Search PubMed⌕ Search

Biomedical subjects

S Nilsson

Publications and source records attributed to S Nilsson.

At least 271 records · Page 15Linked to original sources

Three-dimensional OctreoScan111 SPECT of abdominal manifestation of neuroendocrine tumours.

In the present study we have investigated the three-dimensional (3D) reconstruction of OctreoScan111 SPECT (single photon emission tomography) images in 20 patients with neuroendocrine tumours. All patients had at least 2 tumour lesions as assessed from computerized tomography (CT) and SPECT. The 3D rendering was performed using a software, which produces images by implementing direct rendering from voxels without an intermediate surface data structure. The software has options for a free choice of thresholding and possibilities of clipping in coronal, transversal and sagittal planes. The results obtained showed that 3D reconstruction with volume rendering (3Dvr) gave a superior topographical localization of tumour uptakes when compared with SPECT. The 3Dvr technique was also combined with transversal clipping in rendered volumes (3Dvr+c). The major advantage with the 3Dvr+c technique was found to be an improved visualization of anatomical references as well as improved diagnostic information in a particular, selected, transversal slice, thus facilitating the identification and comparison of individual tumour lesions.

Abdominal Neoplasms↗

Distribution and elimination of the somatostatin analogue (111In-DTPA-D-Phe1)-Octreotide (OctreoScan111).

The distribution and elimination characteristics of the 111In-labelled somatostatin analogue OctreoScan111 were studied in 23 patients with malignant tumours. The substance exhibited a rapid blood elimination following a bi-phasic pattern. The initial part of the elimination curves showed a t1/2a of between 0.27 and 3.6 h. The patients investigated had creatinine clearance rates ranging from 33 to 124 ml/min. However, within this range, no apparent correlation was found between the OctreoScan111 elimination rate and kidney function. Also no correlation was observed between the amount of administered activity and the elimination rate of OctreoScan111. The serum radioactivity of 6 patients was analyzed with respect to molecular size. These experiments showed that OctreoScan111 circulated unbound in serum. About 3% of the radioactivity, most probably representing 111In-chloride of DTPA-111In-chloride, circulated protein-bound. The elimination of OctreoScan111 radioactivity in urine displayed a bi-phasic pattern. Size separation of the radioactivity appearing in the urine after 24 h showed a higher molecular weight when compared with OctreoScan111, indicating the existence of a metabolite of the injected substance. The results obtained are discussed in the light of a potential role for the substance in systemic radiotherapy.

Adenoma, Islet Cell↗

Somatostatin receptor scintigraphy of carcinoid tumours using the [111In-DTPA-D-Phe1]-octreotide.

Somatostatin-receptor scintigraphy using the 111In-labelled somatostatin-analogue octreotide ([111In-DTPA-D-Phe1]-octreotide) was performed in 40 patients with carcinoid tumours. In 31/40 patients, this scintigraphy proved positive compared with the 33/40 patients whose tumours were disclosed on CT scans. In addition, 18 previously unidentified lesions were detected with this scintigraphy. Two of these lesions represented previously undetectable primary tumours. It is concluded that somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]-octreotide has a future role in the staging of patients with carcinoid disease.

Adult↗

Immunotargeting with monoclonal cytokeratin 8 antibodies of human urothelial cancer transplanted to nude mice.

The possibility of using cytokeratin antibodies for the radioimmunolocalization of urinary bladder cancer was studied. A monoclonal murine IgG antibody was raised against cytokeratin 8 and labelled with iodine-125; normal murine IgG was used for control purposes. The urothelial cancer cell line RT4 was transplanted into immunodeficient nude mice. The anti-cytokeratin 8 antibody was administered intraperitoneally and its uptake in the tumour and other organs was analyzed with a computerized gamma camera. Optimal scintigraphic visualization occurred 11 days after antibody administration. The tumour/blood ratio of the specific antibody was 5.64 (+/- 5.01 SD) on day 11, compared with 0.73 (+/- 0.35 SD) in the control. Autoradiography demonstrated antibody uptake preferentially in viable sections of the tumour. The antibody uptake is presumed to be the result mainly of binding to the released cytokeratin in and around cells lysed during natural cellular death. The monoclonal murine anti-cytokeratin antibody is of potential interest in studies aimed at improving the clinical staging of urinary bladder cancer.

Animals↗

Characterization and uptake of radiolabelled meta-iodobenzylguanidine (MIBG) in a human neuroblastoma heterotransplant model in athymic rats.

Cells from an established human neuroblastoma cell line, SH-SY5Y, were demonstrated to grow and form solid tumours in nude rats. This cell line, which is an adrenergic subclone of the SK-N-SH cell line, has previously been used in differentiation model studies. The tumours retained the neuronal phenotype of the cultured cells, as evidenced by the expression of neuron-specific enolase (NSE) and chromogranin A + B. The transcription factor Isl-1, a protein expressed in subsets of neurons and endocrine cells as well as in neuroblastoma cells, was also expressed in the transplanted tumours, thus further verifying the retained phenotype of the cells under in vivo conditions. At scintigraphy utilizing 123I-MIBG the optimal tumour/background ratio was obtained 20 h after injection. The assessment of tissue/serum ratios showed the highest uptake in the spleen (0.067% per gram of inj. activity), neuroblastoma tumours (0.067% per gram of inj. activity) and in the adrenals (0.065% per gram of inj. activity).

3-Iodobenzylguanidine↗

Liver metabolism during treatment with estradiol and natural progesterone.

Serum concentrations of sex hormone-binding globulin (SHBG), corticosteroid binding globulin (CBG), ceruloplasmin, lipoprotein A and liver enzymes were measured in 30 postmenopausal women treated with 2 mg micronized 17 beta-estradiol daily and micronized progesterone orally in doses of 50, 100 and 200 mg daily, as progestogen supplementation. The treatment lasted for 4 months. The serum levels of SHBG and CBG increased during treatment and a weak association between progesterone dosage and CBG was observed. Levels of lipoprotein A and liver enzymes did not change. It is concluded that micronized natural progesterone is an attractive means of progesterone supplementation in postmenopausal hormone replacement therapy without any liver-related side-effects.

Adult↗

Repeated measurements over time: statistical analysis of the angiographic outcomes in the Probucol Quantitative Regression Swedish Trial (PQRST).

An increasing use of non-invasive techniques and arteriographies of the coronary, carotid or femoral arteries has taken place during recent years. This has prompted researchers to perform long-term randomized trials aiming at reducing atherosclerosis progression or achieving regression by cholesterol lowering in high risk populations. These trials are designed to use outcomes such as various indices of atherosclerosis which are assessed repeatedly over time. There are major decisions to be made contingent on the data structures in these trials, such as sphericity, interaction, development over time, missing data, non-normality etc. So, the statistical analysis of such data needs to be planned and specified a priori in a unified manner. This is demonstrated for the Probucol Quantitative Regression Swedish Trial (PQRST) which is designed to answer the question whether the drug probucol, given in combination with diet and cholestyramine, can delay development of atherosclerosis in hypercholesterolemic patients up to 70 years old. Change in atheroma volume is assessed by a newly developed quantitative angiographic technique based on digitized angiograms.

Analysis of Variance↗

Reproducibility of quantitative arteriographic assessment of atherosclerosis in the femoral artery.

Results from computer-analysed angiograms in the Probucol Quantitative Regression Swedish Trial (PQRST) were analysed to determine the reproducibility of the method and any drift in the analysing system. The precision index (P(mu)) for 2 angiography series, made at 10 min intervals, of the femoral artery in 276 patients was 10.5 for lumen volume and 21.9 for roughness (edge irregularity). No difference in reproducibility was found between patients with and without symptoms of peripheral atherosclerosis or when looking at the reproducibility over years. A drift of 0.67% per year in the radiographic equipment (but not in the analysis system) was found, confirmed by use of phantoms. Computer-based analysis of femoral atherosclerosis is a reliable method for follow-up trials, giving high reproducibility even if the trial spans over several years and involves different centres. The use of phantoms is essential for checking the method over time.

Adult↗

Evidence for a non-estrogenic cytostatic effect of estramustine on human prostatic carcinoma cells in vivo.

Estramustine is one of the main metabolites of estramustine phosphate (EstracytR), a drug used in the treatment of advanced prostatic cancer. In the present study the hormone independent human prostatic carcinoma cell line DU 145 implanted subcutaneously in nude mice (NMRI) was used to investigate the mode of action of estramustine in vivo. Metaphase arrest was found in mice treated with estramustine intraperitoneally, 200 and 400 micrograms daily for 2 weeks, 5 days a week. A significant dose dependent decrease in the number of anaphase figures was found. A 7 to 8 fold increase in the number of abnormal metaphases, i.e., highly contracted and unaligned chromosomes, was found. Uptake and retention of 3H-estramustine was found in tumour tissue. No increase in the mitotic index or the number of abnormal metaphases was found in animals treated with polyestradiol phosphate (EstradurinR). This is the first time evidence has been presented demonstrating the anti-mitotic effect of estramustine in vivo.

Animals↗

Radiation sensitization by estramustine studies on cultured human prostatic cancer cells.

In low-stage prostatic carcinoma, local cure can be obtained with radiation therapy alone, while in locally advanced disease the chances for cure are less. In this study, we have addressed the question of whether estramustine (EM), the main cytostatic metabolite of estramustine phosphate (Estracyt), may act as a radiosensitizing agent. This drug accumulates in prostatic cancer and has also been shown to arrest cancer cells at metaphase both in vitro and in vivo. The human prostatic cancer cell line DU 145 was grown as cultures monolayer and incubated with EM in concentrations varying from 1 to 20 micrograms/ml. External beam irradiation was performed with doses ranging from 0 to 8 Gy using gamma rays from a 60Co source. Clonogenic cell survival (CS) was used to analyse the radiation sensitizing effect of EM. The radiation dose modifying factor (DMF) at the survival level 0.1 was found to be 0.77 in the presence of EM (5 micrograms/ml), i.e., 23% sensitization was obtained. When irradiating cells at the standard fraction dose of 2 Gy in the absence of EM, 22% of the cells lost their clonogenic ability. In presence of EM (5 micrograms/ml), 2 Gy caused 40% of the cells to lose their clonogenic ability. Thus a radiation sensitizing effect of EM was established in the CS assay. It was also of interest to determine if the radiosensitizing effect of EM could be confirmed in a rapid assay. The rapid fluorescence assay was used to observe early damage of the cells. Results showed that by 2 days after exposure to irradiation a weak tendency towards sensitization was seen, while a clear sensitization was obtained after 4 days. This indicates that the rapid assay might be developed to a predictive assay for detection of the response of primary prostate tumor cells to the radiation sensitizing effect of EM.

Cell Survival↗

Ultrasonic dating of pregnancies: effect on incidence of SGA diagnoses. A randomised controlled trial.

In order to study the incidence of antenatal identification and postnatal diagnosis of small for gestational age (SGA) infants, 4997 women with optimal menstrual history were randomised. One group had the gestational age estimated from last menstrual period (LMP), the other from ultrasonographically measured biparietal diameter (BPD) in the second trimester. Both the incidence of antenatally suspected and postnatally diagnosed SGA infants were reduced by approximately 30% in the BPD-dated group. It is concluded that this was due to the shift in gestational age estimation.

Female↗

Effects on lipids and lipoproteins in women treated with oestradiol and progesterone.

Thirty women with climacteric symptoms were treated for 4 months with 2 mg 17 beta-oestradiol and different doses of progesterone (50, 100 or 200 mg). The concentrations of total and free cholesterol, phospholipids, triglycerides (TG), apoprotein A1 and apoprotein B were determined in high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) fractions and in serum. HDL levels increased and LDL levels decreased, while TG levels in VLDL remained unchanged, which indicates that the lipoprotein pattern is oestrogen-induced and that progesterone exerts little or no influence.

Adult↗

Latex-based thin-layer immunoaffinity chromatography for quantitation of protein analytes.

A rapid immunochromatographic method for qualitative and quantitative analysis of protein antigens is described. The method is based on the "sandwich" assay format using monoclonal antibodies (Mabs) of two distinct specificities. Mabs of one specificity are covalently immobilized to a defined detection zone on a porous membrane while Mabs of the other specificity are covalently coupled to blue latex particles which serve as a label. The sample is mixed with the Mab-coated particles and allowed to react. The mixture is then passed along a porous membrane by capillary action past the Mabs in the detection zone, which will bind the particles which have antigen bound to their surface, giving a blue color within this detection zone with an intensity logarithmetrically proportional to the antigen concentration in the sample. Analysis is complete in less than 10 min, requires a minimum amount of sample (4 microliters), and has a detection limit below the nanomolar range for the antigen we studied, human chorionic gonadotropin.

Antibody Specificity↗

The expression of estramustine-binding protein in the human prostatic cancer cell line DU 145 is not androgen dependent.

Estramustine-binding protein (EMBP) constitutes one of the major proteins in the prostatic gland, it binds estramustine and estromustine, the active metabolites of estramustine phosphate (Estracyt). Previous studies in rats have indicated that the expression of EMBP is androgen dependent, with diminishing quantities following castration and estrogen treatment as well as restored pre-castration production upon administration of androgens. In this study, we have used the human prostatic cancer cell line DU 145 transplanted in female and male nude mice. This cell line, which is sex hormone independent, gave rise to subcutaneous tumors in the rats with no difference in growth characteristics between the males and females. The expression of EMBP was analysed by radioimmunoassay, immunohistochemical and Western blot techniques. No difference was seen between the two sexes with respect to EMBP content, demonstrating that the expression of EMBP, in contrast to that reported for the normal prostate, is neither androgen- nor estrogen-dependent in tumor tissues.

Animals↗

Correlation between computer-assisted femoral arteriography and physiological tests in hypercholesterolaemic patients: a methodological study with special reference to clinical trials.

The validity of computer-assisted femoral arteriography, for the study of regression/progression of atherosclerosis in follow-up clinical trials, was investigated by comparison with routine physiological estimates of peripheral circulatory function. Thus, in 114 hypercholesterolaemic patients, the results of aorto-femoral arteriography were compared with those of leg segmental blood pressure measurement, oscillometry, digital pulse plethysmography, and bicycle and treadmill exercise tests. In 107 patients, 18 with symptoms of peripheral vascular disease (PVD) and 89 asymptomatic, magnification arteriograms of a 20 cm segment of the right or left superficial femoral artery were obtained. These arteriograms were digitized and the following variables were calculated: arterial lumen volume (corrected for body size), per cent stenosis, and edge roughness. The correlation between arteriographic and physiological variables was investigated with a linear regression model, taking into account the possible interaction with sex, and presence or absence of symptoms of PVD. Lumen volume correlated significantly with all five physiological variables, and per cent stenosis correlated significantly with four of the physiological variables. For the roughness measure, however a significant correlation was found only with plethysmography. By using logistic multiple regression analysis linear functions of physiological variables were constructed to detect ilio-femoral arterial occlusion. The sensitivity/specificity for detection of right-sided, left-sided, and bilateral occlusion was 0.83/0.98, 0.78/0.98, and 0.60/1.00 respectively (N = 108-111). Systolic blood pressure (ankle-arm ratio) was the single variable most closely correlated to the likelihood of arterial occlusions. It is concluded that arterial lumen volume and per cent stenosis, measured for the digitized femoral arteriogram, correlate well with physiological variables, which reflect the state of atherosclerosis both in the femoral arteries and in other arterial beds including the heart, and that routine physiological tests can be used to identify patients with arterial occlusions in the iliac and femoral arteries.

Adult↗

Expression of birch pollen-specific IgE-binding activity in seeds and other plant parts of birch trees (Betula verrucosa Ehrh.).

Dot immunoblotting of crude extracts of various aerial parts of birch trees, using patient serum rich in birch pollen IgE, showed IgE-binding activity in leaves, buds, twigs, seeds, bark, and old male catkins. Seed extracts analysed by SDS-PAGE, electroblotting to nitrocellulose and immune detection using isotope-conjugated anti-IgE verified the presence in seeds of an IgE-binding protein of an approximate molecular weight of 12 kD, distinct from the major allergen (molecular weight 17 kD) of Betula verrucosa pollen. The allergen of birch seeds was readily leachable from the seeds. Many of the birch plant part extracts were active in RAST inhibition using birch pollen RAST discs, but showed low potency relative to the allergenicity of birch pollen allergens.

Allergens↗