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P Magnusson

Publications and source records attributed to P Magnusson.

At least 37 records · Page 2Linked to original sources

Dose response characteristics and basic dose distribution data for a polymerization-based dosemeter gel evaluated using MR.

A safe and reproducible mixing procedure for the manufacture of a polymerization-based dosemeter gel evaluated using MRI (PoMRI) is presented. The dose response, obtained by irradiating gel-filled vials with absorbed doses in the interval 0-20 Gy and evaluated with respect to 1/T2, was found to be linear in the interval 0-8 Gy, with a sensitivity of 0.211 s-1Gy-1 (r2 = 0.998) at 1.5 T. Evaluation of the same set of vials with respect to 1/T1 gave a sensitivity of 0.018 s-1Gy-1 (r2 = 0.960). PoMRI and diode data were compared for standard photon and electron treatment beams. A deviation of less than 3% was found between the two methods for central depth dose curves as well as dose profiles (2 mm for electrons in the steep dose gradient regions). The importance of the method used for background correction for the reliability of the results was also evaluated. Barex (with a wall thickness of 1.5 mm) was investigated for use as phantom material and found to be favourable compared with glass. The results obtained in this study show that PoMRI has excellent potential as a 3D detector.

Dose-Response Relationship, Radiation↗

MRI image plane nonuniformity in evaluation of ferrous sulphate dosimeter gel (FeGel) by means of T1-relaxation time.

MR image nonuniformity can vary significantly with the spin-echo pulse sequence repetition time. When MR images with different nonuniformity shapes are used in a T1-calculation the resulting T1-image becomes nonuniform. As shown in this work the uniformity TR-dependence of the spin-echo pulse sequence is a critical property for T1 measurements in general and for ferrous sulfate dosimeter gel (FeGel) applications in particular. The purpose was to study the characteristics of the MR image plane nonuniformity in FeGel evaluation. This included studies of the possibility of decreasing nonuniformities by selecting uniformity optimized repetition times, studies of the transmitted and received RF-fields and studies of the effectiveness of the correction methods background subtraction and quotient correction. A pronounced MR image nonuniformity variation with repetition and T1 relaxation time was observed, and was found to originate from nonuniform RF-transmission in combination with the inherent differences in T1 relaxation for different repetition times. The T1 calculation itself, the uniformity optimized repetition times, nor none of the correction methods studied could sufficiently correct the nonuniformities observed in the T1 images. The nonuniformities were found to vary considerably less with inversion time for the inversion-recovery pulse sequence, than with repetition time for the spin-echo pulse sequence, resulting in considerably lower T1 image nonuniformity levels.

Background Radiation↗

Ferrous sulphate gel dosimetry and MRI for proton beam dose measurements.

Ferrous sulphate gel dosimetry has the potential for measurement of absorbed dose distributions in proton therapy. The chemical properties of the gel are altered according to the radiation dose and these changes can be evaluated in three dimensions using MRI. The purpose of this work was to investigate the properties of a ferrous gel used with clinical proton beams. The gel was irradiated with both monoenergetic and range-modulated proton beams. It was then evaluated using MRI. The depth dose by means of the 1/T1 distribution was studied and compared with data from a plane-parallel plate ionization chamber. 1/T1 was shown to be proportional to the dose at a mean proton energy of approximately 90 MeV. The dose response was no different from that obtained using photon beams. However, on normalization at the entrance, the relative 1/T1 at the Bragg peak was 15-20% lower than the corresponding ionization chamber data for the monoenergetic proton beam. Better agreement was found for the modulated beam, but with significant differences close to the distal edge of the 1/T1 distribution. The change in sensitivity with depth was explained by means of a linear energy transfer dependence. This property was further studied using Monte Carlo methods.

Calibration↗

Isoforms of bone alkaline phosphatase: characterization and origin in human trabecular and cortical bone.

Alkaline phosphatase (ALP) is a glycoprotein and functions as an ectoenzyme attached to the cell membrane by a hydrophobic glycosyl-phosphatidylinositol (GPI) anchor. Three bone ALP (BALP) isoforms in human serum were separated and quantitated by high-performance liquid chromatography. B/I, a minor fraction, is composed on average of bone (70%) and intestinal (30%) ALP, and two major isoforms, B1 and B2. Treatment with GPI-specific phospholipase C (GPI-PLC) did not influence the activities or retention times for B1 and B2, indicating that the biochemical differences between B1 and B2 are likely to be due to different glycosylation patterns. The B/I fraction in serum, on average 4% of total ALP, was found to be composed of B1 and B2 isoforms, each with an intact hydrophobic GPI cell membrane anchor. We investigated the origin of these three BALP isoforms and osteocalcin in human femora from five healthy individuals (four males), mean age 51 years, obtained from a tissue bank. Bone was sampled from three sites: cortical bone, trabecular bone from the diaphysis, and trabecular bone from the greater trochanter. Trabecular bone, from both sites, had higher BALP activities compared with cortical bone. Conversely, the osteocalcin content of cortical bone was more than 3-fold greater than that of trabecular bone. Cortical bone had approximately 2-fold higher activity of B1 compared with B2, whereas trabecular bone had approximately 2-fold higher activity of B2 compared with B1. We observed a previously undescribed BALP isoform (B1x) in all bone samples. B1x was also observed in sera from some patients (60%) with severe renal insufficiency and on chronic dialysis therapy (n = 20). The isoforms of BALP may provide information relating to bone metabolism within specific bone compartments.

Adult↗

The NIK protein kinase and C17orf1 genes: chromosomal mapping, gene structures and mutational screening in frontotemporal dementia and parkinsonism linked to chromosome 17.

Full exon-intron structures are presented for the NIK serine/threonine protein kinase gene and a novel gene termed C17orf1. By in situ hybridisation and radiation hybrid mapping, a cosmid (cDD-Z) that contains regions of both of these genes has been localised between markers D17S800 and D17S791 at chromosome 17q21. The two genes are thus positional candidates for the mutant locus underlying frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), a disease for which NIK is also a good biological candidate. Using exon-intron maps, a genomic DNA sequencing based mutation screen has been performed for the NIK and C17orf1 genes in a chromosome 17-linked FTDP-17 pedigree. Two silent single-base variations were detected in C17orf1. No alterations were restricted to DNA samples from patients, thus excluding the C17orf1 and NIK genes as likely sites of mutation FTDP-17.

Carrier Proteins↗

Verification of single beam treatment planning using a ferrous dosimeter gel and MRI (FeMRI).

A method for analysing and comparing treatment planning system (TPS) data and ferrous dosimeter gel measurements evaluated with MRI (FeMRI) was developed, including image processing to final absorbed dose images. Measurements were analysed according to this method and FeMRI data were thereby compared with the TPS-calculated dose distribution. For photons, differences between FeMRI- and TPS dose data were mainly within +/- 2%. Minor shortcomings found in both the FeMRI system and the TPS are explained and discussed. For electron beams, there was an overall good agreement. It was found that the TPS underestimates the lateral scattering dose outside the primary beam, but the reported dose difference corresponds to a small spatial deviation (less than 2 mm). It is important to consider this single beam data comparison when the method is extended to more complicated situations, for example when using several beams.

Ferrous Compounds↗

Improvements in absorbed dose measurements for external radiation therapy using ferrous dosimeter gel and MR imaging (FeMRI).

A ferrous gel, based on ferrous (Fe) sulphate and agarose, was used with a clinical magnetic resonance imaging (MRI) scanner to obtain relative dose distribution data from therapeutic photon and electron beams. The FeMRI gel was scanned using a new MRI acquisition protocol optimized for T1 measurements. Thorough comparisons with silicon semiconductor detector and ionization chamber measurements, as well as with Monte Carlo calculations, were performed in order to quantify the improvements obtained using FeMRI for dose estimations. Most of the relative doses measured with FeMRI were within 2% of the doses measured with other methods. The larger discrepancies (2-4%) found at shallow depths are discussed. The uncertainty in relative dose measurements using FeMRI was significantly improved compared with previously reported results (5-10%, one standard deviation, 1 SD), and is today between 1.6% and 3.3% (depending on dose level, 2 SD). This corresponds to an improvement in the minimum detectable dose (3 SD above background) from approximately 2 Gy to better than 0.6 Gy. The results obtained in this study emphasize the importance of obtaining basic FeMRI dose data before the method is extended to complicated treatment regimes.

Electrons↗

Serum levels of insulin-like growth factor binding proteins (IGFBP)-4 and -5 correlate with bone mineral density in growth hormone (GH)-deficient adults and increase with GH replacement therapy.

Adults with growth hormone deficiency (GHD) exhibit low bone mineral density (BMD) which improves by growth hormone (GH) replacement therapy. The insulin-like growth factor (IGF) system has an established role in mediating the effects of GH on bone and IGF binding proteins (IGFBP)-4 and IGFBP-5 have been shown to modulate the effects of IGFs in bone. Therefore, we studied serum levels of IGFBP-4 and IGFBP-5 and their relationship to serum levels of bone biochemical markers and BMD in adults with GH deficiency (GHD) before and during GH therapy. Serum levels of IGFBP-5 and IGFBP-4 were measured on samples from 20 patients (11 males) 22-57 years of age. All had IGF-I serum values below -2 standard deviation score. The first 6 months were placebo controlled and all received 3 years of active treatment with the mean dose 0.23 +/- 0.01 IU/kg/week divided into daily subcutaneous injections. Serum IGFBP-5 levels in GHD adults were low at baseline and positively related to total body, femoral neck, trochanter, and Ward's triangle BMD (r = 0.471, 0.549, 0.462, and 0.470, respectively, p < 0.05). The mean serum IGFBP-5 level increased by about 2-fold within 3 months after the initiation of GH therapy and was correlated with serum IGF-I (r = 0.719, 0.801, and 0.722 before and after 18 and 36 months, respectively,p < 0.001). A positive correlation between serum IGFBP-5 levels and lumbar spine BMD was found during GH treatment but not before. The percentage increase of serum IGFBP-5 after GH therapy showed a positive correlation with the percentage increase of total alkaline phosphate activity (r = 0.347 p < 0.05). In contrast to IGFBP-5, serum IGFBP-4 levels were positively related to body mass index (r = 0.607, p < 0.01). Baseline serum IGFBP-4 levels also correlated with total body, femoral neck, trochanter, and Ward's triangle BMD (r = 0.502, 0.590, 0.612, and 0.471, respectively,p < 0.05). The mean serum IGFBP-4 level was increased by 25% within 3 months after initiation of GH therapy and did not correlate with serum IGF-I levels. Although the above findings are consistent with the idea that GH-induced changes in serum IGFBP-5 and IGFBP-4 levels may in part mediate the anabolic effects of GH on bone tissue in adults with GHD, further studies are needed to establish the cause and effect relationship.

Adult↗

Differences of bone alkaline phosphatase isoforms in metastatic bone disease and discrepant effects of clodronate on different skeletal sites indicated by the location of pain.

We compared clodronate with placebo administration in 42 primarily or secondarily hormone-refractory prostate cancer patients with skeletal metastases and persisting pain. Serum total alkaline phosphatase (ALP), bone ALP isoforms, osteocalcin, cross-linked carboxy-terminal telopeptide of type I collagen, and prostate-specific antigen were analyzed before and after 1 month of treatment. Six ALP isoforms were quantified by HPLC: one bone/intestinal, two bone (B1, B2), and three liver ALP isoforms. The most apparent difference compared with healthy males was observed for the bone ALP isoform B2. Patients and healthy males had a B2 activity corresponding to 75% and 35% of the total ALP activity, respectively (P <0.0001). We propose that the different bone ALP isoforms reflect different stages of osteoblast differentiation during the extracellular matrix maturation phase of osteogenesis. All bone markers except osteocalcin increased after 1 month of clodronate administration. These increases were associated with pain only in the upper part of the body. We suggest that the uptake of clodronate by the skeleton was not uniform during our treatment period.

Aged↗

Isokinetic muscle strength and capacity for muscular knee joint stabilization in elite sailors.

In the present study isokinetic dynamometry was used to evaluate the capacity for dynamic knee joint stabilization via muscle contraction in elite sailors (15 males, SM; 6 females, SF) compared to a group of matched controls (8 males, CM). Maximal concentric, eccentric and isometric moment of force (peak moment and moment at 50 degree knee flexion) was obtained for the knee extensors (quadriceps) and flexors (hamstrings) during isokinetic knee joint movement at angular velocities 0, 30, 120 and 180 degrees x s(-1). High levels of eccentric knee extension strength were observed for the elite sailors compared to the controls (p < 0.05). Based on peak moment and 50 degree moment, respectively, conventional hamstring/quadriceps (H/Q) strength ratio (+/-SD) ranged from 0.37+/-0.06 to 0.54+/-0.06 and from 0.42+/-0.07 to 0.57+/-0.10 across groups, speed and contraction mode. The female elite sailors displayed lower (p<0.05) concentric H/Q ratios at 120 and 180 degrees x s(-1) compared to the controls (0.41-0.45 vs. 0.51-0.56, respectively). The ratio of eccentric hamstring to concentric quadriceps strength (H/Q for extension) or concentric hamstring to eccentric quadriceps strength (H/Q for flexion) may provide a more functional estimate of the capacity for muscular knee joint stabilization (1). Based on peak moment and 50 degree moment, respectively, this "functional" H/Q ratio ranged from 0.24+/-0.03 and 0.25+/-0.02 for knee flexion at 180 degrees x s(-1) to 0.97+/-0.17 and 0.88+/-0.12 for knee extension at 180 degrees x s(-1) among the three groups. Comparable levels of "functional" H/Q ratio were observed (p>0.05) for fast knee extension in the elite sailors (SF:0.81-0.97, SM: 0.88-0.95) and the male controls (CM: 0.80-0.84). In conclusion, a "functional" H/Q ratio of 0.8-1.0 observed for all subjects indicated a significant functional capacity of the hamstring muscles for providing muscular stability at the knee joint in fast knee extension. A significant potential for muscular knee joint stabilization appeared for the elite sailors despite their high maximal quadriceps strength and partially lower (SF) conventional H/Q ratios.

Analysis of Variance↗

Different responses of bone alkaline phosphatase isoforms during recombinant insulin-like growth factor-I (IGF-I) and during growth hormone therapy in adults with growth hormone deficiency.

We studied serum bone alkaline phosphatase (ALP) isoforms and other markers of bone turnover in growth hormone-deficient (GHD) adults (n = 22). The patients were followed during 1 week of insulin-like growth factor-I (IGF-I) administration, 40 micrograms/kg of body weight/day (n = 6), and during 24 months of growth hormone (GH) therapy, 0.125 IU/kg of body weight/week for the first month, and then 0.250 IU/kg of body weight/week (n = 20). Six ALP isoforms were separated and quantified by high-performance liquid chromatography: one bone/intestinal, two bone (B1, B22), and three liver ALP isoforms. At baseline, the mean levels of B1, B22, and osteocalcin were higher in GHD adults than in healthy adults. After 2 week of IGF-I administration and 1 month of GH therapy, only B1 was decreased. We suggest that the initial decrease of B1 during GH therapy could be an effect of endocrine IGF-I action mediated by GH. After 3 months of GH therapy, both B1 and B2 increased as compared with placebo. Osteocalcin, carboxy-terminal propeptide of type I procollagen (PICP), cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and urinary pyridinoline cross-links/creatinine ratio increased during GH therapy. PICP increased significantly before bone ALP and osteocalcin, indicating early stimulation of type I collagen synthesis as previously demonstrated by in vitro models. Different responses of the bone ALP isoforms during IGF-I and during GH therapy suggest different regulations in vivo.

Adult↗

Dosimeter gel and MR imaging for verification of calculated dose distributions in clinical radiation therapy.

A dosimeter gel, based on an agarose gel infused with a ferrous sulphate solution and evaluated in a magnetic resonance scanner, was used for complete verification of calculated dose distributions. Two standard treatment procedures, treatment of cancer in the urinary bladder and treatment of breast cancer after modified radical mastectomy, were examined using pixel-by-pixel and dose volume histogram comparison. The dose distributions calculated with the dose planning system was in very good agreement with the measured ones. However, in the case of the more complicated breast cancer treatment, some discrepancies were found, mainly at the beam abutment region. This may be explained by field displacements errors and by a small limitation of the dose planning utilising small electron beams in this region. The dosimeter gel system have proven to be a useful tool for dosimetry in clinical radiation therapy applications.

Breast Neoplasms↗

Serum osteocalcin and bone and liver alkaline phosphatase isoforms in healthy children and adolescents.

We report reference values for osteocalcin and bone and liver alkaline phosphatase (ALP) isoforms in serum from 114 healthy children and adolescents, age 7-16 y. The bone and liver ALP isoforms were measured by high performance liquid chromatography (HPLC). Six ALP isoforms were separated and quantified in all samples: one bone/intestinal (B/I), two bone (B1 and B2), and three liver ALP isoforms (L1, L2, and L3). It is especially important to make distinctions between ages and gender during puberty in the interpretation of biochemical markers of bone. We observed that girls reached adult levels for osteocalcin, total ALP, and bone ALP isoforms, B/I, B1, and B2, earlier than boys. Girls in the oldest age group (15-16 y) and in the pubertal stage groups IV-V, reached higher levels than boys for the calculated ratio B1/B2 due to a more rapid decline of B2 compared with B1. This observation might indicate that B2, to a higher extent than the B1 isoform, represent a more mature expression of osteoblast differentiation during matrix mineralization in growing bone. Serial measurements of these new bone ALP isoforms could provide new insights into bone and mineral metabolism.

Adolescent↗

Methodological aspects on separation and reaction conditions of bone and liver alkaline phosphatase isoform analysis by high-performance liquid chromatography.

Some methodological aspects and characteristics on analysis of bone and liver alkaline phosphatase (EC 3.1.3.1, ALP) isoforms by high-performance liquid chromatography (HPLC) methods are presented. Factors affecting separation (analytical column type, column temperature, mobile phase buffer, mobile phase salt, gradient elution, flow rate) and reaction conditions (substrate type, substrate concentration, fluorescent substrates, substrate buffer type, substrate buffer concentration, substrate pH, substrate activators, substrate detergent, substrate flow rate, reaction temperature, postcolumn reaction detection) are discussed. Six peaks with ALP activity were separated and quantified by our new HPLC method in normal adult nonplacental serum: one intestinal/bone, two bone, and three liver ALP isoforms. Differences between the six ALP isoforms with respect to diethanolamine buffer concentration and substrate pH were observed. Although our HPLC method offers an improved possibility to clarify the reason for an increased total ALP in the routine clinical chemistry laboratory further research is needed to clarify the cellular origins of the different bone and liver ALP isoforms.

Acetates↗

Determination of alkaline phosphatase isoenzymes in serum by high-performance liquid chromatography with post-column reaction detection.

A weak anion-exchange high-performance liquid chromatographic procedure with post-column reaction detection for simultaneous determination of alkaline phosphatase (EC 3.1.3.1, ALP) isoenzymes is described. We identified six peaks with ALP isoenzyme activity in normal serum. The peaks were, in order of elution, one intestinal/bone, two bone and three liver ALP isoenzymes. This new assay with automatic injection, on-line post-column reaction detection and powerful integration data system could be of significant value in the routine clinical biochemistry laboratory. The advantages include improved sensitivity and selectivity over previous methods for the determination of ALP isoenzymes.

Alkaline Phosphatase↗

Evaluation of micromotion in cemented vs uncemented knee arthroplasty in osteoarthrosis and rheumatoid arthritis. Randomized study using roentgen stereophotogrammetric analysis.

Twenty-four patients (25 knees) with osteoarthrosis (OA) and 19 patients (20 knees) with rheumatoid arthritis (RA) were operated with bi-tricompartmental knee arthroplasty. The patients were randomized to cemented or cementless fixation of the tibial component. The fixation of the tibial components was examined with roentgen stereophotogrammetric analysis (RSA) up to 24 months after operation. The following parameters representing tibial component micromotion were measured: (1) maximum migration of the prosthetic edge (maximum total point motion, MTPM); (2) distal migration of the prosthetic center (subsidence); (3) maximum proximal movements of the prosthetic edge ("lift-off"); and (4) prosthetic rotations, corresponding to internal/external rotation, adduction/abduction, and forward/backward tilt of the tibial component. All prostheses displayed significant micromotions, which tended to decrease 3-6 months after the operation. The average migration after 2 years, when measured as maximum single axis rotation, and MTPM were about 0.9 degrees-1.5 degrees and 1.0-1.5 mm, respectively, in all four groups. There were no statistically significant differences between cemented and cementless prostheses in either the OA or the RA group. The fixation in the RA patients did not significantly differ from that of the OA patients, perhaps because the RA patients had lower weight and were living a more sedentary life.

Aged↗

A randomized study of secondary prevention of early stage problem drinkers in primary health care.

The subjects were recruited from participants in a health examination of random samples of the adult population in Stockholm county. Those aged 18-64 years who admitted a high alcohol consumption (greater than 40 g 100% ethanol/day) among men and greater than 30 g among women) or had an elevated value of serum-gammaglutamyltransferase (GGT) (cut-off point 1.0 microkatal/l for men and 0.6 microkatal/l for women) or had certain other indications of a high alcohol consumption were included. More severe cases, and those with an elevated GGT due to reasons other than alcohol, were excluded. The remaining subjects, 70 men and 13 women, were allocated at random to either an intervention or a comparison group. An elevated GGT was the main inclusion criteria. The subjects in the comparison group were advised by the general practitioner to cut their alcohol consumption, while those in the intervention group made further visits to their general practitioner, who gave general support and used an elevated GGT as an indication of the recent level of alcohol consumption at consecutive visits. There were three visits on average, so we are comparing a group receiving advice with a group receiving further minimal intervention. At the one-year follow-up there were greater, however not significant, reduction in GGT-level, in self-reported alcohol consumption and in a 'problem index' in the minimal intervention group than in the comparison group.

Adolescent↗