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PubMed1999

Chronology of labyrinthitis ossificans induced by Streptococcus pneumoniae meningitis.

OBJECTIVE: Labyrinthitis ossificans consists of novel osteogenesis that fills the normally patent cochlear and vestibular lumen as an end-stage sequelae to various pathologies. This study was designed to establish the sequence of events and chronology of the osteoneogenesis and calcification. STUDY DESIGN: A prospective randomized double-blind study. METHODS: By using serial application of different colored fluorochromes, which deposit in newly forming bone, the timing of bone deposition and bone remodeling can be established. Labyrinthitis ossificans was induced in six groups (n = 5) of gerbils by an intrathecal injection of live Streptococcus pneumoniae. Group 1 received no fluorochrome labels, group 2 received one label, group 3 received three labels, and groups 4, 5, and 6 received four labels. The temporal bones were harvested after 2 weeks (group 1), 1 month (group 2), 3 months (group 3), 4 months (group 4), 6 months (group 5), and 12 months (group 6). RESULTS: Sixteen of the 25 animals that received labels developed ossification, demonstrated with fluorescent microscopy. In the animals that developed labyrinthitis ossificans, newly formed disorganized bone began calcifying as early as 3 weeks (label 1) after S. pneumoniae injection. Osteoneogenesis continued as evidenced by the presence of the other labels when first applied at 6 weeks (label 2), and 10 weeks (label 3). Ossification, calcification, and remodeling proceeded through a 12-month course, wherein a reduction of labels was present at 6 months and total disappearance by 12 months. CONCLUSIONS: The use of fluorescent stains in this animal model provides a means to establish a timeline of the ossification seen in labyrinthitis ossificans.

Animals↗
PubMed2006

Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice.

OBJECTIVE: Functional suitability and phenotypic stability of ectopic transplants are crucial factors in the clinical application of mesenchymal stem cells (MSCs) for articular cartilage repair, and might require a stringent control of chondrogenic differentiation. This study evaluated whether human bone marrow-derived MSCs adopt natural differentiation stages during induction of chondrogenesis in vitro, and whether they can form ectopic stable cartilage that is resistant to vascular invasion and calcification in vivo. METHODS: During in vitro chondrogenesis of MSCs, the expression of 44 cartilage-, stem cell-, and bone-related genes and the deposition of aggrecan and types II and X collagen were determined. Similarly treated, expanded articular chondrocytes served as controls. MSC pellets were allowed to differentiate in chondrogenic medium for 3-7 weeks, after which the chondrocytes were implanted subcutaneously into SCID mice; after 4 weeks in vivo, samples were evaluated by histology. RESULTS: The 3-stage chondrogenic differentiation cascade initiated in MSCs was primarily characterized by sequential up-regulation of common cartilage genes. Premature induction of hypertrophy-related molecules (type X collagen and matrix metalloproteinase 13) occurred before production of type II collagen and was followed by up-regulation of alkaline phosphatase activity. In contrast, hypertrophy-associated genes were not induced in chondrocyte controls. Whereas control chondrocyte pellets resisted calcification and vascular invasion in vivo, most MSC pellets mineralized, in spite of persisting proteoglycan and type II collagen content. CONCLUSION: An unnatural pathway of differentiation to chondrocyte-like cells was induced in MSCs by common in vitro protocols. MSC pellets transplanted to ectopic sites in SCID mice underwent alterations related to endochondral ossification rather than adopting a stable chondrogenic phenotype. Further studies are needed to evaluate whether a more stringent control of MSC differentiation to chondrocytes can be achieved during cartilage repair in a natural joint environment.

Adult↗
PubMed2001

[Osteochondroplastic tracheobronchopathy].

The words tracheobronchopathia osteochondroplastica (TO) were coined by Aschoff in 1910, defining a rare disease of the tracheobronchial system which most often is only "accidentally" discovered in the course of examinations, a bronchoscopy or computerized tomography, which are undertaken for other reasons. A characteristic sign for this disease are multiple cobblestone-like protrusions in the trachea and bronchus which are caused by calcifications, chondrifications and ossifications of the upper layer of the mucous membrane. We report on a 81-year old patient who was diagnosed with the disease while undergoing a fiberoptic bronchoscopy during a prolonged weaning phase. In the beginning we discussed the possibility of a neoplasia or a chronic inflammatory process as differential diagnosis and based on that we considered a dilatative tracheotomy for the weaning period. After histological confirmation of a TO we refrained from the measure, the reason being that in our opinion the patient would not profit from it. To reach a correct diagnosis a good interdisciplinarian cooperation is essential. The patient was successfully extubated on the 11th post-operative day after a patient conventional weaning which was supported by accompanying symptomatic measures. Apart from the case report we present a summary of the literature on TO concerning epidemiology, pathology, diagnosis and therapeutical measures.

Aged↗
PubMed2003

Determination of the complete cDNA sequence of rat type II collagen and evaluation of distinct expression patterns of types IIA and IIB procollagen mRNAs during fracture repair in rats.

Elucidating the molecular mechanisms that underlie fracture healing is crucial to understanding and devising strategies for the management of fractures, especially those associated with a pathological condition such as diabetes or old age. Cartilage formation, and therefore the expression of type II collagen by chondrocytes, is a critical step in frac-ture healing. Two forms of type II collagen, IIA and IIB, are known to be produced by alternative splicing of the Alpha(1) (II) procollagen gene. We have followed the patterns of expression of these two forms of type II collagen to determine the nature of chondrocyte recruitment during fracture healing. First, we sequenced the rat collagen type II cDNA to design the primers. Second, using a competitive quantitative reverse transcription-mediated polymerase chain reaction, we provide evidence that (1) there is a basal level of type IIA collagen expression during the early stages of fracture healing; (2) transient but sharp up-regulation of IIA expression occurs concomitant with chondrogenesis and endochondral ossification; and (3) type IIB collagen is the predominant mRNA variant expressed at virtually all times during fracture repair.

Animals↗
PubMed1975

Articular lesions in experimental Erysipelothrix insidiosa infection in rats.

Articular lesions were studied in the extremities and vertebral column in murine erysipelas infection. Pathologic alterations found in those different joint systems were essentially the same in character. In the early stage of infection, phlegmon-like inflammation was observed in the periarticular loose connective tissue. Abundant fine Gram-positive bacilli were free in inflamed edematous tissue. Then, active serofibrinous exudation and emigration of leukocytes occurred in the synovial membrane, articular cartilage, annulus fibrosus, and nucleus pulposus with the development of the disease. These exudative changes disappeared gradually. Instead of them, proliferation of synovial cells accompanied by dense infiltration with lymphocytes and plasma cells became conspicuous. At the same time, chondro- and osteoclastic activity occurred in the joints of the extremities or regions adjacent to the intervertebral disk. Capsular and subchondral pannus often resulted from an excessive proliferation of granulation tissue. In the late stage, they synovial membrane and granulation tissue underwent fibrosis, adhesion and ossification. Finally, these changes resulted in fibrous or bony ankylosis and deformation. Gram-positive bacilli were hardly detected in histological preparations derived from animals in the chronic stage when proliferative change was predominant in the articular lesions.

Animals↗
PubMed2003

[Multiple pathology in a Merowingian individual of a graveyard near Insheim (Rhineland-Pfalz)].

The following case report describes in detail a 57 years old (+/- 5 years) male individual from a Franconian graveyard in Insheim, Province of Rhineland-Palatinate, dating to between the 6th and 7th century A.D. The individual displays a number of unusual pathologies. The atlas shows a complete aplasia of the posterior arch, probably resulting in a torticollis. The changed static induced a massive spondylar-arthrotic degeneration of the cervical spine on the right-lateral portion. On the fronto-parietal section two fractures are visible which were caused by a sharp and violent force. The area in question measures 7 by 10 cm. It has healed in a dislocated position. The second location displays marks of a 6 cm long sword-cut which did strike the skull obtusely on the left parietal. In addition to the above the skull displays on its right side a great number of small circular hole defects which also appear on ribs, vertebrae, clavicula and the mandible. They present the typical picture of a plasmocytoma. As an expression of a secondary hyperparathyreoidism one can recognize ossifications of soft tissue on the calcaneus, tibia, fibula and patella as well as intravital loss of mandibular dentition. It is quite remarkable that the individual reached a relative old age despite of his numerous and serious physical encroachments due to the apparent and obvious intentions of his aggressive contemporaries to kill him.

Bone and Bones↗
PubMed1998

Anatomical and technical considerations in surface electromyography.

Despite the technical and clinical limitations of surface EMG, it is essential in the physical medicine and rehabilitation field. Surface EMG has evolved from a secondary means of clinical assessment to a primary factor in determining and predicting clinical outcomes. Computer models of electrical muscular activity are currently implemented to assist in designing proper instrumentation and electrode with optimum dimensions. These models could be expanded to simulate pathological motor functions to help understand functional abnormalities even before clinical interventions. Currently, several groups all over the world are investigating the use of multichannel surface EMG. This technological advancement would have an immediate impact on several medical fields. For instance, tendon transfers are performed to improve function in peripheral nerve injury, brachial plexus lesion, spinal cord injury, and cerebral palsy. There are potential uses for multichannel surface EMG, both preoperatively and postoperatively. Preoperatively choosing the muscle for transfer has been largely based on clinical grounds. Multichannel surface EMG could give a more objective database to assess prognosis and determine which muscle to transfer. Postoperatively, multichannel surface EMG can provide a systematic way of assessing changes in gross muscle topography caused by the tendon transfer. Other applications of multichannel surface EMG would be for bony and soft tissue deformity from arthritis, heterotopic ossification, amputation, or burns. Multichannel surface EMG would allow clinicians to get a broader picture of the skeletal muscle activity despite the fact that it is physically impossible for the patient to assume the anatomic position used for traditional isolated electrode placement. Individuals with physical disabilities that affect their ability to assume the usual posture for electrophysiologic testing may benefit considerably from development of multichannel electrophysiologic testing. Patients with abnormalities of tone from various causes such as stroke, traumatic brain injury, and cerebral palsy are at times evaluated with kinesiologic EMG to assess motor control. Multichannel surface EMG could potentially give us much greater insight into motor control disorders.

Cerebral Palsy↗
PubMed2004

Mechanobiological predictions of growth front morphology in developmental hip dysplasia.

Developmental dysplasia of the hip (DDH) is the most common orthopedic problem of newborn children. Most clinicians and researchers agree that the primary cause of DDH is abnormal mechanical forces on the head of the femur due to limb position, pressure from the womb, or ligament laxity. The abnormal mechanical forces result in altered growth and bony deformities, in particular large neck-shaft and anteversion angles in the proximal femur and a shallow acetabulum. Previous studies have suggested that intermittent octahedral shear stress promotes growth and ossification, while intermittent hydrostatic compressive stress inhibits growth and ossification. We implemented these mechanobiological principles into a finite element model to predict the rate of progression of the growth front and the formation of coxa valga (large neck-shaft angle) in DDH. Under the assumed normal fetal loading conditions the hydrostatic stress was even across the growth front, but the octahedral shear stress was higher in the center than at the edges. This stress profile promoted growth in the center and a produced a convex growth front shape. Under loading conditions of the dysplastic hip, the octahedral shear stress was much larger on the medial side than on the lateral side, which promoted growth on the medial side and resulted in coxa valga. These results indicate that abnormal forces on the prenatal hip might influence total bone morphology and the development of DDH. These findings might help in understanding the etiology and pathology of other developmental bone deformities.

Bone Development↗
PubMed2005

Regional difference in the appearance of apoptotic cell death in the ligamentum flavum of the human cervical spine.

Ossification or calcification of the ligamentum flavum (LF) is relatively common in the middle and lower cervical, thoracic, and lumbar spine but extremely rare in the upper cervical region. This clinical fact suggests that there exist local factors promoting or preventing ossification or calcification of LF. However, little is known about the differences in the ultrastructure and cellular alterations of the LF between the different spinal levels, even in the cervical spine. With electron microscopy, we examined samples of LF collected surgically from the upper and lower cervical spine regions; we then studied the apoptotic appearance of ligament cells using a preferential labeling method. We found direct evidence of apoptosis of ligament cells in the LF. Apoptosis was more apparent in the upper region samples than in the lower region samples. The spaces around the normal fibroblasts were filled with thick collagen fibrils, but the collagen fibrils disappeared around the apoptotic bodies and thin fibrils were formed. The difference of the level of apoptosis may correlate to the ultrastructural difference of LF, and our data will benefit further investigations seeking to clarify the mechanism of various pathological conditions in the human LF.

Apoptosis↗
PubMed2000

Role of the extracellular matrix and growth factors in skull morphogenesis and in the pathogenesis of craniosynostosis.

The complex and largely obscure regulatory processes that underlie ossification and fusion of the sutures during skull morphogenesis are dependent on the conditions of the extracellular microenvironment. The concept that growth factors are involved in the pathophysiology of craniosynostosis due to premature fusion of skull bone sutures, is supported by recent genetic data. Crouzon and Apert syndromes, for example, are characterized by point mutations in the extracellular or transmembrane domains of fibroblast growth factor-2 receptor. In primary cultures of periosteal fibroblasts and osteoblasts obtained from Apert and Crouzon patients, we observed that Crouzon and Apert cells behaved differently with respect to normal cells as regards the expression of cytokines and extracellular matrix (ECM) macromolecule accumulation. Further modulation of ECM components observed after the addition of cytokines provides support for an autocrine involvement of these cytokines in Crouzon and Apert phenotype. Changes in ECM composition could explain the altered osteogenic process and account for pathological variations in cranial development. We suggest that a correlation exists between in vitro phenotype, clinical features and genotype in the two craniosynostotic syndromes. New research into signal transduction pathways should establish further connections between the mutated genotype and the molecular biology of the cellular phenotype.

Acrocephalosyndactylia↗
PubMed2002

Intraocular osseous metaplasia. A clinico-pathological study.

PURPOSE: To evaluate the clinico-pathologic features of intraocular osseous metaplasia. METHODS: Pathology specimens of enucleated eyes submitted to the ophthalmic pathology service at a tertiary eye-care referral center between January 1995 and June 1999 were studied for intraocular osseous metaplasia. Specific histopathologic features noted in specimens with osseous metaplasia were the presence of retinal detachment, gliosis, retinal pigment epithelial hyperplasia, drusen, epiretinal membrane, fibrovascular proliferation and inflammation. Immunohistochemistry using monoclonal antibody against glial fibrillary acidic protein was performed to assess the glial component within the membranes and the proliferative vitreoretinal mass. Clinical records were reviewed and correlated with histopathologic findings. RESULTS: Osseous metaplasiaS was noted in 8 of 151 (5.2%) eyes examined. Clinical diagnosis in these was phthisis bulbi, staphyloma, absolute glaucoma and microphthalmos. Enucleation was performed for relief of symptoms (in painful blind eyes) or for cosmesis, and in an eye inciting sympathetic ophthalmia. Retinal detachment, gliosis and retinal pigment epithelial hyperplasia were noted in all the cases. Drusen with calcification or ossification (5 of 8), fibrovascular proliferation in the vitreous (5 of 8) and active inflammation (4 of 8) were the other associated histologic features. Location of ossification was subretinal in 3 cases, preretinal (ora serrata) in 1 case and in both locations in 4 cases. The eyes with subretinal osseous metaplasia had associated calcified drusen, while preretinal ossification was seen within the fibrovascular membranes. CONCLUSION: Chronic retinal detachment, hyperplasia and transdifferentiation of retinal pigment epithelium appear to be a few of the prerequisites for intraocular osseous metaplasia. Ossification can occur at isolated subretinal and preretinal locations or can involve both. Though a larger study is required to postulate the chronology of events, in this small series, isolated subretinal ossification appears to be initiated by calcification and ossification of drusen, while in the pre-retinal region it is associated with vitreoretinal proliferation.

Adolescent↗
PubMed1991

Marshall-Smith syndrome: new radiographic, clinical, and pathologic observations.

Radiographic, clinical, and histologic findings in two infants and a neonate with a syndrome of profoundly accelerated skeletal maturation included features closely resembling those of Marshall-Smith (MS) syndrome, but patients had dysmorphic ears as well as distinctive generalized skeletal abnormalities suggestive of a bone dysplasia. Among these was an instability at the craniocervical junction with severe spinal stenosis. These previously unrecognized abnormalities may represent uncommon manifestations within the spectrum of MS syndrome or indicate the existence of a separate disorder.

Atlanto-Axial Joint↗
PubMed1997

Elongated styloid process: diagnostic problems related to symptomatology.

A certain number of patients with elongated styloid process may not have the classic cervicofacial complaints which were originally described by W. Eagle in 1937. Some of those cases who have radiologic evidence of elongated styloid process are symptom free and can be accepted as normal anatomical variants. On the other hand, some of those symptomatic cases may present uncommon neurologic signs and can be misdiagnosed as neurologic or infectious disease. Sometimes, the radiologic presence of an elongated process may cause the clinician to miss another pathology. Therefore, it is essential for the clinician to be aware of the clinical variants with different symptomatology or to particularly seek the origin of the pain in the head and neck before reaching a conclusion, since the only effective treatment in symptomatic cases is the surgical shortening of the process. We report five patients with elongated processes. Problems related to an elongated styloid process with different symptomatology are discussed and the associated literature is reviewed.

Adult↗
PubMed2004

[Experimental study on treatment of femoral head necrosis with arterial perfusion of marrow stem cells].

OBJECTIVE: To explore the effect of arterial perfusion of marrow multifunctional stem cells (MFSC) in treating femoral head necrosis and its mechanism. METHODS: The rabbit model of femoral head necrosis was established by large dose of methyl-prednisone through Shwartzman response. Bone marrow was extracted from femoral bone of model rabbit and isolated in vitro for culturing and proliferating MFSC. The experimental rabbits were randomly divided into 4 groups, treated with normal saline (A), Salvia + urokinase (B), MFSC (C) and MFSC + Salvia + urokinase (D), respectively, they were sacrificed in batches at 2 and 4 weeks after treatment, and changes in various parameters, including molybdenum target roentgenogram, routine pathology with HE staining, tetracycline labeled fluorescent microscopy and ultrastructure alteration by scanning electron microscope (SEM), were observed. RESULTS: Typical appearance of femoral head necrosis was shown in the successfully modeled rabbits. Two and 4 weeks after treatment by high selective drug via medial and lateral femoral circumflex arterial perfusion, the X-ray examination showed significant improvement of bone density; pathohistologic manifestation showed decrease of empty bone lacuna, increase of osteoblast and new bone formation; tetracycline fluorescent labeled microscopic picture showed bright fluorescent band of increased osteoblasts in necrosis repairing region with widened border; SEM displayed irregularly arranged fibrosis in necrosis region, abundant organelles in osteoblasts with few empty bone lacuna. The above-mentioned improvement was more significant in rabbits treated by MFSC. CONCLUSION: High selective femoral drug arterial perfusion in treating femoral head necrosis could accelerate the process of revascularization and re-ossification in rabbits. As compared with Salvia, MFSC showed quicker and more potent effect.

Animals↗
PubMed1981

Transplacental effects of cortisone acetate on calcification and ossification of long bones in mice.

The transplacental effects of cortisone acetate on the skeleton of neonatal mice has been investigated. Pregnant mice were injected intramuscularly with 0.75 mg cortisone acetate daily on days 11-19 of gestation. The mice were allowed to deliver and pups were weighed on days 1, 3, 5, 10, 15, 20 and 30 and compared to controls. Light microscopy of non-decalcified longitudinal sections of bones revealed mineral precipitates throughout the zone of hypertrophic cartilage most prominent on days 1, 3 and 5 and gradually disappearing on days 10-20. Transmission electron microscopy revealed intracellular calcification of maturing and hypertrophic chondrocytes in addition to abnormal calcification of the interstitial substance. Hydroxylapatite crystals were not necessarily associated with matrix vesicles. Scanning electron microscopy of long bones revealed a wide zone of calcified intercartilagenous matrix representing the calcified proliferating and hypertrophic zones. In this area, the calcospherites varied in size (0.5-1.4 mu in diameter) and were found in both longitudinal and transverse septa. No significant differences in the distribution and shape of cartilage matrix vesicles between experimental and control animals was observed. However, the fact that mineral crystals in experimental animals was not necessarily associated with matrix vesicles points to the possibility that this "pathological calcification" may utilize a different mechanism than the normal process through matrix vesicles.

Animals↗
PubMed1992

Improvement of cortical morphology in infantile hydrocephalic animals after ventriculoperitoneal shunt placement.

As a sequel to our previous descriptions of the pathological changes induced by hydrocephalus in the infantile cerebral cortex, the study presented here has evaluated the effects of surgical decompression on cortical cytology and cytoarchitecture. Hydrocephalus was induced in 14 kittens by the intracisternal injection of kaolin at 4 to 11 days of age. Nine of these hydrocephalic animals received low-pressure ventriculoperitoneal shunts at 9 to 15 days after kaolin injection; these animals were monitored preoperatively and postoperatively by ultrasound and were killed at various postshunt intervals up to 30 days. Five normal or saline-injected animals served as age-matched controls. At the time of shunt placement, the ventricular index confirmed that all recipient animals had attained moderate or severe degrees of ventriculomegaly. Within 3 days after shunt placement, the size of the lateral ventricles had decreased to control levels and was accompanied by rapid and dramatic improvements in behavior and skull ossification. When the animals were killed, gross inspection revealed that about half of the animals exhibited mild to moderate ventriculomegaly, with cortical mantles 50 to 80% their normal thickness. Tissue from frontal (primary motor), parietal (association), and occipital (primary visual) cortical areas was processed for light microscopic analysis. Pyknotic or dark shrunken neurons, which are found typically in hydrocephalic brains, were observed only occasionally in the cortex of shunted animals. Gliosis and mild edema were prevalent, however, in the periventricular white matter. The laminae of the cerebral cortex could be identified in all shunted animals. In those animals with mild residual ventriculomegaly, the entire cortical mantle was somewhat compressed, as evidenced by an increased packing density of neurons. Furthermore, the somata of some neurons were disoriented. Overall, these results indicate that most of the morphological characteristics of the cerebral cortex are preserved after surgical decompression and suggest that ventriculoperitoneal shunts may prevent neuronal damage and/or promote neuronal repair.

Animals↗
PubMed2005

Mechanisms of Disease: new insights into the cellular and molecular pathology of Peyronie's disease.

Peyronie's disease (PD) is characterized by fibrotic plaques in the penile tunica albuginea that cause curvature of the erect penis, and is often accompanied by pain and/or erectile dysfunction. This condition affects up to 9% of men. Treatment is mainly surgical, as pharmacologic therapy has limited efficacy. The pathophysiology of PD is poorly understood, but development of two rat models, extrapolation of what is known about the molecular pathology of other fibrotic conditions, and emphasis on the role of myofibroblasts and adult stem cells are helping to clarify etiology and identify new pharmacologic targets. Recent studies demonstrate a role for oxidative stress and cytokine release-primarily transforming-growth-factor beta1-in development of PD fibrotic plaques. There is evidence indicating that these profibrotic factors interact with antifibrotic defense mechanisms, such as decrease of myofibroblast accumulation, elimination of reactive oxygen species by inducible nitric oxide synthase and neutralization of transforming-growth-factor beta1 by decorin, such that some plaques are in dynamic turnover. Injury to the erect penis is thought to trigger PD by inducing extravasation of fibrin and subsequent synthesis of transforming-growth-factor beta1. Despite the lack of statistical support for a causal association between trauma and PD, it is possible that undetected microtrauma is involved. It is not known whether ossification of PD plaques is linked to fibrosis progression or is a manifestation of an alternative pathway. Both processes seem to be related to activation of fibroblast/myofibroblast differentiation in the tunica albuginea and to osteogenic commitment of stem cells in this tissue.

Disease Progression↗
PubMed1993

Parosteal lipoma with hyperostosis: report of two pathologically proven cases evaluated by magnetic resonance imaging.

The authors describe two cases of parosteal lipoma, an infrequent benign tumour, associated with hyperostosis. The first patient presented with a mass in the posterior neck, the other with one in the proximal forearm. Radiologic diagnosis was facilitated by magnetic resonance imaging (MRI). The MRI images showed the characteristic features of a parosteal lipoma, as well as hyperostotic areas that remained of low signal intensity in both T1-weighted and T2-weighted sequences. MRI is both sensitive and specific for diagnosing these lesions and provides excellent depiction of the anatomic features before surgery.

Adult↗