Rehabilitation research in sports medicine.
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Athletic Injuries↗
Biomedical subjects
P Magnusson
Publications and source records attributed to P Magnusson.
The decrease of IGF-I, IGF-binding protein-3 and bone alkaline phosphatase isoforms during gluten challenge correlates with small intestinal inflammation in children with coeliac disease.
OBJECTIVE: In children with coeliac disease, the ingestion of gluten causes small intestinal inflammation and a clinical picture of malabsorption, weight reduction and short stature. Decreased alkaline phosphatase (ALP) during gluten challenge was found in a previous study. ALP is a marker of bone formation and ALP activities are correlated with growth velocity. The aim of this study was to characterise the previously observed decrease of total ALP by investigating three specific bone ALP isoforms (bone/intestinal, B1 and B2) and three specific liver ALP isoforms (L1, L2 and L3) and, moreover, to correlate these ALP isoforms with other growth factors and growth markers. In addition, we also studied the association with possible weight changes, small intestinal mucosa inflammation, sex, age and gluten dose during gluten challenge. MATERIALS AND METHODS: Bone and liver ALP isoforms, IGF-I, IGF-binding protein (IGFBP)-3 and serum cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were measured together with change in weight and small intestinal mucosa histopathology in 54 children with earlier enteropathy who participated in a 4-week gluten challenge. RESULTS: We observed a decreased total ALP activity after 4 weeks of gluten challenge, 7.8+/-1.8 to 6.5+/-1.7 microkat/l (means +/- s.d.), which was mainly due to a reduction of the bone ALP isoforms. The sum of all three bone ALP isoforms decreased from 6.3+/-1.7 to 5.1+/-1.6 microkat/l. The decreased activities of the bone ALP isoforms correlated with the observed reductions of IGF-I (r=0.74, P<0.001), IGFBP-3 (r=0.51, P<0.001) and ICTP (r=0.57, P<0.001). The decrease of the growth factors and growth markers correlated with weight reduction, but when influences from the change in weight were adjusted for, the partial correlation of the small intestinal mucosa inflammation was significant for IGF-I (r=-0.56, P<0.001) and IGFBP-3 (r=-0.55, P<0.001). CONCLUSION: The decrease of total ALP was due to a reduction of bone ALP. The decrease of IGF-I and IGFBP-3 was independently correlated with weight change and small intestinal inflammation.
Alkaline Phosphatase↗
A prospective study showing long-term infection with human papillomavirus 16 before the development of cervical carcinoma in situ.
Human papillomavirus 16 (HPV16) is a predominant cause of cervical neoplasia. However, no population-based study with long-term follow-up has clarified the temporal relationship between HPV16 infection and occurrence of carcinoma in situ, or the importance of recurrent or persistent infection. This nested case-control study was carried out in a population-based cohort of women participating in cytological screening whose initial smear, taken in 1969-1995, was normal. During up to 26 years of follow-up, carcinoma in situ was diagnosed in 484 eligible women. Archival smears from these women were compared with smears from 619 individually matched controls. After DNA extraction, a highly sensitive PCR system was used to detect HPV16. Among case women, the prevalence of HPV16 positivity was 56% at the time of diagnosis. The relative risk of cervical carcinoma in situ increased from 3.6 (95% confidence interval, 1.2-11.0) 13 years before diagnosis to 11.1 (95% confidence interval, 5.5-22.2) 1 year before diagnosis. Having a positive smear at entry to the cohort increased risk >5-fold, whereas having persistent infection with HPV in two subsequent smears increased risk 30-fold. We estimated that among HPV16-positive women, the median incubation period from infection to carcinoma in situ was 7-12 years. We conclude that evidence of persistent and/or recurrent infection is associated with a drastically higher risk of cervical carcinoma in situ than occasional infection with HPV16.
Adolescent↗
Increased inversion angle replication error in functional ankle instability.
The inversion-angle replication error of the ankle joint was measured in subjects with a functionally stable or unstable ankle. Testing was performed as a passive set-active replication design. The absolute replication error on the unstable side of 23 unilaterally, functionally, and mechanically unstable subjects was found to be significantly greater (2.5 degrees) than the error on the healthy contralateral side (2.0 degrees ; P < 0.05) and the error in a group of 40 ankle healthy controls (1.7 degrees; P < 0.01). In 10 ankle-healthy high-level cross-country runners the replication error was reduced by 38% after warming up (P = 0.04).
Adult↗
Serum isoforms of bone alkaline phosphatase increase during physical exercise in women.
Physical activity is an important factor for maintaining and probably increasing bone mass in humans. However, the mechanism by which this takes place is not completely understood. The purpose of this study was to examine the influence of physical exercise on serum alkaline phosphatase (ALP) and in particular, the bone isoforms of ALP. Six ALP isoforms were quantified by high-performance liquid chromatography: three bone (B/I, B1, and B2), and three liver ALP isoforms. In addition, serum calcium, parathyroid hormone (PTH), and other markers of bone formation and degradation, as measured by osteocalcin and cross-linked carboxyterminal telopeptide of type I collagen (ICTP), were analyzed. The study groups comprised 15 women, 8 postmenopausal (range 51-62 years) and 7 near age of peak bone mass (range 21-27 years). When the postmenopausal women exercised on an ergometer cycle until exhaustion we found significant increases in serum of bone ALP isoforms B1 and B2, and phosphate, even considering the hemoconcentration that occurred during the exercise. When the young women jogged in a moderate tempo for 40-40 minutes the levels of serum B2 and PTH increased. All changes turned towards baseline within 20 minutes after exercise. In conclusion, exercise increased serum ALP bone isoforms B1 and B2, and their responses were differentiated. As B1 and B2 are known to represent specific bone compartments, cortical and trabecular bone, the present findings may indicate different effects on bone of weight- and nonweight-bearing exercise.
Adult↗
Sports medicine update. Perspectives on sports medicine as a specialty.
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Denmark↗
Image analysis methods for assessing levels of image plane nonuniformity and stochastic noise in a magnetic resonance image of a homogeneous phantom.
Magnetic response image plane nonuniformity and stochastic noise are properties that greatly influence the outcome of quantitative magnetic resonance imaging (MRI) evaluations such as gel dosimetry measurements using MRI. To study these properties, robust and accurate image analysis methods are required. New nonuniformity level assessment methods were designed, since previous methods were found to be insufficiently robust and accurate. The new and previously reported nonuniformity level assessment methods were analyzed with respect to, for example, insensitivity to stochastic noise; and previously reported stochastic noise level assessment methods with respect to insensitivity to nonuniformity. Using the same image data, different methods were found to assess significantly different levels of nonuniformity. Nonuniformity levels obtained using methods that count pixels in an intensity interval, and obtained using methods that use only intensity values, were found not to be comparable. The latter were found preferable, since they assess the quantity intrinsically sought. A new method which calculates a deviation image, with every pixel representing the deviation from a reference intensity, was least sensitive to stochastic noise. Furthermore, unlike any other analyzed method, it includes all intensity variations across the phantom area and allows for studies of nonuniformity shapes. This new method was designed for accurate studies of nonuniformities in gel dosimetry measurements, but could also be used with benefit in quality assurance and acceptance testing of MRI, scintillation camera, and computer tomography systems. The stochastic noise level was found to be greatly method dependent. Two methods were found to be insensitive to nonuniformity and also simple to use in practice. One method assesses the stochastic noise level as the average of the levels at five different positions within the phantom area, and the other assesses the stochastic noise in a region outside the phantom area.
Image Processing, Computer-Assisted↗
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↗