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Biomedical subjects

M D Fallon

Publications and source records attributed to M D Fallon.

At least 19 recordsLinked to original sources
PubMed1993

Epithelioid osteosarcoma of bone. Immunocytochemical evidence suggesting divergent epithelial and mesenchymal differentiation in a primary osseous neoplasm.

BACKGROUND: The combination of a primary osteosarcoma of bone with a second carcinomatous cell type has been recognized, although immunohistochemical studies currently have not been performed in an attempt to understand the histogenesis of such a tumor. METHODS: In this report, the authors performed immunohistochemical studies on a primary osseous carcinosarcoma. Using a biotin-streptavidin peroxidase conjugate technique, the expression of keratin, epithelial membrane antigen, and vimentin was analyzed. RESULTS: The epithelial cells expressed cytokeratin and epithelial membrane antigen but did not express vimentin. The mesenchymal cells strongly expressed vimentin, and only rare cells expressed cytokeratin. CONCLUSIONS: The clinical, morphologic, and immunophenotypic data in this instance strongly suggest divergent differentiation of a primitive multipotential uncommitted stem cell in a primary osseous tumor.

Adolescent↗
PubMed1993

Skeletal dysplasia in perinatal lethal osteogenesis imperfecta. A complex disorder of endochondral and intramembranous ossification.

Osteogenesis imperfecta (OI) Type II is a rare heritable disorder of bone matrix that results in catastrophic congenital skeletal dysplasia. Two cases of OI Type II had symmetric rhizomelic skeletal dysplasia apparent on ultrasound at 16 and 20 weeks' gestation. Histologic and histochemical studies performed on skeletal tissue from fetal autopsies showed the following: (1) abnormal growth plate tissue characterized by failure of formation of primary bony spongiosa; (2) persistence of calcified cartilage bars in the diaphysis; (3) metaphyseal microfractures; (4) abundant cartilaginous fracture callus; (5) absence of bony callus; (6) failure of formation of intramembranous cortical diaphyseal bone; (7) angulation of long bones in portions of the metadiaphyses bordered by fracture callus; and (8) mechanical failure of the perichondral ring of LaCroix with a normal fibrous ossification groove of Ranvier. These findings suggest that skeletal dysplasia in OI Type II results from the action of muscular forces on a skeleton weakened by a complex disorder of endochondral and intramembranous ossification. The paucity of primary metaphyseal trabeculae and subperiosteal cortical bone leads to pathologic fractures of the immature fiber bone and an imperfect attempt at fracture repair. Angulation and shortening of long bones occurs between numerous sites of focal endochondral fracture callus. Mechanical failure of the fibrous perichondral ring leads to further collapse and shortening without obvious functional impairment of the fibrous ossification groove. Perinatal lethal OI provides insight into how a molecular disorder predominantly of Type I collagen metabolism results in pathology of numerous tissues, leading to severe skeletal dysplasia without primarily affecting chondrogenesis.

Bone Diseases, Developmental↗
PubMed1993

Enchondroma in a patient with fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare heritable disorder characterized by progressive heterotopic endochondral bone formation arising in ligament, tendon, and the fibrous connective tissue of skeletal muscle. The disorder is almost invariably associated with skeletal malformations of the endochondral anlage of the feet. A 25-year-old woman with FOP had a histopathologically documented phalangeal enchondroma. This common neoplasm of cartilage and bone seems not to have been previously reported in FOP; it may represent a coincidental occurrence, but in the context of the patient's genetic disorder, an enchondroma may represent an unusual and variable expression of the disease.

Adult↗
PubMed1993

Bone densitometry observations of osteopetrosis in response to bone marrow transplantation.

Spinal bone density was measured in eight patients with osteopetrosis to assess the natural history of the disease and to monitor the response to therapy. Quantitative computed tomographic scans of the lumbar vertebra were obtained in seven patients, and dual photon absorptiometric scans were obtained when the technique became available. Six children were afflicted with the infantile malignant recessive condition and two with the less severe dominant condition. In all cases, bone densitometry values ranged from four to five times higher than the mean for normal age and gender-matched controls. In four children with recessive osteopetrosis, quantitative computed tomographic and dual photon absorptiometric scans showed an excellent correlation (R = 0.93) between the methods. Quantitative computed tomographic values ranged from 597 to 730 mg/cm3 (mean = 655 mg/cm3) in children with osteopetrorickets and from 901 to 1000 mg/cm3 (mean = 980 mg/cm3) in the same children when the rickets was cured. In two children treated with bone marrow transplantation, bone densitometry values returned to normal within three years. Bone densitometry provides a safe and noninvasive method for observing the natural history and therapeutic response of the osteopetrotic syndromes.

Absorptiometry, Photon↗
PubMed1993

Osteopetrorickets. The paradox of plenty. Pathophysiology and treatment.

Rickets is a common and paradoxical feature of infantile malignant osteopetrosis and results from the inability of osteoclasts to maintain a normal calcium-phosphorus balance in the extracellular fluid. Despite a markedly positive total body calcium balance, rickets arises when the serum calcium x phosphorus product is insufficient to mineralize newly formed chondroid and osteoid. In five children with malignant infantile osteopetrosis, there were clinical, radiographic, biochemical, and histologic findings of rickets. Characteristic biochemical abnormalities included hypocalcemia, hypophosphatemia, and elevated levels of serum acid phosphatase, alkaline phosphatase, c-terminal parathyroid hormone, and 1,25-dihydroxyvitamin D. The urinary calcium/creatinine ratio was markedly depressed. The serum calcium x phosphorus product was below 30 in all children at the time the rickets was diagnosed, and above 40 by the time the rickets had resolved. Baseline bone density measurements were markedly elevated in all children (> 5 standard deviation above normal) and showed even significant increases (> 7 SD) when the rickets was treated with vitamin D and calcium. The children showed marked clinical improvement, decreased lethargy, increase in mobility and activity, and stimulation of appetite, without any additional adverse hematologic or neurologic effects. The rickets was reversible in all children: in one by HLA-identical sibling bone marrow transplantation and in four by physiologic doses of vitamin D and calcium. The parathyroid and renal responses to hypocalcemia were appropriate, but glucocorticoids, used in treating the hematologic complications of the disease, may have blunted the intestinal response to maximal vitamin D stimulation. This latter blockade can be overcome by increasing dietary calcium. By liberalizing rather than by restricting calcium and phosphorus intake, hypocalcemia can be minimized, phosphorus metabolism can be improved, and rickets can be cured.

Bone Marrow Transplantation↗
PubMed1992

The articular manifestations of Paget's disease of bone. A case report.

Disorders of joints are commonly associated with Paget's disease of bone but are often disregarded or attributed to the underlying Pagetic condition. The authors evaluated a 69-year-old man with extensive Paget's disease of bone, degenerative arthritis, calcific periarthritis, and gout. The degenerative arthritis and calcific periarthritis of the shoulders was originally mistaken for Paget's disease of the proximal humerus. The wrist arthritis was attributed to Paget's disease until evaluation of surgical pathology specimens showed intraarticular gouty granulomas. In evaluating and treating a patient with Paget's disease of bone, the orthopedic surgeon should be aware that the successful treatment of associated articular disorders may require therapeutic measures in addition to those used in treating the Paget's disease.

Aged↗
PubMed1992

Estrogen receptors in fracture healing.

Estrogen has profound effects on the regulation of bone metabolism, but its role in fracture healing is unknown. Several recent reports have documented the presence of estrogen receptors in vitro and in diseased tissue. The authors investigated estrogen receptors in nonneoplastic skeletal tissues by immunohistochemical and radioligand binding techniques. Using a fibular osteotomy model of fracture healing in New Zealand rabbits, radioligand binding detected specific, high affinity, saturable estradiol binding sites at low levels throughout fracture healing, with a trend towards a bimodal distribution. Peaks occurred three and 16 days after osteotomy. No estrogen receptor was found by either method in later fracture callus, growth plate, or periosteum. These findings suggest a possible role for estrogen in the early inductive phase and later phase of endochondral ossification in fracture healing.

Animals↗
PubMed1991

Secondary hyperparathyroidism and osteopenia in women following gastric exclusion surgery for obesity.

Gastric exclusion has been introduced as a surgical treatment for morbid obesity. We describe two women who had undergone gastric bypass for obesity with metabolic bone disease and secondary hyperparathyroidism. In one patient transiliac bone biopsy after double tetracycline labelling demonstrated histologic evidence of hyperparathyroidism with osteitis fibrosa cystica. Six additional women who had undergone gastric exclusion were evaluated. Serum phosphorus, calcium, and creatinine were normal in all but one patient who had hypocalcemia. Serum immunoreactive parathyroid hormone was elevated in seven of eight patients and urinary calcium was less than or equal to 2 mmol/d (80 mg/24 h) in 6 patients. Lumbar spine bone mineral density was 86 +/- 7 (mean +/- SE) per cent of predicted and femoral neck bone mineral density was 89 +/- 6 per cent of predicted. Women who have had gastric exclusion for obesity may develop secondary hyperparathyroidism which could result in loss of bone mass.

Bone Diseases, Metabolic↗
PubMed1991

In vivo and ex vivo magnetic resonance imaging evaluation of early disc degeneration with histopathologic correlation.

The in vivo and ex vivo microanatomic appearance of early disc degeneration were identified by magnetic resonance imaging and correlated with their respective histopathologic findings. Five cadaver spines (18 discs) and 25 patient studies (122 discs) all imaged at 1.5 Tesla were studied. Two signs of early degenerative disc disease were found: infolding and the central dot. Infolding of the central fibers of the outer annulus coalesced into a central dot of low signal intensity that was seen on both the ex vivo and in vivo images. Infolding was seen 29 of 122 times, and the central dot was observed 15 to 122 times on the in vivo images. A later form of degenerative disc disease was identified as a separation of the nucleus pulposus from the hyaline cartilage end-plate. This separation was seen as a linear area of either low or high signal intensity on the ex vivo images but only as a band of high signal intensity on the in vivo spin-echo 2,500-msec/80-msec images. Only 7 of 122 in vivo discs showed this separation. Internal herniation of nucleus pulposus into the outer annulus was seen only on the ex vivo images. Early degenerative disc disease may exist before there is loss of disc height or signal intensity on the long time-to-repetition (TR)/time-to-echo (TE) magnetic resonance images.

Adult↗
PubMed1991

Hurler syndrome with special reference to histologic abnormalities of the growth plate.

Hurler syndrome is a mucopolysaccharide disorder resulting from an heritable deficiency in alpha-L-iduronidase, an enzyme required in the catabolism of heparan sulfate and dermatan sulfate glycosaminoglycan (GAGs). The resultant intracellular accumulation of GAG leads to disruption of the intracellular and extracellular environment and dysfunction of multiple organ systems. Among the most noted manifestations of this disease is disproportionate short trunk dwarfism, which develops during the first years of life. Histochemical and electron-microscopic observations on a 30-month-old child with Hurler syndrome showed marked irregularities in chondrocyte orientation within the growth plate, along with disruption of the normal columnar architecture. Vacuolization with enlargement of the cellular border was the characteristic ultrastructural finding. An heritable abnormality in the enzymatic degradation of structural glycosaminoglycans leads to profound disruption of the normal mechanisms of growth and development.

Cartilage↗
PubMed1990

Fluid-fluid level: a nonspecific finding in tumors of bone and soft tissue.

Fluid-fluid levels have commonly been reported to occur in aneurysmal bone cysts but have also been seen in telangiectatic osteosarcoma, chondroblastoma, and giant cell tumor of bone. The authors reviewed their experience with nine bone and three soft-tissue tumors that showed fluid-fluid levels on computed tomographic or magnetic resonance images. The bone tumors included fibrous dysplasia, simple bone cyst, recurrent malignant fibrous histiocytoma of bone, two classical osteosarcomas, and four aneurysmal bone cysts. The soft-tissue tumors included soft-tissue hemangioma and two synovial sarcomas. Except for aneurysmal bone cysts, these types of tumors have not been reported to be associated with fluid-fluid levels. Radiologic-pathologic correlation was available in seven patients; in all seven, the fluid-fluid levels indicated prior hemorrhage. The authors conclude that the presence of fluid-fluid levels in bone or soft-tissue tumors cannot be considered diagnostic of any particular tumor.

Adolescent↗
PubMed1990

Regional migratory osteoporosis. A case report and review of the literature.

Regional migratory osteoporosis (RMO) is an idiopathic disorder characterized by bouts of severe periarticular lower limb pain associated with rapidly developing localized osteoporosis. Symptoms often reverse spontaneously after six to nine months. Recurrence of symptoms in an adjacent joint is a distinguishing feature. Routine laboratory tests are uninformative. Diagnosis is made after exclusion of more common entities. Knowledge of RMO can prevent unnecessary invasive procedures. Vertebral osteoporosis has recently been associated with RMO. A 50-year-old physician developed the symptoms and signs of RMO superimposed upon well-documented idiopathic vertebral osteoporosis. This association should be recognized when evaluating lower limb pain.

Humans↗
PubMed1989

WR-2721 reduces bone loss after hindlimb tenotomy in rats.

WR-2721 is a thiophosphate analog of cysteamine that produces hypocalcemia in vivo. Previous studies suggest that WR-2721 produces hypocalcemia by independent inhibitory effects on parathyroid hormone (PTH) secretion, osteoclastic bone resorption, and tubular reabsorption of calcium. We sought to determine if WR-2721 would decrease bone loss in an animal model of disuse osteoporosis produced by unilateral knee tenotomy in the rat. Tenotomy significantly increased osteoclast number in tibias on the side of the procedure compared with tibias on the opposite side which had not undergone the procedure at 3 and 14 days. Femoral weight of tenotomized limbs were also reduced significantly compared with the contralateral limb at 3 and 14 days. WR-2721 treatment (240 mg/kg daily) prevented 26% of the loss of femoral dry weight and 29% of the loss of femoral ashed weight produced 14 days after tenotomy. In addition, WR-2721 treated (240 mg/kg daily) animals had fewer osteoclasts in tenotomized tibias than control animals at 3 days (6.6 +/- 0.7/mm versus 10.3 +/- 0.9/mm, p less than 0.02) and at 14 days (5.8 +/- 0.3/mm versus 8.7 +/- 0.4/mm, p less than 0.02). These data suggest that WR-2721 decreases bone loss in this model by decreasing osteoclastic bone resorption.

Amifostine↗
PubMed1989

Paget disease: MR imaging findings.

Magnetic resonance (MR) images of 13 patients with Paget disease were reviewed, and findings were correlated with those from computed tomographic (CT) scans, radiographs, and, in two patients, surgical biopsy. MR imaging findings correlated with CT and radiographic findings of cortical thickening, increased size of bone, and coarse thickened trabeculae. Focal or diffuse decreased signal intensity, representing dense bone, was seen on images obtained with short and long repetition times (TRs) and echo times (TEs); high-signal foci, representing fat collections, were seen on short TR/TE images; and high-signal foci, representing fibrovascular marrow in active Paget disease, were seen on long TR/TE images. Complications of Paget disease-including basilar invagination, spinal stenosis, and sarcoma--were well identified on MR images. Although MR imaging is not generally used in diagnosis of Paget disease, the disease will be encountered more frequently as more MR imaging examinations are performed. An awareness of the range of findings in Paget disease is useful in evaluating MR images of the musculoskeletal and other systems.

Aged↗
PubMed1989

The effect of cyclosporin A administration and its withdrawal on bone mineral metabolism in the rat.

The in vivo administration of cyclosporin A (CsA) has been associated with significant bone loss and increased bone remodeling. To observe whether these changes are reversible, we have investigated the consequences of the administration and withdrawal of CsA immunotherapy on bone mineral metabolism. Three groups of Sprague-Dawley rats were studied for 28 days. Group A received vehicle, and group B received CsA (15 mg/kg BW) for 28 days, while group C received CsA (15 mg/kg BW) for 14 days and then vehicle from days 15-28 by daily gavage. Serum ionized calcium (Ca2+), PTH, bone gla protein, blood urea nitrogen, creatinine, magnesium, phosphorus, and 1.25-dihydroxyvitamin D were measured weekly. Bone histomorphometry was analyzed on days 14 and 28 in groups A and B and on day 28 in group C. CsA administration resulted in reversible hypomagnesemia and mild transient elevation in circulating 1,25-dihydroxyvitamin D levels with no change in Ca2+, PTH, blood urea nitrogen, or phosphorus. Serum bone gla protein levels were significantly increased (P less than 0.002) during CsA therapy, but tended to return to control values after CsA withdrawal. Enhanced bone remodeling and significant trabecular bone loss accompanied CsA administration. Withdrawal of CsA resulted in all of the histomorphometric parameters, except for bone volume, returning to control values within 2 weeks. Incomplete restoration of bone volume occurred 5 weeks after CsA withdrawal. This limited restoration of bone volume despite CsA withdrawal may have important clinical implications.

Animals↗
PubMed1989

Quantitative computed tomography reflects vertebral fracture morbidity in osteopenic patients.

We studied the relationship between spontaneous vertebral compression fractures and lumbar vertebral trabecular bone density in 69 consecutive patients with suspected osteopenia. Seven had biopsy-confirmed osteomalacia. The remaining 62 were divided into three groups: group 1--asymptomatic patients suspected of having osteopenia on plain films, but with no vertebral compression fractures (N = 24); group II--those with one to five vertebral compression fractures (N = 16); and group III--those with six or more vertebral compression fractures (N = 22). A quantitative computed tomographic (QCT) scan of the lumbar spine was performed on all patients. Patients in group I had QCT values of 94 +/- 23 mg/cm3 (mean +/- SE); those in group II had QCT values of 66 +/- 28 mg/cm3; and those in group III had values of 34 +/- 28 mg/cm3. There were significant differences among all groups (P less than .001), although there was considerable overlap of individuals among the groups. There was no significant difference between the mean QCT value of patients with one compression fracture and the value of those with between two and five compression fractures. Patients with biopsy-proven osteomalacia had higher vertebral trabecular bone density than patients with osteoporosis and compression fractures. Our study provides evidence suggesting a strong inverse relationship between QCT-measured vertebral bone density and the presence of vertebral compression fractures in a group of osteopenic patients.

Absorptiometry, Photon↗