepared with D2O. This was the case with probucol incorporated into plasma or serum in vivo or in vitro. Five out of seven LDL isolated with the D2O procedure from different human sera appeared more resistant to Cu(2+)-catalyzed oxidation than those obtained with KBr gradients from the same serum. In addition to the gradient procedure, we also describe a preparative version of the method that can be used with multiple samples.
Animals↗
Monoamine oxidase-B in astrocytes.
In the present report we describe the astrocytic localization and content of monoamine oxidase-B (MAO-B) by means of a 3H-L-deprenyl emulsion autoradiography in primary cultures of rat astrocytes, in cryosectioned astrocytoma surgical specimen, and in cryosections of human spinal cords from patients dying in amyotrophic lateral sclerosis (ALS) and controls. The occurrence of MAO-B enzyme protein depends on the degree of cellular differentiation as demonstrated by studies on astrocytes in primary cultures analyzed at two different stages of maturation. Highly differentiated cells exhibited high relative enzyme concentration whereas glioblasts lacked or showed very low contents of MAO-B enzyme. This was further substantiated by studies performed on human astrocytoma tissue using 3H-L-deprenyl emulsion autoradiography in combination with immunohistochemical detection of glial fibrillary acidic protein (GFAP). Regional increases of MAO-B concentration were found in ALS lumbar sections with quantitative 3H-L-deprenyl autoradiography. On the basis of results obtained from double staining for GFAP and MAO-B, the increase in MAO-B seemed to be due to an increased number of astrocytes as well as an increased content of MAO-B in reactive species of astrocytes. A cell culture model has been used that produces cells with morphology and GFAP-content similar to reactive cells. These astrocytes exhibited high relative content of the MAO-B enzyme protein. In the light of the presented data, taking into account the finding that a subpopulation of reactive cells contained low levels of MAO-B, a heterogeneity among reactive astrocytes was observed.
Amyotrophic Lateral Sclerosis↗
A simplified method to determine galactose elimination capacity in patients with liver disease.
Galactose elimination capacity (GEC) is one of the most widely used liver function tests. It is relatively simple but still involves a number of capillary blood samples and is therefore fairly expensive. In the current study we present a simplified formula, based on GEC investigations in 103 cirrhotic patients, with which it is possible to estimate the GEC with one or two blood samples. Using this formula: GEC = [7.422--corrected B-galactose60 min]/4.575, we could accurately predict GEC in 24 additional patients.
Blood Specimen Collection↗
Positron emission tomography in tumor diagnosis and treatment follow-up.
The technique of positron emission tomography (PET) is described. PET is an in vivo imaging and quantitative technique which allows the visualization of various functional and biochemical parameters. PET is a tracer technique in which bioactive tracer substances are labelled with short-lived positron emitting radionuclides. The most important of these are 15O, 13N, 11C and 18F with decay times ranging from 2 min to 2 h. The radiolabelled substance is injected intravenously and the distribution, uptake and binding are registered externally with the PET camera using of the order of 4,000 small detectors. The camera produces simultaneously 15 tomographic slices in which the absolute concentration of the tracer substance can be measured. Using a dynamic imaging sequence starting after the injection of the tracer, the dynamics of the tracer uptake is recorded and can be used to deduce functional parameters, such as perfusion flow, tracer distribution, binding to receptor or enzyme systems, etc. depending on the choice of tracer substance. The great versatility of PET and its potential of direct noninvasive study of tumor function will make it a very important clinical and research tool in oncology. With the choice of substances selective for a certain aspect of a tumor's biochemistry the potential opens for a better diagnosis, improved differential diagnosis and, especially with the use of metabolic tracers, an improved possibility to evaluate the response to treatment.
Diagnosis, Differential↗
Positron emission tomography (PET) in neuroendocrine gastrointestinal tumors.
Positron emission tomography (PET) makes it possible to study effects of medical treatment in vivo. Carcinoid tumors with liver metastases, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP) and this overproduction contributes to the clinical symptoms of the carcinoid syndrome. Seven patients with histopathologically verified neuroendocrine tumors and liver metastases, five of whom with ileal carcinoids, one a lung carcinoid and one an endocrine pancreatic tumor, were included in the study. All patients had elevation of urinary 5-HIAA with the exception of one patient with a solitary liver metastasis of midgut origin. After an intravenous injection of 11C-5-HTP, PET was performed and the uptake of radioactivity in tumor tissue, normal liver and plasma were compared. All patients with elevated urinary 5-HIAA and also the patient with a solitary liver metastasis and normal urinary 5-HIAA had high accumulation and signs of a high rate of binding of 5-HTP in the liver metastases. The uptake was relatively homogeneous in midgut carcinoid liver metastases but in large necrotic metastases the radioactivity was localized to the periphery. In three patients PET examination was repeated after 3 months of interferon treatment and in agreement with circulating tumor markers and ultrasonography the uptake of 5-HTP was unchanged. Another patient who received the somatostatin analog somatuline progressed on treatment and accordingly the uptake of 5-HTP also increased. The experience with PET in neuroendocrine gastrointestinal tumors is very limited. Our results so far indicate that 5-HTP can be used to visualize serotonin-producing neuroendocrine tumors and furthermore it might prove to be of value to monitor the effects of treatment, possibly also as an early predictive test of the outcome of treatment.
5-Hydroxytryptophan↗
[Health care priorities].
This article describes the STAKES (National Research and Development Centre for Welfare and Health) Priorisation Project which started at the beginning of 1993. The project surveys ethical problems related to welfare and health care resource allocation. It searches for principles which could be applied in setting priorities whether they are aimed at service systems or individuals. A public debate has been instigated on choices, their justification and values which influence them. A conflict arises when medical advances have improved treatment possibilities and the needs have increased, but health care resources have remained on the same level or diminished. The role of nursing is to safeguard the rights of the patients. Now it is more important than ever to base nursing practice on ethical principles.
Consumer Advocacy↗
[Better methods and improved competence is needed within the medical audit].
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Clinical Competence↗
[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↗