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Pitfalls in Tc99m polyphosphate skeletal imaging.

The quality of Tc-PP scans is best in younger patients. In all age groups quality is adversely affected by free TcO4-. This should be suspected if excessive background is present or marked accumulation is noted in the thyroid gland. Direct physician supervision of all studies is recommended. Symptomatic and roentgenographically positive areas may then be determined for special interpretative attention. Objects which attenuate activity should be removed or noted. Potential sources of superficial contamination (product spill, urine, saliva) must be known and considered when extraneous activity does not correlate with skeletal structures or clinical findings. Normal variations in skeletal uptake of Tc-PP include asymmetries between periarticular areas on the right and left, local increases due to physiologic calvarial thickening and uptake in persistently visualized sternal ossification centers. Apparent variations in the vertebral activity may be due to focal plane effects of rectilinear scanners. Hyperemia can cause diffusely increased Tc-PP localization in an entire extremity. This effect may completely obscure a lesion or obscure the extent of a lesion. Tc-PP excretion through the kidneys occasionally provides useful morphologic or functional information concerning the urinary tract which should be inspected on all scans. Abnormal soft tissue uptake occurs in a variety of conditions including healing wounds and some malignant tumors. A large percentage of patients over 40 years of age demonstrate localization of Tc-PP in the walls of the femoral vessels.

Adolescent↗

Collagenase-3 (MMP-13) is expressed during human fetal ossification and re-expressed in postnatal bone remodeling and in rheumatoid arthritis.

To explore possible physiologic functions for the metalloproteinase collagenase-3, we have examined its temporal and spatial expression during human fetal development. Except for mesenchymal cells in the umbilical cord at 4 weeks of gestation, signal for collagenase-3 mRNA was confined to mineralizing skeletal tissue and detected in hypertrophic chondrocytes and osteoblastic cells involved in ossification beginning at 10 weeks and continuing through gestation. These cells were also immunoreactive with collagenase-3 antiserum, indicating their ability to produce collagenase-3 protein. In osteoblastic cells, the expression of membrane-type 1 metalloproteinase and 72-kd gelatinase mRNA, which have the capacity to activate collagenase-3 in vitro, colocalized with that of collagenase-3. In postnatal tissues, collagenase-3 was re-expressed in processes involving skeletal remodeling, such as bone cysts and ectopic bone and cartilage formation. Multinucleated osteoclasts were consistently negative for collagenase-3. Furthermore, in patients with seropositive rheumatoid arthritis, expression of collagenase-3 was prominent in articular cartilage, and collagenase-3 protein was detected by immunoblotting in synovial fluids. Consistent with its substrate specificities, a plausible function for collagenase-3 in these processes is to preferentially degrade type II collagen, thus serving a role during primary ossification, in skeletal remodeling, and in destructive joint disease.

Aged↗

Human osteoblast stimulation by sera from paraplegic patients with heterotopic ossification.

The pathophysiology of heterotopic periarticular ossification is not understood. Though local agents may be responsible, factors present in the serum may be contributory. Sera from 4 paraplegic patients with heterotopic ossification and 4 'normal' paraplegics were incubated with human osteoblasts in tissue culture and their metabolic activity was measured quantitatively. There were significantly greater levels of osteoblast stimulating factors present in the sera of ossifying patients, (p less than 0.01). These factors may contribute to the pathogenesis of heterotopic ossification.

Adult↗

[Histopathological study of aging of the posterior portion of human cervical vertebral bodies and discs--with special reference to the early ossification of the posterior longitudinal ligament].

UNLABELLED: Ossification of the posterior longitudinal ligament ( OPLL ) of the cervical spine is a disease causing spinal canal stenosis and, henceforth , spinal cord compression. This ossification is found approximately in three percent of the adult Japanese, but it is also found to be present among Chinese, Korean and other South-East Asians, whereas the incidence among Caucasians was reported to be significantly low. The etiology of this interesting ossification is still unknown although multidisciplinary studies have been carried out in Japan in recent years. The purpose of the present study is to find an early ossification of the posterior longitudinal ligament of the cervical spine and to see its relationship with other chronological changes of the surrounding structures. MATERIAL AND METHOD: One hundred and forty-one cervical spinal columns were obtained en bloc from C2 to C7 from the autopsied bodies at Juntendo University Hospital and at the Tokyo Metropolitan Medical Examiners' Office. There were 89 males and 52 females with a wide age distribution. A 66 year-old male case with advanced continuous OPLL died at Juntendo University Hospital was added to the study. The specimens were either cross-sectioned or sagittally sectioned, and studied soft-ray-roentgenologically and histopathologically. RESULTS: There were specimens after the third decade of life showing micro-ossification along the midline of the posterior aspect of the vertebral body on cross-section as well as micro-ossification or hyperostosis adjacent to the posterior corner of the vertebral body on sagittal section. These micro-ossification or hyperostosis seemed to be a product of a physiological aging process, but could be considered as a precursor of the OPLL . The periosteum was well demonstrated on the posterior aspect of the vertebral body in the first two decades of life, but it became inconspicuous with age. In the adult spine there was no clear delineation between the deep layer of the posterior longitudinal ligament and the fibrous layer of the periosteum . The cambium layer looked absent on hematoxylin-eosin stain. However, on Giemsa stain there appeared a thin layer which would present increased cellular activity between the body and what appeared to be the fibrous layer of the periosteal. This layer was considered to be a 'sleeping cambium layer' for which it was named 'latent periostium layer (LPL)'.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Mineralization and osteogenesis in the human first rib cartilage.

Mineralization and osteogenesis in the human first rib cartilage were studied radiologically and by means of normal and polarized light microscopy. Onset of mineralization occurs at the end of puberty and is located directly beneath the perichondrium. Bone is formed in a typical spur-like pattern, arising medially from the upper edge of the manubrium sterni and laterally from the caudal rim of the bony part of the rib. From the middle of the second decade, large cartilage canals with several blood vessels and loose perivascular connective tissue are seen in central areas of the first costal cartilage. These parts are the last to be mineralized and ossified in old age. The type of osteogenesis cannot be classified according to common patterns. In spite of the subperichondral localization it cannot be intramembranous, because the new bone is separated from the perichondrium by a layer of mineralized cartilage. Osteogenesis cannot be called endochondral compared with the epiphyseal plate for the following reasons: there are no hypertrophied chondrocytes; an immunoreactivity for collagen type X is missing; areas where bone is formed directly on hyaline cartilage could be proved. Vascularization and onset of osteogenesis are separated in time and localization. Mineralization and osteogenesis in human first rib cartilage are physiological age-related changes, which cannot be regarded as degenerative processes. Ossification is not directly correlated with the invasion of blood vessels and cannot be classified as one of the classical concepts of intramembranous or endochondral osteogenesis.

Adolescent↗

The Chorimac-12. A multichannel cochlear implant for total deafness. Description and clinical results.

More than 90% of cases of patients suffering from acquired or congenital deafness may be provided with some sound sensation owing to the electrical stimulation of the few cochlear nerve fibers that are still present in the deaf cochlea. In order to obtain some speech discrimination without lip reading it is necessary to elicite different frequency sound sensations. Thus electrically proofs compartments must be performed all along the cochlear keyboard. The placement of 12 intra-cochlear electrodes is greatly facilitated by using an electrodes-bearer which is introduced through a very simple and classical surgical procedure. The indications for implanting depend on undiscussible criteria (total deafness, auditory response to electrical stimulation of the round window, patient's motivation). Clinical results consist of psychoaffective improvement and auditory possibilities. All patients are able to discriminate homosyllabic words in closed lists without lips reading, but the percentages of these performances greatly vary from one patient to the other. Some patients, generally suffering from acquired total deafness, are able to discriminate words or sentences without reference list and without help of lips reading. These results depend on the patient's socialization level, on the pre or post-lingual status of the deafness, on an eventual cochlear ossification, and on the value of several pre operative electro physiological data. Associated handicaps (autism, blindness, tetraplegia) are not contra indications and often represent supplementary reasons for implanting. The value of these post-operative results may be predicted owing to a series of electrical pre-operative tests and clinical data. Thus it is possible to determine the respective indications of multi and single channel cochlear implants.

Adolescent↗

Disulfide bridge conformers of mature BMP are inhibitors for heterotopic ossification.

Heterotopic ossification is a frequent complication in patients who have suffered head and neck traumas or undergone total hip replacement. Heterotopic ossification occurs when osteogenic precursor cells present at the ectopic site receive the necessary signal(s) to differentiate into osteoblasts. At the protein level, the key factors in differentiation of cells to the osteogenic lineage are BMPs. Stable BMP variants derived from the identical amino acid sequence but with different disulfide bridge configurations have been investigated and found to be capable of inhibiting ossification in vitro and in vivo in rodents. These findings provide a concept for the straightforward development of a novel class of BMP antagonists that could lead to new treatments for traumatically and genetically induced heterotopic ossification and also, possibly, for disorders in which other members of the TGF-beta superfamily are involved.

Animals↗

Natriuretic peptide regulation of endochondral ossification. Evidence for possible roles of the C-type natriuretic peptide/guanylyl cyclase-B pathway.

The natriuretic peptide family consists of three structurally related endogenous ligands: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). The biological actions of natriuretic peptides are thought to be mediated through the activation of two guanylyl cyclase (GC)-coupled receptor subtypes (GC-A and GC-B). In this study, we examined the effects of ANP and CNP, which are endogenous ligands for GC-A and GC-B, respectively, on bone growth using an organ culture of fetal mouse tibias, an in vitro model of endochondral ossification. CNP increased the cGMP production much more potently than ANP, thereby resulting in an increase in the total longitudinal bone length. Histological examination revealed an increase in the height of the proliferative and hypertrophic chondrocyte zones in fetal mouse tibias treated with CNP. The natriuretic peptide stimulation of bone growth, which was mimicked by 8-bromo-cGMP, was inhibited by HS-142-1, a non-peptide GC-coupled natriuretic peptide receptor antagonist. The spontaneous increase in the total longitudinal bone growth and cGMP production was also inhibited significantly by HS-142-1. CNP mRNA was expressed abundantly in fetal mouse tibias, where no significant amounts of ANP and BNP mRNAs were detected. A considerable amount of GC-B mRNA was present in fetal mouse tibias. This study suggests the physiologic significance of the CNP/GC-B pathway in the process of endochondral ossification.

Animals↗