Science.gov

Sample records for epiphyses

  1. Longitudinal epiphyseal bracket.

    PubMed

    Nguyen, Jimmy Q; Gatewood, Jason B; Beall, Douglas; Herndon, William; Puffinberger, William R; Ly, Justin; Fish, Jon R

    2007-10-01

    A longitudinal epiphyseal bracket (LEB) is a defect of the tubular bones and has been primarily described in the hands and feet, especially the proximal phalanges, metacarpals, and metatarsals. The LEB results from a defective C-shaped secondary ossification center that brackets the diaphysis and metaphysis, causing restricted longitudinal growth in these bones with resultant shortening and angular deformities. Deformities associated with metatarsal epiphyseal bracket include a short, broad metatarsal and medial deviation of the metatarsophalangeal joint (hallux varus deformity). Excision of the cartilaginous LEB has been proposed to prevent future soft tissue contractures and osseous deformities. The LEB has been associated with numerous syndromes including Rubinstein-Taybi syndrome, Cenani-Lenz syndactyly, isolated oligosyndactyly, and Nievergelt syndrome. We describe a two-month-old patient in whom plain film and MR imaging demonstrated bilateral bracketed first metatarsals with associated hallux varus deformities. Bilateral bracket excision was performed with excellent clinical results. PMID:18085094

  2. Epiphyseal injuries in the growing athlete.

    PubMed Central

    Schwab, S. A.

    1977-01-01

    The epiphyses and epiphyseal plates are vital structures in the bone development of the growing athlete. The epiphyseal plate is two to five times weaker than the surrounding fibrous tissue in children and adolescents; consequently a force causing a ligamentous tear in adults is likely to cause an epiphyseal plate injury in growing children. Two types of epiphyseal injury that are common in the growing athlete are (a) separation across the epiphyseal plate, which is usually produced by a direct blow to the joint area or by a strong muscular contraction, and (b) traumatic epiphysitis, the more common of the two, which is usually caused by strong, repetitive contraction of a muscle attached to a traction epiphysis. Each epiphyseal site has specific anatomic features and the forces causing injury differ slightly at each site. An improperly treated separation of an intra-articular pressure epiphysis can have a disastrous effect on the proper functioning of the normally well-fitted articulation of bone ends in the joint. Consequently, proper diagnosis and treatment are essential. Traumatic epiphysitis can result in chronic inflammation or fragmentation, or both, if the condition is not arrested. Therefore the athlete must discontinue the activities that are causing the trauma until the inflammation is completely arrested. Absolute rest may even be required. PMID:902208

  3. [Transitional fractures : Epiphyseal injuries in adolescence].

    PubMed

    Schneidmueller, D; von Rüden, C; Friederichs, J; Bühren, V

    2016-06-01

    The so-called transitional fractures describe articular fractures in adolescents with partial closure of the epiphyseal growth plate. This shows a specific stereotype fracture pattern, which can be differentiated into biplane, triplane I and triplane II fractures depending on the involvement of the metaphysis and the number of fragments. The diagnostics and therapy can differ from fractures where the epiphyseal growth plate is still open. The main focus for surgical treatment is the reconstruction of the articular surface whereas relevant growth disturbances no longer need to be feared when the epiphysis has already begun to close. PMID:27240851

  4. Clinical features of multiple epiphyseal dysplasia expressed in the knee.

    PubMed

    Miura, H; Noguchi, Y; Mitsuyasu, H; Nagamine, R; Urabe, K; Matsuda, S; Iwamoto, Y

    2000-11-01

    The purpose of this study is to clarify the clinical features of the knee affected by multiple epiphyseal dysplasia. Thirty-one cases of multiple epiphyseal dysplasia were reviewed. Of the patients, 11 were male and 20 were female. The average age at onset of symptoms was 22.5 years. The average age at initial visit to the authors' hospital was 28.9 years. Radiographic findings showed epiphyseal abnormality of the knee in all but two (93%) cases. Irregularity, segmentation of the epiphysis, widening of the joint space, and genu valgum deformity were the dominant findings before epiphyseal closure. After epiphyseal closure, the most characteristic finding was a shallow femoral trochlear groove, which was observed in 56.5% of the cases. Other findings in adult patients included early onset osteoarthritic change, genu valgum, depression of the lateral tibial plateau, and multiple free bodies. However, there still is a possibility that multiple epiphyseal dysplasia exists, even if the patient lacks a shallow femoral trochlear groove. If genu valgum or varum, free bodies, and premature osteoarthritis are observed, one should evaluate other joints, keeping a diagnosis of multiple epiphyseal dysplasia in mind. Patients with knees that have a femoral trochlear groove of normal or near normal shape do exist, and premature osteoarthritic changes may develop in such patients. PMID:11064990

  5. Avascular necrosis of the hip in multiple epiphyseal dysplasia

    SciTech Connect

    Mackenzie, W.G.; Bassett, G.S.; Mandell, G.A.; Scott, C.I. Jr. )

    1989-11-01

    We observed radiographic changes of avascular necrosis (AVN) of the capital femoral epiphysis in 9 hips of 11 patients with multiple epiphyseal dysplasia (MED). Plain roentgenography, bone scintigraphy, and magnetic resonance imaging (MRI) studies all revealed characteristic asymmetric changes in the presence of AVN superimposed on dysplastic femoral heads.

  6. Chronic slipping of bilateral distal humeral epiphyses in a gymnastist.

    PubMed

    Oda, Ryo; Fujiwara, Hiroyoshi; Ichimaru, Kozo; Morihara, Toru; Ikeda, Takumi; Kubo, Toshikazu

    2015-01-01

    In children, fracture-separation of the epiphyseal plate near the elbow joint is a common occurrence. However, separation of the distal humeral epiphysis is very rare, and in most cases, it is caused by high-impact trauma. In all reported cases, there has been a clear mechanism of injury. We report a case of an 11-year-old male patient who sustained separation of the distal humeral epiphyses bilaterally after 2 years of gymnastics, without a clear mechanism of injury. This patient had been using the vault since he was 9 years old, although children of that age do not normally perform on the vault. When gymnasts place their hands on the vault with their elbows flexed and subsequently extend their elbows to push off, the biomechanical load is placed equally on the right and left arms. Consequently, this type of repeated stress induces injury to the epiphyseal cartilages bilaterally, resulting in chronic progression of separation of the distal humeral epiphyses. PMID:25438108

  7. Primary Epiphyseal Aneurysmal Bone Cyst Of Distal Ulna

    PubMed Central

    Kapila, Rajesh; Sharma, Rakesh; Sohal, Yadwinder Singh; Singh, Dhalwinder; Singh, Sukhpal

    2015-01-01

    Introduction: Aneurysmal Bone Cyst (ABC) is a benign expansile cystic blood filled reactive lesion of the bone, most common in the first 2 decades of life. Though it can involve any bone in the body but tibia, humerus, femur and posterior elements of spine are most commonly affected. They most commonly involve metaphysis or metaphysio-diaphyseal part of the bone. Primary involvement of epiphysis is rarely reported. Here we present a case of 6 year old male child with an epiphyseal ABC of distal ulna. Its diagnosis, surgical management, clinical outcome with review of literature is discussed. PMID:27299110

  8. Multiparametric MRI of Epiphyseal Cartilage Necrosis (Osteochondrosis) with Histological Validation in a Goat Model

    PubMed Central

    Wang, Luning; Nissi, Mikko J.; Tóth, Ferenc; Shaver, Jonah; Johnson, Casey P.; Zhang, Jinjin; Garwood, Michael; Carlson, Cathy S.; Ellermann, Jutta M.

    2015-01-01

    Purpose To evaluate multiple MRI parameters in a surgical model of osteochondrosis (OC) in goats. Methods Focal ischemic lesions of two different sizes were induced in the epiphyseal cartilage of the medial femoral condyles of goats at 4 days of age by surgical transection of cartilage canal blood vessels. Goats were euthanized and specimens harvested 3, 4, 5, 6, 9 and 10 weeks post-op. Ex vivo MRI scans were conducted at 9.4 Tesla for mapping the T1, T2, T1ρ, adiabatic T1ρ and TRAFF relaxation times of articular cartilage, unaffected epiphyseal cartilage, and epiphyseal cartilage within the area of the induced lesion. After MRI scans, safranin O staining was conducted to validate areas of ischemic necrosis induced in the medial femoral condyles of six goats, and to allow comparison of MRI findings with the semi-quantitative proteoglycan assessment in corresponding safranin O-stained histological sections. Results All relaxation time constants differentiated normal epiphyseal cartilage from lesions of ischemic cartilage necrosis, and the histological staining results confirmed the proteoglycan (PG) loss in the areas of ischemia. In the scanned specimens, all of the measured relaxation time constants were higher in the articular than in the normal epiphyseal cartilage, consistently allowing differentiation between these two tissues. Conclusions Multiparametric MRI provided a sensitive approach to discriminate between necrotic and viable epiphyseal cartilage and between articular and epiphyseal cartilage, which may be useful for diagnosing and monitoring OC lesions and, potentially, for assessing effectiveness of treatment interventions. PMID:26473611

  9. Age estimation from stages of epiphyseal union in the presacral vertebrae.

    PubMed

    Cardoso, Hugo F V; Ríos, Luis

    2011-02-01

    The presacral vertebrae have various secondary centers of ossification, whose timing of fusion can be used for age estimation of human skeletal remains up to the middle to the latter third decade. However, detailed information about the age at which these secondary centers of ossification fuse has been lacking. In this study, the timing of epiphyseal union in presacral vertebrae was studied in a sample of modern Portuguese skeletons (57 females and 47 males) between the ages of 9 and 30, taken from the Lisbon documented skeletal collection. A detailed photographic record of these epiphyses and the age ranges for the different stages of epiphyseal union are provided. Partial union of epiphyses was observed from 11 to 27 years of age. In general, centers of ossification begin to fuse first in the cervical and lumbar vertebrae, followed by centers of ossification in the thoracic region. The first center of ossification to complete fusion is usually that of the mammillary process in lumbar vertebrae. This is usually followed by that of the transverse process, spinous transverse process, and annular ring, regardless of vertebra type. There were no statistically significant sex differences in timing of fusion, but there was a trend toward early maturation in females for some vertebra or epiphyses. Bilateral epiphyses did not show statistically significant differences in timing of fusion. This study offers information on timing of fusion of diverse epiphyseal locations useful for age estimation of complete or fragmented human skeletal remains. PMID:20872802

  10. Time course of epiphyseal growth plate fusion in rat tibiae

    NASA Technical Reports Server (NTRS)

    Martin, E. A.; Ritman, E. L.; Turner, R. T.

    2003-01-01

    Although the rat is the most common animal model used in studying osteoporosis, it is often used inappropriately. Osteoporosis is a disease that most commonly occurs in humans long after growth plate fusion with the associated cessation of longitudinal bone growth, but there has been a question as to when or to what extent the rat growth plate fuses. To investigate this question, we used microcomputed X-ray tomography, at voxel resolutions ranging from (5.7 micro m)(3) to (11 micro m)(3), to image the proximal epiphyseal growth plates of both male (n = 19) and female (n = 15) rat tibiae, ranging in age from 2 to 25 months. The three-dimensional images were used to evaluate fusion of the epiphyseal growth plate by quantitating the amount of cancellous bone that has bridged across the growth plate. The results suggest that the time course of fusion of the epiphyseal growth plate follows a sigmoidal pattern, with 10% of the maximum number of bridges having formed by 3.9 months in the male tibiae and 5.8 months in the female tibiae, 50% of the maximum number of bridges having formed by 5.6 months in the male tibiae and 5.9 months in the female tibiae, and 90% of the total maximum of bridges have formed by 7.4 months for the males and 6.5 months for the females. The total volume of bridges per tibia at the age at which the maximum number of bridges per tibia has first formed is 0.99 mm(3)/tibia for the males and 0.40 mm(3)/tibia for the females. After the maximum number of bridges (-290 for females, -360 for males) have formed the total volume of bridges per tibia continues to increase for an additional 7.0 months in the males and 17.0 months for the females until they reach maximum values (-1.5 mm(3)/tibia for the males and -2.2 mm(3)/tibia for the females).

  11. Bilateral Second Carpal Row Duplication Associated with Multiple Epiphyseal Dysplasia.

    PubMed

    Cladiere-Nassif, Victoire; Delaroche, Caroline; Pottier, Edwige; Feron, Jean-Marc

    2015-11-01

    We report a case of a 75-year-old woman presenting a hitherto undescribed condition of bilateral second carpal row duplication. She was diagnosed in childhood with both Marfan and Ehlers-Danlos syndromes, with no clear evidence and no further medical follow-up. She presented throughout her life with various articular symptoms, which appeared to be compatible with a diagnosis of multiple epiphyseal dysplasia, and underwent several surgical procedures on her knees and hips. Most recently, she was reporting pain at the base of the fifth metacarpal bone of the left hand. X-ray images and computed tomography (CT) were obtained for exploration and showed a total second row duplication in both carpi, with a total number of 18 carpal bones in each wrist. PMID:26649258

  12. Automated Classification of Epiphyses in the Distal Radius and Ulna using a Support Vector Machine.

    PubMed

    Wang, Ya-hui; Liu, Tai-ang; Wei, Hua; Wan, Lei; Ying, Chong-liang; Zhu, Guang-you

    2016-03-01

    The aim of this study was to automatically classify epiphyses in the distal radius and ulna using a support vector machine (SVM) and to examine the accuracy of the epiphyseal growth grades generated by the support vector machine. X-ray images of distal radii and ulnae were collected from 140 Chinese teenagers aged between 11.0 and 19.0 years. Epiphyseal growth of the two elements was classified into five grades. Features of each element were extracted using a histogram of oriented gradient (HOG), and models were established using support vector classification (SVC). The prediction results and the validity of the models were evaluated with a cross-validation test and independent test for accuracy (PA ). Our findings suggest that this new technique for epiphyseal classification was successful and that an automated technique using an SVM is reliable and feasible, with a relative high accuracy for the models. PMID:27404614

  13. Slipped femoral capital epiphyses in irradiated children: dose, volume and age relationships

    SciTech Connect

    Silverman, C.L.; Thomas, P.R.M.; McAlister, W.H.; Walker, S.; Whiteside, L.A.

    1981-10-01

    Between 1960 and 1979, 50 patients under 15 years of age received radiotherapy to the pelvis including the non-fused capital femoral epiphyseal plate. A total of 83 epiphyseal plates were at risk. Eight epiphyseal plates (9.6%) in five patients were abnormal: symptomatic capital femoral epiphyseal slippage--4, asymptomatic slippage--1, severe epiphyseal abnormalities of radiographs--3. No complication occurred below doses of 2,500 rad (25 Gy). Children under the age of 4 at time of irradiation were at a higher risk (7/15-47%) than those over 4 years of age (1/21-4.7%). Most slippages occurred at ages between 8 and 10 years. No dose response curve was obtained--higher doses above the threshold dose of 2,500 rad did not increase the incidence of slippage. A mechanism of action is postulated. This is a preventable complication; judicious use of primary or secondary blocking systems can eliminate or limit the dose to the non-fused epiphyseal plate and prevent later morbid complications.

  14. A systematic approach to magnetic resonance imaging evaluation of epiphyseal lesions.

    PubMed

    Thawait, Shrey K; Thawait, Gaurav K; Frassica, Frank J; Andreisek, Gustav; Carrino, John A; Chhabra, Avneesh

    2013-04-01

    Magnetic Resonance Imaging (MRI) is the preferred modality of choice to image epiphyseal lesions. It provides excellent soft tissue resolution and extent of disease. A wide spectrum of tumor and tumor like lesions can involve the epiphysis. Early and accurate diagnosis as well as appropriate management of epiphyseal lesions is critical as these conditions may lead to disabling complications such as, limb length discrepancy, angular or joint surface deformities and secondary osteoarthritis. In this article, we discuss the role of conventional sequences, such as T1W, fluid sensitive T2W and intravenous (IV) Gadolinium enhanced sequences as well as the additional value of problem solving MRI sequences such as, chemical shift and diffusion weighted imaging. Based on the imaging findings on various MRI sequences and lesion characteristics, a systematic approach directed to the diagnoses of epiphyseal lesions is presented and discussed. MRI features of clinically and biopsy proven examples of the epiphyseal lesions, such as osteomyelitis, intra-osseous abscess, infiltrative malignancy, metastases, transient osteoporosis, subchondral insufficiency fracture, avascular necrosis, osteochondral fracture, osteochondritis dissecans, eosinophilic granuloma and geode are demonstrated. Using this systematic approach, the reader will be able to better characterize epiphyseal lesions with a potential to positively affect patient management. PMID:23102949

  15. Age related changes and osteochondrosis in swine articular and epiphyseal cartilage: light ane electron microscopy.

    PubMed

    Bhatnagar, R; Christian, R G; Nakano, T; Aherne, F X; Thompson, J R

    1981-04-01

    Age related changes and osteochondrosis in swine were studied using light microscopy and electron microscopy in articular cartilage and light microscopy and epiphyseal cartilage of swine from three days to 30 weeks of age. Thickness, cellularity and vascularity of both the epiphyseal and articular cartilage, decreased as the swine aged. Osteochondrotic changes included formation of "plugs" of cartilage indicating localized failure of ossification and separation and space formation in epiphyseal cartilage. Eosinophilic streaks and space formation in epiphyseal cartilage was observed in relation to epiphyseal separation. Electron microscopy showed a continuous fibrillar layer on the surface of the cartilage corresponding to the lamina splendens of light microscopy. This layer increased in the thickness and showed accumulation of amorphous material between the fibrils with aging. In the matrix, the orientation and distribution of the collagen fibers changed with growth and thicker fibers with clear sub banding were more common in older age groups. Also, necrotic cells, glycogen containing bodies and cellular debris were noticed in the matrix of normal cartilage in old animals. Chondrocytes in the younger cartilage showed accumulation of organelles responsible for protein synthesis; while Golgi bodies, vesicles, lysosomes, well developed foot processes and other inclusions were noticed in older cartilage. Cartilage erosions had a clumped and disrupted lamina splendens on the surface and electron lucent patches in the ground substances of the matrix and chondrocyte cytoplasm. PMID:7260732

  16. Cartilaginous Epiphyses in Extant Archosaurs and Their Implications for Reconstructing Limb Function in Dinosaurs

    PubMed Central

    Holliday, Casey M.; Ridgely, Ryan C.; Sedlmayr, Jayc C.; Witmer, Lawrence M.

    2010-01-01

    Extinct archosaurs, including many non-avian dinosaurs, exhibit relatively simply shaped condylar regions in their appendicular bones, suggesting potentially large amounts of unpreserved epiphyseal (articular) cartilage. This “lost anatomy” is often underappreciated such that the ends of bones are typically considered to be the joint surfaces, potentially having a major impact on functional interpretation. Extant alligators and birds were used to establish an objective basis for inferences about cartilaginous articular structures in such extinct archosaur clades as non-avian dinosaurs. Limb elements of alligators, ostriches, and other birds were dissected, disarticulated, and defleshed. Lengths and condylar shapes of elements with intact epiphyses were measured. Limbs were subsequently completely skeletonized and the measurements repeated. Removal of cartilaginous condylar regions resulted in statistically significant changes in element length and condylar breadth. Moreover, there was marked loss of those cartilaginous structures responsible for joint architecture and congruence. Compared to alligators, birds showed less dramatic, but still significant changes. Condylar morphologies of dinosaur limb bones suggest that most non-coelurosaurian clades possessed large cartilaginous epiphyses that relied on the maintenance of vascular channels that are otherwise eliminated early in ontogeny in smaller-bodied tetrapods. A sensitivity analysis using cartilage correction factors (CCFs) obtained from extant taxa indicates that whereas the presence of cartilaginous epiphyses only moderately increases estimates of dinosaur height and speed, it has important implications for our ability to infer joint morphology, posture, and the complicated functional movements in the limbs of many extinct archosaurs. Evidence suggests that the sizes of sauropod epiphyseal cartilages surpassed those of alligators, which account for at least 10% of hindlimb length. These data suggest that

  17. Manganese levels and the morphology of the epiphyseal plate in broilers with slipped tendons.

    PubMed

    Thomas, K W; Lowther, D A

    1976-09-01

    Manganese deficiency in chickens results in perosis and a higher incidence of slipped tendon. Perosis is associated with a disorganization of the epiphyseal growth plates and changes in the chemical composition of the cartilage matrix. Male broilers with slipped tendons were selected from a commercial broiler farm over a 9 week growing period. Their growth rates, epiphyseal cartilage histology and tissue manganese concentrations were examined and compared with (a) normal broilers from the same farm, and (b) similar broilers raised on control and manganese deficient diets. Field broilers with slipped tendons showed no evidence of abnormality in the histological appearance of the proximal tibial growth plate at any of the ages examined. The manganese content of liver and epiphyseal cartilage from field broilers showing slipped tendon was comparable with that present in tissue from normal broilers wither from the field or raised on a chemically defined diey supplemented with managese. The slightly retared growth rate seen in the field broilers was attributed to feeding problems associated with the lameness condition. These results provide conclusive evidence that slipped tendon in field broilers is not dur to a manganese deficiency in the tissues, nor does it appear to be associated with abnormal proliferation of the chondrocytes in the epiphyseal plate. PMID:995818

  18. Age related changes and osteochondrosis in swine articular and epiphyseal cartilage: light ane electron microscopy.

    PubMed Central

    Bhatnagar, R; Christian, R G; Nakano, T; Aherne, F X; Thompson, J R

    1981-01-01

    Age related changes and osteochondrosis in swine were studied using light microscopy and electron microscopy in articular cartilage and light microscopy and epiphyseal cartilage of swine from three days to 30 weeks of age. Thickness, cellularity and vascularity of both the epiphyseal and articular cartilage, decreased as the swine aged. Osteochondrotic changes included formation of "plugs" of cartilage indicating localized failure of ossification and separation and space formation in epiphyseal cartilage. Eosinophilic streaks and space formation in epiphyseal cartilage was observed in relation to epiphyseal separation. Electron microscopy showed a continuous fibrillar layer on the surface of the cartilage corresponding to the lamina splendens of light microscopy. This layer increased in the thickness and showed accumulation of amorphous material between the fibrils with aging. In the matrix, the orientation and distribution of the collagen fibers changed with growth and thicker fibers with clear sub banding were more common in older age groups. Also, necrotic cells, glycogen containing bodies and cellular debris were noticed in the matrix of normal cartilage in old animals. Chondrocytes in the younger cartilage showed accumulation of organelles responsible for protein synthesis; while Golgi bodies, vesicles, lysosomes, well developed foot processes and other inclusions were noticed in older cartilage. Cartilage erosions had a clumped and disrupted lamina splendens on the surface and electron lucent patches in the ground substances of the matrix and chondrocyte cytoplasm. Images Fig. 1. Fig. 2 and 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10 and 11. Fig. 12. Fig. 13. Fig. 14. Fig. 15. Fig. 16. Fig. 17. Fig. 18. PMID:7260732

  19. Sudden death in spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type.

    PubMed

    Dias, Cristina; Cairns, Robyn; Patel, Millan S

    2009-01-01

    The spondylo-meta-epiphyseal dysplasias are an expanding group of skeletal dysplasias with specific features differentiating each subtype. We review the precocious carpal mineralization, unique metacarpal shape, triangular distal phalanges and mushroom cloud-shaped proximal phalanges present at an early age in spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type (SMED SL-AC) and report two patients with clinical and radiographic features consistent with SMED SL-AC, who died suddenly because of spinal cord compression. The patients presented are female siblings, providing further evidence for autosomal recessive inheritance. Cervical cord compression is found in half of reported patients and is the major cause of mortality. SMED SL-AC should be added to the list of genetic causes of sudden death. Radiological features in the hand may be used in the first few years of life to support an early diagnosis and thus allow for prevention of premature demise. PMID:19050401

  20. The effects of low-level laser therapy, 670 nm, on epiphyseal growth in rats.

    PubMed

    de Andrade, Adriana Regina; Meireles, Anamaria; Artifon, Elisangela Lourdes; Brancalhão, Rose Meire Costa; Ferreira, José Roberto Leonel; Bertolini, Gladson Ricardo Flor

    2012-01-01

    The longitudinal growth of long bones is attributed to epiphyseal growth. However, the effects of low-level laser therapy (LLLT) in such structures has still not been studied extensively in the literature. Therefore, the aim of this study was to evaluate the use of LLLT, 670 nm, at three different doses on the epiphyseal growth of the right tibia of rats. Twenty-one Wistar rats, aged four weeks, were subjected to the application of LLLT, with dosage according to the group (G4: were submitted to the application of 4 J/cm(2); G8: were submitted to the application of 8 J/cm(2); G16: were submitted to the application of 16 J/cm(2)). After completion of protocol they were kept until they were 14 weeks of age and then submitted to a radiological examination (evaluation of limb length) and euthanised. The histological analysis of the growth plates (total thickness and hypertrophic and proliferative zones) was then performed. Comparisons were made with the untreated left tibia. No differences were observed in any of the reviews (radiological and histological), when comparing the right sides (treated) to the left (untreated). It was concluded that the treatment with LLLT within the parameters used caused changes neither in areas of the epiphyseal cartilage nor in the final length of limbs. PMID:22654576

  1. Effects of hyperprolactinemia on the tibial epiphyseal plate of mice treated with sex hormones.

    PubMed

    Wolff, Roberta B; Gomes, Regina Celia T; do Amaral, Vinicius C; da Silva, Priscilla L; Simoncini, Tommaso; Prosdocimi, Fabio Cesar; Simoes, Ricardo S; Simões, Manuel Jesus S; Baracat, Edmund C; Soares-Jr, José Maria

    2016-01-01

    The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the tibial epiphyseal plate of hormone-treated oophorectomized mice. For this purpose, 18 animals with intact ovaries were allocated to two groups, M (metoclopramide) and V (vehicle). One hundred and eight oophorectomized animals were allocated to 12 subgroups: Oophx/V (vehicle); Ooph/M (metoclopramide); Oophx/V + E (vehicle + estradiol); Oophx/M + E (metoclopramide + estradiol); Oophx/V + P (vehicle + progesterone); Oophx/M + P (metoclopramide + progesterone); Oophx/V + T (vehicle + testosterone); Oophx/M + T (metoclopramide + testosterone); Oophx/V + E + P (Vehicle + estradiol + progesterone); Oophx/M + E + P (metoclopramide + estradiol + progesterone); Oophx/V + E + P + T (vehicle + estradiol + progesterone + testosterone); Oophx/M + E + P + T (metoclopramide + estradiol + progesterone + testosterone). After a 50-day treatment was performed histomorphometric and immunohistochemical cell death analysis. In the epiphyseal plate of the hyperprolactinemic and/or oophorectomized animals, cell proliferation and bone formation decreased, inducing intensified cell death. In the sex steroid-treated animals, estrogen boosted cell proliferation; progesterone, bone formation and testosterone, both cell proliferation and bone formation. These findings suggest that oophorectomy and hyperprolactinemia changed epiphyseal plate morphology causing cartilage degeneration. Treatment with combined sex steroids may diminish such deleterious effects. PMID:26193892

  2. Delayed hypertrophic differentiation of epiphyseal chondrocytes contributes to failed secondary ossification in mucopolysaccharidosis VII dogs.

    PubMed

    Peck, Sun H; O'Donnell, Philip J M; Kang, Jennifer L; Malhotra, Neil R; Dodge, George R; Pacifici, Maurizio; Shore, Eileen M; Haskins, Mark E; Smith, Lachlan J

    2015-11-01

    Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient β-glucuronidase activity, which leads to the accumulation of incompletely degraded glycosaminoglycans (GAGs). MPS VII patients present with severe skeletal abnormalities, which are particularly prevalent in the spine. Incomplete cartilage-to-bone conversion in MPS VII vertebrae during postnatal development is associated with progressive spinal deformity and spinal cord compression. The objectives of this study were to determine the earliest postnatal developmental stage at which vertebral bone disease manifests in MPS VII and to identify the underlying cellular basis of impaired cartilage-to-bone conversion, using the naturally-occurring canine model. Control and MPS VII dogs were euthanized at 9 and 14 days-of-age, and vertebral secondary ossification centers analyzed using micro-computed tomography, histology, qPCR, and protein immunoblotting. Imaging studies and mRNA analysis of bone formation markers established that secondary ossification commences between 9 and 14 days in control animals, but not in MPS VII animals. mRNA analysis of differentiation markers revealed that MPS VII epiphyseal chondrocytes are unable to successfully transition from proliferation to hypertrophy during this critical developmental window. Immunoblotting demonstrated abnormal persistence of Sox9 protein in MPS VII cells between 9 and 14 days-of-age, and biochemical assays revealed abnormally high intra and extracellular GAG content in MPS VII epiphyseal cartilage at as early as 9 days-of-age. In contrast, assessment of vertebral growth plates and primary ossification centers revealed no significant abnormalities at either age. The results of this study establish that failed vertebral bone formation in MPS VII can be traced to the failure of epiphyseal chondrocytes to undergo hypertrophic differentiation at the appropriate developmental stage, and suggest that aberrant processing of Sox9 protein

  3. Surgical Repair with External Fixation of Epiphyseal Fractures of the Proximal Phalanges of Three Fingers: A Case Report.

    PubMed

    Morisawa, Yasushi; Takayama, Shinichiro; Sato, Kazuki

    2015-10-01

    A 13-year-old girl sustained epiphyseal fractures of the proximal phalanges of the left index, middle, and ring fingers. Though manual reduction of the 3 fingers was possible, it was difficult to maintain the reduction due to severe instability of the middle and ring fingers, and closed reduction with external fixation was performed. At 4 years post-injury, the patient had no impairment of daily activities. The use of external fixation (1) causes no injury to the epiphyseal cartilage, (2) enables accurate reduction and maintenance of reduction, (3) is technically easier than pinning, (4) enables earlier range of motion (ROM) exercises of the proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints of the externally fixated and other fingers, and (5) allows repeated fine adjustments after reduction. External fixation is an option for the treatment of children with highly unstable epiphyseal fractures of the proximal phalanges. PMID:26388013

  4. A case with oto-spondylo-mega-epiphyseal-dysplasia (OSMED): the clinical recognition and differential diagnosis.

    PubMed

    Karaer, Kadri; Rosti, Rasim Ozgür; Torun, Deniz; Sanal, Hatice Tuba; Bahçe, Muhterem; Güran, Sefik

    2011-01-01

    The oto-spondylo-mega-epiphyseal-dysplasia (OSMED) phenotype is an autosomal recessive trait that is a skeletal dysplasia with the hallmark findings of limb shortening, multiple skeletal and radiological abnormalities, mid-face hypoplasia with a flat nasal bridge, small upturned nasal tip, and sensorineural hearing loss. A 3.5-year-old girl born to consanguineous Turkish parents had characteristic facial features at birth: mid-face hypoplasia, mild hypertelorism, upslanting palpebral fissures, prominent supraorbital ridges, depressed nasal bridge, small upturned nasal tip, long philtrum, and micrognathia. Radiological examination at three years of age revealed large flaring metaphyses and wide flat epiphyses. The humerus and femur showed the characteristic dumbbell shape. She had bilateral hearing loss with no ophthalmologic findings. There is continuing debate over the clinical overlap and differential diagnosis of OSMED syndrome. The patient was examined considering Weissenbacher-Zweymuller, Stickler type 3, Marshall syndrome, and Kniest dysplasia as possible differential diagnoses. We believe that the presented patient clinically manifested features of OSMED syndrome. We would like to point out that the management of OSMED calls for a coordinated multidisciplinary approach. PMID:21980822

  5. Discontinuities in the endothelium of epiphyseal cartilage canals and relevance to joint disease in foals.

    PubMed

    Hellings, Ingunn Risnes; Ekman, Stina; Hultenby, Kjell; Dolvik, Nils Ivar; Olstad, Kristin

    2016-01-01

    Cartilage canals have been shown to contain discontinuous blood vessels that enable circulating bacteria to bind to cartilage matrix, leading to vascular occlusion and associated pathological changes in pigs and chickens. It is also inconsistently reported that cartilage canals are surrounded by a cellular or acellular wall that may influence whether bacterial binding can occur. It is not known whether equine cartilage canals contain discontinuous endothelium or are surrounded by a wall. This study aimed to examine whether there were discontinuities in the endothelium of cartilage canal vessels, and whether canals had a cellular or acellular wall, in the epiphyseal growth cartilage of foals. Epiphyseal growth cartilage from the proximal third of the medial trochlear ridge of the distal femur from six healthy foals that were 1, 24, 35, 47, 118 and 122 days old and of different breeds and sexes was examined by light microscopy (LM), transmission electron microscopy (TEM) and immunohistochemistry. The majority of patent cartilage canals contained blood vessels that were lined by a thin layer of continuous endothelium. Fenestrations were found in two locations in one venule in a patent cartilage canal located deep in the growth cartilage and close to the ossification front in the 118-day-old foal. Chondrifying cartilage canals in all TEM-examined foals contained degenerated endothelial cells that were detached from the basement membrane, resulting in gap formation. Thirty-three percent of all canals were surrounded by a hypercellular rim that was interpreted as contribution of chondrocytes to growth cartilage. On LM, 69% of all cartilage canals were surrounded by a ring of matrix that stained intensely eosinophilic and consisted of collagen fibres on TEM that were confirmed to be collagen type I by immunohistochemistry. In summary, two types of discontinuity were observed in the endothelium of equine epiphyseal cartilage canal vessels: fenestrations were observed in

  6. Stimulation of body weight increase and epiphyseal cartilage growth by insulin like growth factor

    NASA Technical Reports Server (NTRS)

    Ellis, S.

    1981-01-01

    The ability of insulin-like growth factor (IGF) to induce growth in hypophysectomized immature rats was tested by continuous infusion of the partially purified factor at daily doses of 6, 21, and 46 mU for an 8-day period. A dose-dependent growth of the proximal epiphyseal cartilage of the tibia and an associated stimulation of the primary spongiosa were produced by these amounts of IGF. The two highest doses of IGF also resulted in dose-dependent increases of body weight. Gel permeation of the sera at neutrality showed that the large-molecular-weight IGF binding protein was not induced by the infusion of IGF, whereas it ws generated in the sera of hypophysectomized rats that were infused with daily doses of 86 mU of human growth hormone.

  7. Late presented case of distal humerus epiphyseal separation in a newborn.

    PubMed

    Mane, Prajwal Prabhudev; Challawar, Nikhil Subhash; Shah, Hitesh

    2016-01-01

    The incidence of traumatic bone injuries occurring during birth is rare (1 per 1000 live births). Of all long bone fractures, the humerus is one of the commonest bones to be involved. However, distal humeral epiphyseal separation is rare and has seldom been written up in case reports and small case series. It warrants some critical assessment and appropriate attention. This injury is sometimes missed as it is difficult to diagnose at initial presentation. It may be mistaken for dislocation of the elbow, osteomyelitis, septic arthritis or brachial plexus injury, owing to lack of movement of the upper limb. Knowledge of its clinical and radiological findings will enable the treating physician to diagnose it at the appropriate time. Masterful observation is adequate treatment for this condition, and leads to a better clinical and radiological outcome. Timely diagnosis with an optimistic prognosis will prevent unnecessary parental apprehension. PMID:27247206

  8. Refinement of the localization of the gene responsible for spondylo epiphyseal dysplasia in Xp22

    SciTech Connect

    Hors-Cayla, M.C.; Heuertz, S.; Smahi, A.

    1994-09-01

    Spondylo epiphyseal dysplasia tarda (SEDL) (MIM 313400) is an X-linked recessive disease characterized by short stature which is caused by a growth defect of the vertebral bodies. Using RFLP markers, we have previously localized the gene responsible to Xp22 between DXS16 and DXS92 in a 13% recombination fraction interval. Further genetic analysis was carried out using microsatellite markers. As their localization with respect to the RFLP markers was unknown, we first obtained a physical map integrating RFLP and microsatellite markers, with the help of a panel of radiation reduced hybrids. Studying recombinants between the SEDL gene and RFLP and microsatellite markers, we refined the position of the gene on Xp22 between DXS16 and DXS987 on a 1 to 2 Mb chromosomal segment.

  9. [Fractures and slipped epiphyses of the proximal humerus in children. Place and methods of surgical treatment].

    PubMed

    Guibert, L; Allouis, M; Bourdelat, D; Catier, P; Bracq, H; Babut, J M

    1983-01-01

    Fractures and Epiphyseal separations of the proximal humerus are usually non-operatively treated with a generally good result. However, sometimes, a surgical treatment may be required. Twenty fractures of the proximal humerus occurring in children were treated operatively. From these 20 cases, the authors precise the indications and the ways of surgical treatment in this type of lesion. They insist upon the value of the angulation on the lateral radiograph of the shoulder which, if important, may often signify an interposition of the tendon of the long head of the biceps between the fracture fragments causing irreductibility; they propose a classification of the fractures referring to this angle. Considering surgical procedure, delto-pectoral approach is the most commonly used, although axillary way is more esthaetic. Kirschner wires and screws are the best means of synthesis. Anyway, this surgical treatment has to remain exceptional. PMID:6627539

  10. Responses of articular and epiphyseal cartilage zones of developing avian radii to estrone treatment and a 2-G environment

    NASA Technical Reports Server (NTRS)

    Negulesco, J. A.; Kossler, T.

    1978-01-01

    Histological measurements of radii from chickens exposed to estrone and hypergravity are reported. Female chicks at two weeks post-hatch were maintained for two weeks at earth gravity or 2 G with daily injections of 0.2 or 0.4 mg estrone. Animals were sacrificed after the last injection, and the radii were processed by described histological techniques. The results suggest that proximal and distal epiphyses of developing radii show different morphological responses to estrone and hypergravity.

  11. Genetic linkage mapping of multiple epiphyseal dysplasia to the pericentromeric region of chromosome 19.

    PubMed Central

    Oehlmann, R.; Summerville, G. P.; Yeh, G.; Weaver, E. J.; Jimenez, S. A.; Knowlton, R. G.

    1994-01-01

    Multiple epiphyseal dysplasia (MED) is an inherited chondrodystrophy that results in deformity of articular surfaces and in subsequent degenerative joint disease. The disease is inherited as an autosomal dominant trait with high penetrance. An MED mutation has been mapped by genetic linkage analysis of DNA polymorphisms in a single large pedigree. Close linkage of MED to 130 tested chromosomal markers was ruled out by discordant inheritance patterns. However, strong evidence for linkage of MED to markers in the pericentromeric region of chromosome 19 was obtained. The most closely linked marker was D19S215, with a maximum LOD score of 6.37 at theta = .05. Multipoint linkage analysis indicated that MED is located between D19S212 and D19S215, a map interval of 1.7 cM. Discovery of the map location of MED in this family will facilitate identification of the mutant gene. The closely linked DNA polymorphisms will also provide the means to determine whether other inherited chondrodystrophies have underlying defects in the same gene. PMID:8279467

  12. Epiphyseal Sparing and Reconstruction by Frozen Bone Autograft after Malignant Bone Tumor Resection in Children

    PubMed Central

    Hamed Kassem Abdelaal, Ahmed; Yamamoto, Norio; Hayashi, Katsuhiro; Takeuchi, Akihiko; Miwa, Shinji; Tsuchiya, Hiroyuki

    2015-01-01

    Limb salvage surgery has become the standard treatment for malignant primary bone tumors in the extremities. Limb salvage represents a challenge in skeletally immature patients. Several treatment options are available for limb reconstruction after tumor resection in children. We report our results using the technique of epiphyseal sparing and reconstruction with frozen autograft bone in 18 children. The mean follow-up period for the all patients included in this study is 72 ± 26 m. Eight patients remained disease-free, seven patients lived with no evidence of disease, two were alive but with disease, and one patient died of the disease. Five- and ten-year rates of survival were 94.4%. Graft survival at 5 and 10 years was 94.4%. Functional outcome using the Enneking scale was excellent in 17 patients (94.4%) and poor in one patient (5.5%). Complications include 2 nonunions, 2 fractures, 2 deep infections, 1 soft tissue recurrence, and leg length discrepancy in 7 cases. This technique is a good reconstructive choice in a child with a nonosteolytic primary or secondary bone tumor, responsive to chemotherapy, without involvement of the articular cartilage. It is a straight forward, effective, and biological technique, which affords immediate mobilization of joints and possible cryoimmune effects, with excellent long term functional outcome and less complication. PMID:27034614

  13. Automatic Segmentation of Phalanx and Epiphyseal/Metaphyseal Region by Gamma Parameter Enhancement Algorithm

    NASA Astrophysics Data System (ADS)

    Hsieh, C. W.; Chen, C. Y.; Jong, T. L.; Liu, T. C.; Chiu, C. H.

    2012-01-01

    The performance of bone age assessment is highly correlated with the extraction of bony tissue from soft tissues, and the key problem is how to successfully separate epiphyseal/metaphyseal region of interests (EMROIs) from the background and soft tissue. In our experiment, a series of image preprocessing procedures are used to exclude the background and locate the EMROIs of left-hand radiographs. Subsequently, automatic gamma parameter enhancement is applied to test the two segmentation methods (adaptive two-means clustering algorithm and gradient vector flow snake) among children of different age (the age from 2 to 16 years for 80 girls and boys). Four error measurements of misclassification error, relative foreground area error, modified Hausdorff distances, and edge mismatch, are included to evaluate the segmentation performance. The result shows that the two segmentation algorithms are corresponding to different ranges of optimal gamma parameters. Furthermore, the margin of EMROIs can be obtained more precisely by developing an automatic bone age assessment method with the gamma parameter enhancement.

  14. ALL‐EPIPHYSEAL ACL RECONSTRUCTION: A THREE‐YEAR FOLLOW‐UP

    PubMed Central

    Akinleye, Sheriff D.; Sewick, Amy

    2013-01-01

    Background/Introduction: With an increasing number of pre‐adolescents participating in sports, anterior cruciate ligament injuries and resultant reconstruction in the skeletally immature athlete are becoming more common. Many different surgical techniques and rehabilitation protocols have been proposed for the treatment of anterior cruciate ligament (ACL) injuries, but there is a lack of agreement as to which approach results in the best outcome. Rehabilitation protocols have marked variation regarding postoperative weight bearing, immobilization, bracing, and length. Case description: This is a case of a ten year old female who sustained bilateral ACL tears within the period of a year. The purpose of this case report is to describe the early result and subsequent rehabilitation following bilateral physeal‐sparing all‐epiphyseal ACL reconstructions on a skeletally immature patient with a three‐year follow‐up. Outcomes: The early post‐surgical recovery period on the first injured knee was complicated by knee stiffness requiring manipulation. Following this minor setback, the patient met all physical therapy goals and had no additional complications. The rehabilitation after the second surgery followed a typical course. At three‐year follow‐up, the patient had grown an additional seven inches, with radiographic evidence of symmetric physeal growth and joint stability. She has returned to playing competitive sports. Discussion and Conclusion: This innovative physeal‐sparing technique has huge implications as, historically; the feared complication of growth disturbance and angular deformity from transphyseal ACL reconstruction has complicated the management of ACL injuries in children and pre‐adolescents. This case report demonstrates the success of this technique, and the subsequent rehabilitation, as this patient did not experience a reduction in long‐term bone growth. Level of Evidence: 5 Case Report PMID:23772346

  15. A mathematical model of epiphyseal development: hypothesis on the cartilage canals growth.

    PubMed

    Garzon-Alvarado, Diego Alexander; Peinado Cortes, Liliana Mabel; Cardenas Sandoval, Rosy Paola

    2010-12-01

    The role of cartilage canals is to transport nutrients and biological factors that cause the appearance of the secondary ossification centre (SOC). The SOC appears in the centre of the epiphysis of long bones. The canal development is a complex interaction between mechanical and biological factors that guide its expansion into the centre of the epiphysis. This article introduces the 'Hypothesis on the growth of cartilage canals'. Here, we have considered that the development of these canals is an essential event for the appearance of SOC. Moreover, it is also considered to be important for the transport of molecular factors (RUNX2 and MMP9) at the ends of such canals. Once the canals are merged in the centre of the epiphysis, these factors are released causing hypertrophy of adjacent cells. This RUNX2 and MMP9 release occurs due to the action of mechanical loads that supports the epiphysis. In order to test this hypothesis, we use a hybrid approach using the finite element method to simulate the mechanical stresses present in the epiphysis and the cellular automata to simulate the expansion of the canals and the hypertrophy factors pathway. By using this hybrid approach, we have obtained as a result the spatial-temporal patterns for the growth of cartilage canals and hypertrophy factors within the epiphysis. The model is in qualitative agreement with experimental results previously reported by other authors. Thus, we conclude that this model may be used as a methodological basis to present a complete mathematical model of the processes involved in epiphyseal development. PMID:20526919

  16. Deletion of IFT80 Impairs Epiphyseal and Articular Cartilage Formation Due to Disruption of Chondrocyte Differentiation

    PubMed Central

    Yuan, Xue; Yang, Shuying

    2015-01-01

    Intraflagellar transport proteins (IFT) play important roles in cilia formation and organ development. Partial loss of IFT80 function leads Jeune asphyxiating thoracic dystrophy (JATD) or short-rib polydactyly (SRP) syndrome type III, displaying narrow thoracic cavity and multiple cartilage anomalies. However, it is unknown how IFT80 regulates cartilage formation. To define the role and mechanism of IFT80 in chondrocyte function and cartilage formation, we generated a Col2α1; IFT80f/f mouse model by crossing IFT80f/f mice with inducible Col2α1-CreER mice, and deleted IFT80 in chondrocyte lineage by injection of tamoxifen into the mice in embryonic or postnatal stage. Loss of IFT80 in the embryonic stage resulted in short limbs at birth. Histological studies showed that IFT80-deficient mice have shortened cartilage with marked changes in cellular morphology and organization in the resting, proliferative, pre-hypertrophic, and hypertrophic zones. Moreover, deletion of IFT80 in the postnatal stage led to mouse stunted growth with shortened growth plate but thickened articular cartilage. Defects of ciliogenesis were found in the cartilage of IFT80-deficient mice and primary IFT80-deficient chondrocytes. Further study showed that chondrogenic differentiation was significantly inhibited in IFT80-deficient mice due to reduced hedgehog (Hh) signaling and increased Wnt signaling activities. These findings demonstrate that loss of IFT80 blocks chondrocyte differentiation by disruption of ciliogenesis and alteration of Hh and Wnt signaling transduction, which in turn alters epiphyseal and articular cartilage formation. PMID:26098911

  17. The aromatase inhibitor letrozole increases epiphyseal growth plate height and tibial length in peripubertal male mice.

    PubMed

    Eshet, R; Maor, G; Ben Ari, T; Ben Eliezer, M; Gat-Yablonski, G; Phillip, M

    2004-07-01

    Sex hormones may influence longitudinal growth, either indirectly, by affecting the growth-hormone-insulin-like growth factor I (IGF-I) axis, or directly, by affecting changes within the epiphyseal growth plate (EGP). The aim of the present study was to investigate the effects of letrozole, an aromatase inhibitor, on longitudinal growth and changes in the EGP in vivo. Eighteen peripubertal male mice were divided into three groups. The first group was killed at baseline, the second was injected with letrozole (Femara) s.c., 2 mg/kg body weight/day, for 10 days, and the third was injected with the vehicle alone. Serum testosterone levels were found to be significantly higher in the treated group than in the controls. Letrozole induced a significant increase in body weight, tail length and serum growth hormone level, but had no significant effect on the level of serum IGF-I. On histomorphometric study, there was a significant increase (12%) in EGP height in the treated animals compared with controls. Immunohistochemistry showed a 3.4-fold letrozole-induced increase in the proliferation of the EGP chondrocytes, as estimated by the number of proliferation cell nuclear antigen-stained cells, and a decrease in the differentiation of the EGP chondrocytes, as estimated by type X collagen staining. Letrozole did not interfere with type II collagen levels. The study group also showed a twofold increase in the number of IGF-I receptor-positive cells compared with controls. In conclusion, the aromatase inhibitor, letrozole, appears to increase the linear growth potential of the EGP in mice. PMID:15225141

  18. Deletion of IFT80 Impairs Epiphyseal and Articular Cartilage Formation Due to Disruption of Chondrocyte Differentiation.

    PubMed

    Yuan, Xue; Yang, Shuying

    2015-01-01

    Intraflagellar transport proteins (IFT) play important roles in cilia formation and organ development. Partial loss of IFT80 function leads Jeune asphyxiating thoracic dystrophy (JATD) or short-rib polydactyly (SRP) syndrome type III, displaying narrow thoracic cavity and multiple cartilage anomalies. However, it is unknown how IFT80 regulates cartilage formation. To define the role and mechanism of IFT80 in chondrocyte function and cartilage formation, we generated a Col2α1; IFT80f/f mouse model by crossing IFT80f/f mice with inducible Col2α1-CreER mice, and deleted IFT80 in chondrocyte lineage by injection of tamoxifen into the mice in embryonic or postnatal stage. Loss of IFT80 in the embryonic stage resulted in short limbs at birth. Histological studies showed that IFT80-deficient mice have shortened cartilage with marked changes in cellular morphology and organization in the resting, proliferative, pre-hypertrophic, and hypertrophic zones. Moreover, deletion of IFT80 in the postnatal stage led to mouse stunted growth with shortened growth plate but thickened articular cartilage. Defects of ciliogenesis were found in the cartilage of IFT80-deficient mice and primary IFT80-deficient chondrocytes. Further study showed that chondrogenic differentiation was significantly inhibited in IFT80-deficient mice due to reduced hedgehog (Hh) signaling and increased Wnt signaling activities. These findings demonstrate that loss of IFT80 blocks chondrocyte differentiation by disruption of ciliogenesis and alteration of Hh and Wnt signaling transduction, which in turn alters epiphyseal and articular cartilage formation. PMID:26098911

  19. Isometric Scaling in Developing Long Bones Is Achieved by an Optimal Epiphyseal Growth Balance

    PubMed Central

    Stern, Tomer; Aviram, Rona; Rot, Chagai; Galili, Tal; Sharir, Amnon; Kalish Achrai, Noga; Keller, Yosi; Shahar, Ron; Zelzer, Elazar

    2015-01-01

    individual epiphyseal plates. PMID:26241802

  20. Recessively inherited multiple epiphyseal dysplasia with normal stature, club foot, and double layered patella caused by a DTDST mutation.

    PubMed

    Superti-Furga, A; Neumann, L; Riebel, T; Eich, G; Steinmann, B; Spranger, J; Kunze, J

    1999-08-01

    We have observed over 25 different mutations in the diastrophic dysplasia sulphate transporter gene (DTDST) in association with the recessive disorders achondrogenesis 1B, atelosteogenesis 2, and diastrophic dysplasia. The c862t (R279W) transition is the most common mutation in non-Finnish patients, but in these disorders it is usually combined with other DTDST mutations. We had not seen a case of homozygosity for c862t (R279W) until we analysed DNA from a 36 year old male with tall-normal stature (180 cm) who asked for genetic counselling for suspected multiple epiphyseal dysplasia. He was treated for club foot and hip dysplasia at birth. Skeletal changes consistent with multiple epiphyseal dysplasia, with the peculiar finding of a double layered patella, were recognised during childhood. Cleft palate, swelling of the ear pinna, and hitch hiker thumb were absent. He was found to be homozygous, and both healthy parents heterozygous, for the R279W mutation in DTDST, and his fibroblasts showed a sulphate incorporation defect typical of DTDST disorders. Counselling was given for a recessive disorder, thereby considerably reducing the probability of affected offspring. Multiple epiphyseal dysplasia is more frequently caused by dominant mutations in the COMP (EDM1, McKusick 132400) and COL9A2 genes (EDM2, McKusick 600204). A few other patients and families with features similar to our proband have been described previously and considered to have autosomal recessive MED (EDM4, McKusick 226900). This observation confirms the existence of this entity and assigns it to the phenotypic spectrum associated with mutations at the DTDST locus. PMID:10465113

  1. Relationship between the chondrocyte maturation cycle and the endochondral ossification in the diaphyseal and epiphyseal ossification centers.

    PubMed

    Pazzaglia, Ugo E; Congiu, Terenzio; Sibilia, Valeria; Pagani, Francesca; Benetti, Anna; Zarattini, Guido

    2016-09-01

    The chondrocyte maturation cycle and endochondral ossification were studied in human, fetal cartilage Anlagen and in postnatal meta-epiphyses. The relationship between the lacunar area, the inter-territorial fibril network variations, and calcium phosphorus nucleation in primary and secondary ossification centers were assessed using light microscopy and scanning electron microscopy (SEM) morphometry. The Anlage topographic, zonal classification was derived from the anatomical nomenclature of the completely developed long bone (diaphysis, metaphyses and epiphyses). A significant increase in the chondrocyte lacunar area was documented in the Anlage of epiphyseal zones 4 and 3 to zone 2 (metaphysis) and zone 1 (diaphysis), with the highest variation from zone 2 to zone 1. An inverse reduction in the intercellular matrix area and matrix interfibrillar empty space was also documented. These findings are consistent with the osmotic passage of free cartilage water from the interfibrillar space into the swelling chondrocytes, which increased the ion concentrations to a critical threshold for mineral precipitation in the matrix. The mineralized cartilage served as a scaffold for osteoblast apposition both in primary and secondary ossification centers and in the metaphyseal growth plate cartilage, though at different periods of bone Anlage development and with distinct patterns for each zone. All developmental processes shared a common initial pathway but progressed at different rates, modes and organization in diaphysis, metaphysis and epiphysis. In the ossification phase the developing vascular supply appeared to play a key role in determining the cortical or trabecular structure of the long bones. J. Morphol. 277:1187-1198, 2016. © 2016 Wiley Periodicals, Inc. PMID:27312928

  2. Galeazzi - Equivalent Pronation Type Injury with Splitting of Ulnar Epiphyseal Plate into Two Fragments – A Rare Case Report and Review of Literature

    PubMed Central

    J, Ashish Suthar; V, Ashish Kothari

    2014-01-01

    Introduction: In children and adolescents distal forearm physeal fractures are common. Usually distal forearm physeal injuries of are common injuries in children and adolescents. Epiphyseal injuries to the distal radius are common in children, but involvement of the distal ulna is rare. Fracture of the distal radius with dislocation of the DRUJ is known as a True Galeazzi fracture dislocation and an epiphyseal separation of the distal ulna occurred instead of dislocation of DRUJ or both)[10] is called Galeazzi equivalent lesions. Galeazzi fractures in children are less common than in adults. [4] These injuries are uncommon and there are few descriptions of them in the current literature. Case Report: Here we report the case of a 13-year-old boy, student with history of RTA presented with pain and swelling of distal forearm diagnosed with closed injury of Galeazzi equivalent type. Here injury to the distal ulnar epiphyseal plate is in the form of epiphyseal separation (Salter Harris type I / Peterson type III) with splitting of epiphysis into two fragment – [ulnar styloid & radial side of ulnar epiphyseal plate] (Salter Harris type III / Peterson type IV) with fracture of metaphysis of lower end radius (Peterson type I) without neurovascular deficit. Patient was given surgical treatment in the form of closed reduction and K-wire fixation for fracture of distal radius and open reduction using extended ulnar approach and fixation with K-wire for ulnar epiphyseal fracture as closed reduction was not possible due to soft tissue interposition. Conclusion: Galeazzi equivalent injury is rare. It may require radiographic comparison of opposite uninvolved distal forearm with wrist, CT or MR imaging to define injury accurately. It may also require open reduction for anatomical or acceptable reduction of fracture to minimize chances of growth arrest which may occur as a complication of injury. It is also necessary for frequent follow up to identify complication early

  3. Multipurpose contrast enhancement on epiphyseal plates and ossification centers for bone age assessment

    PubMed Central

    2013-01-01

    Background The high variations of background luminance, low contrast and excessively enhanced contrast of hand bone radiograph often impede the bone age assessment rating system in evaluating the degree of epiphyseal plates and ossification centers development. The Global Histogram equalization (GHE) has been the most frequently adopted image contrast enhancement technique but the performance is not satisfying. A brightness and detail preserving histogram equalization method with good contrast enhancement effect has been a goal of much recent research in histogram equalization. Nevertheless, producing a well-balanced histogram equalized radiograph in terms of its brightness preservation, detail preservation and contrast enhancement is deemed to be a daunting task. Method In this paper, we propose a novel framework of histogram equalization with the aim of taking several desirable properties into account, namely the Multipurpose Beta Optimized Bi-Histogram Equalization (MBOBHE). This method performs the histogram optimization separately in both sub-histograms after the segmentation of histogram using an optimized separating point determined based on the regularization function constituted by three components. The result is then assessed by the qualitative and quantitative analysis to evaluate the essential aspects of histogram equalized image using a total of 160 hand radiographs that are implemented in testing and analyses which are acquired from hand bone online database. Result From the qualitative analysis, we found that basic bi-histogram equalizations are not capable of displaying the small features in image due to incorrect selection of separating point by focusing on only certain metric without considering the contrast enhancement and detail preservation. From the quantitative analysis, we found that MBOBHE correlates well with human visual perception, and this improvement shortens the evaluation time taken by inspector in assessing the bone age. Conclusions

  4. The canine epiphyseal-derived mesenchymal stem cells are comparable to bone marrow derived-mesenchymal stem cells

    PubMed Central

    CHANG, Ya-Pei; HONG, Hsuan-Ping; LEE, Yen-Hua; LIU, I-Hsuan

    2014-01-01

    Mesenchymal stem cells (MSCs) hold great potential in cell therapy and have attracted increasing interests in a wide range of biomedical sciences. However, the scarcity of MSCs and the prolonged isolation procedure limited the clinical application. To address these 2 issues, we developed a method to isolate MSCs from bone biopsy tissues of euthanized canine body donors. Compared to the traditional method to isolate MSCs from aspirated bone marrow (BMSCs), the isolation procedure for MSCs from harvested epiphyseal cancellous bone (EMSCs) was less time-consuming. The isolated EMSCs had similar plastic-adherence, tri-lineage differentiation and consistent surface marker profiles compared to BMSCs. We harvested BMSCs and EMSCs from 24 euthanized cases from clinics and 42 euthanized donors from a local shelter. The successful rate for EMSC isolation is significantly higher compared to BMSC isolation, while the other properties of the isolated MSCs including the clonogenicity, proliferative potentials and molecular phenotypes were not discernibly different between the MSCs established by the two methods. In conclusion, we demonstrated a new procedure to harvest MSCs by bone biopsy at the epiphyseal region. This method is less time consuming and more reliable, and the resulting MSCs are comparable to those harvested by bone marrow aspiration. The combination of the two methods can greatly improve the efficiency to harvest MSCs. PMID:25391394

  5. SLC26A2 disease spectrum in Sweden - high frequency of recessive multiple epiphyseal dysplasia (rMED).

    PubMed

    Mäkitie, O; Geiberger, S; Horemuzova, E; Hagenäs, L; Moström, E; Nordenskjöld, M; Grigelioniene, G; Nordgren, A

    2015-03-01

    Diastrophic dysplasia (DTD) is an autosomal recessive skeletal dysplasia caused by SLC26A2 mutations. Clinical features include short stature, joint contractures, spinal deformities, and cleft palate. SLC26A2 mutations also result in other skeletal dysplasias, including the milder recessive multiple epiphyseal dysplasia (rMED). DTD is overrepresented in Finland and we speculated that this may have influenced the prevalence and spectrum of SLC26A2-related skeletal conditions also in Sweden. We reviewed the patient registry at Department of Clinical Genetics, Karolinska University Hospital, Stockholm to identify subjects with SLC26A2 mutations. Seven patients from six families were identified; clinical data were available for six patients. All but one patient had one or two copies of the Finnish SLC26A2 founder mutation IVS1+2T>C. Arg279Trp mutation was present in compound heterozygous form in five patients with phenotypes consistent with rMED. Their heights ranged from -2.6 to -1.4 standard deviation units below normal mean and radiographic features included generalised epiphyseal dysplasia and double-layered patellae. Two rMED patients had hypoplastic C2 and cervical kyphosis, a severe manifestation previously described only in DTD. Our study confirms a high prevalence of rMED in Sweden and expands the phenotypic manifestations of rMED. PMID:24598000

  6. Biomechanical reasons for the divergent morphology of the knee joint and the distal epiphyseal suture in hominoids.

    PubMed

    Preuschoft, H; Tardieu, C

    1996-01-01

    The obliquity of the femoral diaphysis accounts for the valgus position of the human knee joint and reduces bending moments in the frontal plane. A high angle of obliquity is considered a hallmark of hominid bipedality, but its functional importance has rarely been identified correctly. A biostatic investigation of the knee joint in various realistic positions unveils resultant joint forces which do not deviate greatly from the long axis of the femoral shaft. This is due to the length of the femur and to the shortness of the human foot. The flat epiphyseal suture is more or less perpendicular to these joint forces, and the equal size of the femoral condyles reflects the even distribution of forces between them. In great apes the resultant forces acting in the knee joint vary considerably in dependence on the degree of flexion and rotation of the knee joint. The resultant joint force may be line with the femur shaft or diverge. The epiphyseal surfaces offer facets to all joint forces found in the course of the study. Due to the pronounced varus position of the knee joint, the joint itself and the adjacent part of the femur are under medially concave bending moments, which lead to higher compressive forces at the medial than at the lateral condyle. The enlarged medial condyle allows the distribution of medially displaced joint forces over a relatively large area, and the elliptic cross-section yields high bending resistance in the frontal plane. A human-like angle of obliquity is present in the early australopithecines, the values being mostly within the range of variation of children. The valgus position of the australopithecine knee joint is considered to be a functional, and epigenetic consequence of habitual bipedality. It is particularly pronounced because of the short length of the femur and the great bitrochanteric width. PMID:8953752

  7. Accuracy of scoring of the epiphyses at the knee joint (SKJ) for assessing legal adult age of 18 years.

    PubMed

    Galić, Ivan; Mihanović, Frane; Giuliodori, Alice; Conforti, Federica; Cingolani, Mariano; Cameriere, Roberto

    2016-07-01

    Important aspects of forensic practice are age estimation and discrimination of individuals of unknown age as adults and minors. The developing knee joint was recognized as a potential site for age examination in late adolescence. We analyzed a sample of anteroposterior x-rays of the knee joints from 446 living individuals from Umbria, Italy (234 males and 212 females), aged between 12 and 26 years. We evaluated the ossification of the distal femoral (DF), proximal tibial (PT), and proximal fibular (PF) epiphyses. We took into account possible persistence of the epiphyseal scars in the ossified epiphyses by the adopted stages of those previously introduced by Cameriere et al. (2012). We also used measurements from all three epiphyses to calculate the total score of maturation for the knee joint (SKJ). Cohen Kappa coefficients of intrarater agreement for staging the DF, PT, and PF epiphyses were 0.839, 0.894, and 0.907, while interrater agreement was 0.919, 0.791, and 0.907, respectively. The resulting receiver operating characteristic (ROC) curves of SKJ show better discriminatory power than those for DF, PT, and PF epiphyses in predicting that the participant, either male or female, was an adult or a minor. The areas under the curves for SKJ were 0.991 and 0.968 vs. 0.944, 0.962, 0.974 and 0.891, 0.910, 0.918 for males and females, respectively. The results of the 2 by 2 contingency tables showed that SKJ score of 4 in males and SKJ score of 5 in females were the most suitable cut-off value in discriminating between adults and minors. Principally, the sensitivity test for males was 0.94, with 95 % confidence interval (95 % CI) 0.90 to 0.97 and specificity was 0.96 (95 % CI 0.91 to 0.98). The proportion of correctly classified individuals was 0.95 (95 % CI 0.91 to 0.97). For females, the sensitivity test was 0.89 (95 % CI 0.84 to 0.92) and specificity was 0.92 (95 % CI 0.87 to 0.96), the proportion of correctly classified individuals was 0.90 (95 % CI 0

  8. Experiment K-6-06. Morphometric and EM analyses of tibial epiphyseal plates from Cosmos 1887 rats

    NASA Technical Reports Server (NTRS)

    Duke, P. J.; Montufar-Solis, D.; Durnova, G.

    1990-01-01

    Light and electron microscopy studies were carried out on decalcified tibial epiphyseal plates of rats flown aboard Cosmos 1887 (12.5d flight plus 53.5h recovery). Analysis of variance showed that the proliferative zone of flight animals was significantly higher than that of synchronous controls, while the hypertrophic/calcification zone was significantly reduced. Flight animals had more cells than synchronous controls in the proliferative zone, and less in the hypertrophic/calcification region. The total number of cells, however, was significantly higher in flight animals. No differences were found for perimeter or shape factor of growth plates, but area was significantly lower in flight animals in comparison to synchronous controls. Collagen fibrils in flight animals were shorter and wider than in synchronous controls. The time required for a cell to cycle through the growth plate is 2 to 3 days, so most of the cells and matrix present were formed after the animals had returned to 1 g, and probably represent stages of recovery from microgravity exposure, which in itself is an interesting question.

  9. Precise localization of multiple epiphyseal dysplasia and pseudoachondroplasia mutations by genetic and physical mapping of chromosome 19

    SciTech Connect

    Knowlton, R.G.; Cekleniak, J.A.; Cohn, D.H.

    1994-09-01

    Multiple epiphyseal dysplasia (EDM1), a dominantly inherited chondrodysplasia resulting in peripheral joint deformities and premature osteoarthritis, and pseudoachondroplasia (PSACH), a more severe disorder associated with short-limbed dwarfism, have recently been mapped to the pericentromeric region of chromosome 19. Chondrocytes from some PSACH patients accumulate lamellar deposits in the endoplasmic reticulum that are immunologically cross-reactive with aggrecan. However, neither aggrecan nor any known candidate gene maps to the EDM1/PSACH region of chromosome 19. Genetic linkage mapping in two lage families had placed the disease locus between D19S215 (19p12) and D19S212 (19p13.1), an interval of about 3.5 Mb. With at least five potentially informative cross-overs within this interval, recombination mapping at greater resolution was undertaken. From cosmids assigned to the region by fluorescence in situ hybridization and contig assembly, dinucleotide repeat tracts were identified for use as polymorphic genetic markers. Linkage data from three new dinucleotide repeat markers from cosmids mapped between D19S212 and D19S215 limit the EDM1/PSACH locus to an interval spanning approximately 2 Mb.

  10. Correlation between primary stability and bone healing of surface treated titanium implants in the femoral epiphyses of rabbits.

    PubMed

    Rozé, Julie; Hoornaert, Alain; Layrolle, Pierre

    2014-08-01

    The aim of this study was to analyse the stability and osseointegration of surface treated titanium implants in rabbit femurs. The implants were either grit-blasted and acid-etched (BE Group), calcium phosphate (CaP) coated by using the electrodeposition technique, or had bioactive molecules incorporated into the CaP coatings: either cyclic adenosine monophosphate (cAMP) or dexamethasone (Dex). Twenty four cylindrical titanium implants (n = 6/group) were inserted bilaterally into the femoral epiphyses of New Zealand White, female, adult rabbits for 4 weeks. Implant stability was measured by resonance frequency analysis (RFA) the day of implantation and 4 weeks later, and correlated to histomorphometric parameters, bone implant contact (BIC) and bone growth around the implants (BS/TS 0.5 mm). The BIC values for the four groups were not significantly different. That said, histology indicated that the CaP coatings improved bone growth around the implants. The incorporation of bioactive molecules (cAMP and Dex) into the CaP coatings did not improve bone growth compared to the BE group. Implant stability quotients (ISQ) increased in each group after 4 weeks of healing but were not significantly different between the groups. A good correlation was observed between ISQ and BS/TS 0.5 mm indicating that RFA is a non-invasive method that can be used to assess the osseointegration of implants. In conclusion, the CaP coating enhanced bone formation around the implants, which was correlated to stability measured by resonance frequency analysis. Furthers studies need to be conducted in order to explore the benefits of incorporating bioactive molecules into the coatings for peri-implant bone healing. PMID:24818874

  11. Clinical use of deslorelin implants for the long-term contraception in prepubertal bitches: effects on epiphyseal closure, body development, and time to puberty.

    PubMed

    Kaya, D; Schäfer-Somi, S; Kurt, B; Kuru, M; Kaya, S; Kaçar, C; Aksoy, Ö; Aslan, S

    2015-04-15

    Long-acting GnRH agonists have been used both for canine estrus induction and prevention. The objective of the study was to investigate the use of a deslorelin implant as a long-term and reversible contraceptive in prepubertal bitches with special regard to the time of epiphyseal closure. Thirteen healthy, crossbreed, medium-sized prepubertal female dogs were used in this study. An implant containing 9.4 mg (G1, n = 5) and 4.7 mg (G2, n = 4) deslorelin acetate (Suprelorin) or a placebo (sodium chloride 0.9%; G3, n = 4) was inserted subcutaneously in the interscapular region. Estrus was monitored once daily by physical and sexual behavioral changes. Body development, vaginal cytology, and serum progesterone and estradiol 17β concentration were monitored weekly for the first 5 weeks, and then every 3 weeks throughout the treatment period. Radiographic examinations were performed monthly to determine the epiphyseal closure. Half of the deslorelin-treated bitches (G1: n = 2 and G2: n = 2) came into estrus during the 83-week observation period. All animals in the control group showed estrus between the 39th and 64th weeks of observation. Time to puberty averaged 82.7 ± 8.9 and 61.9 ± 9.7 weeks in the deslorelin-treated (G1 and G2) and the control bitches, respectively (P < 0.02). Both deslorelin implants (9.4 and 4.7 mg) can be used efficiently for the long-term prevention of estrus in prepubertal bitches; however, epiphyseal closure is clearly delayed which was without any clinical effect in the present study. PMID:25619808

  12. Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene: double-layer patella as a reliable sign.

    PubMed

    Mäkitie, Outi; Savarirayan, Ravi; Bonafé, Luisa; Robertson, Stephen; Susic, Miki; Superti-Furga, Andrea; Cole, William G

    2003-10-15

    Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene result in a family of skeletal dysplasias, which comprise lethal (achondrogenesis type 1B and atelosteogenesis type 2) and non-lethal conditions (diastrophic dysplasia and recessive multiple epiphyseal dysplasia (rMED)). The most frequent mutation is R279W, which in a homozygous state results in rMED with bilateral clubfoot, MED, and "double layered" patella. We describe three patients with rMED caused by a previously unreported homozygous mutation in the DTDST gene. The three patients (from two families) were born to healthy, non-consanguineous parents. All developed signs of hip dysplasia in early childhood and two had episodes of recurrent patella dislocation. Two underwent bilateral total hip replacements at ages 13 and 14 years. The feet, external ears, and palate were normal. Stature was normal in all cases. Radiographs showed dysplastic femoral heads, mild generalized epiphyseal dysplasia, abnormal patella ossification, and normal hands and feet. Direct sequence analysis of genomic DNA demonstrated a homozygous 1984T > A (C653S) change in the DTDST gene in all patients. The clinically normal parents were heterozygous for the change. This is the first description of a homozygous C653S mutation of the DTDST gene. Hip dysplasia and patella hypermobility dominates the otherwise mild phenotype. These patients further expand the range of causative mutations in the DTD skeletal dysplasia family. PMID:12966518

  13. Cellular localization and expression of insulin-like growth factors (IGFs) and IGF binding proteins within the epiphyseal growth plate of the ovine fetus: possible functional implications.

    PubMed

    de los Rios, P; Hill, D J

    1999-04-01

    The insulin-like growth factors (IGFs) are important in the regulation of normal fetal musculoskeletal growth and development, and their actions have been shown to be modulated by IGF binding proteins (IGFBPs). Because the anatomical distribution of IGFBPs is likely to dictate IGF bioavailability, we determined the cellular distribution and expression of IGF-I, IGF-II, and IGFBP-1 to IGFBP-6 in epiphyseal growth plates of the fetal sheep, using immunocytochemistry and in situ hybridization. Little mRNA for IGF-I was detectable within the growth plates, but mRNA for IGF-II was abundant in germinal and proliferative chondrocytes, although absent from some differentiating chondrocytes and hypertrophic cells. Immunohistochemistry for IGF-I and IGF-II showed a presence of both peptides in all chondrocyte zones, including hypertrophic cells. Immunoreactive IGFBP-2 to -5 were localized within the germinal and proliferative zones of chondrocytes, but little immunoreactivity was present within the columns of differentiating cells. IGFBP immunoreactivity again appeared in hypertrophic chondrocytes. IGFBP mRNA in chondrocytes of the epiphyseal growth plate was below the detectable limit of in situ hybridization. However, low levels of mRNAs for IGFBP-2 to -6 were detected by the reverse transcriptase polymerase chain reaction. A co-localization of IGFBPs with IGF peptides in intact cartilage suggests that they may regulate IGF bioavailability and action locally. To test this hypothesis, monolayer cultures of chondrocytes were established from the proliferative zone of the growth plate, and were found to release immunoreactive IGF-II and to express mRNAs encoding IGFBP-2 to -6. Exogenous IGFBP-3, -4, and -5 had an inhibitory action on IGF-II-dependent DNA synthesis. IGFBP-2 had a biphasic effect, potentiating IGF-II action at low concentrations but inhibiting DNA synthesis at equimolar or greater concentrations relative to IGF-II. Long R3 IGF-I, which has a reduced binding

  14. Novel DDR2 mutation identified by whole exome sequencing in a Moroccan patient with spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type.

    PubMed

    Mansouri, Maria; Kayserili, Hülya; Elalaoui, Siham Chafai; Nishimura, Gen; Iida, Aritoshi; Lyahyai, Jaber; Miyake, Noriko; Matsumoto, Naomichi; Sefiani, Abdelaziz; Ikegawa, Shiro

    2016-02-01

    Spondylo-meta-epiphyseal dysplasia (SMED), short limb-abnormal calcification type (SMED, SL-AC), is a very rare autosomal recessive disorder with various skeletal changes characterized by premature calcification leading to severe disproportionate short stature. Twenty-two patients have been reported until now, but only five mutations (four missense and one splice-site) in the conserved sequence encoding the tyrosine kinase domain of the DDR2 gene has been identified. We report here a novel DDR2 missense mutation, c.370C > T (p.Arg124Trp) in a Moroccan girl with SMED, SL-AC, identified by whole exome sequencing. Our study has expanded the mutational spectrum of this rare disease and it has shown that exome sequencing is a powerful and cost-effective tool for the diagnosis of clinically heterogeneous disorders such as SMED. PMID:26463668

  15. Effects of Melatonin and Epiphyseal Proteins on Fluoride-Induced Adverse Changes in Antioxidant Status of Heart, Liver, and Kidney of Rats

    PubMed Central

    Bharti, Vijay K.; Srivastava, R. S.; Kumar, H.; Bag, S.; Majumdar, A. C.; Singh, G.; Pandi-Perumal, S. R.; Brown, Gregory M.

    2014-01-01

    Several experimental and clinical reports indicated the oxidative stress-mediated adverse changes in vital organs of human and animal in fluoride (F) toxicity. Therefore, the present study was undertaken to evaluate the therapeutic effect of buffalo (Bubalus bubalis) epiphyseal (pineal) proteins (BEP) and melatonin (MEL) against F-induced oxidative stress in heart, liver, and kidney of experimental adult female rats. To accomplish this experimental objective, twenty-four adult female Wistar rats (123–143 g body weights) were divided into four groups, namely, control, F, F + BEP, and F + MEL and were administered sodium fluoride (NaF, 150 ppm elemental F in drinking water), MEL (10 mg/kg BW, i.p.), and BEP (100 µg/kg BW, i.p.) for 28 days. There were significantly (P < 0.05) high levels of lipid peroxidation and catalase and low levels of reduced glutathione, superoxide dismutase, glutathione reductase, and glutathione peroxidase in cardiac, hepatic, and renal tissues of F-treated rats. Administration of BEP and MEL in F-treated rats, however, significantly (P < 0.05) attenuated these adverse changes in all the target components of antioxidant defense system of cardiac, hepatic, and renal tissues. The present data suggest that F can induce oxidative stress in liver, heart, and kidney of female rats which may be a mechanism in F toxicity and these adverse effects can be ameliorated by buffalo (Bubalus bubalis) epiphyseal proteins and melatonin by upregulation of antioxidant defense system of heart, liver, and kidney of rats. PMID:24790596

  16. Effects of tiludronate on bone mass, structure, and turnover at the epiphyseal, primary, and secondary spongiosa in the proximal tibia of growing rats after sciatic neurectomy.

    PubMed

    Murakami, H; Nakamura, T; Tsurukami, H; Abe, M; Barbier, A; Suzuki, K

    1994-09-01

    To evaluate the effects of tiludronate on the mass, structure, and turnover of cancellous bone regions in immobilized rat tibiae, we performed a 4 week dosing experiment. The right hindlimbs of 84 Sprague-Dawley rats (5 weeks old) wee neurectomized or sham operated. Animals were assigned to seven groups (n = 12 each); group 1 was sham operated, and groups 2-7 were neurectomized. Groups 1 and 2 were given vehicle only (distilled water), and groups 3, 4, and 5 were given tiludronate orally at doses of 25, 50, and 100 mg/kg body weight (BW)/day, respectively, throughout the experimental period. Group 6 was given 100 mg/kg BW/day of the agent for the first 2 weeks only, and group 7 received vehicle only for the first 2 weeks and then 100 mg/kg BW/day of the agent for the last 2 weeks. After tetracycline labeling was performed, the right tibiae were removed from the animals and processed to yield undecalcified sections. Histomorphometry was performed in the epiphyseal, primary, and secondary spongiosa of the proximal tibia. In group 2, trabecular bone volume (BV/TV) and trabecular number (Tb.N) were significantly decreased in the primary and secondary spongiosae, but this did not occur in the epiphyseal spongiosa. Osteoid surface (OS/BS) was decreased and osteoclast surface (Oc.S/BS) was increased in the secondary spongiosa. Tiludronate increased BV/TV and Tb.N in the primary spongiosa by reducing the values for the parameters of osteoclast surface (Oc.S/BS) and osteoclast number (Oc.N/BS). Osteoid surface in this region was not decreased by the agent. In groups 4 and 5, tiludronate prevented bone loss in the secondary spongiosa by reducing both OS/BS and Oc.S/BS. In group 6, BV/TV in the primary spongiosa was maintained at the level of group 1, but Oc.S/BS and Oc.N/BS were elevated. In the secondary spongiosa, bone mass was preserved and the reduction in these parameters was maintained. In group 7, however, BV/TV was increased in the primary spongiosa as a result of a

  17. A compound heterozygote of novel and recurrent DTDST mutations results in a novel intermediate phenotype of Desbuquois dysplasia, diastrophic dysplasia, and recessive form of multiple epiphyseal dysplasia.

    PubMed

    Miyake, Atsushi; Nishimura, Gen; Futami, Toru; Ohashi, Hirofumi; Chiba, Kazuhiro; Toyama, Yoshiaki; Furuichi, Tatsuya; Ikegawa, Shiro

    2008-01-01

    Diastrophic dysplasia sulfate transporter (DTDST) is required for synthesis of sulfated proteoglycans in cartilage, and its loss-of-function mutations result in recessively inherited chondrodysplasias. The 40 or so DTDST mutations reported to date cause a group of disorders termed the diastrophic dysplasia (DTD) group. The group ranges from the mildest recessive form of multiple epiphyseal dysplasia (r-MED) through the most common DTD to perinatally lethal atelosteogenesis type II and achondrogenesis 1B. Furthermore, the relationship between DTDST mutations, their sulfate transport function, and disease phenotypes has been described. Here we report a girl with DTDST mutations: a compound heterozygote of a novel p.T266I mutation and a recurrent p.DeltaV340 mutation commonly found in severe phenotypes of the DTD group. In infancy, the girl presented with skeletal manifestations reminiscent of Desbuquois dysplasia, another recessively inherited chondrodysplasia, the mutations of which have never been identified. Her phenotype evolved with age into an intermediate phenotype between r-MED and DTD. Considering her clinical phenotypes and known phenotypes of p.DeltaV340, p.T266I was predicted to be responsible for mild phenotypes of the DTD group. Our results further extend the phenotypic spectrum of DTDST mutations, adding Desbuquois dysplasia to the list of differential diagnosis of the DTD group. PMID:18553123

  18. Visualization of sulfur-containing components associated with proliferating chondrocytes from rat epiphyseal growth plate cartilage: Possible proteoglycan and collagen co-migration

    SciTech Connect

    Landis, W.J.; Hodgens, K.J. )

    1990-02-01

    Electron microscopy of epiphyseal growth plate cartilage from normal 4-5-week-old rats has revealed extensive fibrillar aggregates and globules in the pericellular spaces of proliferating chondrocytes. These cells contained small globules and diffusely coiled, fine filaments located within large, membrane-invested vacuoles. All such structures were observed after a variety of different tissue fixation regimes, including glutaraldehyde, osmium tetroxide, and potassium pyroantimonate. The fibrillar aggregates and globules were often overlapping and intermeshed and extended to 0.5 micron in length from their point of origin at cell membranes. Vacuoles were usually found at the periphery of cells, and some, by membrane fusion with the cell envelope, appeared contiguous with extracellular spaces wherein their contents could be discharged. Fine filaments and globules were occasionally observed in the Golgi complex and cisternae of endoplasmic reticulum of the chondrocytes. Further characterization of the cellular and pericellular components by electron microscopic radioautography, electron probe microanalysis, and electron spectroscopic imaging indicated the presence of sulfur, a result suggesting these aggregates, filaments, and globules in part represent proteoglycans in various stages of synthesis, secretion, and assembly. Additional radioautography utilizing 3H-proline implied that filament bundles are also composed of collagen, a result posing the possibility that this protein and the putative proteoglycans may co-migrate both intracellularly and within pericellular matrices. In extracellular matrices adjacent to cell lacunae, the fibrillar aggregates appeared in close association with typical collagen type II fibrils, an observation providing evidence for proteoglycan-collagen network formation in this region of the rat epiphysis.

  19. A new formula for assessing skeletal age in growing infants and children by measuring carpals and epiphyses of radio and ulna.

    PubMed

    De Luca, Stefano; Mangiulli, Tatiana; Merelli, Vera; Conforti, Federica; Velandia Palacio, Luz Andrea; Agostini, Susanna; Spinas, Enrico; Cameriere, Roberto

    2016-04-01

    The aim of this study is to develop a specific formula for the purpose of assessing skeletal age in a sample of Italian growing infants and children by measuring carpals and epiphyses of radio and ulna. A sample of 332 X-rays of left hand-wrist bones (130 boys and 202 girls), aged between 1 and 16 years, was analyzed retrospectively. Analysis of covariance (ANCOVA) was applied to study how sex affects the growth of the ratio Bo/Ca in the boys and girls groups. The regression model, describing age as a linear function of sex and the Bo/Ca ratio for the new Italian sample, yielded the following formula: Age = -1.7702 + 1.0088 g + 14.8166 (Bo/Ca). This model explained 83.5% of total variance (R(2) = 0.835). The median of the absolute values of residuals (observed age minus predicted age) was -0.38, with a quartile deviation of 2.01 and a standard error of estimate of 1.54. A second sample test of 204 Italian children (108 girls and 96 boys), aged between 1 and 16 years, was used to evaluate the accuracy of the specific regression model. A sample paired t-test was used to analyze the mean differences between the skeletal and chronological age. The mean error for girls is 0.00 and the estimated age is slightly underestimated in boys with a mean error of -0.30 years. The standard deviations are 0.70 years for girls and 0.78 years for boys. The obtained results indicate that there is a high relationship between estimated and chronological ages. PMID:26874435

  20. Local Morphological Response of the Distal Femoral Articular–Epiphyseal Cartilage Complex of Young Foals to Surgical Stab Incision and Potential Relevance to Cartilage Injury and Repair in Children

    PubMed Central

    Hendrickson, Eli H.S.; Ekman, Stina; Carlson, Cathy S.; Dolvik, Nils I.

    2013-01-01

    Objective: Describe the local morphological response of the articular–epiphyseal cartilage complex to surgical stab incision in the distal femur of foals, with emphasis on the relationship between growth cartilage injury, enchondral ossification, and repair. Design: Nine foals were induced into general anesthesia at the age of 13 to 15 days. Four full-thickness stab incision defects were created in the cartilage on the lateral aspect of the lateral trochlear ridge of the left distal femur. Follow-up examination was carried out from 1 to 49 days postoperatively, including examination of intact bones, sawed slabs, and histological sections. Results: Incision defects filled with cells displaying fibroblast-, chondrocyte-, and osteoblast-like characteristics, potentially validating the rationale behind the drilling of stable juvenile osteochondritis dissecans lesions in children. Incisions induced necrosis within the cartilage on the margins at all depths of the defects. Sharp dissection may therefore be contraindicated in cartilage repair in young individuals. Incisions caused a focal delay in enchondral ossification in 2 foals, apparently related to the orientation of the incision defect relative to the direction of ossification. Defects became progressively surrounded by subchondral bone, in which granulation tissue containing clasts and foci of osteoblast-like cells was observed. Continued enchondral ossification was therefore likely to result in healing of uncomplicated defects to morphologically normal bone. Conclusions: Epiphyseal growth cartilage injury had the potential to exert a negative effect on enchondral ossification. Enchondral ossification exerted a beneficial effect on repair. This relationship warrants consideration in future studies of cartilage injury and repair within the articular–epiphyseal cartilage complex of all species. PMID:26069670

  1. Forensic age estimation via 3-T magnetic resonance imaging of ossification of the proximal tibial and distal femoral epiphyses: Use of a T2-weighted fast spin-echo technique.

    PubMed

    Ekizoglu, Oguzhan; Hocaoglu, Elif; Inci, Ercan; Can, Ismail Ozgur; Aksoy, Sema; Kazimoglu, Cemal

    2016-03-01

    Radiation exposure during forensic age estimation is associated with ethical implications. It is important to prevent repetitive radiation exposure when conducting advanced ultrasonography (USG) and magnetic resonance imaging (MRI). The purpose of this study was to investigate the utility of 3.0-T MRI in determining the degree of ossification of the distal femoral and proximal tibial epiphyses in a group of Turkish population. We retrospectively evaluated coronal T2-weighted and turbo spin-echo sequences taken upon MRI of 503 patients (305 males, 198 females; age 10-30 years) using a five-stage method. Intra- and interobserver variations were very low. (Intraobserver reliability was κ=0.919 for the distal femoral epiphysis and κ=0.961 for the proximal tibial epiphysis, and interobserver reliability was κ=0.836 for the distal femoral epiphysis and κ=0.885 for the proximal tibial epiphysis.) Spearman's rank correlation analysis indicated a significant positive relationship between age and the extent of ossification of the distal femoral and proximal tibial epiphyses (p<0.001). Comparison of male and female data revealed significant between-gender differences in the ages at first attainment of stages 2, 3, and 4 ossifications of the distal femoral epiphysis and stage 1 and 4 ossifications of the proximal tibial epiphysis (p<0.05). The earliest ages at which ossification of stages 3, 4, and 5 was evident in the distal femoral epiphysis were 14, 17, and 22 years in males and 13, 16, and 21 years in females, respectively. Proximal tibial epiphysis of stages 3, 4, and 5 ossification was first noted at ages 14, 17, and 18 years in males and 13, 15, and 16 years in females, respectively. MRI of the distal femoral and proximal tibial epiphyses is an alternative, noninvasive, and reliable technique to estimate age. PMID:26797254

  2. An unfolded protein response is the initial cellular response to the expression of mutant matrilin-3 in a mouse model of multiple epiphyseal dysplasia

    PubMed Central

    Nundlall, Seema; Rajpar, M. Helen; Bell, Peter A.; Clowes, Christopher; Zeeff, Leo A. H.; Gardner, Benjamin; Thornton, David J.; Boot-Handford, Raymond P.

    2010-01-01

    Multiple epiphyseal dysplasia (MED) can result from mutations in matrilin-3, a structural protein of the cartilage extracellular matrix. We have previously shown that in a mouse model of MED the tibia growth plates were normal at birth but developed a progressive dysplasia characterised by the intracellular retention of mutant matrilin-3 and abnormal chondrocyte morphology. By 3 weeks of age, mutant mice displayed a significant decrease in chondrocyte proliferation and dysregulated apoptosis. The aim of this current study was to identify the initial post-natal stages of the disease. We confirmed that the disease phenotype is seen in rib and xiphoid cartilage and, like tibia growth plate cartilage is characterised by the intracellular retention of mutant matrilin-3. Gene expression profiling showed a significant activation of classical unfolded protein response (UPR) genes in mutant chondrocytes at 5 days of age, which was still maintained by 21 days of age. Interestingly, we also noted the upregulation of arginine-rich, mutated in early stage of tumours (ARMET) and cysteine-rich with EGF-like domain protein 2 (CRELD2) are two genes that have only recently been implicated in the UPR. This endoplasmic reticulum (ER) stress and UPR did not lead to increased chondrocyte apoptosis in mutant cartilage by 5 days of age. In an attempt to alleviate ER stress, mutant mice were fed with a chemical chaperone, 4-sodium phenylbutyrate (SPB). SPB at the dosage used had no effect on chaperone expression at 5 days of age but modestly decreased levels of chaperone proteins at 3 weeks. However, this did not lead to increased secretion of mutant matrilin-3 and in the long term did not improve the disease phenotype. We performed similar studies with a mouse model of Schmid metaphyseal chondrodysplasia, but again this treatment did not improve the phenotype. Electronic supplementary material The online version of this article (doi:10.1007/s12192-010-0193-y) contains supplementary

  3. A novel mutation in DDR2 causing spondylo-meta-epiphyseal dysplasia with short limbs and abnormal calcifications (SMED-SL) results in defective intra-cellular trafficking

    PubMed Central

    2014-01-01

    Background The rare autosomal genetic disorder, Spondylo-meta-epiphyseal dysplasia with short limbs and abnormal calcifications (SMED-SL), is reported to be caused by missense or splice site mutations in the human discoidin domain receptor 2 (DDR2) gene. Previously our group has established that trafficking defects and loss of ligand binding are the underlying cellular mechanisms of several SMED-SL causing mutations. Here we report the clinical characteristics of two siblings of consanguineous marriage with suspected SMED-SL and identification of a novel disease-causing mutation in the DDR2 gene. Methods Clinical evaluation and radiography were performed to evaluate the patients. All the coding exons and splice sites of the DDR2 gene were sequenced by Sanger sequencing. Subcellular localization of the mutated DDR2 protein was determined by confocal microscopy, deglycosylation assay and Western blotting. DDR2 activity was measured by collagen activation and Western analysis. Results In addition to the typical features of SMED-SL, one of the patients has an eye phenotype including visual impairment due to optic atrophy. DNA sequencing revealed a novel homozygous dinucleotide deletion mutation (c.2468_2469delCT) on exon 18 of the DDR2 gene in both patients. The mutation resulted in a frameshift leading to an amino acid change at position S823 and a predicted premature termination of translation (p.S823Cfs*2). Subcellular localization of the mutant protein was analyzed in mammalian cell lines, and it was found to be largely retained in the endoplasmic reticulum (ER), which was further supported by its N-glycosylation profile. In keeping with its cellular mis-localization, the mutant protein was found to be deficient in collagen-induced receptor activation, suggesting protein trafficking defects as the major cellular mechanism underlying the loss of DDR2 function in our patients. Conclusions Our results indicate that the novel mutation results in defective trafficking

  4. Acute epiphyseal osteomyelitis in children

    SciTech Connect

    Rosenbaum, D.M.; Blumhagen, J.D.

    1985-07-01

    Nine children over 20 months of age had acute osteomyelitis of the epiphysis of a long bone. The clinical features varied, but all of the patients had pain at the infected site and an elevated erythrocyte sedimentation rate. The distal femur was involved in seven cases, the proximal tibian in two, and the proximal humerus in one. In two patients there was a contiguous metaphyseal lesion, while the other seven patients (eight sites) had lesions limited to the epiphysis. Bone scintigraphy clearly identified the infected sites in all seven patients in whom it was performed, and allowed an early diagnosis in four cases. Radiographs showed a lytic lesion of the epiphysis that corresponded to the scintigraphic findings in all cases. The epiphysis of the child should be recognized as another site of hematogenous osteomyelitis.

  5. Contact Stress and Kinematic Analysis of All-Epiphyseal and Over-the-Top Pediatric Reconstruction Techniques for the Anterior Cruciate Ligament

    PubMed Central

    McCarthy, Moira M.; Tucker, Scott; Nguyen, Joseph T.; Green, Daniel W.; Imhauser, Carl W.; Cordasco, Frank A.

    2014-01-01

    Background Anterior cruciate ligament (ACL) injuries are an increasingly recognized problem in the pediatric population. Unfortunately, outcomes with conservative treatment are extremely poor. Furthermore, adult reconstruction techniques may be inappropriate to treat skeletally immature patients due to the risk of physeal complications. “Physeal-sparing” reconstruction techniques exist but their ability to restore knee stability and contact mechanics is not well understood. Purpose (1) To assess the ability of the all-epiphyseal (AE) and over-the-top (OT) reconstructions to restore knee kinematics; (2) to assess whether these reconstructions decrease the high posterior contact stresses seen with ACL deficiency; (3) to determine whether the AE or OT produce abnormal tibiofemoral contact stresses. Hypothesis The AE reconstruction will restore contact mechanics and kinematics similarly to that of the ACL intact knee. Methods Ten fresh-frozen human cadaveric knees were tested using a robotic manipulator. Tibiofemoral motions were recorded with the ACL intact, after sectioning the ACL, and after both reconstructions in each of the 10 specimens. The AE utilized an all-inside technique with tunnels exclusively within the epiphysis and fixed with suspensory cortical fixation devices. The OT had a central and vertical tibial tunnel with an over-the-top femur position and was fixed with staples and posts on both ends. Anterior stability was assessed with 134N anterior force at 0, 15, 30, 60, and 90° of knee flexion. Rotational stability was assessed with combined 8 Nm and 4 Nm of abduction and internal rotation, respectively, at 5, 15, and 30° of knee flexion. Results Both reconstruction techniques offloaded the posterior aspect of the tibial plateau compared to the ACL deficient knee in response to both anterior loads and combined moments as demonstrated by reduced contact stresses in this region at all flexion angles. Compared to the ACL intact condition, both the AE

  6. Measurements of developing teeth, and carpals and epiphyses of the ulna and radius for assessing new cut-offs at the age thresholds of 10, 11, 12, 13 and 14 years.

    PubMed

    Cameriere, R; De Luca, S; Cingolani, M; Ferrante, L

    2015-08-01

    The minimum age of criminal responsibility is the youngest age at which children may be held liable for infringements of penal laws. New cut-offs at the age thresholds of 10, 11, 12, 13 and 14 years were determined by applying three different methods: measurement of open apices in tooth roots (T); the ratio between the total area of carpal bones and epiphyses of the ulna and radius (HW); and the combined method (THW). The sample consisted of 291 Italian children (152 boys, 139 girls), aged between 5 and 15 years. The sensitivity and specificity were established. As regards THW, specificity reached the maximum of 95% in boys aged 10, and the minimum of 87% in boys aged 11. The best score of the Positive Predictive Value (PPV) was obtained in boys at 10 years with the THW method and the worst in girls of 12 with the HW method. PMID:26165659

  7. Pseudoachondroplasia and Multiple Epiphyseal Dysplasia: A 7-Year Comprehensive Analysis of the Known Disease Genes Identify Novel and Recurrent Mutations and Provides an Accurate Assessment of Their Relative Contribution

    PubMed Central

    Jackson, Gail C; Mittaz-Crettol, Laureane; Taylor, Jacqueline A; Mortier, Geert R; Spranger, Juergen; Zabel, Bernhard; Le Merrer, Martine; Cormier-Daire, Valerie; Hall, Christine M; Offiah, Amaka; Wright, Michael J; Savarirayan, Ravi; Nishimura, Gen; Ramsden, Simon C; Elles, Rob; Bonafe, Luisa; Superti-Furga, Andrea; Unger, Sheila; Zankl, Andreas; Briggs, Michael D

    2012-01-01

    Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are relatively common skeletal dysplasias resulting in short-limbed dwarfism, joint pain, and stiffness. PSACH and the largest proportion of autosomal dominant MED (AD-MED) results from mutations in cartilage oligomeric matrix protein (COMP); however, AD-MED is genetically heterogenous and can also result from mutations in matrilin-3 (MATN3) and type IX collagen (COL9A1, COL9A2, and COL9A3). In contrast, autosomal recessive MED (rMED) appears to result exclusively from mutations in sulphate transporter solute carrier family 26 (SLC26A2). The diagnosis of PSACH and MED can be difficult for the nonexpert due to various complications and similarities with other related diseases and often mutation analysis is requested to either confirm or exclude the diagnosis. Since 2003, the European Skeletal Dysplasia Network (ESDN) has used an on-line review system to efficiently diagnose cases referred to the network prior to mutation analysis. In this study, we present the molecular findings in 130 patients referred to ESDN, which includes the identification of novel and recurrent mutations in over 100 patients. Furthermore, this study provides the first indication of the relative contribution of each gene and confirms that they account for the majority of PSACH and MED. Hum Mutat 33:144–157, 2012. © 2011 Wiley Periodicals, Inc. PMID:21922596

  8. Intermittent internal fixation with a locking plate to preserve epiphyseal growth function during limb-salvage surgery in a child with osteosarcoma of the distal femur: a case report.

    PubMed

    Mei, Jiong; Ni, Ming; Jia, Guang-Yao; Chen, Yan-Xi; Zhu, Xiao-Zhong

    2015-05-01

    Limb shortening is a problem associated with surgery for osteosarcoma of the lower extremity in adolescents, as the tumors frequently occur near the epiphysis. Herein we report the use of a less invasive stabilization system (LISS) and an intermittent fixation method to preserve the growth function of epiphysis in an 11-year-old patient with an osteosarcoma of the distal femur.The 11-year-old male presented with left knee enlargement and pain for 2 weeks, and magnetic resonance imaging (MRI) and biopsy were consistent with osteosarcoma of the left distal femur. After preoperative chemotherapy, en bloc tumor resection was performed with margins based on MRI findings preserving the epiphyseal growth plate, the tumor cavity was filled with inactivated bone and bone cement, and a LISS was used to stabilize the femur. Aggressive postoperative chemotherapy was given. Approximately 105 weeks after surgery radiography showed that the distal end of the plate had moved superior to the epiphysis along with bone growth. Locking screws were placed in the distal part of the LISS plate to stabilize the re-implanted bone, and external fixation was not needed.The patient was able to walk with the crutches 1 week postoperatively, and bear weight on the extremity 6 weeks postoperatively. At 6 years after surgery, the patient's height had increased 52 cm, shortening of the affected limb was only 1 cm, and the circumference of the affected limb was 2 cm smaller than that of the contralateral limb. There was no significant discomfort in the affected limb, and there was no gait abnormality. The patient could jump and run, and could participate in sports including basketball and badminton to the same degree as his peers.In summary, the novel method of bone reconstruction and fixation provided good results in a child with an osteosarcoma of the distal femur. This fixation method preserves the osteogenic function of the epiphysis and restored bone integrity simultaneously, and

  9. Genetics Home Reference: multiple epiphyseal dysplasia

    MedlinePlus

    ... instructions for making a protein called type IX collagen. Collagens are a family of proteins that strengthen and ... mutations in these genes may cause type IX collagen to accumulate inside the cell or interact abnormally ...

  10. Spaceflight and age affect tibial epiphyseal growth plate histomorphometry

    NASA Technical Reports Server (NTRS)

    Montufar-Solis, Dina; Duke, Pauline J.; Durnova, G.

    1992-01-01

    Growth plate histomorphometry of rats flown aboard the Soviet biosatellite Cosmos 2044, a 14-day spaceflight, was compared with that of control groups. In growth plates of flight animals, there was a significant increase in cell number per column and height of the proliferative zone and a reduction in height and cell number in the hypertrophy/calcification zone. No significant differences were found in matrix organization at the ultrastructural level of flight animals, indicating that although spacefligfht continues to affect bone growth of 15-wk-old rats, extracellular matrix is not altered in the same manner as seen previously in younger animals. All groups showed growth plate characteristics attributed to aging: lack of calcification zone, reduced hypertrophy zone, and unraveling of collagen fibrils. Tail-suspended controls did not differ from other controls in any of the parameters measured. The results suggest that growth plates of older rats are less responsive to unloading by spaceflight or suspension than those of younger rats and provide new evidence about the modifying effect of spaceflight on the growth plate.

  11. Displaced epiphyseal plate of the terminal phalanx in a child.

    PubMed

    Michelinakis, E; Vourexaki, H

    1980-02-01

    A case of mallet finger in a child is described. The epiphysis of the terminal phalanx was displaced dorsally with the extensor tendon attached to it, and was first diagnosed two weeks after injury. The treatment was by open reduction. Radiograph three years later showed that a satisfactory position of the epiphysis and normal growth of the terminal phalanx had occurred. PMID:7364328

  12. Patterns of proteoglycan degradation by a neutral protease from human growth-plate epiphyseal cartilage

    SciTech Connect

    Ehrlich, M.G.; Armstrong, A.L.; Neuman, R.G.; Davis, M.W.; Mankin, H.J.

    1982-12-01

    The hypothesis is widely held that proteolytic degradation of proteoglycans in the lower hypertrophic zone of the growth plate may be involved in the initiation of mineralization in the zone of provisional calcification. However, a neutral protease that is responsible for the degradation of proteoglycans in the growth plate has not been identified, isolated, and characterized. In the work reported here, neutral protease activity in the growth plate is demonstrated for the first time, and some of the properties of the enzyme are described. Proteoglycans subunits were prepared from bovine nasal cartilage and calf costal cartilage by equilibrium density-gradient centrifugation under dissociative conditions. The proteoglycan subunits were labeled with /sup 14/C-formaldehyde. Homogenates from human growth plates were examined for neutral protease activity using the proteoglycan subunits as substrates. Following incubation of the proteoglycan subunits with growth-plate homogenates at pH 5.3 and at pH 7.5 in the presence and absence of ten-millimolar magnesium chloride and calcium chloride, the digestion products were examined by gel chromatography on Sepharose-2B and 6B columns. Column eluants containing proteoglycan-subunit degradation products were monitored for uronic acid, hexose, and radio-activity. Maximum extensive degradation of proteoglycan subunits occurred at pH 7.5 in the presence of ten-millimolar magnesium chloride and calcium chloride.

  13. Histomorphometric and electron microscopic analyses of tibial epiphyseal plates from Cosmos 1887 rats

    NASA Technical Reports Server (NTRS)

    Duke, P. J.; Durnova, G.; Montufar-Solis, D.

    1990-01-01

    Previous studies have shown that the changes seen in the bones of growing rats exposed to microgravity are due in part to changes that occur in the growth plate during spaceflight. In this study, growth plates of rats flown aboard Cosmos 1887 (12.5-day flight plus 53.5-h recovery at 1 g) were analyzed using light and electron microscopy and computerized planimetry. The proliferative zone of flight animals was found to be significantly (P less than or equal to 0.01) larger than that of controls, while the reserve and hypertrophic/calcification zones were significantly reduced. Flight animals also had more cells per column in the proliferative zone than did controls and less in the hypertrophic/calcification region. The total number of cells, however, was significantly greater in flight animals. No difference was found in perimeter or in shape factor, but area was significantly less in flight animals. Electron microscopy showed that collagen fibrils in flight animals were wider than in controls. Since the time required for a cell to cycle through the growth plate is 2-3 days at 1 g, the results reported here represent both the effects of exposure to microgravity and the initial stages of recovery from that exposure.

  14. The locomotion of Babakotia radofilai inferred from epiphyseal and diaphyseal morphology of the humerus and femur.

    PubMed

    Marchi, Damiano; Ruff, Christopher B; Capobianco, Alessio; Rafferty, Katherine L; Habib, Michael B; Patel, Biren A

    2016-09-01

    Palaeopropithecids, or "sloth lemurs," are a diverse clade of large-bodied Malagasy subfossil primates characterized by their inferred suspensory positional behavior. The most recently discovered genus of the palaeopropithecids is Babakotia, and it has been described as more arboreal than Mesopropithecus, but less than Palaeopropithecus. In this article, the within-bone and between-bones articular and cross-sectional diaphyseal proportions of the humerus and femur of Babakotia were compared to extant lemurs, Mesopropithecus and Palaeopropithecus in order to further understand its arboreal adaptations. Additionally, a sample of apes and sloths (Choloepus and Bradypus) are included as functional outgroups composed of suspensory adapted primates and non-primates. Results show that Babakotia and Mesopropithecus both have high humeral/femoral shaft strength proportions, similar to extant great apes and sloths and indicative of forelimb suspensory behavior, with Babakotia more extreme in this regard. All three subfossil taxa have relatively large femoral heads, also associated with suspension in modern taxa. However, Babakotia and Mesopropithecus (but not Palaeopropithecus) have relatively small femoral head surface area to shaft strength proportions suggesting that hind-limb positioning in these taxa during climbing and other behaviors was different than in extant great apes, involving less mobility. Knee and humeral articular dimensions relative to shaft strengths are small in Babakotia and Mesopropithecus, similar to those found in modern sloths and divergent from those in extant great apes and lemurs, suggesting more sloth-like use of these joints during locomotion. Mesopropithecus and Babakotia are more similar to Choloepus in humerofemoral head and length proportions while Palaeopropithecus is more similar to Bradypus. These results provide further evidence of the suspensory adaptations of Babakotia and further highlight similarities to both extant suspensory primates and non-primate slow arboreal climbers and hangers. J. Morphol. 277:1199-1218, 2016. © 2016 Wiley Periodicals, Inc. PMID:27324923

  15. Thompson and Hamilton type IV Freiberg's disease with involvement of multiple epiphyses of both feet.

    PubMed

    Lui, Tun Hing

    2015-01-01

    A 17-year-old boy reported left second and third toe pain after axial loading injury to his left foot. Radiographs showed collapse of the second metatarsal heads and epiphysial irregularities of the fifth metatarsal heads and the condyle of the proximal phalanx of the hallux of both feet. The patient was diagnosed to have Thompson and Hamilton type IV Freiberg's disease. He was screened for epiphysial dysplasia of the other sites. He had on and off bilateral hip and knee pain. Radiographs showed bilateral symmetrical epiphysial abnormalities with morphological change as focal concavity in bilateral femoral heads and fragmentation of the patellar articular surface with preservation of the patellofemoral joint space. PMID:25721826

  16. Epiphyseal chondrocyte secondary ossification centers require thyroid hormone activation of Indian hedgehog and osterix signaling.

    PubMed

    Xing, Weirong; Cheng, Shaohong; Wergedal, Jon; Mohan, Subburaman

    2014-10-01

    Thyroid hormones (THs) are known to regulate endochondral ossification during skeletal development via acting directly in chondrocytes and osteoblasts. In this study, we focused on TH effects on the secondary ossification center (SOC) because the time of appearance of SOCs in several species coincides with the time when peak levels of TH are attained. Accordingly, micro-computed tomography (µCT) evaluation of femurs and tibias at day 21 in TH-deficient and control mice revealed that endochondral ossification of SOCs is severely compromised owing to TH deficiency and that TH treatment for 10 days completely rescued this phenotype. Staining of cartilage and bone in the epiphysis revealed that whereas all of the cartilage is converted into bone in the prepubertal control mice, this conversion failed to occur in the TH-deficient mice. Immunohistochemistry studies revealed that TH treatment of thyroid stimulating hormone receptor mutant (Tshr(-/-) ) mice induced expression of Indian hedgehog (Ihh) and Osx in type 2 collagen (Col2)-expressing chondrocytes in the SOC at day 7, which subsequently differentiate into type 10 collagen (Col10)/osteocalcin-expressing chondro/osteoblasts at day 10. Consistent with these data, treatment of tibia cultures from 3-day-old mice with 10 ng/mL TH increased expression of Osx, Col10, alkaline phosphatase (ALP), and osteocalcin in the epiphysis by sixfold to 60-fold. Furthermore, knockdown of the TH-induced increase in Osx expression using lentiviral small hairpin RNA (shRNA) significantly blocked TH-induced ALP and osteocalcin expression in chondrocytes. Treatment of chondrogenic cells with an Ihh inhibitor abolished chondro/osteoblast differentiation and SOC formation. Our findings indicate that TH regulates the SOC initiation and progression via differentiating chondrocytes into bone matrix-producing osteoblasts by stimulating Ihh and Osx expression in chondrocytes. PMID:24753031

  17. Epiphyseal chondrocyte secondary ossification centers require thyroid hormone activation of Indian hedgehog and osterix signaling

    PubMed Central

    Xing, Weirong; Cheng, Shaohong; Wergedal, Jon; Mohan, Subburaman

    2015-01-01

    Thyroid hormones (TH) are known to regulate endochondral ossification during skeletal development via acting directly in chondrocytes and osteoblasts. In this study, we focused on TH effects on the secondary ossification center (SOC), since the time of appearance of SOCs in several species coincides with the time when peak levels of TH are attained. Accordingly, μCT evaluation of femurs and tibias at day 21 in TH-deficient and control mice revealed that endochondral ossification of SOCs is severely compromised due to TH deficiency and that TH treatment for 10 days completely rescued this phenotype. Staining of cartilage and bone in the epiphysis revealed that while all of the cartilage is converted into bone in the prepubertal control mice, this conversion failed to occur in the TH-deficient mice. Immunohistochemistry studies revealed that TH treatment of Tshr−/− mice induced expression of Ihh and Osx in Col2 expressing chondrocytes in the SOC at day 7 which subsequently differentiate into Col10/osteocalcin expressing chondro-osteoblasts at day 10. Consistent with these data, treatment of tibia cultures from 3-day old mice with10 ng/ml TH increased expression of Osx, Col10, ALP and osteocalcin in the epiphysis by 6–60 fold. Furthermore, knockdown of the TH-induced increase in Osx expression using lentiviral shRNA significantly blocked TH-induced ALP and osteocalcin expression in chondrocytes. Treatment of chondrogenic cells with an Ihh inhibitor abolished chondro-osteoblast differentiation and SOC formation. Our findings indicate that TH regulates the SOC initiation and progression via differentiating chondrocytes into bone matrix producing osteoblasts by stimulating Ihh and Osx expression in chondrocytes. PMID:24753031

  18. An artifacts removal post-processing for epiphyseal region-of-interest (EROI) localization in automated bone age assessment (BAA)

    PubMed Central

    2011-01-01

    Background Segmentation is the most crucial part in the computer-aided bone age assessment. A well-known type of segmentation performed in the system is adaptive segmentation. While providing better result than global thresholding method, the adaptive segmentation produces a lot of unwanted noise that could affect the latter process of epiphysis extraction. Methods A proposed method with anisotropic diffusion as pre-processing and a novel Bounded Area Elimination (BAE) post-processing algorithm to improve the algorithm of ossification site localization technique are designed with the intent of improving the adaptive segmentation result and the region-of interest (ROI) localization accuracy. Results The results are then evaluated by quantitative analysis and qualitative analysis using texture feature evaluation. The result indicates that the image homogeneity after anisotropic diffusion has improved averagely on each age group for 17.59%. Results of experiments showed that the smoothness has been improved averagely 35% after BAE algorithm and the improvement of ROI localization has improved for averagely 8.19%. The MSSIM has improved averagely 10.49% after performing the BAE algorithm on the adaptive segmented hand radiograph. Conclusions The result indicated that hand radiographs which have undergone anisotropic diffusion have greatly reduced the noise in the segmented image and the result as well indicated that the BAE algorithm proposed is capable of removing the artifacts generated in adaptive segmentation. PMID:21952080

  19. A geometric morphometrics comparative analysis of Neandertal humeri (epiphyses-fused) from the El Sidrón cave site (Asturias, Spain).

    PubMed

    Rosas, Antonio; Pérez-Criado, Laura; Bastir, Markus; Estalrrich, Almudena; Huguet, Rosa; García-Tabernero, Antonio; Pastor, Juan Francisco; de la Rasilla, Marco

    2015-05-01

    A new collection of 49,000 year old Neandertal fossil humeri from the El Sidrón cave site (Asturias, Spain) is presented. A total of 49 humeral remains were recovered, representing 10 left and 8 right humeri from adults, adolescents, and a juvenile (not included in the analyses). 3D geometric morphometric (GM) methods as well as classic anthropological variables were employed to conduct a broad comparative analysis by means of mean centroid size and shape comparisons, principal components analysis, and cluster studies. Due to the fragmentary nature of the fossils, comparisons were organized in independent analyses according to different humeral portions: distal epiphysis, diaphysis, proximal epiphysis, and the complete humerus. From a multivariate viewpoint, 3D-GM analyses revealed major differences among taxonomic groups, supporting the value of the humerus in systematic classification. Notably, the Australopithecus anamensis (KP-271) and Homo ergaster Nariokotome (KNM-WT 15000) distal humerus consistently clusters close to those of modern humans, which may imply a primitive condition for Homo sapiens morphology. Australopithecus specimens show a high degree of dispersion in the morphospace. The El Sidrón sample perfectly fits into the classic Neandertal pattern, previously described as having a relatively wide olecranon fossa, as well as thin lateral and medial distodorsal pillars. These characteristics were also typical of the Sima de los Huesos (Atapuerca) sample, African mid-Pleistocene Bodo specimen, and Lower Pleistocene TD6-Atapuerca remains and may be considered as a derived state. Finally, we hypothesize that most of the features thought to be different between Neandertals and modern humans might be associated with structural differences in the pectoral girdle and shoulder joint. PMID:25819346

  20. A compound heterozygote SLC26A2 mutation resulting in robin sequence, mild limbs shortness, accelerated carpal ossification, and multiple epiphysial dysplasia in two Brazilian sisters. A new intermediate phenotype between diastrophic dysplasia and recessive multiple epiphyseal dysplasia.

    PubMed

    Zechi-Ceide, Roseli Maria; Moura, Priscila Padilha; Raskin, Salmo; Richieri-Costa, Antonio; Guion-Almeida, Maria Leine

    2013-08-01

    Mutations in solute carrier family 26 (sulfate transporter), member 2 (SLC26A2) gene result in a spectrum of autosomal recessive chondrodysplasias that range from the mildest recessive form of multiple epiphysial dysplasia (rMED) through the most common diastrophic dysplasia (DTD) to lethal atelosteogenesis type II and achondrogenesis IB. The clinical variability has been ascribed to quantitative effect of mutations of the sulfate transporter activity. Here we describe two Brazilian sisters, born to healthy and non consanguineous parents, with Robin sequence, mild shortening of upper and lower limbs, brachymetacarpalia/tarsalia, additional and accelerated carpal ossification, marked genu valgum, and multiple epiphysial dysplasia. This phenotype was intermediate between DTD and rMED, and both girls have a compound heterozygous mutations for the SLC26A2, a Finnish founder mutation (c.-26 + 2T>C), and R279W. This combination of mutations has been observed in individuals with different phenotypes, including DTD, DTD variant, and rMED. The distinct phenotype of our cases reinforces the hypothesis that other factors may be influencing the phenotype as previously suggested. PMID:23840040

  1. Repopulation of laser-perforated chondroepiphyseal matrix with xenogeneic chondrocytes: An experimental model

    SciTech Connect

    Caruso, E.M.; Lewandrowski, K.U.; Ohlendorf, C.; Tomford, W.W.; Zaleske, D.J.

    1996-01-01

    Growth of chondrocytes into a xenogeneic chondroepiphyseal matrix was investigated in an in vitro experimental model by combining viable calf chondrocytes with chick epiphyseal matrix devoid of viable chondrocytes. The chondrocytes were harvested from the wrist joints of newborn calves and cultured for 2 days. The epiphyses were harvested from the distal femurs and the proximal tibias of fetal chicks after development was arrested at 17 days by freezing. The epiphyseal specimens were prepared in four ways. These included femoral and tibial epiphyses without holes and femoral and tibial epiphyses with holes made by a laser. These epiphyseal specimens were co-cultured with calf chondrocytes for various periods. After digestion of the epiphyseal matrix, viable chondrocytes were counted in suspension. Chondrocyte division in the matrix was assessed by [{sup 3}H]thymidine incorporation. The growth of calf chondrocytes into the xenogeneic chick matrix was evaluated by fluorescence microscopy on fresh thick epiphyseal sections. The percentage of viable chondrocytes in the xenogeneic epiphyseal matrix increased with culture time to a maximum at day 21. The addition of laser-drilled holes was found to extend a plateau of chondrocyte viability until day 29. A decrease in cell viability was detected at later observation points. This study demonstrates that xenogeneic matrix may serve as a morphogenetic scaffold for chondrocytic growth. 22 refs., 3 figs.

  2. [The "candlestick" technique for the correction of certain types of congenital metacarpal synotosis].

    PubMed

    Foucher, G; Medina, J; Bollecker, V; Lorea, P

    2002-10-01

    Metacarpal synostosis is a rare congenital hand malformation requiring only occasionally a surgical correction. However in case of divergent epiphyses there is a progressive accentuation of the deformity. In the "Y" type of symmetrical synostosis, the authors propose a trapezoidal osteotomy with upside down relocation allowing realignement of the epiphyses without distant bone donor site. PMID:12491705

  3. Orthopedic radiology

    SciTech Connect

    Renton, P.

    1989-01-01

    The book is divided into seven major sections on Decrease in bone density, Osteosclerosis, Localized lesions in bone, Lesions affecting the epiphyses, Abnormalities in the region of the metaphysis, Periosteal reactions, and Abnormalities in size and modelling of bone.

  4. Computerized bone analysis of hand radiographs

    NASA Astrophysics Data System (ADS)

    Pietka, Ewa; McNitt-Gray, Michael F.; Hall, Theodore R.; Huang, H. K.

    1992-06-01

    A computerized approach to the problem of skeletal maturity is presented. The analysis of a computed radiography (CR) hand image results in obtaining features, that can be used to assess the skeletal age of pediatric patients. It is performed on a standard left hand radiograph. First, epiphyseal regions of interest (EROI) are located. Then, within each EROI the distals, middles, and proximals are separated. This serves as a basis to locate the extremities of epiphyses and metaphyses. Next, the diameters of epiphyses and metaphyses are calculated. Finally, an epiphyseal diameter and metaphyseal diameter ratio is calculated. A pilot study indicated that these features are sensitive to the changes of the anatomical structure of a growing hand and can be used in the skeletal age assessment.

  5. [Symptomatic calcification in the newborn. Phenocopies of chondrodysplasia punctata].

    PubMed

    Leicher-Düber, A; Schumacher, R; Spranger, J

    1990-04-01

    Stippled epiphyses occur in the new-born and young infant in the different hereditary forms of chondrodysplasia punctata. Symptomatic stippling has been described also in association with chromosomal anomalies, gangliosidosis and drug induced embryopathies. We present patients with Cumarin-embryopathy (2), fetal alcohol syndrome (1), Zellweger-syndrome (2) and chromosomal anomaly 16 (1) and discuss the typical roentgenographic features, distribution and differential diagnosis of epiphyseal stippling. PMID:2160110

  6. Effects of factors of prolonged space flight on conditions of tortoise skeleton

    NASA Technical Reports Server (NTRS)

    Stupakon, G. P.; Volozhin, A. I.; Korzhenyants, V. A.; Yagodovskiy, V. S.; Polyakov, A. N.; Korolev, V. V.; Elivanov, V. A.

    1980-01-01

    After a 60-90 day space flight mild osteoporosis developed in the epiphyses and metaphyses of long tubular bones of tortoises, which was not attributed to reduced mineral saturation of the preserved bone tissue microstructures. The diminished strength of the cancellous bone of the epiphyses in tortoises after space flight was due to the reduced properties of its structure. The strength of the compact substance did not change under the effect of weightlessness.

  7. The development of centres of ossification of bones forming elbow joints in young swine.

    PubMed Central

    Visco, D M; Hill, M A; Van Sickle, D C; Kincaid, S A

    1990-01-01

    Epiphyseal centres of ossification in the bones forming the elbow joints of pigs between one day and 15 weeks of age were examined radiographically, macroscopically, mesoscopically and microscopically. Thoracic limbs from 39 pigs were perfused with India ink or silicone rubber injection compound and the bones were dissected free of soft tissues. The humerus, ulna and radius were fixed in formalin or ethyl alcohol and then cleared by the modified Spalteholz technique. Bones were radiographed, examined grossly, and then cut into slabs for mesoscopical evaluation. Foci considered to be calcifying within cartilaginous anlage were selected for microscopical examination. It was concluded that the epiphyseal centre of ossification develops at different times in different sites in the bones forming the elbow joint. Centres of ossification are initiated when foci of chondrocytes adjacent to one side of a cartilage canal undergo hypertrophy and the inter-territorial matrix becomes calcified. Osteogenesis then proceeds in the calcified focus, presumably with osteoprogenitor cells that originate within the cartilage canals. Subsequently, each epiphyseal centre of ossification enlarges by one of two methods. Firstly, the layer of cartilage adjacent to the centre undergoes endochondral ossification, thus allowing for the circumferential growth of the epiphyseal centre of ossification. Secondly, foci of calcification develop adjacent to the ends of cartilage canals near the epiphyseal centre of ossification and eventually the focus of calcification coalesces with the developing epiphyseal centre of ossification, thus establishing a new ossification front. Endochondral ossification continues at the periphery of the mass of bone. Mesoscopical examination is more useful than radiographical evaluation for identifying small foci of calcification which precede epiphyseal centres of ossification. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:2081708

  8. Bulbous epiphysis and popcorn calcification as related to growth plate differentiation in osteogenesis imperfecta

    PubMed Central

    Brizola, Evelise; McCarthy, Edward; Shapiro, Jay Robert

    2015-01-01

    Summary Background Osteogenesis Imperfecta (OI) is an heritable systemic disorder of connective tissue due to different sequence variants in genes affecting both the synthesis of type I collagen and osteoblast function. Dominant and recessive inheritance is recognized. Approximately 90% of the OI cases are due to mutations in COL1A1/A2 genes. We clinically and radiologically describes an adult male with type III osteogenesis imperfecta who presents a rare bone dysplasia termed bulbous epiphyseal deformity in association with popcorn calcifications. Popcorn calcifications may occur with bulbous epiphyseal deformity or independently. Methods Molecular analysis was performed for COL1A1, COL1A2, LEPRE1 and WNT1 genes. Results An uncommon COL1A1 mutation was identified. Clinical and radiological exams confirmed a distinctive bulbous epiphyseal deformity with popcorn calcifications in distal femurs. We have identified four additional OI patients reported in current literature, whose X-rays show bulbous epiphyseal deformity related to mutations in CR-TAP, LEPRE1 and WNT1 genes. Conclusion The mutation identified here had been previously described twice in OI patients and no previous correlation with bulbous epiphyseal deformity was described. The occurrence of this bone dysplasia focuses attention on alterations in normal growth plate differentiation and the subsequent effect on endochondral bone formation in OI. PMID:26604951

  9. Osteochondrosis Can Lead to Formation of Pseudocysts and True Cysts in the Subchondral Bone of Horses.

    PubMed

    Olstad, K; Østevik, L; Carlson, C S; Ekman, S

    2015-09-01

    Osteochondrosis arises as a result of focal failure of the blood supply to growth cartilage. The current aim was to examine the pathogenesis of pseudocysts and true cysts in subchondral bone following failure of the blood supply to the articular-epiphyseal cartilage complex in horses. Cases were recruited based on identification of lesions (n = 17) that were considered likely to progress to or to represent pseudocysts or true cysts in epiphyseal bone in histological sections and included 10 horses ranging in age from 48 days to 5 years old. Cases comprised 3 warmbloods, 3 Standardbreds, 1 Quarter horse and 1 Arabian with spontaneous lesions and 2 Fjord ponies with experimentally induced lesions. Seven lesions consisted of areas of ischemic chondronecrosis and were compatible with pseudocysts. Two lesions were located at intermediate depth in epiphyseal growth cartilage, 2 lesions were located in the ossification front, 2 lesions were located in epiphyseal bone and 1 lesion was located in the metaphyseal growth plate (physis). Ten lesions contained dilated blood vessels and were compatible with true cysts. In 2 lesions the dilated blood vessels were located within the lumina of failed cartilage canals. In the 8 remaining lesions areas of ischemic chondronecrosis were associated with granulation tissue in the subjacent bone and dilated vessels were located within this granulation tissue. Failure of the blood supply and ischemic chondronecrosis can lead to formation of pseudocysts or dilatation of blood vessels and formation of true cysts in the epiphyseal bone of horses. PMID:25428408

  10. Fracture properties of growth plate cartilage compared to cortical and trabecular bone in ovine femora.

    PubMed

    Tschegg, E K; Celarek, A; Fischerauer, S F; Stanzl-Tschegg, S; Weinberg, A M

    2012-10-01

    Fracture mechanical parameters (notch tensile strength, specific fracture energy/crack resistance and specific crack initiation energy) of epiphyseal plate cartilage, trabecular bone (metaphysis) and cortical bone (diaphysis) were determined on ovine femur specimens. The fracture behaviour before and after crack initiation was recorded in force-displacement diagrams from wedge splitting tests. Crack propagation was stable both during and after the formation of a principal crack. This is the main advantage of the wedge-splitting method by Tschegg in comparison with tensile tests. Microscopy of the epiphyseal plate during fracture showed fibre elongation and tearing in the crack tip region. The results of this study can help to understand the mechanics of epiphyseal plate injuries and the obtained values can be used for computational simulations and models. PMID:23022566

  11. Giant cell tumor of bone arising in long bones possibly originates from the metaphyseal region

    PubMed Central

    FUTAMURA, NAOHISA; URAKAWA, HIROSHI; TSUKUSHI, SATOSHI; ARAI, EISUKE; KOZAWA, EIJI; ISHIGURO, NAOKI; NISHIDA, YOSHIHIRO

    2016-01-01

    Giant cell tumor of bone (GCTB) is a primary benign bone tumor with a locally aggressive character. Definitive descriptions of the site of origin for this type of tumor are not available. The aim of the present study was to evaluate the site of origin of GCTB of long bones with regards to epiphyseal lines by means of radiographic examination. For that purpose, plain X-ray scans of 71 GCTBs arising in long bones were retrospectively reviewed. The tumor locations were the distal femur in 31 cases, proximal femur in 11 cases, proximal tibia in 13 cases, distal radius in 6 cases, proximal humerus in 5 cases and proximal fibula in 5 cases. The vertical center (VC) of the tumor was determined with X-ray anteroposterior view, and the correlation between the VC and the epiphyseal line, and between the distance from the epiphyseal line to the VC and tumor area or volume were analyzed using a regression model equation based on scatter plot diagrams. The VC of the tumor was located in the metaphyseal region in 57 cases, in the epiphyseal line in 11 cases and in the epiphyseal region in 3 cases. In cases of GCTB located in the distal femur or proximal tibia, significant correlations between the distance from the VC to the epiphyseal line and tumor area or volume were identified. The site of origin of GCTB was estimated to be located in the metaphyseal region. GCTB often occurs in mature patients, which renders it challenging to estimate the true site of origin of this lesion, since the metaphyseal line has disappeared in mature patients. The results of the present study suggest that GCTB possibly originates in the metaphyseal region. PMID:27073530

  12. Distal tibial physeal bridge: a complication from a tension band plate and screw construct. Report of a case.

    PubMed

    Oda, Jon E; Thacker, Mihir M

    2013-05-01

    We report on a case of a tension band plate and screw construct (Eight Plate) used over the anterior distal tibia in an 9-year-old girl in an attempt to induce recurvatum of the ankle joint to correct a recalcitrant equinus deformity. With growth of the distal tibial physis, the epiphyseal screw was drawn through the physis into the distal tibial metaphysis, resulting in the creation of a transphyseal bony bar. Caution should be exercised when attempting temporary hemiepiphyseodesis using a plate and screw construct in small epiphyses or in an osteopenic bone. PMID:22158054

  13. Synergistic local drug delivery in a piglet model of ischemic osteonecrosis: a preliminary study.

    PubMed

    Zou, Yuan; Fisher, Paul D; Horstmann, Joanna K; Talwalkar, Vishwas; Milbrandt, Todd A; Puleo, David A

    2015-11-01

    A locally injectable system sequentially delivering an antiresorptive drug (clodronate) followed by an osteogenic agent (simvastatin) was hypothesized to improve femoral head microarchitecture, size, and shape compared with untreated or partial treatment groups in an established piglet osteonecrosis model. After 6 weeks, the clodronate+simvastatin treatment resulted in no collapse, microCT measurements and epiphyseal quotients within 10% of control, normal microstructure, and healthy histology. All other groups exhibited collapse, lower epiphyseal quotients and total femoral head volumes (P<0.05), and abnormal histology. This pilot study provides evidence of synergistic antiresorptive and osteogenic activities, which may prevent femoral head collapse in Perthes disease. PMID:26196370

  14. Contribution of magnetic resonance imaging of the wrist and hand to forensic age assessment.

    PubMed

    Serin, Jeanne; Rérolle, Camille; Pucheux, Julien; Dedouit, Fabrice; Telmon, Norbert; Savall, Frédéric; Saint-Martin, Pauline

    2016-07-01

    Forensic age estimation of living individuals is a controversial subject because of the imprecision of the available methods which leads to errors. Moreover, young persons are exposed to radiation, without diagnostic or therapeutic advantage. Recently, non-invasive imaging techniques such as magnetic resonance imaging (MRI) have been studied in this context. The aim of this work was to study if the analysis of wrist/hand MRI enabled determination of whether a subject was 18 years old. Two observers retrospectively analyzed metaphyseal-epiphyseal fusion of the distal epiphysis of the radius and the ulna and the base of the first metacarpus in wrist/hand MRI of living people between 9 and 25 years of age. A three-stage scoring system was applied to all epiphyses. Intra- and inter-observer variability was excellent. Staging of the distal radial epiphysis allowed the subjects to be correctly evaluated with regard to the 18-year-old threshold in more than 85 % of cases. Analysis of the radius alone was as good as the analysis of the three epiphyses together. Evaluation of the metaphyseal-epiphyseal fusion of the distal radius in wrist MRI gave good results in forensic age estimation. Wrist MRI could meet ethical expectations with regard to the link between the benefit and risk of practicing radiologic examination on individuals in this context. PMID:27025715

  15. ( sup 99m Tc)diphosphonate uptake and hemodynamics in arthritis of the immature dog knee

    SciTech Connect

    Hansen, E.S.; Soballe, K.; Henriksen, T.B.; Hjortdal, V.E.; Buenger, C. )

    1991-03-01

    The relationship between (99mTc)diphosphonate uptake and bone hemodynamics was studied in canine carrageenan-induced juvenile chronic arthritis. Blood flow was determined with microspheres, plasma and red cell volumes were measured by labeled fibrinogen and red cells, and the microvascular volume and mean transit time of blood were calculated. Normal femoral epiphyses had lower central and higher subchondral blood flow and diphosphonate uptake values. Epiphyseal vascular volume was uniform, resulting in a greater transit time of blood centrally. In arthritis, blood flow and diphosphonate uptake were increased subchondrally and unaffected centrally, while epiphyseal vascular volume was increased throughout, leading to prolonged transit time centrally. The normal metaphyses had low blood flow and diphosphonate uptake values in cancellous bone and very high values in growth plates, but a large vascular volume throughout. The mean transit time therefore was low in growth plates and high in adjacent cancellous bone. Arthritis caused decreased blood flow and diphosphonate uptake in growth plates but increased vascular volume and transit time of blood. Diphosphonate uptake correlated positively with blood flow and plasma volume and negatively with red cell volume in a nonlinear fashion. Thus, changes in diphosphonate uptake and microvascular hemodynamics occur in both epiphyseal and metaphyseal bone in chronic synovitis of the immature knee. The (99mTc)diphosphonate bone scan seems to reflect blood flow, plasma volume, and red cell volume of bone.

  16. Injuries to the Young Athlete.

    ERIC Educational Resources Information Center

    Sandusky, Jane C.

    A review of literature on the incidence and nature of injuries to young athletes is presented on the topics of: (1) physiological characteristics of preadolescents, adolescents, and young adults; (2) musculo-skeletal changes in the growing athlete; (3) epiphyseal injuries and their potential for resulting in temporary or permanent impairment; (4)…

  17. Which X-ray views are required in juvenile ankle trauma?

    PubMed

    Heim, M; Blankstein, A; Israeli, A; Horoszowski, H

    1990-01-01

    Although ankle sprains are probably the most common injury in adolescent sports people, epiphyseal injuries are missed on the presumption of a ligamentous tear. The risk of damaged ligaments has been overemphasized while the potentially dangerous epiphyseolysis has been understressed. An oblique X-ray of the ankle joint is indicated prior to "stress" pictures. PMID:2346717

  18. Regeneration of Articular Cartilage in Lizard Knee from Resident Stem/Progenitor Cells

    PubMed Central

    Alibardi, Lorenzo

    2015-01-01

    The epiphysis of femur and tibia in the lizard Podarcis muralis can extensively regenerate after injury. The process involves the articular cartilage and metaphyseal (growth) plate after damage. The secondary ossification center present between the articular cartilage and the growth plate is replaced by cartilaginous epiphyses after about one month of regeneration at high temperature. The present study analyzes the origin of the chondrogenic cells from putative stem cells located in the growing centers of the epiphyses. The study is carried out using immunocytochemistry for the detection of 5BrdU-labeled long retaining cells and for the localization of telomerase, an enzyme that indicates stemness. The observations show that putative stem cells retaining 5BrdU and positive for telomerase are present in the superficial articular cartilage and metaphyseal growth plate located in the epiphyses. This observation suggests that these areas represent stem cell niches lasting for most of the lifetime of lizards. In healthy long bones of adult lizards, the addition of new chondrocytes from the stem cells population in the articular cartilage and the metaphyseal growth plate likely allows for slow, continuous longitudinal growth. When the knee is injured in the adult lizard, new populations of chondrocytes actively producing chondroitin sulfate proteoglycan are derived from these stem cells to allow for the formation of completely new cartilaginous epiphyses, possibly anticipating the re-formation of secondary centers in later stages. The study suggests that in this lizard species, the regenerative ability of the epiphyses is a pre-adaptation to the regeneration of the articular cartilage. PMID:26340619

  19. Stickler-like syndrome due to a dominant negative mutation in the COL2A1 gene.

    PubMed

    Ballo, R; Beighton, P H; Ramesar, R S

    1998-10-30

    The type II collagenopathies include a wide spectrum of phenotypes ranging from mild spondylo epiphyseal dysplasia (SED) to severe achondrogenesis/hypochondrogenesis. Several attempts have been made at providing phenotype-genotype correlations in this group of disorders. In this report we discuss a South African family in which four members have a phenotype resembling Stickler syndrome type 1. Ocular problems and conductive deafness predominate, while skeletal changes resemble those of a mild form of multiple epiphyseal dysplasia (MED). In distinction to the classical form of Stickler syndrome, the affected persons have stubby digits. DNA analysis of the exons of the COL2A1 gene documented a C-T transversion in exon 39, resulting in an Arg704Cys substitution in the triple helical domain of the type II collagen peptide; this nontermination mutation may be indicative of further heterogeneity in the Stickler group of disorders or of a new syndrome amongst the type II collagenopathies. PMID:9800905

  20. Pediatric Frostbite Treated by Negative Pressure Wound Therapy.

    PubMed

    Poulakidas, Stathis J; Kowal-Vern, Areta; Atty, Corinne

    2016-01-01

    Frostbite injury in children can lead to abnormal growth and premature fusion of the epiphyseal cartilage with long-term sequela including, but not limited to, arthroses, deformity, and amputation of the phalanges. This was a retrospective chart review of pediatric frostbite identified in an in-house burn center registry from March 1999 to March 2014. Therapeutic management included negative pressure wound therapy (NPWT). Three patients (age 16-31 months) had frostbitten hands because they were outside in cold weather without gloves. They presented within 24 hours after injury, underwent 5-6 days of NPWT after excision of blisters, and did not lose the distal portion of their digits, or require amputations. On follow-up, all hands were healed well with only minimal or no effect on the growth plate of these pediatric patients. In the early period after frostbite, NPWT may be beneficial in preserving the epiphyseal cartilage in children and preventing long-term complications. PMID:26284629

  1. Jackson-Weiss syndrome: Clinical and radiological findings in a large kindred and exclusion of the gene from 7p21 and 5qter

    SciTech Connect

    Ades, L.C.; Haan, E.A.; Mulley, J.C.; Senga, I.P.; Morris, L.L.; David, D.J.

    1994-06-01

    We describe the clinical and radiological manifestations of the Jackson-Weiss syndrome (JWS) in a large South Australian kindred. Radiological abnormalities not previously described in the hands include coned epiphyses, distal and middle phalangeal hypoplasia, and carpal bone malsegmentation. New radiological findings in the feet include coned epiphyses, hallux valgus, phalangeal, tarso-navicular and calcaneo-navicular fusions, and uniform absence of metatarsal fusions. Absence of linkage to eight markers along the short arm of chromosome 7 excluded allelian between JWS and Saethre-Chotzen syndrome at 7p21. No linkage was detected to D5S211, excluding allelism to another recently described cephalosyndactyly syndrome mapping to 5qter. 35 refs., 5 figs., 4 tabs.

  2. Physes around the shoulder girdle: normal development and injury patterns.

    PubMed

    Anwar, I; Amiras, D; Khanna, M; Walker, M

    2016-07-01

    Traumatic injuries involving the scapula and clavicle in skeletally immature patients have unique characteristics that distinguish them from similar injuries in the mature skeleton. Fractures involving unossified cartilage and unfused epiphyses are difficult to appreciate on plain radiographs and computed tomography (CT) imaging. Knowledge of the developmental anatomy and normal radiological appearances during different stages of development of these bones is an essential prerequisite for the radiologist tasked with interpreting the imaging of such injuries in order to avoid potential diagnostic pitfalls. With increased availability and improved resolution of magnetic resonance imaging (MRI), we are now better able to distinguish between true joint dislocations and epiphyseal injuries. Making this distinction is important because it can have implications with regards to how the patient is managed and the prognosis. PMID:27114286

  3. Acute Primary Hematogenous Osteomyelitis in the Epiphysis of the Distal Tibia: A Case Report With Review of the Literature.

    PubMed

    Hwang, Hyun-Jung; Jeong, Woong-Kyo; Lee, Dae-Hee; Lee, Soon-Hyuck

    2016-01-01

    Osteomyelitis originating in the epiphysis of the long bones is quite rare and is usually found at either the distal femur or the proximal tibia. We report the case of a 12-year-old male with epiphyseal osteomyelitis that had developed in the distal tibia. To the best of our knowledge, this is the first published case report. The patient's history of a trauma that resembled an ankle sprain had delayed the diagnosis and subsequently led him to develop septic arthritis. The ankle is a common site of simple trauma; however, epiphyseal osteomyelitis is rare at this site. Therefore, if the symptoms continue or worsen after trauma, the clinician should check the affected site and take a more aggressive approach to make an early diagnosis. PMID:26878809

  4. [The effect of local exposure to Mg and heat on the biosynthesis of sulfur-containing compounds in the oral tissues].

    PubMed

    Varava, G N; Podorozhnaia, R P; Genesina, T I; Kuz'menko, V E; Totskiĭ, A V

    1989-01-01

    Local Mg electrophoresis was shown to considerably increase the radiolabeled sulphate contents in an application area: gums, mandibular alveolar processes, lower incisors and molars roots. In areas far beyond the phoresis sites (femoral epiphyses and diaphyses) label incorporation was not affected. Mg-free galvanization had no effect on sulphate incorporation into the mineralized tissues. Heating up to 50 C substantially increased the S radioactivity in alveolar processes, molar and incisor roots. Simultaneous heating with Mg electrophoresis produced an additive effect. PMID:2623690

  5. Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism

    SciTech Connect

    Finkelstein, J.S.; Klibanski, A.; Neer, R.M.; Doppelt, S.H.; Rosenthal, D.I.; Segre, G.V.; Crowley, W.F. Jr. )

    1989-10-01

    To assess the effects of gonadal steroid replacement on bone density in men with osteoporosis due to severe hypogonadism, we measured cortical bone density in the distal radius by 125I photon absorptiometry and trabecular bone density in the lumbar spine by quantitative computed tomography in 21 men with isolated GnRH deficiency while serum testosterone levels were maintained in the normal adult male range for 12-31 months (mean +/- SE, 23.7 +/- 1.1). In men who initially had fused epiphyses (n = 15), cortical bone density increased from 0.71 +/- 0.02 to 0.74 +/- 0.01 g/cm2 (P less than 0.01), while trabecular bone density did not change (116 +/- 9 compared with 119 +/- 7 mg/cm3). In men who initially had open epiphyses (n = 6), cortical bone density increased from 0.62 +/- 0.01 to 0.70 +/- 0.03 g/cm2 (P less than 0.01), while trabecular bone density increased from 96 +/- 13 to 109 +/- 12 mg/cm3 (P less than 0.01). Cortical bone density increased 0.03 +/- 0.01 g/cm2 in men with fused epiphyses and 0.08 +/- 0.02 g/cm2 in men with open epiphyses (P less than 0.05). Despite these increases, neither cortical nor trabecular bone density returned to normal levels. Histomorphometric analyses of iliac crest bone biopsies demonstrated that most of the men had low turnover osteoporosis, although some men had normal to high turnover osteoporosis. We conclude that bone density increases during gonadal steroid replacement of GnRH-deficient men, particularly in men who are skeletally immature.

  6. A simple and safe technique for tibial lengthening.

    PubMed

    Rezaian, S M; Abtahi, M

    1986-06-01

    This is a report of long-term results and complications in 62 patients. Closed tibial osteotomy, direct tibial distraction, and simultaneous indirect proximal fibular epiphyseal distraction are the essential features of this new technique. Fibular osteotomy and complications from tibiofibular synostosis are eliminated. Bone graft and plating procedures have been proven to be unnecessary. The patient is ambulated immediately. Hospitalization has been reduced to a few days. PMID:3720089

  7. Anterior Cruciate Ligament Graft Isometry Is Affected by the Orientation of the Femoral Tunnel.

    PubMed

    Ebersole, Gregg M; Eckerle, Paul; Farrow, Lutul D; Cutuk, Adnan; Bledsoe, Gary; Kaar, Scott

    2016-04-01

    Purpose The purpose of this study was to compare anterior cruciate ligament (ACL) graft length and tension throughout knee range of motion with transtibial, anteromedial (AM) portal, and all-epiphyseal drilling techniques with suspensory and apical femoral fixation. Methods The three different femoral tunnel drilling techniques using the same intra-articular starting point within the center of the femoral footprint were performed on fresh-frozen cadaveric specimens. All groups underwent standard tibial drilling in the center of the ACL tibial footprint. FiberWire (Arthrex Inc., Naples, FL) was used to simulate anatomic single bundle reconstructions. Changes in graft length and tension were measured at knee flexion angles of 0, 30, 60, 90, 120, and 135 degrees. Results Graft length and tension decreased from 0 through 60 degrees and subsequently increased from 90 to 135 degrees for all groups. The transtibial, AM portal suspensory, and apical fixation groups were similar. However, the all-epiphyseal tunnel with suspensory fixation had a significantly increased change in length (90, 120, and 135 degrees) and tension (120 and 135 degrees). Conclusion Transtibial and AM portal suspensory fixation and apical fixation demonstrate similar changes in length and tension throughout knee range of motion. The all-epiphyseal tunnel with suspensory fixation was associated with greater length and tension changes at higher degrees of knee flexion. All techniques demonstrated decreased graft length and tension with knee flexion to 60 degrees after which they increased with further knee flexion. Clinical Relevance ACL graft length and tension change throughout knee range of motion and also depend on femoral tunnel orientation and fixation type. The use of an all-epiphyseal tunnel with suspensory fixation should be studied further for evidence of graft elongation. PMID:26190786

  8. Comparison of calcium and phosphorus excretion with bone density changes during restraint in immature Macaca nemestrina primates.

    NASA Technical Reports Server (NTRS)

    Hoffman, R. A.; Hood, W. N.; Mack, P. B.

    1972-01-01

    Calcium and phosphorus balance data on Macaca nemestrina monkeys during immobilization are presented and correlated with X-ray bone densitometry findings. A positive mineral balance was maintained during the immobilized period. A reduced bone density was observed in most skeletal sites examined with increased density observed in epiphyseal regions. Migration of mineral from one site to another is suggested as a possible explanation for the findings.

  9. Crooked fingers and sparse hair: an interesting case of trichorhinophalangeal syndrome type 1.

    PubMed

    Narayanan, Ramakrishna; Chennareddy, Srinivasa

    2015-01-01

    Trichorhinophalangeal syndrome type 1 is a rare skeletal dysplasia of autosomal-dominant inheritance due to defects in the TRPS-1 gene. The syndrome is characterised by sparse slow-growing hair, a bulbous pear-shaped nose, cone-shaped epiphyses and deformities of the interphalangeal joints resembling those in rheumatoid arthritis. We present a case of trichorhinophalangeal syndrome in a 23-year-old man who presented with symmetrical painless progressive deformity of the fingers in both hands. PMID:25628322

  10. Altered lumbar spine structure, biochemistry and biomechanical properties in a canine model of mucopolysaccharidosis type VII

    PubMed Central

    Smith, Lachlan J; Martin, John T; Szczesny, Spencer E; Ponder, Katherine P; Haskins, Mark E; Elliott, Dawn M

    2010-01-01

    Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disorder characterized by a deficiency in β-glucuronidase activity, leading to systemic accumulation of poorly degraded glycosaminoglycans (GAG). Along with other morbidities, MPS VII is associated with paediatric spinal deformity. The objective of this study was to examine potential associations between abnormal lumbar spine matrix structure and composition in MPS VII, and spine segment and tissue-level mechanical properties, using a naturally occurring canine model with a similar clinical phenotype to the human form of the disorder. Segments from juvenile MPS VII and unaffected dogs were allocated to: radiography, gross morphology, histology, biochemistry, and mechanical testing. MPS VII spines had radiolucent lesions in the vertebral body epiphyses. Histologically, this corresponded to a GAG-rich cartilaginous region in place of bone, and elevated GAG staining was seen in the annulus fibrosus. Biochemically, MPS VII samples had elevated GAG in the outer annulus fibrosus and epiphyses, low calcium in the epiphyses, and high water content in all regions except the nucleus pulposus. MPS VII spine segments had higher range of motion and lower stiffness than controls. Endplate indentation stiffness and failure loads were significantly lower in MPS VII samples, while annulus fibrosus tensile mechanical properties were normal. Vertebral body lesions in MPS VII spines suggest a failure to convert cartilage to bone during development. Low stiffness in these regions likely contributes to mechanical weakness in motion segments and is a potential factor in the progression of spinal deformity. PMID:19918911

  11. Hypochondrogenesis.

    PubMed

    Maroteaux, P; Stanescu, V; Stanescu, R

    1983-10-01

    Three clinicopathological observations of a mild form of type II achondrogenesis are presented. The cases were selected from a group of 21 similar cases to illustrate the various degrees of clinical and roentgenological signs that can be found. The cases had various survival periods after birth but not exceeding several months. The roentgenological signs were less severe than those of type II achondrogenesis. Some cases similar to case no. 3 have roentgenological signs very close to spondylo-epiphyseal dysplasia congenita and probably were confused previously with the latter. The name of hypochondrogenesis was proposed for these cases because the lesions of the growth plate are similar although less marked to those found in type II achondrogenesis: high cellularity with poor matrix development; irregular columnization and vascular penetration; large chondrocytes and even more enlarged lacunae; large sclerotic cartilage canals. The clinical and roentgenological diagnosis of hypochondrogenesis could be difficult especially in the less severe forms. The delay in vertebral ossification, the absence of all the epiphyseal nuclei and of the tarsal bones might suggest the diagnosis of hypochondrogenesis, rather than that of spondyloepiphyseal dysplasia. The evolution which seems to be always lethal in a period of several weeks or months would make the diagnosis still more likely and it could be confirmed by histopathological examination. Cases of spondylo-epiphyseal dysplasia congenita might have at birth, roentgenological signs indistinguishable from those of hypochondrogenesis, as was illustrated by case no. 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6641761

  12. Heterochrony and post-natal growth in mammals--an examination of growth plates in limbs.

    PubMed

    Geiger, M; Forasiepi, A M; Koyabu, D; Sánchez-Villagra, M R

    2014-01-01

    Mammals display a broad spectrum of limb specializations coupled with different locomotor strategies and habitat occupation. This anatomical diversity reflects different patterns of development and growth, including the timing of epiphyseal growth plate closure in the long bones of the skeleton. We investigated the sequence of union in 15 growth plates in the limbs of about 400 specimens, representing 58 mammalian species: 34 placentals, 23 marsupials and one monotreme. We found a common general pattern of growth plate closure sequence, but one that is universal neither between species nor in higher-order taxa. Locomotor habitat has no detectable correlation with the growth plate closure sequence, but observed patterns indicate that growth plate closure sequence is determined more strongly through phylogenetic factors. For example, the girdle elements (acetabulum and coracoid process) always ossify first in marsupials, whereas the distal humerus is fused before the girdle elements in some placentals. We also found that heterochronic shifts (changes in timing) in the growth plate closure sequence of marsupials occur with a higher rate than in placentals. This presents a contrast with the more limited variation in timing and morphospace occupation typical for marsupial development. Moreover, unlike placentals, marsupials maintain many epiphyses separated throughout life. However, as complete union of all epiphyseal growth plates is recorded in monotremes, the marsupial condition might represent the derived state. PMID:24251599

  13. Early characteristic findings in bowleg deformities: evaluation using magnetic resonance imaging.

    PubMed

    Mukai, S; Suzuki, S; Seto, Y; Kashiwagi, N; Hwang, E S

    2000-01-01

    We used magnetic resonance imaging (MRI) to evaluate bowleg deformities in infancy. Twenty-five tibiae of 13 infants were examined and divided into two groups based on MRI findings: group A had high intensity area in the medial epiphyseal cartilage on T2-weighted images. Group B had depression of medial physis and abnormal signal in the perichondrial region in addition to the epiphyseal lesion. At the final follow-up, all cases in group A demonstrated normal lower leg alignments, whereas five cases in group B showed characteristic roentogenographic findings of Blount's disease. The improvement rate of metaphyseal-diaphyseal angle was correlated with this classification. These findings suggested that abnormal findings in physis and perichondrial region might be preliminary findings in early stage of Blount's disease. The high intensity areas in the medial epiphyseal cartilage were commonly found among the cases with bowing deformities, which suggested that there might be a common pathomechanism between physiologic bowing and infantile Blount's disease. PMID:11008740

  14. Ossification Pattern of Estuarine Dolphin (Sotalia guianensis) Forelimbs, from the Coast of the State of Espírito Santo, Brazil

    PubMed Central

    Botta, Silvina; de Queiroz, Fábio Ferreira; Campos, Adélia Sepúlveda

    2015-01-01

    The estuarine dolphin, Sotalia guianensis, is one of the most abundant cetacean species in Brazil. Determination of age and of aspects associated with the development of this species is significant new studies. Counts of growth layer groups in dentin are used to estimate age of these animals, though other ways to evaluate development are also adopted, like the measurement of total length (TL). This study presents a procedure to evaluate the development of the estuarine dolphin based on the ossification pattern of forelimbs. Thirty-seven estuarine dolphins found in the state of Espírito Santo, Brazil, were examined. Age was estimated, TL was measured and ossification of epiphyses was examined by radiography. We analyzed results using the Spearman correlation. Inspection of radiographs allowed evaluation of the significance of the correlation between age and development of the proximal (r = 0.9109) and distal (r = 0.9092) radial epiphyses, and of the distal ulnar epiphyses (r = 0.9055). Radiographic analysis of forelimbs proved to be an appropriate method to evaluate physical maturity, and may be a helpful tool to estimate age of these animals in ecological and population studies. PMID:26017269

  15. /sup 99m/Tc-DPD uptake in juvenile hemarthrosis. Scintimetry and autoradiography of the knee in dogs

    SciTech Connect

    Hansen, E.S.; Hjortdal, V.E.; Noer, I.; Christensen, S.B.; Holm, I.E.; Buenger, C.

    1989-03-01

    The pathogenesis of subchondral bone lesions and growth plate affection in hemophilic arthropathy was studied in puppies by means of repeated regional /sup 99m/Tc-diphosphonate scintimetry and contact autoradiography. Unilateral hemarthrosis of the knee was induced by biweekly intraarticular injections of autologous blood for 12 weeks. Hemarthrosis caused an early (2 to 4 weeks) decrease in uptake of /sup 99m/Tc-diphosphonate in the juxtaarticular growth plates (ratio 0.7) and a delayed (8 to 10 weeks) increase in epiphyseal uptake (ratio 1.5). In a recovery phase after hemarthrosis, growth plate uptake returned to normal, while the epiphyseal uptake remained elevated for 8 to 10 weeks. By contact autoradiography, the growth plate uptake was localized to the calcification layer at the metaphyseal aspect of the growth plates, while the epiphyseal uptake mainly was seen in the thin subchondral and subsynovial bone layer and around osteophytes. The changes in uptake of /sup 99m/Tc-diphosphonate following hemarthrosis for 3 months were reversible and could be ascribed to the presence of synovial inflammation.

  16. CT evaluation of medial clavicular epiphysis as a method of bone age determination in adolescents and young adults

    PubMed Central

    Ufuk, Furkan; Agladioglu, Kadir; Karabulut, Nevzat

    2016-01-01

    PURPOSE We aimed to investigate the use of computed tomography (CT) staging of the medial clavicular epiphysis ossification in forensic bone age determination, and find a CT criterion to determine whether an individual is adult or not. METHODS Chest CT and pulmonary CT angiography exams of 354 patients between 10 and 30 years of age (mean, 21.4 years) were retrospectively evaluated for epiphyseal ossification phase of the bilateral medial clavicles (708 clavicles) and compared with the sex and chronologic age of the individuals. The ossification phase of the medial clavicular epiphyses was classified from stage I to stage V using a modified staging system. RESULTS Epiphyseal ossification center appeared from 11 to 21 years of age. Partial fusion occurred between 16 and 23 years of age. Complete fusion was first achieved at the ages of 18 and 19 years for male and female individuals, respectively. The probability of an individual being ≥18 years old was 70.8% in stage III A and 100% in stages III B, IV, and V in females and males. CONCLUSION CT evaluation of the medial clavicular epiphysis is helpful in forensic age determination and stage III B can be used as a criterion to make the prediction that an individual is older than 18 years. PMID:27015321

  17. Ossification Pattern of Estuarine Dolphin (Sotalia guianensis) Forelimbs, from the Coast of the State of Espírito Santo, Brazil.

    PubMed

    de Carvalho, Anna Paula Martins; Lima, Juliana Ywasaki; Azevedo, Carolina Torres; Botta, Silvina; de Queiroz, Fábio Ferreira; Campos, Adélia Sepúlveda; Barbosa, Lupércio de Araújo; da Silveira, Leonardo Serafim

    2015-01-01

    The estuarine dolphin, Sotalia guianensis, is one of the most abundant cetacean species in Brazil. Determination of age and of aspects associated with the development of this species is significant new studies. Counts of growth layer groups in dentin are used to estimate age of these animals, though other ways to evaluate development are also adopted, like the measurement of total length (TL). This study presents a procedure to evaluate the development of the estuarine dolphin based on the ossification pattern of forelimbs. Thirty-seven estuarine dolphins found in the state of Espírito Santo, Brazil, were examined. Age was estimated, TL was measured and ossification of epiphyses was examined by radiography. We analyzed results using the Spearman correlation. Inspection of radiographs allowed evaluation of the significance of the correlation between age and development of the proximal (r = 0.9109) and distal (r = 0.9092) radial epiphyses, and of the distal ulnar epiphyses (r = 0.9055). Radiographic analysis of forelimbs proved to be an appropriate method to evaluate physical maturity, and may be a helpful tool to estimate age of these animals in ecological and population studies. PMID:26017269

  18. Climate-mediated shifts in Neandertal subsistence behaviors at Pech de l'Azé IV and Roc de Marsal (Dordogne Valley, France).

    PubMed

    Hodgkins, Jamie; Marean, Curtis W; Turq, Alain; Sandgathe, Dennis; McPherron, Shannon J P; Dibble, Harold

    2016-07-01

    Neandertals disappeared from Europe just after 40,000 years ago. Some hypotheses ascribe this to numerous population crashes associated with glacial cycles in the late Pleistocene. The goal of this paper is to test the hypothesis that glacial periods stressed Neandertal populations. If cold climates stressed Neandertals, their subsistence behaviors may have changed-requiring intensified use of prey through more extensive nutrient extraction from faunal carcasses. To test this, an analysis of Neandertal butchering was conducted on medium sized bovid/cervid remains composed of predominately red deer (Cervus elaphus), reindeer (Rangifer tarandus), and roe deer (Capreolus caprelous) deposited during global warm and cold phases from two French sites: Pech de l'Azé IV (Pech IV, Bordes' excavation) and Roc de Marsal (RDM). Analysis of surface modification on high survival long bones and proximal and middle phalanges demonstrates that skeletal elements excavated from the cold levels (RDM Level 4, Pech IV Level I2) at each cave have more cut marks and percussion marks than elements from the warm levels (RDM Level 9, Pech IV Level Y-Z) after controlling for fragment size. At both sites, epiphyseal fragments are rare, and although this pattern can result from carnivore consumption, carnivore tooth marks are almost nonexistent (<0.1%). Alternatively, processing epiphyseal ends for bone grease may have been a Neandertal survival strategy, and epiphyses were more intensively percussed in cold levels than in warm levels at both RDM and Pech IV. The exploitation of low marrow yield elements such as phalanges does not show a consistent pattern relating to climate, but may have been a general Neandertal behavioral characteristic, suggesting that these hominids were regularly on the edge of sufficient nutrient availability even during interglacials. Overall, the faunal assemblages from Roc de Marsal and Pech IV provide some support for the hypothesis that Neandertals were processing

  19. Development of an anthropomorphic shoulder phantom model that simulates bony anatomy for sonographic measurement of the acromiohumeral distance.

    PubMed

    Adusumilli, Pratik; McCreesh, Karen; Evans, Tony

    2014-11-01

    The purpose of this project was to create a sonographic phantom model of the shoulder that was accurate in bone configuration. Its main purpose was for operator training to measure the acromiohumeral distance. A computerized 3-dimensional model of the superior half of the humerus and scapula was rendered and 3-dimensionally printed. The bone model was embedded in a gelatin compound and set in a shoulder-shaped mold. The materials used had speeds of sound that were well matched to soft tissue and epiphyseal bone. The model was specifically effective in simulating the acromiohumeral distance because of its accurate bone geometry. PMID:25336490

  20. Del(12)(p11.21p12.2) associated with an asphyxiating thoracic dystrophy or chondroectodermal dysplasia-like syndrome

    SciTech Connect

    Nagai, T.; Kato, R.; Hasegawa, T.

    1995-01-02

    We describe a 5-year-old Japanese boy who has some radiographic findings characteristic of asphyxiating thoracic dystrophy (ATD)-chondroectodermal dysplasia with a de novo chromosome abnormality. He also has mild mental retardation, short stature, hypoplastic hair and skin, oligodontia, small thoracic cage, hypoplastic pelvis and cone-shaped epiphyses of hands. On cytogenetic studies he was found to have a de novo del(12)(p11.21p12.2). These results suggest that the locus of the gene associated with ATD-chondroectodermal dysplasia may be situated at 12p11.21p12.2. 11 refs., 2 figs.

  1. Experimental determinations of carcass processing by Plio-Pleistocene hominids and carnivores at FLK 22 (Zinjanthropus). Olduvai Gorge, Tanzania.

    PubMed

    Capaldo, S D

    1997-11-01

    Published and unpublished skeletal and surface mark data from the large, well-preserved, bovid dominated FLK 22 (Zinjanthropus) archaeofauna are analyzed using data derived from four different experimental control samples. The control samples are realistic because they are based on natural history and paleoecological data collected from FLK 22, and other Olduvai Gorge assemblages; they are precise because independent experimental studies following the same methods have generated the same results; and they restore generality to the study of site formation because each one models a different hominid and/or carnivore scenario of site formation. Comparability between FLK 22 and the control samples is established by excluding specimens from the former which do not meet identification and reporting standards derived from the latter. As in two previous studies, a comprehensive analysis of tooth marks and tool marks on long bone specimens from FLK 22 indicates that they were processed in three stages. In stage one, carnivores defleshed long bones, as inferred from the high percentage of tooth marks on midshaft fragments. In stage two, hominids processed intact long bones for marrow, as inferred from percussion mark percentages. Cut marks suggest that long bones retained flesh, but the amount, as yet, cannot be determined using cut mark percentages. In stage three, carnivores processed long bone epiphyses for grease, as inferred from the under-representation of long bone epiphyses and the high percentage of tooth marks on near-epiphyses and surviving epiphyses. The lack of comprehensive skeletal and surface mark data on cranial, axial, compact, and other specimens currently limits the application of experimental results. However, the available data suggest that the condition and representation of these items in the FLK 22 assemblage are also consistent with a carnivore to hominid to carnivore sequence of site formation. The variety of elements present, and their extensive

  2. Cono-spondylar dysplasia: clinical, radiographic, and molecular findings of a previously unreported disorder.

    PubMed

    Ben-Omran, Tawfeg; Lakhani, Shenela; Almureikhi, Mariam; Ali, Rehab; Takahashi, Atsushi; Miyake, Noriko; Matsumoto, Naomichi; Ikegawa, Shiro; Superti-Furga, Andrea; Unger, Sheila

    2014-09-01

    We report on a consanguineous Arab family in which three sibs had an unusual skeletal dysplasia characterized by anterior defects of the spine leading to severe lumbar kyphosis and marked brachydactyly with cone epiphyses. The clinical phenotype also included dysmorphic facial features, epilepsy, and developmental delay. This constellation likely represents a previously undescribed skeletal dysplasia, most probably inherited in an autosomal recessive pattern. A homozygosity mapping approach has thus far failed to unearth the responsible gene as the region shared by these three sibs is 27.7 Mb in size and contains over 200 genes with no obvious candidate. PMID:24975242

  3. Wolcott-Rallison syndrome.

    PubMed

    Juneja, A; Sultan, A; Bhatnagar, S

    2012-01-01

    Multiple epiphyseal dysplasia with early-onset diabetes mellitus (also known as Wolcott-Rallison syndrome) is a rare autosomal recessive disorder that manifests itself in early infancy with symptoms of diabetes mellitus. Short stature and walking difficulties become evident in the 2 nd year of life when the child starts to walk. These skeletal changes are progressive with age. There is usually a short trunk, excessive lordosis, a short and broad chest, and genu valgum. This report presents a case of Wolcott-Rallison syndrome in a 10 year old child. PMID:23263430

  4. A new type of a lethal osteochondrodysplasia with angel-shaped brachyphalangy.

    PubMed

    Caduff, R; Giedion, A; Briner, J; Martin, E

    1994-01-01

    A hydropic stillborn female fetus of 22 weeks gestation with shortlimbed skeletal dysplasia and brachyphalangy is described. The markedly shortened phalanges of both hands had a most unusual angel-like configuration radiologically. Histological examination and comparison with a normal hand of the same gestational age revealed this appearance to be due to disturbed enchondral ossification with premature calcification of epiphyseal cartilage and thickening and outfolding of diaphyseal bone as wing-shaped appositions. Magnetic resonance imaging of the fetus demonstrated marked hyperplasia of cartilage, most impressive in the pelvis. This new type of lethal bone dysplasia may be placed in the group of metatropic dysplasias and similar disorders. PMID:7981898

  5. Unusual proximal tibiofibular synostosis.

    PubMed

    Takai, S; Yoshino, N; Hirasawa, Y

    1999-01-01

    Proximal tibiofibular synostosis without multiple hereditary exostosis is extremely rare and only 7 cases have been reported in the literature. All of the previously reported cases accompanied deformities such as distal positioning of the proximal tibiofibular joint, leg length discrepancy, bowing of the fibula, and valgus deformity of the knee. The present case of a 24-year-old man had neither a history of trauma nor deformity around the knee. Therefore, it was suggested that this type of synostosis occurred after epiphyseal plate closure. PMID:10741527

  6. Ischial hypoplasia, tibial hypoplasia and facial abnormalities: a new syndrome?

    PubMed

    Nishimura, G; Haga, Y; Aoki, K; Hasegawa, T

    1998-12-01

    A child with facial abnormalities, short stature and a variety of skeletal alterations is reported. The facial abnormalities comprised low-set ears, short nose with a long philtrum, micrognathia and cleft palate. The skeletal alterations included ischial hypoplasia, malformations of the cervical spine, hypoplasia of the lesser trochanters, tibial hypoplasia with bowing of the lower legs, tibio-fibular diastasis with malformed distal tibial epiphyses, clubfeet and brachymesophalangy. The constellation of clinical and radiological findings in the present patient do not fit any known malformation syndrome. PMID:9880644

  7. Osteofibrous dysplasia of the tibia treated by bracing.

    PubMed

    Akamatsu, N; Hamada, Y; Kohno, H; Siddiqi, N A

    1992-01-01

    Osteofibrous dysplasia of the tibia in children will commonly recur after surgical resection. The use of a leg brace until puberty offers a useful method of conservative management. Seven female patients, age three months to nine years at the time of brace treatment, have been followed for 3.5 to 18 years, an average of nine years, with evidence of satisfactory healing of the lesions in all. Three of the cases had recurred after surgery, two with fibular grafts and one required leg lengthening. The use of a brace to control bowing of the tibia while awaiting spontaneous regression is advised until epiphyseal closure. PMID:1428320

  8. Reconstruction of the lateral malleolus in a type-Ib fibular hemimelia with a microvascular proximal fibular flap: a case report.

    PubMed

    Cavadas, Pedro C; Thione, Alessandro

    2015-07-01

    Fibular hemimelia, or fibular hypoplasia-aplasia, is the most frequent congenital long-bone deficiency. There is still some debate on reconstruction versus amputation for the severe type Ib and type II cases. Limb-length discrepancy can be corrected with Ilizarov methods, but ankle stability remains a problem. The absence of the lateral malleolus destabilizes the mortise in valgus and ankle fusion is usually needed. A case of lateral malleolus reconstruction in a teenage patient with severe type-Ib fibular hemimelia using a contralateral free proximal fibular epiphyseal transfer is reported. PMID:26035352

  9. [Possibilities of osteotomy. Osteotomy and corticotomy techniques].

    PubMed

    Baumgart, R; Kettler, M; Zeiler, C; Betz, A; Schweiberer, L

    1997-10-01

    Corrective measures on the bone undertaken after the fusion of epiphyses are only possible through an initial break in its continuity. This paper deals with the different methods of osteotomy available to the orthopaedic or trauma surgeon. After introducing the terminology of the so-called "osteotomy", the vascularity of the bone, special features of the various osteotomy site, the different indications, and particular details of the operative procedures are discussed. Special emphasis is placed on minimally invasive techniques and osteotomies in the framework of callus distraction. In addition to established procedures a new sawing technique for the Küntscher's closed osteotomy is described. PMID:9446235

  10. Short Stature in Chronic Kidney Disease Treated with Growth Hormone and an Aromatase Inhibitor

    PubMed Central

    Mendley, Susan R.; Spyropoulos, Fotios; Counts, Debra R.

    2015-01-01

    We describe an alternative strategy for management of severe growth failure in a 14-year-old child who presented with advanced chronic kidney disease close to puberty. The patient was initially treated with growth hormone for a year until kidney transplantation, followed immediately by a year-long course of an aromatase inhibitor, anastrozole, to prevent epiphyseal fusion and prolong the period of linear growth. Outcome was excellent, with successful transplant and anticipated complete correction of height deficit. This strategy may be appropriate for children with chronic kidney disease and short stature who are in puberty. PMID:26101681

  11. Re-implantation of a degloving amputation of distal index finger caused by fireworks: a case report and literature review.

    PubMed

    Zhang, Q; Cao, X C

    2013-07-01

    Amputations associated with fireworks are customarily treated by stump revision resulting in permanent disability. In this case report, we present an eight-year old boy who suffered an amputation of his right distal index finger at the level of the epiphyseal disk with degloving injury of the amputated finger caused by fireworks. Successful re-implantation was achieved. Two-year follow-up revealed fair cosmesis and acceptable functional and aesthetic recovery though the free distal phalanx had been absorbed completely. Re-implantation of a degloving amputation finger caused by fireworks is possible and can provide good distal soft tissue coverage and recovery of sensory and motor functions. PMID:24756749

  12. Operative management of bilateral Salter-Harris type III fractures of the proximal phalanges of the great toes of a 10-year-old female ballet dancer: a case report.

    PubMed

    Csonka, Akos; Sikarinkul, Eakachit; Gargyan, Istvan; Boa, Kristof; Varga, Endre

    2016-07-01

    Differentiation between the normal variant cleft epiphysis and Salter-Harris type III fracture of the first proximal phalanges of the foot in children might be challenging. The authors describe a case of a 10-year-old ballet dancer girl with bilateral epiphyseal segmentation of the first proximal phalanges of the foot, unresponsive to conservative treatment. Considered a nonhealing stress-induced fracture, operative treatment with closed reduction and Herbert screw insertion was chosen on both sides. Complete union was achieved, with significant reduction of pain. The presented case suggests that internal fixation can be a viable option in the treatment of the problem. PMID:26919623

  13. Fourth case of cerebral, ocular, dental, auricular, skeletal syndrome (CODAS), description of new features and molecular analysis.

    PubMed

    Marlin, S; Ducou Le Pointe, H; Le Merrer, M; Portnoi, M F; Chantot, S; Jonard, L; Mantel-Guiochon, A; Siffroi, J P; Garabedian, E N; Denoyelle, F

    2010-06-01

    Cerebral, ocular, dental, auricular, skeletal syndrome (CODAS, OMIM 600373) is a very rare congenital malformation syndrome. This clinical entity is highly distinctive and associates mental retardation, cataract, enamel abnormalities, malformations of the helix, epiphyseal and vertebral malformations, and characteristic dysmorphic features. Since 1991, only three affected children have been reported. The etiology and pattern of inheritance of CODAS syndrome still remain unknown. We describe a new sporadic case presenting with all the characteristic features of CODAS syndrome associated with previously unreported malformations of the heart, larynx, and liver. All investigations such as karyotype, metabolic screening and array CGH were normal. PMID:20503327

  14. Response of growing bone to irradiation: A proposed late effects scoring system

    SciTech Connect

    Eifel, P.J.; Donaldson, S.S.; Thomas, P.R.M.

    1995-03-30

    The effect of radiation on epiphyseal bone growth is one of the most important dose-limiting factors in the radiotherapeutic management of children with malignant neoplasms. Clinical and laboratory evidence suggest that many factors may influence the severity of radiation-induced growth arrest. However, the absence of a consistent scoring system for late effects has hampered efforts to analyze the influence of various therapeutic maneuvers or to compare and collate results from different reported series. In this review, laboratory and clinical studies of radiation effects on growing bone are summarized, and a late effects scoring system is proposed. 29 refs., 1 fig., 2 tabs.

  15. Skeletal abnormalities of tricho-rhino-phalangeal syndrome type I.

    PubMed

    de Barros, Guilherme Monteiro; Kakehasi, Adriana Maria

    2016-01-01

    The tricho-rhino-phalangeal syndrome (TRPS) type I is a rare genetic disorder related to the TRPS1 gene mutation in chromosome 8, characterized by craniofacial abnormalities and disturbances in formation and maturation of bone matrix. The hallmarks are sparse and brittle hair, tendency to premature baldness, bulbous nose called pear-shaped, long and flat filter and low ear implantation. The most noticeable skeletal changes are clinodactyly, phalangeal epiphyses of the hands appearing as cone-shaped, short stature and hip joint malformations. We report a case of a teenager boy diagnosed with TRPS and referred for rheumatologic evaluation due to joint complaints. PMID:27267340

  16. The time of onset of abnormal calcification in spondylometaepiphyseal dysplasia, short limb-abnormal calcification type.

    PubMed

    Tüysüz, Beyhan; Gazioğlu, Nurperi; Ungür, Savaş; Aji, Dolly Yafet; Türkmen, Seval

    2009-01-01

    A 1-month-old boy with shortness of extremities on prenatal US was referred to our department with a provisional diagnosis of achondroplasia. His height was normal but he had short extremities and platyspondyly, premature carpal epiphyses on both hands, and short tubular bones with irregular metaphyses on radiographs. Re-evaluation of the patient at the age of 1 year revealed very short height and premature calcification of the costal cartilages and epiphyses. Spondylometaepiphyseal dysplasia (SMED), short limb-abnormal calcification type was diagnosed. This condition is a very rare autosomal recessively inherited disorder, and most of the patients die in early childhood due to neurological involvement. At the age of 2 years and 5 months, a CT scan showed narrowing of the cervical spinal canal. One month later he died suddenly because of spinal cord injury. In conclusion early diagnosis is very important because the recurrence risk is high and patients may die due to early neurological complications. The time of onset of abnormal calcifications, a diagnostic finding of the disease, is at the age of around 1 year in most patients. When abnormal calcifications are not yet present, but radiological changes associated with SMED are present, this rare disease must be considered. PMID:19002453

  17. Alpha-gamma equalization-enhanced hand radiographic image segmentation scheme

    NASA Astrophysics Data System (ADS)

    Lin, Hsiu-Hsia; Shu, San-Ging; Kuo, Shiau-Wei; Wang, Chien-Hsuan; Chan, Ya-Ping; Yu, Shyr-Shen

    2009-10-01

    Bone age assessment of children is a procedure frequently performed in pediatric radiology. The feature extractions of metaphyseal and epiphyseal regions are crucial to automatic bone age assessment. The first step of feature extraction is applying a segmentation scheme to find exact regions of epiphysis and metaphysis. A segmentation method is normally based on both intensity information and the relative location of pixels. There is a fundamental problem; when the intensity contrast of soft tissue and bony tissue is poor, bony and soft tissue cannot easily be separated. We propose an α-gamma equalization method to increase the intensity contrast between bony and soft tissue. Sobel, two-means, Canny edge-detection, and watershed methods are applied to illustrate the effect of this method on initial segmentation. Adaptive two-means and gradient vector flow snake are adopted for the final segmentation. Experimental results reveal that α-gamma equalization-enhanced two-means initial segmentation with an adaptive two-means clustering scheme can greatly reduce the average error measurements of segmentations. These are evaluated according to the following measurements: misclassification error, edge mismatch, region nonuniformity, relative foreground area eror, and modified Hausdorff distance. Furthermore, the experimental results show that the proposed scheme provides increased stable performance for the segmentation of epiphyseal/metaphyseal regions.

  18. A Pediatric Comminuted Talar Fracture Treated by Minimal K-Wire Fixation Without Using a Tourniquet

    PubMed Central

    Inal, Sermet; Inal, Canan

    2014-01-01

    Background Pediatric comminuted talar fractures are reported to be rare, and treatment options such as minimal internal K-wire fixation without using a tourniquet to prevent avascular necrosis have not previously been investigated. Case Description We report a case of a comminuted talar body and a non-displaced neck fracture with dislocation of the tibiotalar, talonavicular and subtalar joints with bimalleolar epiphyseal fractures in an 11-year-old boy due to a fall from height. We present radiological findings, the surgical procedure and clinical outcomes of minimal internal K-wire fixation without using a tourniquet. Literature Review Avascular necrosis rates are reported to be between 0 % and 66 % after fractures of the neck of the talus and the talar body in children. The likelihood of developing avascular necrosis increases with the severity of the fracture. Clinical Relevance To avoid avascular necrosis in a comminuted talar fracture accompanied by tibiotalar, talonavicular, subtalar dislocations and bimalleolar epiphyseal fractures, a minimal internal K-wire fixation without the use of a tourniquet was performed. The outcome was evaluated by the American Orthopedic Foot and Ankle Society score (AOFAS). A score of 90 (excellent) was found at the end of the second year of follow up. Radiology revealed preservation of the joint with no evidence of avascular necrosis, and clinical findings revealed a favorable functional outcome after two years. Level of Evidence 4 PMID:25328479

  19. Osteoporosis in men with idiopathic hypogonadotropic hypogonadism

    SciTech Connect

    Finkelstein, J.S.; Klibanski, A.; Neer, R.M.; Greenspan, S.L.; Rosenthal, D.I.; Crowley, W.F. Jr.

    1987-03-01

    To assess the effect of testosterone deficiency on skeletal integrity in men, we determined bone density in 23 hypogonadal men with isolated gonadotropin-releasing hormone deficiency and compared those values with ones from controls. Cortical bone density, as assessed by single-photon absorptiometry of the nondominant radius, ranged from 0.57 to 0.86 g/cm2 (mean +/- SE, 0.71 +/- 0.02) in patients with fused epiphyses and from 0.57 to 0.67 g/cm2 (mean, 0.61 +/- 0.01) in patients with open epiphyses, both of which were significantly (p less than 0.001) lower than normal. Spinal trabecular bone density, as assessed by computed tomography, was similarly decreased (p less than 0.0001) and ranged from 42 to 177 mg K2HPO4/cm3 (mean, 112 +/- 7). Cortical bone density was at least 2 SD below normal in 16 of 23 men, and 8 men had spinal bone densities below the fracture threshold of 80 to 100 mg K2HPO4/cm3. Osteopenia was equally severe in men with immature and mature bone ages, suggesting that abnormal bone development plays an important role in the osteopenia of men with idiopathic hypogonadotropic hypogonadism.

  20. In vivo demonstration of cell types in bone that harbor epidermal growth factor receptors

    SciTech Connect

    Martineau-Doize, B.; Lai, W.H.; Warshawsky, H.; Bergeron, J.J.

    1988-08-01

    The binding and internalization of (/sup 125/I)iodoepidermal growth factor (EGF) by bone cells of the rat was demonstrated in situ by quantitative radioautography. Specific binding sites were observed on a cell profile enriched in endocytic components, including lysosome-like structures, a rough endoplasmic reticulum-rich cell profile, and a cell profile that histologically resembles an undifferentiated precursor cell. By the criteria of gel filtration and precipitability by trichloroacetic acid, most of the bound (/sup 125/I)iodo-EGF was considered intact. By morphological criteria none of the cell profiles that bound (/sup 125/I)iodo-EGF corresponded to fully formed osteoclasts or osteoblasts. The endocytic cell was found in the epiphyseal plate between the invading capillary and the transverse and longitudinal cartilage septa as well as near osteoclasts in the zone of mixed spicules. The rough endoplasmic reticulum-rich cell was present in vacated chondrocyte lacunae of the epiphyseal plate close to the metaphysis, and the poorly differentiated cell was observed between the mixed spicules of the metaphysis. Similar cell types were also found in the alveolar bone surrounding the incisors. These cells may be the origin of established bone cell lines that harbor high concentrations of EGF receptors and may also be responsible for the humoral hypercalcemia in response to the reported actions of injected EGF or transforming growth factor-alpha as well as that of malignancy.

  1. The Endocrine Role of Estrogens on Human Male Skeleton

    PubMed Central

    Rochira, Vincenzo; Kara, Elda; Carani, Cesare

    2015-01-01

    Before the characterization of human and animal models of estrogen deficiency, estrogen action was confined in the context of the female bone. These interesting models uncovered a wide spectrum of unexpected estrogen actions on bone in males, allowing the formulation of an estrogen-centric theory useful to explain how sex steroids act on bone in men. Most of the principal physiological events that take place in the developing and mature male bone are now considered to be under the control of estrogen. Estrogen determines the acceleration of bone elongation at puberty, epiphyseal closure, harmonic skeletal proportions, the achievement of peak bone mass, and the maintenance of bone mass. Furthermore, it seems to crosstalk with androgen even in the determination of bone size, a more androgen-dependent phenomenon. At puberty, epiphyseal closure and growth arrest occur when a critical number of estrogens is reached. The same mechanism based on a critical threshold of serum estradiol seems to operate in men during adulthood for bone mass maintenance via the modulation of bone formation and resorption in men. This threshold should be better identified in-between the ranges of 15 and 25 pg/mL. Future basic and clinical research will optimize strategies for the management of bone diseases related to estrogen deficiency in men. PMID:25873947

  2. Curve progression in Risser stage 0 or 1 patients after posterior spinal fusion for idiopathic scoliosis.

    PubMed

    Roberto, R F; Lonstein, J E; Winter, R B; Denis, F

    1997-01-01

    A retrospective review was performed to determine "crankshaft" prevalence in 86 immature patients who underwent posterior spinal fusion for idiopathic scoliosis. Tanner stage, chronologic age, bone age, and epiphyseal status were used as maturity indicators. Overall, 62 (72%) patients progressed < or = 10 degrees, 18 (21%) patients progressed 11-15 degrees, and six (7%) patients progressed > or = 16 degrees in the coronal plane. Tanner I patients with open triradiate cartilage had the highest rate of crankshaft occurrence; nine (75%) of 12 patients progressed >10 degrees (p < 0.05). Fifty-two percent of Tanner I, 26% of Tanner II, 11% of Tanner III, and no Tanner IV patients progressed >10 degrees (p < 0.05). Cobb angle increases of >10 degrees degrees occurred in 54% of patients with open triradiate cartilage (p < 0.05) and in 48% of patients with open capital femoral epiphyses (p < 0.05). Anterior and posterior spinal fusion should be considered in prepubertal (Tanner I) patients with open triradiate cartilage. PMID:9591972

  3. Metatarsal fusion pattern and developmental morphology of the Olduvai Hominid 8 foot: Evidence of adolescence.

    PubMed

    Susman, Randall L; Patel, Biren A; Francis, Megan J; Cardoso, Hugo F V

    2011-01-01

    The morphology of the Olduvai Hominid (OH) 8 foot and the sequence of metatarsal epiphyseal fusion in modern humans and chimpanzees support the hypothesis that OH 8 belonged to an individual of approximately the same relative age as the OH 7 subadult, the holotype of Homo habilis. Modern humans and chimpanzees exhibit a variety of metatarsal epiphyseal fusion patterns, including one identical to that observed in OH 8 in which metatarsal 1 fuses before metatarsals 2-5. More than the metatarsal fusion sequence, however, the principal evidence of the youthful age of OH 8 lies in the morphology of metatarsals 1, 2, and 3. Because both OH 8 and OH 7 come from the same stratum at the FLK NN type site, the most parsimonious explanation of the OH 8 and OH 7 data is that this material belonged to the same individual, as originally proposed by Louis Leakey. The proposition that OH 8 belonged to an adult is unsupported by morphology, including radiographic evidence, and the fusion sequences in human and chimpanzee skeletal material reported here and in the literature. PMID:21074829

  4. The effect of Solanum malacoxylon on rachitic bone lesions in the rat.

    PubMed

    Kraft, D; van Herrath, D; Offermann, G; Schaefer, K

    1975-01-01

    The plant Solanum malacoxylon (S.M.) is known to cause severe soft tissue calcifications in cattle and sheep and has recently become of special interest since it exerts biological actions which resemble those of vitamin D. In order to investigate whether S.M. is capable to improve the rachitic bone changes in vitamin D and phosphate deficient rats, a watery extract of 50, 100 and 200 mg S.M. was fed daily to these animals over a period of 10 days. The width of epiphyseal plates was compared after the time with those of rats treates with 0, 0.225, 0.45, and 0.9 IU of vitamin D3 daily. There was a dose related curative effect of S.M. on the epiphyseal lesions very similar to that of vitamin D3. The hypercalcemic and hyperphosphatemic effect of S.M. was identical to that of vitamin D3. The 25-hydroxy-vitamin D serum levels remained almost undetectable in the S.M. treated rats as well as in the vitamin D3 treated animals. PMID:170546

  5. Spaceflight-induced bone loss alters failure mode and reduces bending strength in murine spinal segments.

    PubMed

    Berg-Johansen, Britta; Liebenberg, Ellen C; Li, Alfred; Macias, Brandon R; Hargens, Alan R; Lotz, Jeffrey C

    2016-01-01

    Intervertebral disc herniation rates are quadrupled in astronauts following spaceflight. While bending motions are main contributors to herniation, the effects of microgravity on the bending properties of spinal discs are unknown. Consequently, the goal of this study was to quantify the bending properties of tail discs from mice with or without microgravity exposure. Caudal motion segments from six mice returned from a 30-day Bion M1 mission and eight vivarium controls were loaded to failure in four-point bending. After testing, specimens were processed using histology to determine the location of failure, and adjacent motion segments were scanned with micro-computed tomography (μCT) to quantify bone properties. We observed that spaceflight significantly shortened the nonlinear toe region of the force-displacement curve by 32% and reduced the bending strength by 17%. Flight mouse spinal segments tended to fail within the growth plate and epiphyseal bone, while controls tended to fail at the disc-vertebra junction. Spaceflight significantly reduced vertebral bone volume fraction, bone mineral density, and trabecular thickness, which may explain the tendency of flight specimens to fail within the epiphyseal bone. Together, these results indicate that vertebral bone loss during spaceflight may degrade spine bending properties and contribute to increased disc herniation risk in astronauts. PMID:26285046

  6. Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia

    PubMed Central

    Royer-Bertrand, Beryl; Castillo-Taucher, Silvia; Moreno-Salinas, Rodrigo; Cho, Tae-Joon; Chae, Jong-Hee; Choi, Murim; Kim, Ok-Hwa; Dikoglu, Esra; Campos-Xavier, Belinda; Girardi, Enrico; Superti-Furga, Giulio; Bonafé, Luisa; Rivolta, Carlo; Unger, Sheila; Superti-Furga, Andrea

    2015-01-01

    We and others have reported mutations in LONP1, a gene coding for a mitochondrial chaperone and protease, as the cause of the human CODAS (cerebral, ocular, dental, auricular and skeletal) syndrome (MIM 600373). Here, we delineate a similar but distinct condition that shares the epiphyseal, vertebral and ocular changes of CODAS but also included severe microtia, nasal hypoplasia, and other malformations, and for which we propose the name of EVEN-PLUS syndrome for epiphyseal, vertebral, ear, nose, plus associated findings. In three individuals from two families, no mutation in LONP1 was found; instead, we found biallelic mutations in HSPA9, the gene that codes for mHSP70/mortalin, another highly conserved mitochondrial chaperone protein essential in mitochondrial protein import, folding, and degradation. The functional relationship between LONP1 and HSPA9 in mitochondrial protein chaperoning and the overlapping phenotypes of CODAS and EVEN-PLUS delineate a family of “mitochondrial chaperonopathies” and point to an unexplored role of mitochondrial chaperones in human embryonic morphogenesis. PMID:26598328

  7. The development of a mature collagen network in cartilage from human bone marrow stem cells in Transwell culture.

    PubMed

    Murdoch, Alan D; Hardingham, Timothy E; Eyre, David R; Fernandes, Russell J

    2016-03-01

    Damaged hyaline cartilage shows a limited capacity for innate repair. Potential sources of cells to augment the clinical repair of cartilage defects include autologous chondrocytes and mesenchymal stem cells. We have reported that culture of human bone marrow mesenchymal stem cells with specific growth and differentiation factors as shallow multilayers on Transwell permeable membranes provided ideal conditions for chondrogenesis. Rigid translucent cartilaginous disks formed and expressed cartilage-specific structural proteins aggrecan and type II collagen. We report here the analysis of the collagen network assembled in these cartilage constructs and identify key features of the network as it became mature during 28 days of culture. The type II collagen was co-polymerized with types XI and IX collagens in a fibrillar network stabilized by hydroxylysyl pyridinoline cross-links as in epiphyseal and hyaline cartilages. Tandem ion-trap mass-spectrometry identified 3-hydroxylation of Proline 986 and Proline 944 of the α1(II) chains, a post-translational feature of human epiphyseal cartilage type II collagen. The formation of a type II collagen based hydroxy-lysyl pyridinoline cross-linked network typical of cartilage in 28 days shows that the Transwell system not only produces, secretes and assembles cartilage collagens, but also provides all the extracellular mechanisms to modify and generate covalent cross-links that determine a robust collagen network. This organized assembly explains the stiff, flexible nature of the cartilage constructs developed from hMSCs in this culture system. PMID:26523516

  8. The Wnt antagonist Wif-1 interacts with CTGF and inhibits CTGF activity.

    PubMed

    Surmann-Schmitt, Cordula; Sasaki, Takako; Hattori, Takako; Eitzinger, Nicole; Schett, Georg; von der Mark, Klaus; Stock, Michael

    2012-05-01

    Wnt inhibitory factor 1 (Wif-1) is a secreted antagonist of Wnt signalling. We recently demonstrated that this molecule is expressed predominantly in superficial layers of epiphyseal cartilage but also in bone and tendon. Moreover, we showed that Wif-1 is capable of binding to several cartilage-related Wnt ligands and interferes with Wnt3a-dependent Wnt signalling in chondrogenic cells. Here we provide evidence that the biological function of Wif-1 may not be confined to the modulation of Wnt signalling but appears to include the regulation of other signalling pathways. Thus, we show that Wif-1 physically binds to connective tissue growth factor (CTGF/CCN2) in vitro, predominantly by interaction with the C-terminal cysteine knot domain of CTGF. In vivo such an interaction appears also likely since the expression patterns of these two secreted proteins overlap in peripheral zones of epiphyseal cartilage. In chondrocytes CTGF has been shown to induce the expression of cartilage matrix genes such as aggrecan (Acan) and collagen2a1 (Col2a1). In this study we demonstrate that Wif-1 is capable to interfere with CTGF-dependent induction of Acan and Col2a1 gene expression in primary murine chondrocytes. Conversely, CTGF does not interfere with Wif-1-dependent inhibition of Wnt signalling. These results indicate that Wif-1 may be a multifunctional modulator of signalling pathways in the cartilage compartment. PMID:21928342

  9. The Radiograph of the Pelvis as a Window to Skeletal Dysplasias.

    PubMed

    Gajarajulu, Vijayalakshmi; Natarajan, Balakrishnan; Muralinath, S

    2016-06-01

    Skeletal dysplasias are disorders of bone formation. There are many dysplasias that have been identified and studied over the years and long lists of radiological features have been documented; it is not possible to remember all of them, most of which are common to more than one dysplasia. This article is about a practical approach to the radiological diagnosis of skeletal dysplasias by viewing only a few radiographs rather than the entire skeletal survey. The radiographs that are to be studied are AP view of the pelvis, dorsolumbar spine- AP and lateral view and both hands PA view, in that order. The skull lateral view and both knees AP view are sometimes required. The authors advice to set out with the pelvis that provides information of not only the pelvic bones but also parts of the lumbar spine and the upper ends of the femur including their epiphyses, metaphyses and a part of the diaphyses. Sometimes the diagnosis is reached with only this one radiograph, as in achondroplasia or it may indicate a group like mucopolysaccharidoses which can be sorted out with radiographs of the spine and hands or the upper part of the femur can provide a cue to epiphyseal and metaphyseal dysplasias. Gamuts and atlases can be consulted for the rare dysplasias. PMID:26821546

  10. Morphological analysis of the flippers in the Franciscana dolphin, Pontoporia blainvillei, applying X-ray technique.

    PubMed

    Del Castillo, Daniela Laura; Panebianco, María Victoria; Negri, María Fernanda; Cappozzo, Humberto Luis

    2014-07-01

    Pectoral flippers of cetaceans function to provide stability and maneuverability during locomotion. Directional asymmetry (DA) is a common feature among odontocete cetaceans, as well as sexual dimorphism (SD). For the first time DA, allometry, physical maturity, and SD of the flipper skeleton--by X-ray technique--of Pontoporia blainvillei were analyzed. The number of carpals, metacarpals, phalanges, and morphometric characters from the humerus, radius, ulna, and digit two were studied in franciscana dolphins from Buenos Aires, Argentina. The number of visible epiphyses and their degree of fusion at the proximal and distal ends of the humerus, radius, and ulna were also analyzed. The flipper skeleton was symmetrical, showing a negative allometric trend, with similar growth patterns in both sexes with the exception of the width of the radius (P ≤ 0.01). SD was found on the number of phalanges of digit two (P ≤ 0.01), ulna and digit two lengths. Females showed a higher relative ulna length and shorter relative digit two length, and the opposite occurred in males (P ≤ 0.01). Epiphyseal fusion pattern proved to be a tool to determine dolphin's age; franciscana dolphins with a mature flipper were, at least, four years old. This study indicates that the flippers of franciscana dolphins are symmetrical; both sexes show a negative allometric trend; SD is observed in radius, ulna, and digit two; and flipper skeleton allows determine the age class of the dolphins. PMID:24700648

  11. Bilateral posterior sternoclavicular dislocation.

    PubMed

    Baumann, Matthias; Vogel, Tobias; Weise, Kuno; Muratore, Tim; Trobisch, Per

    2010-07-01

    Posterior sternoclavicular dislocations are a rare injury, representing <5% of all sternoclavicular dislocations and 1 in 1600 shoulder girdle injuries. Proper imaging with computed tomography and prompt diagnosis are essential steps in preventing potentially lethal complications observed in approximately 3% of all posterior sternoclavicular dislocations. Surgical treatment is necessary if closed reduction fails. With the medial clavicular epiphysis being the last to close (between ages 22 and 25), children and adolescents typically present with epiphyseal fractures rather than joint dislocations. If closed reduction fails, open reduction and internal fixation (ORIF) should be considered in fractures, whereas complex reconstructions with tendon graft procedures have been recommended for joint dislocations. This article presents a case of a traumatic bilateral posterior sternoclavicular dislocation due to an epiphyseal fracture in a 15-year-old boy. To our knowledge, this is the first reported case of a bilateral posterior sternoclavicular dislocation. Attempted closed reduction failed with redislocation after 2 days. The patient subsequently required ORIF. This article describes our technique with anterior retraction of the medial clavicle, closure of the posterior periosteum, and ORIF using nonabsorbable sutures. Postoperative shoulder mobilization was started on day 1. At final follow-up, the patient was completely asymptomatic. PMID:20608625

  12. Distal radius fixation through a mini-invasive approach of 15 mm. PART 1: a series of 144 cases.

    PubMed

    Lebailly, Frédéric; Zemirline, Ahmed; Facca, Sybille; Gouzou, Stéphanie; Liverneaux, Philippe

    2014-08-01

    The volar Henry approach is becoming the gold standard for distal radius fracture fixation. It decreases the incidence of nonunion, limits complications especially complex regional pain syndrome (CRPS) type I, and allows early mobilization of the wrist. Nonetheless, it has some disadvantages such as the size of the incision, which is not esthetically pleasing, and the loss of ligamentotaxis. This is why some authors have developed a mini-invasive approach. The aim of this work was to evaluate the feasibility of the anterior mini-invasive approach of 15 mm in a clinical series of 144 cases of distal radius fracture. All patients were operated under regional anesthesia using the same techniques by five surgeons of the same team. According to the AO classification, there were 83 type A fractures, 2 type B, and 59 type C. A volar plate (Step One(®), Newclip Technics™, Haute-Goulaine, France) was used in all cases. The 2 proximal metaphyseal screws and the 2 distal central epiphyseal screws were monoaxial locking. The 2 distal ulnar and radial epiphyseal screws were placed in polyaxial locking at 20° angulation maximum. Skin closure without drainage was performed. No postoperative immobilization was prescribed, and patients were encouraged to use their upper limb immediately postoperative. No postoperative physiotherapy was prescribed. The mean follow-up was 4.1 months. The final size of the incision was on average 16.1 mm. Mean pain score was 1.8. The Quick DASH score was average 25. Average range of motion was more than 85 %, and global force of the hand was 67 % compared with contralateral side. On X-ray, the mean radial slope was 22°, the mean radial tilt was 8.3°, and the mean radioulnar variance/index was -0.4 mm. There were nine cases of CRPS type I, which all resolved. Specific complications included two secondary displacements and nine tenosynovitis cases. No tendon rupture was noted. Two intra-articular distal radioulnar joint screws had to be removed at

  13. Bone kinetics of calcium-45 and pyrophosphate labeled with technetium-96: an autoradiographic evaluation. [Rabbits

    SciTech Connect

    Guillemart, A.; Le Pape, A.; Galy, G.; Besnard, J.C.

    1980-05-01

    The uptake of calcium-45 and of pyrophosphate labeled with the long-lived technetium-96 isotope was compared by means of liquid-emulsion microautoradiograms of the epiphyseal plates of 10-week-old rabbits, at 30 min, and 3 and 48 hr after i.v administration. For both tracers, thin sections confirm the significant role of the blood supply, especially shortly after injection. However, other more specific mechanisms lead to a mixing of the calcium in the mineral mass and to a linear deposition of technetium facing the osteoid surfaces. These findings suggest that the tropism of tin-reduced technetium pyrophosphate is not governed by the mineral pool but rather by exchanges inside a still poorly calcified organic matrix.

  14. Unusual Presentation of Giant Cell Tumor in Skeletally Immature Patient in Diaphysis of Ulna

    PubMed Central

    Patel, Maulik T; Nayak, Maunil R

    2015-01-01

    Introduction: Giant cell tumor is a locally aggressive benign tumor. Giant cell tumor of bone is characteristically found in skeletally mature patient at the end of long bones in the epiphyseal region or epiphysio-metaphyseal region. Giant cell tumor is very rare in skeletally immature patient. But we are presenting a very rare case of giant cell tumor in skeletally immature patient in diaphyseal region which is very uncommon location for giant cell tumor. From this case we concluded that irrespective of the location and skeletal maturity, a giant cell tumor should be diagnosed based on its histology because classical clinical-radiological features are not always present. Index case strengthens this view. PMID:27299037

  15. Recurrent Legg-Calvé-Perthes disease revisited: fake or reality?

    PubMed

    Ghanem, Ismat; Khalife, Rami; Haddad, Fadi; Kharrat, Khalil; Dagher, Fernand

    2005-11-01

    The objective of this study was to assess the course, the epidemiologic features and the prognosis of recurrent Legg-Calvé-Perthes disease. We reviewed seven reported cases and one personal case of recurrent Perthes' disease. In all cases, complete recovery from the previous episode was documented, and a thorough diagnostic work-up to rule out other diseases was undertaken. There were five boys. Age at onset ranged from 2 to 6 years. Five patients had bilateral involvement. Recurrence took place 1-5 years after complete healing of the initial one. Clinical and radiological pictures were similar to those found in primary Perthes' disease of the adolescent and consisted in a greater epiphyseal involvement. Recurrent Perthes' disease is very rare. We did not identify any risk factors for recurrence. A worse outcome is more closely related to an older age of the patient at recurrence than to recurrence itself. PMID:16200017

  16. Achondrogenesis type II, abnormalities of extracellular matrix.

    PubMed

    Horton, W A; Machado, M A; Chou, J W; Campbell, D

    1987-09-01

    Immune and lectin histochemical and microchemical methods were employed to study growth cartilage from seven cases of achondrogenesis type II (Langer-Saldino). The normal architecture of the epiphyseal and growth plate cartilage was replaced by a morphologically heterogeneous tissue. Some areas were comprised of vascular canals surrounded by extensive fibrous tissue and enlarged cells that had the appearance and histochemical characteristics of hypertrophic chondrocytes. Other areas contained a mixture of cells ranging from small to the enlarged chondrocytes. The extracellular matrix in the latter areas was more abundant and had characteristics of both precartilage mesenchymal matrix and typical cartilage matrix; it contained types I and II collagen, cartilage proteoglycan, fibronectin, and peanut agglutinin binding glycoconjugate(s). Peptide mapping of cyanogen bromide cartilage collagen peptides revealed the presence of types I and II collagen. These observations could be explained by a defect in the biosynthesis of type II collagen or in chondrocyte differentiation. PMID:3309860

  17. Arthroscopic Microfracture Technique for Cartilage Damage to the Lateral Condyle of the Tibia

    PubMed Central

    Kan, Hiroyuki; Arai, Yuji; Nakagawa, Shuji; Inoue, Hiroaki; Minami, Ginjiro; Ikoma, Kazuya; Fujiwara, Hiroyoshi; Kubo, Toshikazu

    2015-01-01

    This report describes the use of arthroscopic microfracture to treat a 10-year-old female patient with extensive damage to the cartilage of the lateral condyle of the tibia before epiphyseal closure, resulting in good cartilage recovery. Magnetic resonance imaging showed a defect in part of the load-bearing surface of the articular cartilage of the condyle articular of the tibia. The patient was diagnosed with damage to the lateral condyle cartilage of the tibia following meniscectomy, and arthroscopic surgery was performed. The cartilage defect measured approximately 20 × 20 mm, and microfracture was performed. Arthroscopy performed four months postoperatively showed that the cartilage defect was completely covered with fibrous cartilage, and the patient was allowed to resume sports activities. Four years postoperatively, she has had no recurrence of pain or hydrarthrosis. PMID:26345523

  18. Osteochondroma of maxillofacial region: Tumor arising from two different developmental bones.

    PubMed

    Mohanty, Sujata; Gupta, Himanshu; Dabas, Jitender; Kumar, Priyadarshan

    2016-01-01

    Osteochondromas are benign bony tumors which are commonly believed to originate by the proliferation of epiphyseal cartilage into the surrounding tissues. However, this hypothesis cannot explain the occurrence of this tumor in the intramembranous bones and soft tissue. Since most of the craniofacial bones have intramembranous origin, the occurrence of this lesion in this territory is considered rare. Contrary to the above hypothesis, Lichtenstein proposed that this entity arises from the metaplastic changes in the periosteum which explains the occurrence of this tumor in endochondral as well as intramembranous bones and also in soft tissues. Complying with Lichtenstein's hypothesis, the authors are presenting two cases of osteochondromas with one arising from the endochondral bone (the coronoid process of the mandible) and the other from an intramembranous bone (lateral pterygoid plate of the sphenoid). PMID:27601834

  19. The effect of fumonisin B1 on isolated chondrocytes and on bone formation.

    PubMed

    Wu, W; Li, G; Liu, T; Vesonder, R R

    1995-09-01

    Toxic effects of fumonisin B1 (FB1) were observed with cultured chondrocytes isolated from epiphyseal growth plates and with growing broiler chicks. Viability of chondrocytes was reduced after 48 h exposure to FB1, and half lethal concentration of FB1 was estimated to be greater than 250 microM. Increase in cell size was inhibited by as low as 25 microM FB1. Dietary inclusion of fumonisins (55 and 110 ppm) caused a reduction in body weight, increase in liver weight, and decrease in feed efficiency (P < .05). However, diarrhea and bone malformation were not observed. It is concluded that fumonisin by itself is not sufficient to cause skeletal problems in poultry. PMID:7501587

  20. Overuse and throwing injuries in the skeletally immature athlete.

    PubMed

    Hutchinson, Mark R; Ireland, Mary Lloyd

    2003-01-01

    Over 25 million children participate in school-sponsored sports, and an additional 20 million participate in extracurricular organized sports. Over the past decade, increased intensity of training, more pressure for success, new opportunities for structured play, and more organized advanced leagues and traveling teams have led to a corresponding increase in overuse injuries in the skeletally immature athlete. Perhaps the classic sports model for overuse injuries of the upper extremity is baseball. Throwing sports contribute to an increased incidence of elbow and shoulder injuries that might be related to intensity of training, throwing mechanics, and poor conditioning, including core strength. Specific areas of concern regarding overuse injuries in young athletes include such diagnoses as little leaguer's shoulder, little leaguer's elbow, osteochondritis dissecans of the elbow, tennis elbow, and distal radial epiphysitis. Ultimately, overuse injuries, and particularly physeal injuries, should be suspected in any young athlete who has pain in the upper extremity. Comparative bilateral radiographs are the rule in workup. PMID:12690838

  1. Distal radius anatomy applied to the treatment of wrist fractures by plate: a review of recent literature

    PubMed Central

    Obert, Laurent; Loisel, François; Gasse, Nicolas; Lepage, Daniel

    2015-01-01

    Few studies on the anatomy of the radial epiphysis have been published in the past 10 years. However, with the availability of new intra- and extra-medullary implants and the recent rash of avoidable iatrogenic injuries, now is the time for a more detailed description of the metaphyseal-epiphyseal regions in the distal radius. Published studies on distal radius anatomy in recent years have focused on three aspects: distal limit and watershed line, dorsal tubercle, and wrist columns. Furthermore, a fresh look at distal radius biomechanics shows that the loads experienced by the distal radius vary greatly. This information should be taken into account during volar plating of distal radius fractures. PMID:27163070

  2. Changes of cell-vascular complex in zones of adaptive remodeling of the bone tissue under microgravity conditions

    NASA Astrophysics Data System (ADS)

    Rodionova, N. V.; Oganov, V. S.

    2003-10-01

    We examined the peculiarities of the structure of the blood-vascular bed and perivascular cells in zones of osteogenesis in the epiphyses and metaphises of femoral bones of rats, flown aboard the US laboratory SLS-2 for two weeks by electron microscopy and histochemistry. In zones of bone remodeling, there was a tendency for a reduction of sinusoid capillary specific volume. Endotheliocytes preserve the typical structure. In the population of perivascular cells, we discovered differentiating osteogenic cells that contained alkaline phosphomonoesterase as well as cells that don't contain this enzyme and differentiate into fibroblasts. The fibroblasts genesis in zones of adaptive remodeling of spongy bones leads to a further development of fibrous tissue that is not subject to mineralization.

  3. Tricho-rhino-phalangeal syndrome type 1 as an outcome of in vitro fertilization?

    PubMed

    Karaer, K; Yüksel, Z

    2014-01-01

    Trichorhinophalangeal syndrome type I [OMIM #190350] is an autosomal dominant disorder. Common features are: Slowly growing sparse hair, laterally thin eyebrows, bulbous tip of the nose, long philtrum, thin upper lip, protruding ears. Common skeletal anomalies include shortening of phalanges and metacarpals causing mild to severe brachydactyly, cone shaped epiphyses, hip dysplasia and short stature. Recently many reports have been published on the use of assisted reproductive technology (ART) and the increased risk of congenital major malformations or syndromes. We present a 6 years old Turkish Trichorhinophalangeal syndrome (TRPS) case of a twin pair after in vitro fertilization (IVF). TRPS with IVF pregnancy has not been reported previously. This new case reported herein will contribute to a better understanding whether ART pregnancy increases congenital malformations. PMID:24783650

  4. Schimke immune-osseous dysplasia: A case report.

    PubMed

    Bakr, Ashraf; Eid, Riham; Sarhan, Amr; Hammad, Ayman; El-Refaey, Ahmed Mahmoud; El-Mougy, Atef; Zedan, Mohammed Magdy; ElHusseini, Fatma

    2015-09-01

    Schimke immune-osseous dysplasia (SIOD) is a rare autosomal recessive disorder characterized by spondylo-epiphyseal dysplasia (SED), progressive renal insufficiency beginning as steroid-resistant nephrotic syndrome (SRNS) and defective cellular immunity. This article reports a case from Egypt with a mild form of SIOD. A 14.5-year-old male patient presented with disproportionate short stature, SRNS (focal and segmental glomerulosclerosis), laboratory evidence of cellular immune deficiency and radiologic characteristics of SED. He died at the age of 16.5 years with bone marrow failure and severe pneumonia. To the best of our knowledge, this is the first case of SIOD to be reported from Egypt. PMID:26354575

  5. Genetic linkage of mild pseudoachondroplasia (PSACH) to markers in the pericentromeric region of chromosome 19

    SciTech Connect

    Briggs, M.D.; Rasmussen, M.; Garber, P.; Rimoin, D.L.; Cohn, D.H. ); Weber, J.L. ); Yuen, J.; Reinker, K. )

    1993-12-01

    Pseudoachondroplasia (PSACH) is a dominantly inherited form of short-limb dwarfism characterized by dysplastic changes in the spine, epiphyses, and metaphyses and early onset osteoarthropathy. Chondrocytes from affected individuals accumulate an unusual appearing material in the rough endoplasmic reticulum, which has led to the hypothesis that a structural abnormality in a cartilage-specific protein produces the phenotype. The authors recently identified a large family with a mild form of pseudoachondroplasia. By genetic linkage to a dinucleotide repeat polymorphic marker (D19S199), they have localized the disease gene to chromosome 19 (maximum lod score of 7.09 at a recombination fraction of 0.03). Analysis of additional markers and recombinations between the linked markers and the phenotype suggests that the disease gene resides within a 6.3-cM interval in the immediate pericentromeric region of the chromosome. 39 refs., 2 figs., 1 tab.

  6. Characterization of a gene from the EDM1-PSACH region of human chromosome 19p

    SciTech Connect

    Lennon, G.G.; Giorgi, D.; Martin, J.R.

    1994-09-01

    Genetic linkage mapping has indicated that both multiple epiphyseal dysplasia (EDM1), a dominantly inherited chondrodysplasia, and pseudoachondroplasia (PSACH), a skeletal disorder associated with dwarfism, map to a 2-3 Mb region of human chromosome 19p. We have isolated a partial cDNA from this region using hybrid selection, and report on progress towards the characterization of the genomic structure and transcription of the corresponding gene. Sequence analysis of the cDNA to date indicates that this gene is likely to be expressed within extracellular matrix tissues. Defects in this gene or neighboring gene family members may therefore lead to EDM1, PSACH, or other connective tissue and skeletal disorders.

  7. New form of platyspondylic lethal chondrodysplasia.

    PubMed

    Akaba, K; Nishimura, G; Hashimoto, M; Wakabayashi, T; Kanasugi, H; Hayasaka, K

    1996-12-30

    We report on a sporadic case of hitherto unknown lethal skeletal dysplasia. The cardinal clinical manifestations consisted of frontal bossing, cloudy corneae, low nasal ridge, and micrognathia, hypoplastic thorax, and rhizomelic micromelia. Laryngoscopy and neck CT disclosed laryngeal stenosis, and brain CT demonstrated hypoplasia of the corpus callosum. Skeletal survey demonstrated hypoplasia of facial bones and short skull base, extremely severe platyspondyly, hypoplastic ilia, and delayed epiphyseal ossification and rhizomelic shortness of tubular bones. The long bones appeared overtubulated with exaggerated metaphyseal flaring. The humeri were particularly short and bowed. Bowing of the radii and ulnae with subluxation of radial heads presented as a Madelung-like deformity. Unlike the long bones, the short tubular bones were not short and normally modeled. The skeletal changes were superficially similar to those in a group of lethal platyspondylic chondrodysplasias, but were inconsistent with any known subtypes of this group or other lethal skeletal dysplasias. PMID:8989469

  8. Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population

    PubMed Central

    Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

    2015-01-01

    Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias. PMID:26488291

  9. Variability of platyspondylic lethal chondrodysplasia: another case report.

    PubMed

    Nishimura, G; Iwasawa, T; Fukuzawa, R; Hirabayashi, Y; Ito, T

    1998-07-01

    We report the radiological and histological findings of another case of platyspondylic lethal chondrodysplasia. The patient was a girl, who died of respiratory failure at 18 days of age. The radiological changes comprised moderate platyspondyly with ovoid-shaped vertebral bodies, broad and short ilia, rhizomelic shortening and mild bowing of the long bones (particularly of the humeri), relatively long short tubular bones, and retarded epiphyseal ossification and ragged metaphyses, which were most similar to those of a mild variant of this entity, the Luton type. However, the histological findings of cartilage, including hypercellularity of the reserve zone with round resting chondrocytes, relatively normal column formation of the proliferative and hypertrophic zones, and incorporation of hypertrophic cartilage with a columnar arrangement into metaphyseal bony trabeculae, resemble those of a severe variant of this entity, the Torrance type. Our observation provides an insight into the phenotypic variabilities of platyspondylic lethal chondrodysplasia. PMID:9689993

  10. Neandertal postcranial remains from the Sima de las Palomas del Cabezo Gordo, Murcia, southeastern Spain.

    PubMed

    Walker, Michael J; Ortega, Jon; López, Mariano V; Parmová, Klára; Trinkaus, Erik

    2011-04-01

    The Sima de las Palomas, southeastern Spain, has yielded a series of Neandertal postcranial remains, including immature and mature isolated elements and the fragmentary partial skeleton of a young adult (Palomas 92). The remains largely conform to the general late archaic/Neandertal morphological pattern in terms of humeral diaphyseal shape, pectoralis major tuberosity size and pillar thickness, ulnar coronoid process height, manual middle phalangeal epiphyseal breadth, manual distal phalangeal tuberosity shape and breadth, femoral diaphyseal shape, and probably body proportions. Palomas 92 contrasts with the Neandertals in having variably gracile hand remains, a more sellar trapezial metacarpal 1 facet, more anteroposteriorly expanded mid-proximal femoral diaphysis, and less robust pedal proximal phalanges. The Palomas Neandertals contrast with more northern European Neandertals particularly in various reflections of overall body size. PMID:21404228

  11. Role of oestrogen in the regulation of bone turnover at the menarche.

    PubMed

    Eastell, Richard

    2005-05-01

    The rise in oestrogen levels at menarche in girls is associated with a large reduction in bone turnover markers. This reduction reflects the closure of the epiphyseal growth plates, the reduction in periosteal apposition and endosteal resorption within cortical bone, and in bone remodelling within cortical and cancellous bone. Oestrogen promotes these changes, in part, by promoting apoptosis of chondrocytes in the growth plate and osteoclasts within cortical and cancellous bone. The period of early puberty is associated with an increased risk of fracture, particularly of the distal forearm, and this may be related to the high rate of bone turnover. A late menarche is a consistent risk factor for fracture and low bone mineral density in the postmenopausal period; models that might explain this association are considered. PMID:15845915

  12. Deletion at 12p in a Japanese child with brachydactyly overlaps the assignment locus of brachydactyly with hypertension in a Turkish family

    SciTech Connect

    Baehring, S.; Toka, H.R.; Nitz, I.

    1997-03-01

    Positional cloning is occasionally facilitated by the identification of a chromosomal aberration. We are studying a Turkish family, first described by Bilginturan et al., who have a monogenic form of hypertension, and we have reason to believe that a chromosomal aberration in a Japanese child may facilitate our cloning of the responsible gene. The hypertension gene in our family is unique in that it causes, by as yet undefined mechanisms, increased peripheral vascular resistance. Pedigree analysis of the Turkish kindred allowed us to map the gene to 12p11-p12. The kindred has a second trait, brachyclactyly, which cosegregates with the hypertension. The brachyclactyly, which involves both hands and feet, features shortened metacarpals and phalanges, as well as cone-shaped epiphyses. 11 refs., 2 figs.

  13. Effects of radiation therapy on skeletal growth in childhood

    SciTech Connect

    Goldwein, J.W. )

    1991-01-01

    Ionizing radiation was used to treat childhood cancer long before the advent of chemotherapy, and it took little time for physicians to appreciate the deleterious effects it had on skeletal growth. The cause of this complication results predominantly from alteration of chondroblastic activity. This may stem directly from irradiation at the epiphyseal plate or indirectly from irradiation of glands that secrete growth-mediating hormones. The complication can go far beyond the obvious physical afflictions and extend into the psychologic domain, rendering deeper, more permanent scars. Presently, many of these effects are predictable, reducible, and treatable without compromising the cure that so often depends on the use of irradiation. Because of the complexities of childhood cancer therapy, strategies aimed at diminishing these effects are challenging. It is imperative that these effects be understood so that they can be reduced in current patients and prevented in future patients.33 references.

  14. Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population.

    PubMed

    Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

    2015-01-01

    Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias. PMID:26488291

  15. Effects of long-term rotation and hypergravity on developing rat femurs

    NASA Technical Reports Server (NTRS)

    Smith, S. D.

    1975-01-01

    Male and female Sprague-Dawley rats derived from a single mating were raised for three generations under constant centrifugation at 1.03 G (Rotation Controls) and at 2 G. When the third generation rats were 3 months old, they were sacrificed, and their femurs removed. After fixation and cleaning, the femurs were then measured for length and diameter. Then right femurs were sectioned longitudinally, left femurs transversely. After staining with Hematoxylin and Eosin, right femurs were examined for ossification patterns and left femurs were measured for cortical thickness. All rotation control rats showed marked stimulation of ossification in the femoral head, and males showed significant cortical thinning when compared to non-rotated earth gravity controls. All 2 G femurs showed decreased length and aspect (L/D) ratios, and increased cortical thickness/diameter ratios when compared to earth controls or rotation controls. Ossification of the femoral head was slightly advanced, while the distal epiphyseal plate was thinned.

  16. The CHILD syndrome. Congenital hemidysplasia with ichthyosiform erythroderma and limb defects.

    PubMed

    Happle, R; Koch, H; Lenz, W

    1980-06-01

    The term CHILD syndrome is proposed as an acronym for congenital hemidysplasia with ichthyosiform erythroderma and limb defects. The syndrome is characterized by unilateral erythema and scaling, with a distinct demarcation in the middle of the trunk. The dermatosis is either present at birth or develops during the first weeks of life. Ipsilateral limb defects may vary from hypoplasia of some fingers to complete absence of an extremity. In addition, ipsilateral hypoplasia of other parts of the skeleton, as well as defects of the brain and the viscera are found. In some cases, ipsilateral punctate epiphyseal calcifications have been observed. Two further cases of this syndrome are reported, and a review of 18 previous observations is presented. The ratio of females to males is 19 : 1. Apparently, the CHILD syndrome is genetically determined. Arguments are presented in favor of the hypothesis that the conditions is due to an X-linked dominant gene lethal in hemizygous males. PMID:7408908

  17. Juxtaphyseal Intraosseous Hemangioma of Proximal Femur causing Coxa vara and Coxa breva deformity in a growing child

    PubMed Central

    Song, Hae Ryong; Shyam, Ashok K.

    2011-01-01

    Introduction: Bony hemangiomas are rare lesions in growing skeleton. Affection of the epiphyseal plate by a bony hemangioma leading to growth retardation is rare. Case report: We report the radiological picture of a juxtaphyseal osseous hemangioma affecting the capital femoral physis leading to coxa vara and coxa breva deformity. This hemangioma is also a rarity as it has both intracortical and intra medullary components. A diagnostic and therapeutic CT guided core needle biopsy/decompression was performed to confirm the histopathological diagnosis and to decompress the lesion. Patient was treated conservatively with shoe raise and regular checkups and at two year follow-up there were no interval changes noted on the radiographs with patient completely asymptomatic. Conclusion: Juxtaphyseal hemangiomas may be amenable to needle decompression, however longer follow will be required to assess the further response.

  18. Imaging in Erdheim-Chester disease: classic features and new insights.

    PubMed

    Moulis, G; Sailler, L; Bonneville, F; Wagner, T

    2014-01-01

    Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis. Osseous involvement is the most frequent feature with bilateral and symmetric osteosclerotic changes in long bone diaphyseal and metaphyseal regions, classically sparing epiphyses. 99mTc scintigraphy shows bilateral and symmetrical metaphysal and diaphyseal increased uptake in almost all the patients, even asymptomatic. Other classical features on CT-scan, very evocative of Erdheim-Chester disease, must be recognised: e.g. 'coated' aorta, 'hairy kidney' patterns. New imaging techniques such as MRI have led to a better description of cardiac and central nervous system involvements. Pachymeningitis and right atrium wall infiltration are new evocative images of this disease. Fluorodeoxyglucose Positron Emission Tomography in the diagnosis or prognosis assessment is still discussed. The objective of this review is to discuss the place of each imaging technique in Erdheim-Chester disease in 2013. PMID:24428974

  19. Football injury: a literature review *

    PubMed Central

    Kos, John J.

    1979-01-01

    A great deal of concern is recently being expressed relative to the playing of tackle football by adolescent Canadians. The purpose of this literature review is to try to summarize the important data from the available world literature. Very few Canadian statistics are available. Most of the data comes from United States experience. Tackle football injury is examined from various perspectives: 1. Equipment 2. Mechanisms of injury 3. Types of injury, with some emphasis on epiphyseal injury 4. Prevention 5. Comparison with other sports Although no “hard and fast” conclusion is drawn, the paper tends to show that: 1. Football is dangerous 2. Football is damaging to many body systems 3. Prevention of injury is difficult under present conditions 4. Alternate games, such as soccer and rugby seem to provide the same benefits with less catastrophic injuries

  20. Bilateral Simultaneous Avulsion Fractures of the Proximal Tibia in a 14-Year-Old Athlete with Vitamin-D Deficiency

    PubMed Central

    Harb, Ziad; Malhi, Arfan

    2015-01-01

    Fractures involving the proximal tibial epiphysis are rare and form 0.5% of all epiphyseal injuries. The specific anatomical and developmental features of the proximal tibial epiphysis make it vulnerable to unique patterns of fractures. Vitamin-D plays a vital role in bone homeostasis and its deficiency has an impact on fracture risk and healing. We present the first ever reported case of simultaneous bilateral proximal tibial physeal fractures in an athlete with vitamin-D deficiency. Treatment consisted of plaster immobilisation, and the patient made a full recovery and returned to preinjury level of activities. We report this case for its uniqueness and as an educational review of the importance of the developmental anatomy of the proximal tibia. We review the literature and discuss how the stages of the growing physis determine the type of fracture sustained. PMID:26425381

  1. Osteochondroma of maxillofacial region: Tumor arising from two different developmental bones

    PubMed Central

    Mohanty, Sujata; Gupta, Himanshu; Dabas, Jitender; Kumar, Priyadarshan

    2016-01-01

    Osteochondromas are benign bony tumors which are commonly believed to originate by the proliferation of epiphyseal cartilage into the surrounding tissues. However, this hypothesis cannot explain the occurrence of this tumor in the intramembranous bones and soft tissue. Since most of the craniofacial bones have intramembranous origin, the occurrence of this lesion in this territory is considered rare. Contrary to the above hypothesis, Lichtenstein proposed that this entity arises from the metaplastic changes in the periosteum which explains the occurrence of this tumor in endochondral as well as intramembranous bones and also in soft tissues. Complying with Lichtenstein's hypothesis, the authors are presenting two cases of osteochondromas with one arising from the endochondral bone (the coronoid process of the mandible) and the other from an intramembranous bone (lateral pterygoid plate of the sphenoid). PMID:27601834

  2. Muscle and bone plasticity after spinal cord injury: Review of adaptations to disuse and to electrical muscle stimulation

    PubMed Central

    Dudley-Javoroski, Shauna; Shields, Richard K.

    2009-01-01

    The paralyzed musculoskeletal system retains a remarkable degree of plasticity after spinal cord injury (SCI). In response to reduced activity, muscle atrophies and shifts toward a fast-fatigable phenotype arising from numerous changes in histochemistry and metabolic enzymes. The loss of routine gravitational and muscular loads removes a critical stimulus for maintenance of bone mineral density (BMD), precipitating neurogenic osteoporosis in paralyzed limbs. The primary adaptations of bone to reduced use are demineralization of epiphyses and thinning of the diaphyseal cortical wall. Electrical stimulation of paralyzed muscle markedly reduces deleterious post-SCI adaptations. Recent studies demonstrate that physiological levels of electrically induced muscular loading hold promise for preventing post-SCI BMD decline. Rehabilitation specialists will be challenged to develop strategies to prevent or reverse musculoskeletal deterioration in anticipation of a future cure for SCI. Quantifying the precise dose of stress needed to efficiently induce a therapeutic effect on bone will be paramount to the advancement of rehabilitation strategies. PMID:18566946

  3. Klinefelter's syndrome with renal tubular acidosis: impact on height.

    PubMed

    Jebasingh, F; Paul, T V; Spurgeon, R; Abraham, S; Jacob, J J

    2010-02-01

    A 19-year-old Indian man presented with a history of proximal muscle weakness, knock knees and gynaecomastia. On examination he had features of rickets and bilateral small testes. Karyotyping revealed a chromosomal pattern of 47,XXX, confirming the diagnosis of Klinefelter's syndrome. He was also found to have hyperchloraemic metabolic acidosis with hypokalaemia, hypophosphataemia, phosphaturia and glycosuria, which favoured a diagnosis of proximal renal tubular acidosis. Patients with Klinefelter's syndrome typically have a tall stature due to androgen deficiency, resulting in unfused epiphyses and an additional X chromosome. However, this patient had a short stature due to associated proximal renal tubular acidosis. To the best of our knowledge, this is the second case of Klinefelter's syndrome with short stature due to associated renal tubular acidosis reported in the literature. This report highlights the need to consider other causes when patients with Klinefelter's syndrome present with a short stature. PMID:20358137

  4. Osgood Schlatter lesion: histologic features of slipped anterior tibial tubercle.

    PubMed

    Falciglia, F; Giordano, M; Aulisa, A G; Poggiaroni, A; Guzzanti, V

    2011-01-01

    No study reports the histological features of the various zone of the anterior tubercle of the tibia in the different stages of the Osgood-Schlatter (O-S) lesion. For this reason we carried on an histological study. Specimens were taken from 13 patients with O-S lesion prior to surgery. In 4 cases in the apophyseal stage lesions were present in an altered fibrocartilage anterior to the ossification centre. In 9 cases in the epiphyseal stage varying degrees of reparative tissues were observed in the bed of the fragment of the secondary ossification centre. In 3 of them a zone of lesion was observed within the fibrocartilage anterior to the ossification centre. These results suggest that the slippage of the patellar tendon insertion may be progressive and caused by pathological fibrocartilage. PMID:21669134

  5. 'Hip' pain.

    PubMed

    Zacher, Josef; Gursche, Angelika

    2003-02-01

    'Hip' pain is usually located in the groin, upper thigh or buttock and is a common complaint. Slipped capital femoral epiphysis, avascular femoral head necrosis and apophyseal avulsion are the most common diagnoses in childhood and adolescents. Strains and fractures are common in sport-active adults. Osteoarthritis occurs in middle-aged and older adults. Trauma may result in femoral head fracture or typical muscle and tendon sprains and bursitis. Septic or inflammatory arthritis can occur at every age. Septic arthritis, fractures and acute epiphyseal slipping are real emergency cases. Congenital dysplasia of the hip joint may lead to labral tears and early osteoarthritis. The most important hip problems in children, adolescents, adult and older people are discussed; these problems originate from intra-articular disorders and the surrounding extra-articular soft tissues. Medical history, clinical examination and additional tests, including imaging, will be demonstrated. Principles of treatment are given for specific disorders. PMID:12659822

  6. Tumeur à cellules géantes du fémur proximal traitée par arthroplastie totale de hanche

    PubMed Central

    Mhammdi, Younes; Kharmaz, Mohamed

    2016-01-01

    The authors report the case of a giant cell tumor grade 1 of the proximal femur, diagnosed in a young patient of 18 years. The diagnosis was suspected on a standard x-ray complemented by MRI, it was confirmed on histological examination after biopsy. The tumor was a metaphyseal-epiphyseal location above the level of the femoral cut on preoperative planning. The management had combined two surgical techniques, with a marginal resection of the femoral head and neck, and femoral curettage-filling of the metaphyseal region with implantation of a total cemented hip prosthesis. After 2 years of follow up, the result is very satisfactory with good functional recovery and no signs of recurrence. PMID:27279937

  7. Suppressed osteoclast differentiation at the chondro-osseous junction mediates endochondral ossification retardation in long bones of Wistar fetal rats with prenatal ethanol exposure.

    PubMed

    Pan, Zhengqi; Zhang, Xianrong; Shangguan, Yangfan; Hu, Hang; Chen, Liaobin; Wang, Hui

    2016-08-15

    Prenatal ethanol exposure (PEE) inhibits longitudinal growth of fetal bones, but the underlying mechanisms remain unknown. In this study, we aimed to investigate how PEE induces the retardation of long bone development in fetal rats. Pregnant Wistar rats were treated with ethanol or distilled water (control group) by gavage from gestational day (GD) 9 to 20. Fetuses were delivered by cesarean section on GD20. Fetal sera were collected for assessing corticosterone (CORT) level. Fetal long bones were harvested for histochemical, immunohistochemical and gene expression analysis. Primary chondrocytes were treated with ethanol or CORT for analyzing genes expression. PEE fetuses showed a significant reduction in birth weight and body length. The serum CORT concentration in PEE group was significantly increased, while the body weight, body length and femur length all were significantly decreased in the PEE group. The length of the epiphyseal hypertrophy zone was enlarged, whereas the length of the primary ossification center was significantly reduced in PEE fetuses. TUNEL assay showed reduced apoptosis in the PEE group. Further, the gene expression of osteoprotegerin (OPG) was markedly up-regulated. In vitro experiments showed that CORT (but not ethanol) treatment significantly activated the expression of OPG, while the application of glucocorticoid receptor inhibitor, mifepristone, attenuated these change induced by CORT. These results indicated that PEE-induced glucocorticoid over-exposure enhanced the expression of OPG in fetal epiphyseal cartilage and further lead to the suppressed osteoclast differentiation in the chondro-osseous junction and consequently inhibited the endochondral ossification in long bones of fetal rats. PMID:27338645

  8. Ectopic bone formation and chondrodysplasia in transgenic mice carrying the rat C3(1)/T{sub AG} fusion gene

    SciTech Connect

    Green, J.E.; Maroulakou, I.G.; Anver, M.

    1994-09-01

    Transgenic mice expressing the SV40 large T-antigen (T{sup AG}) under the regultory control of the hormone-responsive rat C3(1) prostatein promoter develop unusual bone and cartilage lesions, as well as ectopic bone and cartilage formation. Two lines of transgenic animals have been propagated in which the expression of the transgene in chondrocytes results in a mild to moderate generalized disorganization of cartilage growth which appears to affect multiple tissues, including the trachea, ear pinna and articular cartilage. The epiphyseal plates are also affected with normal architecture of the zones of proliferation and maturation, but marked elongation of the zone of hypertrophy. Immunocytochemistry demonstrates that expression of T{sup AG} is limited to the zone of hypertropny in the epiphyseal plates, suggesting that the chondrocytes become hormone-responsive at this particular stage of differentiation. Normal mineralization and trabecular formation in long bone appears to occur. Ectopic bone and cartilage formation occurs in the foot pads of the fore- and hind- feet over the course of several months. This is preceded by proliferation of sweat gland epithelial cells followed by the appearance of nodules of cartilage and bone. The nodules are closely associated with proliferating epithelium but are not contiguous with bony structures normally found in the feet. The roles of BMP`s, growth factors, oncogenes and hormones in the development of these lesions will be presented. These transgenic animals may provide new insights into hormone-responsiveness of chondrocytes, as well as factors involved in the processes of bone and cartilage differentiation and growth. These transgenic animals may serve as a useful model for human heterotopic bone formation.

  9. Levels of Evidence in the Treatment of Slipped Capital Femoral Epiphysis: A Systematic Review.

    PubMed

    Moriarity, Andrew; Kennedy, Jim; Baker, Joe; Kiely, Pat

    2016-06-27

    The primary aim of this study was to analyze the current level of evidence available on the surgical management of Slipped Capital Femoral Epiphysis (SCFE). Secondary aims were to correlate the level of evidence with the impact factor of the journal to evaluate the level of evidence over time, and to evaluate the geographic distribution of the studies. Therapeutic studies published in English between January 1991 and August 2014 that reported on SCFE were identified via electronic search was performed using the databases PubMed, EMBASE, and the Cochrane Library. The search terms used included: Slipped capital femoral epiphyses OR SCFE OR Slipped upper femoral epiphyses OR SUFE AND Management OR Treatment. Correlation between the level of evidence and the impact factor of the journal were analyzed together with linear regression models to reveal any significant trends over time. A total of 1516 studies were found, of which 321 were included in the final analysis. The most frequent study type was the case series (51.1%) followed by case reports (22.4%) and expert opinion (14.0%). Randomized control trial accounted for only 0.6%. The Journal of Pediatric Orthopedics (American) had the most studies (22.6%) and the highest number of level 2 (n=1) and level 3 (n=15) type evidence. There was no progression of level of evidence over time. There was no correlation between level of evidence and impact factor of journal. The majority of therapeutic studies on SCFE are of low level of evidence. High-level RCTs are difficult to perform in pediatric orthopedic surgery, however the management of SCFE would benefit from well-designed, multicenter, clinical RCTs to advance evidence-based practice. PMID:27433299

  10. Osteochondritis dissecans and Osgood Schlatter disease in a family with Stickler syndrome

    PubMed Central

    Al Kaissi, Ali; Klaushofer, Klaus; Grill, Franz

    2009-01-01

    Purpose Stickler syndrome is among the most common autosomal dominant connective tissue disorders but is often unrecognised and therefore not diagnosed by clinicians. Despite much speculation, the cause of osteochondrosis in general and osteochondritis dissecans (OCD) and Osgood Schlatter syndrome (OSS) in particular remain unclear. Etiological understanding is essential. We describe a pair of family subjects presented with OCD and OSS as a symptom complex rather than a diagnosis. Methods Detailed clinical and radiographic examinations were undertaken with emphasis on the role of MRI imaging. Magnetic resonance imaging may allow early prediction of articular lesion healing potential in patients with Stickler syndrome. Results The phenotype of Stickler syndrome can be diverse and therefore misleading. The expectation that the full clinical criteria of any given genetic disorder such as Stickler syndrome will always be present can easily lead to an underestimation of these serious inheritable disorders. We report here two family subjects, a male proband and his aunt (paternal sister), both presented with the major features of Stickler syndrome. Tall stature with marfanoid habitus, astigmatism/congenital vitreous abnormality and submucus cleft palate/cleft uvula, and enlarged painful joints with early onset osteoarthritis. Osteochondritis dissecans (OCD) and Osgood Schlatter syndrome (OSS) were the predominating joint abnormalities. Conclusion We observed that the nature of the articular and physeal abnormalities was consistent with a localised manifestation of a more generalised epiphyseal dysplasia affecting the weight-bearing joints. In these two patients, OCD and OSS appeared to be the predominant pathologic musculoskeletal consequences of an underlying Stickler's syndrome. It is empirical to consider generalised epiphyseal dysplasia as a major underlying causation that might drastically affect the weight-bearing joints. PMID:19193224

  11. Trafficking defects and loss of ligand binding are the underlying causes of all reported DDR2 missense mutations found in SMED-SL patients.

    PubMed

    Ali, Bassam R; Xu, Huifang; Akawi, Nadia A; John, Anne; Karuvantevida, Noushad S; Langer, Ruth; Al-Gazali, Lihadh; Leitinger, Birgit

    2010-06-01

    Spondylo-meta-epiphyseal dysplasia (SMED) with short limbs and abnormal calcifications (SMED-SL) is a rare, autosomal recessive human growth disorder, characterized by disproportionate short stature, short limbs, short broad fingers, abnormal metaphyses and epiphyses, platyspondyly and premature calcifications. Recently, three missense mutations and one splice-site mutation in the DDR2 gene were identified as causative genetic defects for SMED-SL, but the underlying cellular and biochemical mechanisms were not explored. Here we report a novel DDR2 missense mutation, c.337G>A (p.E113K), that causes SMED-SL in two siblings in the United Arab Emirates. Another DDR2 missense mutation, c.2254C>T (p.R752C), matching one of the previously reported SMED-SL mutations, was found in a second affected family. DDR2 is a plasma membrane receptor tyrosine kinase that functions as a collagen receptor. We expressed DDR2 constructs with the identified point mutations in human cell lines and evaluated their localization and functional properties. We found that all SMED-SL missense mutants were defective in collagen-induced receptor activation and that the three previously reported mutants (p.T713I, p.I726R and p.R752C) were retained in the endoplasmic reticulum. The novel mutant (p.E113K), in contrast, trafficked normally, like wild-type DDR2, but failed to bind collagen. This finding is in agreement with our recent structural data identifying Glu113 as an important amino acid in the DDR2 ligand-binding site. Our data thus demonstrate that SMED-SL can result from at least two different loss-of-function mechanisms: namely defects in DDR2 targeting to the plasma membrane or the loss of its ligand-binding activity. PMID:20223752

  12. Undersulfation of proteoglycans synthesized by chondrocytes from a patient with achondrogenesis type 1B homozygous for an L483P substitution in the diastrophic dysplasia sulfate transporter.

    PubMed

    Rossi, A; Bonaventure, J; Delezoide, A L; Cetta, G; Superti-Furga, A

    1996-08-01

    Achondrogenesis type 1B is an autosomal recessive, lethal chondrodysplasia caused by mutations in the gene encoding a sulfate/chloride antiporter of the cell membrane (Superti-Furga, A., Hästbacka, J., Wilcox, W. R., Cohn, D. H., van der Harten, J. J., Rossi, A., Blau, N., Rimoin, D. L., Steinmann, B., Lander, E. S., and Gitzelmann, R.(1996) Nat. Genet. 12, 100-102). To ascertain the consequences of the sulfate transport defect on proteoglycan synthesis, we studied the structure and sulfation of proteoglycans in cartilage tissue and in fibroblast and chondrocyte cultures from a fetus with achondrogenesis 1B. Proteoglycans extracted from epiphyseal cartilage and separated on agarose gels migrated more slowly than controls and stained poorly with alcian blue. The patient's cultured cells showed reduced incorporation of [35S]sulfate relative to [3H]glucosamine, impaired uptake of sulfate, and higher resistance to chromate toxicity compared to control cells. Epiphyseal chondrocytes cultured in alginate beads synthesized proteoglycans of normal molecular size as judged by gel filtration chromatography, but undersulfated as judged by ion exchange chromatography and by the amount of nonsulfated disaccharide. High performance liquid chromatography analysis of chondroitinase-digested proteoglycans showed that sulfated disaccharides were present, although in reduced amounts, indicating that at least in vitro, other sources of sulfate can partially compensate for sulfate deficiency. A t1475c transition causing a L483P substitution in the eleventh transmembrane domain of the sulfate/chloride antiporter was present on both alleles in the patient who was the product of a consanguineous marriage. The results indicate that the defect of sulfate transport is expressed in both chondrocytes and fibroblasts and results in the synthesis of proteoglycans bearing glycosaminoglycan chains which are poorly sulfated but of normal length. PMID:8702490

  13. The ultrastructure of the organic phase associated with the inorganic substance in calcified tissues.

    PubMed

    Bonucci, E; Silvestrini, G; Di Grezia, R

    1988-08-01

    An organic phase is closely associated with the mineral substance is all calcified matrices, where it can be demonstrated as crystal-bound proteins by biochemical methods and as crystal ghosts by electron microscopy. Interest in crystal ghosts derives chiefly from the observation that they have the same shape, arrangement, and orientation as inorganic crystallites, which suggests they may have a role in their formation. Histochemically, crystal ghosts of epiphyseal cartilage react with colloidal iron (pH 2.0), acidic phosphotungstic acid, ruthenium red, and a number of cations including calcium, barium, magnesium, lanthanum, strontium, and terbium chloride. Their reactivity is removed by methylation and only incompletely restored by saponification. Moreover, the crystal ghosts located at the periphery of the calcified areas contain vic-glycol groups, as shown by their reactivity with periodic acid-silver nitrate and periodic acid-thiosemicarbazide-osmium. All these reactions show that the crystal ghosts of epiphyseal cartilage contain acidic, probably sulfate groups and, at least initially, vic-glycol groups. Their reactivity decreases as the calcification process is completed. Although the available data are not sufficient to allow a full understanding of the nature and function of these structures, they seem to play an important role in calcification. The hypothesis is presented that crystal ghosts are preformed in calcifying matrices and are activated by the unmasking of the reactive groups in their polymeric molecule; the unmasked groups then link up with inorganic ions in such a way to form organic-inorganic structures the inorganic ions of which are arranged in an apatitelike configuration and the filamentlike shape of which is the same as that of the polymeric molecule. PMID:3042232

  14. Corrections of diverse forms of lower limb deformities in patients with mucopolysaccharidosis type IVA (Morquio syndrome)

    PubMed Central

    Al Kaissi, Ali; Kenis, Vladimir; Melchenko, Eugeniy; Ghachem, Maher Ben; Csepan, Robert; Grill, Franz; Ganger, Rudolf

    2016-01-01

    Background: Thoracolumbar kyphosis has been considered as the first presenting deformity and is often a key diagnostic clue noted in children with mucopolysaccharidosis (MPS) type IV (Morquio's syndrome). However, we observed that the progressive irregularities of the epiphyses of the long bones were the most prominent skeletal pathology, causing effectively the development of diverse forms of lower limbs deformities with extreme variation in age of onset. Materials and Methods: Ten patients (seven children and three adults) with an average age of 15 years have been enrolled in this study. Age of diagnosis of MPS IVA has a variable age of onset and a MISLEADING rate of severity. Hip dislocations, genu valgum, protrusio acetabuli and osteoarthritis were the most common lower limbs deformities in these patients. Clinical and radiographic phenotypes were the baseline tools of documentation. Urinary screening and genotypic characterizations have been applied accordingly. Results: Combined pelvic and femoral procedures for hip dislocation, epiphysiodeses and supracondylar osteotomy for genu valgum and hip arthroplasty for protrusio acetabuli have been performed. All patients manifested insufficient activity of N-acetylgalactosamine-6-sulphate sulphatase, an enzyme that degrades keratin sulphate and chondroitin-6 sulphate. Conclusion: The extensive clinical heterogeneity contributed significantly in the delay in establishing the diagnosis particularly in adult patients with MPS IV. The epiphyseal irregularities of the long bones and the progressive flattening pathology of MPS IV A were the reason to falsely diagnose some patients as spondyloepiphyseal dysplasia congenital and/or tarda. Proximal femoral osteotomy, realignment osteotomy and total hip arthroplasty have been performed for coxa vara, genu valgum and protrusio acetabuli, respectively, in children and adult group of patients. The importance of early diagnosis on MPS IV A is to receive enzyme replacement therapy

  15. Ultrasound Examination of Pediatric Musculoskeletal Diseases and Neonatal Spine.

    PubMed

    Karnik, Alka Sudhir; Karnik, Alpana; Joshi, Alpana

    2016-06-01

    Ultrasound (US) is a simple, non-invasive imaging modality which allows high-resolution imaging of the musculoskeletal (MSK) system. Its increasing popularity in pediatrics is due to the fact that it does not involve radiation, has an ability to visualize non-ossified cartilaginous and vascular structures, allows dynamic imaging and quick contralateral comparison. US is the primary imaging modality in some pediatric MSK conditions like infant hip in developmental dysplasia (DDH), hip joint effusion, epiphyseal trauma and evaluation of the neonatal spine. US is the modality of choice in infants with DDH, both in the initial evaluation and post-treatment follow-up. US has a sensitivity equivalent to MRI in evaluation of the neonatal spine in experienced hands and is a good screening modality in neonates with suspected occult neural tube defects. In other MSK applications, it is often used for the initial diagnosis or in addition to other imaging modalities. In trauma and infections, US can often detect early and subtle soft tissue abnormalities and a quick comparison with the contralateral side aids in diagnoses. Dynamic imaging is crucial in evaluating congenital instabilities and dislocations, soft tissue and ligamentous injuries, epiphyseal injuries and fracture separations. High-resolution imaging along with color Doppler (CD) is useful in the characterization of soft tissue masses. This article reviews the applications of US in pediatric MSK with emphasis on conditions where it is a primary modality. Limitations of US include inability to penetrate bone, hence, limited diagnosis of intraosseous pathology and operator dependency. PMID:26830280

  16. Pharmacological inhibition of lysosomes activates the MTORC1 signaling pathway in chondrocytes in an autophagy-independent manner

    PubMed Central

    Newton, Phillip T; Vuppalapati, Karuna K; Bouderlique, Thibault; Chagin, Andrei S

    2015-01-01

    Mechanistic target of rapamycin (serine/threonine kinase) complex 1 (MTORC1) is a protein-signaling complex at the fulcrum of anabolic and catabolic processes, which acts depending on wide-ranging environmental cues. It is generally accepted that lysosomes facilitate MTORC1 activation by generating an internal pool of amino acids. Amino acids activate MTORC1 by stimulating its translocation to the lysosomal membrane where it forms a super-complex involving the lysosomal-membrane-bound vacuolar-type H+-ATPase (v-ATPase) proton pump. This translocation and MTORC1 activation require functional lysosomes. Here we found that, in contrast to this well-accepted concept, in epiphyseal chondrocytes inhibition of lysosomal activity by v-ATPase inhibitors bafilomycin A1 or concanamycin A potently activated MTORC1 signaling. The activity of MTORC1 was visualized by phosphorylated forms of RPS6 (ribosomal protein S6) and EIF4EBP1, 2 well-known downstream targets of MTORC1. Maximal RPS6 phosphorylation was observed at 48-h treatment and reached as high as a 12-fold increase (p < 0.018). This activation of MTORC1 was further confirmed in bone organ culture and promoted potent stimulation of longitudinal growth (p < 0.001). Importantly, the same effect was observed in ATG5 (autophagy-related 5)-deficient bones suggesting a macroautophagy-independent mechanism of MTORC1 inhibition by lysosomes. Thus, our data show that in epiphyseal chondrocytes lysosomes inhibit MTORC1 in a macroautophagy-independent manner and this inhibition likely depends on v-ATPase activity. PMID:26259639

  17. Levels of Evidence in the Treatment of Slipped Capital Femoral Epiphysis: A Systematic Review

    PubMed Central

    Moriarity, Andrew; Kennedy, Jim; Baker, Joe; Kiely, Pat

    2016-01-01

    The primary aim of this study was to analyze the current level of evidence available on the surgical management of Slipped Capital Femoral Epiphysis (SCFE). Secondary aims were to correlate the level of evidence with the impact factor of the journal to evaluate the level of evidence over time, and to evaluate the geographic distribution of the studies. Therapeutic studies published in English between January 1991 and August 2014 that reported on SCFE were identified via electronic search was performed using the databases PubMed, EMBASE, and the Cochrane Library. The search terms used included: Slipped capital femoral epiphyses OR SCFE OR Slipped upper femoral epiphyses OR SUFE AND Management OR Treatment. Correlation between the level of evidence and the impact factor of the journal were analyzed together with linear regression models to reveal any significant trends over time. A total of 1516 studies were found, of which 321 were included in the final analysis. The most frequent study type was the case series (51.1%) followed by case reports (22.4%) and expert opinion (14.0%). Randomized control trial accounted for only 0.6%. The Journal of Pediatric Orthopedics (American) had the most studies (22.6%) and the highest number of level 2 (n=1) and level 3 (n=15) type evidence. There was no progression of level of evidence over time. There was no correlation between level of evidence and impact factor of journal. The majority of therapeutic studies on SCFE are of low level of evidence. High-level RCTs are difficult to perform in pediatric orthopedic surgery, however the management of SCFE would benefit from well-designed, multicenter, clinical RCTs to advance evidence-based practice. PMID:27433299

  18. The arterial anatomy of the developing human dorsal and lumbar vertebral body. A microarteriographic study.

    PubMed

    Ratcliffe, J F

    1981-12-01

    The arterial anatomy of 60 lumbar and lower dorsal vertebral bodies from eight subjects aged between 29 weeks gestation and 15 years was studied. The arteries had been injected with a suspension of barium sulphate and the vertebrae decalcified, sectioned and radiographed. In the specimen of 29 weeks gestation, the equatorial arteries were present. Precursors of the metaphyseal arteries lay obliquely over and completely outside the ossification centre. These precursors originated from an irregular network of perichondral arteries near the equator. By six months of age, the perichondral arteries had migrated discally and had become well organized metaphyseal anastomoses while the metaphyseal arteries had become horizontal. Also by six months, the extra-osseous longitudinal anastomoses had developed into the adult pattern. In the 36 weeks fetus, the ends of the unbranching metaphyseal arteries were incorporated into the ossification centre. This central relationship was maintained into adult life, but, as the ossification centre expanded, the branches of the intra-osseous arteries followed the zone of ossification in a centrifugal manner. In infancy, the metaphyseal arteries were approximately equal in length and the equatorial arteries divided in the middle of the vertebral body; by the age of 15 years, the metaphyseal arteries arising from the anterolateral surfaces were longer than those which arose from the posterior surface, and the equatorial arteries divided behind the mid-point. From these arterial observations, a number of deductions concerning the mode of growth of the vertebral body have been drawn. Preterminal coils and typical peripheral arteries, frequent features in the adult vertebral body, were not seen in any of these specimens. There was no evidence of any epiphyseal growth plate, nor of epiphyseal arteries in these specimens. PMID:7333964

  19. Automatic segmentation of bones from digital hand radiographs

    NASA Astrophysics Data System (ADS)

    Liu, Brent J.; Taira, Ricky K.; Shim, Hyeonjoon; Keaton, Patricia

    1995-05-01

    The purpose of this paper is to develop a robust and accurate method that automatically segments phalangeal and epiphyseal bones from digital pediatric hand radiographs exhibiting various stages of growth. The algorithm uses an object-oriented approach comprising several stages beginning with the most general objects to be segmented, such as the outline of the hand from background, and proceeding in a succession of stages to the most specific object, such as a specific phalangeal bone from a digit of the hand. Each stage carries custom operators unique to the needs of that specific stage which will aid in more accurate results. The method is further aided by a knowledge base where all model contours and other information such as age, race, and sex, are stored. Shape models, 1-D wrist profiles, as well as an interpretation tree are used to map model and data contour segments. Shape analysis is performed using an arc-length orientation transform. The method is tested on close to 340 phalangeal and epiphyseal objects to be segmented from 17 cases of pediatric hand images obtained from our clinical PACS. Patient age ranges from 2 - 16 years. A pediatric radiologist preliminarily assessed the results of the object contours and were found to be accurate to within 95% for cases with non-fused bones and to within 85% for cases with fused bones. With accurate and robust results, the method can be applied toward areas such as the determination of bone age, the development of a normal hand atlas, and the characterization of many congenital and acquired growth diseases. Furthermore, this method's architecture can be applied to other image segmentation problems.

  20. Bacterial chondronecrosis with osteomyelitis and lameness in broilers: a review.

    PubMed

    Wideman, Robert F

    2016-02-01

    This review focuses on a specific cause of lameness known as bacterial chondronecrosis with osteomyelitis (BCO) in broilers. Rapid increases in body weight impose excessive torque and shear stress on structurally immature epiphyseal and physeal cartilage, primarily in the proximal femora, proximal tibiae, and flexible thoracic vertebrae. Excessive mechanical stress creates osteochondrotic clefts among the chondrocytes of susceptible growth plates. These wound sites are colonized by hematogenously distributed opportunistic bacteria, culminating in the gross abscesses and necrotic voids that are pathognomonic for terminal BCO. Lameness attributable to characteristic BCO lesions can be reproduced by rearing broilers on wire flooring to create persistent footing instability and physiological stress, without the need to inoculate the birds with pathogenic bacteria that presumably are present but quiescent within the bird's microbial communities or in the environment. Experiments using the wire-flooring model revealed innate differences in the susceptibility of broiler lines to BCO, and demonstrated that BCO incidences can be reduced by prophylactically providing probiotics in the feed, by prophylactically adding 25-hydroxy vitamin D3 to the drinking water, or by therapeutically adding the antibiotic enrofloxacin to the drinking water. Hatchery and chick quality issues clearly influence the susceptibility of broilers to BCO. When broilers remain in a sitting posture for prolonged periods, the major arteries supplying their legs may be compressed. These episodes of inadequate blood flow may prevent chondrocyte maturation and trigger focal necrosis, thereby making the epiphyseal and physeal cartilage highly susceptible to osteochondrosis and BCO. Much remains to be revealed regarding the pathogenesis of BCO. Further revelations will be facilitated by the availability of the now-validated wire-flooring models that consistently trigger high incidences of BCO in experimental

  1. Effects of neonatal enzyme replacement therapy and simvastatin treatment on cervical spine disease in mucopolysaccharidosis I dogs.

    PubMed

    Chiaro, Joseph A; O'Donnell, Patricia; Shore, Eileen M; Malhotra, Neil R; Ponder, Katherine P; Haskins, Mark E; Smith, Lachlan J

    2014-12-01

    Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease characterized by deficient α-L-iduronidase activity, leading to the accumulation of poorly degraded glycosaminoglycans (GAGs). Children with MPS I exhibit high incidence of spine disease, including accelerated disc degeneration and vertebral dysplasia, which in turn lead to spinal cord compression and kyphoscoliosis. In this study we investigated the efficacy of neonatal enzyme replacement therapy (ERT), alone or in combination with oral simvastatin (ERT + SIM) for attenuating cervical spine disease progression in MPS I, using a canine model. Four groups were studied: normal controls; MPS I untreated; MPS I ERT-treated; and MPS I ERT + SIM-treated. Animals were euthanized at age 1 year. Intervertebral disc condition and spinal cord compression were evaluated from magnetic resonance imaging (MRI) images and plain radiographs, vertebral bone condition and odontoid hypoplasia were evaluated using micro-computed tomography (µCT), and epiphyseal cartilage to bone conversion was evaluated histologically. Untreated MPS I animals exhibited more advanced disc degeneration and more severe spinal cord compression than normal animals. Both treatment groups resulted in partial preservation of disc condition and cord compression, with ERT + SIM not significantly better than ERT alone. Untreated MPS I animals had significantly lower vertebral trabecular bone volume and mineral density, whereas ERT treatment resulted in partial preservation of these properties. ERT + SIM treatment demonstrated similar, but not greater, efficacy. Both treatment groups partially normalized endochondral ossification in the vertebral epiphyses (as indicated by absence of persistent growth plate cartilage), and odontoid process size and morphology. These results indicate that ERT begun from a very early age attenuates the severity of cervical spine disease in MPS I, particularly for the vertebral bone and odontoid process

  2. Growth in patients with isolated gonadotrophin deficiency.

    PubMed Central

    Dickerman, Z; Cohen, A; Laron, Z

    1992-01-01

    The growth pattern of 66 patients (50 males, 16 females) with isolated gonadotrophin deficiency (IGnD), who had reached their final height with epiphyseal closure, was evaluated. For the purpose of analysis the males were divided into two groups according to age at referral: group 1 less than 16 years (n = 23) and group 2 greater than or equal to 16 years (n = 27). Sex hormone treatment was initiated at a mean (SD) chronological age of 15.8 (1.3) and 18.6 (1.2) years in groups 1 and 2 in the males and at 15.3 (1.3) years in the females. The duration of treatment (until epiphyseal closure) in the males was 3.9 (1.5) years in group 1 and 2.1 (1.0) years in group 2 and 2.8 (1.3) years in the females. There was no significant difference between the mean final height in groups 1 and 2, but it was significantly higher than the mean parental height (mean height SD score (HtSDS): 0.1 (1.1) v -0.8 (0.9)) and they were significantly correlated. For females the mean HtSDS compared with parental height was 0.4 (1.5) v -0.6 (1.2). It is concluded that the timing of induction of puberty by sex hormones in males and females with IGnD has no significant effect on final height provided that moderate doses are used. Furthermore final height was significantly correlated to mid-parental height. PMID:1580683

  3. A serum component mediates food restriction-induced growth attenuation.

    PubMed

    Pando, Rakefet; Shtaif, Biana; Phillip, Moshe; Gat-Yablonski, Galia

    2014-03-01

    Proper nutrition in terms of calories and essential food components is required to maximize longitudinal growth in children. Our previous study showed that prepubertal male rats subjected to 10 days of 40% food restriction (RES) exhibited a dramatic reduction in weight and epiphyseal growth plate height, as well as changes in gene expression and microRNAs (miRNAs) in the epiphyseal growth plate. These findings reversed rapidly after renewal of the regular food supply (catch-up [CU]). To further elucidate the mechanisms underlying the nutrition-growth association, serum collected from the RES and CU rats and control rats fed ad libitum (AL) was added to the culture medium of the chondrocyte cell line ATDC5 (instead of fetal calf serum). Serum from the RES group induced a reduction in cell viability (25%, P < .05) concomitant with an increase in cell differentiation compared with that for the AL group serum. The most interesting observation, in our opinion, was the significant reduction in the expression of specific miRNAs, including the chondro-specific miR-140. These effects were not observed for serum from refed (CU) rats. Serum levels of IGF-I, leptin, and fibroblast growth factor 21 were reduced by food restriction. The addition of IGF-I and leptin to the culture increased cell viability, whereas fibroblast growth factor 21 reduced it, suggesting the involvement of IGF-I, leptin, and possibly other still unidentified serum factors in chondrocyte cell growth. In conclusion, specific miRNAs respond to nutritional cues, and these effects are mediated by serum-borne factors. These results may promote the development of superior interventions for children with malnutrition and growth abnormalities. PMID:24456162

  4. Rampant infections of bone marrow stem cell niches as triggers for spondyloarthropathies and rheumatoid arthritis.

    PubMed

    Berthelot, Jean-Marie; Sibilia, Jean

    2016-01-01

    Tropheryma Whipplei can induce rheumatism mimicking SpA or RA, but even more rampant bacterial/viral infections in epiphyseal bones could also contribute to the onset of RA and SpA. Indeed, as bone marrow stem cell niches are enriched in Tregs and myeloid derived suppressor cells, these areas are favourable for the persistence of quiescent viruses and/or dormant bacteria. This review focuses on the possibility that such silent infections of bone marrow stem cell niches might contribute to the pathogenesis of SpA and RA, at least during their onset. Some infections can affect the bone marrow mesenchymal stem cells, which can transmit these pathogens to their progeny. Transient but repeated revivals of viruses or dormant bacteria could promote the conversion of marrow regulatory T cells into effector phenotypes, leading to autoimmunity in the epiphyseal bone marrow, entheses and adjacent synovium. This scenario would also fit the flares of rheumatic disorders and explain why some joints or enthuses can be severely involved whereas their neighbours remain intact. The efficiency of anti-TNF drugs does not rule out a role of persistent infections in SpA and RA. These drugs do not affect chlamydial clearance, or the reactivation of latent Salmonella enterica serovar Typhimurium in mice or Epstein-Barr virus in humans. Anti-TNF might even prevent, rather than foster, the revival of dormant bacteria and viruses in marrow stem cell niches. Indeed, anti-TNF enhance the maturation of the immunosuppressive immature myeloid cells around stem cells into dendritic cells and macrophages, thus restoring immune responses in these areas. PMID:26886813

  5. Pathogenesis of lumbar spine disease in mucopolysaccharidosis VII

    PubMed Central

    Smith, Lachlan J; Baldo, Guilherme; Wu, Susan; Liu, Yuli; Whyte, Michael P; Giugliani, Roberto; Elliott, Dawn M; Haskins, Mark E; Ponder, Katherine P

    2012-01-01

    Mucopolysaccharidosis type VII (MPS VII) is characterized by deficient β-glucuronidase (GUSB) activity, which leads to accumulation of chondroitin, heparan and dermatan sulfate glycosaminoglycans (GAGs), and multisystemic disease. MPS VII patients can develop kypho-scoliotic deformity and spinal cord compression due to disease of intervertebral discs, vertebral bodies, and associated tissues. We have previously demonstrated in MPS VII dogs that intervertebral discs degenerate, vertebral bodies have irregular surfaces, and vertebral body epiphyses have reduced calcification, but the pathophysiological mechanisms underlying these changes are unclear. We hypothesized that some of these manifestations could be due to upregulation of destructive proteases, possibly via the binding of GAGs to Toll-like receptor 4 (TLR4), as has been proposed for other tissues in MPS models. In this study, the annulus fibrosus of the intervertebral disc of 6 month-old MPS VII dogs had cathepsin B and K activities that were 117- and 2-fold normal, respectively, which were associated with elevations in mRNA levels for cathepsins as well as TLR4. The epiphyses of MPS VII dogs had a marked elevation in mRNA for the cartilage-associated gene collagen II, consistent with a developmental delay in the conversion of the cartilage to bone in this region. A spine from a human patient with MPS VII exhibited similar increased cartilage in the vertebral bodies adjacent to the end plates, disorganization of the intervertebral discs, and irregular vertebral end plate morphology. These data suggest that the pathogenesis of destructive changes in the spine in MPS VII may involve upregulation of cathepsins. Inhibition of destructive proteases, such as cathepsins, might reduce spine disease in patients with MPS VII or related disorders. PMID:22513347

  6. In vivo Delivery of Fluoresceinated Dextrans to the Murine Growth Plate: Imaging of Three Vascular Routes by Multiphoton Microscopy

    PubMed Central

    Farnum, Cornelia; Lenox, Michelle; Zipfel, Warren; Horton, William; Williams, Rebecca

    2008-01-01

    Bone elongation by endochondral ossification occurs through the differentiation cascade of chondrocytes of cartilaginous growth plates. Molecules from the systemic vasculature reach the growth plate from three different directions: epiphyseal, metaphyseal, and via a ring vessel and plexus associated with the perichondrium. This study is an analysis of the real-time dynamics of entrance of fluoresceinated tracers of different molecular weights into the growth plate from the systemic vasculature, and tests the hypothesis that molecular weight is a key variable in the determination of both the directionality and the extent of tracer movement into the growth plate. Multiphoton microscopy was used for direct in vivo imaging of the murine proximal tibial growth plate in anesthetized 4-5-week-old transgenic mice with green fluorescent protein linked to the collagen II promoter. Mice were given an intracardiac injection of either fluorescein (332.3 Da), or fluoresceinated dextrans of 3, 10, 40, 70 kDa, singly or sequentially. For each tracer, directionality and rate of arrival, together with extent of movement within the growth plate, were imaged in real time. For small molecules (up to 10 kDa) vascular access from all three directions was observed and entrance was equally permissive from the metaphyseal and the epiphyseal sides. Within our detection limit (a few per cent of vascular concentration) 40 kDa and larger dextrans did not enter. These results have implications both for understanding systemic and paracrine regulation of growth plate chondrocytic differentiation, as well as variables associated with effective drug delivery to growth plate chondrocytes. PMID:16342207

  7. Role of dehydroepiandrosterone in management of glucocorticoid-induced secondary osteoporosis in female rats.

    PubMed

    Ahmed, Hanaa H; Morcos, Nadia Y S; Eskander, Emad F; Seoudi, Dina M S; Shalby, Aziza B

    2012-09-01

    The current study aimed to evaluate the potential role of dehydroepiandrosterone (DHEA) in the protection and intervention of glucocorticoid-induced secondary osteoporosis in female rats. For this purpose this study was conducted on five groups of female Sprague Dawley rats which were classified into: (1) negative control group received saline as vehicle, (2) osteoporotic group orally administered with prednisolone (5 mg/kg b.wt.) daily for six months, (3) positive control group orally administered with DHEA (250 mg/kg b.wt.) three times weekly for six months, (4) protective group orally administered with prednisolone daily with simultaneous oral administration of DHEA three times weekly for six months and (5) therapeutic group orally administered with prednisolone daily for six months then orally administered with DHEA three times weekly for other six months. The obtained data revealed that prednisolone administration resulted in significant decrease in serum osteocalcin (OC), 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2) D(3)) and osteoprotegerin (OPG) levels accompanied with significant increase in serum parathyroid hormone (PTH) and receptor activator nuclear factor kappa B ligand (RANKL) levels. Histopathological investigation of left femur bone showed that prednisolone administration produced compression of the reduced articular surface and atrophy of the epiphyseal bone. On the other hand, DHEA supplementation to osteoporotic rats increased serum OC, 1,25-(OH)(2) D(3) and OPG levels while decreased serum PTH and RANKL levels. Moreover, DHEA administration resulted in restoration of intact epiphyseal bony structure and articular surface. In conclusion, DHEA via its control on glucocorticoid activity and androgenic action provided potent effect on bone. PMID:21310600

  8. Effects of Neonatal Enzyme Replacement Therapy and Simvastatin Treatment on Cervical Spine Disease in Mucopolysaccharidosis I Dogs

    PubMed Central

    Chiaro, Joseph A; O’Donnell, Patricia; Shore, Eileen M; Malhotra, Neil R; Ponder, Katherine P; Haskins, Mark E; Smith, Lachlan J

    2014-01-01

    Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease characterized by deficient α-L-iduronidase activity, leading to the accumulation of poorly degraded glycosaminoglycans (GAGs). Children with MPS I exhibit high incidence of spine disease, including accelerated disc degeneration and vertebral dysplasia, which in turn lead to spinal cord compression and kypho-scoliosis. In this study we investigated the efficacy of neonatal enzyme replacement therapy (ERT), alone or in combination with oral simvastatin (ERT+SIM) for attenuating cervical spine disease progression in MPS I, using a canine model. Four groups were studied: normal controls; MPS I untreated; MPS I ERT treated; and MPS I ERT+SIM treated. Animals were euthanized at one year-of-age. Intervertebral disc condition and spinal cord compression were evaluated from MRIs and plain radiographs, vertebral bone condition and odontoid hypoplasia were evaluated using microcomputed tomography, and epiphyseal cartilage to bone conversion was evaluated histologically. Untreated MPS I animals exhibited more advanced disc degeneration and more severe spinal cord compression than normal animals. Both treatment groups resulted in partial preservation of disc condition and cord compression, with ERT+SIM not significantly better than ERT alone. Untreated MPS I animals had significantly lower vertebral trabecular bone volume and mineral density, while ERT treatment resulted in partial preservation of these properties. ERT+SIM treatment demonstrated similar, but not greater, efficacy. Both treatment groups partially normalized endochondral ossification in the vertebral epiphyses (as indicated by absence of persistent growth plate cartilage), and odontoid process size and morphology. These results indicate that ERT begun from a very early age attenuates the severity of cervical spine disease in MPS I, particularly for the vertebral bone and odontoid process, and that additional treatment with simvastatin does not

  9. Tracheomalacia in a neonate with kniest dysplasia: histopathologic and ultrastructural features.

    PubMed

    Hicks, J; De Jong, A; Barrish, J; Zhu, S H; Popek, E

    2001-01-01

    Kniest dysplasia is an autosomal-dominant chondrodysplastic condition characterized by disproportionate dwarfism, short trunk, small pelvis, kyphoscoliosis, short limbs, prominent joints, premature osteoarthritis, and craniofacial manifestations. The craniofacial abnormalities include tracheomalacia, midface hypoplasia, cleft palate, early onset myopia, retinal detachment, prominent eyes, and sensorineural hearing loss. Radiologic features include dumbbell-shaped femora, platyspondylia with anterior wedging of vertebral bodies, coronal clefts of thoracolumbar vertebral bodies, low broad ilia, and short tubular bones with broad metaphyses and deformed large epiphyses. This form of chondrodysplasia is associated with mutations in type II collagen splicing sequences. Mutations have been identified in the COL2A1 (type II collagen) gene between exons 12 and 24. Type II collagen is the predominant structural protein in cartilage, and mutations in this collagen account for the Kniest dysplasia phenotype. Histopathologic and ultrastructural features of epiphyseal plate cartilage have been described, but tracheal cartilage in an affected neonate has not been examined. The authors report the histopathologic and ultrastructural findings of anterior tracheal cartilage from a 35-day-old female with suspected chondrodysplasia who had tracheomalacia with airway obstruction. The tracheal cartilage was moderately cellular, but lacked cystic and myxoid changes in its matrix. The chondrocytes had abundant cytoplasmic PAS-positive inclusions. Some of these inclusions were diastase-resistant and were also highlighted on Alcian blue staining. Ultrastructural examination revealed chondrocytes with greatly dilated rough endoplasmic reticulum containing granular proteinaceous material. There were also frequent aggregates of typical glycogen. The defect in the COL2A1 gene is secondary to mutations, especially at splice junctions, and this markedly disrupts triple helix formation. The

  10. Improved Visualization of Cartilage Canals Using Quantitative Susceptibility Mapping

    PubMed Central

    Nissi, Mikko J.; Tóth, Ferenc; Wang, Luning; Carlson, Cathy S.; Ellermann, Jutta M.

    2015-01-01

    Purpose Cartilage canal vessels are critical to the normal function of epiphyseal (growth) cartilage and damage to these vessels is demonstrated or suspected in several important developmental orthopaedic diseases. High-resolution, three-dimensional (3-D) visualization of cartilage canals has recently been demonstrated using susceptibility weighted imaging (SWI). In the present study, a quantitative susceptibility mapping (QSM) approach is evaluated for 3-D visualization of the cartilage canals. It is hypothesized that QSM post-processing improves visualization of the cartilage canals by resolving artifacts present in the standard SWI post-processing while retaining sensitivity to the cartilage canals. Methods Ex vivo distal femoral specimens from 3- and 8-week-old piglets and a 1-month-old human cadaver were scanned at 9.4 T with a 3-D gradient recalled echo sequence suitable for SWI and QSM post-processing. The human specimen and the stifle joint of a live, 3-week-old piglet also were scanned at 7.0 T. Datasets were processed using the standard SWI method and truncated k-space division QSM approach. To compare the post-processing methods, minimum/maximum intensity projections and 3-D reconstructions of the processed datasets were generated and evaluated. Results Cartilage canals were successfully visualized using both SWI and QSM approaches. The artifactual splitting of the cartilage canals that occurs due to the dipolar phase, which was present in the SWI post-processed data, was eliminated by the QSM approach. Thus, orientation-independent visualization and better localization of the cartilage canals was achieved with the QSM approach. Combination of GRE with a mask based on QSM data further improved visualization. Conclusions Improved and artifact-free 3-D visualization of the cartilage canals was demonstrated by QSM processing of the data, especially by utilizing susceptibility data as an enhancing mask. Utilizing tissue-inherent contrast, this method allows

  11. Melanocortin 1 Receptor-Signaling Deficiency Results in an Articular Cartilage Phenotype and Accelerates Pathogenesis of Surgically Induced Murine Osteoarthritis

    PubMed Central

    Hackmayer, Gerit; Greth, Carina; Bauer, Richard J.; Kleinschmidt, Kerstin; Bettenworth, Dominik; Böhm, Markus; Grifka, Joachim; Grässel, Susanne

    2014-01-01

    Proopiomelanocortin-derived peptides exert pleiotropic effects via binding to melanocortin receptors (MCR). MCR-subtypes have been detected in cartilage and bone and mediate an increasing number of effects in diathrodial joints. This study aims to determine the role of MC1-receptors (MC1) in joint physiology and pathogenesis of osteoarthritis (OA) using MC1-signaling deficient mice (Mc1re/e). OA was surgically induced in Mc1re/e and wild-type (WT) mice by transection of the medial meniscotibial ligament. Histomorphometry of Safranin O stained articular cartilage was performed with non-operated controls (11 weeks and 6 months) and 4/8 weeks past surgery. µCT–analysis for assessing epiphyseal bone architecture was performed as a longitudinal study at 4/8 weeks after OA-induction. Collagen II, ICAM-1 and MC1 expression was analysed by immunohistochemistry. Mc1re/e mice display less Safranin O and collagen II stained articular cartilage area compared to WT prior to OA-induction without signs of spontaneous cartilage surface erosion. This MC1-signaling deficiency related cartilage phenotype persisted in 6 month animals. At 4/8 weeks after OA-induction cartilage erosions were increased in Mc1re/e knees paralleled by weaker collagen II staining. Prior to OA-induction, Mc1re/e mice do not differ from WT with respect to bone parameters. During OA, Mc1re/e mice developed more osteophytes and had higher epiphyseal bone density and mass. Trabecular thickness was increased while concomitantly trabecular separation was decreased in Mc1re/e mice. Numbers of ICAM-positive chondrocytes were equal in non-operated 11 weeks Mc1re/e and WT whereas number of positive chondrocytes decreased during OA-progression. Unchallenged Mc1re/e mice display smaller articular cartilage covered area without OA-related surface erosions indicating that MC1-signaling is critical for proper cartilage matrix integrity and formation. When challenged with OA, Mc1re/e mice develop a more severe OA

  12. Structural analysis of the human tibia in men with spinal cord injury by tomographic (pQCT) serial scans.

    PubMed

    Rittweger, Jörn; Goosey-Tolfrey, Vicky L; Cointry, Gustavo; Ferretti, José Luis

    2010-09-01

    Spinal cord injury (SCI), as a primarily neurological disorder that causes muscular atrophy, is well known to be associated with sub-lesional bone losses. These losses are more pronounced from epiphyseal than from diaphyseal regions. We hypothesized that this discrepancy may be explained by anatomical variation in endocortical circumference. Nine men who had attracted SCI 9 to 32 (mean 21.4) years prior to study inclusion were matched to able bodied control (Ctrl) people by age, height and weight. Serial scans by peripheral quantitative computed tomography were obtained from the tibia at steps corresponding to 5%-steps of the tibias length (s05 to s95, from distal to the proximal end of the tibia). As expected, SCI people had lower total bone mineral content (vBMC.tot) than able bodied control people (P<0.001 at all sites). This group difference (DeltavBMC.tot) was more pronounced at the distal and proximal tibia than in the shaft (P<0.001), and it amounted to 51% at s05, to 22% at s40, and to 47% at s95. Both endocortical and periosteal circumference were better predictors of DeltavBMC.tot (R(2)=0.98 and R(2)=0.97, respectively; P<0.001 in both cases) than vBMC.tot (R(2)=0.58, P<0.001), suggesting that anatomical variation in geometry, rather than in bone mass can explain differential rates of bone loss after SCI. Moreover, the s04:s38 ratio in vBMC.tot was found to be 1.00 (95% confidence interval: 0.95-1.05) in the Ctrl group, and 0.63 in the SCI group (P<0.001, 95% confidence interval: 0.54-0.68). These findings offer a rationale to account for the discrepancy between epiphyseal and diaphyseal bone losses following SCI. The suggestion is that the bone adaptive responses involved are limited in time, and that the reduced surface:volume ratio constitutes a limit within the available time window, in particular in the diaphysis. Finally, the drastically reduced s04:s38 vBMC.tot ratio observed in the SCI group in this study provides a rationale to scrutinize this

  13. A review of epidemiology of paediatric elbow injuries in sports.

    PubMed

    Magra, Merzesh; Caine, Dennis; Maffulli, Nicola

    2007-01-01

    The elbow is a common site of orthopaedic injury in the paediatric population. The number of these injuries continues to rise following increased levels of participation in paediatric recreational and competitive sport. Injuries to the paediatric elbow can be classified as either overuse or acute. Delineating injury patterns to the elbow in children can be challenging, given the cartilaginous composition of the distal humerus and the multiple secondary ossification centres that appear and unite with the epiphysis at defined ages. Pitching in baseball, serving in tennis, spiking in volleyball, passing in American football and launching in javelin-throwing can all produce elbow pathology by forceful valgus stress, with medial stretching, lateral compression and posterior impingement. In children and adolescents, the epiphyseal plate is weaker than the surrounding ligaments, predisposing them to epiphyseal plate injuries. On the other hand, post-pubescent or skeletally mature athletes are more prone to tendinous or ligamentous injury. Injuries may cause significant impact on the athlete, parents and healthcare system. With the exception of baseball, there are few prospective cohort studies on the epidemiological trends of childhood elbow injuries in other sports. This paper aims to describe the epidemiological trends in paediatric elbow injuries related to sports, suggests prevention strategies and discusses the scope for further research. A web-based search of existing articles pertaining to paediatric elbow injuries in sports was performed. The implications of acute and overuse injuries and the possibility of permanent damage should be understood by parents, coaches and the athletes. Proper understanding of the intrinsic and extrinsic risk factors that could lead to elbow injuries is thus required. Measures to prevent elbow injuries should include proper coaching, warm-up, officiation, legislation, medical expertise and protective gear. There are still many

  14. Inactivation of Fam20B in Joint Cartilage Leads to Chondrosarcoma and Postnatal Ossification Defects.

    PubMed

    Ma, Pan; Yan, Wenjuan; Tian, Ye; Wang, Jingya; Feng, Jian Q; Qin, Chunlin; Cheng, Yi-Shing Lisa; Wang, Xiaofang

    2016-01-01

    During endochondral ossification, chondrocytes embed themselves in a proteoglycan-rich matrix during the proliferation-maturation transition. Accumulating evidence shows that proteoglycans are essential components for chondrocyte proliferation and differentiation. When we conditionally inactivated FAM20B (Family with sequence similarity 20 member-B), which is a newly identified xylose kinase essential for glycosaminoglycan (GAG) formation on the protein core of proteoglycans, from the dental mesenchyme using Osr2-Cre, which is also strongly expressed in joint cartilage, we found chondrosarcoma in the knee joint and remarkable defects of postnatal ossification in the long bones. Mechanistic analysis revealed that the defects were associated with gain of function in multiple signaling pathways in the epiphyseal chondrocytes, such as those derived by WNT, BMP, and PTHrP/IHH molecules, suggesting that the FAM20B-catalyzed proteoglycans are critical mediators for a signaling balance in the regulatory network controlling chondrocyte differentiation and proliferation. In particular, we demonstrated that the WNT inhibitor was able to rescue part of the bone defects in Osr2-Cre;Fam20B(fl/fl) mice, indicating that FAM20B-catalyzed proteoglycans regulate postnatal endochondral ossification partially through the mediation of WNT signaling. PMID:27405802

  15. Inactivation of Fam20B in Joint Cartilage Leads to Chondrosarcoma and Postnatal Ossification Defects

    PubMed Central

    Ma, Pan; Yan, Wenjuan; Tian, Ye; Wang, Jingya; Feng, Jian Q.; Qin, Chunlin; Cheng, Yi-Shing Lisa; Wang, Xiaofang

    2016-01-01

    During endochondral ossification, chondrocytes embed themselves in a proteoglycan-rich matrix during the proliferation-maturation transition. Accumulating evidence shows that proteoglycans are essential components for chondrocyte proliferation and differentiation. When we conditionally inactivated FAM20B (Family with sequence similarity 20 member-B), which is a newly identified xylose kinase essential for glycosaminoglycan (GAG) formation on the protein core of proteoglycans, from the dental mesenchyme using Osr2-Cre, which is also strongly expressed in joint cartilage, we found chondrosarcoma in the knee joint and remarkable defects of postnatal ossification in the long bones. Mechanistic analysis revealed that the defects were associated with gain of function in multiple signaling pathways in the epiphyseal chondrocytes, such as those derived by WNT, BMP, and PTHrP/IHH molecules, suggesting that the FAM20B-catalyzed proteoglycans are critical mediators for a signaling balance in the regulatory network controlling chondrocyte differentiation and proliferation. In particular, we demonstrated that the WNT inhibitor was able to rescue part of the bone defects in Osr2-Cre;Fam20Bfl/fl mice, indicating that FAM20B-catalyzed proteoglycans regulate postnatal endochondral ossification partially through the mediation of WNT signaling. PMID:27405802

  16. [Basophilic line of the articular cartilage in normal and various pathological states].

    PubMed

    Gongadze, L R

    1987-04-01

    Epiphyses of long tubular bones in the man and animals of various age, as well as experimental material of the adjuvant arthritis, with special reference to the basal part of the articular cartilage have been studied by means of histological, histochemical and histometrical methods. The structural-chemical organization of the basophilic line (tidemark) of the articular cartilage ensures its barrier role and participation in regulating selective permeability. Reconstruction of the tidemark in the process of physiological ageing and in cases of the articular pathology is aimed to preserve its integrity and in this way a complete differentiation of the noncalcified and calcified structures is secured. Disturbance of the basophilic line results in changes of the articular selective permeability, in invasion of vessels and structural elements of the bone marrow, and in development of profound distrophic and destructive changes of the cartilage--in deforming artrosis. Deflations in the structural-chemical organization of the tidemark indicate certain disturbances in the state of the system articular cartilage--subchondral bone. These data can be of prognostic importance. PMID:3606408

  17. In vivo radiometric analysis of glucose uptake and distribution in mouse bone

    PubMed Central

    Zoch, Meredith L; Abou, Diane S; Clemens, Thomas L; Thorek, Daniel L J; Riddle, Ryan C

    2016-01-01

    Bone formation and remodeling occurs throughout life and requires the sustained activity of osteoblasts and osteoclasts, particularly during periods of rapid bone growth. Despite increasing evidence linking bone cell activity to global energy homeostasis, little is known about the relative energy requirements or substrate utilization of bone cells. In these studies, we measured the uptake and distribution of glucose in the skeleton in vivo using positron-emitting 18F-fluorodeoxyglucose ([18F]-FDG) and non-invasive, high-resolution positron emission tomography/computed tomography (PET/CT) imaging and ex vivo autoradiography. Assessment of [18F]-FDG uptake demonstrated that relative to other tissues bone accumulated a significant fraction of the total dose of the glucose analog. Skeletal accumulation was greatest in young mice undergoing the rapid bone formation that characterizes early development. PET/CT imaging revealed that [18F]-FDG uptake was greatest in the epiphyseal and metaphyseal regions of long bones, which accords with the increased osteoblast numbers and activity at this skeletal site. Insulin administration significantly increased skeletal accumulation of [18F]-FDG, while uptake was reduced in mice lacking the insulin receptor specifically in osteoblasts or fed a high-fat diet. Our results indicated that the skeleton is a site of significant glucose uptake and that its consumption by bone cells is subject to regulation by insulin and disturbances in whole-body metabolism. PMID:27088042

  18. Central Precocious Puberty: Update on Diagnosis and Treatment.

    PubMed

    Chen, Melinda; Eugster, Erica A

    2015-08-01

    Central precocious puberty (CPP) is characterized by the same biochemical and physical features as normally timed puberty but occurs at an abnormally early age. Most cases of CPP are seen in girls, in whom it is usually idiopathic. In contrast, ~50% of boys with CPP have an identifiable cause. The diagnosis of CPP relies on clinical, biochemical, and radiographic features. Untreated, CPP has the potential to result in early epiphyseal fusion and a significant compromise in adult height. Thus, the main goal of therapy is preservation of height potential. The gold-standard treatment for CPP is gonadotropin-releasing hormone (GnRH) analogs (GnRHa). Numerous preparations with a range of delivery systems and durations of action are commercially available. While the outcomes of patients treated for CPP have generally been favorable, more research about the psychological aspects, optimal monitoring, and long-term effects of all forms of GnRHa treatment is needed. Several potential therapeutic alternatives to GnRHa exist and await additional investigation. PMID:25911294

  19. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway.

    PubMed

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development. PMID:26434683

  20. New Options for Vascularized Bone Reconstruction in the Upper Extremity

    PubMed Central

    Houdek, Matthew T.; Wagner, Eric R.; Wyles, Cody C.; Nanos, George P.; Moran, Steven L.

    2015-01-01

    Originally described in the 1970s, vascularized bone grafting has become a critical component in the treatment of bony defects and non-unions. Although well established in the lower extremity, recent years have seen many novel techniques described to treat a variety of challenging upper extremity pathologies. Here the authors review the use of different techniques of vascularized bone grafts for the upper extremity bone pathologies. The vascularized fibula remains the gold standard for the treatment of large bone defects of the humerus and forearm, while also playing a role in carpal reconstruction; however, two other important options for larger defects include the vascularized scapula graft and the Capanna technique. Smaller upper extremity bone defects and non-unions can be treated with the medial femoral condyle (MFC) free flap or a vascularized rib transfer. In carpal non-unions, both pedicled distal radius flaps and free MFC flaps are viable options. Finally, in skeletally immature patients, vascularized fibular head epiphyseal transfer can provide growth potential in addition to skeletal reconstruction. PMID:25685100

  1. Further evidence of POP1 mutations as the cause of anauxetic dysplasia.

    PubMed

    Elalaoui, Siham Chafai; Laarabi, Fatima Zahra; Mansouri, Maria; Mrani, Nidal Alaoui; Nishimura, Gen; Sefiani, Abdelaziz

    2016-09-01

    Anauxetic dysplasia (AAD, OMIM 607095) is a rare skeletal dysplasia inherited as an autosomal recessive trait, which is caused by mutations in RMRP and allelic to a more common disorder, cartilage hair hypoplasia (CHH). CHH is a multi-system disorder with a variety of extraskeletal changes. Whereas AAD is a bone-restricted disorder with a more severe skeletal phenotype: affected individuals are extremely short and complicated by orthopedic morbidity, and the radiological changes include modification of the vertebral bodies and epiphyseal dysplasia of the hip, as well as generalized metaphyseal dysplasia and severe brachydactyly. Recently, genetic heterogeneity for AAD was proposed, because a familial case (two affected sibs) with an AAD-identical phenotype had compound heterozygous mutations in POP1, encoding a molecule functionally related to the gene product of RMRP. We report here a 5-year-old boy with the same phenotype born to a consanguineous couple. We identified a novel homozygous POP1 mutation (c.1744C>T, p.P582S) in the boy and the heterozygosity in the parents. It may be rational to coin the POP1-associated skeletal phenotype AAD type 2. © 2016 Wiley Periodicals, Inc. PMID:27380734

  2. Measuring apparent trabecular structure with pQCT: a comparison with HR-pQCT.

    PubMed

    Lala, Deena; Cheung, Angela M; Lynch, Cheryl L; Inglis, Dean; Gordon, Chris; Tomlinson, George; Giangregorio, Lora

    2014-01-01

    We evaluated how comparable peripheral quantitative computed tomography (pQCT) measurements of cortical thickness, density, and apparent trabecular structure at the ultradistal tibia were with those measured with high-resolution pQCT (HR-pQCT). We also examined whether the accuracy of the pQCT-based trabecular and cortical measurements improved with reductions in slice thickness from the standard 2.2mm to 1.1 and 0.6mm. We immersed 15 dry tibia specimens in saline in a sealed cylinder and scanned 22.5mm from the distal tibia plateau using pQCT and HR-pQCT. pQCT underestimated cortical thickness by Stratec (CThStratec) and trabecular spacing (Tb.Sp) by 21.4% and 72.9%, whereas bone volume to total volume (BV/TV) and cortical density (CDen) were overestimated by 265.8% and 13.1%, respectively. Measurements of trabecular volumetric bone mineral density, trabecular area, total area, cortical thickness by custom software were comparable, but for CThStratec, Tb.Sp, BV/TV, and CDen, the differences between imaging devices varied with magnitude of the estimate. We recommend that researchers or clinicians interested in using pQCT to measure apparent trabecular structure or cortical thickness at the epiphyses, or in comparing findings from different devices, be aware of the differences between HR-pQCT and pQCT. PMID:23567093

  3. Identical male twins and brother with Cockayne syndrome.

    PubMed

    Houston, C S; Zaleski, W A; Rozdilsky, B

    1982-10-01

    The clinical, radiological, and neuropathological findings in early onset Cockayne syndrome are illustrated in identical twins and their brother. Their appearance of dwarfism with small head and prominent beaked nose strongly resembled that seen in the Seckel syndrome, but unlike patients with that syndrome they had a normal birth weight (for twins), thick cranial vaults, intracranial calcification, and a severe degree of mental retardation. The twins were deaf and blind, with optic atrophy and retinal pigmentation, while their brother had cataracts. Their hands and feet were large in proportion to their small trunk. They had cutaneous sensitivity to any slight exposure to ultraviolet light and severe neurologic problems with incoordination and spasticity. Radiologic findings included microcephaly, a thick cranial vault, a small pelvis, coxa valga, and "ivory epiphyses" in terminal phalanges of hands and feet. Pathologic findings included atrophy of white matter with widespread patchy demyelination, and massive siderocalcific deposits in the brain, particularly in the basal ganglia and cerebellum. While autosomal recessive inheritance is most likely, formally X-linked inheritance cannot be excluded. PMID:6890311

  4. Autocrine effects of neuromedin B stimulate the proliferation of rat primary osteoblasts.

    PubMed

    Saito, Hiroki; Nakamachi, Tomoya; Inoue, Kazuhiko; Ikeda, Ryuji; Kitamura, Kazuo; Minamino, Naoto; Shioda, Seiji; Miyata, Atsuro

    2013-05-01

    Neuromedin B (NMB) is a mammalian bombesin-like peptide that regulates exocrine/endocrine secretion, smooth muscle contraction, body temperature, and the proliferation of some cell types. Here, we show that mRNA encoding Nmb and its receptor (Nmbr) are expressed in rat bone tissue. Immunohistochemical analysis demonstrated that NMB and NMBR colocalize in osteoblasts, epiphyseal chondrocytes, and proliferative chondrocytes of growth plates from mouse hind limbs. Then, we investigated the effect of NMB on the proliferation of rat primary cultured osteoblasts. Proliferation assays and 5-bromo-2'-deoxyuridine incorporation assays demonstrated that NMB augments the cell number and enhances DNA synthesis in osteoblasts. Pretreatment with the NMBR antagonist BIM23127 inhibited NMB-induced cell proliferation and DNA synthesis. Western blot analysis showed that NMB activates ERK1/2 MAPK signaling in osteoblasts. Pretreatment with the MAPK/ERK kinase inhibitor U0126 attenuated NMB-induced cell proliferation and DNA synthesis. We also investigated the effects of molecules that contribute to osteoblast proliferation and differentiation on Nmb expression in osteoblasts. Real-time PCR analysis demonstrated that 17β-estradiol (E2) and transforming growth factor β1 increase and decrease Nmb mRNA expression levels respectively. Finally, proliferation assays revealed that the NMBR antagonist BIM23127 suppresses E2-induced osteoblast proliferation. These results suggest that NMB/NMBR signaling plays an autocrine or paracrine role in osteoblast proliferation and contributes to the regulation of bone formation. PMID:23428580

  5. Strength Training in Children and Adolescents

    PubMed Central

    Dahab, Katherine Stabenow; McCambridge, Teri Metcalf

    2009-01-01

    Context: Strength training in children, in combination with plyometric and/or agility training, has become an increasingly popular tactic for athletes to gain a competitive edge during the off-season. The present review clarifies some common myths associated with strength training in children, and it outlines the most current recommendations. Evidence Acquisition: Relevant studies on strength training in children and adolescents were reviewed (search results included studies indexed in PubMed and MEDLINE from 1980 through 2008). Also reviewed were recommendations from consensus guidelines and position statements applicable to strength training in youth. Results: Children can improve strength by 30% to 50% after just 8 to 12 weeks of a well-designed strength training program. Youth need to continue to train at least 2 times per week to maintain strength. The case reports of injuries related to strength training, including epiphyseal plate fractures and lower back injuries, are primarily attributed to the misuse of equipment, inappropriate weight, improper technique, or lack of qualified adult supervision. Conclusion: Youth—athletes and nonathletes alike—can successfully and safely improve their strength and overall health by participating in a well-supervised program. Trained fitness professionals play an essential role in ensuring proper technique, form, progression of exercises, and safety in this age group. PMID:23015875

  6. Traumatic Fracture in a patient of Osteopoikilosis with Review of Literature

    PubMed Central

    Bansal, Rohan; Pathak, Aditya C; Sheth, Binoti; Patil, Atul K

    2013-01-01

    Introduction: Osteopoikilosis or osteopathia condensans disseminata is a rare hereditary autosomal dominant sclerosing bone dysplasia. Patients are usually asymptomatic and the diagnosis is usually made incidentally on radiographs which show presence of symmetric, multiple, well defined, small ovoid areas of increased radiodensity clustered in peri-articular osseous regions with propensity for epiphyseal and metaphyseal involvement. There are no increased risks of pathological fracture in a case of osteopoikilosis and traumatic fracture healing in a case of osteopoikilosis is similar to fracture occurring in other normal patients. Case Report: A 34 years male, electrician came with history of accidental fall from height while working in office leading to development of pain and swelling over left lower leg and ankle diagnosed with Ruedi-Allgower classification type I pilon fracture(without fibula fracture) no distal neuro-vascular deficit. Patient was offered surgical treatment in form of open reduction and internal fixation of tibial fracture by plate osteosynthesis using antero-medial approach, showed complete union and was followed up for eight months. Conclusion: Osteopoikilosis has a benign course and it should always be kept as a possible differential diagnosis for osteoblastic metastasis to avoid diagnositic dilemma. Diagnosis can be settled by routine x-rays (for type, extent and site of lesions, bones affected), clinical features of patient, histopathology and other systemic or pre-existing conditions. PMID:27298900

  7. The Clinical Approach Toward Giant Cell Tumor of Bone

    PubMed Central

    van der Heijden, Lizz; Dijkstra, P.D. Sander; van de Sande, Michiel A.J.; Kroep, Judith R.; Nout, Remi A.; van Rijswijk, Carla S.P.; Bovée, Judith V.M.G.; Hogendoorn, Pancras C.W.

    2014-01-01

    We provide an overview of imaging, histopathology, genetics, and multidisciplinary treatment of giant cell tumor of bone (GCTB), an intermediate, locally aggressive but rarely metastasizing tumor. Overexpression of receptor activator of nuclear factor κB ligand (RANKL) by mononuclear neoplastic stromal cells promotes recruitment of numerous reactive multinucleated giant cells. Conventional radiographs show a typical eccentric lytic lesion, mostly located in the meta-epiphyseal area of long bones. GCTB may also arise in the axial skeleton and very occasionally in the small bones of hands and feet. Magnetic resonance imaging is necessary to evaluate the extent of GCTB within bone and surrounding soft tissues to plan a surgical approach. Curettage with local adjuvants is the preferred treatment. Recurrence rates after curettage with phenol and polymethylmethacrylate (PMMA; 8%–27%) or cryosurgery and PMMA (0%–20%) are comparable. Resection is indicated when joint salvage is not feasible (e.g., intra-articular fracture with soft tissue component). Denosumab (RANKL inhibitor) blocks and bisphosphonates inhibit GCTB-derived osteoclast resorption. With bisphosphonates, stabilization of local and metastatic disease has been reported, although level of evidence was low. Denosumab has been studied to a larger extent and seems to be effective in facilitating intralesional surgery after therapy. Denosumab was recently registered for unresectable disease. Moderate-dose radiotherapy (40–55 Gy) is restricted to rare cases in which surgery would lead to unacceptable morbidity and RANKL inhibitors are contraindicated or unavailable. PMID:24718514

  8. Sex Assessment Using the Femur and Tibia in Medieval Skeletal Remains from Ireland: Discriminant Function Analysis.

    PubMed

    Novak, Mario

    2016-04-01

    Sex determination based on discriminant function analysis of skeletal measurements is probably the most effective method for assessment of sex in archaeological and contemporary populations due to various reasons, but it also suffers from limitations such as population specificity. In this paper standards for sex assessment from the femur and tibia in the medieval Irish population are presented. Six femoral and six tibial measurements obtained from 56 male and 45 female skeletons were subjected to discriminant function analysis. Average accuracies obtained by this study range between 87.1 and 97%. The highest level of accuracy (97%) was achieved when using combined variables of the femur and tibia (maximum diameter of femoral head and circumference at tibial nutrient foramen), as well as two variables of the tibia (proximal epiphyseal breadth and circumference at nutrient foramen). Discriminant functions using a single variable provided accuracies between 87.1 and 96% with the circumference at the level of the tibial nutrient foramen providing the best separation. High accuracy rates obtained by this research correspond to the data recorded in other studies thus confirming the importance of discriminant function analysis in assessment of sex in both archaeological and forensic contexts. PMID:27301232

  9. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

    NASA Astrophysics Data System (ADS)

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-10-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.

  10. Bone age assessment by content-based image retrieval and case-based reasoning

    NASA Astrophysics Data System (ADS)

    Fischer, Benedikt; Welter, Petra; Grouls, Christoph; Günther, Rolf W.; Deserno, Thomas M.

    2011-03-01

    Skeletal maturity is assessed visually by comparing hand radiographs to a standardized reference image atlas. Most common are the methods by Greulich & Pyle and Tanner & Whitehouse. For computer-aided diagnosis (CAD), local image regions of interest (ROI) such as the epiphysis or the carpal areas are extracted and evaluated. Heuristic approaches trying to automatically extract, measure and classify bones and distances between bones suffer from the high variability of biological material and the differences in bone development resulting from age, gender and ethnic origin. Content-based image retrieval (CBIR) provides a robust solution without delineating and measuring bones. In this work, epiphyseal ROIs (eROIS) of a hand radiograph are compared to previous cases with known age, mimicking a human observer. Leaving-one-out experiments are conducted on 1,102 left hand radiographs and 15,428 metacarpal and phalangeal eROIs from the publicly available USC hand atlas. The similarity of the eROIs is assessed by a combination of cross-correlation, image distortion model, and Tamura texture features, yielding a mean error rate of 0.97 years and a variance of below 0.63 years. Furthermore, we introduce a publicly available online-demonstration system, where queries on the USC dataset as well as on uploaded radiographs are performed for instant CAD. In future, we plan to evaluate physician with CBIR-CAD against physician without CBIR-CAD rather than physician vs. CBIR-CAD.

  11. Content-based image retrieval applied to bone age assessment

    NASA Astrophysics Data System (ADS)

    Fischer, Benedikt; Brosig, André; Welter, Petra; Grouls, Christoph; Günther, Rolf W.; Deserno, Thomas M.

    2010-03-01

    Radiological bone age assessment is based on local image regions of interest (ROI), such as the epiphysis or the area of carpal bones. These are compared to a standardized reference and scores determining the skeletal maturity are calculated. For computer-aided diagnosis, automatic ROI extraction and analysis is done so far mainly by heuristic approaches. Due to high variations in the imaged biological material and differences in age, gender and ethnic origin, automatic analysis is difficult and frequently requires manual interactions. On the contrary, epiphyseal regions (eROIs) can be compared to previous cases with known age by content-based image retrieval (CBIR). This requires a sufficient number of cases with reliable positioning of the eROI centers. In this first approach to bone age assessment by CBIR, we conduct leaving-oneout experiments on 1,102 left hand radiographs and 15,428 metacarpal and phalangeal eROIs from the USC hand atlas. The similarity of the eROIs is assessed by cross-correlation of 16x16 scaled eROIs. The effects of the number of eROIs, two age computation methods as well as the number of considered CBIR references are analyzed. The best results yield an error rate of 1.16 years and a standard deviation of 0.85 years. As the appearance of the hand varies naturally by up to two years, these results clearly demonstrate the applicability of the CBIR approach for bone age estimation.

  12. Pediatric osteomyelitis and septic arthritis: the pathology of neonatal disease.

    PubMed Central

    Ogden, J. A.

    1979-01-01

    The morphologic and histologic examination of over fifty-five foci of metaphyseal/epiphyseal osteomyelitis and eleven septic joints from five cases of neonatal osteomyelitis and joint sepsis are described in detail. The severity of the bone and joint involvement varied considerably, allowing a better understanding of the pathophysiologic sequence of events in the disease in the neonatal time period. Of particular importance were (1) the multifocal nature of the disease, (2) the highly variable destruction of the growth plate (physis) by several discrete mechanisms, and (3) the invasion of the chondroepiphysis through the cartilage canal systems. Two of the cases died from respiratory complications several months following presumed successful treatment of their skeletal infections. S&pecimens showed significant growth plate damage continuing beyond the neonatal period. These findings support the need for rapid diagnosis and drainage, whenever feasible, to prevent long-term skeletal growth damage. The severity of involvement also should emphasize that this disease, especially in the neonate, is not an innocuous condition, as a recent review suggested. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 FIG. 7 FIG. 8 FIG. 9 FIG. 10 FIG. 11 FIG. 12 FIG. 13 FIG. 14 FIG. 15 FIG. 16 FIG. 17 FIG. 18 FIG. 19 FIG. 20 PMID:524924

  13. Resistance to thyroid hormone due to defective thyroid receptor alpha

    PubMed Central

    Moran, Carla; Chatterjee, Krishna

    2015-01-01

    Thyroid hormones act via nuclear receptors (TRα1, TRβ1, TRβ2) with differing tissue distribution; the role of α2 protein, derived from the same gene locus as TRα1, is unclear. Resistance to thyroid hormone alpha (RTHα) is characterised by tissue-specific hypothyroidism associated with near-normal thyroid function tests. Clinical features include dysmorphic facies, skeletal dysplasia (macrocephaly, epiphyseal dysgenesis), growth retardation, constipation, dyspraxia and intellectual deficit. Biochemical abnormalities include low/low-normal T4 and high/high-normal T3 concentrations, a subnormal T4/T3 ratio, variably reduced reverse T3, raised muscle creatine kinase and mild anaemia. The disorder is mediated by heterozygous, loss-of-function, mutations involving either TRα1 alone or both TRα1 and α2, with no discernible phenotype attributable to defective α2. Whole exome sequencing and diagnostic biomarkers may enable greater ascertainment of RTHα, which is important as thyroxine therapy reverses some metabolic abnormalities and improves growth, constipation, dyspraxia and wellbeing. The genetic and phenotypic heterogeneity of RTHα and its optimal management remain to be elucidated. PMID:26303090

  14. Resistance to thyroid hormone due to defective thyroid receptor alpha.

    PubMed

    Moran, Carla; Chatterjee, Krishna

    2015-08-01

    Thyroid hormones act via nuclear receptors (TRα1, TRβ1, TRβ2) with differing tissue distribution; the role of α2 protein, derived from the same gene locus as TRα1, is unclear. Resistance to thyroid hormone alpha (RTHα) is characterised by tissue-specific hypothyroidism associated with near-normal thyroid function tests. Clinical features include dysmorphic facies, skeletal dysplasia (macrocephaly, epiphyseal dysgenesis), growth retardation, constipation, dyspraxia and intellectual deficit. Biochemical abnormalities include low/low-normal T4 and high/high-normal T3 concentrations, a subnormal T4/T3 ratio, variably reduced reverse T3, raised muscle creatine kinase and mild anaemia. The disorder is mediated by heterozygous, loss-of-function, mutations involving either TRα1 alone or both TRα1 and α2, with no discernible phenotype attributable to defective α2. Whole exome sequencing and diagnostic biomarkers may enable greater ascertainment of RTHα, which is important as thyroxine therapy reverses some metabolic abnormalities and improves growth, constipation, dyspraxia and wellbeing. The genetic and phenotypic heterogeneity of RTHα and its optimal management remain to be elucidated. PMID:26303090

  15. Osteosclerotic metaphyseal dysplasia with extensive interstitial pulmonary lesions: a case report and literature review.

    PubMed

    Zheng, Helin; Cai, Jinhua; Wang, Longlun; He, Xiaoya

    2015-10-01

    Osteosclerotic metaphyseal dysplasia (OMD) is a very rare sclerosing bone disorder. To date, four cases have been documented in three reports. Here, we present the case of a 12-year-old girl with a history of recurrent respiratory infections, hypotonia, developmental delay, genu valgum, and hepatosplenomegaly. Radiographs revealed profound, ivory-white sclerosis of the metaphyses and epiphyses of the long bones in both the upper and lower extremities. Sclerosis also affected the ends or margins of the flat bones, including the mandible, clavicles, scapulae, ribs, iliac crests, ischia, pubic bones, talus, calcaneus, and some vertebrae, to varying degrees. Based on the clinical, radiographic, and laboratory findings, a diagnosis of OMD was made. Our patient is the fifth case of OMD reported in the international literature and shares clinical and radiological similarities with four other reported cases of OMD. However, the extensive interstitial pulmonary lesions observed on computed tomography images in the present case have not been previously documented. This pulmonary disorder, which may be associated with OMD, should be evaluated in subsequently encountered cases. PMID:26084987

  16. Mutations in DDR2 gene cause SMED with short limbs and abnormal calcifications.

    PubMed

    Bargal, Ruth; Cormier-Daire, Valerie; Ben-Neriah, Ziva; Le Merrer, Martine; Sosna, Jacob; Melki, Judith; Zangen, David H; Smithson, Sarah F; Borochowitz, Zvi; Belostotsky, Ruth; Raas-Rothschild, Annick

    2009-01-01

    The spondylo-meta-epiphyseal dysplasia [SMED] short limb-hand type [SMED-SL] is a rare autosomal-recessive disease, first reported by Borochowitz et al. in 1993.(1) Since then, 14 affected patients have been reported.(2-5) We diagnosed 6 patients from 5 different consanguineous Arab Muslim families from the Jerusalem area with SMED-SL. Additionally, we studied two patients from Algerian and Pakistani ancestry and the parents of the first Jewish patients reported.(1) Using a homozygosity mapping strategy, we located a candidate region on chromosome 1q23 spanning 2.4 Mb. The position of the Discoidin Domain Receptor 2 (DDR2) gene within the candidate region and the similarity of the ddr2 knockout mouse to the SMED patients' phenotype prompted us to study this gene(6). We identified three missense mutations c.2254 C > T [R752C], c. 2177 T > G [I726R], c.2138C > T [T713I] and one splice site mutation [IVS17+1g > a] in the conserved sequence encoding the tyrosine kinase domain of the DDR2 gene. The results of this study will permit an accurate early prenatal diagnosis and carrier screening for families at risk. PMID:19110212

  17. Lower Paleolithic bone tools from the 'Spear Horizon' at Schöningen (Germany).

    PubMed

    Van Kolfschoten, Thijs; Parfitt, Simon A; Serangeli, Jordi; Bello, Silvia M

    2015-12-01

    The Lower Paleolithic locality of Schöningen 13 II-4 is famous for the discovery of wooden spears found amongst the butchered remains of numerous horses and other large herbivores. Although the spears have attracted the most interest, other aspects of the associated artifact assemblage have received less attention. Here we describe an extraordinary assemblage of 88 bone tools from the 'Spear Horizon.' This sample includes numerous long-bone shaft fragments (mostly of horse), three ribs used as 'retouchers' to resharpen flint tools, and a complete horse innominate that was used as an anvil in bipolar knapping. Most of the retouchers were prepared by scraping the diaphysis of fresh and dry long-bones. Technological analysis of the associated lithic assemblage demonstrates exhaustive resharpening to maintain functional cutting edges. Whereas the flint tools were brought to the site, curated, and maintained, the retouchers had a shorter use-history and were either discarded after a limited period or broken to extract marrow. Horse and bison metapodials with flaked and rounded epiphyses are interpreted as hammers used to break marrow bones. Several of the 'metapodial hammers' were additionally used as knapping percussors. These constitute the earliest evidence of multi-purpose bone tools in the archeological record. Our results highlight the advanced knowledge in the use of bones as tools during the Lower Paleolithic, with major implications for understanding aspects of non-lithic technology and planning depth in early hominins. PMID:26653208

  18. A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome

    SciTech Connect

    Muenke, M.; Gripp, K.W.; McDonald-McGinn, D.M.

    1997-03-01

    The underlying basis of many forms of syndromic craniosynostosis has been defined on a molecular level. However, many patients with familial or sporadic craniosynostosis do not have the classical findings of those craniosynostosis syndromes. Here we present 61 individuals from 20 unrelated families where coronal synostosis is due to an amino acid substitution (Pro250Arg) that results from a single point mutation in the fibroblast growth factor receptor 3 gene on chromosome 4p. In this instance, a new clinical syndrome is being defined on the basis of the molecular finding. In addition to the skull findings, some patients had abnormalities on radiographs of hands and feet, including thimble-like middle phalanges, coned epiphyses, and carpal and tarsal fusions. Brachydactyly was seen in some cases; none had clinically significant syndactyly or deviation of the great toe. Sensorineural hearing loss was present in some, and developmental delay was seen in a minority. While the radiological findings of hands and feet can be very helpful in diagnosing this syndrome, it is not in all cases clearly distinguishable on a clinical basis from other craniosynostosis syndromes. Therefore, this mutation should be tested for in patients with coronal synostosis. 54 refs., 4 figs., 2 tabs.

  19. Genotype-phenotype correlation in DTDST dysplasias: Atelosteogenesis type II and diastrophic dysplasia variant in one family.

    PubMed

    Dwyer, Ellen; Hyland, James; Modaff, Peggy; Pauli, Richard M

    2010-12-01

    Mutations in diastrophic dysplasia sulfate transporter (DTDST) cause a spectrum of autosomal recessive chondrodysplasias. In decreasing order of severity, they include processes designated as achondrogenesis type IB (ACG-1B), atelosteogenesis type II (AO2), diastrophic dysplasia (DTD), diastrophic dysplasia variant (DTDv), and recessively inherited multiple epiphyseal dysplasia (rMED). This is the first report of an extended family with unequivocally distinct phenotypes on the DTDST spectrum. Two siblings have DTDv and their first cousin had AO2. They all share the common Finnish mutation (IVS1 + 2C>T). The two patients with DTDv have the previously reported R279W extracellular domain missense mutation. The second mutation in the patient with AO2 is c.172delA, a deletion of one nucleotide causing a previously unreported frameshift mutation. This is the first published case of an individual with a frameshift mutation combined with the Finnish mutation. These three patients provide an opportunity, in concert with a review of previous literature, to further examine the genotype-phenotype correlation of DTDST. Analysis suggests that, while the DTDST family of disorders contains at least seven different conditions, mutations in the DTDST gene, in fact, appear to cause a phenotypic continuum. Furthermore, DTDST genotype alone is an imperfect predictor of clinical severity along this continuum. PMID:21077202

  20. In vitro proteoglycan sulfation derived from sulfhydryl compounds in sulfate transporter chondrodysplasias.

    PubMed

    Rossi, Antonio; Cetta, Giuseppe; Piazza, Rocco; Bonaventure, Jacky; Steinmann, Beat; Supereti-Furga, Andrea

    2003-01-01

    Mutations in a sulfate-chloride antiporter gene, the diastrophic dysplasia sulfate transporter (DTDST), have been associated with a family of skeletal dysplasias including recessive multiple epiphyseal dysplasia, diastrophic dysplasia (DTD), atelosteogenesis type 2, and achondrogenesis type 1B (ACG1B). DTDST function is crucial for uptake of extracellular sulfate required for proteoglycan (PG) sulfation; the tissue-specific expression of the clinical phenotype may be the consequence of the high rate of PG synthesis in chondrocytes and the ensuing high sulfate requirement. We have studied the contribution of cysteine and its derivatives to PG sulfation in fibroblast and chondrocyte cultures from sulfate transporter dysplasia patients. Incubation of ACG1B fibroblasts in medium containing different concentrations of cystine indicated partial recovery of PG sulfation as measured by HPLC disaccharide analysis of chondroitin sulfate PGs; similar results were observed after incubation with N-acetylcysteine. When both compounds were tested in primary chondrocytes from a DTD patient, partial rescue of PG sulfation was observed, suggesting that the metabolic pathways producing cytoplasmic sulfate from thiols are also active in this cell type. PMID:14692227

  1. Pathogenetics of the human SLC26 transporters.

    PubMed

    Dawson, P A; Markovich, D

    2005-01-01

    Over the past decade, 11 human genes belonging to the solute linked carrier (SLC) 26 family of transporters, have been identified. The SLC26 proteins, which include SAT-1, DTDST, DRA/CLD, pendrin, prestin, PAT-1/CFEX and Tat-1, are structurally related and have been shown to transport one or more of the following substrates: sulfate, chloride, bicarbonate, iodide, oxalate, formate, hydroxyl or fructose. Special interest has focused on four members of the SLC26 family that are associated with distinct recessive diseases: (i) Mutations in SLC26A2 lead to four different chondrodysplasias (diastrophic dysplasia, atelosteogenesis type II, achondrogenesis type IB and multiple epiphyseal dysplasia); (ii) SLC26A3 is associated with congenital chloride diarrhea; (iii) SLC26A4 is associated with Pendred syndrome and non-syndromic deafness, DFNB4; and (iv) SLC26A5 is defective in non-syndromic hearing impairment. This review article summarizes current information on the pathophysiological consequences of mutations in the human SLC26A2 to A5 genes. PMID:15720248

  2. Identification of a novel COL2A1 mutation (c.1744G>A) in a Japanese family: a case report

    PubMed Central

    2014-01-01

    Introduction Mutations in the gene encoding the type II collagen gene (COL2A1) have been found to affect the entire skeletal system. Recently, inheritable skeletal dysplasia caused by novel COL2A1 mutations has been linked to an inherited disease of the hip joint that neither involves the entire skeletal system nor is characterized by the presence of concomitant disorders, such as spinal or ocular abnormalities. Case presentation A 27-year-old Japanese woman previously diagnosed with avasucular necrosis (AVN) of the femoral head on the basis of radiological findings was referred to the study site for surgical management of a painful hip joint. She had no history of disease but suffered from bilateral hip joint lesions. Analysis of her pedigree revealed that bilateral hip joint lesions affected more than three generations of her family. Based on these findings, haplotype analysis of her and her family members was performed by examining select candidate genes from the critical interval for epiphyseal dysplasia of the femoral head on 12q13 and sequencing the promoter and exonic regions of COL2A1. Conclusion A novel COL2A1 mutation (c.1744G>A) was identified within one Japanese family. PMID:25124518

  3. Congenital generalised bone dysplasias: a clinical, radiological, and epidemiological survey.

    PubMed

    Andersen, P E; Hauge, M

    1989-01-01

    The point prevalence at birth of generalised bone dysplasias was estimated by a study of all children born between 1 January 1970 and 31 December 1983 in the county of Fyn (Denmark). Additionally the population prevalence on 31 December 1983 of all patients with generalised bone dysplasias in this county was determined. The county is a well defined, representative subregion of Denmark which demographically comprises a cross section of about 9% of the Danish population. In total, bone dysplasias were found to be more frequent than generally assumed. Achondroplasia was, however, less common with a point prevalence at birth of 1.3 per 100,000, while osteogenesis imperfecta (21.8), multiple epiphyseal dysplasia tarda (9.0), achondrogenesis (6.4), osteopetrosis (5.1), and thanatophoric dysplasia (3.8) were found more frequently. It is striking how many bone dysplasias are still erroneously classified as achondroplasia. Correct diagnosis is important for a valid prognosis, for treatment, and for genetic counselling. The diagnosis relies almost exclusively on the radiographical findings. PMID:2783977

  4. Sulfate in fetal development.

    PubMed

    Dawson, Paul A

    2011-08-01

    Sulfate (SO(4)(2-)) is an important nutrient for human growth and development, and is obtained from the diet and the intra-cellular metabolism of sulfur-containing amino acids, including methionine and cysteine. During pregnancy, fetal tissues have a limited capacity to produce sulfate, and rely on sulfate obtained from the maternal circulation. Sulfate enters and exits placental and fetal cells via transporters on the plasma membrane, which maintain a sufficient intracellular supply of sulfate and its universal sulfonate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) for sulfate conjugation (sulfonation) reactions to function effectively. Sulfotransferases mediate sulfonation of numerous endogenous compounds, including proteins and steroids, which biotransforms their biological activities. In addition, sulfonation of proteoglycans is important for maintaining normal structure and development of tissues, as shown for reduced sulfonation of cartilage proteoglycans that leads to developmental dwarfism disorders and four different osteochondrodysplasias (diastrophic dysplasia, atelosteogenesis type II, achondrogenesis type IB and multiple epiphyseal dysplasia). The removal of sulfate via sulfatases is an important step in proteoglycan degradation, and defects in several sulfatases are linked to perturbed fetal bone development, including mesomelia-synostoses syndrome and chondrodysplasia punctata 1. In recent years, interest in sulfate and its role in developmental biology has expanded following the characterisation of sulfate transporters, sulfotransferases and sulfatases and their involvement in fetal growth. This review will focus on the physiological roles of sulfate in fetal development, with links to human and animal pathophysiologies. PMID:21419855

  5. A compound heterozygote harboring novel and recurrent DTDST mutations with intermediate phenotype between atelosteogenesis type II and diastrophic dysplasia.

    PubMed

    Maeda, Koichi; Miyamoto, Yoshinari; Sawai, Hideaki; Karniski, Lawrence P; Nakashima, Eiji; Nishimura, Gen; Ikegawa, Shiro

    2006-06-01

    Diastrophic dysplasia sulfate transporter (DTDST) is a sulfate transporter required for the synthesis of sulfated proteoglycans in the cartilage. Over 30 mutations have been described in the DTDST gene, which result in a continuous clinical spectrum of recessively inherited chondrodysplasias, including, in order of increasing severity, a recessive form of multiple epiphyseal dysplasia (rMED), diastrophic dysplasia (DTD), atelosteogenesis type II (AO-II) and achondrogenesis 1B (ACG-1B). Correlation between disease severity and residual sulfate transport activity has been reported. Here we report a patient with DTDST mutations, whose manifestations fell in a range between AO-II and DTD. The patient was a compound heterozygote for the recurrent c.835C>T (p.R279W) and novel c.1987G>A (p.G663R) mutations. Immunocytochemical analysis in HEK293 cells showed that the p.G663R mutation was localized within the cytoplasm, and not to the cell membrane, suggesting p.G663R is a loss-of-function mutation. Our case supports the previously described correlation between the severity of the phenotype and the putative level of residual transport function. PMID:16642506

  6. SLC26A2 (diastrophic dysplasia sulfate transporter) is expressed in developing and mature cartilage but also in other tissues and cell types.

    PubMed

    Haila, S; Hästbacka, J; Böhling, T; Karjalainen-Lindsberg, M L; Kere, J; Saarialho-Kere, U

    2001-08-01

    Mutated alleles of the SLC26A2 (diastrophic dysplasia sulfate transporter or DTDST) gene cause each of the four recessive chondrodysplasias, i.e., diastrophic dysplasia (DTD), multiple epiphyseal dysplasia (MED), atelosteogenesis Type II (AO2), and achondrogenesis Type IB (ACG1B). SLC26A2 acts as an Na(+)-independent sulfate/chloride antiporter and belongs to the SLC26 anion transporter gene family, currently consisting of six homologous human members. Although Northern analysis has indicated some expression in all tissues studied, the only tissue known to be affected by SLC26A2 mutations is cartilage. Abundant SLC26A2 expression has previously been detected in normal human colon by in situ hybridization. We have used in situ hybridization and immunohistochemistry to examine multiple normal tissues for the expression of human SLC26A2. As expected, a strong signal for SLC26A2 mRNA and protein immunostaining were detected in developing fetal hyaline cartilage, while bronchial cartilage showed mRNA expression in adult tissues. SLC26A2 expression could also be detected in eccrine sweat glands, in bronchial glands, and in placental villi. In addition, immunoreactivity for the SLC26A2 protein was observed in exocrine pancreas. Our results suggest a more limited expression pattern for SLC26A2 than that found by Northern analysis. However, SLC26A2 expression is also detected in tissues not affected in chondrodysplasias caused by SLC26A2 mutations. PMID:11457925

  7. Achondrogenesis type IB: agenesis of cartilage interterritorial matrix as the link between gene defect and pathological skeletal phenotype.

    PubMed

    Corsi, A; Riminucci, M; Fisher, L W; Bianco, P

    2001-10-01

    Achondrogenesis type IB is a lethal osteochondrodysplasia caused by mutations in the diastrophic dysplasia sulfate transporter gene. How these mutations lead to the skeletal phenotype is not known. Histology of plastic-embedded skeletal fetal achondrogenesis type IB samples suggested that interterritorial epiphyseal cartilage matrix was selectively missing. Cartilage was organized in "chondrons" separated by cleft spaces; chondrocyte seriation, longitudinal septa, and, in turn, mineralized cartilaginous septa were absent. Agenesis of interterritorial matrix as the key histologic change was confirmed by immunohistology using specific markers of territorial and interterritorial matrix. Biglycan-enriched territorial matrix was preserved; decorin-enriched interterritorial areas were absent, although immunostaining was observed within chondrocytes. Thus, in achondrogenesis type IB: (1) a complex derangement in cartilage matrix assembly lies downstream of the deficient sulfate transporter activity; (2) the severely impaired decorin deposition participates in the changes in matrix organization with lack of development of normal interterritorial matrix; and (3) this change determines the lack of the necessary structural substrate for proper endochondral bone formation and explains the severe skeletal phenotype. PMID:11570921

  8. Clinical and molecular characterization of Diastrophic Dysplasia in the Portuguese population.

    PubMed

    Barbosa, M; Sousa, A B; Medeira, A; Lourenço, T; Saraiva, J; Pinto-Basto, J; Soares, G; Fortuna, A M; Superti-Furga, A; Mittaz, L; Reis-Lima, M; Bonafé, L

    2011-12-01

    SLC26A2-related dysplasias encompass a spectrum of diseases: from lethal achondrogenesis type 1B (ACG1B; MIM #600972) and atelosteogenesis type 2 (AO2; MIM #256050) to classical diastrophic dysplasia (cDTD; MIM #222600) and recessive multiple epiphyseal dysplasia (rMED; MIM #226900). This study aimed at characterizing clinically, radiologically and molecularly 14 patients affected by non-lethal SLC26A2-related dysplasias and at evaluating genotype-phenotype correlation. Phenotypically, eight patients were classified as cDTD, four patients as rMED and two patients had an intermediate phenotype (mild DTD - mDTD, previously 'DTD variant'). The Arg279Trp mutation was present in all patients, either in homozygosity (resulting in rMED) or in compound heterozygosity with the known severe alleles Arg178Ter or Asn425Asp (resulting in DTD) or with the mutation c.727-1G>C (causing mDTD). The 'Finnish mutation', c.-26+2T>C, and the p.Cys653Ser, both frequent mutations in non-Portuguese populations, were not identified in any of the patients of our cohort and are probably very rare in the Portuguese population. A targeted mutation analysis for p.Arg279Trp and p.Arg178Ter in the Portuguese population allows the identification of approximately 90% of the pathogenic alleles. PMID:21155763

  9. Insights from a transgenic mouse model on the role of SLC26A2 in health and disease.

    PubMed

    Forlino, Antonella; Gualeni, Benedetta; Pecora, Fabio; Della Torre, Sara; Piazza, Rocco; Tiveron, Cecilia; Tatangelo, Laura; Superti-Furga, Andrea; Cetta, Giuseppe; Rossi, Antonio

    2006-01-01

    Mutations in the SLC26A2 cause a family of recessive chondrodysplasias that includes in order of decreasing severity achondrogenesis 1B, atelosteogenesis 2, diastrophic dysplasia and recessive multiple epiphyseal dysplasia. The gene encodes for a widely distributed sulfate/chloride antiporter of the cell membrane whose function is crucial for the uptake of inorganic sulfate that is needed for proteoglycan sulfation. To investigate the mechanisms leading to skeletal dysplasia, we generated a transgenic mouse with a mutation in Slc26a2 causing a partial loss of function of the sulfate transporter. Homozygous mutant mice were characterized by skeletal dysplasia with chondrocytes of irregular size, delay in the formation of the secondary ossification centre and osteoporosis of long bones. Impaired sulfate uptake was demonstrated in chondrocytes, osteoblasts and fibroblasts, but proteoglycan undersulfation was detected only in cartilage. The similarity with human diastrophic dysplasia makes this mouse a model to explore pathogenetic and therapeutic aspects of SLC26A2-related disorders. PMID:17120769

  10. Diastrophic dysplasia and atelosteogenesis type II as expression of compound heterozygosis: first report of a Mexican patient and genotype-phenotype correlation.

    PubMed

    Macías-Gómez, Nelly Margarita; Mégarbané, André; Leal-Ugarte, Evelia; Rodríguez-Rojas, Lisa Ximena; Barros-Núñez, Patricio

    2004-08-30

    The osteochondrodysplasias represent a heterogeneous group of cartilage and bone diseases. Among these, achondrogenesis 1B, atelosteogenesis type II, diastrophic dysplasia, and autosomal recessive multiple epiphyseal dysplasia are caused by mutations in the solute carrier family 26 (sulfate transporter), member 2 gene (SLC26A2). This group of osteochondrodysplasias shows a continuous spectrum of clinical variability and shares many features in common. Usually, it is difficult to distinguish clinically among these patients. To date, several efforts have been made to correlate mutations in the SLC26A2 gene with phenotypic severity in the patients. We report on a Mexican girl with diastrophic dysplasia presenting some unusual clinical and radiographic features that are usually observed in atelosteogenesis type II. Molecular analysis of the SLC26A2 gene in this patient showed compound heterozygosity for the R178X and R279W mutations. In this patient, the combination of a mild and a severe mutation has apparently led to an intermediate or transitional clinical picture, showing an apparent genotype-phenotype correlation. PMID:15316973

  11. Multiple bilateral lower limb fractures in a 2-year-old child: previously unreported injury with a unique mechanism.

    PubMed

    Repswal, Basant; Jain, Anuj; Gupta, Sunil; Aggarwal, Aditya; Kohli, Tushar; Pathrot, Devendra

    2014-01-01

    Fall from height is a common cause of unintentional injuries in children and accounts for 6% of all trauma-related childhood deaths, usually from head injury. We report a case of a 2-year-old child with multiple fractures of the bilateral lower limbs due to this reason. A child fell from a height of around 15 feet after toppling from a balcony. He developed multiple fractures involving the right femoral shaft, right distal femoral epiphysis (Salter Harris type 2), right distal metaphysis of the tibia and fibula, and undisplaced Salter Harris type 2 epiphyseal injury of the left distal tibia. There were no head, abdominal or spinal injuries. The patient was taken into emergency operation theatre after initial management which consisted of intravenous fluids, blood transfusion, and splintage of both lower limbs. Fracture of the femoral shaft was treated by closed reduction and fixation using two titanium elastic nails. Distal femoral physeal injury required open reduction and fixation with K wires. Distal tibia fractures were closely reduced and managed nonoperatively in both the lower limbs. All the fractures united in four weeks. At the last follow-up, the child had no disability and was able to perform daily activities comfortably. We also proposed the unique mechanism of injury in this report. PMID:25293902

  12. Hyperostosis frontalis interna (HFI) and castration: the case of the famous singer Farinelli (1705–1782)

    PubMed Central

    Belcastro, Maria Giovanna; Todero, Antonio; Fornaciari, Gino; Mariotti, Valentina

    2011-01-01

    The famous castrato singer Farinelli (1705–1782) was exhumed by our research group in July 2006 for the purpose of gaining some insight into his biological profile through a study of his skeletal remains. Farinelli was castrated before puberty to preserve the treble pitch of the boy's voice into adult life. His powerful and sweet voice became legendary. In spite of its bad preservation state, the skeleton displayed some interesting characteristics that are probably related to the effects of castration, including long limb-bones, persistence of epiphyseal lines and osteoporosis. In particular, the frontal bone was affected by severe hyperostosis frontalis interna (HFI). This condition consists in a symmetrical thickening of the inner table of the bone. The epidemiology of HFI shows that it is relatively common in postmenopausal women but very rare in men. Men affected by this pathology suffer from diseases, syndromes or treatments causing androgen deficiency. In the case of Farinelli, castration was probably responsible for the onset and development of this lesion. PMID:21740437

  13. Variation in mammalian proximal femoral development: comparative analysis of two distinct ossification patterns

    PubMed Central

    Serrat, Maria A; Reno, Philip L; McCollum, Melanie A; Meindl, Richard S; Lovejoy, C Owen

    2007-01-01

    The developmental anatomy of the proximal femur is complex. In some mammals, including humans, the femoral head and greater trochanter emerge as separate ossification centres within a common chondroepiphysis and remain separate throughout ontogeny. In other species, these secondary centres coalesce within the chondroepiphysis to form a single osseous epiphysis much like the proximal humerus. These differences in femoral ontogeny have not been previously addressed, yet are critical to an understanding of femoral mineralization and architecture across a wide range of mammals and may have key implications for understanding and treating hip abnormalities in humans. We evaluated femora from 70 mammalian species and categorized each according to the presence of a ‘separate’ or ‘coalesced’ proximal epiphysis based on visual assessment. We found that ossification type varies widely among mammals: taxa in the ‘coalesced’ group include marsupials, artiodactyls, perissodactyls, bats, carnivores and several primates, while the ‘separate’ group includes hominoids, many rodents, tree shrews and several marine species. There was no clear relationship to body size, phylogeny or locomotion, but qualitative and quantitative differences between the groups suggest that ossification type may be primarily an artefact of femoral shape and neck length. As some osseous abnormalities of the human hip appear to mimic the normal morphology of species with coalesced epiphyses, these results may provide insight into the aetiology and treatment of human hip disorders such as femoroacetabular impingement and early-onset osteoarthritis. PMID:17331175

  14. Scurvy in pediatric age group - A disease often forgotten?

    PubMed

    Agarwal, Anil; Shaharyar, Abbas; Kumar, Anubrat; Bhat, Mohd Shafi; Mishra, Madhusudan

    2015-06-01

    Scurvy is caused by prolonged severe dietary deficiency of vitamin C. Being rare as compared to other nutritional deficiencies, it is seldom suspected and this frequently leads to delayed recognition of this disorder. Children with abnormal dietary habits, mental illness or physical disabilities are prone to develop this disease. The disease spectrum of scurvy is quite varied and includes dermatological, dental, bone and systemic manifestations. Subperiosteal hematoma, ring epiphysis, metaphyseal white line and rarefaction zone along with epiphyseal slips are common radiological findings. High index of suspicion, detailed history and bilateral limb radiographs aids physician in diagnosing this eternal masquerader. We searched Pubmed for recent literature (2009-2014) with search terms "scurvy" "vitamin C deficiency" "ascorbic acid deficiency" "scurvy and children" "scurvy and pediatric age group". There were a total of 36 articles relevant to pediatric scurvy in children (7 reviews and 29 case reports) which were retrieved. The review briefly recapitulates the role of vitamin C, the various disease manifestations and the treatment of scurvy to create awareness of the disease which still is reported from our country, although sporadically. The recent advances related to scurvy and its management in pediatric age group are also incorporated. PMID:25983516

  15. Effectors of mTOR-autophagy pathway: targeting cancer, affecting the skeleton.

    PubMed

    Chagin, Andrei S

    2016-06-01

    Although some modulators of autophagy are emerging as drugs or supplements for anti-cancer therapy, the effects of these compounds on normal tissues must be examined carefully. Here, I review the role of autophagy in skeletal tissues in this context. First, I briefly review preclinical studies indicating the role of autophagy in cancer, as well as related on-going clinical trials. Thereafter, the role of autophagy in the physiology of skeletal tissues is discussed, with a focus on recent genetic preclinical studies. Specifically, I discuss the mTOR-autophagy pathway in relationship to epiphyseal chondrocytes, articular chondrocytes, osteoblasts, osteocytes and osteoclasts and potential side effects of targeting either mTOR pathway or autophagy in general in connection with anti-cancer therapy. Current preclinical findings indicate that inhibiting autophagy will not seriously reduce bone mass and enhance osteoporosis. However, inhibition of autophagy might damage articular cartilage and cause osteoarthritis, whereas treatment with rapalogs might result in relatively beneficial effects on articular cartilage. Modulation of the mTOR pathway or autophagy during childhood may have an undesirable influence on adult height, as well as acquisition of bone mass. PMID:26921601

  16. Significant effects of mild endogenous hormonal changes in humans: considerations for low-dose testing.

    PubMed Central

    Brucker-Davis, F; Thayer, K; Colborn, T

    2001-01-01

    We review the significant and adverse health effects that can occur with relatively small endogenous hormonal changes in pubertal and adult humans. We discuss the effects of hormonal changes that occur within normal physiologic ranges--such as the rising levels of estrogen in peripuberty, which cause growth spurts at low levels and then the fusion of epiphyses at higher levels--and the hormonal variations during the menstrual cycle and their relation to genital phenotypic changes and intercurrent disease evolution. We turn next to adaptive changes in gonadal and other functions during aging, exercise, stress, starvation, and chronic diseases, which can serve as models for the effects of exogenous, hormonally active compounds. Then we review the states of borderline hormonal imbalances such as subclinical (having few or very mild symptoms, if any) hypothyroidism or hyperthyroidism, glucose intolerance, and other endocrine conditions. Finally, we review the deleterious systemic effects of gonadal imbalance. Information stemming from clinical observations leads to the concept of "no threshold" within the endocrine system and thus illustrates the importance of considering low-dose testing for chemicals that interfere with hormonal activity. We also urge attention to more sensitive, less visible end points such as osteoporosis, increased risk for cardiovascular disease, or cognitive changes. PMID:11250802

  17. Mutations Preventing Regulated Exon Skipping in MET Cause Osteofibrous Dysplasia.

    PubMed

    Gray, Mary J; Kannu, Peter; Sharma, Swarkar; Neyt, Christine; Zhang, Dongping; Paria, Nandina; Daniel, Philip B; Whetstone, Heather; Sprenger, Hans-Georg; Hammerschmidt, Philipp; Weng, Angela; Dupuis, Lucie; Jobling, Rebekah; Mendoza-Londono, Roberto; Dray, Michael; Su, Peiqiang; Wilson, Megan J; Kapur, Raj P; McCarthy, Edward F; Alman, Benjamin A; Howard, Andrew; Somers, Gino R; Marshall, Christian R; Manners, Simon; Flanagan, Adrienne M; Rathjen, Karl E; Karol, Lori A; Crawford, Haemish; Markie, David M; Rios, Jonathan J; Wise, Carol A; Robertson, Stephen P

    2015-12-01

    The periosteum contributes to bone repair and maintenance of cortical bone mass. In contrast to the understanding of bone development within the epiphyseal growth plate, factors that regulate periosteal osteogenesis have not been studied as intensively. Osteofibrous dysplasia (OFD) is a congenital disorder of osteogenesis and is typically sporadic and characterized by radiolucent lesions affecting the cortical bone immediately under the periosteum of the tibia and fibula. We identified germline mutations in MET, encoding a receptor tyrosine kinase, that segregate with an autosomal-dominant form of OFD in three families and a mutation in a fourth affected subject from a simplex family and with bilateral disease. Mutations identified in all families with dominant inheritance and in the one simplex subject with bilateral disease abolished the splice inclusion of exon 14 in MET transcripts, which resulted in a MET receptor (MET(Δ14)) lacking a cytoplasmic juxtamembrane domain. Splice exclusion of this domain occurs during normal embryonic development, and forced induction of this exon-exclusion event retarded osteoblastic differentiation in vitro and inhibited bone-matrix mineralization. In an additional subject with unilateral OFD, we identified a somatic MET mutation, also affecting exon 14, that substituted a tyrosine residue critical for MET receptor turnover and, as in the case of the MET(Δ14) mutations, had a stabilizing effect on the mature protein. Taken together, these data show that aberrant MET regulation via the juxtamembrane domain subverts core MET receptor functions that regulate osteogenesis within cortical diaphyseal bone. PMID:26637977

  18. Chondroblastoma of the Clivus: Case Report and Review

    PubMed Central

    Liu, Jonathan; Ahmadpour, Arjang; Bewley, Arnaud F.; Lechpammer, Mirna; Bobinski, Matthew; Shahlaie, Kiarash

    2015-01-01

    Background and Importance Chondroblastoma is a benign primary bone tumor that typically develops in the epiphyses of long bones. Chondroblastoma of the craniofacial skeleton is extremely rare, with most cases occurring in the squamosal portion of the temporal bone. In this report, we describe the first case of chondroblastoma of the clivus presenting with cranial neuropathy that was treated with endoscopic endonasal resection. We review the literature on craniofacial chondroblastomas with particular emphasis on extratemporal lesions. Case Presentation A 27-year-old woman presented with severe headache, left facial dysesthesias, and diplopia. Physical examination revealed hypesthesia in the left maxillary nerve dermatome, and complete left abducens nerve palsy. Imaging demonstrated an expansile intraosseous mass originating in the upper clivus with extension superiorly into the sella turcica and laterally to involve the medial wall of the left cavernous sinus. The tumor was completely resected via an endoscopic endonasal approach, with postoperative improvement in lateral gaze palsy. Histopathology was consistent with chondroblastoma. Conclusion Chondroblastoma is a rare tumor of the craniofacial skeleton that should be included in the differential diagnosis of an osteolytic lesion of the clivus. Complete surgical resection remains the mainstay of treatment. PMID:26623238

  19. [Forensic age estimation in juveniles and young adults: Reducing the range of scatter in age diagnosis by combining different methods].

    PubMed

    Schmidt, Sven; Schramm, Danilo; Ribbecke, Sebastian; Schulz, Ronald; Wittschieber, Daniel; Olze, Andreas; Vieth, Volker; Ramsthaler, H Frank; Pfischel, Klaus; Pfeiffer, Heidi; Geserick, Gunther; Schmeling, Andreas

    2016-01-01

    The dramatic rise in the number of refugees entering Germany means that age estimation for juveniles and young adults whose age is unclear but relevant to legal and official procedures has become more important than ever. Until now, whether and to what extent the combination of methods recommended by the Study Group on Forensic Age Diagnostics has resulted in a reduction of the range of scatter of the summarized age diagnosis has been unclear. Hand skeletal age, third molar mineralization stage and ossification stage of the medial clavicular epiphyses were determined for 307 individuals aged between 10 and 29 at time of death on whom autopsies were performed at the Institutes of Legal Medicine in Berlin, Frankfurt am Main and Hamburg between 2001 and 2011. To measure the range of scatter, linear regression analysis was used to calculate the standard error of estimate for each of the above methods individually and in combination. It was found that combining the above methods led to a reduction in the range of scatter. Due to various limitations of the study, the statistical parameters determined cannot, however, be used for age estimation practice. PMID:26934764

  20. Feature description with SIFT, SURF, BRIEF, BRISK, or FREAK? A general question answered for bone age assessment.

    PubMed

    Kashif, Muhammad; Deserno, Thomas M; Haak, Daniel; Jonas, Stephan

    2016-01-01

    Solving problems in medical image processing is either generic (being applicable to many problems) or specific (optimized for a certain task). For example, bone age assessment (BAA) on hand radiographs is a frequent but cumbersome task for radiologists. For this problem, many specific solutions have been proposed. However, general-purpose feature descriptors are used in many computer vision applications. Hence, the aim of this study is (i) to compare the five leading keypoint descriptors on BAA, and, in doing so, (ii) presenting a generic approach for a specific task. Two methods for keypoint selection were applied: sparse and dense feature points. For each type, SIFT, SURF, BRIEF, BRISK, and FREAK feature descriptors were extracted within the epiphyseal regions of interest (eROI). Classification was performed using a support vector machine. Reference data (1101 radiographs) of the University of Southern California was used for 5-fold cross-validation. The data was grouped into 30 classes representing the bone age range of 0-18 years. With a mean error of 0.605 years, dense SIFT gave best results and outperforms all published methods. The accuracy was 98.36% within the range of 2 years. Dense SIFT represents a generic method for a specific question. PMID:26623943

  1. The Transcription Factor Hand1 Is Involved In Runx2-Ihh-Regulated Endochondral Ossification

    PubMed Central

    Laurie, Lindsay E.; Kokubo, Hiroki; Nakamura, Masataka; Saga, Yumiko; Funato, Noriko

    2016-01-01

    The developing long bone is a model of endochondral ossification that displays the morphological layers of chondrocytes toward the ossification center of the diaphysis. Indian hedgehog (Ihh), a member of the hedgehog family of secreted molecules, regulates chondrocyte proliferation and differentiation, as well as osteoblast differentiation, through the process of endochondral ossification. Here, we report that the basic helix-loop-helix transcription factor Hand1, which is expressed in the cartilage primordia, is involved in proper osteogenesis of the bone collar via its control of Ihh production. Genetic overexpression of Hand1 in the osteochondral progenitors resulted in prenatal hypoplastic or aplastic ossification in the diaphyses, mimicking an Ihh loss-of-function phenotype. Ihh expression was downregulated in femur epiphyses of Hand1-overexpressing mice. We also confirmed that Hand1 downregulated Ihh gene expression in vitro by inhibiting Runx2 transactivation of the Ihh proximal promoter. These results demonstrate that Hand1 in chondrocytes regulates endochondral ossification, at least in part through the Runx2-Ihh axis. PMID:26918743

  2. Radiological imaging in pediatric rheumatic diseases

    PubMed Central

    Matuszewska, Genowefa; Zaniewicz-Kaniewska, Katarzyna; Włodkowska-Korytkowska, Monika; Smorawińska, Patrycja; Saied, Fadhil; Kunisz, Wojciech; Sudoł-Szopińska, Iwona

    2014-01-01

    Summary Radiological imaging plays a fundamental role in the diagnosis and monitoring of rheumatic diseases. The basic method of imaging is a classic X-ray picture, which for many years has been used as a single method for the recognition and evaluation of the effects of disease management. In today’s modern day treatment of rheumatic diseases, ultrasonography and magnetic resonance are more commonly performed for early detection of inflammatory changes in the region of soft tissue, subchondral bone and bone marrow. In spite of their usefulness and fundamental role in the diagnosis, X-ray still remains an essential tool in the diagnosis of rheumatoid arthritis in children and is complementary to today’s methods of imaging diagnostics. In clinical practice, X-ray imaging is still an important examination performed not only to recognize the disorders, but also to provide a differential diagnosis. It helps estimate disease progression and is used to monitor the effects of treatment and the development of possible complications. Differential diagnosis of rheumatic diseases is performed on the basis of localization and type of radiographic changes. The surrounding periarticular soft tissues, bone structures, joint space, with special attention to articular bone surfaces and epiphyses, are analyzed. The aim of this work is to describe characteristic inflammatory changes present on X-ray imaging typical for the most commonly diagnosed rheumatic diseases in children, such as juvenile idiopathic arthritis, systemic lupus erythematosus, systemic scleroderma, mixed connective tissue disease, juvenile dermatomyositis, juvenile spondyloarthropathy and systemic vascular disease. PMID:24669280

  3. Skeletal Deformity Associated with SHOX Deficiency.

    PubMed

    Seki, Atsuhito; Jinno, Tomoko; Suzuki, Erina; Takayama, Shinichiro; Ogata, Tsutomu; Fukami, Maki

    2014-07-01

    SHOX haploinsufficiency due to mutations in the coding exons or microdeletions involving the coding exons and/or the enhancer regions accounts for approximately 80% and 2-16% of genetic causes of Leri-Weill dyschondrosteosis and idiopathic short stature, respectively. The most characteristic feature in patients with SHOX deficiency is Madelung deformity, a cluster of anatomical changes in the wrist that can be attributed to premature epiphyseal fusion of the distal radius. Computed tomography of SHOX-deficient patients revealed a thin bone cortex and an enlarged total bone area at the diaphysis of the radius, while histopathological analyses showed a disrupted columnar arrangement of chondrocytes and an expanded hypertrophic layer of the growth plate. Recent studies have suggested that perturbed programmed cell death of hypertrophic chondrocytes may underlie the skeletal changes related to SHOX deficiency. Furthermore, the formation of an aberrant ligament tethering the lunate and radius has been implicated in the development of Madelung deformity. Blood estrogen levels and mutation types have been proposed as phenotypic determinants of SHOX deficiency, although other unknown factors may also affect clinical severity of this entity. PMID:25110390

  4. New X linked spondyloepimetaphyseal dysplasia: report on eight affected males in the same family.

    PubMed Central

    Camera, G; Stella, G; Camera, A

    1994-01-01

    We report on a probably new form of spondyloepimetaphyseal dysplasia (SEMD) with an X linked inheritance pattern. Eight males were affected in the same family. We were able to examine three adult patients and we studied the skeletal radiological aspect of one of these patients at 2 years 6 months and at 9 years of age. The main clinical features are severe short trunked dwarfism, brachydactyly, normal facies, and normal intelligence. Radiologically, the diaphyses of all the long bones are short and broad. The epiphyses of the distal portion of the femora and those of the proximal and distal portions of the tibia are embedded in their metaphyses and there is marked narrowing of the intercondylar groove. There is moderate platyspondyly. Several vertebrae show an anterior tongue in infancy and severe irregularities of the upper and lower surfaces are present in adulthood. The 11th or 12th thoracic vertebra is wedge shaped. The pelvis is narrow. The distal ulnae and fibulae are disproportionately long. The hands show radial deviation and brachydactyly is present in the hands and feet. This X linked SEMD was not detectable at birth. Images PMID:8064814

  5. Diffusion-weighted imaging in pediatric body MR imaging: principles, technique, and emerging applications.

    PubMed

    Chavhan, Govind B; Alsabban, Zehour; Babyn, Paul S

    2014-01-01

    Diffusion-weighted (DW) imaging is an emerging technique in body imaging that provides indirect information about the microenvironment of tissues and lesions and helps detect, characterize, and follow up abnormalities. Two main challenges in the application of DW imaging to body imaging are the decreased signal-to-noise ratio of body tissues compared with neuronal tissues due to their shorter T2 relaxation time, and image degradation related to physiologic motion (eg, respiratory motion). Use of smaller b values and newer motion compensation techniques allow the evaluation of anatomic structures with DW imaging. DW imaging can be performed as a breath-hold sequence or a free-breathing sequence with or without respiratory triggering. Depending on the mobility of water molecules in their microenvironment, different normal tissues have different signals at DW imaging. Some normal tissues (eg, lymph nodes, spleen, ovarian and testicular parenchyma) are diffusion restricted, whereas others (eg, gallbladder, corpora cavernosa, endometrium, cartilage) show T2 shine-through. Epiphyses that contain fatty marrow and bone cortex appear dark on both DW images and apparent diffusion coefficient maps. Current and emerging applications of DW imaging in pediatric body imaging include tumor detection and characterization, assessment of therapy response and monitoring of tumors, noninvasive detection and grading of liver fibrosis and cirrhosis, detection of abscesses, and evaluation of inflammatory bowel disease. PMID:24819803

  6. CB1 cannabinoid receptors mediate endochondral skeletal growth attenuation by Δ9-tetrahydrocannabinol.

    PubMed

    Wasserman, Elad; Tam, Joseph; Mechoulam, Raphael; Zimmer, Andreas; Maor, Gila; Bab, Itai

    2015-01-01

    The endocannabinoid (EC) system regulates bone mass. Because cannabis use during pregnancy results in stature shorter than normal, we examined the role of the EC system in skeletal elongation. We show that CB1 and CB2 cannabinoid receptors are expressed specifically in hypertrophic chondrocytes of the epiphyseal growth cartilage (EGC), which drives vertebrate growth. These cells also express diacylglycerol lipases, critical biosynthetic enzymes of the main EC, and 2-arachidonoylglycerol (2-AG), which is present at significant levels in the EGC. Femora of CB1- and/or CB2-deficient mice at the end of the rapid growth phase are longer compared to wild-type (WT) animals. We find that Δ(9) -tetrahydrocannabinol (THC) slows skeletal elongation of female WT and CB2-, but not CB1-, deficient mice, which is reflected in femoral and lumbar vertebral body length. This in turn results in lower body weight, but unaltered fat content. THC inhibits EGC chondrocyte hypertrophy in ex vivo cultures and reduces the hypertrophic cell zone thickness of CB1-, but not CB2-, deficient mice. These results demonstrate a local growth-restraining EC system in the EGC. The relevance of the present findings to humans remains to be studied. PMID:25573322

  7. Evaluation of four biodegradable, injectable bone cements in an experimental drill hole model in sheep.

    PubMed

    von Rechenberg, Brigitte; Génot, Oliver R; Nuss, Katja; Galuppo, Larry; Fulmer, Mark; Jacobson, Evan; Kronen, Peter; Zlinszky, Kati; Auer, Jörg A

    2013-09-01

    Four cement applications were tested in this investigation. Two dicalcium phosphate dihydrate (DCPD-brushite) hydraulic cements, an apatite hydraulic fiber loaded cement, and a calcium sulfate cement (Plaster of Paris) were implanted in epiphyseal and metaphyseal cylindrical bone defects in sheep. The in vivo study was performed to assess the biocompatibility and bone remodeling of four cement formulations. After time periods of 2, 4, and 6 months, the cement samples were clinically and histologically evaluated. Histomorphometrically, the amount of new bone formation, fibrous tissue, and bone marrow and the area of remaining cement were measured. In all specimens, no signs of inflammation were detectable either macroscopically or microscopically. Cements differed mainly in their resorption time. Calcium sulfate was already completely resorbed at 2 months and showed a variable amount of new bone formation and/or fibrous tissue in the original drill hole over all time periods. The two DCPD cements in contrast were degraded to a large amount at 6 months, whereas the apatite was almost unchanged over all time periods. PMID:23680585

  8. A novel TRPS1 gene mutation causing trichorhinophalangeal syndrome with growth hormone responsive short stature: a case report and review of the literature.

    PubMed

    Merjaneh, Lina; Parks, John S; Muir, Andrew B; Fadoju, Doris

    2014-01-01

    The role of growth hormone (GH) and its therapeutic supplementation in the trichorhinophalangeal syndrome type I (TRPS I) is not well delineated. TRPS I is a rare congenital syndrome, characterized by craniofacial and skeletal malformations including short stature, sparse, thin scalp hair and lateral eyebrows, pear-shaped nose, cone shaped epiphyses and hip dysplasia. It is inherited in an autosomal dominant manner and caused by haploinsufficiency of the TRPS1 gene. We report a family (Mother and 3 of her 4 children) with a novel mutation in the TRPS1 gene. The diagnosis was suspected only after meeting all family members and comparing affected and unaffected siblings since the features of this syndrome might be subtle. The eldest sibling, who had neither GH deficiency nor insensitivity, improved his growth velocity and height SDS after 2 years of treatment with exogenous GH. No change in growth velocity was observed in the untreated siblings during this same period. This report emphasizes the importance of examining all family members when suspecting a genetic syndrome. It also demonstrates the therapeutic effect of GH treatment in TRPS I despite normal GH-IGF1 axis. A review of the literature is included to address whether TRPS I is associated with: a) GH deficiency, b) GH resistance, or c) GH-responsive short stature. More studies are needed before recommending GH treatment for TRPS I but a trial should be considered on an individual basis. PMID:25177352

  9. [Effect of dosed diet restriction on physiological remodeling and bioelectric properties of bone].

    PubMed

    Levashov, M I; Ianko, R V; Chaka, E G; Safonov, S L

    2014-07-01

    The effect of dosed diet restriction on the physiological remodeling and bioelectric properties of bone tissue was studied in 48 male Wistar rats 3- and 18-months of age. The rate of bone tissue apposition was studied by the dynamic histomorphometry method (intravital tetracycline labeling). Electric potentials on the periosteal surface of the freshly isolated femurs were recorded. The magnitude of dielectric loss factor was determined to assess the quality of bone tissue. The control rats received a standard diet. The experimental rats received a limited diet (60 % of the standard mass) for 28 days. The magnitude and rate of the bone tissue apposition on the endosteal and periosteal surface of the tibia were less by 38.4% and 122.7% respectively in experimental rats after dosed diet restriction. Electric potential in the metaphyseal-epiphyseal growth zones of the femur was 29.7% lower, and the dielectric loss factor increased by 15.8%. The bone tissue apposition rate and the electric potential magnitude were increased 10 days after completion of the dosed diet restriction. The magnitude of the dielectric loss factor decreased after returning to the standard diet. Key words: dosed diet restriction, bone, remodelling, bioelectric properties. PMID:25669112

  10. Asparaginase Potentiates Glucocorticoid-Induced Osteonecrosis in a Mouse Model

    PubMed Central

    Liu, Chengcheng; Janke, Laura J.; Kawedia, Jitesh D.; Ramsey, Laura B.; Cai, Xiangjun; Mattano, Leonard A.; Boyd, Kelli L.; Funk, Amy J.; Relling, Mary V.

    2016-01-01

    Osteonecrosis is a common dose-limiting toxicity of glucocorticoids. Data from clinical trials suggest that other medications can increase the risk of glucocorticoid-induced osteonecrosis. Here we utilized a mouse model to study the effect of asparaginase treatment on dexamethasone-induced osteonecrosis. Mice receiving asparaginase along with dexamethasone had a higher rate of osteonecrosis than those receiving only dexamethasone after 6 weeks of treatment (44% vs. 10%, P = 0.006). Similarly, epiphyseal arteriopathy, which we have shown to be an initiating event for osteonecrosis, was observed in 58% of mice receiving asparaginase and dexamethasone compared to 17% of mice receiving dexamethasone only (P = 0.007). As in the clinic, greater exposure to asparaginase was associated with greater plasma exposure to dexamethasone (P = 0.0001). This model also recapitulated other clinical risk factors for osteonecrosis, including age at start of treatment, and association with the systemic exposure to dexamethasone (P = 0.027) and asparaginase (P = 0.036). We conclude that asparaginase can potentiate the osteonecrotic effect of glucocorticoids. PMID:26967741

  11. One carbon metabolism and bone homeostasis and remodeling: A review of experimental research and population studies.

    PubMed

    Feigerlova, Eva; Demarquet, Lea; Guéant, Jean-Louis

    2016-07-01

    Homocysteine (HCY) is a degradation product of the methionine pathway. The B vitamins, in particular vitamin B12 and folate, are the primary nutritional determinant of HCY levels and therefore their deficiencies result in hyperhomocysteinaemia (HHCY). Prevalence of hyperhomocysteinemia (HHCY) and related dietary deficiencies in B vitamins and folate increase with age and have been related to osteoporosis and abnormal development of epiphyseal cartilage and bone in rodents. Here we provide a review of experimental and population studies. The negative effects of HHCY and/or B vitamins and folate deficiencies on bone formation and remodeling are documented by cell models, including primary osteoblasts, osteoclast and bone progenitor cells as well as by animal and human studies. However, underlying pathophysiological mechanisms are complex and remain poorly understood. Whether these associations are the direct consequences of impaired one carbon metabolism is not clarified and more studies are still needed to translate these findings to human population. To date, the evidence is limited and somewhat conflicting, however further trials in groups most vulnerable to impaired one carbon metabolism are required. PMID:27086080

  12. In vivo radiometric analysis of glucose uptake and distribution in mouse bone.

    PubMed

    Zoch, Meredith L; Abou, Diane S; Clemens, Thomas L; Thorek, Daniel L J; Riddle, Ryan C

    2016-01-01

    Bone formation and remodeling occurs throughout life and requires the sustained activity of osteoblasts and osteoclasts, particularly during periods of rapid bone growth. Despite increasing evidence linking bone cell activity to global energy homeostasis, little is known about the relative energy requirements or substrate utilization of bone cells. In these studies, we measured the uptake and distribution of glucose in the skeleton in vivo using positron-emitting (18)F-fluorodeoxyglucose ([(18)F]-FDG) and non-invasive, high-resolution positron emission tomography/computed tomography (PET/CT) imaging and ex vivo autoradiography. Assessment of [(18)F]-FDG uptake demonstrated that relative to other tissues bone accumulated a significant fraction of the total dose of the glucose analog. Skeletal accumulation was greatest in young mice undergoing the rapid bone formation that characterizes early development. PET/CT imaging revealed that [(18)F]-FDG uptake was greatest in the epiphyseal and metaphyseal regions of long bones, which accords with the increased osteoblast numbers and activity at this skeletal site. Insulin administration significantly increased skeletal accumulation of [(18)F]-FDG, while uptake was reduced in mice lacking the insulin receptor specifically in osteoblasts or fed a high-fat diet. Our results indicated that the skeleton is a site of significant glucose uptake and that its consumption by bone cells is subject to regulation by insulin and disturbances in whole-body metabolism. PMID:27088042

  13. Inhibitory effects of a polypeptide thymic factor on the development of 7,12-dimethylbenz(a)anthragene-induced mammary adenocarcinoma in female rats

    SciTech Connect

    Anisimov, V.N.; Danetskaya, E.V.; Morozov, V.G.; Khavinson, V.Kh.

    1980-01-01

    It has come to be recognized that tumor growth is accompanied by inhibition of cellular immunity and the function of the T lymphocytes. Restitution of T lymphocyte function by means of several pharmacologic agents such as levamisole, phenformin, or epithalamin (an epiphyseal factor) has, in a number of cases, been accompanied by growth inhibition of both spontaneous and induced tumors. In addition, the importance of the thymus in the regulation of T lymphocytes and in antitumor immunity has been recognized. Several indicators point to the fact that the thymus contains physiologically active substances which stimulate T cell-dependent immunity and prevent the occurrence of neoplasms. These considerations have led to attempts at isolation of active thymic factors and studies on their effects on the appearance and growth of tumors. Previously, a thymic factor - thymarin - had been isolated which imparted immunocompetence to the T lymphocytes. This factor differs from other thymic preparations, including thymosine, in terms of a number of physicochemical characteristics and is a polypeptide with a molecular weight of 5000. This study is concerned with its effects on tumor development - mammary gland adenocarcinoma induced in animals with a chemical carcinogen.

  14. Asparaginase Potentiates Glucocorticoid-Induced Osteonecrosis in a Mouse Model.

    PubMed

    Liu, Chengcheng; Janke, Laura J; Kawedia, Jitesh D; Ramsey, Laura B; Cai, Xiangjun; Mattano, Leonard A; Boyd, Kelli L; Funk, Amy J; Relling, Mary V

    2016-01-01

    Osteonecrosis is a common dose-limiting toxicity of glucocorticoids. Data from clinical trials suggest that other medications can increase the risk of glucocorticoid-induced osteonecrosis. Here we utilized a mouse model to study the effect of asparaginase treatment on dexamethasone-induced osteonecrosis. Mice receiving asparaginase along with dexamethasone had a higher rate of osteonecrosis than those receiving only dexamethasone after 6 weeks of treatment (44% vs. 10%, P = 0.006). Similarly, epiphyseal arteriopathy, which we have shown to be an initiating event for osteonecrosis, was observed in 58% of mice receiving asparaginase and dexamethasone compared to 17% of mice receiving dexamethasone only (P = 0.007). As in the clinic, greater exposure to asparaginase was associated with greater plasma exposure to dexamethasone (P = 0.0001). This model also recapitulated other clinical risk factors for osteonecrosis, including age at start of treatment, and association with the systemic exposure to dexamethasone (P = 0.027) and asparaginase (P = 0.036). We conclude that asparaginase can potentiate the osteonecrotic effect of glucocorticoids. PMID:26967741

  15. Presence of repeating hyperostotic bones in dorsal pterygiophores of the oarfish, Regalecus russellii.

    PubMed

    Paig-Tran, E W Misty; Barrios, Andrew S; Ferry, Lara A

    2016-10-01

    Hyperostosis, excessive bone growth along bone that stems from bone, periosteum or articular or epiphyseal cartilage, occurs in at least 22 families of fishes most of which are tropical or subtropical marine species. While the presence of hyperostosis is well documented in fishes, the mechanism driving the development of the excessive bone growth is unclear. This study documented hyperostosis along the dorsal pterygiophores in both sexes of oarfish, Regalecus russellii; however, it was not present in all specimens examined. This is the second lampridiform fish with hyperostoses and the first case documented in a deeper-water, epi-mesopelagic fish. In oarfish, the majority of the dorsal pterygiophores tissues are poorly mineralized, anosteocytic bones with some fish displaying localized stiffened, hyperostotic growths near the distal edge. Oarfish lack a swim bladder so they must continuously beat their bi-directional dorsal fin to maintain position within the water column while engaged in locomotory behavior. These fishes have areas of localized, hyperostotic skeletal elements along the dorsal pterygiophores that, presumably, function as a stiffened lever system to support fin undulation. It was noted that hyperossification was not present in all fish examined and was only documented in fish with total lengths greater than 3 m. PMID:27296623

  16. The role of energy dissipation of polymeric scaffolds in the mechanobiological modulation of chondrogenic expression.

    PubMed

    Abdel-Sayed, Philippe; Darwiche, Salim E; Kettenberger, Ulrike; Pioletti, Dominique P

    2014-02-01

    Mechanical stimulation has been proposed to induce chondrogenesis in cell-seeded scaffolds. However, the effects of mechanical stimuli on engineered cartilage may vary substantially between different scaffolds. This advocates for the need to identify an overarching mechanobiological variable. We hypothesize that energy dissipation of scaffolds subjected to dynamic loading may be used as a mechanobiology variable. The energy dissipation would furnish a general criterion to adjust the mechanical stimulation favoring chondrogenesis in scaffold. Epiphyseal chondro-progenitor cells were then subject to unconfined compression 2 h per day during four days in different scaffolds, which differ only by the level of dissipation they generated while keeping the same loading conditions. Scaffolds with higher dissipation levels upregulated the mRNA of chondrogenic markers. In contrast lower dissipation of scaffolds was associated with downregulation of chondrogenic markers. These results showed that energy dissipation could be considered as a mechanobiology variable in cartilage. This study also indicated that scaffolds with energy dissipation level close to the one of cartilage favors chondrogenic expression when dynamical loading is present. PMID:24331703

  17. Skeletal Deformity Associated with SHOX Deficiency

    PubMed Central

    Seki, Atsuhito; Jinno, Tomoko; Suzuki, Erina; Takayama, Shinichiro; Ogata, Tsutomu; Fukami, Maki

    2014-01-01

    Abstract. SHOX haploinsufficiency due to mutations in the coding exons or microdeletions involving the coding exons and/or the enhancer regions accounts for approximately 80% and 2–16% of genetic causes of Leri-Weill dyschondrosteosis and idiopathic short stature, respectively. The most characteristic feature in patients with SHOX deficiency is Madelung deformity, a cluster of anatomical changes in the wrist that can be attributed to premature epiphyseal fusion of the distal radius. Computed tomography of SHOX-deficient patients revealed a thin bone cortex and an enlarged total bone area at the diaphysis of the radius, while histopathological analyses showed a disrupted columnar arrangement of chondrocytes and an expanded hypertrophic layer of the growth plate. Recent studies have suggested that perturbed programmed cell death of hypertrophic chondrocytes may underlie the skeletal changes related to SHOX deficiency. Furthermore, the formation of an aberrant ligament tethering the lunate and radius has been implicated in the development of Madelung deformity. Blood estrogen levels and mutation types have been proposed as phenotypic determinants of SHOX deficiency, although other unknown factors may also affect clinical severity of this entity. PMID:25110390

  18. Metaphyseal dysplasia of Braun-Tinschert type: report of a Japanese girl.

    PubMed

    Takata, Shinjiro; Nishimura, Gen; Ikegawa, Shiro; Kuroda, Yasuhiro; Nishino, Mizuho; Matsui, Yoshito; Yasui, Natsuo

    2006-06-01

    We report on a 7-year-old Japanese girl with metaphyseal dysplasia (MD) of Braun-Tinschert type, a recently recognized, autosomal dominant sclerosing bone dysplasia. All individuals with the disorder from four families in the literature originated from a small town in Bohemia or its vicinity. The occurrence of the disorder in a Japanese girl indicates that it is not restricted to Germans. The radiographic hallmarks of the disorder include metaphyseal undermodeling (Erlenmeyer-flask deformity); osteosclerosis of the chondroosseous junctions, metaphyseal cortices, and epiphyseal margins; and exostosis-like bone excrescences at the metaphyseal-diaphyseal junctions. In the girl we described, the latter two findings were conspicuous at age 4 years, but became less prominent with increasing age. The metaphyseal trabeculae were somewhat coarse. The humeri exhibited varus deformity, and the ulnae and fibulae mild bowing. The mean bone mineral density of the lumbar spine was lower than that of age-matched controls. The patient exhibited premature loss of primary teeth, likely to be a sign of increased periodontal bone resorption. Markers of bone formation and resorption were both increased, an indication of a high rate of bone turnover. PMID:16691581

  19. Differential limb scaling in the american alligator (Alligator mississippiensis) and its implications for archosaur locomotor evolution.

    PubMed

    Livingston, Victoria J; Bonnan, Matthew F; Elsey, Ruth M; Sandrik, Jennifer L; Wilhite, D Ray

    2009-06-01

    Bipedalism evolved multiple times within archosaurs, and relatively shorter forelimbs characterize both crocodyliforms and nonavian dinosaurs. Analysis of a comprehensive ontogenetic sequence of specimens (embryo to adult) of the sauropodomorph Massospondylus has shown that bipedal limb proportions result from negative forelimb allometry. We ask, is negative forelimb allometry a pattern basal to archosaurs, amplified in certain taxa to produce bipedalism? Given the phylogenetic position of extant crocodylians and their relatively shorter forelimb, we tested the hypothesis that prevalent negative forelimb allometry is present in Alligator mississippiensis from a sample of wild specimens from embryonic to adult sizes. Long bone lengths (humerus, radius, ulna, femur, tibia, fibula, third metapodials) were measured with their epiphyseal cartilage intact at all sizes. Our results show an overall isometric pattern for most elements regressed on femur length, humerus length, or total limb length. However, negative allometry was prevalent for the ulna, and the third metapodials scale with positive allometry embryonically. These data suggest that the general forelimb proportions in relation to the hindlimb do not change significantly with increasing size in A. mississippiensis. The negative allometry of the ulna and embryonicaly positive allometry of the third metapodials appears to be related to maintaining the functional integrity of the limbs. We show that this pattern is different from that of the sauropodomorph Massospondylus, and we suggest that if bipedalism in archosaurs is tied, in part, to negative forearm allometry, it was either secondarily lost through isometric scaling, or never developed in the ancestor of A. mississippiensis. PMID:19462445

  20. Burnt bone assemblages from El Esquilleu cave (Cantabria, Northern Spain): deliberate use for fuel or systematic disposal of organic waste?

    NASA Astrophysics Data System (ADS)

    Yravedra, J.; Uzquiano, P.

    2013-05-01

    Bones or fossil fuels associated with combustion structures have been widely discussed in several works related to Neanderthal lifestyles and subsistence patterns during the MIS 3. El Esquilleu cave (western Cantabria, Spain) can significantly contribute to this issue, particularly with the taphonomic study of layers 21 and 23, which are characterized by the presence of hearths containing abundant burnt and charred faunal remains of ibex. The fragmentation and burning rates as well as bone presence within hearths may suggest that they were used as a supplementary fuel resource. Following previous research on the suitability of bones as a supplement to firewood in hearth combustions, a series of experiments are here presented using goat bones, in consistency with the faunal record present at El Esquilleu. Our experiments proved that small-sized animal (<100 kg in weight) bones also possess appropriate qualities for their use as fuel, particularly epiphyseal and axial parts. This paper critically evaluates whether bones could have been used as fuel by the Neanderthal groups at El Esquilleu or whether their combustion resulted from other behavioural practises. In this sense, we compare our results with different proxy data from this site as well as with the palaeoenvironmental information available for the MIS 3 chronological period in Western Europe.

  1. In situ hybridization and immunohistochemistry of versican, aggrecan and link protein, and histochemistry of hyaluronan in the developing mouse limb bud cartilage

    PubMed Central

    Shibata, S; Fukada, K; Imai, H; Abe, T; Yamashita, Y

    2003-01-01

    We investigated the expression pattern of versican, aggrecan, link protein and hyaluronan in the developing limb bud cartilage of the fetal mouse using in situ hybridization and/or immunohistochemistry. Versican mRNA and immunostaining were detected in the mesenchymal cell condensation of the future digital bone at E13. Versican mRNA expression rapidly disappeared from the tibial cartilage, as cartilage formation progressed during E13–15, but the immunostaining was gradually replaced by aggrecan immunostaining from the diaphysis. Immunostaining for both molecules thus had a ‘nega-posi’ pattern and consequently versican immunostaining was still detected at the epiphyseal end at E15. This result indicated that versican functions as a temporary framework in newly formed cartilage matrix. An aggrecan-positive region within the cartilage invariably had intense hyaluronan staining, whereas a versican-positive region also had affinity for hyaluronan within the cartilage, but not in the mesenchymal cell condensation. Therefore, the presence of versican aggregates was not confirmed in the developing limb bud cartilage. Furthermore, although link protein was more closely related with aggrecan than versican during limb bud cartilage formation, there was a discrepancy between the expression of aggrecan and link protein in tibial cartilage at E15. In particular, only a link protein-positive region was present in the marginal area of the metaphysis and the epiphysis at this stage. This finding may indicate a novel role for link protein. PMID:14620382

  2. Histologic Examination of an Assemblage of Psittacosaurus (Dinosauria: Ceratopsia) Juveniles From the Yixian Formation (Liaoning, China).

    PubMed

    Bo, Zhao; Hedrick, Brandon P; Chunling, Gao; Tumarkin-Deratzian, Allison R; Fengjiao, Zhang; Caizhi, Shen; Dodson, Peter

    2016-05-01

    Psittacosaurus is one of the most abundant dinosaurs known, which allows for extensive study of its growth and form. Previous studies have evaluated growth trajectories of Psittacosaurus using bone histology. However, we present the first study of Psittacosaurus comparative juvenile histology and describe the histology of Psittacosaurus within its first year of life based on multiple sections taken from an exquisite monospecific assemblage of juveniles from the Yixian Formation in Liaoning, China. Specimens studied had femur lengths ranging from 30 to 36 mm. The five juveniles examined all have similar histologic patterns in the midshaft and epiphyseal regions showing that there is limited plasticity in bone development in juvenile Psittacosaurus and that all of the specimens in the assemblage were likely the same age. The microstructure patterns are compatible with the hypothesis that Psittacosaurus was precocial and that these juveniles were neonates. Based on comparisons with other juvenile ornithischians, juvenile Psittacosaurus had a growth rate similar to Orodromeus, slower than that of Maiasaura, Dysalotosaurus, or hadrosaurs consistent with small body size. Our results support previous studies that demonstrated that the orientation of vascular canals is likely not solely reflective of growth rate, but is also affected by underlying biomechanical, structural processes. The number of studies done on theropod and sauropodomorph histology dwarfs those of ornithischians. More studies of ornithischian histology are necessary in order to better establish phylogenetic trends in microstructure and to learn more about growth in this important clade. PMID:26864238

  3. Complete Traumatic Separation of Proximal Femoral Epiphysis in A 2 Year Old Child

    PubMed Central

    Pal, Chandra Prakash; Kumar, Deepak; Singh, Pulkesh; Gaurav, Vishal

    2014-01-01

    Introduction: Hip fractures are very common in adults, but are rare in children, comprising less than 1% of all pediatric fractures. Separation of the proximal femoral epiphysis can occur in a child with a traumatic hip dislocation and an open epiphysis. Regardless of the mechanism of proximal femoral epiphyseal separation, the prognosis is poor secondary to the development of osteonecrosis. Case Report: Here we are reporting a case of complete separation of the proximal epiphysis of the femur in a 2 year old female child. She was treated by open reduction and internal fixation by a single k-wire of proximal femoral epiphysis. Regular follow up showed fusion of proximal femoral epiphysis at about 3 months of post operative period. After 8 months of follow up she can stand and walk without support. Long term outcome is awaited. Conclusion: Traumatic separation of the proximal femoral epiphysis is a rare but devastating injury because osteonecrosis occurs in most cases. In our study we found fusion of the proximal femoral epiphysis to the neck after 3 months of postoperative period. But to comment upon the final outcome a long follow up is awaited.

  4. A review of terminology for equine juvenile osteochondral conditions (JOCC) based on anatomical and functional considerations.

    PubMed

    Denoix, J-M; Jeffcott, L B; McIlwraith, C W; van Weeren, P R

    2013-07-01

    This manuscript describes a new classification of the various joint-related lesions that can be seen in the young, growing horse based on their anatomical and functional aetiopathogenesis. Juvenile osteochondral conditions (JOCC) is a term that brings together specific disorders according to their location in the joint and their biomechanical origin. When a biomechanical insult affects the process of endochondral ossification different types of osteochondrosis (OC) lesions may occur, including osteochondral fragmentation of the articular surface or of the periarticular margins, or the formation of juvenile subchondral bone cysts. In severe cases, osteochondral collapse of the articular surface or the epiphysis or even an entire small bone may occur. Tension on ligament attachments may cause avulsion fractures of epiphyseal (or metaphyseal) ossifying bone, which are classified as JOCC, but do not result from a disturbance of the process of endochondral ossification and are not therefore classified as a form of OC. The same applies to 'physitis' which can result from damage to the physeal growth plate. PMID:23683533

  5. Development of vascularization in the chondroepiphysis of the rabbit.

    PubMed

    Ganey, T M; Love, S M; Ogden, J A

    1992-07-01

    Although numerous studies have addressed the presence of cartilage canals within developing epiphyses, the chronology of their appearance and their vascular contribution to the developing chondroepiphysis remain to be studied. We have selected a model, similar to the developing human skeletal system, in which extensive cartilage canal development precedes the subsequent secondary ossification process. In the rabbit proximal tibia, both chondroepiphyseal and vascular (cartilage canals) development were quantified from the first evidence of vessels until the formation of the secondary center of ossification. The volume of hyaline cartilage increased 25 times after intraepiphyseal vessels were initially observed. The blood supply, measured in cartilage canal volume, increased 400-fold over the same period. Three distinct cartilage canal morphologies were identifiable before the formation of the secondary center of ossification: (a) an early phase, in which the canals appeared as infoldings derived from the perichondrium; (b) a reactive phase, occurring simultaneously with chondrocyte hypertrophy and characterized by a very large increase in mesenchymal cells within the cartilage canal; and (c) a vascular phase, coincident with mineralization of the matrix, in which the familiar, unitary canal morphology was replaced by that of a vascular plexus. While matrix mineralization and the formation of bone seem dependent on critical cellular events, notably chondrocyte hypertrophy, the role that the vascular supply plays in developing sufficient biological inertia for the ossifying transition must not be underestimated. PMID:1613625

  6. The Olduvai Hominid 8 foot: adult or subadult?

    PubMed

    DeSilva, Jeremy M; Zipfel, Bernhard; Van Arsdale, Adam P; Tocheri, Matthew W

    2010-05-01

    Olduvai Hominid 8 (OH 8), an articulating set of fossil hominin tarsal and metatarsal bones, is critical to interpretations of the evolution of hominin pedal morphology and bipedal locomotion. It has been suggested that OH 8 may represent the foot of a subadult and may be associated with the OH 7 mandible, the type specimen of Homo habilis. This assertion is based on the presence of what may be unfused distal metatarsal epiphyses. Accurately assessing the skeletal maturity of the OH 8 foot is important for interpretations of the functional morphology and locomotor behavior of Plio-Pleistocene hominins. In this study, we compare metatarsal fusion patterns and internal bone morphology of the lateral metatarsals among subadult hominines (85 modern humans, 48 Pan, and 25 Gorilla) to assess the likelihood that OH 8 belonged to either an adult or subadult hominin. Our results suggest that if OH 8 is indeed from a subadult, then it displays a metatarsal developmental pattern that is unobserved in our comparative sample. In OH 8, the fully fused base of the first metatarsal and the presence of trabecular bone at the distal ends of the second and third metatarsal shafts make it highly improbable that it belonged to a subadult, let alone a subadult that matches the developmental age of the OH 7 mandible. In total, the results of this study suggest that the OH 8 foot most likely belonged to an adult hominin. PMID:20416928

  7. Bioactivity and bone healing properties of biomimetic porous composite scaffold: in vitro and in vivo studies.

    PubMed

    Veronesi, Francesca; Giavaresi, Gianluca; Guarino, Vincenzo; Raucci, Maria Grazia; Sandri, Monica; Tampieri, Anna; Ambrosio, Luigi; Fini, Milena

    2015-09-01

    Tissue engineering (TE) represents a valid alternative to traditional surgical therapies for the management of bone defects that do not regenerate spontaneously. Scaffolds, one of the most important component of TE strategy, should be biocompatible, bioactive, osteoconductive, and osteoinductive. The aim of this study was to evaluate the biological properties and bone regeneration ability of a porous poly(ɛ-caprolactone) (PCL) scaffold, incorporating MgCO3 -doped hydroxyapatite particles, uncoated (PCL_MgCHA) or coated by apatite-like crystals via biomimetic treatment (PCL_MgCHAB). It was observed that both scaffolds are not cytotoxic and, even if cell viability was similar on both scaffolds, PCL_MgCHAB showed higher alkaline phosphatase and collagen I (COLL I) production at day 7. PCL_MgCHA induced more tumor necrosis factor-α release than PCL_MgCHAB, while osteocalcin was produced less by both scaffolds up to 7 days and no significant differences were observed for transforming growth factor-β synthesis. The percentage of new bone trabeculae growth in wide defects carried out in rabbit femoral distal epiphyses was significantly higher in PCL_MgCHAB in comparison with PCL_MgCHA at 4 weeks and even more at 12 weeks after implantation. This study highlighted the role of a biomimetic composite scaffold in bone regeneration and lays the foundations for its future employment in the clinical practice. PMID:25689266

  8. Medial and lateral segond fractures in a skeletally immature patient: a radiographic marker for the multiply injured knee.

    PubMed

    Kwon, Oh Soo; Park, Min Jung; Tjoumakaris, Fotios P

    2011-11-01

    Marginal fractures of the medial tibial plateau have been reported in the literature as a secondary type of Segond fracture. Some reports described this entity in the setting of combined injuries such as root avulsions of the medial meniscus, complete disruption of the posterior cruciate ligament (PCL), partial tear of the anterior cruciate ligament (ACL), and tears of the medial meniscus and medial collateral ligament. It has been postulated that medial marginal fractures are secondary to compression of the medial aspect of the femoral condyle and tibial plateau with a corresponding posterolateral corner injury. However, this mechanism of injury may not always be as straightforward.This article presents a case of an alternate injury pattern in a skeletally immature patient. A 16-year-old boy sustained a varus force and twisting injury to his knee, resulting in radiographic evidence of multiple avulsion fractures of the knee, including a fibular epiphyseal avulsion fracture and medial and lateral Segond fractures. Usually, the avulsion fractures serve as markers for significant ligamentous injuries in adult patients, but our patient had minimal injury to the PCL, ACL, and posterolateral corner. Further physical examination and imaging studies revealed an anterior horn root avulsion, meniscocapsular separation, and anterior cortical rim fracture. A combination of imaging modalities helped us further characterize the injury pattern to devise the optimal surgical plan, especially the fixation of the anterior cortical fracture of the tibia. PMID:22049962

  9. Long bone histology of the stem salamander Kokartus honorarius (Amphibia: Caudata) from the Middle Jurassic of Kyrgyzstan.

    PubMed

    Skutschas, Pavel; Stein, Koen

    2015-04-01

    Kokartus honorarius from the Middle Jurassic (Bathonian) of Kyrgyzstan is one of the oldest salamanders in the fossil record, characterized by a mixture of plesiomorphic morphological features and characters shared with crown-group salamanders. Here we present a detailed histological analysis of its long bones. The analysis of a growth series demonstrates a significant histological maturation during ontogeny, expressed by the progressive appearance of longitudinally oriented primary vascular canals, primary osteons, growth marks, remodelling features in primary bone tissues, as well as progressive resorption of the calcified cartilage, formation of endochondral bone and development of cartilaginous to bony trabeculae in the epiphyses. Apart from the presence of secondary osteons, the long bone histology of Kokartus is very similar to that of miniaturized temnospondyls, other Jurassic stem salamanders, miniaturized seymouriamorphs and modern crown-group salamanders. We propose that the presence of secondary osteons in Kokartus honorarius is a plesiomorphic feature, and the loss of secondary osteons in the long bones of crown-group salamanders as well as in those of miniaturized temnospondyls is the result of miniaturization processes. Hitherto, all stem salamander long bong histology (Kokartus, Marmorerpeton and 'salamander A') has been generally described as having paedomorphic features (i.e. the presence of Katschenko's Line and a layer of calcified cartilage), these taxa were thus most likely neotenic forms. The absence of clear lines of arrested growth and annuli in long bones of Kokartus honorarius suggests that the animals lived in an environment with stable local conditions. PMID:25682890

  10. Mutations Preventing Regulated Exon Skipping in MET Cause Osteofibrous Dysplasia

    PubMed Central

    Gray, Mary J.; Kannu, Peter; Sharma, Swarkar; Neyt, Christine; Zhang, Dongping; Paria, Nandina; Daniel, Philip B.; Whetstone, Heather; Sprenger, Hans-Georg; Hammerschmidt, Philipp; Weng, Angela; Dupuis, Lucie; Jobling, Rebekah; Mendoza-Londono, Roberto; Dray, Michael; Su, Peiqiang; Wilson, Megan J.; Kapur, Raj P.; McCarthy, Edward F.; Alman, Benjamin A.; Howard, Andrew; Somers, Gino R.; Marshall, Christian R.; Manners, Simon; Flanagan, Adrienne M.; Rathjen, Karl E.; Karol, Lori A.; Crawford, Haemish; Markie, David M.; Rios, Jonathan J.; Wise, Carol A.; Robertson, Stephen P.

    2015-01-01

    The periosteum contributes to bone repair and maintenance of cortical bone mass. In contrast to the understanding of bone development within the epiphyseal growth plate, factors that regulate periosteal osteogenesis have not been studied as intensively. Osteofibrous dysplasia (OFD) is a congenital disorder of osteogenesis and is typically sporadic and characterized by radiolucent lesions affecting the cortical bone immediately under the periosteum of the tibia and fibula. We identified germline mutations in MET, encoding a receptor tyrosine kinase, that segregate with an autosomal-dominant form of OFD in three families and a mutation in a fourth affected subject from a simplex family and with bilateral disease. Mutations identified in all families with dominant inheritance and in the one simplex subject with bilateral disease abolished the splice inclusion of exon 14 in MET transcripts, which resulted in a MET receptor (METΔ14) lacking a cytoplasmic juxtamembrane domain. Splice exclusion of this domain occurs during normal embryonic development, and forced induction of this exon-exclusion event retarded osteoblastic differentiation in vitro and inhibited bone-matrix mineralization. In an additional subject with unilateral OFD, we identified a somatic MET mutation, also affecting exon 14, that substituted a tyrosine residue critical for MET receptor turnover and, as in the case of the METΔ14 mutations, had a stabilizing effect on the mature protein. Taken together, these data show that aberrant MET regulation via the juxtamembrane domain subverts core MET receptor functions that regulate osteogenesis within cortical diaphyseal bone. PMID:26637977

  11. Effects of electrical stimulation on rat limb regeneration, a new look at an old model

    PubMed Central

    Leppik, Liudmila P.; Froemel, Dara; Slavici, Andrei; Ovadia, Zachri N.; Hudak, Lukasz; Henrich, Dirk; Marzi, Ingo; Barker, John H.

    2015-01-01

    Limb loss is a devastating disability and while current treatments provide aesthetic and functional restoration, they are associated with complications and risks. The optimal solution would be to harness the body’s regenerative capabilities to regrow new limbs. Several methods have been tried to regrow limbs in mammals, but none have succeeded. One such attempt, in the early 1970s, used electrical stimulation and demonstrated partial limb regeneration. Several researchers reproduced these findings, applying low voltage DC electrical stimulation to the stumps of amputated rat forelimbs reporting “blastema, and new bone, bone marrow, cartilage, nerve, skin, muscle and epiphyseal plate formation”. In spite of these encouraging results this research was discontinued. Recently there has been renewed interest in studying electrical stimulation, primarily at a cellular and subcellular level, and studies have demonstrated changes in stem cell behavior with increased proliferation, differentiation, matrix formation and migration, all important in tissue regeneration. We applied electrical stimulation, in vivo, to the stumps of amputated rat limbs and observed significant new bone, cartilage and vessel formation and prevention of neuroma formation. These findings demonstrate that electricity stimulates tissue regeneration and form the basis for further research leading to possible new treatments for regenerating limbs. PMID:26678416

  12. Object-oriented approach to the automatic segmentation of bones from pediatric hand radiographs

    NASA Astrophysics Data System (ADS)

    Shim, Hyeonjoon; Liu, Brent J.; Taira, Ricky K.; Hall, Theodore R.

    1997-04-01

    The purpose of this paper is to develop a robust and accurate method that automatically segments phalangeal and epiphyseal bones from digital pediatric hand radiographs exhibiting various stages of growth. The development of this system draws principles from object-oriented design, model- guided analysis, and feedback control. A system architecture called 'the object segmentation machine' was implemented incorporating these design philosophies. The system is aided by a knowledge base where all model contours and other information such as age, race, and sex, are stored. These models include object structure models, shape models, 1-D wrist profiles, and gray level histogram models. Shape analysis is performed first by using an arc-length orientation transform to break down a given contour into elementary segments and curves. Then an interpretation tree is used as an inference engine to map known model contour segments to data contour segments obtained from the transform. Spatial and anatomical relationships among contour segments work as constraints from shape model. These constraints aid in generating a list of candidate matches. The candidate match with the highest confidence is chosen to be the current intermediate result. Verification of intermediate results are perform by a feedback control loop.

  13. Genetic mapping of a locus for multiple ephiphyseal dysplasia (EDM2) to a region of chromosome 1 containing a type IX collagen gene

    SciTech Connect

    Briggs, M.D.; Choi, HiChang; Warman, M.L.; Loughlin, J.A.; Wordsworth, P.; Sykes, B.C.; Irven, C.M.M.; Smith, M.; Wynne-Davies, R.; Lipson, M.H.

    1994-10-01

    Multiple epiphyseal dysplasia (MED) is a dominantly inherited chondrodysplasia characterized by mild short stature and early-onset osteoarthrosis. Some forms of MED clinically resemble another chondrodysplasia phenotype, the mild form of pseudoachondroplasia (PSACH). On the basis of their clinical similarities as well as similar ultra-structural and biochemical features in cartilage from some patients, it has been proposed that MED and PSACH belong to a single bone-dysplasia family. Recently, both mild and severe PSACH as well as a form of MED have been linked to the same interval on chromosome 19, suggesting that they may be allelic disorders. Linkage studies with the chromosome 19 markers were carried out in a large family with MED and excluded the previously identified interval. Using this family, we have identified a MED locus on the short arm of chromosome 1, in a region containing the gene (COL9A2) that encodes the {alpha}2 chain of type IX collagen, a structural component of the cartilage extracellular matrix. 39 refs., 3 figs., 3 tabs.

  14. Management of Late Onset Perthes: Evaluation of Distraction by External Fixator—5-Year Follow-Up

    PubMed Central

    Srivastava, Rajeshwar N.; Shukla, Prashant; Pushkar, Amit; Ali, Sabir

    2014-01-01

    Background. Hip distraction in Perthes' disease unloads the joint, which negates the harmful effect of the stresses on the articular surfaces, which may promote the sound healing of the area of necrosis. We have examined the effect of arthrodiastasis on the preservation of the femoral head in older children with Perthes' disease. Methods and Materials. Twelve children with age more than 8 years with Perthes' disease of less than one year were treated with hip distraction by a hinged monolateral external fixator. Observation and Results. Mean duration of distraction was 13.9 days. These children were evaluated by clinicoradiological parameters for a mean period of 32.4 months. There was a significant improvement in the range of movements and mean epiphyseal index, but the change in the percentage of uncovered head femur was insignificant. There was significant improvement in Harris Hip score. Conclusions. Hip distraction by hinged monolateral external fixator seems to be a valid treatment option in cases with Perthes' disease in the selected group of patients, where poor results are expected from conventional treatment. PMID:25580302

  15. Hunter-McAlpine craniosynostosis phenotype associated with skeletal anomalies and interstitial deletion of chromosome 17q

    SciTech Connect

    Thomas, J.; Prescott, K.; Milner, R.

    1994-09-01

    Syndromic craniosynostosis is frequently associated with skeletal abnormalities, but the biological basis for this association is unclear. Molecular genetic studies have the biological basis for this association is unclear. Molecular genetic studies have identified a number of loci and at least one candidate gene, the MSX2 gene. We recently encountered a 9 y.o. boy with moderate mental retardation, congenital craniosynostosis, and multiple skeletal anomalies. Physical features strongly suggested Hunter-McAlpine syndrome (HMS). Specifically, he had triangular facies with a small mouth prominent chin, bulbous nose, thin vermillion border, malaligned and malformed teeth, and low set, rudimentary ears. Skeletal features included: bilambdoidal, bicoronal, and sagittal craniosynostosis; right preaxial polydactyly; bilateral talipes; coxa valga; genu valgum; bilateral fusion of the hamate and capitate; scoliosis; and small, irregular middle phalangeal epiphyses. High resolution chromosome analysis revealed an interstitial deletion of G negative material of subbands q23.1{r_arrow}23.3 or q23.3{r_arrow}q24.2 of a No. 17 homologue. HMS, a presumed autosomal dominant disorder associated with characteristic facies, variable degrees of mental retardation, craniosynostosis, and minor acral-skeletal anomalies, proved to be the most likely explanation for this patient`s findings. We propose that our patient has a new mutation for HMS with more severe skeletal involvement than previously reported. Linkage studies are in progress to test the hypothesis that familial HMS may be localized to chromosome 17.

  16. Evaluation of extremity pain in children using technetium-99m MDP bone scan: A general hospital experience

    SciTech Connect

    Park, H.M.; Rothschild, P.A.; Kernek, C.B.

    1984-01-01

    This study was undertaken to evaluate the efficacy of three-phase bone scan in detection of significant pathology i.e., osteomyelitis (OM), septic joint, cellulitis, etc., in children with symptoms of extremity pain. A total of 100 consecutive patients (age 9 days - 16 yrs, 63 boys and 37 girls) were studied. The authors reviewed their scans, x-rays and hospital records. The final diagnoses were based on the findings of needle aspiration, surgical drainage, biopsy, culture, and on the therapeutic response. In 87%, sufficiently long clinical follow-up was available to confirm the final diagnoses. In the remaining 13%, the symptoms resolved quickly and follow-up was not felt necessary. The scan was essential in pinpointing the lesions in pts with referred or nonlocalizing extremity pain. The +ve and -ve predictive values of the scan and OM were 89% and 96% respectively. One spiral fracture was misinterpreted as diffuse OM. One ''Subacute epiphyseal OM'' was not detected. In two cases, cellulitis and septic joint obscured underlying OM. Prior antibotic therapy resulted in one equivocal scan. Although less sensitive (29%) in early OM, radiographs play an important complimentary role. Bone scans detected underlying pathology for extremity pain in 61% of all pts studied.

  17. A novel form of chondrocyte stress is triggered by a COMP mutation causing pseudoachondroplasia.

    PubMed

    Suleman, Farhana; Gualeni, Benedetta; Gregson, Hannah J; Leighton, Matthew P; Piróg, Katarzyna A; Edwards, Sarah; Holden, Paul; Boot-Handford, Raymond P; Briggs, Michael D

    2012-01-01

    Pseudoachondroplasia (PSACH) results from mutations in cartilage oligomeric matrix protein (COMP) and the p.D469del mutation within the type III repeats of COMP accounts for approximately 30% of PSACH. To determine disease mechanisms of PSACH in vivo, we introduced the Comp D469del mutation into the mouse genome. Mutant animals were normal at birth but grew slower than their wild-type littermates and developed short-limb dwarfism. In the growth plates of mutant mice chondrocyte columns were reduced in number and poorly organized, while mutant COMP was retained within the endoplasmic reticulum (ER) of cells. Chondrocyte proliferation was reduced and apoptosis was both increased and spatially dysregulated. Previous studies on COMP mutations have shown mutant COMP is co-localized with chaperone proteins, and we have reported an unfolded protein response (UPR) in mouse models of PSACH-MED (multiple epiphyseal dysplasia) harboring mutations in Comp (T585M) and Matn3, Comp etc (V194D). However, we found no evidence of UPR in this mouse model of PSACH. In contrast, microarray analysis identified expression changes in groups of genes implicated in oxidative stress, cell cycle regulation, and apoptosis, which is consistent with the chondrocyte pathology. Overall, these data suggest that a novel form of chondrocyte stress triggered by the expression of mutant COMP is central to the pathogenesis of PSACH. PMID:22006726

  18. A NURBS-based technique for subject-specific construction of knee bone geometry.

    PubMed

    Au, Anthony G; Palathinkal, Darren; Liggins, Adrian B; Raso, V James; Carey, Jason; Lambert, Robert G; Amirfazli, A

    2008-10-01

    Subject-specific finite element (FE) models of bones that form the knee joint require rapid and accurate geometry construction. The present study introduces a semi-automatic non-uniform rational B-spline (NURBS) technique to construct knee bone geometries from computed tomography (CT) images using a combination of edge extraction and CAD surface generation. In particular, this technique accurately constructs endosteal surfaces and can accommodate thin cortical bone by estimating the cortical thickness from well-defined surrounding bone. A procedure is also introduced to overcome the bifurcation at the femoral condyles during surface generation by combining transverse and sagittal plane CT data. Available voxel- and NURBS-based subject-specific construction techniques accurately capture periosteal surfaces but are limited in their ability to capture endosteal geometry. In this study, the proposed NURBS-based technique and a typical voxel mesh technique captured periosteal surfaces within an order of magnitude of image resolution. The endosteum of diaphyseal bone was also captured with similar accuracy by both techniques. However, the voxel mesh model failed to accurately capture the metaphyseal and epiphyseal endosteum due to the poor CT contrast of thin cortical bone, resulting in gross overestimation of cortical thickness. The proposed technique considered both the local and global nature of CT images to arrive at a description of cortical bone thickness accurate to within 2 pixel lengths. PMID:18644314

  19. PCR assay confirms diagnosis in syndrome with variably expressed phenotype: mutation detection in Stickler syndrome.

    PubMed Central

    Ahmad, N N; McDonald-McGinn, D M; Dixon, P; Zackai, E H; Tasman, W S

    1996-01-01

    Stickler syndrome is an autosomal dominant disease with ocular (severe myopia, vitreal degeneration, and retinal detachment) and other systemic manifestations (hearing loss, cleft palate, epiphyseal dysplasia, and premature osteoarthritis). As with other dominantly inherited conditions, the clinical phenotype of Stickler syndrome varies considerably. To date, all mutations have been located in the type II procollagen (COL2A1) gene. Analysis of a C-->T mutation we had identified previously, in COL2A1 gene in exon 40, in a three generation pedigree showed the loss of a cleavage site for the TaqI restriction enzyme. We designed a rapid PCR based restriction enzyme assay to detect this mutation and used it to establish the diagnosis in a neonate from the same pedigree, presenting with the first occurrence of the Pierre-Robin sequence in the family and minimal ocular findings. These results underline the potential diagnostic value of many as yet undetected DNA mutations in families affected with Stickler syndrome, since the variability of the phenotype can impede accurate diagnosis, appropriate genetic counselling, and effective intervention and prophylactic treatment for affected people. Images PMID:8863161

  20. Mechanical Influences on Morphogenesis of the Knee Joint Revealed through Morphological, Molecular and Computational Analysis of Immobilised Embryos

    PubMed Central

    Roddy, Karen A.; Prendergast, Patrick J.; Murphy, Paula

    2011-01-01

    Very little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint. PMID:21386908

  1. MRI of the wrist is not recommended for age determination in female football players of U-16/U-17 competitions.

    PubMed

    Tscholl, P M; Junge, A; Dvorak, J; Zubler, V

    2016-03-01

    Age determination on magnetic resonance imaging (MRI) of the wrist is a reliable method in male football players to evaluate their eligibility to participate in Under 17 tournaments. MRI of the wrist was performed in 487 female volunteers aged 13-19 years from Brazil, Germany, Malaysia, and Tanzania, and in 139 female football players participating in Under-16 and Under-17 football tournaments. A previously validated method for grading fusion of the distal radial epiphysis in male adolescent was used. Moderate correlation of chronological age and epiphyseal fusion was found in the normative control group (r = .59) and weak correlation in female football players (r = .27). Complete fusion of the distal radial epiphysis was observed in two 15-year-old volunteers of the control group (1.7%) and in 17.6% (3 of 17) of 14-year-old football players. Up to 10.8% (47 of 437) in the control group and 14.4% (20 of 139) of the football players 17 years or younger had complete fused epiphysis. Because of earlier osseous maturity in female adolescents, the grade of fusion of the distal radial epiphysis on MRI is not recommended for pretournament age determination for the age of 17 and younger in female. PMID:25880786

  2. Regulation of chondrocyte terminal differentiation in the postembryonic growth plate: the role of the PTHrP-Indian hedgehog axis.

    PubMed

    Farquharson, C; Jefferies, D; Seawright, E; Houston, B

    2001-09-01

    Chondrocyte differentiation during embryonic bone growth is controlled by interactions between PTHrP and Indian hedgehog. We have now determined that the major components of this signaling pathway are present in the postembryonic growth plate. PTHrP was immunolocalized throughout the growth plate, and semiquantitative RT-PCR analysis of maturationally distinct chondrocyte fractions indicated that PTHrP, Indian hedgehog, and the PTH/PTHrP receptor were expressed at similar levels throughout the growth plate. However, patched, the hedgehog receptor, was more highly expressed in proliferating chondrocytes. Although all fractionated cells responded to PTHrP in culture by increasing thymidine incorporation and cAMP production and decreasing alkaline phosphatase activity, the magnitude of response was greatest in the proliferative chondrocytes. Bone morphogenetic proteins are considered likely intermediates in PTHrP signaling. Expression of bone morphogenetic protein-2 and 4--7 was detected within the growth plate, and PTHrP inhibited the expression of bone morphogenetic protein-4 and 6. Although organ culture studies indicated a possible paracrine role for epiphyseal chondrocyte-derived PTHrP in regulating growth plate chondrocyte differentiation, the presence within the postembryonic growth plate of functional components of the PTHrP-Indian hedgehog pathway suggests that local mechanisms intrinsic to the growth plate exist to control the rate of endochondral ossification. PMID:11517192

  3. Sequential differentiation of mesenchymal stem cells in an agarose scaffold promotes a physis-like zonal alignment of chondrocytes.

    PubMed

    Schmitt, Jacqueline Frida; See, Kwee Hua; Hua, See Kwee; Yang, Zheng; Zheng, Yang; Hui, James Hoi Po; Po, James Hui Hoi; Lee, Eng Hin; Hin, Lee Eng

    2012-11-01

    Chondrocytes of the epiphyseal growth plate (physis) differentiate and mature in defined linear zones. The current study examines the differentiation of human bone marrow derived mesenchymal stem cells (hBMSCs) into zonal physeal cartilage. hBMSCs were embedded in an agarose scaffold with only the surface of the scaffold in direct contact with the culture medium. The cells were differentiated using a two-step system involving the sequential addition of TGFβ followed by BMP2. The resultant samples displayed a heterogenic population of physis-like collagen type 2 positive cells including proliferating chondrocytes and mature chondrocytes showing hypertrophy, expression of early bone markers and matrix mineralization. Histological analysis revealed a physis-like linear zonal alignment of chondrocytes in varying stages of differentiation. The less mature chondrocytes were seen at the base of the construct while hypertrophic chondrocytes and matrix mineralization was observed closer to the surface of the construct. The described differentiation protocol using hBMSCs in an agarose scaffold can be used to study the factors and conditions that influence the differentiation, proliferation, maturation, and zonal alignment of physeal chondrocytes. PMID:22517299

  4. Femoral development in chronically centrifuged rats

    NASA Technical Reports Server (NTRS)

    Smith, S. D.

    1977-01-01

    Groups of 30-d-old male and female rats were centrifuged at 2.00 G (RE, Rotation Experimental), 1.05 G (RC, Rotation Control) or exposed to the noise and wind of the centrifuge at 1.00 G (EC, Earth Control) for periods of 1, 2, 4, 8, and 16 weeks. Measurements of their femurs indicated that exposure to centrifugation a) decreased femoral length in RE animals, b) increased femoral length in RC animals, c) reduced femoral diameter in RE and RC animals, d) increased L/D ratios in RC animals, e) decreased L/D ratios in RE animals, f) increased femur length/body weight in RE animals, g) decreased cortical thickness (CT) in RE animals, h) increased relative CT in RE animals, and decreased it in RC animals, i) accelerated ossification in RC femoral heads, j) thinned and distorted RE epiphyseal plates, and k) thickened condylar cartilage in RE females. The effects tended to be strongly sexually dimorphic, with females more severely affected by the stress than males.

  5. A comprehensive approach to the spectrum of abnormal pubertal development.

    PubMed

    Appelbaum, Heather; Malhotra, Shilpa

    2012-04-01

    Puberty is the biological transition from childhood to adulthood. The process involves the coordination of hormonal, physical, psychosocial, and cognitive systems to result in physiologic change. Precocious puberty is defined as pubertal development beginning earlier than expected based on normal standards. Gonadotropin dependent precocious puberty is caused by premature activation of the hypothalamus resulting in pulsatile secretion of GnRH. Gonadotropin independent precocious puberty is caused by excess sex hormones from peripheral or external sources. Treatment with GnRH agonists should be offered to prevent early fusion of the epiphyseal plates to avoid unnecessary short stature and should not be based on perceived psychosocial consequences of early puberty. Delayed puberty is the absence of or incomplete development of secondary sexual characteristics. Hypergonadotropic hypogonadism or primary hypogonadism may result from genetic mutation syndromes or can be acquired from antiovarian antibodies, exposure to radiation or chemotherapy, inflammatory insult, or surgical removal of the gonads. Hypogonadotropic hypogonadism or secondary hypogonadism is due to hypothalamic dysfunction resulting in impaired secretion of GnRH. The long-term goal for patients with inadequate estrogen stimulation is to maintain the serum concentration of sex steroids within the normal adult range to promote the development of secondary sexual characteristics, prevent premature bone loss, and ultimately to induce fertility when indicated. PMID:22764552

  6. Structural analysis of rat bone explants kept in vitro in simulated microgravity conditions.

    PubMed

    Cosmi, F; Steimberg, N; Dreossi, D; Mazzoleni, G

    2009-04-01

    Skeletal abnormalities reported in humans and laboratory animals after spaceflight, include cancellous osteopenia, decreased cortical and cancellous bone formation, aberrant matrix ultrastructure, decreased mineralization and reduced bone strength. Although considerable effort has been made up to now to understand the skeletal effects of spaceflight, in order to estimate health risk, our knowledge in this area is still largely incomplete. It is widely accepted that the mechanical strength of cancellous bone is related not only to the mineral content, but also to the trabecular micro-architecture arrangement. Three-dimensional numerical analysis of bone volumes has been shown to be an important tool in this field. The Cell Method, a recently introduced numerical method, has been applied to static analysis of structures obtained from 3D reconstruction of micro-computed tomography scans performed at the Elettra Synchrotron facility (Trieste, Italy) in order to quantify changes in trabecular bone architecture. In the present study, the Cell Method model is used to compare the micro-tomographed structure of fragments of rats bone explants (tibial proximal epiphyses) harvested after 3 days and after 1, 2, 3 and 4 weeks of culture in the RCCS bioreactor, which represents the unique existing bioreactor, operating on the Earth's surface, capable of successfully reproducing, in vitro, optimal conditions in order to simulate a microgravity environment. Although preliminary, our results seem to suggest that the exposure of tibial bone explants to simulated microgravity conditions obtained by the RCCS bioreactor, are consistent with skeletal changes observed after spaceflight. PMID:19627820

  7. Phenotypic expressions of a Gly154Arg mutation in type II collagen in two unrelated patients with spondyloepimetaphyseal dysplasia (SEMD)

    SciTech Connect

    Kaitila, I.; Marttinen, E.; Koerkkoe, J.; Ala-Kokko, L.

    1996-05-03

    Type II collagenopathies consist of chondrodysplasia ranging from lethal to mild in severity. A large number of mutations has been found in the COL2A1 gene. Glycine substitutions have been the most common types of mutation. Genotype-phenotype correlations in type II collagenopathies have not been established, partly because of insufficient clinical and radiographic description of the patients. We found a glycine-to-arginine substitution at position 154 in type II collagen in two unrelated isolated propositi with spondyloepimetaphyseal dysplasia and provide a comparative clinical and radiographic analysis from birth to young adulthood for this condition. The clinical phenotype was disproportionate short stature with varus/valgus deformities of the lower limbs requiring corrective osteotomies, and lumbar lordosis. The skeletal radiographs showed an evolution from short tubular bones, delayed epiphyseal development, and mild vertebral involvement to severe metaphyseal dysplasia with dappling irregularities, and hip {open_quotes}dysplasia.{close_quotes} The metaphyseal abnormalities disappeared by adulthood. 27 refs., 11 figs., 1 tab.

  8. Hip injuries in children and adolescents.

    PubMed

    Craig, C L

    1980-10-01

    Hip injuries in children present a wide spectrum of problems. Frequently because of the severity of the trauma involved, other injuries may take precedence and may require modification of the usual approaches to treatment. However, certain precepts are essential to the successful treatment of these injuries and should be kept in mind regardless of the milieu in which they are found. In the child with a hip dislocation, the potential presence of an acetabular, femoral head, femoral shaft, patellar or tibial plateau fracture must always be considered. Specialized x-ray views are necessary for this evaluation. Laminography and arthrography may also be required. The essential feature of successful subsequent treatment is a gentle closed reduction performed within 24 hours of injury. Treatment of displaced fractures of the femoral neck remains an unresolved issue. Accurate reduction held with adequate internal fixation would appear to offer the best chance for a successful result. The possible complications of avascular necrosis, delayed union and non-union, coxa vara, premature closure of the epiphyseal plate, and shortening should be appreciated. Early institution of appropriate treatment may mitigate the ultimate effect of these potentially devastating problems. PMID:7454245

  9. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

    PubMed Central

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development. PMID:26434683

  10. Proximal humerus fractures in children and adolescents.

    PubMed

    Lefèvre, Y; Journeau, P; Angelliaume, A; Bouty, A; Dobremez, E

    2014-02-01

    Proximal humerus fractures are rare in paediatric traumatology. Metaphyseal fractures account for about 70% of cases and epiphyseal separation for the remaining 30%. The development and anatomy of the proximal humerus explain the various fracture types, displacements, and potential complications; and also help in interpreting the radiographic findings, most notably in young children. Physicians should be alert to the possibility of an underlying lesion or pathological fracture requiring appropriate diagnostic investigations, and they should consider child abuse in very young paediatric patients. Although the management of proximal humerus fractures remains controversial, the extraordinary remodelling potential of the proximal humerus in skeletally immature patients often allows non-operative treatment without prior reduction. When the displacement exceeds the remodelling potential suggested by the extent of impaction, angulation, and patient age, retrograde elastic stable intramedullary nailing (ESIN) provides effective stabilisation. As a result, the thoraco-brachial abduction cast is less often used, although this method remains a valid option. Retrograde ESIN must be performed by a surgeon who is thoroughly conversant with the fundamental underlying principles. Direct percutaneous pinning is a fall-back option when the surgeon's experience with ESIN is insufficient. Finally, open reduction is very rarely required and should be reserved for severely displaced fractures after failure of closed reduction. When these indications are followed, long-term outcomes are usually excellent, with prompt resumption of previous activities and a low rate of residual abnormalities. PMID:24394917

  11. Osseointegration of Ti-6Al-4V alloy implants with a titanium nitride coating produced by a PIRAC nitriding technique: a long-term time course study in the rat.

    PubMed

    Sovak, Guy; Gotman, Irena; Weiss, Anna

    2015-02-01

    This study examined bone tissue responses to Ti-6Al-4V alloy implants with a hard TiN coating applied by an original powder immersion reaction-assisted coating (PIRAC) nitriding method. Progression of implant fixation in the distal epiphysis and within the medullary cavity of the rat femur was evaluated between 3 days and 6 months postimplantation by scanning electron microscopy, oxytetracycline incorporation, and histochemistry. After 6 months, successful osseointegration was achieved in both epiphyseal and diaphyseal sites. Throughout, implant portions located within the epiphysis remained in close contact with bone trabeculae that gradually engulfed the implant forming a bone collar continuous with the trabecular network of the epiphysis. In the diaphysis, woven bone was first formed within the marrow cavity around the implant and later was replaced by a shell of compact bone around the implant. In general, higher osseointegration rates were measured for TiN-coated versus the uncoated implants, both in the epiphysis and in the diaphysis. In conclusion, our findings indicate an excellent long-term biocompatibility of TiN coatings applied by the PIRAC nitriding technique and superior osteoinductive ability in comparison with uncoated Ti-6Al-4V alloy. Such coatings can, therefore, be considered for improving the corrosion and wear resistance of titanium-based orthopedic implants. PMID:25482093

  12. Scurvy in pediatric age group – A disease often forgotten?

    PubMed Central

    Agarwal, Anil; Shaharyar, Abbas; Kumar, Anubrat; Bhat, Mohd Shafi; Mishra, Madhusudan

    2015-01-01

    Scurvy is caused by prolonged severe dietary deficiency of vitamin C. Being rare as compared to other nutritional deficiencies, it is seldom suspected and this frequently leads to delayed recognition of this disorder. Children with abnormal dietary habits, mental illness or physical disabilities are prone to develop this disease. The disease spectrum of scurvy is quite varied and includes dermatological, dental, bone and systemic manifestations. Subperiosteal hematoma, ring epiphysis, metaphyseal white line and rarefaction zone along with epiphyseal slips are common radiological findings. High index of suspicion, detailed history and bilateral limb radiographs aids physician in diagnosing this eternal masquerader. We searched Pubmed for recent literature (2009–2014) with search terms “scurvy” “vitamin C deficiency” “ascorbic acid deficiency” “scurvy and children” “scurvy and pediatric age group”. There were a total of 36 articles relevant to pediatric scurvy in children (7 reviews and 29 case reports) which were retrieved. The review briefly recapitulates the role of vitamin C, the various disease manifestations and the treatment of scurvy to create awareness of the disease which still is reported from our country, although sporadically. The recent advances related to scurvy and its management in pediatric age group are also incorporated. PMID:25983516

  13. Uncoupling of chondrocyte differentiation and perichondrial mineralization underlies the skeletal dysplasia in tricho-rhino-phalangeal syndrome

    PubMed Central

    Napierala, Dobrawa; Sam, Kathy; Morello, Roy; Zheng, Qiping; Munivez, Elda; Shivdasani, Ramesh A.; Lee, Brendan

    2008-01-01

    Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal dominant craniofacial and skeletal dysplasia that is caused by mutations involving the TRPS1 gene. Patients with TRPS have short stature, hip abnormalities, cone-shaped epiphyses and premature closure of growth plates reflecting defects in endochondral ossification. The TRPS1 gene encodes for the transcription factor TRPS1 that has been demonstrated to repress transcription in vitro. To elucidate the molecular mechanisms underlying skeletal abnormalities in TRPS, we analyzed Trps1 mutant mice (Trps1ΔGT mice). Analyses of growth plates demonstrated delayed chondrocyte differentiation and accelerated mineralization of perichondrium in Trps1 mutant mice. These abnormalities were accompanied by increased Runx2 and Ihh expression and increased Indian hedgehog signaling. We demonstrated that Trps1 physically interacts with Runx2 and represses Runx2-mediated trans-activation. Importantly, generation of Trps1ΔGT/+;Runx2+/− double heterozygous mice rescued the opposite growth plate phenotypes of single mutants, demonstrating the genetic interaction between Trps1 and Runx2 transcription factors. Collectively, these data suggest that skeletal dysplasia in TRPS is caused by dysregulation of chondrocyte and perichondrium development partially due to loss of Trps1 repression of Runx2. PMID:18424451

  14. Skeletal development and performance of broilers

    SciTech Connect

    El-Deeb, M.A.

    1989-01-01

    The effect of high dietary copper supplementation has been shown to promote growth rate. The results of the experiments reported herein indicated that copper supplementation of 100 ppm with zinc at the requirement level had no effect on growth rate or bone mineralization. However, when various levels of copper and zinc were added to the diet, significant changes in bone mineralization and liver zinc and copper concentrations occurred. In further studies, the effect of dietary supplementation with vitamin D{sub 3} or its metabolite 1,25(OH){sub 2}D{sub 3} on the incidence of tibial dyschondroplasia and related bone abnormalities in broiler chicks was investigated. The results indicated that feeding 1,25(OH){sub 2}D{sub 3} at 5ug/Kg diet as the sole source of vitamin D{sub 3} steroid was sufficient to maintain a calcium homeostasis in the chicks. The effect of growth hormone (GH) injections on the metabolism of tibial epiphyseal growth plant (EGP) in broiler chicks either genetically susceptible or resistant to tibial dyschondroplasia (HTD and LTD respectively) was investigated. GH injection increased {sup 3}H-thymidine uptake, indicating a direct effect of GH on cell replication in EGP.

  15. Age-related differential gene and protein expression in postnatal cartilage canal and osteochondral junction chondrocytes.

    PubMed

    Duesterdieck-Zellmer, Katja; Semevolos, Stacy; Kinsley, Marc; Riddick, Tara

    2015-01-01

    Wnt/β-catenin, Indian hedgehog (Ihh)/Parathyroid-related peptide (PTHrP) and retinoid signaling pathways regulate cartilage differentiation, growth, and function during development and play a key role in endochondral ossification. The objective of this study was to elucidate the gene and protein expression of signaling molecules of these regulatory pathways in chondrocytes surrounding cartilage canals and the osteochondral junction during neonatal and pre-adolescent development. This study revealed cell-specific and age-related differences in gene and protein expression of signaling molecules of these regulatory pathways. A trend for higher gene expression of PTHrP along the cartilage canals and Ihh along the osteochondral junction suggests the presence of paracrine feedback in articular-epiphyseal cartilage. Differential expression of canonical (β-catenin, Wnt-4, Lrp4, Lrp6) and noncanonical Wnt signaling (Wnt-5b, Wnt-11) and their inhibitors (Dkk1, Axin1, sFRP3, sFRP5, Wif-1) surrounding the cartilage canals and osteochondral junction provides evidence of the complex interactions occurring during endochondral ossification. PMID:25479004

  16. MR Imaging in Postreduction Assessment of Developmental Dysplasia of the Hip: Goals and Obstacles.

    PubMed

    Rosenbaum, Daniel G; Servaes, Sabah; Bogner, Eric A; Jaramillo, Diego; Mintz, Douglas N

    2016-01-01

    Developmental dysplasia of the hip is a spectrum disorder of hip development that ranges in severity from abnormal acetabular morphology to complete hip dislocation. While treatment with a Pavlik harness is highly effective in infants younger than 6 months, older infants and children and those with orthotic failure often warrant surgical reduction and placement of a spica cast, which limits subsequent imaging evaluation. Magnetic resonance (MR) imaging has been described in the evaluation of the adequacy of hip reduction for more than 2 decades, but the practice is still not widespread and is performed routinely at relatively few centers. MR imaging is a robust tool for outcome assessment after hip reduction and placement of a spica cast, facilitating multiplanar confirmation of concentric reduction independent of an ossific nucleus or orthopedic hardware. Excellent image contrast of soft tissues allows identification of obstacles to concentric reduction, which may be extra-articular or intra-articular. Extra-articular obstacles include tightening of the adductor muscles and tightening of the iliopsoas tendon with constriction of the joint capsule. Intra-articular obstacles include limbus formation, labral inversion, an enlarged pulvinar, and hypertrophy of the ligamentum teres and/or the transverse acetabular ligament. Intravenous contrast material administration may demonstrate altered epiphyseal blood flow and help identify patients at risk for early ischemia. Imaging technique and image interpretation can be optimized to facilitate the performance of postreduction MR imaging studies where they may be of benefit. (©)RSNA, 2016. PMID:27035836

  17. Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat

    NASA Technical Reports Server (NTRS)

    Wang, T. M.; Hsu, J. F.; Jee, W. S.; Matthews, J. L.

    1993-01-01

    The histomorphometric changes in the proximal tibial metaphysis and epiphyseal growth plate and midtibial shaft of 26-week-old spontaneously hypertensive rats (SHR) compared with those of the corresponding normotensive Wistar-Kyoto (WKY) rats were studied. A decrease in body weight, growth plate thickness, and longitudinal growth rate of the proximal tibial epiphysis, trabecular bone volume, trabecular thickness and number, the number of osteoblasts and osteoprogenitor cells per millimeter square surface of the proximal tibial metaphysis, periosteal and endocortical apposition rate and bone formation rate of the tibial diaphysis were observed in the SHR. Additionally, systolic blood pressure, the number of osteoclasts per millimeter square surface and average number of nuclei per osteoclast of the proximal tibial metaphysis were significantly increased. Thus, osteoclastic activity is dominant over osteoblastic and chondroblastic activity in the SHR that results in a cancellous bone deficit in the skeleton. It will require additional work to ascertain the underlying cause for this condition as several factors in the SHR with a potential for causing this change are present, including elevated parathyroid hormone (PTH), depressed 1,25-(OH)2D3, low calcium absorption, reduced body weight (reduced loading) elevated blood pressure and possibly other direct cell differences in the mutant strain. At present elevated PTH and adaptation to underloading from reduced weight are postulated to be a likely cause, but additional studies are required to test this interpretation.

  18. Historical ESWT Paradigms Are Overcome: A Narrative Review

    PubMed Central

    Nauck, Tanja; Korakakis, Vasileios; Malliaropoulos, Nikos

    2016-01-01

    Extracorporeal Shock Wave Therapy (ESWT) is a conservative treatment modality with still growing interest in musculoskeletal disorders. This narrative review aims to present an overview covering 20-year development in the field of musculoskeletal ESWT. Eight historical paradigms have been identified and put under question from a current perspective: energy intensity, focus size, anesthesia, imaging, growth plates, acuteness, calcifications, and number of sessions. All paradigms as set in a historical consensus meeting in 1995 are to be revised. First, modern musculoskeletal ESWT is divided into focused and radial technology and the physical differences are about 100-fold with respect to the applied energy. Most lesions to be treated are easy to reach and clinical focusing plays a major role today. Lesion size is no longer a matter of concern. With the exception of nonunion fractures full, regional, or even local anesthesia is not helpful in musculoskeletal indications. Juvenile patients can also effectively be treated without risk of epiphyseal damage. Further research is needed to answer the question about if and which acute injuries can be managed effectively. Treatment parameters like the number of sessions are still relying on empirical data and have to be further elucidated. PMID:27493955

  19. Functional bone histology of zebrafish reveals two types of endochondral ossification, different types of osteoblast clusters and a new bone type.

    PubMed

    Weigele, Jochen; Franz-Odendaal, Tamara A

    2016-07-01

    The zebrafish is as an important vertebrate animal model system for studying developmental processes, gene functions and signalling pathways. It is also used as a model system for the understanding of human developmental diseases including those related to the skeleton. However, surprisingly little is known about normal zebrafish skeletogenesis and osteogenesis. As in most vertebrates, it is commonly known that the bones of adult zebrafish are cellular unlike that of some other teleosts. After careful histological analyses of each zebrafish adult bone, we identified several acellular bones, with no entrapped osteocytes in addition to several cellular bones. We show that both cellular and acellular bones can even occur within the same skeletal element and transitions between these two cell types can be found. Furthermore, we describe two types of osteoblast clusters during skeletogenesis and two different types of endochondral ossification. The epiphyseal plate, for example, lacks a zone of calcification and a degradation zone with osteoblasts. A new bone type that we term tubular bone was also identified. This bone is completely filled with adipose tissue, unlike spongy bones. This study provides important insight on how osteogenesis takes place in zebrafish, and especially on the transition from cellular to acellular bones. Overall, this study leads to a deeper understanding of the functional histological composition of adult zebrafish bones. PMID:27278890

  20. Effects of Balsamodendron mukul Gum Resin Extract on Articular Cartilage in Papain-induced Osteoarthritis.

    PubMed

    Manjhi, Jayanand; Gupta, Maneesh; Sinha, Anvesha; Rawat, Beena; Rai, Durg V

    2016-07-01

    . Outcome Measures • The articular cartilages from the knee joints and epiphyseal bones of the femur and tibia were extracted from the right- and left-side limbs to perform the biochemical, microarchitectural, and histological analyses. Results • The total protein and collagen content of the articular cartilage of the knees were significantly higher in all treated groups when compared with the OA group of rats. The histological analysis revealed a thicker cartilage and a higher trabecular density of the subchondral bone (epiphyseal bone) in BDM-treated rats. Conclusions • The oral dose of BDM gum resin extract was shown to relieve OA pain, regenerate the cartilaginous matrix, and increase the subchondral bone components. On the basis of the findings, the research team suggests that the BDM gum resin extract may be used for therapeutic interventions for reversal of OA and reduction in its related inflammatory pain. PMID:27548493

  1. MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature.

    PubMed

    Wit, Jan M; Oostdijk, Wilma; Losekoot, Monique; van Duyvenvoorde, Hermine A; Ruivenkamp, Claudia A L; Kant, Sarina G

    2016-04-01

    The fast technological development, particularly single nucleotide polymorphism array, array-comparative genomic hybridization, and whole exome sequencing, has led to the discovery of many novel genetic causes of growth failure. In this review we discuss a selection of these, according to a diagnostic classification centred on the epiphyseal growth plate. We successively discuss disorders in hormone signalling, paracrine factors, matrix molecules, intracellular pathways, and fundamental cellular processes, followed by chromosomal aberrations including copy number variants (CNVs) and imprinting disorders associated with short stature. Many novel causes of GH deficiency (GHD) as part of combined pituitary hormone deficiency have been uncovered. The most frequent genetic causes of isolated GHD are GH1 and GHRHR defects, but several novel causes have recently been found, such as GHSR, RNPC3, and IFT172 mutations. Besides well-defined causes of GH insensitivity (GHR, STAT5B, IGFALS, IGF1 defects), disorders of NFκB signalling, STAT3 and IGF2 have recently been discovered. Heterozygous IGF1R defects are a relatively frequent cause of prenatal and postnatal growth retardation. TRHA mutations cause a syndromic form of short stature with elevated T3/T4 ratio. Disorders of signalling of various paracrine factors (FGFs, BMPs, WNTs, PTHrP/IHH, and CNP/NPR2) or genetic defects affecting cartilage extracellular matrix usually cause disproportionate short stature. Heterozygous NPR2 or SHOX defects may be found in ∼3% of short children, and also rasopathies (e.g., Noonan syndrome) can be found in children without clear syndromic appearance. Numerous other syndromes associated with short stature are caused by genetic defects in fundamental cellular processes, chromosomal abnormalities, CNVs, and imprinting disorders. PMID:26578640

  2. Increased Classical Endoplasmic Reticulum Stress Is Sufficient to Reduce Chondrocyte Proliferation Rate in the Growth Plate and Decrease Bone Growth

    PubMed Central

    Kung, Louise H. W.; Rajpar, M. Helen; Preziosi, Richard; Briggs, Michael D.; Boot-Handford, Raymond P.

    2015-01-01

    Mutations in genes encoding cartilage oligomeric matrix protein and matrilin-3 cause a spectrum of chondrodysplasias called multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH). The majority of these diseases feature classical endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) as a result of misfolding of the mutant protein. However, the importance and the pathological contribution of ER stress in the disease pathogenesis are unknown. The aim of this study was to investigate the generic role of ER stress and the UPR in the pathogenesis of these diseases. A transgenic mouse line (ColIITgcog) was generated using the collagen II promoter to drive expression of an ER stress-inducing protein (Tgcog) in chondrocytes. The skeletal and histological phenotypes of these ColIITgcog mice were characterised. The expression and intracellular retention of Tgcog induced ER stress and activated the UPR as characterised by increased BiP expression, phosphorylation of eIF2α and spliced Xbp1. ColIITgcog mice exhibited decreased long bone growth and decreased chondrocyte proliferation rate. However, there was no disruption of chondrocyte morphology or growth plate architecture and perturbations in apoptosis were not apparent. Our data demonstrate that the targeted induction of ER stress in chondrocytes was sufficient to reduce the rate of bone growth, a key clinical feature associated with MED and PSACH, in the absence of any growth plate dysplasia. This study establishes that classical ER stress is a pathogenic factor that contributes to the disease mechanism of MED and PSACH. However, not all the pathological features of MED and PSACH were recapitulated, suggesting that a combination of intra- and extra-cellular factors are likely to be responsible for the disease pathology as a whole. PMID:25693198

  3. Embryonic, Larval, and Juvenile Development of the Sea Biscuit Clypeaster subdepressus (Echinodermata: Clypeasteroida)

    PubMed Central

    Vellutini, Bruno C.; Migotto, Alvaro E.

    2010-01-01

    Sea biscuits and sand dollars diverged from other irregular echinoids approximately 55 million years ago and rapidly dispersed to oceans worldwide. A series of morphological changes were associated with the occupation of sand beds such as flattening of the body, shortening of primary spines, multiplication of podia, and retention of the lantern of Aristotle into adulthood. To investigate the developmental basis of such morphological changes we documented the ontogeny of Clypeaster subdepressus. We obtained gametes from adult specimens by KCl injection and raised the embryos at 26C. Ciliated blastulae hatched 7.5 h after sperm entry. During gastrulation the archenteron elongated continuously while ectodermal red-pigmented cells migrated synchronously to the apical plate. Pluteus larvae began to feed in 3 d and were 20 d old at metamorphosis; starved larvae died 17 d after fertilization. Postlarval juveniles had neither mouth nor anus nor plates on the aboral side, except for the remnants of larval spicules, but their bilateral symmetry became evident after the resorption of larval tissues. Ossicles of the lantern were present and organized in 5 groups. Each group had 1 tooth, 2 demipyramids, and 2 epiphyses with a rotula in between. Early appendages consisted of 15 spines, 15 podia (2 types), and 5 sphaeridia. Podial types were distributed in accordance to Lovén's rule and the first podium of each ambulacrum was not encircled by the skeleton. Seven days after metamorphosis juveniles began to feed by rasping sand grains with the lantern. Juveniles survived in laboratory cultures for 9 months and died with wide, a single open sphaeridium per ambulacrum, aboral anus, and no differentiated food grooves or petaloids. Tracking the morphogenesis of early juveniles is a necessary step to elucidate the developmental mechanisms of echinoid growth and important groundwork to clarify homologies between irregular urchins. PMID:20339592

  4. Toxic Effects of Levofloxacin on Rat Annulus Fibrosus Cells: An In-vitro Study

    PubMed Central

    Bai, Zhi-Long; Chen, Qian; Yang, Si-Dong; Zhang, Feng; Wang, Hai-Ying; Yang, Da-Long; Ding, Wen-Yuan

    2014-01-01

    Background Fluoroquinolones are in wide clinical use as safe and effective antibiotics. Articular cartilage, tendons, and epiphyseal growth plates have been recognized as targets of fluoroquinolone-induced connective tissue toxicity. However, the effects of fluoroquinolones on annulus fibrosus (AF) cells are still unknown. Material/Methods The main objective of this study was to investigate the effects of levofloxacin, a typical fluoroquinolone antibiotic drug, on rat AF cells in vitro. Rat annulus fibrosus (RAF) cells were treated with levofloxacin at different concentrations (0, 10, 20, 30, 40, 60, 80, and 90 μg/ml) and were assessed to determine the possible cytotoxic effects of levofloxacin. Inverted phase-contrast microscopy was used to accomplish the morphological observation of apoptosis of treated cells. Western blot and real-time quantitative RT-PCR (qPCR) was used to explore the expression of active caspase-3 and MMP-3. Flow cytometry was used to measure the apoptotic incidences. Results Our study showed that levofloxacin, with concentrations at 30, 60, and 90 μg/ml, induced dose-dependent RAF cell apoptosis and higher expression of caspase-3 and MMP-3. More apoptotic cells were observed by inverted phase-contrast microscopy. Moreover, levofloxacin increased the activity of caspase-3, and it also reduced cell viability with different concentrations ranging from 10 to 80 μg/ml. Conclusions Our study results suggest that levofloxacin has cytotoxic effects on RAF cells, characterized by enhancing apoptosis and reducing cell viability, and indicate a potential toxic effect of fluoroquinolones on RAF cells. PMID:25380657

  5. Syndrome disintegration: Exome sequencing reveals that Fitzsimmons syndrome is a co-occurrence of multiple events.

    PubMed

    Armour, Christine M; Smith, Amanda; Hartley, Taila; Chardon, Jodi Warman; Sawyer, Sarah; Schwartzentruber, Jeremy; Hennekam, Raoul; Majewski, Jacek; Bulman, Dennis E; Suri, Mohnish; Boycott, Kym M

    2016-07-01

    In 1987 Fitzsimmons and Guilbert described identical male twins with progressive spastic paraplegia, brachydactyly with cone shaped epiphyses, short stature, dysarthria, and "low-normal" intelligence. In subsequent years, four other patients, including one set of female identical twins, a single female child, and a single male individual were described with the same features, and the eponym Fitzsimmons syndrome was adopted (OMIM #270710). We performed exome analysis of the patient described in 2009, and one of the original twins from 1987, the only patients available from the literature. No single genetic etiology exists that explains Fitzsimmons syndrome; however, multiple different genetic causes were identified. Specifically, the twins described by Fitzsimmons had heterozygous mutations in the SACS gene, the gene responsible for autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS), as well as a heterozygous mutation in the TRPS1, the gene responsible in Trichorhinophalangeal syndrome type 1 (TRPS1 type 1) which includes brachydactyly as a feature. A TBL1XR1 mutation was identified in the patient described in 2009 as contributing to his cognitive impairment and autistic features with no genetic cause identified for his spasticity or brachydactyly. The findings show that these individuals have multiple different etiologies giving rise to a similar phenotype, and that "Fitzsimmons syndrome" is in fact not one single syndrome. Over time, we anticipate that continued careful phenotyping with concomitant genome-wide analysis will continue to identify the causes of many rare syndromes, but it will also highlight that previously delineated clinical entities are, in fact, not syndromes at all. © 2016 Wiley Periodicals, Inc. PMID:27133561

  6. Morphogenetically active scaffold for osteochondral repair (polyphosphate/alginate/N,O-carboxymethyl chitosan).

    PubMed

    Müller, W E; Neufurth, M; Wang, S; Tolba, E; Schröder, H C; Wang, X

    2016-01-01

    Here we describe a novel bioinspired hydrogel material that can be hardened with calcium ions to yield a scaffold material with viscoelastic properties matching those of cartilage. This material consists of a negatively charged biopolymer triplet, composed of morphogenetically active natural inorganic polyphosphate (polyP), along with the likewise biocompatible natural polymers N,O-carboxymethyl chitosan (N,O-CMC) and alginate. The porosity of the hardened scaffold material obtained after calcium exposure can be adjusted by varying the pre-processing conditions. Various compression tests were applied to determine the local (nanoindentation) and bulk mechanical properties (tensile/compression test system for force measurements) of the N,O-CMC-polyP-alginate material. Determinations of the Young's modulus revealed that the stiffness of this comparably water rich (and mouldable) material increases during successive compression cycles to values measured for native cartilage. The material not only comprises viscoelastic properties suitable for a cartilage substitute material, but also displays morphogenetic activity. It upregulates the expression of genes encoding for collagen type II and aggrecan, the major proteoglycan within the articular cartilage, in human chondrocytes, and the expression of alkaline phosphatase in human bone-like SaOS-2 cells, as revealed in RT qPCR experiments. Further, we demonstrate that the new polyP-based material can be applied for manufacturing 3D solid models of cartilage bone such as of the tibial epiphyseal plate and the superior articular cartilage surface. Since the material is resorbable and enhances the activity of cells involved in regeneration of cartilage tissue, this material has the potential to be used for artificial articular cartilage implants. PMID:26898843

  7. Intrapopulational body size variation and cranial capacity variation in Middle Pleistocene humans: the Sima de los Huesos sample (Sierra de Atapuerca, Spain).

    PubMed

    Lorenzo, C; Carretero, J M; Arsuaga, J L; Gracia, A; Martínez, I

    1998-05-01

    A sexual dimorphism more marked than in living humans has been claimed for European Middle Pleistocene humans, Neandertals and prehistoric modern humans. In this paper, body size and cranial capacity variation are studied in the Sima de los Huesos Middle Pleistocene sample. This is the largest sample of non-modern humans found to date from one single site, and with all skeletal elements represented. Since the techniques available to estimate the degree of sexual dimorphism in small palaeontological samples are all unsatisfactory, we have used the bootstraping method to asses the magnitude of the variation in the Sima de los Huesos sample compared to modern human intrapopulational variation. We analyze size variation without attempting to sex the specimens a priori. Anatomical regions investigated are scapular glenoid fossa; acetabulum; humeral proximal and distal epiphyses; ulnar proximal epiphysis; radial neck; proximal femur; humeral, femoral, ulnar and tibial shaft; lumbosacral joint; patella; calcaneum; and talar trochlea. In the Sima de los Huesos sample only the humeral midshaft perimeter shows an unusual high variation (only when it is expressed by the maximum ratio, not by the coefficient of variation). In spite of that the cranial capacity range at Sima de los Huesos almost spans the rest of the European and African Middle Pleistocene range. The maximum ratio is in the central part of the distribution of modern human samples. Thus, the hypothesis of a greater sexual dimorphism in Middle Pleistocene populations than in modern populations is not supported by either cranial or postcranial evidence from Sima de los Huesos. PMID:9590522

  8. Nutritional catch-up growth.

    PubMed

    Gat-Yablonski, Galia; Pando, Rakefet; Phillip, Moshe

    2013-01-01

    Malnutrition, marked by variant nutrient deficiencies, is considered a leading cause of stunted growth worldwide. In developing countries, malnutrition is caused mainly by food shortage and infectious diseases. Malnutrition may also be found in the developed world, where it is due mostly to prematurity, chronic diseases, and anorexia nervosa. In most cases, when food consumption is corrected, spontaneous catch-up (CU) growth occurs. However, CU growth is not always complete, leading to growth deficits. Therefore, it is important to understand the mechanisms that govern this process. Using a rat model of food restriction followed by refeeding, we established a nutrition-induced CU growth model. Levels of leptin and insulin-like growth factor-1 were found to significantly decrease when food was restricted and to increase already 1 day after refeeding. Gene expression analysis of the growth plate revealed that food restriction specifically affects transcription factors such as the hypoxia inducible factor-1 and its downstream targets on the one hand, and global gene expression, indicating epigenetic regulation, on the other. Food restriction also reduced the level of several microRNAs, including the chondrocyte-specific miR-140, which led to an increase in its target, SIRT1, a class III histone deacetylase. These findings may explain the global changes in gene expression observed under nutritional manipulation. We suggest that multiple levels of regulation, including transcription factors, epigenetic mechanisms, and microRNAs respond to nutritional cues and offer a possible explanation for some of the effects of food restriction on epiphyseal growth plate growth. The means whereby these components sense changes in nutritional status are still unknown. Deciphering the role of epigenetic regulation in growth may pave the way for the development of new treatments for children with growth disorders. PMID:23428685

  9. Targeted Disruption of Shp2 in Chondrocytes Leads to Metachondromatosis With Multiple Cartilaginous Protrusions

    PubMed Central

    Kim, Harry KW; Feng, Gen-Sheng; Chen, Di; King, Philip D; Kamiya, Nobuhiro

    2014-01-01

    Metachondromatosis is a benign bone disease predominantly observed in the hands and feet of children or young adults demonstrating two different manifestations: a cartilage-capped bony outgrowth on the surface of the bone called exostosis and ectopic cartilaginous nodules inside the bone called enchondroma. Recently, it has been reported that loss-of-function mutations of the SHP2 gene, which encodes the SHP2 protein tyrosine phosphatase, are associated with metachondromatosis. The purpose of this study was to investigate the role of SHP2 in postnatal cartilage development, which is largely unknown. We disrupted Shp2 during the postnatal stage of mouse development in a chondrocyte-specific manner using a tamoxifen-inducible system. We found tumor-like nodules on the hands and feet within a month after the initial induction. The SHP2-deficient mice demonstrated an exostosis-like and enchondroma-like phenotype in multiple bones of the hands, feet, and ribs as assessed by X-ray and micro-computed tomography (CT). Histological assessment revealed the disorganization of the growth plate cartilage, a cartilaginous protrusion from the epiphyseal bone, and ectopic cartilage nodules within the bones, which is consistent with the pathological features of metachondromatosis in humans (ie, both exostosis and enchondroma). At molecular levels, we observed an abundant expression of Indian hedgehog protein (IHH) and fibroblast growth factor 2 (FGF2) and impaired expression of mitogen-activated protein kinases (MAPK) in the affected cartilage nodules in the SHP2-deficient mice. In summary, we have generated a mouse model of metachondromatosis that includes manifestations of exostosis and enchondroma. This study provides a novel model for the investigation of the pathophysiology of the disease and advances the understanding of metachondromatosis. This model will be useful to identify molecular mechanisms for the disease cause and progression as well as to develop new therapeutic

  10. Ontogeny of the female femur: geometric morphometric analysis applied on current living individuals of a Spanish population.

    PubMed

    Pujol, Aniol; Rissech, Carme; Ventura, Jacint; Badosa, Joaquim; Turbón, Daniel

    2014-09-01

    In this study we describe the development of the female femur based on the analysis of high-resolution radiographic images by means of geometric morphometrics, while assessing the usefulness of this method in these kinds of studies. The material analysed consisted of digital images in DICOM format (telemetries), corresponding to 184 left femora in anterior view, obtained from the database of the Hospital Sant Joan de Déu of Barcelona (Spain). Bones analysed corresponded to individuals from 9 to 14 years old. Size and shape variation of the entire femur was quantified by 22 two-dimensional landmarks. Landmark digitisation errors were assessed using Procrustes anova test. Centroid size (CS) variation with age was evaluated by an anova test. Shape variation was assessed by principal component analysis. A mancova test between the first five principal components and age, using the CS as covariable, was applied. Results indicated that both size and shape vary significantly with age. Several age-related shape changes remained significant after removing the allometric effect. In general, an increase in the robustness of the bone and noticeable phenotypic changes in certain areas of the femur were observed. During growth in the proximal region of the femur, the collo-diaphyseal angle decreases, the neck of the femur widens and the fovea moves to a lower position, standing more in line with the plane of the neck. Likewise, the size of the greater and lesser trochanters increase. In the distal region, a significant increase of epiphyseal dimensions was recorded, mainly in the medial condyle. The angular remodelling of the neck and the bicondylar region of the femur in females continues until 13 years old. The information provided in the present study increases our knowledge on the timing and morphology of the femur during development, and in particular the morphology of the different femoral ossification centres during development. PMID:24975495

  11. Capturing fast relaxing spins with SWIFT adiabatic rotating frame spin-lattice relaxation (T1ρ ) mapping.

    PubMed

    Zhang, J; Nissi, M J; Idiyatullin, D; Michaeli, S; Garwood, M; Ellermann, J

    2016-04-01

    Rotating frame spin-lattice relaxation, with the characteristic time constant T1ρ , provides a means to access motion-restricted (slow) spin dynamics in MRI. As a result of their restricted motion, these spins are sometimes characterized by a short transverse relaxation time constant T2 and thus can be difficult to detect directly with conventional image acquisition techniques. Here, we introduce an approach for three-dimensional adiabatic T1ρ mapping based on a magnetization-prepared sweep imaging with Fourier transformation (MP-SWIFT) sequence, which captures signal from almost all water spin populations, including the extremely fast relaxing pool. A semi-analytical procedure for T1ρ mapping is described. Experiments on phantoms and musculoskeletal tissue specimens (tendon, articular and epiphyseal cartilages) were performed at 9.4 T for both the MP-SWIFT and fast spin echo (FSE) read outs. In the phantom with liquids having fast molecular tumbling and a single-valued T1ρ time constant, the measured T1ρ values obtained with MP-SWIFT and FSE were similar. Conversely, in normal musculoskeletal tissues, T1ρ values measured with MP-SWIFT were much shorter than the values obtained with FSE. Studies of biological tissue specimens demonstrated that T1ρ -weighted SWIFT provides higher contrast between normal and diseased tissues relative to conventional acquisitions. Adiabatic T1ρ mapping with SWIFT readout captures contributions from the otherwise undetected fast relaxing spins, allowing more informative T1ρ measurements of normal and diseased states. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26811973

  12. Indications of that migration of stem cells is influenced by the extra cellular matrix architecture in the mammalian intervertebral disk region.

    PubMed

    Henriksson, H Barreto; Papadimitriou, N; Tschernitz, S; Svala, E; Skioldebrand, E; Windahl, S; Junevik, K; Brisby, H

    2015-10-01

    Disk-degeneration is believed a major cause for lumbar pain. Previously, potential stem cell niches in the intervertebral disk (IVD) region, located adjacent to epiphyseal plate, was reported. The aim of the study was to examine migration of mesenchymal stem cells (MSCs), extracellular matrix (ECM) architecture in a potential cellular migration route (CMR; area located between the niche and IVD) and in the IVD in non-degenerated lapine- and in human degenerated IVD tissues. Human MSCs (n=3), human degenerated IVD tissues (n=10) and lapine IVDs (n=10) were collected. The samples were examined by immunohistochemistry for stem cell markers; CD90, OCT3/4, pre-chondrocytic marker; GDF5, catabolic markers; MMP9, MMP13, inflammatory marker; IL1R, cellular migration markers; SNAI1, SNAI2, adhesion markers; β1-INTEGRIN and DDR2. In addition, gene-expression analyses (Real time PCR) were performed on additional samples. Further, time lapse studies were performed with hMSCs cultured on aligned COLL-I-fibers-coated glass-slides in DMEM-LG, 10% human serum containing fibroblast growth factor (bFGF). Presence of stem cells (CD90+, OCT3/4+), pre-chondocytic cells (GDF5+) and cells positive for migration markers (SNAI1+, SNAI2+), catabolic markers (MMP9+, MMP13+), inflammatory marker (IL1R+), adhesion markers (DDR2+, B1-INTEGRIN+) were detected (gene- and protein level) in investigated CMR and IVD regions. In the time lapse studies, MSCs alignment and protrusions were observed orientated in the same direction as collagen fibers. Results display influence of ECM collagen architecture and collagen fiber spatial direction on migration of stem cells. The results can be useful when developing tissue-engineering strategies for disk-degeneration. PMID:26337726

  13. Androgen-dependent somatotroph function in a hypogonadal adolescent male: evidence for control of exogenous androgens on growth hormone release

    SciTech Connect

    Mauras, N.; Blizzard, R.M.; Rogol, A.D.

    1989-03-01

    A 14(10/12)-year-old white male with primary gonadal failure following testicular irradiation for acute lymphocytic leukemia was evaluated for poor growth. He had received 2400 rad of prophylactic cranial irradiation. The growth velocity had decelerated from 7 to 3.2 cm/yr over 3 years. His bone age was 12(0/12) years (by TW2-RUS), and his peak growth hormone (GH) response to provocative stimuli was 1.4 ng/mL. The 24-hour GH secretion was studied by drawing blood every 20 minutes for 24 hours. The resulting GH profile was analyzed by a computerized pulse detection algorithm, CLUSTER. Timed serum GH samples were also obtained after a 1 microgram/kg IV bolus injection of the GH releasing factor (GRH). The studies showed a flat 24-hour profile and a peak GH response to GRH of 3.9 ng/ml. Testosterone enanthate treatment was started, 100 mg IM every 4 weeks. Ten months after the initiation of therapy the calculated growth rate was 8.6 cm/yr. The 24-hour GH study and GRH responses were repeated at the time, showing a remarkably normal 24-hour GH secretory pattern and a peak GH response to GRH of 14.4 ng/mL. Testosterone therapy was discontinued, and 4 months later similar studies were repeated. A marked decrease in the mean 24-hour GH secretion and mean peak height occurred, but with maintenance of the GH pulse frequency. The GH response to GRH was intermediate, with a peak of 8 ng/mL. There was no further growth during those 4 months despite open epiphyses.

  14. Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat

    SciTech Connect

    Cocchi, Daniela; Tulipano, Giovanni; Colciago, Alessandra; Sibilia, Valeria; Pagani, Francesca; Vigano, Daniela; Rubino, Tiziana; Parolaro, Daniela; Bonfanti, Patrizia; Colombo, Anita; Celotti, Fabio

    2009-06-01

    Polychlorinated biphenyls (PCBs) are pollutants detected in animal tissues and breast milk. The experiments described in the present paper were aimed at evaluating whether the four PCB congeners most abundant in animal tissues (PCB-138, -153, -180 and -126), administered since fetal life till weaning, can induce long-term alterations of GH-axis activity and bone mass in the adult rat. We measured PCB accumulation in rat brain and liver, somatic growth, pituitary GH expression and plasma hormone concentrations at different ages. Finally, we studied hypothalamic somatostatin expression and bone structure in adulthood, following long-term PCB exposure. Dams were treated during pregnancy from GD15 to GD19 and during breast-feeding. A constant reduction of the growth rate in both male and female offspring from weaning to adulthood was observed in exposed animals. Long-lasting alterations on hypothalamic-pituitary GH axis were indeed observed in PCB-exposed rats in adulthood: increased somatostatin expression in hypothalamic periventricular nucleus (both males and females) and lateral arcuate nucleus (males, only) and decreased GH mRNA levels in the pituitary of male rats. Plasma IGF-1 levels were higher in PCB-exposed male and female animals as compared with controls at weaning and tended to be higher at PN60. Plasma testosterone and thyroid hormone concentrations were not significantly affected by exposure to PCBs. In adulthood, PCBs caused a significant reduction of bone mineral content and cortical bone thickness of tibiae in male rat joint to increased width of the epiphyseal cartilage disk. In conclusion, the developmental exposure to the four selected PCB compounds used in the present study induced far-reaching effects in the adult offspring, the male rats appearing more sensitive than females.

  15. The lameness of King Philip II and Royal Tomb I at Vergina, Macedonia.

    PubMed

    Bartsiokas, Antonis; Arsuaga, Juan-Luis; Santos, Elena; Algaba, Milagros; Gómez-Olivencia, Asier

    2015-08-11

    King Philip II was the father of Alexander the Great. He suffered a notorious penetrating wound by a lance through his leg that was nearly fatal and left him lame in 339 B.C.E. (i.e., 3 y before his assassination in 336 B.C.E.). In 1977 and 1978 two male skeletons were excavated in the Royal Tombs II and I of Vergina, Greece, respectively. Tomb I also contained another adult (likely a female) and a newborn skeleton. The current view is that Philip II was buried in Tomb II. However, the male skeleton of Tomb II bears no lesions to his legs that would indicate lameness. We investigated the skeletal material of Tomb I with modern forensic techniques. The male individual in Tomb I displays a conspicuous case of knee ankylosis that is conclusive evidence of lameness. Right through the overgrowth of the knee, there is a hole. There are no obvious signs that are characteristic of infection and osteomyelitis. This evidence indicates that the injury was likely caused by a severe penetrating wound to the knee, which resulted in an active inflammatory process that stopped years before death. Standard anthropological age-estimation techniques based on dry bone, epiphyseal lines, and tooth analysis gave very wide age ranges for the male, centered around 45 y. The female would be around 18-y-old and the infant would be a newborn. It is concluded that King Philip II, his wife Cleopatra, and their newborn child are the occupants of Tomb I. PMID:26195763

  16. A diastrophic dysplasia sulfate transporter (SLC26A2) mutant mouse: morphological and biochemical characterization of the resulting chondrodysplasia phenotype.

    PubMed

    Forlino, Antonella; Piazza, Rocco; Tiveron, Cecilia; Della Torre, Sara; Tatangelo, Laura; Bonafè, Luisa; Gualeni, Benedetta; Romano, Assunta; Pecora, Fabio; Superti-Furga, Andrea; Cetta, Giuseppe; Rossi, Antonio

    2005-03-15

    Mutations in the diastrophic dysplasia sulfate transporter (DTDST or SLC26A2) cause a family of recessively inherited chondrodysplasias including, in order of decreasing severity, achondrogenesis 1B, atelosteogenesis 2, diastrophic dysplasia (DTD) and recessive multiple epiphyseal dysplasia. The gene encodes a widely distributed sulfate/chloride antiporter of the cell membrane whose function is crucial for the uptake of inorganic sulfate, which is needed for proteoglycan sulfation. To provide new insights in the pathogenetic mechanisms leading to skeletal and connective tissue dysplasia and to obtain an in vivo model for therapeutic approaches to DTD, we generated a Dtdst knock-in mouse with a partial loss of function of the sulfate transporter. In addition, the intronic neomycine cassette in the mutant allele contributed to the hypomorphic phenotype by inducing abnormal splicing. Homozygous mutant mice were characterized by growth retardation, skeletal dysplasia and joint contractures, thereby recapitulating essential aspects of the DTD phenotype in man. The skeletal phenotype included reduced toluidine blue staining of cartilage, chondrocytes of irregular size, delay in the formation of the secondary ossification center and osteoporosis of long bones. Impaired sulfate uptake was demonstrated in chondrocytes, osteoblasts and fibroblasts. In spite of the generalized nature of the sulfate uptake defect, significant proteoglycan undersulfation was detected only in cartilage. Chondrocyte proliferation and apoptosis studies suggested that reduced proliferation and/or lack of terminal chondrocyte differentiation might contribute to reduced bone growth. The similarity with human DTD makes this mouse strain a useful model to explore pathogenetic and therapeutic aspects of DTDST-related disorders. PMID:15703192

  17. Sulphate in pregnancy.

    PubMed

    Dawson, Paul A; Elliott, Aoife; Bowling, Francis G

    2015-03-01

    Sulphate is an obligate nutrient for healthy growth and development. Sulphate conjugation (sulphonation) of proteoglycans maintains the structure and function of tissues. Sulphonation also regulates the bioactivity of steroids, thyroid hormone, bile acids, catecholamines and cholecystokinin, and detoxifies certain xenobiotics and pharmacological drugs. In adults and children, sulphate is obtained from the diet and from the intracellular metabolism of sulphur-containing amino acids. Dietary sulphate intake can vary greatly and is dependent on the type of food consumed and source of drinking water. Once ingested, sulphate is absorbed into circulation where its level is maintained at approximately 300 μmol/L, making sulphate the fourth most abundant anion in plasma. In pregnant women, circulating sulphate concentrations increase by twofold with levels peaking in late gestation. This increased sulphataemia, which is mediated by up-regulation of sulphate reabsorption in the maternal kidneys, provides a reservoir of sulphate to meet the gestational needs of the developing foetus. The foetus has negligible capacity to generate sulphate and thereby, is completely reliant on sulphate supply from the maternal circulation. Maternal hyposulphataemia leads to foetal sulphate deficiency and late gestational foetal death in mice. In humans, reduced sulphonation capacity has been linked to skeletal dysplasias, ranging from the mildest form, multiple epiphyseal dysplasia, to achondrogenesis Type IB, which results in severe skeletal underdevelopment and death in utero or shortly after birth. Despite being essential for numerous cellular and metabolic functions, the nutrient sulphate is largely unappreciated in clinical settings. This article will review the physiological roles and regulation of sulphate during pregnancy, with a particular focus on animal models of disturbed sulphate homeostasis and links to human pathophysiology. PMID:25746011

  18. Undersulfation of cartilage proteoglycans ex vivo and increased contribution of amino acid sulfur to sulfation in vitro in McAlister dysplasia/atelosteogenesis type 2.

    PubMed

    Rossi, A; Bonaventure, J; Delezoide, A L; Superti-Furga, A; Cetta, G

    1997-09-15

    Mutations in the diastrophic dysplasia sulfate transporter gene cause a family of chondrodysplasias including, in order of increasing severity, diastrophic dysplasia, atelosteogenesis type 2 and achondrogenesis type 1B. McAlister dysplasia is a lethal chondrodysplasia considered on the basis of minor radiographic features to be a disorder different from atelosteogenesis type 2. Here, we demonstrate that McAlister dysplasia arises from mutations in the diastrophic dysplasia sulfate transporter gene and that this disorder essentially coincides on molecular and biochemical grounds with atelosteogenesis type 2. The fetus affected by McAlister dysplasia we have studied is a compound heterozygote for mutations leading to R279W and N425D substitutions in the diastrophic dysplasia sulfate transporter. Proteoglycan sulfation was studied in epiphyseal cartilage and in chondrocyte cultures of the patient by high performance liquid chromatography of chondrotinase digested proteoglycans; a high amount of non-sulfated disaccharide was observed as a consequence of the alteration of the transporter function caused by the mutations. However, sulfated disaccharides were detectable even if in low amounts, both in cultured cells and tissue. Functional impairment of the sulfate transporter was demonstrated in vitro by reduced incorporation of [35S]sulfate relative to [3H]glucosamine in proteoglycans synthesized by chondrocytes and by sulfate-uptake assays in fibroblasts. Parallel in vitro studies in a patient with achondrogenesis 1B indicated that the severity of the clinical phenotype seems to be correlated to the residual activity of the sulfate transporter. The capacity of fibroblasts to use cysteine as an alternative source of sulfate was evaluated by double-labeling experiments. Relative incorporation of [35S]cysteine-derived sulfate in the glycosaminoglycan chains was increased in the patient's cells, indicating that, in vitro, the catabolism of sulfur-containing amino acids can

  19. Sulphate in Pregnancy

    PubMed Central

    Dawson, Paul A.; Elliott, Aoife; Bowling, Francis G.

    2015-01-01

    Sulphate is an obligate nutrient for healthy growth and development. Sulphate conjugation (sulphonation) of proteoglycans maintains the structure and function of tissues. Sulphonation also regulates the bioactivity of steroids, thyroid hormone, bile acids, catecholamines and cholecystokinin, and detoxifies certain xenobiotics and pharmacological drugs. In adults and children, sulphate is obtained from the diet and from the intracellular metabolism of sulphur-containing amino acids. Dietary sulphate intake can vary greatly and is dependent on the type of food consumed and source of drinking water. Once ingested, sulphate is absorbed into circulation where its level is maintained at approximately 300 μmol/L, making sulphate the fourth most abundant anion in plasma. In pregnant women, circulating sulphate concentrations increase by twofold with levels peaking in late gestation. This increased sulphataemia, which is mediated by up-regulation of sulphate reabsorption in the maternal kidneys, provides a reservoir of sulphate to meet the gestational needs of the developing foetus. The foetus has negligible capacity to generate sulphate and thereby, is completely reliant on sulphate supply from the maternal circulation. Maternal hyposulphataemia leads to foetal sulphate deficiency and late gestational foetal death in mice. In humans, reduced sulphonation capacity has been linked to skeletal dysplasias, ranging from the mildest form, multiple epiphyseal dysplasia, to achondrogenesis Type IB, which results in severe skeletal underdevelopment and death in utero or shortly after birth. Despite being essential for numerous cellular and metabolic functions, the nutrient sulphate is largely unappreciated in clinical settings. This article will review the physiological roles and regulation of sulphate during pregnancy, with a particular focus on animal models of disturbed sulphate homeostasis and links to human pathophysiology. PMID:25746011

  20. Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene: correlation between sulfate transport activity and chondrodysplasia phenotype.

    PubMed

    Karniski, L P

    2001-07-01

    The diastrophic dysplasia sulfate transporter (DTDST) gene encodes a transmembrane protein that transports sulfate into chondrocytes to maintain adequate sulfation of proteoglycans. Mutations in this gene are responsible for four recessively inherited chondrodysplasias that include diastrophic dysplasia, multiple epiphyseal dysplasia, atelosteogenesis type 2 and achondrogenesis 1B (ACG-1B). To determine whether the DTDST mutations found in individuals with these chondrodysplasias differ functionally from each other, we compared the sulfate transport activity of 11 reported DTDST mutations. Five mutations, G255E, Delta a1751, L483P, R178X and N425D, had minimal sulfate transport function following expression in Xenopus laevis oocytes. Two mutations, Delta V340 and R279W, transported sulfate at rates of 17 and 32%, respectively, of wild-type DTDST. Four mutations, A715V, C653S, Q454P and G678V, had rates of sulfate transport nearly equal to that of wild-type DTDST. Transport kinetics were not different among the four mutations with near-normal sulfate transport function and wild-type DTDST. When the sulfate transport function of the different DTDST mutations are grouped according to the general phenotypes, individuals with the most severe form, ACG-1B, tend to be homozygous for null mutations, individuals with the moderately severe atelosteogenesis type 2 have at least one allele with a loss-of-function mutation, and individuals with the mildest forms are typically homozygous for mutations with residual sulfate transport function. However, in the X.laevis oocyte expression system, the correlation between residual transport function and the severity of phenotype was not absolute, suggesting that factors in addition to the intrinsic sulfate transport properties of the DTDST protein may influence the phenotype in individuals with DTDST mutations. PMID:11448940

  1. Functional expression and cellular distribution of diastrophic dysplasia sulfate transporter (DTDST) gene mutations in HEK cells.

    PubMed

    Karniski, Lawrence P

    2004-10-01

    Defects in sulfate transport in chondrocytes lead to undersulfation of the cartilage extracellular matrix proteoglycans. Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene have been linked to four chondrodysplasias of varying severity. To characterize disease-causing mutations of DTDST, we expressed DTDST-mediated sulfate transport in mammalian HEK-293 cells and determined that the wild-type protein is glycosylated and localized to the cell plasma membrane. Four mutations, A715V, C653S, Q454P and R279W, stimulated sulfate transport at rates only 39-62% of wild-type DTDST. These four mutations were expressed on the plasma membrane of the cell, but the amount of expressed protein was reduced when compared with wild-type DTDST. The Q454P mutant is unique in that it is not properly glycosylated in HEK cells. There was no difference in sulfate transport activity between cells transfected with either the DeltaV340 or the G678V mutations and control HEK cells. Furthermore, the G678V mutation is not expressed along the plasma membrane, but is trapped within the cytoplasm. When comparing the sulfate transport capacity of each DTDST mutation with the chondrodysplasia in which it has been identified, we find that individuals with severe achondrogenesis 1B phenotype have null mutations on both DTDST alleles. Heterozygotes for both a null mutation and a partial-function mutation result in either atelosteogenesis type 2 or DTD, whereas the milder, recessive multiple epiphyseal dysplasia phenotype is homozygous for partial-function mutations. In contrast to previous studies in Xenopus laevis oocytes, we find a strong correlation between the severity of the phenotype and the level of residual transport function in mammalian cells. PMID:15294877

  2. Mycoplasma corogypsi associated polyarthritis and tenosynovitis in black vultures (Coragyps atratus)

    PubMed Central

    Van Wettere, A. J.; Ley, D. H.; Scott, D. E.; Buckanoff, H. D.; Degernes, L. A.

    2013-01-01

    Three wild American black vultures (Coragyps atratus) were presented to rehabilitation centers with swelling of multiple joints, including elbows, stifles, hocks, and carpal joints, and of the gastrocnemius tendons. Cytological examination of the joint fluid exudate indicated heterophilic arthritis. Radiographic examination in 2 vultures demonstrated periarticular soft tissue swelling in both birds and irregular articular surfaces with subchondral bone erosion in both elbows in 1 bird. Prolonged antibiotic therapy administered in 2 birds did not improve the clinical signs. Necropsy and histological examination demonstrated a chronic lymphoplasmacytic arthritis involving multiple joints and gastrocnemius tenosynovitis. Articular lesions varied in severity and ranged from moderate synovitis and cartilage erosion and fibrillation to severe synovitis, diffuse cartilage ulceration, subchondral bone loss and/or sclerosis, pannus, synovial cysts, and epiphyseal osteomyelitis. No walled bacteria were observed or isolated from the joints. However, mycoplasmas polymerase chain reactions were positive in at least 1 affected joint from each bird. Mycoplasmas were isolated from joints of 1 vulture that did not receive antibiotic therapy. Sequencing of 16S rRNA gene amplicons from joint samples and the mycoplasma isolate identified Mycoplasma corogypsi in 2 vultures and was suggestive in the third vulture. Mycoplasma corogypsi identification was confirmed by sequencing the 16S-23S intergenic spacer region of mycoplasma isolates. This report provides further evidence that M. corogypsi is a likely cause of arthritis and tenosynovitis in American black vultures. Cases of arthritis and tenosynovitis in New World vultures should be investigated for presence of Mycoplasma spp, especially M. corogypsi. PMID:22903399

  3. A novel mutation in the sulfate transporter gene SLC26A2 (DTDST) specific to the Finnish population causes de la Chapelle dysplasia

    PubMed Central

    Bonafé, L; Hästbacka, J; de la Chapelle, A; Campos-Xavier, A B; Chiesa, C; Forlino, A; Superti-Furga, A; Rossi, A

    2015-01-01

    Background Mutations in the sulfate transporter gene SLC26A2 (DTDST) cause a continuum of skeletal dysplasia phenotypes that includes achondrogenesis type 1B (ACG1B), atelosteogenesis type 2 (AO2), diastrophic dysplasia (DTD), and recessive multiple epiphyseal dysplasia (rMED). In 1972, de la Chapelle et al reported two siblings with a lethal skeletal dysplasia, which was denoted “neonatal osseous dysplasia” and “de la Chapelle dysplasia” (DLCD). It was suggested that DLCD might be part of the SLC26A2 spectrum of phenotypes, both because of the Finnish origin of the original family and of radiographic similarities to ACG1B and AO2. Objective To test the hypothesis whether SLC26A2 mutations are responsible for DLCD. Methods We studied the DNA from the original DLCD family and from seven Finnish DTD patients in whom we had identified only one copy of IVS1+2T>C, the common Finnish mutation. A novel SLC26A2 mutation was found in all subjects, inserted by site-directed mutagenesis in a vector harbouring the SLC26A2 cDNA, and expressed in sulfate transport deficient Chinese hamster ovary (CHO) cells to measure sulfate uptake activity. Results We identified a hitherto undescribed SLC26A2 mutation, T512K, homozygous in the affected subjects and heterozygous in both parents and in the unaffected sister. T512K was then identified as second pathogenic allele in the seven Finnish DTD subjects. Expression studies confirmed pathogenicity. Conclusions DLCD is indeed allelic to the other SLC26A2 disorders. T512K is a second rare “Finnish” mutation that results in DLCD at homozygosity and in DTD when compounded with the milder, common Finnish mutation. PMID:18708426

  4. Manipulation of Ovarian Function Significantly Influenced Trabecular and Cortical Bone Volume, Architecture and Density in Mice at Death

    PubMed Central

    Mason, Jeffrey B.; Terry, Boston C.; Merchant, Samer S.; Mason, Holly M.; Nazokkarmaher, Mahdi

    2015-01-01

    Previously, transplantation of ovaries from young, cycling mice into old, postreproductive-age mice increased life span and decreased cardiomyopathy at death. We anticipated that the same factors that increased life span and decreased cardiomyopathy could also influence the progression of orthopedic disease. At 11 months of age, prepubertally ovariectomized and ovary-intact mice (including reproductively cycling and acyclic mice) received new 60-day-old ovaries. At death, epiphyseal bone in the proximal tibia and the distal femur and mid-shaft tibial and femoral diaphyseal bone was analyzed with micro-computed tomography. For qualitative analysis of osteophytosis, we also included mineralized connective tissue within the stifle joint. Prepubertal ovariectomy had the greatest influence on bone volume, ovarian transplantation had the greatest influence on bone architecture and both treatments influenced bone density. Ovarian transplantation increased cortical, but not trabecular bone density and tended to increase osteophytosis and heterotopic mineralization, except in acyclic recipients. These effects may have been dictated by the timing of the treatments, with ovariectomy appearing to influence early development and ovarian transplantation limited to influencing only the postreproductive period. However, major differences observed between cycling, acyclic and ovariectomized recipients of new ovaries may have been, in part due to differences in the levels of hormone receptors present and the responsiveness of specific bone processes to hormone signaling. Changes that resulted from these treatments may represent a compensatory response to normal age-associated, negative, orthopedic changes. Alternatively, differences between treatments may simply be the 'preservation' of unblemished orthopedic conditions, prior to the influence of negative, age-associated effects. These findings may suggest that in women, tailoring hormone replacement therapy to the patient's current

  5. Exome Sequencing Identifies PDE4D Mutations as Another Cause of Acrodysostosis

    PubMed Central

    Michot, Caroline; Le Goff, Carine; Goldenberg, Alice; Abhyankar, Avinash; Klein, Céline; Kinning, Esther; Guerrot, Anne-Marie; Flahaut, Philippe; Duncombe, Alice; Baujat, Genevieve; Lyonnet, Stanislas; Thalassinos, Caroline; Nitschke, Patrick; Casanova, Jean-Laurent; Le Merrer, Martine; Munnich, Arnold; Cormier-Daire, Valérie

    2012-01-01

    Acrodysostosis is a rare autosomal-dominant condition characterized by facial dysostosis, severe brachydactyly with cone-shaped epiphyses, and short stature. Moderate intellectual disability and resistance to multiple hormones might also be present. Recently, a recurrent mutation (c.1102C>T [p.Arg368∗]) in PRKAR1A has been identified in three individuals with acrodysostosis and resistance to multiple hormones. After studying ten unrelated acrodysostosis cases, we report here de novo PRKAR1A mutations in five out of the ten individuals (we found c.1102C>T [p.Arg368∗] in four of the ten and c.1117T>C [p.Tyr373His] in one of the ten). We performed exome sequencing in two of the five remaining individuals and selected phosphodiesterase 4D (PDE4D) as a candidate gene. PDE4D encodes a class IV cyclic AMP (cAMP)-specific phosphodiesterase that regulates cAMP concentration. Exome analysis detected heterozygous PDE4D mutations (c.673C>A [p.Pro225Thr] and c.677T>C [p.Phe226Ser]) in these two individuals. Screening of PDE4D identified heterozygous mutations (c.568T>G [p.Ser190Ala] and c.1759A>C [p.Thr587Pro]) in two additional acrodysostosis cases. These mutations occurred de novo in all four cases. The four individuals with PDE4D mutations shared common clinical features, namely characteristic midface and nasal hypoplasia and moderate intellectual disability. Metabolic screening was normal in three of these four individuals. However, resistance to parathyroid hormone and thyrotropin was consistently observed in the five cases with PRKAR1A mutations. Finally, our study further supports the key role of the cAMP signaling pathway in skeletogenesis. PMID:22464250

  6. Developmental dysplasia of the hip in the newborn: A systematic review

    PubMed Central

    Gulati, Vivek; Eseonu, Kelechi; Sayani, Junaid; Ismail, Nizar; Uzoigwe, Chika; Choudhury, Muhammed Zaki; Gulati, Pooja; Aqil, Adeel; Tibrewal, Saket

    2013-01-01

    Developmental dysplasia of the hip (DDH) denotes a wide spectrum of conditions ranging from subtle acetabular dysplasia to irreducible hip dislocations. Clinical diagnostic tests complement ultrasound imaging in allowing diagnosis, classification and monitoring of this condition. Classification systems relate to the alpha and beta angles in addition to the dynamic coverage index (DCI). Screening programmes for DDH show considerable geographic variation; certain risk factors have been identified which necessitate ultrasound assessment of the newborn. The treatment of DDH has undergone significant evolution, but the current gold standard is still the Pavlik harness. Duration of Pavlik harness treatment has been reported to range from 3 to 9.3 mo. The beta angle, DCI and the superior/lateral femoral head displacement can be assessed via ultrasound to estimate the likelihood of success. Success rates of between 7% and 99% have been reported when using the harness to treat DDH. Avascular necrosis remains the most devastating complication of harness usage with a reported rate of between 0% and 28%. Alternative non-surgical treatment methods used for DDH include devices proposed by LeDamany, Frejka, Lorenz and Ortolani. The Rosen splint and Wagner stocking have also been used for DDH treatment. Surgical treatment for DDH comprises open reduction alongside a combination of femoral or pelvic osteotomies. Femoral osteotomies are carried out in cases of excessive anteversion or valgus deformity of the femoral neck. The two principal pelvic osteotomies most commonly performed are the Salter osteotomy and Pemberton acetabuloplasty. Serious surgical complications include epiphyseal damage, sciatic nerve damage and femoral neck fracture. PMID:23610749

  7. [Treatment of unstable fractures of the proximal end of the humerus using elastic curved intramedullary wires].

    PubMed

    Zifko, B; Zifko, B; Poigenfürst, J

    1987-04-01

    At the Accident Hospital Lorenz Böhler and the Accident Hospital Meidling in Vienna, 48 patients with proximal humeral fractures were treated by closed reduction, intramedullary fixation with elastic pins and immobilization for two weeks in a Velpeau type stockinette (Gilchrist) between February 1985 and February 1986. The pins have a diameter of 2 mm. At there lower end there is a 20 mm long elastic curve which is ment to anker the pin in the entry hole to the intramedullary cavity, preventing sliding out of the implant. At the upper end the last 20 mm of the wire are angulated for 15 degrees. AO-classification was used. 39 patients had surgical neck-fractures. There were 34 displaced fractures (AO-type A 2/2), six dislocation- and more segment fractures and three epiphyseal separations of the adductiontype. The functional results of 36 patients were evaluated according to Neer's table. 29 patients had more than 80 points, four patients had more than 70 points and three had poor results. Reason for poor results was in one case a fracture with dislocation of the greater tuberosity which should have been treated by open reduction and the age in a 82 year old patient, who had a poor functional result after twelve weeks of treatment despite good fracture healing. There were no problems with wound healing, infections, myositis ossificans or Sudeck disease. Closed reductions of unstable surgical neck fractures and intramedullary fixation causes least damage to the soft tissues of the shoulder, leading to early good functional results. PMID:3603877

  8. Recent origin of low trabecular bone density in modern humans.

    PubMed

    Chirchir, Habiba; Kivell, Tracy L; Ruff, Christopher B; Hublin, Jean-Jacques; Carlson, Kristian J; Zipfel, Bernhard; Richmond, Brian G

    2015-01-13

    Humans are unique, compared with our closest living relatives (chimpanzees) and early fossil hominins, in having an enlarged body size and lower limb joint surfaces in combination with a relatively gracile skeleton (i.e., lower bone mass for our body size). Some analyses have observed that in at least a few anatomical regions modern humans today appear to have relatively low trabecular density, but little is known about how that density varies throughout the human skeleton and across species or how and when the present trabecular patterns emerged over the course of human evolution. Here, we test the hypotheses that (i) recent modern humans have low trabecular density throughout the upper and lower limbs compared with other primate taxa and (ii) the reduction in trabecular density first occurred in early Homo erectus, consistent with the shift toward a modern human locomotor anatomy, or more recently in concert with diaphyseal gracilization in Holocene humans. We used peripheral quantitative CT and microtomography to measure trabecular bone of limb epiphyses (long bone articular ends) in modern humans and chimpanzees and in fossil hominins attributed to Australopithecus africanus, Paranthropus robustus/early Homo from Swartkrans, Homo neanderthalensis, and early Homo sapiens. Results show that only recent modern humans have low trabecular density throughout the limb joints. Extinct hominins, including pre-Holocene Homo sapiens, retain the high levels seen in nonhuman primates. Thus, the low trabecular density of the recent modern human skeleton evolved late in our evolutionary history, potentially resulting from increased sedentism and reliance on technological and cultural innovations. PMID:25535354

  9. Recent origin of low trabecular bone density in modern humans

    PubMed Central

    Chirchir, Habiba; Kivell, Tracy L.; Ruff, Christopher B.; Hublin, Jean-Jacques; Carlson, Kristian J.; Zipfel, Bernhard; Richmond, Brian G.

    2015-01-01

    Humans are unique, compared with our closest living relatives (chimpanzees) and early fossil hominins, in having an enlarged body size and lower limb joint surfaces in combination with a relatively gracile skeleton (i.e., lower bone mass for our body size). Some analyses have observed that in at least a few anatomical regions modern humans today appear to have relatively low trabecular density, but little is known about how that density varies throughout the human skeleton and across species or how and when the present trabecular patterns emerged over the course of human evolution. Here, we test the hypotheses that (i) recent modern humans have low trabecular density throughout the upper and lower limbs compared with other primate taxa and (ii) the reduction in trabecular density first occurred in early Homo erectus, consistent with the shift toward a modern human locomotor anatomy, or more recently in concert with diaphyseal gracilization in Holocene humans. We used peripheral quantitative CT and microtomography to measure trabecular bone of limb epiphyses (long bone articular ends) in modern humans and chimpanzees and in fossil hominins attributed to Australopithecus africanus, Paranthropus robustus/early Homo from Swartkrans, Homo neanderthalensis, and early Homo sapiens. Results show that only recent modern humans have low trabecular density throughout the limb joints. Extinct hominins, including pre-Holocene Homo sapiens, retain the high levels seen in nonhuman primates. Thus, the low trabecular density of the recent modern human skeleton evolved late in our evolutionary history, potentially resulting from increased sedentism and reliance on technological and cultural innovations. PMID:25535354

  10. Perichondrium phenotype and border function are regulated by Ext1 and heparan sulfate in developing long bones: a mechanism likely deranged in Hereditary Multiple Exostoses.

    PubMed

    Huegel, Julianne; Mundy, Christina; Sgariglia, Federica; Nygren, Patrik; Billings, Paul C; Yamaguchi, Yu; Koyama, Eiki; Pacifici, Maurizio

    2013-05-01

    During limb skeletogenesis the cartilaginous long bone anlagen and their growth plates become delimited by perichondrium with which they interact functionally. Yet, little is known about how, despite being so intimately associated with cartilage, perichondrium acquires and maintains its distinct phenotype and exerts its border function. Because perichondrium becomes deranged and interrupted by cartilaginous outgrowths in Hereditary Multiple Exostoses (HME), a pediatric disorder caused by EXT mutations and consequent heparan sulfate (HS) deficiency, we asked whether EXT genes and HS normally have roles in establishing its phenotype and function. Indeed, conditional Ext1 ablation in perichondrium and lateral chondrocytes flanking the epiphyseal region of mouse embryo long bone anlagen - a region encompassing the groove of Ranvier - caused ectopic cartilage formation. A similar response was observed when HS function was disrupted in long bone anlagen explants by genetic, pharmacological or enzymatic means, a response preceded by ectopic BMP signaling within perichondrium. These treatments also triggered excess chondrogenesis and cartilage nodule formation and overexpression of chondrogenic and matrix genes in limb bud mesenchymal cells in micromass culture. Interestingly, the treatments disrupted the peripheral definition and border of the cartilage nodules in such a way that many nodules overgrew and fused with each other into large amorphous cartilaginous masses. Interference with HS function reduced the physical association and interactions of BMP2 with HS and increased the cell responsiveness to endogenous and exogenous BMP proteins. In sum, Ext genes and HS are needed to establish and maintain perichondrium's phenotype and border function, restrain pro-chondrogenic signaling proteins including BMPs, and restrict chondrogenesis. Alterations in these mechanisms may contribute to exostosis formation in HME, particularly at the expense of regions rich in progenitor

  11. Epigenetic regulation of Tbx18 gene expression during endochondral bone formation.

    PubMed

    Haraguchi, Ryuma; Kitazawa, Riko; Kitazawa, Sohei

    2015-02-01

    Endochondral bone formation is tightly regulated by the spatial and sequential expression of a series of transcription factors. To disclose the roles of TBX18, a member of the T-box transcription factor family, during endochondral bone formation, its spatial and temporal expression patterns were characterized in the limb skeletal region of the developing mouse together with those of established osteochondrogenic markers Sox9, Col2a1, and Runx2. TBX18 expression first appeared in condensed mesenchymal cells (chondro-progenitors) in embryonic-day-10.5 (E10.5) limb bud and was co-localized with Sox9 expression, whereas at E11.5 and E12.5, it became undetectable in mesenchymal cells committed to the chondrocyte lineage. From E13.5 to E18.5, TBX18 expression reappeared in chondrocytes, correlating strongly with Col2a1 expression; furthermore, low level TBX18 expression was found in the Runx2-positive perichondral osteoblastic cell lineage. At the postnatal stage, TBX18 expression was observed in epiphyseal chondrocytes and osteocytes within the lacunae of mature trabecular bone. On the assumption that such characteristic Tbx18 gene expression is epigenetically regulated during mouse limb development, we examined the methylation status of the CpG-island in the mouse Tbx18 gene by methylation-specific polymerase chain reaction. Hypermethylation of the Tbx18 gene promoter became evident at an early embryonic stage in TBX18-negative cells and then disappeared at a late embryonic stage in TBX18-positive cells. Therefore, the temporal suppression of Tbx18 gene expression by the hypermethylation of its promoter seems to trigger the differentiation of mesenchymal cells into hypertrophic chondrocytes in the early stages of endochondral ossification. PMID:25380565

  12. Beaulieu-Boycott-Innes syndrome: an intellectual disability syndrome with characteristic facies.

    PubMed

    Casey, Jillian; Jenkinson, Allan; Magee, Alex; Ennis, Sean; Monavari, Ahmad; Green, Andrew; Lynch, Sally A; Crushell, Ellen; Hughes, Joanne

    2016-10-01

    We report a female child from an Irish Traveller family presenting with severe intellectual disability, dysmorphic features, renal anomalies, dental caries and cyclical vomiting. Current health issues include global developmental delay, mild concentric left ventricular hypertrophy, dental malocclusion and caries and a single duplex left kidney. The proband and her mother also have multiple epiphyseal dysplasia. Whole-exome sequencing was performed to identify the underlying genetic cause. DNA from the proband was enriched with the Agilent Sure Select v5 Exon array and sequenced on an Illumina HiSeq. Rare homozygous variants were prioritized. Whole-exome sequencing identified three linked homozygous missense variants in THOC6 (c.298T>A, p.Trp100Arg; c.700G>C, p.Val234Leu; c.824G>A, p.Gly275Asp) as the likely cause of this child's intellectual disability syndrome, resulting in a molecular diagnosis of Beaulieu-Boycott-Innes syndrome (BBIS). This is the first report of BBIS in Europe. BBIS has been reported previously in two Hutterite families and one Saudi family. A review of all patients to date shows a relatively homogenous phenotype. Core clinical features include low birth weight with subsequent growth failure, short stature, intellectual disability with language delay, characteristic facies, renal anomalies and dental malocclusion with caries. Some patients also have cardiac defects. All patients show characteristic dysmorphic facial features including a tall forehead with high anterior hairline and deep-set eyes with upslanting palpebral fissures. The coexistence of intellectual disability together with these characteristic facies should provide a diagnostic clue for BBIS during patient evaluation. PMID:27295358

  13. Whole-Body and Microenvironmental Localization of Radium-223 in Naïve and Mouse Models of Prostate Cancer Metastasis

    PubMed Central

    Abou, Diane S.; Ulmert, David; Doucet, Michele; Hobbs, Robert F.; Riddle, Ryan C.

    2016-01-01

    Background: Bone-metastatic, castration-resistant prostate cancer (bmCRPC) represents a lethal stage of the most common noncutaneous cancer in men. The recent introduction of Radium-223 dichloride, a bone-seeking alpha particle (α)–emitting radiopharmaceutical, demonstrates statistically significant survival benefit and palliative effect for bmCRPC patients. Clinical results have established safety and efficacy, yet questions remain regarding pharmacodynamics and dosing for optimized patient benefit. Methods: We elucidated the biodistribution of 223Ra as well as interaction with the bone and tumor compartments in skeletally mature mice (C57Bl/6 and CD-1, n = 3–6) and metastasis models (LNCaP and PC3, n = 4). Differences in uptake were evaluated by µCT and histological investigation. Novel techniques were leveraged on whole-mount undecalcified cryosections to determine microdistribution of Radium-223. All statistical tests were two-sided. Results: 223Ra uptake in the bones (>30% injected activity per gram) at 24 hours was also accompanied by non-negligible remnant activity in the kidney (2.33% ± 0.36%), intestines (5.73% ± 2.04%), and spleen (10.5% ± 5.9%) Skeletal accumulation across strains did not correspond with bone volume or surface area but instead to local blood vessel density (P = .04). Microdistribution analysis by autoradiography and α camera revealed targeting of the ossifying surfaces adjacent to the epiphyseal growth plate. In models of PCa metastasis, radioactivity does not localize directly within tumors but instead at the apposite bone surface. Osteoblastic and lytic lesions display similar intensity, which is comparable with uptake at sites of normal bone remodeling. Conclusions: Profiling the macro- and microdistribution of 223Ra in healthy and diseased models has important implications to guide precision application of this emerging α-therapy approach for bmCRPC and other bone metastastic diseases. PMID:26683407

  14. The lameness of King Philip II and Royal Tomb I at Vergina, Macedonia

    PubMed Central

    Bartsiokas, Antonis; Arsuaga, Juan-Luis; Santos, Elena; Algaba, Milagros; Gómez-Olivencia, Asier

    2015-01-01

    King Philip II was the father of Alexander the Great. He suffered a notorious penetrating wound by a lance through his leg that was nearly fatal and left him lame in 339 B.C.E. (i.e., 3 y before his assassination in 336 B.C.E.). In 1977 and 1978 two male skeletons were excavated in the Royal Tombs II and I of Vergina, Greece, respectively. Tomb I also contained another adult (likely a female) and a newborn skeleton. The current view is that Philip II was buried in Tomb II. However, the male skeleton of Tomb II bears no lesions to his legs that would indicate lameness. We investigated the skeletal material of Tomb I with modern forensic techniques. The male individual in Tomb I displays a conspicuous case of knee ankylosis that is conclusive evidence of lameness. Right through the overgrowth of the knee, there is a hole. There are no obvious signs that are characteristic of infection and osteomyelitis. This evidence indicates that the injury was likely caused by a severe penetrating wound to the knee, which resulted in an active inflammatory process that stopped years before death. Standard anthropological age-estimation techniques based on dry bone, epiphyseal lines, and tooth analysis gave very wide age ranges for the male, centered around 45 y. The female would be around 18-y-old and the infant would be a newborn. It is concluded that King Philip II, his wife Cleopatra, and their newborn child are the occupants of Tomb I. PMID:26195763

  15. Intermittent applied mechanical loading induces subchondral bone thickening that may be intensified locally by contiguous articular cartilage lesions

    PubMed Central

    Poulet, B.; de Souza, R.; Kent, A.V.; Saxon, L.; Barker, O.; Wilson, A.; Chang, Y.-M.; Cake, M.; Pitsillides, A.A.

    2015-01-01

    Summary Objectives Changes in subchondral bone (SCB) and cross-talk with articular cartilage (AC) have been linked to osteoarthritis (OA). Using micro-computed tomography (micro-CT) this study: (1) examines changes in SCB architecture in a non-invasive loading mouse model in which focal AC lesions are induced selectively in the lateral femur, and (2) determines any modifications in the contralateral knee, linked to changes in gait, which might complicate use of this limb as an internal control. Methods Right knee joints of CBA mice were loaded: once with 2weeks of habitual use (n = 7), for 2weeks (n = 8) or for 5weeks (n = 5). Both left (contralateral) and right (loaded) knees were micro-CT scanned and the SCB and trabecular bone analysed. Gait analysis was also performed. Results These analyses showed a significant increase in SCB thickness in the lateral compartments in joints loaded for 5weeks, which was most marked in the lateral femur; the contralateral non-loaded knee also showed transient SCB thickening (loaded once and repetitively). Epiphyseal trabecular bone BV/TV and trabecular thickness were also increased in the lateral compartments after 5 weeks of loading, and in all joint compartments in the contralateral knee. Gait analysis showed that applied loading only affected gait in the contralateral himd-limb in all groups of mice from the second week after the first loading episode. Conclusions These data indicate a spatial link between SCB thickening and AC lesions following mechanical trauma, and the clear limitations associated with the use of contralateral joints as controls in such OA models, and perhaps in OA diagnosis. PMID:25655679

  16. Osteoarthritis among the prehispanic population from La Gomera and El Hierro (Canary Islands): a comparative study.

    PubMed

    Castañeyra-Ruiz, María; Trujillo-Mederos, Aioze; Arnay-de-la-Rosa, Matilde; González-Reimers, Emilio

    2015-01-01

    The pathogenesis of osteoarthritis is still unclear, and several factors may play a role in its development, including joint trauma or microtrauma (usually related to lifestyle), local inflammation, loading charge, and genetics. Assessment of osteoarthritis among ancient populations is important, since it may yield information relative to life habits. Therefore, we have performed the present study in order to assess the prevalence of osteoarthritis among the prehispanic populations from La Gomera and El Hierro, two islands of the Canary Archipelago with a similar size and altitude which were colonized by individuals of North African origin about 2000 - 2500 years ago. The economy of these people was based on goat herding, shellfishing, and agriculture together with consumption of some wild vegetal species. However, despite a similar geographic environment and a similar economic pattern, prevalence of osteoarthritis was by far higher among the population from La Gomera (78.57 % vs 15.85 %, p < 0.001), and that of eburnation, 11.65 % and 1.05 %, respectively (p = 0.016); in contrast, the population of El Hierro was markedly more robust than that of La Gomera. Globally, a trend to an inverse relationship was observed between epiphyseal robusticity index and the presence of osteoarthritis, which was statistically significant when only men were analysed. However, after performing a multivariate analysis, the only factor that was independently related to the presence of osteoarthritis was the variable "island" (i.e., population group), suggesting that - possibly - genetic factors played a major role in the differences observed. PMID:26244897

  17. Effects of physical exercise on the cartilage of ovariectomized rats submitted to immobilization

    PubMed Central

    Simas, José Martim Marques; Kunz, Regina Inês; Brancalhão, Rose Meire Costa; Ribeiro, Lucinéia de Fátima Chasko; Bertolini, Gladson Ricardo Flor

    2015-01-01

    ABSTRACT Objective To analyze the effects of physical exercise on cartilage histomorphometry in osteoporosis-induced rats subjected to immobilization. Methods We used 36 Wistar rats that were separated into six groups: G1, G2 and G3 submitted to pseudo-oophorectomy, and G4, G5 and G6 submitted to oophorectomy. After 60 days at rest, G2, G3, G5 and G6 had the right hind limbs immobilized for 15 days, followed by the same period in remobilization, being free in the box to G2 and G5, and climb ladder to G3 and G6. At the end of the experiment, the rats were euthanized, their tibias bilaterally removed and submitted to histological routine. Results There was significant increase in thickness of the articular cartilage (F(5;29)=13.88; p<0.0001) and epiphyseal plate (F(5;29)=14.72; p<0.0001) as the number of chondrocytes (F(5;29)=5.11; p=0.0021) in ovariectomized rats, immobilized and submitted to exercise. In the morphological analysis, degeneration of articular cartilage with subchondral bone exposure, loss of cellular organization, discontinuity of tidemark, presence of cracks and flocculation in ovariectomized, immobilized and free remobilization rats were found. In ovariectomized and immobilized remobilization ladder rats, signs of repair of the cartilaginous structures in the presence of clones, pannus, subcortical blood vessel invasion in the calcified zone, increasing the amount of isogenous groups and thickness of the calcified zone were observed. Conclusion Exercise climb ladder was effective in cartilaginous tissue recovery process damaged by immobilization, in model of osteoporosis by ovariectomy in rats. PMID:26761556

  18. Articular soft tissue anatomy of the archosaur hip joint: Structural homology and functional implications.

    PubMed

    Tsai, Henry P; Holliday, Casey M

    2015-06-01

    Archosaurs evolved a wide diversity of locomotor postures, body sizes, and hip joint morphologies. The two extant archosaurs clades (birds and crocodylians) possess highly divergent hip joint morphologies, and the homologies and functions of their articular soft tissues, such as ligaments, cartilage, and tendons, are poorly understood. Reconstructing joint anatomy and function of extinct vertebrates is critical to understanding their posture, locomotor behavior, ecology, and evolution. However, the lack of soft tissues in fossil taxa makes accurate inferences of joint function difficult. Here, we describe the soft tissue anatomies and their osteological correlates in the hip joint of archosaurs and their sauropsid outgroups, and infer structural homology across the extant taxa. A comparative sample of 35 species of birds, crocodylians, lepidosaurs, and turtles ranging from hatchling to skeletally mature adult were studied using dissection, imaging, and histology. Birds and crocodylians possess topologically and histologically consistent articular soft tissues in their hip joints. Epiphyseal cartilages, fibrocartilages, and ligaments leave consistent osteological correlates. The archosaur acetabulum possesses distinct labrum and antitrochanter structures on the supraacetabulum. The ligamentum capitis femoris consists of distinct pubic- and ischial attachments, and is homologous with the ventral capsular ligament of lepidosaurs. The proximal femur has a hyaline cartilage core attached to the metaphysis via a fibrocartilaginous sleeve. This study provides new insight into soft tissue structures and their osteological correlates (e.g., the antitrochanter, the fovea capitis, and the metaphyseal collar) in the archosaur hip joint. The topological arrangement of fibro- and hyaline cartilage may provide mechanical support for the chondroepiphysis. The osteological correlates identified here will inform systematic and functional analyses of archosaur hindlimb evolution and

  19. Naturally occurring secondary nutritional hyperparathyroidism in cattle egrets (Bubulcus ibis) from Central Texas

    USGS Publications Warehouse

    Phalen, D.N.; Drew, M.L.; Contreras, C.; Roset, K.; Mora, M.

    2005-01-01

    Naturally occurring secondary nutritional hyperparathyroidism is described in the nestlings of two colonies of cattle egrets (Bubulcus ibis) from Central Texas (Bryan and San Antonio, Texas, USA). Nestlings from a third colony (Waco, Texas, USA) were collected in a subsequent year for comparison. Birds from the first two colonies consistently had severe osteopenia and associated curving deformities and folding fractures of their long bones. These birds also had reduced bone ash, increased osteoclasia, a marked decrease in osteoblast activity, variable lengthening and shortening of the hypertrophic zone of the epiphyseal cartilage, decreased and disorganized formation of new bone, and a marked hypertrophy and hyperplasia of the parathyroid glands as compared to birds collected from the third colony. Fibrous osteodystrophy was found in all of the birds from San Antonio and Bryan. Evidence of moderate to severe calcium deficiency was also identified in 33% of the cattle egrets collected from Waco. Gut contents of affected chicks contained predominately grasshoppers and crickets; vertebrate prey items were absent from the Bryan birds. Grasshoppers and crickets collected from fields frequented by the adult egrets in 1994 had 0.12-0.28% calcium and 0.76-0.81% phosphorus. Pooled grasshoppers and crickets collected during a subsequent wet early spring averaged 0.24% calcium and 0.65% phosphorus. Although the phosphorus content of the insect prey was adequate for growth, calcium was approximately one-third the minimum calcium requirement needed for growth for other species of birds. It was postulated that cattle egrets breeding in Central Texas have expanded their range into habitat that contains less vertebrate prey, and as a result, many nestling egrets are being fed diets that contain suboptimal calcium. Therefore, in years where vertebrate prey is scarce and forage for insect prey is reduced in calcium, nestling egrets are at risk for developing secondary nutritional

  20. The role of carnivores and their relationship to hominin settlements in the TD6-2 level from Gran Dolina (Sierra de Atapuerca, Spain)

    NASA Astrophysics Data System (ADS)

    Saladié, Palmira; Rodríguez-Hidalgo, Antonio; Huguet, Rosa; Cáceres, Isabel; Díez, Carlos; Vallverdú, Josep; Canals, Antoni; Soto, María; Santander, Boris; Bermúdez de Castro, José María; Arsuaga, Juan Luis; Carbonell, Eudald

    2014-06-01

    Pleistocene level TD6-2 of the Gran Dolina site (Sierra de Atapuerca, Spain) is the result of anthropogenic accumulation. Hominin groups occupied the cave as a home base, where they brought in, butchered and consumed the carcasses of ungulates and other hominins. In this paper, we reassess the role of carnivores in the formation and/or modification of the assemblage. We employed different methods to explore the scenario in which the TD6-2 assemblage was formed: (1) identifying the actor responsible for tooth marks; (2) determining the frequency of carnivore tooth marks and their distribution; (3) identifying the co-occurrence of modifications (butchering marks and carnivore tooth marks); (4) calculating the percentage of change and the epiphysis to shaft ratio. Carnivore tooth marks are scarce, as is the co-occurrence of hominin and carnivore modifications. However, not all tooth marks have been attributed to a particular agent due to the high equifinality between human and carnivore tooth marks. For these reasons, the frequency of tooth marks and the co-occurrence of modifications have been of little help in interpreting the role of carnivores. Axial skeletal remains and the epiphyses of the long bones are in large part missing. The percentage of change and the epiphysis to shaft ratio suggest moderate carnivore ravaging activity. Our data indicate that the role of carnivores in TD6-2 seems to have had an impact on the original assemblage after hominins had extracted a large amount of nutrients from the carcasses. Cannibalized hominin remains showed no carnivore tooth marks and have a greater presence of low survival bones compared to ungulate remains. These findings point to a different taphonomic history suggesting that TD6-2 represents a succession of settlements having different characteristics.

  1. Effect of dietary calcium on bone metabolism in young and aged female rats using a short-term in vivo model

    SciTech Connect

    Sinha, R.; Smith, J.C. Jr.; Soares, J.H. Jr.

    1988-10-01

    The use of high dietary calcium supplementation in the treatment of patients with osteoporosis is controversial. The present study examined the mechanisms underlying the effects of calcium supplementation by investigating the influence of dietary calcium on bone dynamics in young and aged rats. A 2 x 2 x 2 factorial design was utilized with 0.2% (low) or 1.0% (high) calcium, 2- or 24-m-old female Long-Evans rats that were implanted subcutaneously with demineralized (DB) and mineralized (MB) bone powder. The four groups of rats were fed each of the respective diets for 11 wk and then implanted with one number5 gelatin capsule containing 30 mg of DB and another containing 100 mg of MB powder. The animals were injected intraperitoneally with 0.1 microCi/g body weight with 45Ca 14 h before the end of experiment. The ectopic bone as well as the right femurs were harvested 14 d after the rats were implanted. Marker enzyme activities (alkaline-formation and acid-resorption phosphatase), 45Ca uptake and calcium content were measured in the implants and the distal epiphyses of the right femurs. Bone turnover was higher in the young rats than in the old animals, and high dietary calcium in the young animals increased bone formation, as indicated by alkaline phosphatase activity. Dietary calcium level did not affect ectopic bone formation or resorption in the aged rats. The results indicate that high dietary intake of calcium does not affect bone dynamics in aged female rats but does increase bone formation in young rats.

  2. A Systematic Review of Selected Musculoskeletal Late Effects in Survivors of Childhood Cancer

    PubMed Central

    Gawade, Prasad L.; Hudson, Melissa M.; Kaste, Sue C.; Neglia, Joseph P.; Wasilewski-Masker, Karen; Constine, Louis S.; Robison, Leslie L.; Ness, Kirsten K.

    2014-01-01

    Survivors of childhood cancer are at risk for treatment-related musculoskeletal late effects. Early detection and orthopedic intervention can help ameliorate musculoskeletal late effects and prevent subsequent complications. This systematic review summarizes the literature describing associations between cancer, its treatment, and musculoskeletal late effects. We searched PubMed and Web of Science for English language articles published between January 1970 and December 2012. The search was limited to investigations with at least 15 participants and conducted at least 2 years after completion of therapy for childhood, adolescent, or young adult cancer. Some late skeletal effects, including low bone mineral density, osteonecrosis, slipped capital femoral epiphyses, oncogenic rickets, and hormone-related growth disturbances have been previously reviewed and were excluded, as were outcomes following amputation and limb-salvage procedures. Of 2347 references identified, 30 met inclusion criteria and were retained. An additional 54 studies that met inclusion criteria were found in reference lists of retained studies. Of 84 studies, 60 focused on associations between radiotherapy, six between chemotherapy, and 18 between surgery and musculoskeletal late effects. We found that younger age, higher radiation dosage, and asymmetric or partial bone radiation volume influences the effects of radiation on the musculoskeletal system. Methotrexate and vincristine are associated with long-term muscular strength and flexibility deficits. Laminectomy and chest wall resection are associated with spinal malalignment, and enucleation is associated with orbital deformities among survivors. Radiotherapy, chemotherapy, and surgery are associated with musculoskeletal late effects independently and additively. Associations are additionally influenced by host and treatment characteristics. PMID:25403639

  3. Bone age assessment meets SIFT

    NASA Astrophysics Data System (ADS)

    Kashif, Muhammad; Jonas, Stephan; Haak, Daniel; Deserno, Thomas M.

    2015-03-01

    Bone age assessment (BAA) is a method of determining the skeletal maturity and finding the growth disorder in the skeleton of a person. BAA is frequently used in pediatric medicine but also a time-consuming and cumbersome task for a radiologist. Conventionally, the Greulich and Pyle and the Tanner and Whitehouse methods are used for bone age assessment, which are based on visual comparison of left hand radiographs with a standard atlas. We present a novel approach for automated bone age assessment, combining scale invariant feature transform (SIFT) features and support vector machine (SVM) classification. In this approach, (i) data is grouped into 30 classes to represent the age range of 0- 18 years, (ii) 14 epiphyseal ROIs are extracted from left hand radiographs, (iii) multi-level image thresholding, using Otsu method, is applied to specify key points on bone and osseous tissues of eROIs, (iv) SIFT features are extracted for specified key points for each eROI of hand radiograph, and (v) classification is performed using a multi-class extension of SVM. A total of 1101 radiographs of University of Southern California are used in training and testing phases using 5- fold cross-validation. Evaluation is performed for two age ranges (0-18 years and 2-17 years) for comparison with previous work and the commercial product BoneXpert, respectively. Results were improved significantly, where the mean errors of 0.67 years and 0.68 years for the age ranges 0-18 years and 2-17 years, respectively, were obtained. Accuracy of 98.09 %, within the range of two years was achieved.

  4. At the moment of occurrence of a fragility hip fracture, men have higher mechanical properties values in comparison with women

    PubMed Central

    2013-01-01

    Background It is well established that males have lower fracture risk in comparison with females, which suggests a higher bone resistance in men. The aim of our study was to find out if in older patients with hip fragility fractures, gender has also an impact on trabecular bone material behaviour, specifically to determine whether trabecular mechanical properties under compressive loading differ between men and women who suffered a fragility hip fracture. Methods Femoral epiphyses were consecutively collected during hip replacement surgery due to proximal femur fragility fracture. Trabecular bone cylinders were drilled and submitted to uniaxial compression tests and mechanical properties were assessed. Results Seventy-three patients, 55 women (mean age 81 years and standard deviation of 7 years) and 18 men (mean age 81 years and standard deviation of 8 years) were evaluated. The ultimate stress of trabecular bone was significantly higher in men than in women: the median values and the interquartile range (IQR) were respectively 8.04(5.35-10.90) MPa vs. 4.46(3.02-7.73) MPa, (p-value = 0.005). The same difference between male and female was observed in the Young’s modulus: 293.68(166.67-538.18) MPa vs. 174.26(73.07-322.28) MPa, (p-value = 0.028), and also in the energy to failure: 0.25(0.07-0.42) MJ/m3 vs. 0.11(0.05-0.25) MJ/m3, (p-value = 0.058). These differences were also verified after adjusting the analysis for age in a multivariate model analysis. Conclusions Our observations demonstrated that, even in a population who suffered a fragility hip fracture, men still have higher trabecular bone mechanical properties in comparison with women. PMID:24131745

  5. A study of the clinical and radiological features in a cohort of 93 patients with a COL2A1 mutation causing spondyloepiphyseal dysplasia congenita or a related phenotype.

    PubMed

    Terhal, Paulien A; Nievelstein, Rutger Jan A J; Verver, Eva J J; Topsakal, Vedat; van Dommelen, Paula; Hoornaert, Kristien; Le Merrer, Martine; Zankl, Andreas; Simon, Marleen E H; Smithson, Sarah F; Marcelis, Carlo; Kerr, Bronwyn; Clayton-Smith, Jill; Kinning, Esther; Mansour, Sahar; Elmslie, Frances; Goodwin, Linda; van der Hout, Annemarie H; Veenstra-Knol, Hermine E; Herkert, Johanna C; Lund, Allan M; Hennekam, Raoul C M; Mégarbané, André; Lees, Melissa M; Wilson, Louise C; Male, Alison; Hurst, Jane; Alanay, Yasemin; Annerén, Göran; Betz, Regina C; Bongers, Ernie M H F; Cormier-Daire, Valerie; Dieux, Anne; David, Albert; Elting, Mariet W; van den Ende, Jenneke; Green, Andrew; van Hagen, Johanna M; Hertel, Niels Thomas; Holder-Espinasse, Muriel; den Hollander, Nicolette; Homfray, Tessa; Hove, Hanne D; Price, Susan; Raas-Rothschild, Annick; Rohrbach, Marianne; Schroeter, Barbara; Suri, Mohnish; Thompson, Elizabeth M; Tobias, Edward S; Toutain, Annick; Vreeburg, Maaike; Wakeling, Emma; Knoers, Nine V; Coucke, Paul; Mortier, Geert R

    2015-03-01

    Type 2 collagen disorders encompass a diverse group of skeletal dysplasias that are commonly associated with orthopedic, ocular, and hearing problems. However, the frequency of many clinical features has never been determined. We retrospectively investigated the clinical, radiological, and genotypic data in a group of 93 patients with molecularly confirmed SEDC or a related disorder. The majority of the patients (80/93) had short stature, with radiological features of SEDC (n = 64), others having SEMD (n = 5), Kniest dysplasia (n = 7), spondyloperipheral dysplasia (n = 2), or Torrance-like dysplasia (n = 2). The remaining 13 patients had normal stature with mild SED, Stickler-like syndrome or multiple epiphyseal dysplasia. Over 50% of the patients had undergone orthopedic surgery, usually for scoliosis, femoral osteotomy or hip replacement. Odontoid hypoplasia was present in 56% (95% CI 38-74) and a correlation between odontoid hypoplasia and short stature was observed. Atlanto-axial instability, was observed in 5 of the 18 patients (28%, 95% CI 10-54) in whom flexion-extension films of the cervical spine were available; however, it was rarely accompanied by myelopathy. Myopia was found in 45% (95% CI 35-56), and retinal detachment had occurred in 12% (95% CI 6-21; median age 14 years; youngest age 3.5 years). Thirty-two patients complained of hearing loss (37%, 95% CI 27-48) of whom 17 required hearing aids. The ophthalmological features and possibly also hearing loss are often relatively frequent and severe in patients with splicing mutations. Based on clinical findings, age at onset and genotype-phenotype correlations in this cohort, we propose guidelines for the management and follow-up in this group of disorders. PMID:25604898

  6. The lateral clavicular epiphysis: fusion timing and age estimation.

    PubMed

    Langley, Natalie R

    2016-03-01

    This study utilizes a forensic autopsy sample of twentieth century American Whites (the McCormick Clavicle Collection) to describe the morphology, variation, and fusion timing of the lateral clavicle epiphysis. Clavicles from individuals between 11 and 25 years at the time of death were used to document fusion of the lateral epiphysis (n= 133, 38 females and 95 males). The lateral epiphysis was scored as unfused, fusing, or fused. A linear weighted kappa indicates that this scoring method is highly replicable with almost perfect inter-rater agreement (kappa = 0.849), according to a widely used standard for assessing kappa values. Transition analysis, or probit regression, was employed to quantify fusion timing of the lateral epiphysis. The transition from "unfused" to "fusing" is most likely to occur at 16.5 years in females and 17.5 years in males. The transition from "fusing" to "fused" occurs at age 21 in females and age 20 in males. The earliest age at which fusion began was 15 years (n = 1), but the majority began fusing between 17 and 20 years. Most individuals (98.5 % of the sample) aged >24 years had fused lateral epiphyses. The epiphysis assumes one of two forms: (1) a separate bony flake fusing to the diaphysis or (2) a mound of bone glazing/smoothing over the diaphyseal surface. As socioeconomic status has been cited as the most influential variable on skeletal maturation rates, the fusion ages offered here should not be applied to populations with a socioeconomic status different from the greater US population. PMID:26253853

  7. MicroCT Morphometry Analysis of Mouse Cancellous Bone: Intra- and Inter-system Reproducibility

    PubMed Central

    Verdelis, K.; Lukashova, L.; Atti, E.; Mayer-Kuckuk, P.; Peterson, M.G.E.; Tetradis, S.; Boskey, A.L.; van der Meulen, M.C.H.

    2012-01-01

    The agreement between measurements and the relative performance reproducibility among different microcomputed tomography (microCT) systems, especially at voxel sizes close to the limit of the instruments, is not known. To compare this reproducibility 3D morphometric analyses of mouse cancellous bone from distal femoral epiphyses were performed using three different ex vivo microCT systems: GE eXplore Locus SP, Scanco μCT35 and Skyscan 1172. Scans were completed in triplicate at 12μm and 8μm voxel sizes and morphometry measurements, from which relative values and dependence on voxel size were examined. Global and individual visually assessed thresholds were compared. Variability from repeated scans at 12μm voxel size was also examined. Bone volume fraction and trabecular separation values were similar, while values for relative bone surface, trabecular thickness and number varied significantly across the three systems. The greatest differences were measured in trabecular thickness (up to 236%) and number (up to 218%). The relative dependence of measurements on voxel size was highly variable for the trabecular number (from 0% to 20% relative difference between measurements from 12μm and 8μm voxel size scans, depending on the system). The intra-system reproducibility of all trabecular measurements was also highly variable across the systems and improved for BV/TV in all the systems when a smaller voxel size was used. It improved using a smaller voxel size in all the other parameters examined for the Scanco system, but not consistently so for the GE or the Skyscan system. Our results indicate trabecular morphometry measurements should not be directly compared across microCT systems. In addition, the conditions, including voxel size, for trabecular morphometry studies in mouse bone should be chosen based on the specific microCT system and the measurements of main interest. PMID:21621659

  8. Use of aromatase inhibitors to increase final height.

    PubMed

    Dunkel, Leo

    2006-07-25

    During puberty in both sexes, the mechanism involved in epiphyseal fusion is mediated by the action of estrogen through a cascade of events including proliferation, differentiation, and apoptosis of chondrocytes. The enzyme P450 aromatase catalyzes the aromatization of C19 androgens (androstenedione and testosterone) to C18 estrogens (estrone and estradiol). Inhibition of estrogen action by aromatase inhibitors (AIs) appears to decelerate the process of growth plate fusion, and thus AIs may be used therapeutically to increase adult height. The clinical experience with AIs in the pediatric setting is limited to testolactone, fadrozole, letrozole, and anastrozole. Testolactone, a nonselective steroidal AI, has been used successfully as an adjunct to antiandrogen and gonadotropin-releasing hormone analogue (GnRHa), therapy for children with familial male-limited precocious puberty (FMPP) and congenital adrenal hyperplasia (CAH), and with some success in girls with McCune-Albright syndrome. The limitations of testolactone include its relatively low potency and the need for frequent dosing. Results of a randomized placebo-controlled trial in boys with delayed puberty treated with letrozole, a selective nonsteroidal AI, found that boys treated with letrozole + testosterone experienced delayed bone maturation and good growth response and achieved an increase in predicted adult height. In this study, only minor differences in bone density were seen between the placebo and letrozole treatment groups, both of which were receiving concomitant testosterone therapy. No adverse effects on testis size or inhibin B concentration were noted. The therapeutic value of AIs in growth promotion now remains to be substantiated in future controlled clinical trials. PMID:16766117

  9. Beneath the minerals, a layer of round lipid particles was identified to mediate collagen calcification in compact bone formation.

    PubMed

    Xu, Shaohua; Yu, Jianqing J

    2006-12-01

    Astronauts lose 1-2% of their bone minerals per month during space flights. A systematic search for a countermeasure relies on a good understanding of the mechanism of bone formation at the molecular level. How collagen fibers, the dominant matrix protein in bones, are mineralized remains mysterious. Atomic force microscopy was carried out, in combination with immunostaining and Western blotting, on bovine tibia to identify unrecognized building blocks involved in bone formation and for an elucidation of the process of collagen calcification in bone formation. Before demineralization, tiles of hydroxyapatite crystals were found stacked along bundles of collagen fibers. These tiles were homogeneous in size and shape with dimensions 0.69 x 0.77 x 0.2 micro m(3). Demineralization dissolved these tiles and revealed small spheres with an apparent diameter around 145 nm. These spheres appeared to be lipid particles since organic solvents dissolved them. The parallel collagen bundles had widths mostly <2 micro m. Composition analysis of compact bones indicated a high content of apolar lipids, including triglycerides and cholesterol esters. Apolar lipids are known to form lipid droplets or lipoproteins, and these spheres are unlikely to be matrix vesicles as reported for collagen calcification in epiphyseal cartilages. Results from this study suggest that the layer of round lipid particles on collagen fibers mediates the mineral deposition onto the fibers. The homogeneous size of these lipid particles and the presence of apolipoprotein in demineralized bone tissue suggest the possibility that these particles might be of lipoprotein origin. More studies are needed to verify the last claim and to exclude the possibility that they are secreted lipid droplets. PMID:16980361

  10. Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature.

    PubMed

    Ozbek, M Nuri; Senée, Valérie; Aydemir, Sehnaz; Kotan, L Damla; Mungan, Neslihan O; Yuksel, Bilgin; Julier, Cécile; Topaloglu, A Kemal

    2010-06-01

    Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by an early-infancy-onset diabetes mellitus associated with a variety of multisystemic clinical manifestations. Here, we present six patients with WRS, carrying the same homozygous mutation (EIF2AK3-W522X), from two unrelated Turkish families. This is the largest series of patients with the same mutation for this rare syndrome. In this communication we compare clinical features of these six patients with the other 34 patients who have been reported to date, and review the clinical features of WRS. All WRS patients presented first with symptoms of insulin dependent diabetes mellitus, with a mean age at onset of 2 months. All patients had skeletal dysplasia or early signs of it, and growth retardation. Many of the patients with WRS have been reported to have developmental delay, mental retardation, and learning difficulties; in contrast, none of our patients showed abnormal development at age up to 30 months. Acute attacks of hepatic failure were reported in 23 cases out of 37 patients; in 15 of those 23 cases an acute attack of renal failure accompanied the liver failure. Exocrine pancreatic deficiency has been reported in only four cases other than our four patients. Central hypothyroidism was observed in six of 28 cases. We propose that central hypothyroidism is not a component of WRS, but rather a reflection of euthyroid sick syndrome. Four of our patients experienced severe neutropenia, compared to only five of the 27 other cases, suggesting that the W522X mutation may be specifically associated with neutropenia. Other than the consistent features of diabetes mellitus and epiphyseal dysplasia, WRS patients are otherwise characterized by extensive phenotypic variability that correlates poorly to genotype. PMID:20202148

  11. Skeletal effect of casein and whey protein intake during catch-up growth in young male Sprague-Dawley rats.

    PubMed

    Masarwi, Majdi; Gabet, Yankel; Dolkart, Oleg; Brosh, Tamar; Shamir, Raanan; Phillip, Moshe; Gat-Yablonski, Galia

    2016-07-01

    The aim of the present study was to determine whether the type of protein ingested influences the efficiency of catch-up (CU) growth and bone quality in fast-growing male rats. Young male Sprague-Dawley rats were either fed ad libitum (controls) or subjected to 36 d of 40 % food restriction followed by 24 or 40 d of re-feeding with either standard rat chow or iso-energetic, iso-protein diets containing milk proteins - casein or whey. In terms of body weight, CU growth was incomplete in all study groups. Despite their similar food consumption, casein-re-fed rats had a significantly higher body weight and longer humerus than whey-re-fed rats in the long term. The height of the epiphyseal growth plate (EGP) in both casein and whey groups was greater than that of rats re-fed normal chow. Microcomputed tomography yielded significant differences in bone microstructure between the casein and whey groups, with the casein-re-fed animals having greater cortical thickness in both the short and long term in addition to a higher trabecular bone fraction in the short term, although this difference disappeared in the long term. Mechanical testing confirmed the greater bone strength in rats re-fed casein. Bone quality during CU growth significantly depends on the type of protein ingested. The higher EGP in the casein- and whey-re-fed rats suggests a better growth potential with milk-based diets. These results suggest that whey may lead to slower bone growth with reduced weight gain and, as such, may serve to circumvent long-term complications of CU growth. PMID:27189324

  12. Atypical tibial tuberosity fracture in an adolescent.

    PubMed

    Jalgaonkar, Azal A; Dachepalli, Sunil; Al-Wattar, Zaid; Rao, Sudhir; Kochhar, Tony

    2011-06-01

    Avulsion fractures of the tibial tuberosity are typically sustained by adolescent males during sporting activities. Tibial tuberosity avulsions with simultaneous proximal tibial epiphyseal fractures are rare injuries. We present an unusual case of Ogden type IIIA avulsion fracture of tibial tuberosity with a Salter Harris type IV posterior fracture of proximal tibial epiphysis in a 13-year-old boy. We believe that the patient sustained the tibial tuberosity avulsion during the take-off phase of a jump while playing basketball due to sudden violent contraction of the quadriceps as the knee was extending. This was then followed by the posterior Salter Harris type IV fracture of proximal tibial physis as he landed on his leg with enormous forces passing through the knee. Although standard radiographs were helpful in diagnosing the complex fracture pattern, precise configuration was only established by computed tomography (CT) scan. The scan also excluded well-recognized concomitant injuries including ligament and meniscal injuries. Unlike other reported cases, our patient did not have compartment syndrome. Anatomic reduction and stabilization with a partially threaded transepiphyseal cannulated screw and a metaphyseal screw followed by early mobilization ensured an excellent recovery by the patient.Our case highlights the importance of vigilance and a high index of suspicion for coexisting fractures or soft tissue injuries when treating avulsion fractures of tibial tuberosity. A CT scan is justified in such patients to recognize complex fracture configurations, and surgical treatment should be directed appropriately to both the fractures followed by early rehabilitation. Patients with such injuries warrant close monitoring for compartment syndrome during the perioperative period. PMID:21667912

  13. An Update on the Pathogenesis of Osteochondrosis.

    PubMed

    Olstad, K; Ekman, S; Carlson, C S

    2015-09-01

    Osteochondrosis is defined as a focal disturbance in endochondral ossification. The cartilage superficial to an osteochondrosis lesion can fracture, giving rise to fragments in joints known as osteochondrosis dissecans (OCD). In pigs and horses, it has been confirmed that the disturbance in ossification is the result of failure of the blood supply to epiphyseal growth cartilage and associated ischemic chondronecrosis. The earliest lesion following vascular failure is an area of ischemic chondronecrosis at an intermediate depth of the growth cartilage (osteochondrosis latens) that is detectable ex vivo, indirectly using contrast-enhanced micro- and conventional computed tomography (CT) or directly using adiabatic T1ρ magnetic resonance imaging. More chronic lesions of ischemic chondronecrosis within the ossification front (osteochondrosis manifesta) are detectable by the same techniques and have also been followed longitudinally in pigs using plain CT. The results confirm that lesions sometimes undergo spontaneous resolution, and in combination, CT and histology observations indicate that this occurs by filling of radiolucent defects with bone from separate centers of endochondral ossification that form superficial to lesions and by phagocytosis and intramembranous ossification of granulation tissue that forms deep to lesions. Research is currently aimed at discovering the cause of the vascular failure in osteochondrosis, and studies of spontaneous lesions suggest that failure is associated with the process of incorporating blood vessels into the advancing ossification front during growth. Experimental studies also show that bacteremia can lead to vascular occlusion. Future challenges are to differentiate between causes of vascular failure and to discover the nature of the heritable predisposition for osteochondrosis. PMID:26080832

  14. Further characterization of ATP-initiated calcification by matrix vesicles isolated from rachitic rat cartilage. Membrane perturbation by detergents and deposition of calcium pyrophosphate by rachitic matrix vesicles.

    PubMed

    Hsu, H H; Camacho, N P; Anderson, H C

    1999-01-12

    Although membrane associated enzymes such as ATPase, alkaline phosphatase, and NTP pyrophosphohydrolase in matrix vesicles (MVs) may underlie the mechanisms of ATP-promoted calcification, prior to the current investigation, the role of the MV membrane in calcification had not been addressed. In this study, various perturbations were introduced to the MV membrane in in vitro calcification systems to determine ideal conditions for ATP-initiated calcification by MVs isolated from rachitic rat epiphyseal cartilage. Membrane integrity appears to be required, since the rupture of the vesicular membrane by vigorously mixing with 10% butanol abolished calcification. In contrast, a mild treatment of MVs with low concentrations (e.g., 0.01%, which is much below the critical concentration for micelle formation) of either neutral Triton X-100 or anionic deoxycholate stimulated calcification by >2-fold, without inducing obvious changes in vesicular appearance. Fourier transform infrared spectroscopic studies were done to identify the mineral phase formed in these experiments. For the first time, rachitic MVs were shown to induce the formation of a calcium pyrophosphate dihydrate-like phase after their exposure to calcifying medium with 1 mM ATP. The integration of spectral areas indicated that calcification was enhanced by Triton X-100. The detergent effect was reversible and appeared to be not mediated through activation of ATPase, alkaline phosphatase, or ATP pyrophosphohydrolase. In contrast to neutral Triton X-100 and anionic deoxycholate, cationic cetyltrimethylammonium bromide inhibited both ATPase activity (I50=10 microM) and ATP-initiated calcification. These observations suggest that membrane perturbations can affect calcification and that the presence of NTP-pyrophosphohydrolase in MVs may play a role in the deposition of CaPPi in rachitic cartilage. PMID:9889389

  15. Maternal Flaxseed Oil During Lactation Enhances Bone Development in Male Rat Pups.

    PubMed

    Pereira, Aline D'Avila; Ribeiro, Danielle Cavalcante; de Santana, Fernanda Carvalho; de Sousa Dos Santos, Aline; Mancini-Filho, Jorge; do Nascimento-Saba, Celly Cristina Alves; Velarde, Luis Guillermo Coca; da Costa, Carlos Alberto Soares; Boaventura, Gilson Teles

    2016-08-01

    Flaxseed oil is an alpha linolenic acid source important in the growth and body development stage; furthermore, this acid acts on adipose tissue and bone health. The aim of this study was to evaluate body composition, fatty acid composition, hormone profile, retroperitoneal adipocyte area and femur structure of pups at weaning, whose mothers were fed a diet containing flaxseed oil during lactation. After birth, pups were randomly assigned: control (C, n = 12) and flaxseed oil (FO, n = 12), rats whose mothers were treated with diet containing soybean or flaxseed oil. At 21 days, the pups were weaned and body mass, length, body composition, biochemical parameter, leptin, osteoprotegerin, osteocalcin, fatty acids composition, intra-abdominal fat mass and femur structure were analyzed. FO showed (p < 0.05): higher body mass (+12 %) and length (+9 %); body fat mass (g, +45 %); bone mineral density (+8 %), bone mineral content (+55 %) and bone area (+35 %), osteocalcin (+173 %) and osteoprotegerin (+183 %). Arachidonic acid was lower (p < 0.0001), alpha-linolenic and eicosapentaenoic were higher (p < 0.0001). Intra-abdominal fat mass was higher (+25 %), however, the retroperitoneal adipocytes area was lower (-44 %). Femur mass (+10 %), distance between epiphyses (+4 %) and bone mineral density (+13 %) were higher. The study demonstrates that adequate flaxseed oil content during a lactation diet plays an important role in the development of pups. PMID:27256330

  16. Bone marrow changes in adolescent girls with anorexia nervosa.

    PubMed

    Ecklund, Kirsten; Vajapeyam, Sridhar; Feldman, Henry A; Buzney, Catherine D; Mulkern, Robert V; Kleinman, Paul K; Rosen, Clifford J; Gordon, Catherine M

    2010-02-01

    Early osteoporosis is common among adolescent girls with anorexia nervosa (AN) and may result from premature conversion of red (RM) to yellow bone marrow. We performed right knee magnetic resonance imaging (MRI) on a 1.0 T extremity scanner in 20 patients and 20 healthy controls, aged 16.2 +/- 1.6 years (mean +/- SD). Coronal T(1)-weighted (T(1)W) images and T(1) maps were generated from T(1) relaxometry images. Blinded radiologists visually assessed RM in the distal femoral and proximal tibial metaphyses in T(1)W images using a scale of signal intensity from 0 (homogeneous hyperintensity, no RM) to 4 (all dark, complete RM). Subjects with AN exhibited nearly twofold lower metaphyseal RM scores in both the femur (0.64 versus 1.22, p = .03) and tibia (0.54 versus 0.96, p = .08). In relaxometric measurements of four selected regions (femur and tibia amd epiphysis and metaphysis), subjects with AN showed higher mean epiphyseal but lower metaphyseal T(1). The net AN-control difference between epiphysis and metaphysis was 70 ms in the femur (+31 versus -35 ms, p = .02) and of smaller magnitude in the tibia. In relaxometry data from the full width of the femur adjacent to the growth plate, AN subjects showed mean T(1) consistently lower than in controls by 30 to 50 ms in virtually every part of the sampling region. These findings suggest that adolescents with AN exhibit premature conversion of hematopoietic to fat cells in the marrow of the peripheral skeleton potentially owing to adipocyte over osteoblast differentiation in the mesenchymal stem cell pool. PMID:19653811

  17. Management of neglected lateral condyle fractures of humerus in children: A retrospective study

    PubMed Central

    Agarwal, Anil; Qureshi, Nadeem Akhtar; Gupta, Neeraj; Verma, Indreshwar; Pandey, Devreshi Kumar

    2012-01-01

    Background: Late presentation of humeral lateral condylar fracture in children is a surgical dilemma. Osteosynthesis of the fracture fragment or correction of elbow deformity with osteotomies and ulnar nerve transposition or sometimes both procedures combined is a controversial topic. We retrospectively evaluated open reduction and fixation cases in late presentation of lateral humeral condyle fracture in pediatric cases with regards to union and functional results. Materials and Methods: Twenty two pediatric (≤12 years) patients with fractures of lateral condyle presenting 4 weeks or more post injury between the study period of 2006 and 2010 were included. Multiple K-wires / with or without screws along with bone grafting were used. At final evaluation, union (radiologically) and elbow function (Liverpool Elbow Score, LES) was assessed. Results: There were 19 boys and 3 girls. Followup averaged 33 months. Pain (n=9), swelling (n=6), restriction of elbow motion (n=6), prominence of lateral condylar region (n=4), valgus deformity (n=4) were the main presenting symptoms. Ulnar nerve function was normal in all patients. There were nine Milch type I and 13 type II fractures. Union occurred in 20 cases. One case had malunion and in another case there was resorption of condyle following postoperative infection and avascular necrosis. Prominent lateral condyles (4/12), fish tail appearance (n=7), premature epiphyseal closure (n=2) were other observations. LES averaged 8.12 (range, 6.66-9.54) at final followup. Conclusions: There is high rate of union and satisfactory elbow function in late presenting lateral condyle fractures in children following osteosynthesis attempt. Our study showed poor correlation between patient's age, duration of late presentation or Milch type I or II and final elbow function as determined by LES. PMID:23325975

  18. How much more would KNM-WT 15000 have grown?

    PubMed

    Ruff, Christopher B; Burgess, M Loring

    2015-03-01

    Because of its completeness, the juvenile Homo ergaster/erectus KNM-WT 15000 has played an important role in studies of the evolution of body form in Homo. Early attempts to estimate his adult body size used modern human growth models. However, more recent evidence, particularly from the dentition, suggests that he may have had a more chimpanzee-like growth trajectory. Here we re-estimate his adult stature and body mass using ontogenetic data derived from four African ape taxa: Pan troglodytes troglodytes, Pan troglodytes schweinfurthii, Pan paniscus, and Gorilla gorilla gorilla. The average percentage change in femoral and tibial lengths and femoral head breadth between individuals at the same stage of dental development as KNM-WT 15000 - eruption of M2s but not M3s - and adult individuals with fully fused long bone epiphyses, was determined. Results were then applied to KNM-WT 15000, and his adult size estimated from skeletal dimensions using modern human prediction formulae. Using this approach, adult stature best estimates of 176-180 cm and body mass best estimates of 80-83 kg were obtained. These estimates are close to those estimated directly from longitudinal changes in body length and body mass between 8 and 12 years of age in chimpanzees, the suggested chronological equivalent to KNM-WT 15000's remaining growth period. Thus, even using an African ape growth model, it is likely that KNM-WT 15000 would have attained close to 180 cm in stature (without a slight reduction for his lower cranial height) and 80 kg in body mass as an adult. Other evidence from the East African Early Pleistocene indicates that KNM-WT 15000 was not unusually large-bodied for his time period. PMID:25449954

  19. The effect of prenatal indium chloride exposure on chondrogenic ossification.

    PubMed

    Ungváry, G; Tátrai, E; Szakmáry, E; Náray, M

    2001-03-01

    Daily indium chloride doses of control (0) or 400 mg/kg were administered orally to pregnant Sprague-Dawley (SD) rats by gavage, on d 20 of gestation. Indium concentration was determined in the maternal and fetal blood, livers, kidneys, skulls, and femurs by atomic absorption spectrometry. Further groups of pregnant rats were treated with control (0) or 400 mg/kg indium chloride orally, during the whole gestation period. The fetuses were examined on d 21 of gestation, using histological and histochemical methods. Four hours after the administration indium concentration was found to be significant in the blood, liver, and kidneys of the dams. Twenty-four hours later it increased in the blood but not in the liver and kidney. Fetal indium concentrations were 40-50% of the maternal levels due to a barrier of the placenta. In the skull and the femur, indium was already detectable at 4 h after the administration, and by the end of 24 h, metal concentration was several times higher than that at 4 h, indicating accumulation. Furthermore, it was found that the birefringency of collagen detectable by picrosirius red staining in polarized light around the chondrocytes disappeared and became irregular. In the matrix of the epiphyseal cartilage, the regular, birefringent network demonstrable by Rivanol reaction became irregular and hardly recognizable. In the cytoplasm of the chondrocytes, the diffuse, evenly distributed positive Ricinus communis agglutinin reaction became irregular or disappeared. Similar but much weaker changes were observed with concanavalin A and wheat germ agglutinin stainings. It was concluded that the missing femur and micromelia diagnosed by alizarin staining is the consequence of a specific toxic effect of indium that inhibits chondrogenic ossification. No similar histochemical changes were observed in the bones of the skull developing by desmogenic ossification, despite the presence of indium. Data indicate that the mechanisms of the effects of indium

  20. Expression of mutant cartilage oligomeric matrix protein in human chondrocytes induces the pseudoachondroplasia phenotype.

    PubMed

    Merritt, Thomas M; Alcorn, Joseph L; Haynes, Richard; Hecht, Jacqueline T

    2006-04-01

    Over 70 mutations in the cartilage oligomeric matrix protein (COMP), a large extracellular pentameric glycoprotein synthesized by chondrocytes, have been identified as causing two skeletal dysplasias: multiple epiphyseal dysplasia (MED/EDM1), and a dwarfing condition, pseudoachondroplasia (PSACH). These mutations induce misfolding of intracellular COMP, resulting in retention of the protein in the rough endoplasmic reticulum (rER) of chondrocytes. This accumulation of COMP in the rER creates the phenotypic enlarged rER cisternae in the cells, which is believed to compromise chondrocyte function and eventually cause cell death. To study the molecular mechanisms involved with the disease, we sought to develop an in vitro model that recapitulates the PSACH phenotype. Normal human chondrocytes were transfected with wildtype (wt-) COMP or with mutant COMP (D469del; mt-) recombinant adenoviruses and grown in a nonattachment redifferentiating culture system that provides an environment allowing formation of a differentiated chondrocyte nodule. Visualization of normal cells expressing COMP suggested the hallmarks of the PSACH phenotype. Mutant COMP expressed in normal cells was retained in enlarged rER cisternae, which also retained IX collagen (COL9) and matrilin-3 (MATN3). Although these proteins were secreted normally into the ECM of the wt-COMP nodules, reduced secretion of these proteins was observed in nodules composed of cells transfected with mt-COMP. The findings complement those found in chondrocytes from PSACH patient growth plates. This new model system allows for production of PSACH chondrocyte pathology in normal costochondral chondrocytes and can be used for future mechanistic and potential gene therapy studies. PMID:16514635

  1. [Coxitis fugax. The role of diagnostic imaging].

    PubMed

    de Pellegrin, M; Fracassetti, D; Ciampi, P

    1997-10-01

    Between 1990 and 1996, 129 children (mean age 4.8 years) with hip pain were examined consecutively. In group I (n = 100, mean age 4.14 +/- 2.2), transient synovitis of the hip was diagnosed; group II (n = 29, mean age 7.3 +/- 2.1) showed the following diagnoses: Perthes' disease (n = 12), early slipped capital femoral epiphysis (n = 5), Meyer's dysplasia (n = 2), septic arthritis of the hip (n = 2), osteomyelitis of the acetabulum (n = 1), abscess of the psoas (n = 1), chondromatosis of the hip joint (n = 1), Ewing's sarcoma of the os pubis (n = 1), hip dysplasia (n = 1). Three patients who had synovitis developed Perthes' disease and were assigned to group II. The efficiency of ultrasound, scintigraphy and MRI as diagnostic tools was tested in the examination of painful hip. A capsular distension was present in 73 cases and showed a significant statistical difference (t-test, P < 0.001) in group I between affected and unaffected hips. There were no differences in the measurements of the epiphyseal and metaphyseal width in group I between the affected and the nonaffected side (t-test, P = 0.91, P = 0.57) and between the first sonographic evaluation at presentation and at the follow-up (t-test, P = 0.053, P = 0.75). MRI was performed, because of persistent joint effusion, in 10 cases in group I, and Perthes' disease was excluded. In group II the use of an MRI allowed the diagnosis in 89% of the cases. Sonographic examination, together with X-ray examination and serological testing, represent the first choices in the evaluation of a painful hip at presentation and in the follow-up of transient synovitis. MRI should always be performed when abnormalities are present at the clinical and sonographic examination, and when the X-ray does not allow a clear diagnosis. PMID:9446093

  2. Distal Ulna Reconstruction using the Second Metatarsal: Anatomical Study.

    PubMed

    Cavadas, Pedro C; Thione, Alessandro; Martinez, Isabel Elía

    2016-05-01

    Background The ulnar head is a key stabilizer of the wrist and forearm. The authors investigated the possibility of using the second metatarsal bone to replace the distal ulna in an anatomical study. Methods The morphology of the distal ulna and the head of the second metatarsal (MT2) were studied using three-dimensional computerized tomographic (CT) scans of the wrist and foot in 52 patients without pathology related to these two areas, and 11 cadaveric specimens. The radius and height of the best-fit cylinder for both epiphyses were measured in the CT scans and compared. In the cadaveric specimens an osteotomy of the metatarsal neck was performed to rotate 90 degrees the head of the MT2 to match the shape of the distal ulna. Results The osseous morphology of the distal ulna and the head of the MT2 are roughly cylindrical, but differently oriented relative to the diaphyseal axes. In the osteotomized cadaveric MT2specimens, the overall morphology was relatively similar that of the distal ulna. The mean length of the MT2 after the osteotomy was 65 mm. Conclusion The head of the MT2 was found to have a similar cylindrical morphology to that of the ulnar head, with a different orientation. The radius of the cylinder was similar, although the height was bigger for the MT2. After a rotation osteotomy of the neck of the MT2 the overall shape and orientation of the epiphysis was more similar to the distal ulna. A vascularized transfer of an osteotomized MT2 would be an option for autologous reconstruction of the distal ulna in selected patients, but further study is needed in terms of the vascular supply, ligamentous reconstruction, and reconstruction of the sigmoid notch. Level of Evidence Therapeutic, level IV. PMID:27104084

  3. Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis.

    PubMed

    Michot, Caroline; Le Goff, Carine; Goldenberg, Alice; Abhyankar, Avinash; Klein, Céline; Kinning, Esther; Guerrot, Anne-Marie; Flahaut, Philippe; Duncombe, Alice; Baujat, Genevieve; Lyonnet, Stanislas; Thalassinos, Caroline; Nitschke, Patrick; Casanova, Jean-Laurent; Le Merrer, Martine; Munnich, Arnold; Cormier-Daire, Valérie

    2012-04-01

    Acrodysostosis is a rare autosomal-dominant condition characterized by facial dysostosis, severe brachydactyly with cone-shaped epiphyses, and short stature. Moderate intellectual disability and resistance to multiple hormones might also be present. Recently, a recurrent mutation (c.1102C>T [p.Arg368*]) in PRKAR1A has been identified in three individuals with acrodysostosis and resistance to multiple hormones. After studying ten unrelated acrodysostosis cases, we report here de novo PRKAR1A mutations in five out of the ten individuals (we found c.1102C>T [p.Arg368(∗)] in four of the ten and c.1117T>C [p.Tyr373His] in one of the ten). We performed exome sequencing in two of the five remaining individuals and selected phosphodiesterase 4D (PDE4D) as a candidate gene. PDE4D encodes a class IV cyclic AMP (cAMP)-specific phosphodiesterase that regulates cAMP concentration. Exome analysis detected heterozygous PDE4D mutations (c.673C>A [p.Pro225Thr] and c.677T>C [p.Phe226Ser]) in these two individuals. Screening of PDE4D identified heterozygous mutations (c.568T>G [p.Ser190Ala] and c.1759A>C [p.Thr587Pro]) in two additional acrodysostosis cases. These mutations occurred de novo in all four cases. The four individuals with PDE4D mutations shared common clinical features, namely characteristic midface and nasal hypoplasia and moderate intellectual disability. Metabolic screening was normal in three of these four individuals. However, resistance to parathyroid hormone and thyrotropin was consistently observed in the five cases with PRKAR1A mutations. Finally, our study further supports the key role of the cAMP signaling pathway in skeletogenesis. PMID:22464250

  4. Radiographic and Tomographic Analysis in Patients with Stickler Syndrome Type I

    PubMed Central

    Al Kaissi, Ali; Chehida, Farid Ben; Ganger, Rudolf; Kenis, Vladimir; Zandieh, Shahin; Hofstaetter, Jochen G; Klaushofer, Klaus; Grill, Franz

    2013-01-01

    Objective: To further investigate the underlying pathology of axial and appendicular skeletal abnormalities such as painful spine stiffness, gait abnormalities, early onset osteoarthritis and patellar instability in patients with Stickler syndrome type I. Radiographic and tomographic analyses were organized. Methods: From a series of Stickler syndrome patients followed from early life to late childhood. Ten patients (6 boys and four girls of different ethnic origins were consistent with the diagnosis of Stickler syndrome type I ). Phenotypic characterization was the baseline tool applied for all patients and genotypic correlation was performed on four families Results: A constellation of axial abnormalities namely; anterolateral ossification of the anterior longitudinal spinal ligament with subsequent fusion of two cervical vertebrae, early onset Forestier disease (progressive spinal hyperostosis with subsequent vertebral fusion on top of bridging osteophytes and “Bamboo-like spine” resembling ankylosing spondylitis) and severe premature spine degeneration were evident. Appendicular abnormalities in connection with generalized epiphyseal dysplasia were the underlying aetiology in patients with Intoeing gait and femoral anteversion, early onset severe osteoarthritis of the weight bearing joint. Remarkable trochleo-patellar dysplasia secondary to severe osteoarthritis causing effectively the development of patellar instability was additional pathology. Mutation of COL2A1 has been confirmed as the causative gene for Stickler syndrome type I Conclusion: We concluded that conventional radiographs and the molecular determination of a COL2A1 in patients with (Stickler syndrome type I) are insufficient tools to explain the reasons behind the tremendous magnitude of axial and appendicular skeletal abnormalities. We were able to modify the criteria of the clinical phenotype as designated by Rose et al in accordance with the novel axial and appendicular criteria as

  5. Flexor Tendon Entrapment at the Malunited Base Fracture of the Proximal Phalanx of the Finger in Child: A Case Report.

    PubMed

    Lee, Young-Keun; Park, Soojin; Lee, Malrey

    2015-09-01

    The proximal phalangeal base is the most commonly fractured hand bone in children. Such fractures are rarely reported as irreducible due to flexor tendon entrapment. Here, we describe a patient who sustained a malunited fracture on the right fifth finger proximal phalanx with flexor tendon entrapment after treatment with closed reduction with K-wires fixation.A 13-year-old patient came to the clinic following a bicycle accident 6 weeks ago. He presented with flexion limitation in his small finger on the right hand. During physical examination, the patient felt no pain, and the neurovascular structures were intact. However range of motion (ROM) in his small finger was not normal. Plain radiographs displayed a Salter-Harris type II fracture of the small finger proximal phalanx base and volar angulation with callus formation. During the operation, it was established that the flexor digitorum superficialis (FDS) around the fracture had a severe adhesion, whereas the flexor digitorum profundus (FDP) was entrapped between the volarly displaced metaphyses and the epiphyses and united with the bone. We removed the volarly displaced metaphyses and freed FDP and repaired the A2 pulley. The bone was anatomically fixed with K-wires. In the treatment after the operation, on the 2nd day, the patient was permitted the DIP joint motion by wearing a dynamic splint.At the 12-months follow-up, the patient had regained full ROM with no discomfort and the proximal phalanx growth plate of the small finger closed naturally with normal alignment.When treating a proximal phalangeal base fracture in children, the possibility of flexor tendon entrapment should be considered and should be carefully dealt with in its treatment. PMID:26334897

  6. Long-term therapeutic efficacy of allogenic bone marrow transplantation in a patient with mucopolysaccharidosis IVA

    PubMed Central

    Chinen, Yasutsugu; Higa, Takeshi; Tomatsu, Shunji; Suzuki, Yasuyuki; Orii, Tadao; Hyakuna, Nobuyuki

    2014-01-01

    Mucopolysaccharidosis IVA (MPS IVA) is one of the lysosomal storage diseases. It is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of the specific glycosaminoglycans keratan sulfate and chondroitin-6-sulfate. This accumulation has a direct impact on cartilage and bone development, resulting in systemic skeletal dysplasia. There is no curative therapy for this skeletal dysplasia. This report describes long-term therapeutic efficacy in a 15-year-old boy with a severe form of MPS IVA who received successful allogeneic bone marrow transplantation (BMT) from his HLA-identical carrier sister. The level of the GALNS enzyme in the recipient’s lymphocytes reached almost half of normal level within two years after BMT. For the successive 9+ years post-BMT, GALNS activity in his lymphocytes maintained the same level as the donor’s, and the level of urinary uronic acid was reduced. Lumbar bone mineral density increased around 50% one year later post-BMT and was kept consistent. Radiographs showed that the figures of trochanter major and minor appeared, while the epiphyseal dysplasia in the femoral cap was almost unchanged. Loud snoring and apnea disappeared. Vital capacity increased to around 20% for the first two years and was maintained. Activity of daily life (ADL) was improved in work/study efficacy, respiratory status, sleep, joint pain, and frequency of infection. In conclusion, the long-term study of hematopoetic stem cell transplantation has shown clinical improvements in respiratory function, radiograph findings, ADL, and biochemical findings, suggesting that it is a potential therapeutic option for patients with MPS IVA. PMID:25593792

  7. Bone quality is affected by food restriction and by nutrition-induced catch-up growth.

    PubMed

    Pando, Rakefet; Masarwi, Majdi; Shtaif, Biana; Idelevich, Anna; Monsonego-Ornan, Efrat; Shahar, Ron; Phillip, Moshe; Gat-Yablonski, Galia

    2014-12-01

    Growth stunting constitutes the most common effect of malnutrition. When the primary cause of malnutrition is resolved, catch-up (CU) growth usually occurs. In this study, we have explored the effect of food restriction (RES) and refeeding on bone structure and mechanical properties. Sprague-Dawley male rats aged 24 days were subjected to 10 days of 40% RES, followed by refeeding for 1 (CU) or 26 days long-term CU (LTCU). The rats fed ad libitum served as controls. The growth plates were measured, osteoclasts were identified using tartrate-resistant acid phosphatase staining, and micro-computed tomography (CT) scanning and mechanical testing were used to study structure and mechanical properties. Micro-CT analysis showed that RES led to a significant reduction in trabecular BV/TV and trabecular number (Tb.N), concomitant with an increase in trabecular separation (Tb.Sp). Trabecular BV/TV and Tb.N were significantly greater in the CU group than in the RES in both short- and long-term experiments. Mechanical testing showed that RES led to weaker and less compliant bones; interestingly, bones of the CU group were also more fragile after 1 day of CU. Longer term of refeeding enabled correction of the bone parameters; however, LTCU did not achieve full recovery. These results suggest that RES in young rats attenuated growth and reduced trabecular bone parameters. While nutrition-induced CU growth led to an immediate increase in epiphyseal growth plate height and active bone modeling, it was also associated with a transient reduction in bone quality. This should be taken into consideration when treating children undergoing CU growth. PMID:25248555

  8. PCR diagnostics of Mycobacterium tuberculosis in historic human long bone remains from 18th century burials in Kaiserebersdorf, Austria

    PubMed Central

    Bachmann, Lutz; Däubl, Barbara; Lindqvist, Charlotte; Kruckenhauser, Luise; Teschler-Nicola, Maria; Haring, Elisabeth

    2008-01-01

    Background In the present pilot study we applied recently published protocols for detecting Mycobacterium tuberculosis in human remains. We screened long bones from an 18th century cemetery and skulls from the anatomical "Weisbach collection" (19th century). In addition, besides the study of abundance of tuberculosis in inmates of the poorhouse itself, we were interested to test whether in this particular instance tuberculosis can be identified from cortical bones, which are rarely affected by tuberculosis, but mostly better preserved than the vertebral bodies or epiphyses. Method The DNA extractions from the bone samples were obtained following established ancient DNA protocols. Subsequently extracts were subjected to a series of PCR amplifications using primer pairs published previously [1,2]. PCR products of the expected size were subsequently sequenced. Results Only primers targeting the repetitive IS6110 insertion sequence yielded PCR products of appropriate size. In one sample only (skull sample WB354 of the "Weisbach collection") sequence analysis revealed an authentic M. tuberculosis sequence that matched to a reference sequence from GenBank. Conclusion With a variety of established PCR approaches we failed to detect M. tuberculosis DNA in historic human femurs from an 18th century cemetery relating to a poor house in Kaiserebersdorf, Austria. Our data may indicate that in this particular case, thoracic or lumbar vertebrae, i.e. bones that are severely affected by the disease, would be more suitable for molecular diagnostics than long bones. However, the unpredictable state of DNA preservation in bones from museum collections does not allow any general recommendation of any type of bone. PMID:18799009

  9. CRTAP AND LEPRE1 MUTATIONS IN RECESSIVE OSTEOGENESIS IMPERFECTA

    PubMed Central

    Baldridge, Dustin; Schwarze, Ulrike; Morello, Roy; Lennington, Jennifer; Bertin, Terry K.; Pace, James M.; Pepin, Melanie G.; Weis, MaryAnn; Eyre, David R.; Walsh, Jennifer; Lambert, Deborah; Green, Andrew; Robinson, Haynes; Michelson, Melonie; Houge, Gunnar; Lindman, Carl; Martin, Judith; Ward, Jewell; Lemyre, Emmanuelle; Mitchell, John J.; Krakow, Deborah; Rimoin, David L.; Cohn, Daniel H.; Byers, Peter H.; Lee, Brendan

    2009-01-01

    Autosomal dominant osteogenesis imperfecta (OI) is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen. Recently, dysregulation of hydroxylation of a single proline residue at position 986 of both the triple-helical domains of type I collagen α1(I) and type II collagen α1(II) chains has been implicated in the pathogenesis of recessive forms of OI. Two proteins, CRTAP, or cartilage-associated protein, and prolyl-3-hydroxylase-1 (P3H1, encoded by the LEPRE1 gene) form a complex that performs the hydroxylation and brings the prolyl cis-trans isomerase cyclophilin-B (CYPB) to the unfolded collagen. In our screen of 78 subjects diagnosed with OI type II or III, we identified three probands with mutations in CRTAP and sixteen with mutations in LEPRE1. The latter group includes a mutation in patients from the Irish Traveller population, a genetically isolated community with increased incidence of OI. The clinical features resulting from CRTAP or LEPRE1 loss of function mutations were difficult to distinguish at birth. Infants in both groups had multiple fractures, decreased bone modeling (affecting especially the femurs), and extremely low bone mineral density. Interestingly, “popcorn” epiphyses may reflect underlying cartilaginous and bone dysplasia in this form of OI. These results expand the range of CRTAP/LEPRE1 mutations that result in recessive OI and emphasize the importance of distinguishing recurrence of severe OI of recessive inheritance from those that result from parental germline mosaicism for COL1A1 or COL1A2 mutations. PMID:18566967

  10. Cyp26b1 within the growth plate regulates bone growth in juvenile mice

    SciTech Connect

    Minegishi, Yoshiki; Sakai, Yasuo; Yahara, Yasuhito; Akiyama, Haruhiko; Yoshikawa, Hideki; Hosokawa, Ko; Tsumaki, Noriyuki

    2014-11-07

    Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1{sup Δchon} cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone.

  11. Descriptions of the lower limb skeleton of Homo floresiensis.

    PubMed

    Jungers, W L; Larson, S G; Harcourt-Smith, W; Morwood, M J; Sutikna, T; Due Awe, Rokhus; Djubiantono, T

    2009-11-01

    Bones of the lower extremity have been recovered for up to nine different individuals of Homo floresiensis - LB1, LB4, LB6, LB8, LB9, LB10, LB11, LB13, and LB14. LB1 is represented by a bony pelvis (damaged but now repaired), femora, tibiae, fibulae, patellae, and numerous foot bones. LB4/2 is an immature right tibia lacking epiphyses. LB6 includes a fragmentary metatarsal and two pedal phalanges. LB8 is a nearly complete right tibia (shorter than that of LB1). LB9 is a fragment of a hominin femoral diaphysis. LB10 is a proximal hallucal phalanx. LB11 includes pelvic fragments and a fragmentary metatarsal. LB13 is a patellar fragment, and LB14 is a fragment of an acetabulum. All skeletal remains recovered from Liang Bua were extremely fragile, and some were badly damaged when they were removed temporarily from Jakarta. At present, virtually all fossil materials have been returned, stabilized, and hardened. These skeletal remains are described and illustrated photographically. The lower limb skeleton exhibits a uniquely mosaic pattern, with many primitive-like morphologies; we have been unable to find this combination of ancient and derived (more human-like) features in either healthy or pathological modern humans, regardless of body size. Bilateral asymmetries are slight in the postcranium, and muscle markings are clearly delineated on all bones. The long bones are robust, and the thickness of their cortices is well within the ranges seen in healthy modern humans. LB1 is most probably a female based on the shape of her greater sciatic notch, and the marked degree of lateral iliac flaring recalls that seen in australopithecines such as "Lucy" (AL 288-1). The metatarsus has a human-like robusticity formula, but the proximal pedal phalanges are relatively long and robust (and slightly curved). The hallux is fully adducted, but we suspect that a medial longitudinal arch was absent. PMID:19062072

  12. The utility of mouse models to provide information regarding the pathomolecular mechanisms in human genetic skeletal diseases: The emerging role of endoplasmic reticulum stress (Review).

    PubMed

    Briggs, Michael D; Bell, Peter A; Pirog, Katarzyna A

    2015-06-01

    Genetic skeletal diseases (GSDs) are an extremely diverse and complex group of rare genetic diseases that primarily affect the development and homeostasis of the osseous skeleton. There are more than 450 unique and well-characterised phenotypes that range in severity from relatively mild to severe and lethal forms. Although individually rare, as a group of related genetic diseases, GSDs have an overall prevalence of at least 1 per 4,000 children. Qualitative defects in cartilage structural proteins result in a broad spectrum of both recessive and dominant GSDs. This review focused on a disease spectrum resulting from mutations in the non-collagenous glycoproteins, cartilage oligomeric matrix protein (COMP) and matrilin-3, which together cause a continuum of phenotypes that are amongst the most common autosomal dominant GSDs. Pseudoachondroplasia (PSACH) and autosomal dominant multiple epiphyseal dysplasia (MED) comprise a disease spectrum characterised by varying degrees of disproportionate short stature, joint pain and stiffness and early-onset osteoarthritis. Over the past decade, the generation and deep phenotyping of a range of genetic mouse models of the PSACH and MED disease spectrum has allowed the disease mechanisms to be characterised in detail. Moreover, the generation of novel phenocopies to model specific disease mechanisms has confirmed the importance of endoplasmic reticulum (ER) stress and reduced chondrocyte proliferation as key modulators of growth plate dysplasia and reduced bone growth. Finally, new insight into related musculoskeletal complications (such as myopathy and tendinopathy) has also been gained through the in-depth analysis of targeted mouse models of the PSACH-MED disease spectrum. PMID:25824717

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

    PubMed

    Tesch, W; Vandenbos, T; Roschgr, P; Fratzl-Zelman, N; Klaushofer, K; Beertsen, W; Fratzl, P

    2003-01-01

    Tissue nonspecific alkaline phosphatase (TNALP) is thought to play an important role in mineralization processes, although its exact working mechanism is not known. In the present investigation we have studied mineral crystal characteristics in the developing skeleton of TNALP-deficient mice. Null mutants (n = 7) and their wild-type littermates (n = 7) were bred and killed between 8 and 22 days after birth. Skeletal tissues were processed to assess mineral characteristics (small angle X-ray scattering, quantitative backscattered electron imaging), and to analyze bone by light microscopy and immunolabeling. The results showed a reduced longitudinal growth and a strongly delayed epiphyseal ossification in the null mutants. This was accompanied by disturbances in mineralization pattern, in that crystallites were not orderly aligned with respect to the longitudinal axis of the cortical bone. Among the null mutants, a great variability in the mineralization parameters was noticed. Also, immunolabeling of osteopontin (OPN) revealed an abnormal distribution pattern of the protein within the bone matrix. Whereas in the wild-type animals OPN was predominantly observed in cement and reversal lines, in the null mutants, OPN was also randomly dispersed throughout the nonmineralized matrix, with focal densities. In contrast, the distribution pattern of osteocalcin (OC) was comparable in both types of animals. It is concluded that ablation of TNALP results not only in hypomineralization of the skeleton, but also in a severe disorder of the mineral crystal alignment pattern in the corticalis of growing long bone in association with a disordered matrix architecture, presumably as a result of impaired bone remodeling and maturation. PMID:12510812

  14. The girl from the church of the sacrament: a case of congenital syphilis in XVIII century Lisbon.

    PubMed

    de Souza, Sheila Mendonça; Codinha, Sonia; Cunha, Eugénia

    2006-12-01

    Syphilis is a sexually or congenitally transmitted infectious disease with an impact on the health of human populations that has undergone important cycles in different countries and periods of history. Its presence was first diagnosed in Europe in the late XIV century. In Portugal, although there are various written records of the infection in the last centuries, there are rare references to it in archeological findings (mummified bodies are also rare in Portugal). The current study describes a probable case of congenital syphilis in an 18-month-old girl buried in the Church of the Sacrament in Lisbon. Her body, dating to the XVIII century, was found mummified together with dozens of others, still not studied. Symmetrical periostitis of the long bones, osteitis, metaphyseal lesions, left knee articular, and epiphyseal destruction, and a rarefied lesion with a radiological appearance compatible with Wimberger's sign all point to a diagnosis of congenital syphilis. The diagnosis of this severe form of the infection, possibly related to the cause of death in this upper-class girl, calls attention to the disease's presence in XVIII century Lisbon and is consistent with the intense mobilization at the time in relation to the risks posed by so-called heredosyphilis. It is the first case of congenital syphilis in a child reported in archeological findings in Portugal, and can be correlated with other cases in skeletons of adults buried in cemeteries in Lisbon (in the XVI to XVIII centuries) and Coimbra (XIX century). Finally, this finding highlights the need to study the entire series of mummified bodies in the Church of the Sacrament in order to compare the paleopathological findings and existing historical documents on syphilis, so as to expand the paleoepidemiological knowledge of this infection in XVIII century Lisbon. PMID:17308818

  15. A method for estimating age of Danish medieval sub-adults based on long bone length.

    PubMed

    Primeau, Charlotte; Friis, Laila; Sejrsen, Birgitte; Lynnerup, Niels

    2012-07-01

    The preferred method for aging archaeological sub-adult skeletons is by dental examination. In cases where no dental records are available, age estimation may be performed according to epiphyseal union, skeletal elements or diaphyseal lengths. Currently no data have been produced specifically for aging archaeological Danish sub-adults from the medieval period based on diaphyseal lengths. The problem with using data on Danish samples, which have been derived from a different population, is the possibility of skewing age estimates. In this study 58 Danish archaeological sub-adults were examined, aged from approximately six years to twenty-one years. The samples were aged according to two dental methods: Haavikko and Ubelaker. Regression formulae were constructed for aging according to their diaphyseal lengths both for individual long bones and combinations of upper and lower long bones. This study indicated that with the regression formulae developed, estimation of age can be done with reasonable results on Danish sub-adults. The Danish data were then compared to data from a different archaeological sample and a modern sample. It showed that the modern data indicated a consistently lower age compared to this sample which increased until reaching a maximum of nearly five years and six months. When comparing the archaeological data to this study, the growth profile crossed over at 12.5 years with a maximum age difference before the cross point of two years and three months lower for the archaeological data. After the cross point there was a maximum difference of three years and four months higher for the archaeological data. This study has shown the importance of using data for age estimation for archaeological material which has been developed specifically for that population. In addition it has presented a possible solution for Danish sub-adult material when dental material is not available. PMID:22928354

  16. Ontogeny of the female femur: geometric morphometric analysis applied on current living individuals of a Spanish population

    PubMed Central

    Pujol, Aniol; Rissech, Carme; Ventura, Jacint; Badosa, Joaquim; Turbón, Daniel

    2014-01-01

    In this study we describe the development of the female femur based on the analysis of high-resolution radiographic images by means of geometric morphometrics, while assessing the usefulness of this method in these kinds of studies. The material analysed consisted of digital images in DICOM format (telemetries), corresponding to 184 left femora in anterior view, obtained from the database of the Hospital Sant Joan de Déu of Barcelona (Spain). Bones analysed corresponded to individuals from 9 to 14 years old. Size and shape variation of the entire femur was quantified by 22 two-dimensional landmarks. Landmark digitisation errors were assessed using Procrustes anova test. Centroid size (CS) variation with age was evaluated by an anova test. Shape variation was assessed by principal component analysis. A mancova test between the first five principal components and age, using the CS as covariable, was applied. Results indicated that both size and shape vary significantly with age. Several age-related shape changes remained significant after removing the allometric effect. In general, an increase in the robustness of the bone and noticeable phenotypic changes in certain areas of the femur were observed. During growth in the proximal region of the femur, the collo-diaphyseal angle decreases, the neck of the femur widens and the fovea moves to a lower position, standing more in line with the plane of the neck. Likewise, the size of the greater and lesser trochanters increase. In the distal region, a significant increase of epiphyseal dimensions was recorded, mainly in the medial condyle. The angular remodelling of the neck and the bicondylar region of the femur in females continues until 13 years old. The information provided in the present study increases our knowledge on the timing and morphology of the femur during development, and in particular the morphology of the different femoral ossification centres during development. PMID:24975495

  17. Effects of microgravity on rat bone, cartlage and connective tissues

    NASA Technical Reports Server (NTRS)

    Doty, S.

    1990-01-01

    The response to hypogravity by the skeletal system was originally thought to be the result of a reduction in weight bearing. Thus a reduced rate of new bone formation in the weight-bearing bones was accepted, when found, as an obvious result of hypogravity. However, data on non-weight-bearing tissues have begun to show that other physiological changes can be expected to occur to animals during spaceflight. This overview of the Cosmos 1887 data discusses these results as they pertain to individual bones or tissues because the response seems to depend on the architecture and metabolism of each tissue under study. Various effects were seen in different tissues from the rats flown on Cosmos 1887. The femur showed a reduced bone mineral content but only in the central region of the diaphysis. This same region in the tibia showed changes in the vascularity of bone as well as some osteocytic cell death. The humerus demonstrated reduced morphometric characteristics plus a decrease in mechanical stiffness. Bone mineral crystals did not mature normally as a result of flight, suggesting a defect in the matrix mineralization process. Note that these changes relate directly to the matrix portion of the bone or some function of bone which slowly responds to changes in the environment. However, most cellular functions of bone are rapid responders. The stimulation of osteoblast precursor cells, the osteoblast function in collagen synthesis, a change in the proliferation rate of cells in the epiphyseal growth plate, the synthesis and secretion of osteocalcin, and the movement of water into or out of tissues, are all processes which respond to environmental change. These rapidly responding events produced results from Cosmos 1887 which were frequently quite different from previous space flight data.

  18. Effects of excess maternal thyroxin on the bones of rat offspring from birth to the post-weaning period.

    PubMed

    Maia, Mariana Zanini; Santos, Gianne Karla; Batista, Ana Claudia Moura; Reis, Amanda Maria Sena; Silva, Juneo Freitas; Ribeiro, Lorena Gabriela Rocha; Ocarino, Natália de Melo; Serakides, Rogéria

    2016-04-01

    Objective To evaluate, in rat offspring, bone changes induced by excess maternal thyroxin during pregnancy and lactation, and to assess the reversibility of these changes after weaning. Material and methods Twenty Wistar rats were distributed in two groups, hyperthyroid and control, that were treated daily with L-thyroxin (50 mcg/animal) and placebo, respectively. The treatment was initiated seven days before mating and continued throughout pregnancy and lactation. From every female of each of the two groups, two offspring were euthanized after birth, two at 21 days of age (weaning), and two at 42 days of age (21 days after weaning). In newborns, the length of pelvic and thoracic limbs were measured, and in the other animals, the length and width of the femur and humerus were measured. Bones were dissected, decalcified, embedded in paraffin, and analyzed histomorphometrically. Results Excess maternal thyroxin significantly reduced the length of the pelvic limb in neonates. In 21-day-old individuals, excess maternal thyroxine reduced the length and the width of the femur and the humerus. It also increased thickness of the epiphyseal plate and the percentage of trabecular bone tissue. In 42-day-old individuals, there were no significant differences between groups in relation to the parameters evaluated in the previous periods. Conclusion Excess maternal thyroxine reduced growth in suckling rats both at birth and at weaning, and it also increased the percentage of trabecular bone tissue in 21-day-old animals. These changes, however, were reversible at 42 days, i.e., 21 days after weaning. Arch Endocrinol Metab. 2016;60(2):130-7. PMID:27191047

  19. [Retrosternal luxation of the clavicle. Apropos of 4 cases surgically treated using a temporary screwed anterior plate and review of the literature].

    PubMed

    Asfazadourian, H; Kouvalchouk, J F

    1997-01-01

    The authors report 4 new cases of retrosternal dislocation of the clavicle operated by capsular and ligament restoration, and temporary stabilization by anterior plating. The 4 patients were men with a mean age of 17.5 years. The lesion was caused by a sports injury (football, rugby) in 3 out of 4 cases and was related to an indirect mechanism. Clinical examination allowed the diagnosis, was related to based on painful palpation of a dip over the joint, supported by radiology and computed tomography. CT did not reveal the epiphyseal separation present in two cases. Complications were frequent: 1 case of tracheal compression, 2 cases of temporary paresthesia of the upper limb, 2 cases of venous compression with one case of subclavian and medial jugularis venous thrombosis, 1 hemopneumothorax. Surgical reduction was performed in all 4 cases after 2 failures of attempted orthopedic treatment under general anesthesia. All patients recovered a full range of movement, a painless shoulder and no recurrence has been observed. All complications resolved after reduction. Venous thrombosis responded favourably after 6 months of anticoagulant therapy. One plate breakage was observed with no clinical implications. On the basis of an extensive review of the literature, the authors discuss the epidemiology, pathology and the importance of associated injuries, which are frequent and sometimes serious, justifying urgent reduction. Computed tomography is the most useful radiologic modality, both for diagnosis and for investigation of complications. Orthopedic treatment must be attempted first (especially in children) according to a well systematized technique. One third of attempts fail, and cases of delayed diagnosis and serious vascular complications, then require surgical treatment. The costoclavicular ligament is repaired either by Burrows's ligamentoplasty or by bone suture; the clavicle is stabilized by bone suture or by anterior plating. The authors do not advocate either

  20. Sulfation of chondroitin. Specificity, degree of sulfation, and detergent effects with 4-sulfating and 6-sulfating microsomal systems.

    PubMed

    Sugumaran, G; Silbert, J E

    1988-04-01

    Microsomal preparations from chondroitin 6-sulfate-producing chick embryo epiphyseal cartilage, and from chondroitin 4-sulfate-producing mouse mastocytoma cells, were incubated with UDP-[14C]glucuronic acid and UDP-N-acetylgalactosamine to form non-sulfated proteo[14C]chondroitin. Aliquots of the incubations were then incubated with 3'-phosphoadenylylphosphosulfate (PAPS) in the presence or absence of various detergents. In the absence of detergents, there was good sulfation of this endogenous proteo[14C]chondroitin by the original microsomes from both sources. Detergents, with the exception of Triton X-100, markedly inhibited sulfation in the mast cell system but not in the chick cartilage system. These results indicate that sulfation and polymerization are closely linked on cell membranes and that in some cases this organization can be disrupted by detergents. When aliquots of the original incubation were heat inactivated, and then reincubated with new microsomes from chick cartilage and/or mouse mastocytoma cells plus PAPS, there was no significant sulfation of this exogenous proteo[14C] chondroitin with either system unless Triton X-100 was added. Sulfation of exogenous chondroitin and chondroitin hexasaccharide was compared with sulfation of endogenous and exogenous proteo[14C]chondroitin. Sulfate incorporation into hexasaccharide and chondroitin decreased as their concentrations (based on uronic acid) approached that of the proteo[14C]chondroitin. At the same time, the degree of sulfation in percent of substituted hexosamine increased. However, the degree of sulfation did not reach that of the endogenous proteo[14C]chondroitin. Hexasaccharide and chondroitin sulfation were stimulated by the presence of Triton X-100. However, in contrast to the exogenous proteo[14C]chondroitin, there was some sulfation of hexasaccharide and chondroitin in the absence of this detergent. These results indicate that the intact microsomal system was not accessible to the larger

  1. Three-Dimensional Quantitative Morphometric Analysis (QMA) for In Situ Joint and Tissue Assessment of Osteoarthritis in a Preclinical Rabbit Disease Model

    PubMed Central

    Stok, Kathryn S.; Besler, Bryce A.; Steiner, Thomas H.; Villarreal Escudero, Ana V.; Zulliger, Martin A.; Wilke, Markus; Atal, Kailash; Quintin, Aurelie; Koller, Bruno; Müller, Ralph; Nesic, Dobrila

    2016-01-01

    This work utilises advances in multi-tissue imaging, and incorporates new metrics which define in situ joint changes and individual tissue changes in osteoarthritis (OA). The aims are to (1) demonstrate a protocol for processing intact animal joints for microCT to visualise relevant joint, bone and cartilage structures for understanding OA in a preclinical rabbit model, and (2) introduce a comprehensive three-dimensional (3D) quantitative morphometric analysis (QMA), including an assessment of reproducibility. Sixteen rabbit joints with and without transection of the anterior cruciate ligament were scanned with microCT and contrast agents, and processed for histology. Semi-quantitative evaluation was performed on matching two-dimensional (2D) histology and microCT images. Subsequently, 3D QMA was performed; including measures of cartilage, subchondral cortical and epiphyseal bone, and novel tibio-femoral joint metrics. Reproducibility of the QMA was tested on seven additional joints. A significant correlation was observed in cartilage thickness from matching histology-microCT pairs. The lateral compartment of operated joints had larger joint space width, thicker femoral cartilage and reduced bone volume, while osteophytes could be detected quantitatively. Measures between the in situ tibia and femur indicated an altered loading scenario. High measurement reproducibility was observed for all new parameters; with ICC ranging from 0.754 to 0.998. In conclusion, this study provides a novel 3D QMA to quantify macro and micro tissue measures in the joint of a rabbit OA model. New metrics were established consisting of: an angle to quantitatively measure osteophytes (σ), an angle to indicate erosion between the lateral and medial femoral condyles (ρ), a vector defining altered angulation (λ, α, β, γ) and a twist angle (τ) measuring instability and tissue degeneration between the femur and tibia, a length measure of joint space width (JSW), and a slope and intercept

  2. Ihh and PTH1R signaling in limb mesenchyme is required for proper segmentation and subsequent formation and growth of digit bones.

    PubMed

    Amano, Katsuhiko; Densmore, Michael; Fan, Yi; Lanske, Beate

    2016-02-01

    Digit formation is a process, which requires the proper segmentation, formation and growth of phalangeal bones and is precisely regulated by several important factors. One such factor is Ihh, a gene linked to BDA1 and distal symphalangism in humans. In existing mouse models, mutations in Ihh have been shown to cause multiple synostosis in the digits but lead to perinatal lethality. To better study the exact biological and pathological events which occur in these fused digits, we used a more viable Prx1-Cre;Ihh(fl/fl) model in which Cre recombinase is expressed during mesenchymal condensation in the earliest limb buds at E9.5 dpc and found that mutant digits continuously fuse postnatally until phalanges are finally replaced by an unsegmented "one-stick bone". Mutant mice displayed osteocalcin-positive mature osteoblasts, but had reduced proliferation and abnormal osteogenesis. Because of the close interaction between Ihh and PTHrP during endochondral ossification, we also examined the digits of Prx1-Cre;PTH1R(fl/fl) mice, where the receptor for PTHrP was conditionally deleted. Surprisingly, we found PTH1R deletion caused symphalangism, demonstrating another novel function of PTH1R signaling in digit formation. We characterized the symphalangism process whereby initial cartilaginous fusion prevented epiphyseal growth plate formation, resulting in resorption and replacement of the remaining cartilage by bony tissue. Chondrocyte differentiation displayed abnormal directionality in both mutants. Lastly, Prx1-Cre;Ihh(fl/fl);Jansen Tg mice, in which a constitutively active PTH1R allele was introduced into Ihh mutants, were established to address the possible involvement of PTH1R signaling in Ihh mutant digits. These rescue mice failed to show significantly improved phenotype, suggesting that PTH1R signaling in chondrocytes is not sufficient to restore digit formation. Our results demonstrate that Ihh and PTH1R signaling in limb mesenchyme are both essential to regulate

  3. Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene (SLC26A2): 22 novel mutations, mutation review, associated skeletal phenotypes, and diagnostic relevance.

    PubMed

    Rossi, A; Superti-Furga, A

    2001-03-01

    Mutations in the DTDST gene can result in a family of skeletal dysplasia conditions which comprise two lethal disorders, achondrogenesis type 1B (ACG1B) and atelosteogenesis type 2 (AO2); and two non-lethal disorders, diastrophic dysplasia (DTD) and recessive multiple epiphyseal dysplasia (rMED). The gene product is a sulfate-chloride exchanger of the cell membrane. Inactivation of the sulfate exchanger leads to intracellular sulfate depletion and to the synthesis of undersulfated proteoglycans in susceptible cells such as chondrocytes and fibroblasts. Genotype-phenotype correlations are recognizable, with mutations predicting a truncated protein or a non-conservative amino acid substitution in a transmembrane domain giving the severe phenotypes, and non-transmembrane amino acid substitutions and splice site mutations giving the milder phenotypes. The clinical phenotype is modulated strictly by the degree of residual activity. Over 30 mutations have been observed, including 22 novel mutations reported here. The most frequent mutation, 862C>T (R279W), is a mild mutation giving the rMED phenotype when homozygous and mostly DTD when compounded; occurrence at a CpG dinucleotide and its panethnic distribution suggest independent recurrence. Mutation IVS1+2T>C is the second most common mutation, but is very frequent in Finland. It produces low levels of correctly spliced mRNA, and results in DTD when homozygous. Two other mutations, 1045-1047delGTT (V340del) and 558C>T (R178X), are associated with severe phenotypes and have been observed in multiple patients. Most other mutations are rare. Heterozygotes are clinically unaffected. When clinical samples are screened for radiologic and histologic features compatible with the ACG1B/AO2/DTD/rMED spectrum prior to analysis, the mutation detection rate is high (over 90% of alleles), and appropriate genetic counseling can be given. The sulfate uptake or sulfate incorporation assays in cultured fibroblasts have largely been

  4. Bed rest suppresses bioassayable growth hormone release in response to muscle activity

    NASA Technical Reports Server (NTRS)

    McCall, G. E.; Goulet, C.; Grindeland, R. E.; Hodgson, J. A.; Bigbee, A. J.; Edgerton, V. R.

    1997-01-01

    Hormonal responses to muscle activity were studied in eight men before (-13 or -12 and -8 or -7 days), during (2 or 3, 8 or 9, and 13 or 14 days) and after (+2 or +3 and +10 or +11 days) 17 days of bed rest. Muscle activity consisted of a series of unilateral isometric plantar flexions, including 4 maximal voluntary contractions (MVCs), 48 contractions at 30% MVC, and 12 contractions at 80% MVC, all performed at a 4:1-s work-to-rest ratio. Blood was collected before and immediately after muscle activity to measure plasma growth hormone by radioimmunoassay (IGH) and by bioassay (BGH) of tibia epiphyseal cartilage growth in hypophysectomized rats. Plasma IGH was unchanged by muscle activity before, during, or after bed rest. Before bed rest, muscle activity increased (P < 0.05) BGH by 66% at -13 or -12 days (2,146 +/- 192 to 3,565 +/- 197 microg/l) and by 92% at -8 or -7 days (2,162 +/- 159 to 4,161 +/- 204 microg/l). After 2 or 3 days of bed rest, there was no response of BGH to the muscle activity, a pattern that persisted through 8 or 9 days of bed rest. However, after 13 or 14 days of bed rest, plasma concentration of BGH was significantly lower after than before muscle activity (2,594 +/- 211 to 2,085 +/- 109 microg/l). After completion of bed rest, muscle activity increased BGH by 31% at 2 or 3 days (1,807 +/- 117 to 2,379 +/- 473 microg/l; P < 0.05), and by 10 or 11 days the BGH response was similar to that before bed rest (1,881 +/- 75 to 4,160 +/- 315 microg/l; P < 0.05). These data demonstrate that the ambulatory state of an individual can have a major impact on the release of BGH, but not IGH, in response to a single bout of muscle activity.

  5. Role of Growth Hormone, Exercise and Serum Phosphorus in Unloaded Bone of Young Rats

    NASA Technical Reports Server (NTRS)

    Arnnaud, Sara B.; Harper, J. S.; Gosselink, K. L.; Navidi, M.; Fung, P.; Grindeland, R. E.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Growth hormone, known to be stimulated by exercise, is suppressed in rats after space flight and in a ground-based model in which the hind-limbs are unloaded (S). To determine the role of GH in the osteopenia of unloaded bones of S rats, young males were treated with GH combined with insulin-like growth factor-1 (IGF-1), a peptide that mediates the local actions of the hormone. 200 g rats, hypophysectomized (hypox) 17 d earlier, were treated with 1 mg/kg/d GH/IGF-1 (H) or saline (C) in 3 divided daily doses x10 d. Hind-limb bones were unloaded (S), ambulated (A) or exercised (X) by climbing a ladder while carrying a weight. Growth was monitored daily. Tibial growth plate (Tepi) was measured with a micrometer, and femoral (F) area, length, and mineral content (BMC) by DEXA. Parameters of calcium metabolism were measured by autoanalyzer and calciotropic hormones by radioimmunoassay. F bone density, g/square cm, (BMD) or BW were not affected by S in Hypox. However, FBMD was lower in S+H than A+H (p is less than 0.002) and H stimulated whole body growth in S (5.2 g/d) and SX (5.6 g/d) to a lesser extent than in A (6.6 g/d) (p is less than 0.05). Adjusted for BW, Tepi showed the greatest increase in S+H+X (64%), the next highest increase in S+H (50%) and no change in S+X. F area, length and BMC/100 g BW were lower in all H groups than respective C's. By multiple regression analysis, serum phosphorus (Pi) which correlated with Tepi (r = 0.88, p is less than 0.001) and was inversely related to FBMC (r = -0.68, p is less than 0.001) proved to be the most significant determinant of BMC. This illustrates the dependence of osteopenia in S on GH, the maximizing effect of X for epiphyseal growth and the major role of Pi metabolism on BMC in weight bearing bone during growth.

  6. Bone adaptation to altered loading after spinal cord injury: a study of bone and muscle strength.

    PubMed

    Rittweger, J; Gerrits, K; Altenburg, T; Reeves, N; Maganaris, C N; de Haan, A

    2006-01-01

    Bone loss from the paralysed limbs after spinal cord injury (SCI) is well documented. Under physiological conditions, bones are adapted to forces which mainly emerge from muscle pull. After spinal cord injury (SCI), muscles can no longer contract voluntarily and are merely activated during spasms. Based on the Ashworth scale, previous research has suggested that these spasms may mitigate bone losses. We therefore wished to assess muscle forces after SCI with a more direct measure and compare it to measures of bone strength. We hypothesized that the bones in SCI patients would be in relation to the loss of muscle forces. Six male patients with SCI 6.4 (SD 4.3) years earlier and 6 age-matched, able-bodied control subjects were investigated. Bone scans from the right knee were obtained by pQCT. The knee extensor muscles were electrically stimulated via the femoral nerve, isometric knee extension torque was measured and patellar tendon force was estimated. Tendon force upon electrical stimulation in the SCI group was 75% lower than in the control subjects (p<0.01). Volumetric bone mineral density of the patella and of the proximal tibia epiphysis were 50% lower in the SCI group than in the control subjects (p<0.01). Cortical area was lower by 43% in the SCI patients at the proximal tibia metaphysis, and by 33% at the distal femur metaphysis. No group differences were found in volumetric cortical density. Close curvilinear relationships were found between stress and volumetric density for the tibia epiphysis (r(2)=0.90) and for the patella (r(2)=0.91). A weaker correlation with the tendon force was found for the cortical area of the proximal tibia metaphysis (r(2)=0.63), and none for the distal femur metaphysis. These data suggest that, under steady state conditions after SCI, epiphyseal bones are well adapted to the muscular forces. For the metaphysis of the long bones, such an adaptation appears to be less evident. The reason for this remains unclear. PMID:17142949

  7. A rationale for treating leg length discrepancy using photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Bisland, Stuart K.; Johnson, Crystal; Diab, Mohammed; Wilson, Brian C.; Burch, Shane

    2005-09-01

    This study investigates the use of photodynamic therapy (PDT) in regulating bone development with a view to its potential role in treating Juvenile leg length discrepancy (LLD). Transgenic mice expressing the luciferase firefly gene upon activation of a promoter sequence specific to the vascular endothelial growth factor (VEGF) gene were subject to benzoporphyrin derivative monoacid (BPD-MA)-mediated PDT in the right, tibial epiphyseal growth plate at the age of 3 weeks. BPD-MA was administered intracardially (2mg/kg) followed 10 mins later by a laser light (690 +/- 5 nm) at a range of doses (5-27J, 50 mW output) delivered either as a single or repeat regimen (x2-3). Contra-lateral legs served as no-light controls. Further controls included animals that received light treatment in the absence of photosensitizer or no treatment. Mice were imaged for VEGF related bioluminescence (photons/sec/steradian) at t= 0, 24, 48, 72 h and 1-4 weeks post PDT. FaxitronTM x-ray images provided accurate assessment of bone morphometry. Upon sacrifice, the tibia and femur of the treated and untreated limbs were harvested, imaged and measured again and prepared for histology. A number of animals were sacrificed at 24 h post PDT to allow immunohistochemical staining for CD31, VEGF and hypoxia-inducible factor (HIF-1 alpha) within the bone. PDT-treated (10 J, x2) mice displayed enhanced bioluminescence at the treatment site (and ear nick) for up to 4 weeks post treatment while control mice were bioluminescent at the ear-nick site only. Repeat regimens provided greater shortening of the limb than the corresponding single treatment. PDT-treated limbs were shorter by 3-4 mm on average as compared to the contra lateral and light only controls (10 J, x2). Immunohistochemistry confirmed the enhanced expression VEGF and CD31 at 4 weeks post-treatment although no increase in HIF-1α was evident at either 24 h or 4 weeks post PDT treatment. Results confirm the utility of PDT to provide localized

  8. Characterization of epiphycan, a small proteoglycan with a leucine-rich repeat core protein.

    PubMed

    Johnson, H J; Rosenberg, L; Choi, H U; Garza, S; Höök, M; Neame, P J

    1997-07-25

    The epiphysis of developing bones is a cartilaginous structure that is eventually replaced by bone during skeletal maturation. We have separated a dermatan sulfate proteoglycan, epiphycan, from decorin and biglycan by using dissociative extraction of bovine fetal epiphyseal cartilage, followed by sequential ion-exchange, gel permeation, hydrophobic, and Zn2+ chelate chromatographic steps. Epiphycan is a member of the small leucine-rich proteoglycan family, contains seven leucine-rich repeats (LRRs), is related to osteoglycin (osteoinductive factor) (Bentz, H., Nathan, R. M., Rosen, D. M., Armstrong, R. M., Thompson, A. Y., Segarini, P. R., Mathews, M. C., Dasch, J., Piez, K. A., and Seyedin, S. M. (1989) J. Biol. Chem. 264, 20805-20810), and appears to be the bovine equivalent of the chick proteoglycan PG-Lb (Shinomura, T., and Kimata, K. (1992) J. Biol. Chem. 267, 1265-1270). The intact proteoglycan had a median size of approximately 133 kDa. The core protein was 46 kDa by electrophoretic analysis, had a calculated size of 34,271 Da, and had two approximately equimolar N termini (APTLES ... and ETYDAT ... ) separated by 11 amino acids. There were at least three O-linked oligosaccharides in the N-terminal region of the protein, based on blank cycles in Edman degradation and corresponding serine or threonine residues in the translated cDNA sequence. The glycosaminoglycans ranged in size from 23 to 34 kDa were more heterogeneous than those in other dermatan sulfate small leucine-rich proteoglycans and were found in the acidic N-terminal region of the protein core, N-terminal to the LRRs. A four-cysteine cluster was present at the N terminus of the LRRs, and a disulfide-bonded cysteine pair was present at the C terminus of the protein core. The seventh LRR and an N-linked oligosaccharide were between the two C-terminal cysteines. An additional potential N-glycosylation site near the C terminus did not appear to be substituted at a significant level. PMID:9228042

  9. The effects of levofloxacin on rabbit anterior cruciate ligament cells in vitro

    SciTech Connect

    Deng, Yu; Chen, Biao; Qi, Yongjian; Magdalou, Jacques; Wang, Hui; Chen, Liaobin

    2011-11-15

    Articular cartilage, epiphyseal growth plate and tendons have been recognized as targets of fluoroquinolone-induced connective tissue toxicity. The effects of fluoroquinolones on ligament tissues are still unknown. The aim of this study was to investigate the effects of levofloxacin, a typical fluoroquinolone antibiotic drug, on rabbit anterior cruciate ligament (ACL) cells in vitro. Rabbit ACL cells were treated with levofloxacin at different concentrations (0, 14, 28, 56, 112 and 224 {mu}M) and were assessed to determine the possible cytotoxic effects of levofloxacin on ACL cells. Levofloxacin, with concentrations ranging from 28 to 224 {mu}M, induced dose-dependent ACL cell apoptosis. Characteristic markers of programmed cell death and degenerative changes were identified by electron microscopy in the ACL cells treated with 28 {mu}M of levofloxacin. Moreover, levofloxacin significantly increased the mRNA expression of matrix metalloproteinase 3 (MMP-3) and MMP-13 and decreased the expression of tissue inhibitors of metalloproteinase 1 (TIMP-1) in a concentration-dependent manner; TIMP-3 and collagen type I alpha 1 (Col1A1) mRNA expression was not affected. Immunocytochemical analysis indicated that levofloxacin markedly increased the expression of active caspase-3 within a concentration range of 28 to 224 {mu}M, whereas a clear-cut decrease in Col1A1 expression was found with levofloxacin treatment concentrations of 112 and 224 {mu}M, compared to controls. Our data suggest that levofloxacin has cytotoxic effects on ACL cells characterized by enhanced apoptosis and decreased extracellular matrix, which suggest a potential adverse effect of fluoroquinolones. -- Highlights: Black-Right-Pointing-Pointer Levofloxacin has cytotoxic effect on rabbit ACL cells in vitro. Black-Right-Pointing-Pointer Levofloxacin induces apoptosis in ACL cells. Black-Right-Pointing-Pointer It decreases extracellular matrix by upregulation of matrix degrading enzymes. Black

  10. Early outcomes of one-stage combined osteotomy in Legg-Calve´-Perthes disease

    PubMed Central

    Bhuyan, Basant Kumar

    2016-01-01

    Background: Legg-Calve´-Perthes disease (LCPD) is an idiopathic avascular necrosis of the femoral head. There are multiple approaches to the treatment of LCPD ranging from conservative management to a wide variety of surgical methods. Conservative management necessitates extreme degrees of abduction in an orthosis for a longer period of time which further jeopardize capital femoral head vascularity. Surgical containment methods are used in cases where it is desirable. Initial surgical containment methods are varus or varus-derotational osteotomy of the proximal femur or an innominate osteotomy as described by Salter and other pelvic osteotomies. The purpose of this study was to describe the early results of containment methods by one-stage combined osteotomy (femoral varus osteotomy and Salter innominate osteotomy) in patients with severe LCPD. Materials and Methods: 23 children were operated in the age group of 4–9 years for LCPD by one-stage combined osteotomy procedure between January 2005 and June 2012. There were 19 boys and 4 girls, left hip involved in 10 cases and right in 13 cases. Preoperatively, they were classified according to Catterall, Joseph's stage and lateral pillar (LP) classification. Postoperatively, clinical results were evaluated in accordance with Ratliff classification and radiological assessment was made by Mose's index, modified Stulberg classification and Epiphyseal extrusion index. Results: Seventeen hips were Catterall group III, 6 in group IV and all had two or more “head-at-risk” signs. There were 2 patients with stage IIA, 15 were in stage IIB and 6 were in stage IIIA as classified by Joseph's stage of disease. According to LP classification, 11 patients were group B, 3 were group B/C and 9 were in group C. At an average followup of 5.4 years (range 2–9.5 years), the clinical results were good in 12, fair in 9 and poor in 2. According to Mose scale, 8 patients had good results, 13 fair results and 2 had poor results. Based

  11. Fixation of Intertrochanteric Valgus Osteotomy with T Plate in Treatment of Developmental Coxa Vara

    PubMed Central

    Khairy, Hosam Mohamed

    2016-01-01

    Background Although the valgus subtrochanteric osteotomy is considered as a standard surgical treatment for coxa vara, there is no consensus on the optimal method of fixation and osteotomy technique. Fixation of the osteotomy has been achieved by various methods including external fixation and internal fixation with pins and cerclage and a variety of plates. The aim of this study is the evaluation of the results of developmental coxa treated by Y intertrochanteric valgus osteotomy fixed with a T-buttress plate compared with other methods of fixation in the literature. Methods Eighteen corrective valgus intertrochanteric femoral osteotomies were performed in 18 patients (18 hips) for treatment of unilateral developmental coxa vara deformity and fixed with a T plate. There were 12 males and 6 females. The right hip was affected in 10 patients and the left hip in 8 patients. Clinically, patients were evaluated by Larson hip score. Radiographically, anteroposterior view of the pelvis and frog leg lateral views of the affected hip were taken preoperatively and compared with the findings at the final follow-up. Results The average follow-up was 29 months (range, 24 to 36 months). Clinical results showed improvement of the mean Larson hip score from 57.8 to 97.0 (p < 0.001). Radiological results showed that all osteotomies were completely united in 2.4 months (range, 2 to 3 months) with the achievement of the planned correction angle. The average correction of Hilgenreiner's epiphyseal angle improved from 78.2° to 27.8° (p < 0.001) at the final follow-up. The femoral neck shaft angle was improved from 93.7° to 129.9° (p < 0.001) at the final follow-up. Shortening of the affected limb was corrected from 2.8 cm to 1.3 cm (p < 0.001) at the last follow-up. No major serious complications were recorded in the present study. Conclusions Intertrochanteric valgus osteotomy of the proximal femur fixed with a T plate may be efficient for treatment of developmental coxa vara

  12. Ankle Deformity Secondary to Acquired Fibular Segmental Defect in Children

    PubMed Central

    Kang, Soo Hwan; Song, Seok Whan; Chung, Jin Wha; Kim, Yoon Chung; Suhl, Kyung Hwan

    2010-01-01

    ankle deformities and supramalleolar corrective osteotomy to correct them in children are effective initially. However, both procedures cannot maintain the permanent ankle stability during skeletal maturity. Therefore any type of prophylactic surgery should be carried out before epiphyseal closure of the distal tibia occurs, but the possibility of a recurrence of the ankle deformities and the need for final corrective surgery after skeletal maturity should be considered. PMID:20808590

  13. Similar cellular migration patterns from niches in intervertebral disc and in knee-joint regions detected by in situ labeling: an experimental study in the New Zealand white rabbit

    PubMed Central

    2013-01-01

    Introduction Potential stem cell niches (SNs) were recently reported in intervertebral discs (IVDs) and knee joints (KJs) in different mammals (located adjacent to the epiphyseal plate; EP). The aim here was to examine further possible cellular migration and migration directions of cells originating from niches possibly involved in regeneration of cartilaginous tissues in the IVD and in the KJ regions in adult mammals. Methods In total, 33 rabbits were used in studies A through C. A. IVD cells were sorted; fluorescence-activated cell sorting (FACS) by size (forward scatter; ≤10 μm or >10 μm or GDF5+ cells (anti-GDF5 antibody). Sorted cells, labeled with cell tracer (carboxyfluorescein-diacetate-succinimidyl ester; CDFA-SE) were applied on IVD explants in vitro. Migrating cells/distance was evaluated by fluorescence- and confocal-microscopy (FC). B. DNA labeling was performed with BrdU (oral administration). Animals were killed (14 to 56 days), KJs collected, and BrdU+ cells visualized with immunohistochemistry (IHC)/anti-BrdU antibody in SN and articular cartilage (AC). C. Cell tracer: (Fe-nanoparticles: Endorem) were injected into SNs of IVDs (LI-LV) and KJs (tibia). Animals were killed after 2 to 6 weeks. Fe-labeled cells were traced by ferric-iron staining (Prussian blue reaction; Mallory method). Results A. GDF5+ cells and ≤10-μm cells displayed the best migration capability in IVD explants. GDF5+ cells were detected at a tissue depth of 1,300 μm (16 days). B. BrdU+ cells were observed in early time points in niches of KJs, and at later time points in AC, indicating a gradual migration of cells. C. Fe+ cells were detected in IVDs; in annulus fibrosus (AF) in 11 of 12 animals and in nucleus pulposus (NP) in two of 12 animals. In AC (tibia), Fe+ cells were detected in six of 12 animals. In the potential migration route (PMR), from niches toward the IVD, Fe+ cells (three of 12 animals) and in PMR toward AC (KJs) (six of 12 animals) were detected

  14. Differentiations and Functional State of Osteogenic Cells in Conditions of Microgravity

    NASA Astrophysics Data System (ADS)

    Onishchenko, Ganna; Rodionova, Natalia; Markevich, Ganna; Markevich, Ganna

    The space flight factors (space radiation, magnetic fields etc.) affect considerably the state of bone tissue, leading to the development of osteoporosis and osteopenia in the bone skeleton. Many aspects of reactions of bone tissue cells still remain unclear until now. With the use of electron microscopy and autoradiography with 3H-thymidine we studied the samples gathered from the femoral bone epiphyses and metaphyses of rats flown on board American Spacelab -2 and in experiments with modeling of microgravity ("tail suspension" method). In our work the main attention is focused on studying the ultrastructure and metabolism of osteogenetic cells. The degree of differentiation and functional state are evaluated according to the degree of development of organelles for specific biosynthesis: rough endoplasmic reticulum (RER), Golgy complex (GC), as well as the state of mitochondria and cell nucleus. As compared with a control, the population of osteogenetic cells from zones of bone reconstruction shows a decrease in the number of functionally active forms. We can judge of this from the reduction volume of RER, GC, mitochondria in osteoblasts. RER loses architectonics typical for osteoblasts and, as against the control, is represented by short narrow canaliculi distributed throughout the cy-toplasm; some canals disintegrate. GC is slightly pronounced, mitochondria become smaller in size and acquire an optically dark matrix. These phenomena are supposed to be associated with the desorganization of microtubules and microfilaments in the cells under microgravity condi-tions. The number of degrading and apoptotic cells increases in the population of osteoblasts. The dynamics of labeled cells following various intervals after 3H-thymidine injection testifies to a delay in the rates of osteoblasts' differentiation and their transformation to osteocytes in the experiment animals. A lower 3H-glycine uptake by the osteogenic cells and bone matrix as compared with a control is

  15. Chondrogenesis in the regenerating antler tip in red deer: expression of collagen types I, IIA, IIB, and X demonstrated by in situ nucleic acid hybridization and immunocytochemistry.

    PubMed

    Price, J S; Oyajobi, B O; Nalin, A M; Frazer, A; Russell, R G; Sandell, L J

    1996-03-01

    The annual regrowth of antlers in male deer is a unique example of complete bone regeneration occurring in an adult animal. Growth is initiated at the distal antler tip, which is similar to the epiphyseal growth plate in some respects. However, there is some debate as to whether this process represents "true" endochondral ossification. As part of the characterization of the developmental process in pre-osseus antler tissue, we have studied, by in situ hybridization, the spatial expression of mRNAs for types I, II, and X collagen. Viewed in a coronal plane, type I procollagen mRNA was observed in skin, the fibrous perichondrium, and the densely cellular area immediately adjacent to the perichondrium. Below this area, as cells began to assume a columnar arrangement and coincident with the appearance of a vasculature and synthesis of a cartilaginous matrix, transcripts for types I, IIA, IIB procollagen and X collagen were detected. Further down in the cartilage zone, the pattern of type I procollagen mRNA expression was altered. Here, the signal was detected only in a morphologically distinct subpopulation of small, flattened cells within the intercellular matrix at the periphery of the columns of chondrocytes. The alternative splice form of type II procollagen mRNA (IIA), characteristic of chondroprogenitor cells (Sandell et al. [1991] J. Cell Biol. 114:1307-1319), was expressed by a subset of cells in the upper region of the columns, indicating that this zone contains a population of prechondrocytic cells. Positive hybridization to type IIA was most abundant in these cells. In contrast, transcripts for the other procollagen splice form (IIB) and type X collagen were expressed by chondrocytes throughout the whole of the cartilage region studied. The translation and export of type II collagen and type X collagen were confirmed by detecting specific immunoreactivity for each. The spatial distribution of immunoreactivity for collagen types II and X was consistent with

  16. Effect of trabecular bone loss on cortical strain rate during impact in an in vitro model of avian femur

    PubMed Central

    Reich, Tal; Gefen, Amit

    2006-01-01

    Background Osteoporotic hip fractures occur due to loss of cortical and trabecular bone mass and consequent degradation in whole bone strength. The direct cause of most fractures is a fall, and hence, characterizing the mechanical behavior of a whole osteopenic bone under impact is important. However, very little is known about the mechanical interactions between cortical and trabecular bone during impact, and it is specifically unclear to what extent epiphyseal trabecular bone contributes to impact resistance of whole bones. We hypothesized that trabecular bone serves as a structural support to the cortex during impact, and hence, loss of a critical mass of trabecular bone reduces internal constraining of the cortex, and, thereby, decreases the impact tolerance of the whole bone. Methods To test this hypothesis, we conducted cortical strain rate measurements in adult chicken's proximal femora subjected to a Charpy impact test, after removing different trabecular bone core masses to simulate different osteopenic severities. Results We found that removal of core trabecular bone decreased by ~10-fold the cortical strain rate at the side opposite to impact (p < 0.01), i.e. from 359,815 ± 1799 μm/m per second (mean ± standard error) for an intact (control) specimen down to 35,997 ± 180 μm/m per second where 67% of the total trabecular bone mass (~0.7 grams in adult chicken) were removed. After normalizing the strain rate by the initial weight of bone specimens, a sigmoid relation emerged between normalized strain rate and removed mass of trabecular bone, showing very little effect on the cortex strain rate if below 10% of the trabecular mass is removed, but most of the effect was already apparent for less than 30% trabecular bone loss. An analytical model of the experiments supported this behavior. Conclusion We conclude that in our in vitro avian model, loss of over 10% of core trabecular bone substantially altered the deformation response of whole bone to impact

  17. [Spasm of the adductor muscles, pre-dislocations and dislocations of the hip joints in children and adolescents with cerebral palsy. Clinical observations on aetiology, pathogenesis, therapy and rehabilitation. Part II. The importance of the iliopsoas tendon, its tenotomy, of the coxa valga antetorta, and correction through osteotomy turning the hip into varus (author's transl)].

    PubMed

    Fettweis, E

    1979-02-01

    The following factors besides spasm and contraction of the adductor muscles contribute to the occurrence of dislocations of the hip in spastic paralysis: Spasm and contraction of the iliopsoas muscle and enhanced valgus position and antetorsion. The author holds the opinion that in case of malformation of the proximal end of the femur, it is not only the indirect action of the spastic musculature via the proximal femur-epiphyseal cartilage which is responsible for this phenomen in accordance with the law on functional adaption through longitudinal growth (Pauwels), but also the direct traction of the iliopsoas tendon. A clue in this direction is the often very pronounced elongation or enlargement of the trochanter minor. The author demonstrates the pathogenetic importance of iliopsoas contracture and malpositioning of the neck of the femur by means of analyses of the course in two patients. The following principles of treatment are postulated for spastic dislocation of the hip: Elimination of the pathogenetic factors through myotenotomy of the adductor muscles and complete resection of the obturator nerve, with observation of strict aftertreatment criteria, tenotomy of the iliopsoas, repositioning and osteotomy with turning into varus. Osteotomy without previous elimination of the pathogenetically acting muscular forces does not appear useful. Likewise, permanent re-positioning by means of muscle-relaxing operation cannot be sufficiently safe-guarded without additional osteotomy once the dislocation has taken place. In twelve patients with spastic dislocation of the hip, treated in accordance with these guidelines (two without osteotomy) aged 6 6/12 and 19 5/12 years, a roentgenologically good result was obtained in half of the cases, whereas the functional result was satisfactory not only with these patients but also with part of the other patients. If surgical treatment is instituted early enough, and if the experiences described here are taken into consideration

  18. Characterization of gsp-mediated growth hormone excess in the context of McCune-Albright syndrome.

    PubMed

    Akintoye, Sunday O; Chebli, Caroline; Booher, Susan; Feuillan, Penelope; Kushner, Harvey; Leroith, Derek; Cherman, Natasha; Bianco, Paolo; Wientroub, Shlomo; Robey, Pamela Gehron; Collins, Michael T

    2002-11-01

    McCune-Albright syndrome (MAS) is a disorder characterized by the triad of café-au-lait skin pigmentation, polyostotic fibrous dysplasia of bone, and hyperfunctioning endocrinopathies, including GH excess. The molecular etiology of the disease is postzygotic activating mutations of the GNAS1 gene product, G(s)alpha. The term gsp oncogene has been assigned to these mutations due to their association with certain neoplasms. The aim of this study was to estimate the prevalence of GH excess in MAS, characterize the clinical and endocrine manifestations, and describe the response to treatment. Fifty-eight patients with MAS were screened, and 22 with stigmata of acromegaly and/or elevated GH or IGF-I underwent oral glucose tolerance testing. Twelve patients (21%) had GH excess, based on failure to suppress serum GH on oral glucose tolerance test, and underwent a TRH test, serial GH sampling from 2000-0800 h, and magnetic resonance imaging of the sella. We found that vision and hearing deficits were more common in patients with GH excess (4 of 12, 33%) than those without (2 of 56, 4%). Of interest, patients with a history of precocious puberty and GH excess who had reached skeletal maturity achieved normal adult height despite a history of early epiphyseal fusion. All 9 patients tested had an increase in serum GH after TRH, 11 of 12 (92%) had hyperprolactinemia, and all 8 tested had detectable or elevated nighttime GH levels. Pituitary adenoma was detected in 4 of 12 (33%) patients. All patients with elevated IGF-I levels were treated with cabergoline (7 patients), long-acting octreotide (LAO; 8 patients), or a combination of cabergoline and LAO (4 patients). In six of the seven patients (86%) treated with cabergoline, serum IGF-I decreased, but not to the normal range. In the eight patients treated with LAO alone, IGF-I decreased, and, in four, returned to the normal range. The remaining 4 patients were treated with a combination of cabergoline and LAO. For them

  19. The effects of hydraulic resistance strength training in pre-pubertal males.

    PubMed

    Weltman, A; Janney, C; Rians, C B; Strand, K; Berg, B; Tippitt, S; Wise, J; Cahill, B R; Katch, F I

    1986-12-01

    .4% (l X min-1), +13.8% (ml X kg X min-1)] after the experimental period. Musculoskeletal scintigraphy revealed no evidence of damage to epiphyses, bone, or muscle as a result of strength training. Only one strength training-related injury was reported (left shoulder pain, 3 strength training sessions missed). In contrast, six strength training subjects sustained injuries during activities of daily living, resulting in 47 missed strength training sessions. It was concluded that, in the short term, supervised concentric strength training using hydraulic resistance equipment is safe and effective in pre-pubertal boys. PMID:2946921

  20. The demographics of slipped capital femoral epiphysis. An international multicenter study.

    PubMed

    Loder, R T

    1996-01-01

    One thousand six hundred thirty children with 1993 slipped capital femoral epiphyses were reviewed; 41.2% were girls and 58.8% were boys. There were 47.5% white, 24.8% black, 16.9% Amerindian, 7.4% Indonesian-Malay, 2.1% Native Australian/Pacific Islands, and 1.3% Indo-Mediterranean children. The diseased hip was unilateral in 77.7% and bilateral in 22.3% of the children, and chronic in 85.5% and acute in 14.5% of the children. Of the unilateral slips, 40.3% involved the right hip and 59.7% the left hip. The child's weight was greater than or equal to the ninetieth percentile in 63.2% of the children. The average age for the girls and boys was 12 and 13.5 years. The age at diagnosis decreased with increasing obesity. The youngest children were the Native Australian/Pacific Island children (11.8 years) and the oldest were the white and Indo-Mediterranean children (13 years). The Indonesian-Malay and Indo-Mediterranean children were the lightest in weight, and the black children the heaviest. The Indo-Mediterranean children had the highest proportion of boys (90.5%), and the Native Australian/Pacific Island children the lowest (50%). The highest percentage of bilaterality was in the Native Australian/Pacific Island children (38.2%), and the lowest in the Amerindian children (16.5%). The relative racial frequency of slipped capital femoral epiphysis compared with the white population was 4.5 for the Polynesian, 2.2 for the black, 1.05 for the Amerindian, 0.5 for the Indonesian-Malay, and 0.1 for the Indo-Mediterranean children. In children with unilateral involvement, the age at presentation was younger for those children in whom bilateral disease later developed (12 versus 12.9 years old). In 82% of the children with sequential bilateral slips, the second slip was diagnosed within 18 months of the first slip. PMID:8542716

  1. Prophylactic administration of a combined prebiotic and probiotic, or therapeutic administration of enrofloxacin, to reduce the incidence of bacterial chondronecrosis with osteomyelitis in broilers.

    PubMed

    Wideman, R F; Al-Rubaye, A; Kwon, Y M; Blankenship, J; Lester, H; Mitchell, K N; Pevzner, I Y; Lohrmann, T; Schleifer, J

    2015-01-01

    Bacteria entering the bloodstream via translocation from the gastrointestinal tract spread hematogenously and can trigger bacterial chondronecrosis with osteomyelitis (BCO) by infecting osteochondrotic microfractures in the epiphyseal-physeal cartilage of the proximal femora and tibiae. In experiment 1, broilers were fed control feed or the same feed containing BacPack 2X, which includes the prebiotic IMW50 (a mannan oligosaccharide beta-glucan yeast cell wall product) plus the probiotic Calsporin (Bacillus subtilis C-3102). Broilers reared on wire flooring consistently developed higher incidences of BCO than hatchmates reared on wood shavings litter (≥24 vs. ≤4%, respectively; P=0.001). Adding BacPack 2X to the feed on d 1 through 56 delayed the age of onset and reduced the cumulative incidence of BCO on wire flooring when compared with broilers fed the control feed (24.0 vs. 40.7%, respectively; P=0.003). In experiment 2, broilers reared on wire flooring received tap water on d 1 through 62 (control group) or therapeutic levels of the potent fluoroquinolone antimicrobial enrofloxacin in the water on d 35 through 54 (enrofloxacin group). During enrofloxacin administration, half as many birds developed BCO in the enrofloxacin group when compared with the control group (8.1 vs. 19.5%, respectively, on d 35 through 54; P=0.001), whereas both groups had similar BCO incidences subsequent to withdrawing enrofloxacin on d 55 through 62 (14.8 vs. 18.2% for the enrofloxacin vs. control groups; P=0.386). Cumulative lameness incidences for d 1 through 62 were higher for the control group than for the enrofloxacin group (39.0 vs. 25.8%, respectively; P=0.003). These results demonstrate that wire flooring imposes a rigorous challenge that leads to high incidences of BCO that can be difficult to suppress, even with therapeutic doses of enrofloxacin. Prophylactically adding BacPack 2X to the feed reduced the incidence of BCO lameness by a proportion similar to that achieved

  2. The phylogeny of varanoid lizards and the affinities of snakes

    PubMed Central

    Lee, M. S. Y.

    1997-01-01

    Evidence that platynotan squamates (living varanoid lizards, snakes and their fossil relatives) are monophyletic is presented. Evolutionary relationships within this group are then ascertained through a cladistic analysis of 144 osteological characters. Mosasauroids (aigialosaurs and mosasaurs), a group of large marine lizards, are identified as the nearest relatives of snakes, thus resolving the long-standing problem of snake affinities. The mosasauroid–snake clade (Pythonomorpha) is corroborated by 40 derived characters, including recumbent replacement teeth, thecodonty, four or fewer premaxillary teeth, supratemporal–prootic contact, free mandibular tips, crista circumfenestralis, straight vertical splenio-angular joint, loss of posterior ramus of the coronoid, reduced basipterygoid processes, reduced interpterygoid vacuity, zygosphene–zygantral articulations, and absence of epiphyses on the axial skeleton and skull. After mosasauroids, the next closest relatives of snakes are varanids (Varanus, Saniwa and Saniwides) and lanthanotids (Lanthanotus and Cherminotus). Derived features uniting varanids and lanthanotids include nine cervical vertebrae and three or fewer pairs of sternal ribs. The varanid–lanthanotid–pythonomorph clade, here termed Thecoglossa, is supported by features such as the anteriorly positioned basal tubera, and the loss of the second epibranchial. Successive outgroups to thecoglossans are Telmasaurus, an unresolved polytomy (Estesia, Gobidermatidae and Helodermatidae), Paravaranus and Proplatynota. The 'necrosaurs' are demonstrated to be an artificial (polyphyletic) assemblage of primitive platynotans that are not particularly closely related to each other. Snakes are presumed to have evolved from small, limbless, burrowing lizards and the inability of previous analyses to resolve the affinities of snakes has been attributed to extensive convergence among the numerous lineages of such lizards. The present study contradicts this claim

  3. The p27 Pathway Modulates the Regulation of Skeletal Growth and Osteoblastic Bone Formation by Parathyroid Hormone-Related Peptide.

    PubMed

    Zhu, Min; Zhang, Jing; Dong, Zhan; Zhang, Ying; Wang, Rong; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

    2015-11-01

    Parathyroid hormone-related peptide (PTHrP) 1-84 knock-in mice (Pthrp KI) develop skeletal growth retardation and defective osteoblastic bone formation. To further examine the mechanisms underlying this phenotype, microarray analyses of differential gene expression profiles were performed in long bone extracts from Pthrp KI mice and their wild-type (WT) littermates. We found that the expression levels of p27, p16, and p53 were significantly upregulated in Pthrp KI mice relative to WT littermates. To determine whether p27 was involved in the regulation by PTHrP of skeletal growth and development in vivo, we generated compound mutant mice, which were homozygous for both p27 deletion and the Pthrp KI mutation (p27(-/-) Pthrp KI). We then compared p27(-/-) Pthrp KI mice with p27(-/-), Pthrp KI, and WT littermates. Deletion of p27 in Pthrp KI mice resulted in a longer lifespan, increased body weight, and improvement in skeletal growth. At 2 weeks of age, skeletal parameters, including length of long bones, size of epiphyses, numbers of proliferating cell nuclear antigen (PCNA)-positive chondrocytes, bone mineral density, trabecular bone volume, osteoblast numbers, and alkaline phosphatase (ALP)-, type I collagen-, and osteocalcin-positive bone areas were increased in p27(-/-) mice and reduced in both Pthrp KI and p27(-/-) Pthrp KI mice compared with WT mice; however, these parameters were increased in p27(-/-) Pthrp KI mice compared with Pthrp KI mice. As well, protein expression levels of PTHR, IGF-1, and Bmi-1, and the numbers of total colony-forming unit fibroblastic (CFU-f) and ALP-positive CFU-f were similarly increased in p27(-/-) Pthrp KI mice compared with Pthrp KI mice. Our results demonstrate that deletion of p27 in Pthrp KI mice can partially rescue defects in skeletal growth and osteoblastic bone formation by enhancing endochondral bone formation and osteogenesis. These studies, therefore, indicate that the p27 pathway may function downstream in the action

  4. IGF-I Signaling in Osterix-Expressing Cells Regulates Secondary Ossification Center Formation, Growth Plate Maturation, and Metaphyseal Formation During Postnatal Bone Development.

    PubMed

    Wang, Yongmei; Menendez, Alicia; Fong, Chak; ElAlieh, Hashem Z; Kubota, Takuo; Long, Roger; Bikle, Daniel D

    2015-12-01

    To investigate the role of IGF-I signaling in osterix (OSX)-expressing cells in the skeleton, we generated IGF-I receptor (IGF-IR) knockout mice ((OSX)IGF-IRKO) (floxed-IGF-IR mice × OSX promoter-driven GFP-labeled cre-recombinase [(OSX)GFPcre]), and monitored postnatal bone development. At day 2 after birth (P2), (OSX)GFP-cre was highly expressed in the osteoblasts in the bone surface of the metaphysis and in the prehypertrophic chondrocytes (PHCs) and inner layer of perichondral cells (IPCs). From P7, (OSX)GFP-cre was highly expressed in PHCs, IPCs, cartilage canals (CCs), and osteoblasts (OBs) in the epiphyseal secondary ossification center (SOC), but was only slightly expressed in the OBs in the metaphysis. Compared with the control mice, the IPC proliferation was decreased in the (OSX)IGF-IRKOs. In these mice, fewer IPCs invaded into the cartilage, resulting in delayed formation of the CC and SOC. Immunohistochemistry indicated a reduction of vessel number and lower expression of VEGF and ephrin B2 in the IPCs and SOC of (OSX)IGF-IRKOs. Quantitative real-time PCR revealed that the mRNA levels of the matrix degradation markers, MMP-9, 13 and 14, were decreased in the (OSX)IGF-IRKOs compared with the controls. The (OSX)IGF-IRKO also showed irregular morphology of the growth plate and less trabecular bone in the tibia and femur from P7 to 7 weeks, accompanied by decreased chondrocyte proliferation, altered chondrocyte differentiation, and decreased osteoblast differentiation. Our data indicate that during postnatal bone development, IGF-I signaling in OSX-expressing IPCs promotes IPC proliferation and cartilage matrix degradation and increases ephrin B2 production to stimulate vascular endothelial growth factor (VEGF) expression and vascularization. These processes are required for normal CC formation in the establishment of the SOC. Moreover, IGF-I signaling in the OSX-expressing PHC is required for growth plate maturation and osteoblast differentiation in

  5. AB132. Neonatal diabetes in Wolcott-Rallison syndrome: a case report

    PubMed Central

    Can, Ngoc Thi Bich; Vu, Dung Chi; Flanagan, Sarah; Ellard, Sian

    2015-01-01

    Background Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by the association of permanent neonatal or early-infancy insulin-dependent diabetes, multiple epiphyseal dysplasia and growth retardation, and other variable multisystem clinical manifestations. Objective To describe clinical characteristics and genetic finding in the first Vietnamese patient with EIF2AK3 mutation. Methods Clinical features, biochemical finding, mutation analysis and management in a 64-day-old girl was study. Based on analysis of a 64-day-old girl’s clinical symptoms associated with biochemical examination, the diagnosis of WRS was therefore made. Genomic DNAs were extracted from peripheral blood leukocytes from the patient and her parents with their informed consent for genetic studies. The coding and flanking intronic regions of the EIFAK3 gene was analysed by sequencing. Results and conclusions The patient had gestation age of 41 weeks, birth weight of 3,200 g, and onset of the disease at 64 days of age. She was admitted with the features of convulsion, anemia, jaundice, diabetic ketoacidosis with pH of 7.27, HCO3− of 17.8 mmoL/L, BE of −8 mmoL/L, blood glucose 42.46 mmoL/L, HbA1C 6.5%, total bilirubin 59.2 µmoL/L, direct bilirubin 29.7 µmoL/L, AST 3,742.2 U/L, ALT 1,927 U/L. PCR of CMV, EBV, HAV were negative. Abdominal ultrasound did not find any sign of cholestasis. Sequencing analysis of patient’s EIF2AK3 gene has identified a homozygous missense mutation, p.R632W. The parents are carriers of heterozygous EIF2AK3 missense mutation, p.R632W. Now she is 3 years and 3 months old, she has normal development, good blood glucose control with the insulin dose of 1.0 UI/kg/day, no jaundice, HbA1c 5.8% (normal range, 4-6%), AST 30.43 UI/L, ALT 17.09 UI/L, not yet skeletal symtoms. Combining mutation screening of EIF2AK3 gene with clinical manifestations and effective examination may provide a reliable diagnostic method for patients.

  6. Contemporary management of metastatic bone disease: tips and tools of the trade for general practitioners.

    PubMed

    Quinn, Robert H; Randall, R Lor; Benevenia, Joseph; Berven, Sigurd H; Raskin, Kevin A

    2014-01-01

    Metastatic bone disease has a significant effect on a patient's mortality and health-related quality of life. An aging US population and improved survival rates of patients with cancer have led to an increase in the incidence of symptomatic bony metastatic lesions that may require orthopaedic care. Skeletal-related events in neoplastic disease include pain, pathologic fracture, hypercalcemia, and neural compression, including spinal cord compression. The clinical evaluation and diagnostic study of a patient with a skeletal lesion of unknown etiology should be approached carefully. In patients with widespread metastatic disease, the treatment of a skeletal-related event may be limited to stabilization of the pathologic fracture or local disease control. The treatment of metastatic bone disease is guided by the nature of the skeletal-related event, the responsiveness of the lesion to adjuvant care, and the overall condition and survival expectations of the patient. Impending pathologic fractures are often more easily treated, with less morbidity and easier recovery for patients, than completed fractures. Quality of life is the most important outcome measure in these patients. When surgery is indicated, the approach, choice of fixation, and use of adjuvant should allow for immediate and unrestricted weight bearing. Because metastatic lesions to the skeleton have a limited capacity for spontaneous healing, surgical fixation should be durable for the life expectancy of the patient. In the epiphyseal region of long bones, replacement arthroplasty is generally preferred over internal fixation. Metaphyseal and diaphyseal regions can generally be addressed with intramedullary nailing or plate fixation with adjuvant. The specific treatment of acetabular lesions is dictated by the anatomy and the degree of bone loss. Spinal stability and neural compromise are important considerations in choosing a strategy for managing spine tumors. Effective surgical approaches to metastatic

  7. Chemical and biomechanical characterization of hyperhomocysteinemic bone disease in an animal model

    PubMed Central

    Massé, Priscilla G; Boskey, Adele L; Ziv, Israel; Hauschka, Peter; Donovan, Sharon M; Howell, David S; Cole, David EC

    2003-01-01

    Background Classical homocystinuria is an autosomal recessive disorder caused by cystathionine β-synthase (CBS) deficiency and characterized by distinctive alterations of bone growth and skeletal development. Skeletal changes include a reduction in bone density, making it a potentially attractive model for the study of idiopathic osteoporosis. Methods To investigate this aspect of hyperhomocysteinemia, we supplemented developing chicks (n = 8) with 0.6% dl-homocysteine (hCySH) for the first 8 weeks of life in comparison to controls (n = 10), and studied biochemical, biomechanical and morphologic effects of this nutritional intervention. Results hCySH-fed animals grew faster and had longer tibiae at the end of the study. Plasma levels of hCySH, methionine, cystathionine, and inorganic sulfate were higher, but calcium, phosphate, and other indices of osteoblast metabolism were not different. Radiographs of the lower limbs showed generalized osteopenia and accelerated epiphyseal ossification with distinct metaphyseal and suprametaphyseal lucencies similar to those found in human homocystinurics. Although biomechanical testing of the tibiae, including maximal load to failure and bone stiffness, indicated stronger bone, strength was proportional to the increased length and cortical thickness in the hCySH-supplemented group. Bone ash weights and IR-spectroscopy of cortical bone showed no difference in mineral content, but there were higher Ca2+/PO43- and lower Ca2+/CO32- molar ratios than in controls. Mineral crystallization was unchanged. Conclusion In this chick model, hyperhomocysteinemia causes greater radial and longitudinal bone growth, despite normal indices of bone formation. Although there is also evidence for an abnormal matrix and altered bone composition, our finding of normal biomechanical bone strength, once corrected for altered morphometry, suggests that any increase in the risk of long bone fracture in human hyperhomocysteinemic disease is small. We

  8. Ontogeny and phylogeny of femoro-tibial characters in humans and hominid fossils: functional influence and genetic determinism.

    PubMed

    Tardieu, C

    1999-11-01

    Three different human femoro-tibial characters are selected as functionally relevant and derived hominid characters: femoral bicondylar angle, shape of the femoral distal epiphysis, and the tibial insertion of the lateral meniscus. The timing and mode of formation of these characters are investigated during human ontogeny and are shown to differ considerably. The available hominid fossils (Australopithecus afarensis and early Homo) are interpreted in the light of this ontogenetic analysis with the conclusion that, during hominid evolution, different modes of selection of these features must have occurred. In modern humans, the femoral bicondylar angle proves to be an epigenetic functional feature, which develops during early childhood growth. It is present in all australopithecines and we suggest that it developed following a change in their locomotor behavior and not upon a genomic change: the early practice of bipedal walking, with adducted knee joints, in the locomotor repertoire of infant australopithecines, was sufficient to promote this angle. Later in hominid evolution, the knee joint evolved from having a single insertion of the lateral meniscus on the tibia to a double one. While Australopithecus afarensis exhibits a single insertion, early Homo clearly exhibits a double insertion of the lateral meniscus on the tibia. The double insertion restricts the mobility of the meniscus on the tibial plateau, indicating a habitual practice of full extension movements of the knee joint. Among modern humans, the posterior insertion of the lateral meniscus appears early in fetal life. Consequently in early Homo, this new selected feature developed directly as a result of a genomic change. The derived shape of human distal femoral epiphysis includes a prominence of the lateral lip of the femoral trochlea, an elliptical profile of the lateral condyle, and an anteroposterior lengthening of the epiphysis. Analysis of human fetal and neonatal distal epiphyses shows that the

  9. Three-Dimensional Quantitative Morphometric Analysis (QMA) for In Situ Joint and Tissue Assessment of Osteoarthritis in a Preclinical Rabbit Disease Model.

    PubMed

    Stok, Kathryn S; Besler, Bryce A; Steiner, Thomas H; Villarreal Escudero, Ana V; Zulliger, Martin A; Wilke, Markus; Atal, Kailash; Quintin, Aurelie; Koller, Bruno; Müller, Ralph; Nesic, Dobrila

    2016-01-01

    This work utilises advances in multi-tissue imaging, and incorporates new metrics which define in situ joint changes and individual tissue changes in osteoarthritis (OA). The aims are to (1) demonstrate a protocol for processing intact animal joints for microCT to visualise relevant joint, bone and cartilage structures for understanding OA in a preclinical rabbit model, and (2) introduce a comprehensive three-dimensional (3D) quantitative morphometric analysis (QMA), including an assessment of reproducibility. Sixteen rabbit joints with and without transection of the anterior cruciate ligament were scanned with microCT and contrast agents, and processed for histology. Semi-quantitative evaluation was performed on matching two-dimensional (2D) histology and microCT images. Subsequently, 3D QMA was performed; including measures of cartilage, subchondral cortical and epiphyseal bone, and novel tibio-femoral joint metrics. Reproducibility of the QMA was tested on seven additional joints. A significant correlation was observed in cartilage thickness from matching histology-microCT pairs. The lateral compartment of operated joints had larger joint space width, thicker femoral cartilage and reduced bone volume, while osteophytes could be detected quantitatively. Measures between the in situ tibia and femur indicated an altered loading scenario. High measurement reproducibility was observed for all new parameters; with ICC ranging from 0.754 to 0.998. In conclusion, this study provides a novel 3D QMA to quantify macro and micro tissue measures in the joint of a rabbit OA model. New metrics were established consisting of: an angle to quantitatively measure osteophytes (σ), an angle to indicate erosion between the lateral and medial femoral condyles (ρ), a vector defining altered angulation (λ, α, β, γ) and a twist angle (τ) measuring instability and tissue degeneration between the femur and tibia, a length measure of joint space width (JSW), and a slope and intercept

  10. Bone age assessment using cephalometric photographs

    PubMed Central

    Durka-Zając, Magdalena; Marcinkowska, Agata; Mituś-Kenig, Maria

    2013-01-01

    Summary Background: The assessment of bone age comprises the basic element of orthodontic diagnostics as it enables the recognition of deviations from normal growth, determines the choice of treatment, helps determine the appropriate moment to begin treatment, establish prognosis and plan a retention strategy. In order to make an assessment of skeletal maturity possible in a single examination, radiological methods were adopted. The following characteristics are evaluated on a radiograph: the appearance, size and shape of ossification centers, the width and the shape of growth cartilage and the degree of fusion between diaphyses and epiphyses. In order to assess the maturity of bones, hand-wrist radiographs were introduced in the second decade of the 20th century. Bone age assessment of bone age could also be made based on an analysis of a morphological maturity of cervical vertebrae utilizing cephalometric radiographs. Objective: The objective of the study was to evaluate the correspondence between bone age assessments made from hand-wrist radiographs and those from cephalometric radiographs. Material/Methods: In order to fulfill the objectives, hand-wrist radiographs as well as cephalometric radiographs of 30 patients (15 girls and 15 boys) between 10 and 17 years of age were collected. Bone age of hand, wrist and cervical spine was assessed. Bone age on hand-wrist radiographs was evaluated using the Björk method, whereas cephalometric radiographs were analyzed by the Baccetti et al. method. Results: A strong and statistically highly significant (r=0.98; p<0.00001) Pearson’s correlation was found between bone age assessed from hand-wrist radiographs using Björk’s method and bone age assessed from cephalometric radiographs using the method by Baccetti et al. Conclusions: The analysis of cervical vertebrae in cephalometric radiographs appears to be the most desirable method of bone age assessment. Performing the analysis on routinely taken cephalograms

  11. Industrial fluoride pollution. Chronic fluoride poisoning in Cornwall Island cattle.

    PubMed

    Krook, L; Maylin, G A

    1979-04-01

    An aluminum plant on the south bank of the St. Lawrence river, southwest of Cornwall Island, Ontario, Canada, has emitted 0.816 metric tons of fluoride daily since 1973; considerably higher amounts were emitted from 1959 to 1973. The plant has been designated as the "major source of fluoride emissions impacting on Cornwall Island." Chronic fluoride poisoning in Cornwall island cattle was manifested clinically by stunted growth and dental fluorosis to a degree of severe interference with drinking and mastication. Cows died at or were slaughtered after the third pregnancy. The deterioration of cows did not allow further pregnancies. Fluoride concentrations in ash of biopsied coccygeal vertebrae increased significantly with age and were dependent on distance from and direction to the aluminum plant. Fluoride in bone ash of a 7-month old-fetus exceeded 500 ppm; fluoride thus was passed transplacentally. Analyses of fluoride in ash of bones obtained at necropsy of cattle from 4 months of age to 4 to 5 years of age showed increased amounts with age. Cancellous bone retained far higher amounts than cortical bone, a reflection of the normally higher metabolic rate of cancellous bone. Concentrations exceeding 10,000 ppm fluoride were recorded in cancellous bone of a 4-to 5-year-old cow. The target cells for fluoride in chronic fluorosis were shown to be the ameloblasts, the dental pulp cells and the odontoblasts and, in bone, primarily the resorbing osteocytes and also the osteoblasts. Atrophy and necrosis of the ameloblasts were responsible for enamel defects. The existing enamel showed brown discoloration from fluoride deposits. The pulp cells underwent fibrous and osseous metaplasia and necrosis of the ectopic bone occurred. The odontoblasts were atrophic and the dentin showed brown discoloration. The resorbing osteocytes were inactive and osteosclerosis resulted. This was especially pronounced in areas of normally great apposition, i.e. in the metaphyses. The epiphyseal

  12. Analysis of the Tibial Epiphysis in the Skeletally Immature Knee Using Magnetic Resonance Imaging

    PubMed Central

    Davis, Derik L.; Almardawi, Ranyah; Mitchell, Jason W.

    2016-01-01

    corresponding to the maximum and safe lengths are more acute than commonly thought, measuring approximately 40° and 30°, respectively. All prepubescent knees and intermediate-risk females should receive careful attention before ACL reconstruction due to the relative smaller size of their tibial epiphyses. Clinical Relevance: Physeal-sparing ACL reconstruction is gaining acceptance as a surgical option for complete ACL tear in skeletally immature knees. Iatrogenic growth disturbance after violation of an open growth remains a real concern for surgeons tasked with providing operative management for the unstable pediatric knee. Inadvertent iatrogenic growth plate injury to the tibial physis has been shown to occur more commonly than surgeons would intend during physeal-sparing ACL reconstruction. PMID:27482528

  13. Effect of space flight factors on osteogenetic processes in the bone skeleton

    NASA Astrophysics Data System (ADS)

    Rodionova, Natalia Vasilievna; Oganov, Victor Sumbatovich

    The space flight factors (space radiation, magnetic fields etc.) affect considerably the state of bone tissue, leading to the development of osteoporosis and osteopenia in the bone skeleton. Many aspects of reactions of bone tissue cells still remain unclear until now. With the use of electron microscopy we studied the samples gathered from the femoral bone epiphyses and metaphyses of rats flown on board the space laboratory (Spacelab - 2) during 2 weeks. It was established, that under microgravity conditions there occur remodelling processes in a spongy bone related with a deficit of support load. In this work the main attention is focused on studying the ultrastructure of osteogenetic cells and osteoclasts. The degree of differentiation and functional state are evaluated according to the degree of development of organelles for specific biosynthesis: rough endoplasmic reticulum (RER), Golgy complex (GC), as well as the state of mitochondria and cell nucleus. As compared with a synchronous control, the population of osteogenetic cells from zones of bone reconstruction shows a decrease in the number of functionally active forms. We can judge of this from the reduction of a specific volume of RER, GC, mitochondria in osteoblasts. RER loses architectonics typical for osteoblasts and, as against the control, is represented by short narrow canaliculi distributed throughout the cytoplasm; some canals disintegrate. GC is slightly pronounced, mitochondria become smaller in size and acquire an optically dark matrix. These phenomena are supposed to be associated with the desorganization of microtubules and microfilaments in the cells under microgravity conditions. The population of osteogenetic cells shows a decrease in the number of differentiating osteoblasts and an increase in the number of little-differentiated stromal cells. In the population of osteoblasts, degrading and apoptotic cells are sometimes encountered. Such zones show a numerical increase of monocytic cells

  14. Connexin43 gap junctions in normal, regenerating, and cultured mouse bone marrow and in human leukemias: their possible involvement in blood formation.

    PubMed Central

    Krenacs, T.; Rosendaal, M.

    1998-01-01

    their membrane replicas. In normocellular human bone marrow, gap junctions were as rare as in adult mouse and similarly distributed, except that they were also on adipocytic membranes. In a few leukemic samples, characterized by an increased stromal/hematopoietic cell ratio, there were two- to fourfold more Cx43 (2.8 x 10(5) to 3.9 x 10(5)/mm3) than in the normal (1.0 x 10(5) to 1.2 x 10(5)/mm3). The cases included a hypoplastic acute lymphoblastic leukemia, an acute myeloid leukemia (French-American-British classification M4-5), a case of myelodysplastic syndrome with elevated number of megakaryocytes, and a CD34+ acute hemoblastosis, probably acute myeloid leukemia (French-American-British classification M7). Taken together, our results indicate that direct cell-cell communication may be involved in hematopoiesis, ie, in developmentally active epiphyseal bone marrow and when there is a demand for progenitors in regeneration. However, gap junctions may not play as important a role in resting adult hematopoiesis and in leukemias. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 10 PMID:9546360

  15. Effects of the oral antidiabetic repaglinide on the reproduction of rats.

    PubMed

    Viertel, B; Güttner, J

    2000-05-01

    underlined by the death of individual animals (W 3, W 4 and W 5). Offspring survival during the last trimester of pregnancy and during lactation was affected in the 'fertility study' and in the 'peri-postnatal study' after 30 and 80 mg/kg and in the 'supplementary study' slightly in W 3 and more pronounced in W 4 and W 5. Changes of the skeleton in the extremities of the offspring were observed in all studies where the animals were exposed to repaglinide during late pregnancy (i.e. after completion of organogenesis) and/or lactation. At radiography the skeletal alterations comprised deformities of the coracoid process and acromion process, of the proximal humeral epiphysis, and of the epiphysis distalis and the condylus distalis of the femur. Deltoids of the humerus showed a slight increase of height and a length reduction. The radius and ulna were slightly bent. The most marked effects and the highest incidence were induced during the first half of lactation (W 4). As age of offspring increased the changes were more pronounced and occurred with a higher incidence. Correspondingly, ash weight, calcium, magnesium and phosphorus content of bones were reduced, but the proportions remained constant. Histopathological examination (supplementary study) showed that small fibrotic foci were formed in the area of dislocation of parts of the epiphyseal plate and that the remaining hyaline cartilage was thinner than normal (W 3, W 4 and W 5). Additionally, the longitudinal axis of the diaphysis juxtaposed to the growth zone was markedly bent, becoming convex to the lateral side. The studies clearly demonstrated that long bone development was not impaired during embryogenesis and early fetogenesis but after completition of organogenesis exclusively, indicating that repaglinide was not teratogenic. Effects of repaglinide were clearly effects on growth. The effects seen in all studies only occurred at excessively high plasma concentrations which will not be reached at human therapeutic