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Biomedical subjects

M Bergström

Publications and source records attributed to M Bergström.

At least 109 records · Page 6Linked to original sources

Accurate detection of Helicobacter pylori infection with a simplified 13C urea breath test.

The urea breath test (UBT) has been shown to be a reliable non-invasive method for detection of H. pylori infection. There is widespread use of a test meal in the 13C UBT, but to what extent exclusion of the test meal actually influences the accuracy of the test has been poorly investigated. In addition, there is variability between test protocols in breath sampling frequency. In this evaluation, 91 patients with dyspeptic symptoms were investigated in an out-patient endoscopy ward, using a simplified 13C UBT without a test meal, and a single point breath evaluation after ingestion of 13C-labelled urea. Helicobacter pylori infection was diagnosed on upper endoscopy by histology and rapid urease tests on biopsies from the antrum and corpus mucosa of the stomach. Fifty-four percent of the patients had H. pylori infection. With the chosen cut-off level, the sensitivity and specificity of the 13C UBT were 92% and 95%, respectively. We conclude that this simplified 13C UBT is easy to perform and a very reliable test for detecting H. pylori infection, making it a suitable test in routine clinical work.

Adult↗

Positron emission tomography with 11C-D-deprenyl in patients with rheumatoid arthritis. Evaluation of knee joint inflammation before and after intra-articular glucocorticoid treatment.

Seven patients with arthritic disease and with clinical signs of inflammation of the knee joint, were investigated with positron emission tomography (PET) after injection of [N-methyl-11C]-D-deprenyl. Two healthy volunteers were included as controls. In five patients the investigation was repeated after an intra-articular injection of glucocorticoids. All patients showed very high uptake of the tracer in the paraarticular structures of the joint. After treatment there was approximately a 50% reduction of the uptake in the treated knees, both in the high uptake regions and in the surrounding soft tissues. No change was observed in the non-treated knees. In the healthy volunteers, only soft tissue surrounding the joint showed an uptake of the tracer, but at a magnitude which was 6-8 times lower than the high uptake regions in the arthritis patients. Although the mechanisms for the high uptake of 11C-D-deprenyl in affected joints of patients with arthritis is not clear, the present work points to a potential of PET for the assessment of disease intensity and monitoring of treatment.

Adult↗

Receptor imaging technique with 11C-labeled receptor ligands in living brain slices: its application to time-resolved imaging and saturation analysis of benzodiazepine receptor using [11C]Ro15-1788.

Recently we developed a novel imaging technique using positron emitter-labeled compounds as probes and a storage phosphor screen as a detector. This approach makes it possible to follow a variety of biochemical processes with spatial information in living brain slices. Further technical development is reported here in terms of time-resolved imaging and receptor characterization in a real equilibrium state. The method was validated by use of [11C]Ro15-1788, a benzodiazepine receptor antagonist. Fresh brain slices were incubated with [11C]Ro15-1788 in oxygenated Krebs-Ringer solution at 37 degrees C, in a specially designed chamber. By placing the chamber on a storage phosphor screen, we could obtain two-dimensional images of radioactivity in the slices. Time-resolved imaging was made at 5 min intervals, revealing that it took 60 min to reach equilibrium binding. The dissociation process was observed by adding an excess amount of unlabeled Ro15-1788 to the chamber, 25 min was required for the full dissociation. In the equilibrium state, i.e. in the presence of free radio-ligand, Scatchard plot analysis was performed on the cerebral cortex (Kd = 7.4 nM, Bmax = 146 fmol/mg tissue) and striatum (Kd = 7.5 nM, Bmax = 107 fmol/mg tissue), suggesting the presence of a single component of binding site in these two regions. The present method, for the first time, made it possible to study a ligand-receptor interaction in living brain slices with temporal and spatial resolutions. This technique should prove useful for studies of receptor function under physiological conditions.

Animals↗

Infections after hysterectomy. A prospective nation-wide Swedish study. The Study Group on Infectious Diseases in Obstetrics and Gynecology within the Swedish Society of Obstetrics and Gynecology.

BACKGROUND: An increased use of prophylactic antibiotics to avoid postoperative infections in women undergoing hysterectomy has been observed in Sweden. This investigation was performed a) to study the infection rate to enable future evaluation of the effect of prophylactic antibiotic regimens and b) to identify subgroups suitable for intervention. METHOD: A prospective study comprising all women undergoing pelvic surgery with hysterectomy during a two month period at forty-two Departments of Obstetrics and Gynecology in Sweden. Relevant information regarding the surgical procedure and the postoperative course was included in a standardized form at discharge from hospital and at a follow-up visit 4 to 6 weeks after surgery. RESULTS: Of the 1060 women included in the study, 23% developed postoperative infections: 9.4% had wound-, cuff-, and/or deep infections, 13% urinary tract infections, and 4% other infections unrelated to the surgical site. Only half of the wound/cuff-/deep infections were diagnosed before discharge from the hospital. Wertheim-Meigs procedures, bleedings per-operatively exceeding 1000 ml, and presence of bacterial vaginosis (BV) were associated with an increased risk of postoperative infections. Among women undergoing abdominal hysterectomy for benign reasons, (n = 159), wound-cuff/deep infection was significantly associated with preoperative BV, i.e. 7 of 28 (25%) vs. 11 of 131 (8%), respectively (relative risk = 3.0, p = 0.01). Infection was associated with prolonged postoperative hospital stay. Antibiotics were given pre- or postoperatively to 236 (22%) of the 1060 women. Reduction in the postoperative infection rate was seen among women undergoing vaginal hysterectomy who were given pre- or postoperative antibiotics. CONCLUSION: The postoperative infection rate after hysterectomy was clinically significant in this population. Wertheim-Meigs procedures, peroperative bleeding > 1000 ml and BV were identified as risk factors for postoperative infections after hysterectomy.

Anti-Bacterial Agents↗

Catechol-O-methyltransferase inhibition increases the uptake of 11C-3-(3,4-dihydroxyphenyl)-L-alanine in the rat pancreas.

BACKGROUND: The objective of the present investigation was to evaluate the uptake and metabolism of 3-(3,4-dihydroxyphenyl-L-alanine) (L-DOPA) in the rat pancreas. METHODS: The procedure included intravenous injection of the positron-emitting radiotracer L-[beta-11C] DOPA (DOP) into unanaesthetized male Sprague-Dawley rats and evaluation of uptake of radioactivity in organs in animals only given the tracer and in animals given therapeutic doses of three different catechol-O-methyltransferase (COMT) inhibitors, OR-486, OR-611, or Ro 41-0960. Selected pancreati were homogenized, and the chemical form bearing the radioactivity was analysed with high-performance liquid chromatography (HPLC). RESULTS: The main finding was that the tracer uptake in the pancreas increased fourfold when the rats were pretreated with COMT inhibitors. Half maximum effect of OR-486 was found at a dose of 0.2 mg/kg. HPLC analysis showed that with COMT inhibitor, the radioactivity in the pancreas consisted of 90% DOPAC. When administering MAO-A and COMT inhibitor together, the pancreas radioactivity corresponded to dopamine. Also in the pig pancreas a significant increase of DOP was observed after COMT inhibition. CONCLUSIONS: This study has shown a high turnover of L-DOPA in the rat pancreas, which can be modulated to give enhanced levels of DOPAC or dopamine by COMT and MAO inhibition.

Analysis of Variance↗

In vivo demonstration of enzyme activity in endocrine pancreatic tumors: decarboxylation of carbon-11-DOPA to carbon-11-dopamine.

METHODS: We used PET to characterize the uptake and decarboxylation of 11C-L-DOPA in vivo in two patients with endocrine pancreatic tumors: one glucagonoma and one gastrinoma. RESULTS: With L-DOPA labeled with 11C in the beta position, in which the radioactive label follows the molecule through decarboxylation to dopamine, significant uptake was observed in the tumors. With L-DOPA labeled in the carboxyl group, in which the label is rapidly eliminated from the tissue as 11CO2 if decarboxylation takes place, an almost complete lack of uptake is noted. CONCLUSION: This study shows that, using selective position labeling, an in vivo action of enzymatic activity can be observed with PET and that significant decarboxylation occurs in the tested endocrine pancreatic tumors. Also, marked retention of radioactivity occurs after treatment with somatostatin analogs. It is hypothesized that this is a reflection of a reduction of exocytosis which is induced by this treatment.

Aged↗

PET and parathyroid L-[carbon-11]methionine accumulation in hyperparathyroidism.

UNLABELLED: The study was designed to characterize L-[methyl-11 C]methionine accumulation in abnormal parathyroid tissues of hyperparathyroidism (HPT). METHODS: Thirty-four patients with primary (n = 32) or secondary HPT were investigated with PET before primary or reoperative (n = 25) parathyroid surgery. Parathyroid 11C-methionine accumulation was analyzed for integrated uptake values in defined tissue volumes standardized for the injected dose and body weight (SUV), four contiguous pixels of maximal accumulation (SUVhs), SUV multiplied by area of region of interest (SUVr) and by the excised tissue weight (SUVw). Transport rate constants (slope, slopehs) were calculated according to Patlak's formula using plasma 11C activity corrected for 11C-methionine metabolites. RESULTS: True-positive localization was achieved in 85% of patients in whom 81% of the excised parathyroid lesions were visualized; no false-positive results were obtained. Corresponding proportions were 59% and 57% for CT and 55% and 52% for ultrasound, respectively. In the true-positive cases, parathyroid SUV, SUVhs and transport rate constants were consistently higher (p < 0.01) than in the thyroid, pharynx-esophagus, neck muscle and apical lung. Parathyroid SUV, SUVhs and SUVr increased with intact serum parathyroid hormone and calcium values (p = 0.0001-0.031), and weight of the excised tissue correlated with SUV and SUVhs (p = 0.024, 0.044). Parathyroid SUVhs varied strongly with the transport rate constants (p = 0.0008), and SUVr as well as s-calcium values differed significantly between parathyroid adenomas (n = 11), chief cell hyperplasias (n = 13), inadvertent implants (n = 3) and parathyroid cancers (n = 3). CONCLUSION: Carbon-11-methionine PET has potential application in preoperative localization and metabolic characterization of abnormal parathyroid tissues in human HPT.

Adenoma↗

[PET in clinical work. A refined instrument for imaging].

Positron emission tomography (PET) enables in vivo studies to be performed in patients to investigate the binding or metabolism of biologically/functionally active substances labelled with short-lived positron-emitting radionuclides. The procedure has been used for discriminative analysis of physiology and function, both normal and pathological. The range of clinical applications includes studies of cerebral ischaemia and heart diseases, tumor diagnosis and treatment follow-up, presurgical work-up in cases of epilepsy, and characterization and treatment follow-up in cases of dementia. The clinical uses of PET are outlined in a review of the last three years' experience at the PET centre at Uppsala University.

Alzheimer Disease↗

Regional deposition of inhaled 11C-nicotine vapor in the human airway as visualized by positron emission tomography.

The deposition of 11C-nicotine in the respiratory tract from a nicotine vapor inhaler was studied by means of positron emission tomography (PET) in an intrasubject comparison of six healthy smokers using two modes of inhalation: one with shallow, frequent inhalations ("buccal mode") and one with deep inhalations ("pulmonary mode"). An average of 15% of the radioactivity was released from the vapor inhaler after 5 minutes of inhalation. Approximately 45% of the dose released was found in the oral cavity. A significant amount of radioactivity, 10%, was observed in the esophagus, suggesting transfer of a major fraction of the dose to the stomach. Only a minor fraction, 5%, was found in the lungs, followed by 2% in the bronchi and 1% in the trachea. The deposition in the oral cavity closely followed a linear pattern during the 5 minutes of inhalation and was followed by a rapid elimination from the oral cavity, with an average half-life of 18 minutes. Only 8% of the dose released remained in the oral cavity 45 minutes after the end of inhalation. On the other hand, the dose fraction of about 14% distributed into the body tissue compartment at the end of inhalation had risen to 60% at that late time point. No statistically or clinically important differences were observed between the buccal and the pulmonary mode of inhalation in either deposition pattern or elimination rates.

Administration, Inhalation↗

In vitro positron emission tomography (PET): use of positron emission tracers in functional imaging in living brain slices.

Positron-emitting radionuclides have short half-lives and high radiation energies compared with radioisotopes generally used in biomedical research. We examined the possibility of applying positron emitter-labeled compounds to functional imaging in brain slices kept viable in an oxygenated buffer solution. Brain slices (300 microns thick) containing the striatum were incubated with positron emitter-labeled tracers for 30-45 min. The slices were then rinsed and placed on the bottom of a Plexiglas chamber filled with oxygenated Krebs-Ringer solution. The bottom of the chamber consisted of a thin polypropylene film to allow good penetration of beta+ particles from the brain slices. The chamber was placed on a storage phosphor screen, which has a higher sensitivity and a wider dynamic range than X-ray films. After an exposure period of 15-60 min, the screen was scanned by the analyzer and radioactivity images of brain slices were obtained within 20 min. We succeeded in obtaining quantitative images of (1) [18F]fluorodeoxyglucose uptake, (2) dopamine D2 receptor binding, (3) dopa-decarboxylase activity, and (4) release of [11C]dopamine preloaded as L-[11C]DOPA in the brain slice preparation. These results demonstrate that positron emitter-labeled tracers in combination with storage phosphor screens are useful for functional imaging of living brain slices as a novel neuroscience technique.

Animals↗

Labelling of polysaccharides using [11C]cyanogen bromide. In vivo and in vitro evaluation of 11C-hyaluronan uptake kinetics.

A method for the 11C-labelling of polysaccharides in high specific radioactivity is described. Dextran and hyaluronan were treated with [11C]cyanogen bromide in aqueous solution at pH 11.5 to give 30-47% radiochemical yields with higher than 98% radiochemical purity in synthesis times of 24-26 min counted from the end of bombardment. Specific radioactivities at the end of synthesis ranged from 0.12 to 3.1 Ci/mumol. The biodistribution kinetics of [11C]hyaluronan injected intravenously was studied in rats by means of positron emission tomography, showing a rapid and displaceable uptake in liver. Uptake and displacement of [11C]hyaluronan was also demonstrated in cultured rat liver endothelial cells.

Animals↗

Positron emission tomography with [11C]deuterium-deprenyl in temporal lobe epilepsy.

We performed positron emission tomography (PET) with [11C]deuterium-deprenyl in 9 patients with temporal lobe epilepsy (TLE) undergoing evaluation for possible epilepsy surgery. Seven patients had unilateral and 2 had bilateral mesiotemporal epileptic foci based on the preoperative investigation including ictal EEG discharges and PET with 2-[18F]fluoro-2-deoxyglucose (FDG). Deprenyl is an irreversible inhibitor of monoamine oxidase type B (MAO-B) with a very high affinity for the enzyme. In the brain, MAO-B is preferentially located in astrocytes, and a previous in vitro study showed increased binding of the ligand in sclerotic hippocampi. Dynamically acquired N-[methyl-11C]-a,a-di-deutero-L-deprenyl distribution in PET images were analyzed graphically, and the focus regions were assessed visually on the PET images. In addition, the accumulation rate and distribution volume of the tracer relative to the cerebellar cortex were measured in standardized homologous temporal regions by semiquantitative methods. Uptake of [11C]deuterium-deprenyl was significantly increased in the epileptogenic temporal lobes, both apparently and semiquantitatively. By calculating mean interlobar ratios, we identified the temporal lobe containing the epileptic focus in six unilateral cases. One case was ambiguous but was not falsely localized. The two bilateral cases were correctly identified as such. Our results suggest that PET with [11C]deuterium-deprenyl might be a useful method for identification of epileptogenic temporal lobes.

Adult↗

Pancreatic neuroendocrine tumors: diagnosis with PET.

PURPOSE: To evaluate the use of carbon-11-labeled L-dihydroxyphenylalanine (L-DOPA) and hydroxytryptophan (5-HTP) in the diagnosis of pancreatic endocrine tumors with positron emission tomography (PET). MATERIALS AND METHODS: Twenty-two consecutive patients with clinically and biochemically verified pancreatic endocrine tumors were examined with computed tomography (CT) and PET with L-DOPA alone (n = 16) or both C-11-L-DOPA and C-11-5-HTP (n = 6). RESULTS: Tumor uptake of L-DOPA was found in 11 patients, eight of whom had metastatic disease. Heterogeneity of tracer uptake was noted among different lesions in the same patient (ie, high uptake in some lesions and low uptake in others). Results in patients examined with both L-DOPA and 5-HTP correlated well, but the uptake levels of 5-HTP were higher in two of three patients with positive findings. In two additional patients, CT enabled detection of tumors not detected at PET. CONCLUSION: The current PET technique can be a valuable complement to CT in demonstration of functional pancreatic endocrine tumors, in particular, glucagonomas, but is less useful in detection of nonfunctional tumors.

Adenoma, Islet Cell↗