[Therapy of the hypertensive crisis].
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Antihypertensive Agents↗
Biomedical subjects
R Ziegler
Publications and source records attributed to R Ziegler.
Glucocorticoids regulate the expression of the human osteoblastic endothelin A receptor gene.
The endothelial cell-derived peptide endothelin 1 (ET1) stimulates cell proliferation and differentiated functions of human osteoblastic cells (HOC), and HOC constitutively express the endothelin A receptor (ETRA). Therefore, ET1 may play an important role in the regulation of bone cell metabolism. As glucocorticoids (GC) exert a profound influence on bone metabolism and increase the effects of ET1 on bone cell metabolism in vitro, the effects of GC on ETRA expression in HOC were investigated. Dexamethasone (DEX) increased ETRA mRNA levels in a dose- and time-dependent fashion. The effects of dexamethasone, prednisolone, and deflazacort on the increase of ETRA mRNA levels correlate positively with their binding affinity to the GC receptor. Scatchard analysis of ET1 binding data to HOC revealed that DEX increased the binding capacity for ET1 from 25,300 to 62,800 binding sites per osteoblastic cell, leading to an enhanced mitogenic effect of ET1 on HOC after preincubation with DEX. Transiently transfected primary HOC with a reporter gene construct, containing the 5'-flanking region of the ETRA gene fused to luciferase gene, showed a promoter-dependent expression of the reporter gene and the induction of reporter gene expression by DEX treatment. Total RNA extracts of femoral head biopsies with osteonecrotic lesions from GC-treated patients showed threefold higher ETRA mRNA levels compared with extracts of bone biopsies from patients with traumatically induced osteonecrosis and coxarthrosis. Furthermore, GC treatment increased plasma ET1 levels by 50% compared with pretreatment values. These findings suggest that GC induced upregulation of ETRA, and ET1 plasma levels enhance ET1's anabolic action on bone cell metabolism. Increased ET1 concentrations may also impair bone perfusion by vasoconstriction in a metabolically activated skeletal region.
Adult↗
Identification of four genes in endothelial cells whose expression is affected by tumor cells and host immune status--a study in ex vivo-isolated endothelial cells.
A spontaneously metastasizing, well-defined mouse lymphoma was chosen as an in vivo model to study the effect of tumor-host interaction on gene expression in liver sinusoidal endothelial cells. Forty-nine bovine aortic endothelial cell (BAEC) genes, recently isolated by a differential screening approach of a cDNA library enriched for tumor necrosis factor-alpha (TNF-alpha) suppressed genes, were investigated. Four of these genes were finally selected because they were affected differentially by host immuno-competence, TNF-alpha, and tumor cells. Sequence analysis showed them to encode the bovine polyubiquitin (A4), elongation factor 1alpha (B2), the acidic ribosomal phosphoprotein PO (C3), and the ribosomal protein S2 (E10). Gene expression was analyzed by dot-blot or Northern blot analysis. TNF-alpha and tumor cell conditioned supernatant suppressed the genes additive in BAEC but not in other endothelial cells except for bovine capillary endothelial cells. Ex vivo-isolated liver endothelial cells of tumor-bearing syngeneic DBA/2 mice showed strong downregulation of these four genes in comparison to normal control values. In contrast, endothelial cells of tumor-bearing immuno-incompetent Balb/c (nu/nu) mice showed no downregulation but upregulation of these genes. Consistently, all four genes were also downregulated when BAEC were incubated with supernatants derived from ex vivo-isolated liver metastases from immuno-competent but not from -incompetent mice. Thus, the expression of a group of genes involved in protein translation and processing was more profoundly altered in endothelial cells in vivo than in vitro, suggesting that microenviromental factors and cell-cell and cell-matrix interactions play an important role.
Amino Acid Sequence↗
[Changes in thyroxine-binding globulin: pitfalls in thyroid function diagnosis].
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False Negative Reactions↗
[Multiple endocrine neoplasia associated with multiple lipomas].
BACKGROUND: Multiple endocrine neoplasia type 1 (MEN-1) is characterized by tumors of the parathyroids, the neuroendocrine pancreas-duodenum and the anterior pituitary, but shows also a wide clinical variety of other symptoms. CASE REPORT: We present a case of a 68-year-old woman with a 18 year history of MEN-1 consisting of gastrinoma and primary hyperparathyroidism. Beside these typical symptoms, the patient suffered from thyroid adenoma, malignant kidney tumor and multiple subcutaneous lipomas. RESULT: While the number of autopsies declined from 113 in 1977 to 66 in 1984, the number of diagnostic techniques used increased continuously (94, 107, 118 and 140, amounting to 0.83, 1.34, 1.76 and 2.12 per patient). The premortal detection of abdominal abnormalities increased globally from 16.8 to 32.5%. This increase was largely due to better diagnosis of liver and gallbladder abnormalities which were in most cases of little relevance. CONCLUSION: Whether these non-endocrine tumors are associated to MEN-1 is unclear and has to be tested by examining the chromosomal regions 11q13 and 11q24/25 of the tumors sample, in which the possible MEN-1 involved tumor suppressor genes are located.
Aged↗
[Effect of pamidronate on clinical symptoms and bone metabolism in fibrous dysplasia and McCune-Albright syndrome].
BACKGROUND: Patients with fibrous dysplasia and the McCune-Albright syndrome which is characterized by additional endocrine dysfunctions, such as pubertas precox, suffer from a regional impairment in the differentiation of osteoblasts that is acquired during early embryogenesis and results in fibrous bone lesions. These lesions may cause bone deformities, fractures and chronical pain in the affected skeletal regions. We here report about our experience with a systemic treatment of the bisphosphonate pamidronate. PATIENTS: We treated 3 patients with fibrous dysplasia and 5 patients with McCune-Albright syndrome over a cumulative period of 37 patient-years. RESULTS: In all patients who suffered from painful lesions, intravenous infusions of 60 mg pamidronate resulted in an improvement of pain that lasted up to 6 months. In 2 patients we also observed a reduction in the size of some of the osteolytic lesions. Side effects were limited to asymptomatical fever and a small decline in total serum calcium within the physiological limits during the infusions. CONCLUSION: Pamidronate appears to be an effective and well tolerable treatment option for patients with fibrous dysplasia.
Adolescent↗
Thrombomodulin modulates growth of tumor cells independent of its anticoagulant activity.
Thrombomodulin (TM), recognized as an essential vessel wall cofactor of the antithrombotic mechanism, is also expressed by a wide range of tumor cells. Tumor cell lines subcloned from four patients with malignant melanoma displayed a negative correlation between TM expression and cell proliferation in vitro and in vivo. Overexpression of wild-type TM decreased cell proliferation in vitro and tumor growth in vivo. TM mutants with altered protein C activation capacity lead to a similar effect. In contrast, transfection of melanoma cells with mutant TM constructs, in which a portion of the cytoplasmic or lectin domain was deleted, abrogated the antiproliferative effect associated with overexpression of wild-type TM. Experiments performed with either peptide agonists/antagonists of the thrombin receptor, with hirudin, or with inhibitors of thrombin-TM interaction did not alter the growth inhibitory effect of TM overexpression. These data suggest that TM exerts an effect on cell proliferation independent of thrombin and the thrombin receptor, possibly related to the binding of novel ligands to determinants in the lectin domain which might trigger signal transduction pathways dependent on the cytoplasmic domain.
Animals↗
[Epidemiology of osteoporosis].
Epidemiological studies have identified osteoporosis as a disease of significant public health impact and have delineated numerous potential risk factors. Nevertheless, it has proven difficult to establish preventive strategies for several reasons. First, there has been no final agreement on the definition of osteoporosis, which has hampered efforts to characterize the magnitude of the problem as a whole. Secondly, as osteoporosis is a multifactorial chronic disorder, effective programs for risk assessment and intervention depend on the development of complex disease models. In summarizing the contributions of epidemiological studies to the current understanding of osteoporosis this review intends to outline the scientific background for the European Vertebral Osteoporosis Study (EVOS) and its successors.
Cross-Sectional Studies↗
[Vertebral deformity as an index of osteoporosis-induced spinal fracture--an external validity construct based on bone density data].
BACKGROUND: In order to test the validity of vertebral morphometry for the assessment of prevalent vertebral osteoporotic fractures, we examined the association between vertebral deformities and bone mineral density (BMD). METHOD: The study population consisted of 595 postmenopausal women and 581 men aged 50 to 82 years who participated in the baseline survey of the European Vertebral Osteoporosis Study (EVOS) in Germany and received BMD measurements by dual-X-ray-absorptiometry (DXA) at the femur and the lumbar spine. RESULTS: In both sexes only vertebral deformities defined by more stringent morphometric criteria (McCloskey; Eastell 4 SD criterion) were significantly and inversely related to BMD (odds ratios 1.42 to 3.21 for a 1 SD [standard deviation] reduction in BMD; p < 0.05). The strength of the association depended on the stringency of the morphometric algorithm applied, and on the site of BMD measurement. The strongest associations were observed with femoral neck BMD in women and with BMD at the lumbar spine in men. In contingency analyses between vertebral deformities and osteoporosis (WHO criteria; European young female BMD reference values), vertebral deformities proved to be highly specific by all methods, even slightly more so in men (87.8 to 97.5%) than in women (86.3 to 96.7%). The predictive value of a positive test with respect to vertebral osteoporosis reached a maximum value of about 50% in both sexes. It further increased up to 72%, when the definition of osteoporosis was based on low BMD values at either the spine or the femoral neck, but only in women. CONCLUSIONS: In conclusion, for both men and women the likelihood of vertebral deformities to be related to osteoporosis increases with the stringency of the morphometric method, with a similar probability of major deformities to represent vertebral osteoporotic fractures in men as in women. Nevertheless, even the most stringent morphometric criteria are not sufficiently valid instruments for the assessment of the prevalence of vertebral osteoporotic fractures in epidemiological studies.
Aged↗
[Osteosonography of the phalanges of men].
BACKGROUND: The distal metaphysis of the first phalanx of the fingers II to V is, like the vertebral body, a useful site for the measurement of mineralisation and structure of the bone, because of the simultaneous presence of compact and trabecular bone. METHOD: With an osteosonographic device (DBM sonic 1200, IGEA, Italy) we measured in 38 young and healthy men, 14 elderly and healthy men, 18 men with osteopenia, 8 men with osteoporosis and vertebral fractures and 10 men with long-standing cortisone medication, the adSOS (amplitude-dependent speed of sound) and the UBPS (ultrasound bone profile score) at the phalanges, as well as bone mineral density (BMD) at lumbar spine using dual-X-ray absorptiometry (DXA). RESULTS: There was no correlation between adSOS or UBPS and lumbar BMD (DXA). There was a significant positive correlation between adSOS and UBPS, r = 0.826 (p < 0.00001). AdSOS declined with age (r = 0.694, p = 0.021); the UBPS was not age-dependent (r = -0.15, p = n.s.), as expected. AdSOS and UBPS could discriminate significantly between the young and healthy controls and the men with osteopenia/vertebral fractures or oral steroids (p < 0.00001). The DXA could be significantly discriminate all healthy controls from the patients with osteopenia or vertebral fractures. It could not significantly discriminate the healthy controls from the patients taking oral glucoconticoids. Only the UBPS could significantly discriminate this group from the healthy controls. CONCLUSION: These results show, that adSOS and UBPS are precise parameters to be measured at the phalanges. The detection level of pathological changes in osteoporosis are similar between adSOS and lumbar BMD (DXA) and improved by using UBPS. This might be explained by the influence of structural changes in bone on UBPS, rather than changes in bone mineral alone. Prospective studies have to clarify the role of adSOS and UBPS in fracture prediction.
Adult↗
Virtual reality: preparation and execution of sinus surgery.
Endonasal sinus surgery requires a great deal of training before it can be performed adequately. Due to the complex and variable anatomy and the proximity of important structures, severe complications are possible, even for experienced surgeons. The nasal endoscopy simulator (NES) is an interactive training system for nasal endoscopy and endonasal sinus surgery that combines computer graphics and virtual reality (VR) techniques. This system consists of a graphics workstation, a tracking system for measuring the position of the endoscope and surgical instruments in space, a head model, image data sets of the nasal cavity and paranasal sinus area, and complementary software. The current NES is a visual and auditory VR system that provides both educational and planning options for sinus surgery. The usual resistance when touching relevant anatomical structures is not provided by this release. Therefore, a "force feedback system" is implemented that allows for such a response. VR simulation will become an important part of surgical education and planning for individual sinus surgery procedures. The ongoing development of the NES will lead to an improved educational environment for residents in training and practitioners.
Computer Graphics↗
Effects of angiotensin II on bone cells in vitro.
Other than its known effects on the cardiovascular system, angiotensin II (Ang II) stimulates cell growth in several cell types. In this study, we examined whether it also might affect bone cell metabolism. Ang II stimulated DNA and collagen synthesis and decreased alkaline phosphatase (AP) activity in bone cell populations derived from the periosteum of fetal rat calvariae. Similar effects of Ang II were observed on human adult bone cells obtained by collagenase digestion from trabecular bone. Clonal cell analysis, autoradiographic studies, and receptor subtype analysis suggested the presence of specific Ang II receptor subtype 1 (AT1) binding sites on AP+ osteoblastic precursor cells. Ang II had no direct effects on osteoblastic cells with a mature phenotype, but paracrine effects of Ang II on mature osteoblasts could be observed upon coculture with Ang II-responsive bone cell populations. Because Ang II is known to be locally generated by endothelial cells, Ang II might play an important role in coordinating capillary cell growth and osteoblastic bone formation during bone remodeling.
Angiotensin II↗
Mammalian fauna and biostratigraphy of the pre-Neandertal site of Reilingen, Germany.
In 1978 three well-preserved pieces of a fossil human cranium (i.e., fused parietals, occipital and temporal) were found in a gravel pit near the southwest German town of Reilingen. It was recovered, with an accompanying mammalian fauna, as a side-product of commercial gravel mining. The sample was sorted from the dredgings of a boat-mounted crane reaching to a depth of 28 m below the surface. Here we present the mammalian fauna and discuss its biostratigraphical relevance. The fauna represents a mixture of Holstein interglacial to Würm glacial species. The occurrence of Holsteinian faunal components is indicated by presence of the extinct beaver, Trogontherium. Given the good preservation of specimens found at the lowest levels we can rule out reworking. The accompanying fauna indicates a Holstein to Würm time span bracketing the fossil hominid population.
Animals↗
On the phylogenetic position of the pre-Neandertal specimen from Reilingen, Germany.
This paper describes the morphology and phylogenetic significance of a well-preserved fossil human cranium found near Reilingen, Germany in 1978. The specimen consists of two complete parietals, most of the right temporal, and 70% of the occipital. The specimen displays several features characteristic of early "archaic" Homo sapiens: maximum breadth at the supramastoid crests, roughly pentagonal occipital view, an angular torus, superoinferiorly elongate/ anteroposterior shortened squamous temporal, strong mastoid, and separation of the tympanic and mastoid temporal portions. Other features align the Reilingen cranium with the "classic" Neandertals: developed suprainiac fossa, bilaterally protuberant occipital torus, strong juxtamastoid eminence, a highly convex occipital plane, and lambdoid flattening. This morphology and our cephalometric analysis support the assignment of this specimen to a Stage 2 "pre-Neandertal" group (e.g., Steinheim, Swanscombe, and Atapuerca [SH site]). Following an "Accretion Model" of European hominid evolution, Stage 2 succeeds Stage 1 European "early-pre-Neandertals" (e.g., Mauer and Petralona), and precedes both the Saale-Eem Stage 3 "early Neandertals" (e.g., Biache 1), which present greater platycephaly, a reduced mastoid process, an enlarged juxtamastoid eminence, and true "en-bombe" (parieto-occipital form), and Weichsel Stage 4 "Neandertals" (sensu stricto, i.e., "classic" Neandertals).
Animals↗
[Biphosphonate therapy in the management of skeletal metastases].
Bisphosphonates are a new theraeutic option in the treatment of bone diseases. They inhibit osteoclastic bone resorption and are established in the treatment of osteoporosis, Paget's disease of bone and especially in tumor bone disease. The effects of pamidronate, clodronate and ibandronate in the treatment of hypercalcemia of malignancy and osteolytic bone disease have been extensively studied. These drugs represent the treatment of choice in hypercalcemia of malignancy. The regular application of bisphosphonates reduces skeletal-related events like pathologic fracture, bone pain or hypercalcemia of malignancy, especially in breast cancer and multiple myeloma. Of great interest are the ongoing studies concerning prophylactic application of bisphosphonates in tumors bearing a high risk for bone metastases, especially since the first results suggest a significant reduction in the development of bone metastases in breast cancer patients.
Bone Neoplasms↗
Reduced pulmonary function in patients with spinal osteoporotic fractures.
Vertebral deformation in spinal osteoporosis results in spinal and thoracic deformation, causing pain, disability and an overall decrease in quality of life. We sought to determine whether thoracic spinal deformation may lead to impaired pulmonary function. We studied expiratory relaxed vital capacity (VC) and forced expiratory volume in 1 s (FEV1) in 34 patients with spinal osteoporotic fractures and 51 patients with chronic low back pain (CLBP) due to reasons other than osteoporosis. Measurements of pulmonary function tests were calculated as a percentage of the normal range adjusting for age, sex, and height using the equations for normal values of the EKGS (Europäische Gesellschaft für Kohle und Stahl). Severity of osteoporosis was determined by calculation of the spine deformity index (SDI-total and SDI-anterior) on lateral radiographs of the spine and clinical measures of body stature (height reduction, distance from lowest ribs to iliac crest and distance from the occiput to the wall). Patients with osteoporosis had a lower vital capacity (%VC of the reference value) than patients with CLBP. The differences were more prominent (p < 0.05) when the previous body height, at age 25 years, was used as reference for calculation of VC (mean +/- SD: 93.6% +/- 15.3% in patients with osteoporosis v 105.6% +/- 15.1% in patients with CLBP). FEV1 was significantly (p < 0.05) lower in patients with osteoporosis when previous body height was considered, in comparison with patients with CLBP (mean +/- SD: 85.0% +/- 14.2% in patients with osteoporosis v 92.4% +/- 13.6% in patients with CLBP). In patients with osteoporosis VC (standardized on previous body height) was significantly negatively correlated with SDI-anterior (r = -0.4, p < 0.03). Furthermore, VC standardized on previous body height showed a weak but significant negative correlation with some clinical measures of osteoporosis (height reduction vs %VC: r = -0.34, p < 0.05; distance from the lowest ribs to iliac crest vs %VC: r = 0.35, p < 0.04). In conclusion, we found that pulmonary function is significantly diminished in patients with spinal osteoporotic fractures as compared with CLBP patients without evidence of manifest osteoporosis. Reduction of pulmonary function is correlated significantly with clinical and radiological measures of severity of spinal deformation due to osteoporotic fractures.
Aged↗
Ultrasound measurements at the proximal phalanges in healthy women and patients with hip fractures.
Measurements of bone mineral density (BMD) are useful for the assessment of fracture risk in osteoporosis. First prospective studies showed that quantitative ultrasound as measured at the calcaneus also predicts future hip fracture risk, independently of BMD and as accurately as BMD. The aim of this study was to compile a reference population for a new ultrasound device that determines amplitude-dependent speed of sound (AD-SOS) through the proximal phalanges of the hand and to prove its ability to distinguish between health volunteers and osteoporotic patients. In a case-control study we examined 139 healthy women aged 21-94 years and a group of 24 female patients aged 69-94 years with recent hip fractures. In the healthy reference population additional BMD measurements were performed with dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound measurements at the calcaneus were carried out. In vivo precision of AD-SOS measurements through the phalanges was 0.52% CV. Simple regression analyses showed a negative correlation with age (r = -0.73, p < 0.001); modest significant correlations with BMD of the lumbar spine (r = 0.36, p < 0.001) and BMD of the femoral neck (r = 0.37, p = 0.002) as measured with DXA were shown. The comparison with another ultrasound device measuring SOS and broadband ultrasound attenuation (BUA) through the calcaneus showed correlation with SOS (r = 0.50, p < 0.001); no significant correlation was found with BUA measurements. Furthermore a dependency of AD-SOS values in anthropometric factors such as body mass index (r = 0.37, p < 0.001), height (r = 0.40, p < 0.001) and weight (r = 0.23, p < 0.05) was shown. First study results on 24 clinically diagnosed osteoporotic patients, defined as patients with recent (< 1 week) pertrochanteric or femoral neck fractures, showed a good separation between age- and sex-matched controls and osteoporotic patients (Z = -2.0 SD). Receiver operating characteristic (ROC) curves showed an area under the fitted curve of 0.83 +/- 0.06. These results are powerful for a device measuring AD-SOS through the proximal phalanges of the hand, and further prospective studies have proven the capability of phalangeal ultrasound in fracture risk assessment.
Absorptiometry, Photon↗