Biomedical subjects

K Klaushofer

Publications and source records attributed to K Klaushofer.

At least 19 recordsLinked to original sources

PubMed2007

Three-dimensional growth behavior of osteoblasts on biomimetic hydroxylapatite scaffolds.

The authors used rapid prototyping to produce three-dimensional hydroxylapatite scaffolds with controlled, fully interconnected porosity. The purpose of this study was to illuminate the effect of hormones on the osteogenic differentiation and to investigate how osteoblasts colonize the three-dimensional scaffold focusing on the formation of the cellular network. Preosteoblasts were seeded onto scaffolds, were optionally treated with the osteogenic hormones triiodo-L-thyronine (T3) and 1,25-dihydroxyvitamin-D3 (D3), and the expression of osteoblastic marker genes was investigated. Confocal laser scanning microscopy was used to investigate the three-dimensional growth behavior. Culturing cells on scaffolds strongly increased the expression of osteocalcin, osteoprotegerin, Runx2, and receptor activator of NFkB-ligand (RANKL). Treatment with T3 increased the expression of osteocalcin but did not change that of osteoprotegerin and Runx2. Treatment with D3 inhibited the expression of osteocalcin, Runx2, and osteoprotegerin. Both hormones had similar effects in the three-dimensional system as found in two-dimensional cultures although more accentuated, indicating that preosteoblasts behave more naturally on three-dimensional structures. The osteoblasts colonized the three-dimensional squared pores of scaffolds by forming a cellular network with a round central channel keeping it into the depth and depositing collagen fibrils. These results provide insight how osteoblasts colonize a three-dimensional system and underline the importance of this environment in osteoblastic differentiation studies.

Animals↗

PubMed2006

Complementary information on in vitro conversion of amorphous (precursor) calcium phosphate to hydroxyapatite from Raman microspectroscopy and wide-angle X-ray scattering.

In addition to mechanical functions, bones have an essential role in metabolic activity as mineral reservoirs that are able to absorb and release ions. Bioapatite, considered the major component in the mineralized part of mammalian bones, is a calcium phosphate mineral with a structure that closely resembles hydroxyapatite (HA, Ca10[PO4]6[OH]2) with variable chemical substitutions. It is important to note that it continues to be chemically active long after it has been initially deposited. Detailed understanding of changes in the mineral phase as HA matures is essential for understanding how normal bone achieves its remarkable mechanical performance, how it is altered in disease, as well as the effects of therapeutic interventions. A model system for investigation of the in vivo maturation of HA is available, namely, the in vitro conversion of amorphous calcium phosphate (ACP) to HA in a supersaturated solution of calcium and phosphate ions. In the present study, this system was employed to correlate with the changes in chemistry and poorly crystalline HAP crystal size, shape, and habit. The results of the X-ray diffraction as well as Raman analyses showed that as the crystallites mature in the 002 and 310 directions both the full width at half-height and wavelength at maximum of the Raman peaks change as a function of reaction extent and crystallite maturation, size, and shape. Moreover, such analyses can be performed in intact bone specimens through Raman microspectroscopic and imaging analyses with a spatial resolution of 0.6-1 mu, by far superior to the one offered by other microspectroscopic techniques, thus potentially yielding important new information on the organization and mineral quality of normal and fragile bone.

Calcium Phosphates↗

PubMed2006

Bone osteonal tissues by Raman spectral mapping: orientation-composition.

Bone is a composite material with a hierarchical structure. Its strength depends on its structural and material properties. In the present study, Raman microspectroscopic and Imaging analyses were employed to study 12 osteons in tissue sections from the femoral midshaft of a healthy human female, with a spatial resolution of approximately 1mum. Spatial changes in amount of mineral and organic matrix, as well as the variation in the mineral content were determined, imaged, and plotted as a function of the polarization of incident light. The results showed that the prominent bands, such as nu(1) PO(4) and amide I, commonly used for the determination of mineral and organic compositions, are quite sensitive to the orientation and the polarization direction of the incident light. On the other hand, bands such as amide III, nu(2) PO(4) and nu(4) PO(4) are less susceptible to the orientational effects. As a result, exclusive consideration of the nu(1) PO(4) and amide I bands for the calculation of material properties might lead to erroneous conclusions. Amide III, nu(2) PO(4) and nu(4) PO(4) Raman bands should also be taken into consideration for compositional analysis of bone structures, especially ones with unknown orientational features. Moreover, the results of the present study demonstrate the versatility of the analytical technique, and provide insights into the organization of bone tissue at the ultrastructural level.

Bone Density↗

PubMed2005

Association of COLIA1 Sp1 alleles with defective bone nodule formation in vitro and abnormal bone mineralization in vivo.

Previous work identified a G/T polymorphism affecting a Sp1 binding site in a regulatory region of the COLIA1 gene that predisposes to osteoporotic fractures by affecting bone strength through mechanisms that are partly independent of differences in bone mineral density (BMD). To clarify the mechanisms by which COLIA1 Sp1 alleles influence bone strength we used quantitative backscattered electron imaging (qBEI) to characterize bone mineralization in biopsy samples from subjects of different COLIA1 genotype and studied the ability of osteoblast-like cells cultured from subjects of different genotypes to form mineralized bone nodules. The qBEI analysis showed a significant (P = 0.014) reduction in mineralization in bone biopsies from G/T heterozygotes (n = 6) compared with G/G homozygotes (n = 7) and a significant increase in heterogeneity of mineralization (P = 0.017). The in vitro studies showed that osteoblasts derived from G/T heterozygotes (n = 5) were significantly less able to produce mineralized bone nodules than G/G homozygotes (n = 10) at all time-points examined (P < 0.0001). We conclude that carriage of the COLIA1 Sp1 "T" allele is associated with an impaired ability of osteoblast-like cells to form mineralized bone nodules in vitro and with abnormalities of bone mineralization in vivo. This suggests that the increased bone fragility in carriers of the COLIA1 Sp1 allele may result in part from defects in bone mineralization.

Aged↗

PubMed2005

Combined treatment with PTH (1-34) and OPG increases bone volume and uniformity of mineralization in aged ovariectomized rats.

The combination of PTH with OPG has been proposed as a potential therapy in patients with severe osteoporosis. In the present study, we examined the bone material of aged ovariectomized (OVX) rats treated either with PTH (1-34) or OPG alone or in combination of both. The micro- and nanostructural characteristics of the mineralized bone were evaluated using quantitative backscattered electron imaging (qBEI) and small-angle X-ray scattering (SAXS). Rats (n=68) were either sham-operated or ovariectomized (OVX) at the age of 3 months, and 15 months later, OVX animals were treated either with vehicle, OPG (10 mg/kg), PTH (80 microg/kg) or a combination of both during 5.5 months. All treatments were by subcutaneous injection, 3 days per week. Secondary metaphyseal spongiosa from distal femora was assessed for mineralized bone volume (BV/TV), for the mean Ca-concentration (Camean), the width of the bone mineralization density distribution (Cawidth), as well as the average mineral particle thickness parameter (T) and the degree of alignment of the mineral particles (rho). A remarkable increase of BV/TV up to 139% (P<0.001) was observed in the PTH-treated groups independently of OPG. Camean was slightly increased (+1.7%, P<0.05) in the OPG-treated group. Cawidth was reduced (-6.4%, P<0.01, and -8.9%, P<0.001) in animals treated with OPG and PTH+OPG, respectively. In contrast, Cawidth in sham-operated rats was 16.0% (P<0.001) higher than in OVX. The T parameter was not altered in the trabecular bone within the group of treated and untreated OVX rats. However, the non-ovariectomized animals exhibited a significantly lower T value (-7.1%, P<0.01) with respect to OVX. In conclusion, qBEI and SAXS data of OVX rats suggest that PTH alone was responsible for increase of bone volume, whereas OPG positively influenced the homogeneity and density of mineralization without affecting the nanostructure of the bone material.

Animals↗

PubMed2005

Two different correlations between nanoindentation modulus and mineral content in the bone-cartilage interface.

The biomechanical properties of the zone of calcified cartilage (ZCC) in articulating joints are of clinical relevance due to the role ZCC plays in load transfer from cartilage to bone. To determine the micron-level mechanical properties and their correlation to mineral concentration in the ZCC, we combined nanoindentation (for micrometer level stiffness E(r) and hardness H) and quantitative back-scattered electron imaging or qBEI (for micrometer level mean calcium concentration Ca(Mean)) to study the ZCC-subchondral bone junction in 3 embedded human patellae. Nanoindentation line scans were correlated to qBEI analysis in the ZCC. The correlation between local stiffness and local mineral content was different in calcified cartilage compared to bone. The stiffness and hardness of calcified cartilage was typically lower than subchondral bone for the same mineral content. ZCC showed a wider range of variation in calcium content (1-28 wt %) compared to subchondral bone (16-26 wt %). 2D material property maps of the ZCC were generated from the mechanical-mineral correlation, showing that bands of high and low stiffness were found between the bone and tidemark, and between the ZCC and the unmineralized cartilage.

Adult↗

PubMed2004

Synchrotron diffraction study of deformation mechanisms in mineralized tendon.

The high stiffness and toughness of biomineralized tissues are related to the material deformation mechanisms at different levels of organization, from trabeculae and osteons at the micrometer level to the mineralized collagen fibrils at the nanometer length scale. Quantitatively little is known about the sub-micrometer deformation mechanisms under applied load. Using a parallel-fibred mineralized tissue from the turkey leg tendon as a model for the mineralized collagen fibrils, we used in situ tensile testing with synchrotron x-ray diffraction to measure the average fibril deformation with applied external strain. Diffraction peak splitting occurred at large strains, implying an inhomogeneous elongation of collagen fibrils. Scanning electron microscopy measurements lead us to conclude that the inhomogeneous mineralization in mineralized tendon is at the origin of the high fracture strain.

Animals↗

PubMed2004

Triiodothyronine (T3) and 1,25-dihydroxyvitamin D3 (1,25D3) inversely regulate OPG gene expression in dependence of the osteoblastic phenotype.

Both thyroid hormones and 1,25-dihydroxyvitamin D3 (1,25D3) are essential for normal development and maintenance of the skeleton. They regulate osteoblastic differentiation by influencing expression of osteoblast specific genes like osteocalcin (OCN). Mice deficient in OCN, the most abundant noncollagenous protein of the bone matrix, develop a phenotype characterized by higher bone mass and bone of improved quality. Osteoprotegerin (OPG), another protein important for bone metabolism, protects bone and is a regulator of the osteoclast development. 1,25D3 down regulates the basal expression of these two proteins in osteoblasts and osteoblast-like cells. The involvement of these hormones and proteins in the bone metabolism guided us to compare their regulation in cell lines with different osteoblastic phenotypes. We found that T3 increased OCN mRNA levels in MC3T3-E1 osteoblastic cells independent from their phenotype albeit with different potency but not in the bone marrow-derived stromal cell line ST2. OPG mRNA expression levels were only stimulated by T3 in mature MC3T3-E1 cells, which have the capacity to mineralize, but not in pre-osteoblastic MC3T3-E1 cells or in ST2 cells. In the mineralizing osteoblastic cells 1,25D3 inhibited T3-induced expression for OPG mRNA but not OCN mRNA. In the pre-osteoblastic cell line with undetectable OPG mRNA levels, either basal or T3-stimulated, 1,25D3 inhibited OCN mRNA expression completely. Our results emphasize the importance of balanced regulation of mRNA transcript levels for OPG and OCN, by both hormones and probably other systemic factors to enable a fine-tuning of bone metabolism at specific skeletal sites.

3T3 Cells↗

PubMed2004

Normal mineralization and nanostructure of sclerotic bone in mice overexpressing Fra-1.

Increased bone mass due to elevated number of active osteoblasts has been reported for transgenic mice overexpressing the transcription factor Fra-1. To explore the potential of the anabolic action of Fra-1 in treatment of osteoporosis, we examined the integrity of bone matrix generated in Fra-1 transgenic mice. Femora from Fra-1 transgenic (Fra-1 tg) and wild-type littermates were analyzed for bone mineralization density distribution (BMDD) and nanostructure using quantitative backscattered electron imaging (qBEI) and scanning small angle X-ray scattering (scanning-SAXS), respectively. For comparison, we studied mice lacking c-Fos (Fos-/-), which develop osteopetrosis because of the absence of osteoclasts. Morphometrical analysis of metaphyseal spongiosa revealed an up to 5-fold increase in bone volume for Fra-1 transgenic compared to wild type. BMDD indicated a transient lower mineralization of bone for Fra-1 transgenic at 5 and 8 weeks, which became comparable to that of wild-type mice by 8 months. The homogeneity of mineralization was not altered in the Fra-1 transgenic mice at any ages examined. However, it was strikingly reduced in Fos-/- due to an abundance of hypermineralized cartilage. The bone nanostructure did not show abnormalities in Fra-1 transgenic or Fos-/-. These results provide a rationale for the development of therapeutic applications involving Fra-1-induced bone formation.

Animals↗

PubMed2003

Mineralized microstructure of calcified avian tendons: a scanning small angle X-ray scattering study.

The micrometer level spatial distribution of the size, shape, and orientation of mineral crystallites in the calcifying matrix of tendons near the edge of the mineralizing front was investigated by scanning small angle X-ray scattering using synchrotron X-ray radiation. Using a special microbeam arrangement enabling 20 microm beam resolution and short measurement times, linear diffraction scans were made on sections from the normally calcifying tendons (tibialis cranialis) from the domestic turkey, which calcify in the distal to proximal direction. A change in shape and arrangement of mineral crystals was observed within the first 200 microm of the mineralization front, and the mineral crystal distribution was highly anisotropic with crystals aligned parallel to the fiber axis. In a cross-section of the tendon cut at right angles to the fiber axis, the orientation distribution of crystals was not azimuthally symmetric, and showed a small but nonzero anisotropy and a continuous change in mean orientation angle across the width of the tendon cross-section.

Animals↗

PubMed2003

Targeted overexpression of vitamin D receptor in osteoblasts increases calcium concentration without affecting structural properties of bone mineral crystals.

Increased cross-sectional area and strength of long bones has been observed in transgenic mice with 2-fold (OSV9) and 3-fold (OSV3) elevation of osteoblast vitamin D receptor (VDR) levels. In the present study, mineralization density distributions, including typical calcium content (Ca(Peak)) and homogeneity of mineralization (Ca(Width)) of femoral bone and growth plate cartilage, were determined by quantitative backscattered electron imaging (qBEI). Fourier-transform infrared (FTIR) microspectroscopy was used to examine mineral content, collagen and crystal maturation, and scanning small angle X-ray scattering (scanning-SAXS) for studying mineral particle thickness and alignment. In addition, X-ray diffraction (XRD) of distal tibiae revealed mineral particle c-axis size. In trabecular bone, the increase in Ca(Peak) was significant for both OSV9 (+ 3.14%, P = 0.03) and OSV3 (+ 3.43%, P = 0.02) versus controls with 23.61 +/- 0.45 S.D. wt% Ca baseline values. In cortical bone, Ca(Peak) was enhanced for the OSV3 mice (+ 1.84%, P = 0.02) versus controls with 26.61 +/- 0.28 S.D. wt% Ca, and OSV9 having intermediate values. Additionally, there was significantly increased homogeneity of mineralization as denoted by a reduction of Ca(Width) (-8.4%, P = 0.01) in primary spongiosa. FTIR microspectroscopy, with the exception of an increased collagen maturity in OSV3 trabecular bone (+ 9.9%, P = 0.02), XRD, and scanning-SAXS indicated no alterations in the nanostructure of transgenic bone. These findings indicate that elevation of osteoblastic vitamin D response led to formation of normal bone with higher calcium content. These material properties, together with indications of decreased bone resorption in secondary spongiosa and increased cortical periosteal bone formation, appear to contribute to the improved mechanical properties of their long bones and suggest an important physiological role of the vitamin D-endocrine system in normal bone mineralization.

Animals↗

PubMed2003

Characteristics of mineral particles in the human bone/cartilage interface.

Bone and cartilage consist of different organic matrices, which can both be mineralized by the deposition of nano-sized calcium phosphate particles. We have studied these mineral particles in the mineralized cartilage layer between bone and different types of cartilage (bone/articular cartilage, bone/intervertebral disk, and bone/growth cartilage) of individuals aged 54 years, 12 years, and 6 months. Quantitative backscattered electron imaging and scanning small-angle X-ray scattering at a synchrotron radiation source were combined with light microscopy to determine calcium content, mineral particle size and alignment, and collagen orientation, respectively. Mineralized cartilage revealed a higher calcium content than the adjacent bone (p<0.05 for all samples), whereas the highest values were found in growth cartilage. Surprisingly, we found the mineral platelet width similar for bone and mineralized cartilage, with the exception of the growth cartilage sample. The most striking result, however, was the abrupt change of mineral particle orientation at the interface between the two tissues. While the particles were aligned perpendicular to the interface in cartilage, they were oriented parallel to it in bone, reflecting the morphology of the underlying organic matrices. The tight bonding of mineralized cartilage to bone suggests a mechanical role for the interface of the two elastically different tissues, bone and cartilage.

Bone and Bones↗

PubMed2003

Constant mineralization density distribution in cancellous human bone.

The degree of mineralization of bone matrix is an important factor in determining the mechanical competence of bone. The remodeling and modeling activities of bone cells together with the time course of mineralization of newly formed bone matrix generate a characteristic bone mineralization density distribution (BMDD). In this study we investigated the biological variance of the BMDD at the micrometer level, applying a quantitative backscattered electron imaging (qBEI) method. We used the mean calcium concentration (Ca(Mean)), the most frequent calcium concentration (Ca(Peak)), and full width at half maximum (Ca(Width)) to characterize the BMDD. In none of the BMDD parameters were statistically significant differences found due to ethnicity (15 African-American vs. 27 Caucasian premenopausal women), skeletal site variance (20 ilium, 24 vertebral body, 13 patella, 13 femoral neck, and 13 femoral head), age (25 to 95 years), or gender. Additionally, the interindividual variance of Ca(Mean) and Ca(Peak), irrespective of biological factors, was found to be remarkably small (SD < 2.1% of means). However, there are significant changes in the BMDD in the case of bone diseases (e.g., osteomalacia) or following clinical treatment (e.g., alendronate). From the lack of intraindividual changes among different skeletal sites we conclude that diagnostic transiliac biopsies can be used to determine the BMDD variables of cancellous bone for the entire skeleton of the patient. In order to quantify deviations from normal mineralization, a reference BMDD for adult humans was calculated using bone samples from 52 individuals. Because we find the BMDD to be essentially constant in healthy adult humans, qBEI provides a sensitive means to detect even small changes in mineralization due to bone disease or therapeutic intervention.

Adult↗

PubMed2003

Assessment of vitamin D and calcium status in healthy adult Austrians.

BACKGROUND: Because there is reason to assume that also in Austria calcium and vitamin D malnutrition is wide-spread, we initiated a comprehensive study on calcium and vitamin D status in relation to bone health in a large group of the normal adult population. SUBJECTS AND METHODS: We assessed dietary calcium and vitamin D intake, serum concentrations of Ca2+, phosphate, alkaline phosphatase, 25(OH)D, 1,25(OH)2D, parathyroid hormone (PTH), follicle-stimulating hormone (FSH), sex hormones and bone mineral density (BMD) by double-energy X-ray absorptiometry at five different skeletal sites in 648 females and 400 males (age 21-76 years). RESULTS: Mean daily intake of vitamin D (101 IU, range 0.2-320) and calcium (569 mg, range 40-2170) was significantly less than the respective recommended dietary allowances. Two hundred and seventy-one (26%) individuals had hypovitaminosis D with serum 25(OH)D < 12 ng mL(-1), while serum Ca2+ was less than normal in 82 (7.8%) subjects. Multiple regression analysis revealed significant correlations between mean calcium intake and BMD in the femoral region in the men (r = 0.13, P < 0.05) though not in the women. No consistent data could be obtained for associations between BMD and vitamin D status, except for 25(OH)D and BMD at the spine in the men (r = 0.10, P < 0.05). 25(OH)D correlated negatively (P < 0.05) with age in the women (r = -0.11) and with PTH in the women (r = -0.11) and men (r = -0.16). Inversely, a significant (P < 0.001) age-related increase in PTH was observed in both sexes (men, r = 0.19; women, r = 0.14). CONCLUSIONS: Prevalence of hypovitaminosis D in adult Austrians is an imminent risk for development of secondary hyperparathyroidism with advancing age, and requires timely correction of nutritional deficits.

Absorptiometry, Photon↗

PubMed2003

Normative data of bone mineral density in an unselected adult Austrian population.

BACKGROUND: There is increasing evidence that correct interpretation of bone mineral density (BMD) measurements by dual energy X-ray absorptiometry (DEXA) requires a population-specific reference range. We therefore collected data on age-related BMD in a random sample of the normal adult Austrian population to establish an appropriate normative database. METHODS: We measured BMD by DEXA at five different skeletal sites in 1089 subjects, i.e. 654 females and 435 males, aged between 21-76 years, who had been recruited by 17 centres across Austria. RESULTS: Age-related bone loss was observed until age 65 years with significant changes at the lumbar spine (r = -0.23), total hip (r = -0.07), trochanter (r = -0.10), femoral neck (r = -0.30) and Ward's triangle (r = -0.40) in the women but only at the femoral neck (r = -0.23) and at Ward's triangle (r = -0.40) in the men. When we calculated T scores from the BMD data of the young normal adult study population and used the T score set points according to the WHO classification of osteopenia and osteoporosis, we found that, depending on the skeletal site measured, 7.6-27.4% of the women and 16-41% of the men in our study group had low bone mass, whereas 0.6-2.7% of the female and 0.2-1.0% of the male study population were osteoporotic. However, osteoporosis was indicated in 4-9-fold more females and 5-15-fold more males when we based our estimates on the normative data provided by the manufacturers of the DEXA systems. CONCLUSION: Our data underscore the importance of using a population-specific reference range for DEXA measurements to avoid overdiagnosis of osteoporosis.

Absorptiometry, Photon↗

PubMed2003

Orientation of mineral crystallites and mineral density during skeletal development in mice deficient in tissue nonspecific alkaline phosphatase.

Tissue nonspecific alkaline phosphatase (TNALP) is thought to play an important role in mineralization processes, although its exact working mechanism is not known. In the present investigation we have studied mineral crystal characteristics in the developing skeleton of TNALP-deficient mice. Null mutants (n = 7) and their wild-type littermates (n = 7) were bred and killed between 8 and 22 days after birth. Skeletal tissues were processed to assess mineral characteristics (small angle X-ray scattering, quantitative backscattered electron imaging), and to analyze bone by light microscopy and immunolabeling. The results showed a reduced longitudinal growth and a strongly delayed epiphyseal ossification in the null mutants. This was accompanied by disturbances in mineralization pattern, in that crystallites were not orderly aligned with respect to the longitudinal axis of the cortical bone. Among the null mutants, a great variability in the mineralization parameters was noticed. Also, immunolabeling of osteopontin (OPN) revealed an abnormal distribution pattern of the protein within the bone matrix. Whereas in the wild-type animals OPN was predominantly observed in cement and reversal lines, in the null mutants, OPN was also randomly dispersed throughout the nonmineralized matrix, with focal densities. In contrast, the distribution pattern of osteocalcin (OC) was comparable in both types of animals. It is concluded that ablation of TNALP results not only in hypomineralization of the skeleton, but also in a severe disorder of the mineral crystal alignment pattern in the corticalis of growing long bone in association with a disordered matrix architecture, presumably as a result of impaired bone remodeling and maturation.

Alkaline Phosphatase↗

PubMed2003

1,25-Dihydroxyvitamin D3 inhibits thyroid hormone-induced osteocalcin expression in mouse osteoblast-like cells via a thyroid hormone response element.

Thyroid hormones are important regulators of bone development and metabolism. We have demonstrated that tri-iodothyronine (T3) increased and 1,25-dihydroxyvitamin D3 (1,25D3) attenuated the T3-stimulated expression of osteocalcin (OCN) in the osteoblast-like cell line MC3T3-E1. By means of transfection of promoter-reporter gene constructs we investigated the basal and the regulated transcription of this gene by both hormones. We found that a 0.67 kbp and a 1.3 kbp fragment of the mouse OCN OG2 promoter containing two Runx2 binding sites were significantly more active than a smaller fragment containing only one Runx2 binding site. The longer promoter fragments showed a higher reporter gene expression when the transfected cells were treated with 10(-7) M T3. This expression was attenuated by 1,25D3 dose-dependently. These fragments contain a sequence homologue to the recently identified binding site for the 1,25D3 receptor (VDR) in the rat OCN promoter. Deletion of a part of the promoter containing this VDR response element-like sequence (VDRE) resulted in a higher basal expression but abrogated the regulation by T3 and 1,25D3. Electrophoretic mobility shift assays revealed that the deleted sequence was able to bind both in vitro-translated chicken thyroid hormone receptor (TR) and proteins from nuclear extracts that reacted with an antiserum against TR. From these data we conclude that the VDRE-like sequence of the OG2 promoter contains a thyroid hormone response element.

3T3 Cells↗

PubMed2002

[Chronic pain management under daily clinical conditions].

BACKGROUND: For lack of specialized pain centers patients with chronic pain are referred to medical, neurological or geriatric departments. One third of these patients are dissatisfied with pain management during stay in hospital (patients interviews 1998). To improve this situation, a pain management system was developed and tested under daily clinical conditions. METHODS: If the history-taking resulted chronic pain (longer than 3 months), the first step was staging the chronicity of pain by the Mainz Pain Staging System. In case of advanced chronic pain (stages II or III), a comprehensive history-taking of the patient's pain including psychometric tests (ADS, SES, PDI) followed. For each patient we worked out an individual and interdisciplinary therapy. To verify the results, each patient was interviewed on the day before dismissal. RESULTS: 27,8% of our patients in half a year period (n = 381) suffered from chronic pain. By pain management activities we were able to rise significantly the satisfaction of the patients with pain therapy. DISCUSSION: It is necessary to search consequently for chronic pain. Especially elder people do not mention their suffer, often believing, that pain is an unavoidable sign of old age. Concentrating on medical reports alone is not adequate for chronic pain and even can aggravate the condition to a significant extent. Chronic pain can neither be explained nor treated without integrating psychological and social factors. A routine diagnostic- and therapy-practice facilitates an interdisciplinary pain therapy, raises the therapeutic capability of the staff and increases the therapeutic outcome.

Chronic Disease↗