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In a woman with chronic renal failure due to interstitial nephritis after chronic analgesic abuse, secondary hyperparathyroidism was at first the predominant feature during a one-year period of dialysis. After parathyroidectomy severe aluminium-induced osteomalacia dominated the picture in the final phase. Surprisingly hyperparathyroidism recurred despite removal of all glandular tissue, and there also developed--previously undescribed--Paget's disease.

HISTORY AND CLINICAL FINDINGS Floor-of-the-mouth cancer had been diagnosed and surgically treated in a 55-year-old man 4 years before the latest admission. For the last 3 years he had been fed through a percutaneous endoscopic gastrostomy (PEG). Since then he had experienced reflux oesophagitis which was being treated with aluminium-containing antacids. He was hospitalized for the surgical treatment of bilateral fractures of the neck of the femur. A surgical biopsy revealed osteomalacia but no metastasis. INVESTIGATIONS The serum phosphate level was significantly reduced (0.21 mmol/l) and there was no detectable phosphate excretion in the 24-hour urine. Serum calcium concentration was unremarkable, but there was hypercalciuria (34.4 mmol/d). Alkaline phosphate activity was significantly raised (393 U/l) and parathormone level reduced (7 ng/l). Vitamin D concentration was unremarkable. TREATMENT AND COURSE The phosphate content in the parenteral feed was at first increased and additional phosphate was given by mouth. The calcium and phosphate levels slowly became normal only after medication had been changed from antacids to H2-blockers. CONCLUSIONS In this case osteomalacia was caused not by vitamin D deficiency but by a lack of phosphate. The reduced intestinal phosphate absorption by the antacids only partially explains the pronounced clinical signs. If antacids are taken over long periods the phosphate balance should be carefully monitored to avoid osteomalacia.

Introduction: Chondrosarcomas belong to the most common malignomas of the skeletal system. The vast majority is located at the epiphysis of the long bones or in the pelvis. Less than 10% of chondrosarcomas are located in the head and neck area, most common in the bony viscerocranium and the larynx. Five histological variants can be differentiated: conventional, mesenchymal, myxoid, dedifferentiated and in less than 5% clear cell chondrosarcomas (CCCS). This case report gives the first description of a CCCS originating from the nasal septum. Case Report: A 79 year old female complaining about a 6 month history of nasal obstruction revealed a huge ballooning of the basal septum in anterior rhinoscopy. Computed tomography exhibited a septal tumor with amorphous calcification. Histology of the tumor resected via lateral rhinotomy confirmed a diagnosis of CCCS. Because of clear surgical margins no radiation therapy was performed. The patient stayed free of recurrence during follow-up of sixteen months. Discussion: The patient presented with typical symptoms of nasoseptal tumors as well as representative CT-scans and histologic findings of CCCS. Because of the complete resection and the CCCS-subtype, the patient is expected to have a positive prognosis.

PURPOSE Evaluation of the influence of an iron-containing MR contrast agent on the signal behaviour and the relaxation time of the bone marrow at 1.5 tesla after repeated doses. ANIMALS AND METHODS 14 pigs received i.v. on days 1, 9, and 15 ultra-small (core diameter 6-8 nm) superparamagnetic iron oxide particles at doses of 20 (low dose = LD) or 200 mumol/kg body weight (high dose = HD). RESULTS Following the first administration a dose-independent reduction in the bone-marrow signal intensity in the T2-weighted gradient-echo sequence (FFE) was observed together with a reduction in the T1 and T2 relaxation times. Following the second application there were no further signal-reductions in the HD-group; in contrast, there was a signal reduction in the LD-group, made possible by a signal recovery in the meantime. On the other hand, the relaxation times T1 and T2 were shortened after each administration of contrast medium. CONCLUSION Nano-SIPS result at both doses in a signal reduction in the bone marrow. Only in the LD-group may repeated examinations with new contrast agent offer diagnostically sufficient images. Relaxometry shows a shortening of T1 as well as T2. This effect could be summed up after repeated doses. Almost no iron remained in the medullary space three weeks after i.v. administration of the contrast agent, which suggests mobilization and metabolization.

We analyzed 14 native osteosarcoma tissue samples for alterations of the tumor suppressor genes RB1 and p53 on the DNA level, and as far as possible, the RNA level. Southern blot analyses concerning both tumor suppressor genes were carried out in all osteosarcomas. In two cases we could demonstrate a deletion within the RB1 gene. DNA analysis of a third osteosarcoma patient revealed a rearrangement of the p53 gene. We had the opportunity of performing corresponding northern analyses in eight native osteosarcoma specimens. The RB1 gene expression was significantly decreased or completely absent in six tumor samples. In two of these tissue probes the expression of both tumor suppressor genes was missing. We determined coexistence of decreased expression of both tumor suppressor genes in one additional case. In summary, 7/14 or 6/8 cases of osteosarcomas (including only those cases which allowed both analyses) showed RB1 gene alteration. In 3/14 or 3/8 osteosarcomas we could determine p53 gene abnormalities. This may indicate that either loss of p53 function is etiologically important only for the development of some osteosarcomas, or a major part of p53 gene mutations are subtle ones and their detection requires more sophisticated techniques, which are currently under development.

In a native osteosarcoma specimen from a patient cured of bilateral retinoblastoma eight years ago, we found a deletion of a 7.5 kb HindIII fragment within the retinoblastoma gene. Our results contribute further evidence that the 7.5 kb fragment harbors a Breakpoint Cluster Region (BCR) in osteosarcoma. In tumor tissue of another osteosarcoma patient the retinoblastoma gene did not reveal any defect on DNA or mRNA level, suggesting different transforming events in this patient.

The 'deleted in colon carcinoma' (DCC) gene has been considered a candidate tumour-suppressor gene that encodes for a transmembrane protein with strong structural similarity to members of the superfamily of neural cell adhesion molecules. It has been mapped to the chromosomal region 18q21.1 and it is implicated in cellular differentiation and developmental processes. In human osteosarcoma allelic loss frequently occurs on the long arm of chromosome 18, suggesting a possible involvement of the DCC gene in the pathogenesis of this tumour entity. In the present study the mRNA and protein expression and rearrangements at the DNA level of the DCC gene were addressed in 25 osteosarcomas and several tumour cell lines, including osteosarcoma- and colon carcinoma-derived cell lines. Using an reverse transcriptase polymerase chain reach in (RT-PCR)-based approach DCC expression was found to be lost or substantially reduced in 14 of 19 high-grade osteosarcomas, in three of six lower grade osteosarcomas and most of the tumour cell lines, in contrast to normally differentiated osteoblasts. Immunohistochemical studies on DCC protein expression of 14 selected tumours correlated well with the RT-PCR-based results. In view of the putative tumour-suppressor characteristics of the DCC gene its loss or reduction of expression could be a specific event in the development or progression of many high-grade osteosarcomas. Images Figure 2 Figure 3 Figure 4

Bone is a common site for metastasis of malignant tumors. These can be recognized radiologically as either lytic or sclerotic lesions since the tumor cells stimulate resident bone cells to cause excessive local resorption or new bone formation. The osteoclast, as the only cell being capable of resorbing bone, is of major importance for the homing of tumor cells in bone and progression of metastasis due to bone destruction. Thus, the improvement of our means of therapeutic intervention towards prevention of tumor progression and pathological fractures will depend on our better understanding of both the molecular basis of bone resorption and the cellbiology of the osteoclast. This article presents our current opinion of the molecular mechanisms of bone resorption by the osteoclast. After describing the morphological features of the osteoclast, aspects such as cell mobility, attachment, enzymes synthesis, transmembrane transport, osteoclast differentiation and function, as well as the protooncogenes c-src and c-cbl and their role in bone resorption are presented in detail.

We have observed 87 cases of spondylosclerosis hemispherica. This lesion has a multiple aetiology, including bacterial causes (florid or low grade infections), stress due to scoliosis, ankylosing spondylitis, dorsal disc prolapse or diffuse disc degeneration. In the majority of cases it is possible to ascertain the aetiology from a consideration of the clinical and serological findings, together with ordinary radiography, conventional tomography or computed tomography. Appropriate treatment can then be given.

This article reviews the applications of SEM methods to human bone pathologies referring to studies made at UCL. We consider the methods which may be most suitable; these prove to be not "routine" in the context of most bio-medical applications of SEM. Valuable information can be obtained from a bone sample if its edges are ground flat, before making either (a) a matrix surface preparation by washing away all the cells or (b) a mineralising front preparation, by also dissolving the osteoid -for which hydrogen peroxide is recommended to produce a robust specimen. BSE contrast from a cut block surface can be used to measure bone phase volume. SE contrasts from natural surfaces (trabeculae, canals and lacunae) can be used to study forming, resting and resorbing* surfaces both qualitatively and quantitatively (*except in the case of histological osteomalacia, where the existence of osteoid will go undetected and reversal lines will be difficult to distinguish from recently resorbed surfaces). We also recommend the use of PMMA embedded bone blocks, which can be used as obtained from the pathologist, but are better embedded by a more rigorous procedure. BSE image analysis can be used to quantitate bone density fractions opening up a completely new investigative method for the future. Osteoid can be measured automatically using CL if the bone sample is block stained with brilliant sulphaflavine before embedding or if a scintillant is added to the embeddant. We give examples of observations made from a number of bone diseases: vitamin D resistant rickets, ostegenesis imperfecta; osteomalacia; osteoporosis; hyperparathyroidism; fluorosis; Paget 's disease; tumour metastasis to bone.

In der Abteilung fur padiatrische Genetik und pranatale Diagnostik der Kinderpoliklinik der Universitat Munchen werden Forschungsarbeiten auf dem Gebiet der Definition und Diagnostik von Dysmorphiesyndromen durchgefuhrt. Schwerpunkte bilden die Erfassung und standardisierte Beschreibung von Phanotypmerkmalen von Syndrompatienten aus eigener Praxis und aus der Literatur, sowie die Erstellung von Syndromkarten, welche die typischen Merkmalskombinationen einzelner Syndrome beschreiben.

On the basis of the current ASTM and ISO standard proposals, a simplified test procedure for spinal fixation implants has been developed. It comprises static and dynamic tests aimed at evaluating the stiffness and strength of various different internal implants. Different methods of mounting the pedicle screws to the test device are shown to significantly affect the characteristic values and failure mechanisms of the implants. The feasibility of the procedure was investigated by comparing 7 different internal fixation implants. The reproducible results revealed general differences associated with the material, dimensions and design, which latter in particular correlated with the specific failure mechanisms. For longer-term in situ duration, testing of these implants should be expanded to include an analysis of wear and corrosion properties.