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PubMed1975

The pathological basis for skeletal scintigraphy.

Skeletal scintigraphy, which has now been established as a useful and accurate method of detecting early skeletal metastases and assessing their response to treatment, has been investigated for its pathological basis. Histological examination of several hyndred necropsy specimens, from sixty-eight patients who died from malignant disease, showed a significant increase of osteoid and immature woven bone in the presence of metastatic cancer. Tumour-cell suspensions of the VX2 carcinoma were injected into the medullary cavity or on to the periosteal surface of the ilia or tibiae of New Zealand white rabbits. A combination of bone destruction and new bone formation, similar to the autopsy material, was seen. There were at least two mechanisms for the new bone production. Initially, intramembranous ossification was seen in the fibrous stroma surrounding the tumour. Once the cortex was involved and cortical bone destruction had occurred, large amounts of woven bone resembling fracture callus were laid down. The new bone had a markedly increased avidity for bone-seeking isotopes, indicating why skeletal scintigraphy was useful. A further twenty rabbits, in whose ilia the VX2 carcinoma was growing, were treated by local irradiation. When treatment was successful the tumour was destroyed, the production of new bone ceased, and the lesion lost its increased avidity for bone-seeking isotopes, indicating that skeletal scintigraphy could be used to assess the response of skeletal metastases to therapy.

Animals↗
PubMedDate not supplied

[Potentialities of temporal bone computed tomography in the identification of causes of hypoacusis of postinflammatory genesis].

Temporal bone computed tomography (CT) was used to examine 64 patients with impaired hearing due to inflammatory diseases of the middle year. In 21 patients, the pathological process was bilateral. A total of 85 series of temporal bone CT scans were analyzed. The patients' age ranged from 2 to 66 years. CT verified adhesive otitis media in 62 cases, otosclerosis in 7, local malformation of the auditory ossicles and/or the labyrinthine fenestrae in 11. No CT changes were revealed in 5 cases. The CT symptoms of adhesive otitis media were identified. These included soft tissue bands and/or soft tissue-density portions that fix the auditory ossicles or block the niches of the labyrinthine fenestrae (31 temporal bones); sclerosis or ossification of the ligaments and tendons of the middle ear (7 temporal bones); calcification foci in the tympanic cavity (9 cases); osteosclerotic changes in the epitympanus (2 cases); cicatricial changes in the tympanic membrane (24 cases); destructive changes in the auditory ossicles (19 temporal bones). There has been evidence that CT may be used for the differential diagnosis of adhesive otitis media from otosclerosis and congenital malformations of the structures of the middle ear.

Adolescent↗
PubMedDate not supplied

CT anatomy of the craniovertebral junction in infants and children.

Computed tomographic (GE 9800) images of 129 patients (from newborn to 18 years old) with no evidence of cervical spine pathology were reviewed retrospectively from available material to evaluate normal anatomic appearances in childhood. The synchondroses may appear solid at soft-tissue window settings, while, with appropriate bone-window settings, a lucent line will be seen. Residual lucency and then (generally) sclerosis were seen at synchondroses past the age of classic anatomic fusion. A transversely oriented groove on the undersurfaces of the occipital condyles was imaged in children ages 5-12 years. This groove is described radiologically in that age range for the first time in this report. The development of the ossification centers of C1 was illustrated with CT. The two vertically oriented, rod-shaped ossification centers of the lower dens develop a bilobed appearance in axial section when they begin to fuse. An apparent deficiency of the cortex seen posteriorly in this area (in children as old as 7 years) represents the last remnant of the cleft between the dens centers. The cord was always outlined distinctly by CSF at soft-tissue settings at the foramen magnum and C1 levels without intrathecal or IV contrast enhancement. This anatomic feature is particularly useful since it enables the evaluation of the spinal canal in this region in some cases (especially craniovertebral junction anomalies) without the need for intrathecal contrast materials.

Adolescent↗
PubMed1982

Cloverleaf skull syndrome. An autopsy case and review of literature.

An autopsy case of cloverleaf skull deformity associated with hydrocephalus, systemic skeletal malformation including facial dysostosis, fused elbow, syndactyly of the toes, odd digits and striking anomaly of tracheal cartilage is presented. Extra-skeletal abnormalities included covered anus, dermal sinus and the absence of corpus callosum and the septum pellucidum. Several basal skull deformity appeared to be a primary morphologic alteration associated with premature closure of the specific sutures, which terminally resulted in life-threatening hydrocephalus. Histological investigation showed the abnormalities of endochondral ossification in the cartilage at the epi- and meta-physis of the fused elbows. In addition, electron microscopical study revealed unusual fat droplet-containing chondrocytes even in the resting and multiplicative phase. Association of the tracheal anomaly with this syndrome was disclosed in this case. Generalized bone and cartilage abnormalities not only in the skeletal system but also in the internal organs strongly suggest that this disorder involves generalized osteocartilagenous system. The present case makes a total of 14 cases of the cloverleaf skull syndrome reported in the Japanese literatures to date. Major clinical and pathologic findings of these cases were summerized.

Abnormalities, Multiple↗
PubMed1997

[Contrast analysis of clinical and pathological staging of supraglottic carcinomas].

To evaluate the accuracy of clinical staging of supraglottic carcinomas, a retrospective histopathological study of larynges from 53 patients who had undergone total laryngectomy was adopted. All larynges were processed as whole-organ serial sections in coronal plane. The results showed that clinical underestimation had been made in 24.5% of all laryngeal cancer cases. Clinical underestimation occured in 54.5%, 33.3% of T2, T3 laryngeal cancer cases, respectively. There was no overestimation in clinical staging. The important factors that affected clinical underestimation were invasion of the pre-epiglottic space and thyroid cartilage. It is suggested that the pre-epiglottic space should be resected in early supraglottic carcinoma. The thyroid cartilage involvement should be suspected in laryngeal cancer with extensive invasion of anterior commisure or extensive invasion of the paraglottic space accompanied by cartilage ossification.

Adult↗
PubMedDate not supplied

[Diagnosis of dystrophic lesions of the muscular and ligamentous tendons].

The authors presented the results of investigations of the humoral, ulnar, hip, knee joints and calcanei in 4140 patients. Histology has shown that calcifications and ossifications at the sites of tendon fixation are localized in tendons. The substitution of tendinous tissue for a bone results from calcareous dystrophy. Three stages can be singled out: (I) the substitution of a tendon portion for a fibrillar cartilage; (II) the calcification of a cartilage; (III) the substitution of a calcified cartilage for a newly developed spongy bone. According to the preliminary data, similar changes can bep6 observed in ligaments, too. The clinical and x-ray examination have shown the frequency of tendinous and ligamentous lesions (tendinosis and ligamentosis) of different sites. They were shown to be pathology that may not be accompanied by pains. The appearance of the pain syndrome means the development of disease.

Humans↗
PubMedDate not supplied

Influence of inoculation sites and tumor cell culture techniques on the phenotype of a mixed cartilage- and bone-producing mouse mammary tumor.

We have previously reported the characterization of an intraperitoneally (IP) transplantable bone-forming MXT tumor. However, the question was unresolved as whether the bone-forming cells originated from either the host animal or from the neoplasm itself. The present work attempts to answer this question by studying the influences of inoculation sites (subcutaneously, SC; intraperitoneally, IP; in the brain, IB; intracranially, ICR) on both the cartilage- and bone-forming tumor phenotypes. Furthermore the influence of cell culture procedures (two- and three- dimensional cultures) on these phenotypes was investigated. SC administered MXT cancer cells never produce bone-forming tumors, suggesting the existence in the dermis of substance(s) inhibitory to the formation of cartilage or bone. On the contrary, our data clearly demonstrate that bone-forming tumors can be obtained by either IP route, in a way which mimics endochondral ossification, or in the brain (IB), a region usually devoid of connective tissue. This observation substantiates the hypothesis according to which the tumor itself is able to produce osseous tissue. Another main finding is the increasing occurrence of skeletal tissues produced by cells proceeding from three-dimensional culture. Finally, ICR and IB tumors exerted a bone-lytic action against the host skull suggesting that tumor cells either produce osteolytic substances (prostaglandins, enzymes) and/or that they contain various cell types exhibiting different properties toward osteogenesis. This model offers new perspectives for studying the mechanisms of both normal and pathologic osteogenesis.

Animals↗
PubMed1997

The Apert syndrome hand: pathologic anatomy and clinical manifestations.

The Apert syndrome hand demonstrates many typical clinical features including syndactyly, symbrachyphalangism, and growth disturbances. This is due to the grossly abnormal anatomy of both the skeletal and soft-tissue structures associated with a progressive disease process. This paper presents a clinical, radiologic, and histologic analysis of the Apert syndrome hand anatomy and correlates it with the clinical manifestations. It also links hand and craniofacial dysplasia to other regions of the skeleton as well as the overall disease process. From our analysis, we conclude that there is a genetic anomaly causing variable and uncoordinated differentiation of the mesenchyme at the time of embryologic separation into its various skeletal components, particularly in the distal limb bud and craniofacial skeleton. This disease process continues postnatally in endochondral bone growth center malformation and malfunction as well as ectopic cartilage ossification in soft tissues. We discuss the role of abnormal musculotendinous anatomy and altered biomechanical forces in relation to these processes.

Acrocephalosyndactylia↗
PubMed1979

[Physiology and pathology of the epiphyseal cartilage (author's transl)].

Knowledge of the physiology of the epiphyseal cartilage, respectively epiphyseal plate, is essential for an understanding of defective growth and abnormal modeling of the long bones. The epiphyseal cartilage develops from the embryonal, cartilaginous long bone structure. The histology of the epiphyseal cartilage is characterised by definable zones representing the individual differentiation steps from the reformation of cartilage to chondrolysis. Modeling of the ends of the long bones is also influenced by a transversal and longitudinal direction of growth in the epiphyseal cartilage. The intercellular substance mainly contains collagin, proteoglycanes and non-collagenic proteins. These macromolecules are compounded by means of physicochemical bonds and are responsible for the special mechanical qualities of the hyaline cartilage. The process of mineralisation at the base of the epiphyseal cartilage is an essential differentiating step for the ossification processes which take place in the metaphysis. Two pathogenetic principles at the epiphyseal cartilage appear to be important for the defective growth of the long bones. On the one hand, the flowing equilibrium between the differentiation steps of cartilage reformation, transformation of the hyaline cartilage into a mineralised cartilaginous tissue and chondrolysis is changed, whereas on the other hand the turnover of these differentiation steps is retarded or accelerated.

Animals↗
PubMed1981

Wilms tumor: ultrasonic features, pathologic correlation, and diagnostic pitfalls.

The gray-scale ultrasonic features of Wilms tumor are reported with pathologic comparison. The most consistent ultrasonic features are large size, sharp margination, and echogenic heterogeneity. The frequently observed anechoic areas correlated with hemorrhage and necrosis. A rare case of mesoblastic nephroma is included for comparison. Pitfalls in diagnosis are discussed.

Child↗
PubMed1999

Cathepsin expression during skeletal development.

Cysteine proteinases, cathepsins B, H, K, L and S, have been implicated in several proteolytic processes during development, growth, remodeling and aging, as well as in a variety of pathological processes. For systematic analysis of cathepsin gene expression we have produced cDNA clones for mouse and human cysteine cathepsins. Northern analysis of a panel of total RNAs isolated from 16-19 different human and mouse tissues revealed the presence of mRNAs for cathepsin B, H, K, L and S in most tissues, but each with a distinct profile. Of the different cathepsin mRNAs, those for cathepsin K were clearly the highest in bone and cartilage. However, relatively high mRNA levels for the other cathepsins were also present in these tissues. To better understand the roles of different cathepsins during endochondral ossification in mouse long bones, cathepsin mRNAs were localized by in situ hybridization. Cathepsin K mRNAs were predominantly seen in multinucleated chondroclastic and osteoclastic cells at the osteochondral junction and on the surface of bone spicules. The other cathepsin mRNAs were also seen in osteoclasts, and in hypertrophic and proliferating chondrocytes. These observations were confirmed by immunohistochemistry and suggest that all cysteine cathepsins are involved in matrix degradation during endochondral ossification.

Amino Acid Sequence↗
PubMed1989

Ultrasonography and radiography of the hip in infants.

Both hip joints in 156 children, aged 2 months to 2 years, were examined by ultrasonography (ultrasound) and radiography. Pathologic findings were based on an increased acetabular index, bony defects of the lateral acetabular rim, and lateral and/or proximal displacement of the proximal femur. Each hip was classified as normal, dysplasia, subluxation, or dislocation. The same diagnosis was reached by ultrasound and radiography in 303 of the 312 hips. The accordance was good in normal joints, in subluxation, and in dislocation. However in 7 of the 15 hips with radiographic dysplasia, ultrasound was normal. These patients were not treated, and spontaneous normalization or improvement occurred in all of them. One parameter only, the distance from the lateral margin of the ossification center of the femoral head to Perkins' line, was measured by both ultrasound and radiography; the correlation was high (r = 0.73). We recommend ultrasound as the primary imaging technique when congenital dislocation is suspected clinically.

Aging↗
PubMed1985

Degenerative diseases of the vertebral column.

Several distinct degenerative processes affect the articulations of the vertebral column; each is associated with characteristic radiographic and pathologic abnormalities, and many are accompanied by significant clinical manifestations. A discussion of these processes is best accomplished according to the type of joint that is involved. With regard to cartilaginous articulations, of which the intervertebral disk is most important, intervertebral (osteo)chondrosis, spondylosis deformans, and, in the cervical spine, uncovertebral arthrosis are the major degenerative disorders. Osteoarthritis (osteoarthrosis) affects any of the synovium-lined joints of the vertebral column, including the apophyseal, costovertebral, transitional lumbosacral, median atlantoaxial, and sacroiliac articulations. Fibrous articulations, ligaments, or entheses (sites of tendon or ligament attachment to bone) are involved in diffuse idiopathic skeletal hyperostosis, ossification of the posterior spinal ligaments, and Baastrup disease. Of the many complications of these degenerative processes, alignment abnormalities (including segmental instability, degenerative spondylolisthesis, senile kyphosis, and degenerative scoliosis), intervertebral disk displacement, calcification or ossification, and spinal stenosis are the most important.

Humans↗
PubMed1993

Osteogenic melanoma. A rare variant of malignant melanoma.

Osteogenic melanoma is a rare variant of malignant melanoma; only eight cases have been reported. To characterize this unusual neoplasm further, we present four new cases. Two patients were men and two were women (average age, 56 years; range, 47-78 years). All tumors arose from acral lentiginous melanomas. Three were subungual finger lesions and one was on the sole of the foot. All four had been previously diagnosed as or were suspected to have been primary osseous lesions. The vertical growth components were high-grade, amelanotic sarcomatoid malignancies with abundant osteoid matrix. Two tumors also had chondroblastic differentiation. Cells with epithelioid features, including prominent eosinophilic nucleoli, were discernible in every tumor. Regional lymph node metastases in two cases retained osteocartilaginous differentiation, whereas metastatic cells in another case were purely epithelioid. Tumor cells in every case were immunoreactive for S-100 protein and vimentin, and non-reactive for cytokeratin. Two tumors also expressed HMB-45. Melanosomes were identified ultrastructurally in every tumor. Follow-up information was available on every patient. Three developed regional lymph node metastases and are currently alive and well after 14, 39, and 101 months. The fourth patient died of metastatic uterine carcinoma 20 months postoperatively. The differential diagnosis of osteogenic melanoma includes osteosarcoma as well as atypical fibro-osseous proliferations. Clinico-pathologic features that support a diagnosis of osteogenic melanoma include junctional activity, absence of primary bony involvement, regional nodal metastases, immunoreactivity for S-100 protein and/or HMB-45, lack of cytokeratin reactivity, and ultrastructural identification of melanosomes.

Aged↗
PubMed2005

Can the growth factors PTHrP, Ihh and VEGF, together regulate the development of a long bone?

Endochondral ossification is the process of differentiation of cartilaginous into osseous tissue. Parathyroid hormone related protein (PTHrP), Indian hedgehog (Ihh) and vascular endothelial growth factor (VEGF), which are synthesized in different zones of the growth plate, were found to have crucial roles in regulating endochondral ossification. The aim of this study was to evaluate whether the three growth factors PTHrP, Ihh and VEGF, together, could regulate longitudinal growth in a normal human, fetal femur. For this purpose, a one-dimensional finite element (FE) model, incorporating growth factor signaling, was developed of the human, distal, femoral growth plate. It included growth factor synthesis in the relevant zones, their transport and degradation and their effects. Simulations ran from initial hypertrophy in the center of the bone until secondary ossification starts at approximately 3.5 months postnatal. For clarity, we emphasize that no mechanical stresses were considered. The FE model showed a stable growth plate in which the bone growth rate was constant and the number of cells per zone oscillated around an equilibrium. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates resulted, respectively, in more and less cells per zone and in increased and decreased bone growth rates. The FE model correctly reflected the development of a growth plate and the rate of bone growth in the femur. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates reflected growth plate pathologies and growth plates in PTHrP-/- and Ihh-/- mice. The three growth factors, PTHrP, Ihh and VEGF, could potentially together regulate tissue differentiation.

Animals↗
PubMed1986

Fetal mucolipidosis II (I-cell disease): radiologic and pathologic correlation.

A pregnant woman whose previous child had a diagnosis of I-cell disease was referred for evaluation of the fetus. Fluid obtained by amniocentesis and maternal serum showed abnormally increased levels of lysosomal enzymes suggesting that the fetus had I-cell disease. Sonography at 18 weeks showed abnormally short femurs and intrauterine growth retardation. The pregnancy was electively terminated at 19 weeks' gestation and the diagnosis was confirmed. Radiographs of the fetus demonstrated that the bony dysplasia is present early in fetal life with diffuse decrease in bone mineralization, a coarse, lacy, trabecular pattern, overall shortening and under-modelling of the long bones, subperiosteal bone deficiency in the diaphysis giving the appearance of periosteal new bone, hypoplasia of the anterior superior aspect of the upper lumbar vertebral bodies, broad ribs, abnormal pelvis with squared iliac wings and flattened acetabular roofs, and a small irregular calcaneal ossification center. There was good correlation between the radiographic findings and the microscopic findings in the bones. We observed deficient endosteal bone formation, small epiphyses, and poorly developed intervertebral discs. We speculate that this indicates impaired production of extra-cellular matrix by several different types of specialized mesenchymal cells. Abnormalities of transport of glycoproteins other than lysosomal enzymes or excess of extracellular acid hydrolases may be involved in the pathogenesis.

Bone and Bones↗
PubMed1998

Induction of labyrinthitis ossificans after pneumococcal meningitis: an animal model.

Newly formed disorganized bone fills the open spaces within the otic capsule in various pathologic conditions, resulting in labyrinthitis ossificans. The pathologic mechanisms of this disease remain poorly understood. To better study the sequence of events and contributing mechanisms involved in labyrinthitis ossificans, an animal model was developed. Three groups of Mongolian gerbils received either an intralabyrinthine injection of normal saline solution (group 1) or Streptococcus pneumoniae polysaccharide capsule antigens (groups 2 and 3). The temporal bones were harvested after 3 months and serially sectioned. None of the eight control animals (group 1), which received intralabyrinthine injections of normal saline solution had any histologic changes in their temporal bones. Nine of the surviving 19 animals in groups 2 and 3 had fibrosis or evidence of early ossification. A fourth group of Mongolian gerbils received two intrathecal injections of live S. pneumoniae organisms. The temporal bones were harvested after 3 months and serially sectioned. Fourteen of the surviving 15 animals had fibrosis or ossification or both. This animal model will provide a method for study of the mechanisms of labyrinthitis ossificans.

Animals↗
PubMed1998

Impaired expression of noncollagenous bone matrix protein mRNAs during fracture healing in ascorbic acid-deficient rats.

In scorbutic patients, fractures are slow to heal because of impaired collagen synthesis. To investigate the influence of impaired collagen synthesis on the differentiation and proliferation of osteogenic and chondrogenic cells, we examined the expression of genes encoding bone matrix proteins, including osteonectin (ON), osteopontin (OPN), osteocalcin (OC), and matrix Gla protein (MGP), as differentiation markers for osteogenic and chondrogenic cells during fracture healing in Osteogenic Disorder Shionogi (ODS) rats, which have a hereditary defect in the ability to synthesize ascorbic acid (Asc). In ODS rats without Asc supplementation, intramembranous ossification was completely inhibited. Although a few fibroblast-like cells expressing ON mRNA were observed, no OPN mRNA-expressing cells were detected. During endochondral ossification, a small amount of metachromatic staining cartilage appeared at the fracture site, but there was no provisional calcification zone in the cartilage. Chondrocytes expressed ON and MGP mRNAs, but not OPN mRNA. When Asc was given to these rats, callus formation was soon detected around the fracture site, while OPN mRNA was expressed by differentiated osteoblasts and hypertrophic chondrocytes. Our data indicate that impaired collagen synthesis due to Asc deficiency inhibited the increase of ON and MGP mRNA-expressing cells as well as the appearance of OPN mRNA-expressing cells. Since OPN is considered to play an important role in normal and pathological mineralization, lack of OPN mRNA expression accompanying impaired collagen synthesis may have a role in defective mineralization and delayed fracture healing in scurvy.

Animals↗