RESUMO
The objective of the study was to analyze and compare the abilities of various human cell types with inherently dissimilar osteogenic potentials to induce heterotopic bone formation following ex vivo transduction with two distinct adenoviral vectors encoding bone morphogenetic protein type 2 (BMP2). The cells comprised primary human bone marrow mesenchymal stem cells (BM-MSCs), primary human skin fibroblasts (SFs), and a human diploid fetal lung cell line (MRC-5). The vectors included adenovirus type 5 or a chimeric adenovirus type 5 with the fiber gene of adenovirus type 35 (Ad5F35-BMP2), both demonstrating significantly different expression of BMP2 in vitro. The experimental groups consisted of the three human cell types transduced with each of the two adenoviral vectors. Using nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice, the transduced cells were injected intramuscularly following ex vivo adenoviral transduction. The nature and extent of heterotopic bone formation were analyzed radiographically and histologically. At 14 days postinjection, abundant, highly mineralized bone was formed in mice injected with Ad5F35-BMP2-transduced cells irrespective of the cell type. There was no statistically significant difference in the amount of bone formed between BM-MSCs, SFs, and MRC-5 cells transduced with Ad5F35-BMP2, as assessed from bone surface area on biplanar plain radiography. Substantially lesser amounts or no bone could be detected in mice injected with cells transduced with Ad5-BMP2. Immunohistochemical analysis confirmed the presence of human cells in muscle as early as 2 days postdelivery; however, at 6-7 days after injection, the transduced cells could not be detected in surrounding muscle, or in the heterotopic bone, indicating the host origin of the newly formed bone. The results of the study demonstrate no significant difference in osteoinductive properties between BM-MSCs, SFs, and MRC-5 cells transduced ex vivo with the same type of adenovirus encoding BMP2. The level of BMP2 expression appears to be a crucial factor determining the extent of heterotopic bone formation and was significantly affected by the type of adenovirus used. In the cell types studied, Ad5F35-BMP2 was more efficacious than Ad5-BMP2 in providing adequate levels of BMP2 for efficient osteoinduction.
Assuntos
Proteínas Morfogenéticas Ósseas/genética , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Osteogênese , Transdução Genética/métodos , Fator de Crescimento Transformador beta , Adenoviridae/genética , Animais , Proteína Morfogenética Óssea 2 , Proteínas Morfogenéticas Ósseas/metabolismo , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Linhagem Celular , Células Cultivadas , Humanos , Injeções Intramusculares , Camundongos , Camundongos SCID , RadiografiaRESUMO
True giant cell tumors of the larynx (GCTL) are quite rare, and only individual case reports are documented in the literature. Eight cases of GCTL were identified in the Otorhinolaryngic Pathology Tumor Registry between 1966 and 2000. There were 2 women and 6 men, ages 26 to 62 years (mean, 44.5 yrs). Patients presented with a palpable neck mass (n = 5), airway obstruction (n = 3), hoarseness (n = 3), and dysphagia (n = 2). All tumors involved the thyroid cartilage, a few with local extension. The mean tumor size was 4.1 cm. Histologically, the tumors showed no connection to the surface epithelium and arose in sites of ossification. The tumors had an expansile, infiltrative growth and consisted of numerous multinucleated osteoclast-like giant cells within a cellular stroma composed of plump, oval mononuclear cells. Of interest was that the nuclei of the giant cells were similar to the nuclei of the stromal cells. Treatment included biopsy only with adjuvant therapy (n = 2), local resection (n = 3), and total laryngectomy (n = 3). Follow-up showed 5 patients were alive without evidence of disease (mean follow-up, 6.9 yrs); 2 died of unrelated causes (mean survival, 22.2 yrs). No patients developed recurrences. GCTL are rare tumors that can cause significant airway obstruction. Complete surgical resection yields an excellent outcome without adjuvant therapy.
Assuntos
Tumores de Células Gigantes/patologia , Neoplasias Laríngeas/patologia , Adulto , Feminino , Tumores de Células Gigantes/diagnóstico por imagem , Tumores de Células Gigantes/cirurgia , Humanos , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/cirurgia , Masculino , Pessoa de Meia-Idade , Radiografia , Radioterapia Adjuvante , Cartilagem Tireóidea/patologia , Resultado do TratamentoRESUMO
The radiologic features of giant cell tumor (GCT) and giant cell reparative granuloma (GCRG) of bone often strongly suggest the diagnosis and reflect their pathologic appearance. At radiography, GCT often demonstrates a metaepiphyseal location with extension to subchondral bone. GCRG has a similar appearance but most commonly affects the mandible, maxilla, hands, or feet. Computed tomography and magnetic resonance (MR) imaging are helpful in staging lesions, particularly in delineating soft-tissue extension. Cystic (secondary aneurysmal bone cyst) components are reported in 14% of GCTs. However, biopsy must be directed at the solid regions, which harbor diagnostic tissue. These solid components demonstrate low to intermediate signal intensity at T2-weighted MR imaging, a feature that can be helpful in diagnosis. Multiple GCTs, although rare, do occur and may be associated with Paget disease. Malignant GCT accounts for 5%-10% of all GCTs and is usually secondary to previous irradiation of benign GCT. Treatment of GCT usually consists of surgical resection. Recurrence is seen in 2%-25% of cases, and imaging is vital for early detection. Recognition of the spectrum of radiologic appearances of GCT and GCRG is important in allowing prospective diagnosis, guiding therapy, and facilitating early detection of recurrence.
Assuntos
Doenças Ósseas/diagnóstico , Doenças Ósseas/patologia , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/patologia , Tumor de Células Gigantes do Osso/diagnóstico , Tumor de Células Gigantes do Osso/patologia , Granuloma de Células Gigantes/diagnóstico , Granuloma de Células Gigantes/patologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Cintilografia , Tomografia Computadorizada por Raios XRESUMO
Fibrodysplasia ossificans progressiva (FOP) is a catastrophic genetic disorder of progressive heterotopic ossification associated with dysregulated production of bone morphogenetic protein 4 (BMP4), a potent osteogenic morphogen. Postnatal heterotopic ossification in FOP is often heralded by hectic episodes of severe post-traumatic connective tissue swelling and intramuscular edema, followed by an intense and highly angiogenic fibroproliferative mass. The abrupt appearance, intense size, and rapid intrafascial spread of the edematous preosseous fibroproliferative lesions implicate a dysregulated wound response mechanism and suggest that cells and mediators involved in inflammation and tissue repair may be conscripted in the growth and progression of FOP lesions. The central and coordinate role of inflammatory mast cells and their mediators in tissue edema, wound repair, fibrogenesis, angiogenesis, and tumor invasion prompted us to investigate the potential involvement of mast cells in the pathology of FOP lesions. We show that inflammatory mast cells are present at every stage of the development of FOP lesions and are most pronounced at the highly vascular fibroproliferative stage. Mast cell density at the periphery of FOP lesional tissue is 40- to 150-fold greater than in normal control skeletal muscle or in uninvolved skeletal muscle from FOP patients and 10- to 40-fold greater than in any other inflammatory myopathy examined. These findings document mobilization and activation of inflammatory mast cells in the pathology of FOP lesions and provide a novel and previously unrecognized target for pharmacologic intervention in this extremely disabling disease.
Assuntos
Mastócitos/patologia , Músculo Esquelético/patologia , Miosite Ossificante/patologia , Contagem de Células , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Músculo Esquelético/fisiopatologia , Miosite Ossificante/fisiopatologiaRESUMO
BACKGROUND: Primary osteosarcomas of the head and neck in the pediatric age group, not associated with previous irradiation or a known syndrome, are rare. The literature contains several single cases and small study series; however, to the authors's knowledge, there has been no comprehensive large study to evaluate the clinicopathologic aspects of these tumors. METHODS: Twenty-two cases of osteosarcomas of the head and neck in patients 18 years of age or younger, diagnosed between 1970 and 1997, were retrieved from the Otorhinolaryngic-Head & Neck Tumor Registry of the Armed Forces Institute of Pathology (AFIP). No secondary sarcomas (radiation-induced or those arising after chemotherapy) or those associated with known syndromes were included. Clinical, radiographic, and histologic features were reviewed, and patient follow-up was obtained. RESULTS: The patients included 11 girls and 11 boys, 1-18 years of age (mean, 12.2 yrs). Patient symptoms related to tumor location were painless swelling, loss of teeth, headaches, or a mass lesion, present for an average of 5.9 months. No genetic abnormalities were documented. The tumors most frequently involved the mandible (n = 19), followed by the sphenoid sinus (n = 2) and the maxilla (n = 1). The tumors ranged in size from 1.1-10.0 cm (mean, 4.5 cm). All tumors were invasive and malignant by radiology and/or histology. The tumors were Grade 1 (n = 11), Grade 2 (n = 8), or Grade 3 (n = 3). All cases, except one chondroblastic osteosarcoma, were osteoblastic osteosarcomas. Thirteen patients underwent initial surgical resection with (n = 5) or without (n = 9) additional radiation and/or chemotherapy. The remaining 9 patients had an initial biopsy for diagnosis followed by surgery (n = 4) or surgery and radiation and/or chemotherapy (n = 5). Follow-up was available for 19 patients: 13 were alive at last follow-up with no evidence of disease (mean, 13.1 yrs); 1 was alive with disease (1.3 yrs); 3 had died without evidence of disease (mean, 23.2 yrs); and 2 had died of disease (mean, 7.8 yrs). The 3 patients with high-grade osteosarcoma were alive without disease (mean, 20.0 yrs). CONCLUSIONS: Primary head and neck osteosarcomas in the pediatric population are typically low- to moderate-grade lesions in the mandible. Despite the invasive nature and high grade of a few of these tumors, there is an excellent overall long-term prognosis for patients in this age group with tumors in these locations.
Assuntos
Neoplasias Ósseas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Osteossarcoma/patologia , Adolescente , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Lactente , Masculino , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , RadiografiaRESUMO
OBJECTIVES/HYPOTHESIS: To study the effects of bone involvement in experimentally induced sinusitis and the effect of involved bone on the overlying mucosa. STUDY DESIGN: Animal study. METHODS: Sinusitis was induced unilaterally with Pseudomonas aeruginosa in the maxillary sinus of 19 New Zealand white rabbits. At 6 weeks, the pathogenic organism was confirmed by culture, and a segment of the bone from the medial wall of the sinus implanted in a submucosal pocket in the opposite sinus. The rabbits were killed at predetermined time intervals up to 13 weeks from sinusitis induction, and en bloc sinus sections were decalcified and stained. RESULTS: The implanted bone reabsorbed partially or totally in all specimens. However, the study revealed clear histological evidence of bone involvement adjacent to the infected sinuses and the bony changes extended to the noninfected side in all specimens. The histological findings were identical to those seen in chronic osteomyelitis. CONCLUSIONS: This study demonstrates the ability for pseudomonal sinusitis, at least in the presence of surgical intervention, to involve bone at a distance from the site of primary infection in the absence of intervening mucosal disease. If confirmed with additional organisms and models, these findings have significant implications for the therapeutic management of chronic sinus disease.
Assuntos
Sinusite Maxilar/patologia , Osso Nasal/patologia , Infecções por Pseudomonas/patologia , Animais , Feminino , Sinusite Maxilar/microbiologia , Mucosa Nasal/patologia , Septo Nasal/patologia , CoelhosRESUMO
We describe a new familial metabolic bone disease characterized by expanding hyperostotic long bones, early onset deafness, premature tooth loss, and episodic hypercalcemia. The condition affects a mother and daughter studied at the age of 36 years and 11 years, respectively. Both individuals lost all hearing in early childhood and suffered premature shedding of teeth. Skeletal pains began just before puberty. Swelling and aching of most middle phalanges in the hands is an especially troublesome manifestation. The mother also had episodes of symptomatic hypercalcemia first documented in late childhood and subsequently during intercurrent illness and postpartum lactation. Radiographs show hyperostosis and/or osteosclerosis predominantly in the skull and appendicular skeleton. Long bones also are expanded considerably, especially the middle phalanges in the fingers. The mother's skeletal abnormalities are more severe. Biochemical parameters of bone turnover, including serum alkaline phosphatase (ALP) activity, are elevated substantially. In the proposita, dynamic histomorphometry of nondecalcified sections of iliac crest revealed rapid skeletal remodeling. In the mother, who had been treated with bisphosphonates, electron microscopy (EM) showed disorganized collagen bundles as well as necrotic and apoptotic bone cells but no osteocytic osteolysis. Measles virus gene transcripts were not detected in peripheral blood monocytes. Karyotyping was normal, 46,XX. Hyperphosphatasia with bone disease previously has been reported as either a sporadic or autosomal recessive condition. Expansile skeletal hyperphosphatasia (ESH) is probably inherited as an autosomal dominant trait with a high degree of penetrance.
Assuntos
Fosfatase Alcalina/sangue , Doenças Ósseas Metabólicas , Genes Dominantes , Adulto , Densidade Óssea , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/patologia , Criança , Surdez/genética , Feminino , Humanos , Hipercalcemia/genética , Hiperostose/genética , Osteosclerose/genética , Radiografia , Perda de Dente/genéticaRESUMO
We evaluated a 7-year-old girl with severe platelike osteoma cutis (POC), a variant of progressive osseous heteroplasia (POH). The child had congenital heterotopic ossification of dermis and subcutaneous fat that progressed to involve deep skeletal muscles of the face, scalp, and eyes. Although involvement of skeletal muscle is a prominent feature of POH, heterotopic ossification has not been observed in the head, face, or extraocular muscles. The cutaneous ossification in this patient was suggestive of Albright hereditary osteodystrophy (AHO); however, none of the other characteristic features of AHO were expressed. Inactivating mutations of the GNAS1 gene, which encodes the alpha-subunit of the stimulatory G protein of adenylyl cyclase, is the cause of AHO. Mutational analysis of GNAS1 using genomic DNA of peripheral blood and of lesional and nonlesional tissue from our patient revealed a heterozygous 4-base pair (bp) deletion in exon 7, identical to mutations that have been found in some AHO patients. This 4-bp deletion in GNAS1 predicts a protein reading frameshift leading to 13 incorrect amino acids followed by a premature stop codon. To investigate pathways of osteogenesis by which GNAS1 may mediate its effects, we examined the expression of the obligate osteogenic transcription factor Cbfa1/RUNX2 in lesional and uninvolved dermal fibroblasts from our patient and discovered expression of bone-specific Cbfa1 messenger RNA (mRNA) in both cell types. These findings document severe heterotopic ossification in the absence of AHO features caused by an inactivating GNAS1 mutation and establish the GNAS1 gene as the leading candidate gene for POH.
Assuntos
Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Mutação , Proteínas de Neoplasias , Ossificação Heterotópica/genética , Ossificação Heterotópica/patologia , Fatores de Transcrição/genética , Sequência de Aminoácidos , Sequência de Bases , Osso e Ossos/metabolismo , Linhagem Celular , Criança , Subunidade alfa 1 de Fator de Ligação ao Core , Éxons , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Displasia Fibrosa Poliostótica/etiologia , Testa/patologia , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Regulação da Expressão Gênica , Humanos , Dados de Sequência Molecular , Especificidade de Órgãos , Ossificação Heterotópica/congênito , RNA Mensageiro/metabolismo , Pele/metabolismo , Pele/patologia , Fatores de Transcrição/metabolismo , Transcrição GênicaRESUMO
Osteochondroma represents the most common bone tumor and is a developmental lesion rather than a true neoplasm. It constitutes 20%-50% of all benign bone tumors and 10%-15% of all bone tumors. Its radiologic features are often pathognomonic and identically reflect its pathologic appearance. Osteochondromas are composed of cortical and medullary bone with an overlying hyaline cartilage cap and must demonstrate continuity with the underlying parent bone cortex and medullary canal. Osteochondromas may be solitary or multiple, the latter being associated with the autosomal dominant syndrome, hereditary multiple exostoses (HME). Complications associated with osteochondromas are more frequent with HME and include deformity (cosmetic and osseous), fracture, vascular compromise, neurologic sequelae, overlying bursa formation, and malignant transformation. Malignant transformation is seen in 1% of solitary osteochondromas and in 3%-5% of patients with HME. Continued lesion growth and a hyaline cartilage cap greater than 1.5 cm in thickness, after skeletal maturity, suggest malignant transformation. Variants of osteochondroma include subungual exostosis, dysplasia epiphysealis hemimelica, turret and traction exostoses, bizarre parosteal osteochondromatous proliferation, and florid reactive periostitis. Recognition of the radiologic spectrum of appearances of osteochondroma and its variants usually allows prospective diagnosis and differentiation of the numerous potential complications, thus helping guide therapy and improving patient management.
Assuntos
Neoplasias Ósseas/diagnóstico , Imageamento por Ressonância Magnética , Osteocondroma/diagnóstico , Tomografia Computadorizada por Raios X , Biópsia , Diagnóstico Diferencial , HumanosRESUMO
The formation of heterotopic bone within soft connective tissue is a common feature of at least three distinct genetic disorders of osteogenesis in humans: fibrodysplasia ossificans progressiva; progressive osseous heteroplasia; and Albright hereditary osteodystrophy. The pathobiologic characteristics of osteogenic induction, the histopathologic features of osteogenesis, the anatomic distribution of heterotopic lesions, and the developmental patterns of disease progression differ among all three conditions. The molecular and cellular basis of redirecting a mature connective tissue phenotype to form bone is a remarkable biological phenomenon with enormous implications for the control of bone regeneration, fracture healing, and disorders of osteogenesis.
Assuntos
Displasia Fibrosa Poliostótica/genética , Miosite Ossificante/genética , Ossificação Heterotópica/genética , Diagnóstico Diferencial , Displasia Fibrosa Poliostótica/patologia , Displasia Fibrosa Poliostótica/terapia , Humanos , Biologia Molecular , Mutação/genética , Miosite Ossificante/patologia , Miosite Ossificante/terapia , Ossificação Heterotópica/patologia , Ossificação Heterotópica/terapiaRESUMO
BACKGROUND: Primary chondrosarcoma of the head and neck in the pediatric age group is rare. The literature contains several single cases and small series; however, to the authors' knowledge, there has been no previous comprehensive larger study to evaluate the clinicopathologic aspects of these tumors. METHODS: Fourteen cases of chondrosarcoma of the head and neck from patients age 18 years or younger, diagnosed between 1970 and 1997, were retrieved from the Otorhinolaryngic-Head & Neck Tumor Registry of the Armed Forces Institute of Pathology. No secondary sarcomas (radiation-induced or arising in association with Maffucci syndrome or Ollier disease) were included. Clinical, radiographic, and histologic features were reviewed and patient follow-up obtained. RESULTS: The patients included 6 girls and 8 boys ages 3-18 years (mean, 11.8 years). Patient symptoms (nasal stuffiness or discharge, sinusitis, headaches, or a mass lesion) were related to tumor location and were present for an average of 7.2 months. No genetic abnormalities were documented. The tumors most frequently involved the maxillary sinus (n=4), followed by the mandible (n=3), nasal cavity (n=2), and neck (n=2), with 1 each of the nasopharynx, orbit, and base of the skull. The tumors ranged in size from 2.0 to 15.0 cm (mean, 3.1 cm). All tumors were invasive and malignant as determined by radiology and/or histology. The tumors were Grade 1 (n=9), Grade 2 (n=1), or Grade 3 (mesenchymal, n=2; dedifferentiated n=2). All patients were treated by surgery, followed by radiation (n=5) and/or chemotherapy (n=2). Follow-up was available for 11 patients; all were alive (at a mean of 14.8 years), with only a single patient demonstrating evidence of residual/ recurrent tumor (at 16.6 years). CONCLUSIONS: Primary head and neck chondrosarcoma in the pediatric population is typically low grade and occurs in the maxillary sinus or mandible. Despite the invasive and high grade nature of some of these tumors, there is an excellent long term prognosis for patients in this age group with tumors in these locations.
Assuntos
Condrossarcoma/patologia , Neoplasias de Cabeça e Pescoço/patologia , Adolescente , Quimioterapia Adjuvante , Criança , Pré-Escolar , Condrossarcoma/diagnóstico , Condrossarcoma/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/cirurgia , Cefaleia/diagnóstico , Humanos , Masculino , Neoplasias Mandibulares/patologia , Neoplasias do Seio Maxilar/patologia , Obstrução Nasal/diagnóstico , Invasividade Neoplásica , Neoplasias Nasais/patologia , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Rinite/diagnóstico , Sinusite/diagnósticoRESUMO
Vitamin D deficiency rickets was diagnosed in three juvenile chimpanzees (Pan troglodytes) raised indoors under skylights and consuming only breast milk. Two cases detected early had mild but characteristic radiographic changes. More advanced disease presented with florid x-ray features of rickets and pathologic fractures, as well as hypocalcemia, hypophosphatemia, and low serum 25-hydroxyvitamin D levels. Treatment by a single injection of vitamin D2 in sesame oil (slow release) followed by daily oral supplementation with vitamin D2 corrected the condition. On the basis of experience with these cases and comparison with rickets in humans, a prevention protocol for mother-reared, inside-housed, chimpanzee juveniles was developed. Injection with slow release vitamin D2 (5,000 IU i.m. once) at 4 mo of age, followed by oral supplementation of 400 IU vitamin D2 daily until weaning, prevents rickets in juvenile chimpanzees raised indoors.
Assuntos
Doenças dos Primatas/prevenção & controle , Raquitismo/veterinária , Administração Oral , Animais , Animais de Zoológico , Osso e Ossos/diagnóstico por imagem , Cálcio/sangue , Dieta/veterinária , Suplementos Nutricionais , Ergocalciferóis/administração & dosagem , Ergocalciferóis/uso terapêutico , Feminino , Masculino , Pan troglodytes , Doenças dos Primatas/dietoterapia , Radiografia , Raquitismo/dietoterapia , Raquitismo/prevenção & controle , Óleo de GergelimRESUMO
The clinical significance of positive bacterial cultures in chronic sinusitis is often difficult to assess. Contaminants from surface colonization of the sinus mucosa may be difficult to distinguish from true intramucosal or bone involvement. Furthermore, tissue Gram stains are frequently unable to demonstrate the presence of bacteria in tissue despite endoscopic evidence of active sinusitis. In situ hybridization (ISH) techniques using bacterial rRNA probes were applied to evaluate the presence of intramucosal and intraosseous bacteria in chronic sinusitis surgical specimens. A total of 22 specimens of chronically inflamed human ethmoid bone were evaluated by ISH and by Gram stain. In three specimens, ISH identified bacterial rRNA within sinus mucosa and mucin. Notably, in these three ISH-positive specimens, Gram stain was negative in two. No specimen showed evidence of bacterial rRNA within bone. These preliminary results suggest that in situ hybridization may be a useful adjunct to current methods of detecting microorganisms within chronically infected sinus tissue.
Assuntos
Hibridização In Situ/métodos , Sinusite/diagnóstico , Adulto , Doença Crônica , Humanos , Projetos Piloto , Estudos Prospectivos , RNA Bacteriano/análise , RNA Ribossômico/análise , Sinusite/microbiologia , Sinusite/cirurgia , Coloração e Rotulagem/métodosRESUMO
BACKGROUND AND AIM OF THE STUDY: Cardiac valve calcification is the predominant pathology in patients needing valve replacement. The aim of this study was to determine if aortic valve cells calcify spontaneously and, if so, to characterize the nodular complex and response to growth factors. METHODS: Aortic valves were obtained from humans undergoing surgical valve replacement, and from female dogs. The valvular endothelium was removed and explants cultured in medium. RESULTS: A population of valvular interstitial cells spontaneously formed distinct calcified nodules containing hydroxyapatite within two to three weeks in canine and within six weeks in human aortic valves. The nodules contained an inner ring of dead cells surrounded by an outer ring of living cells. Cells associated with nodules had osteoblast-like characteristics and stained positively for extracellular bone matrix proteins. Incubating canine cells with potential calcifying stimuli tested the stimulus for calcification. The rate of nodule formation was increased with transforming growth factor beta-1 (+25 nodules), 25-hydroxycholesterol (+9 nodules) and bone morphogenetic protein 2 (+4 nodules) as compared with vehicle control (+3 nodules) over 25 days. CONCLUSIONS: We identified a population of valvular interstitial cells with osteoblast-like characteristics that spontaneously form calcific nodules in cell culture. In addition, the rate of calcific nodule formation was increased with transforming growth factor beta-1 and 25-hydroxycholesterol. Further study of these 'calcifying valve cells' may yield a new in vitro model for testing therapy aimed at preventing calcific valve stenosis.
Assuntos
Valva Aórtica/citologia , Calcinose/patologia , Animais , Células Cultivadas , Cães , Feminino , Humanos , Imuno-HistoquímicaRESUMO
OBJECTIVE: A histomorphometric analysis of patellae from necropsies on persons between the third and tenth decades of life was carried out to trace the natural history of osteoarthritis. DESIGN: Minutiae of the histological changes in the surface and basilar portions of the articular cartilage were developed as criteria for the quantitation. A total of 99 patellas were harvested in the stated age range. The present study reports the results of ten grossly and radiologically normal specimens from subjects 23-32 years old served as controls. RESULTS: None of the control patellae were entirely histologically normal. Abnormality of the cartilage surface did not consistently proceed remodeling at the attachment to the subchondral plate. CONCLUSIONS: This observation throws into question the concept that osteoarthritis has a single histogenesis or always arises in articular cartilage.
Assuntos
Envelhecimento/patologia , Osteoartrite do Joelho/patologia , Patela/patologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Patela/anatomia & histologia , Distribuição por SexoRESUMO
Although extensive research regarding the treatment of calvarial defects has been done in adult models, little is known about the response in the maturing skeleton. The role of coralline hydroxyapatite and expanded polytetrafluoroethylene membrane in augmenting bone growth and repair of calvarial defects in a neonatal model is explored. Utilizing a 3-week-old neonatal swine model, bone growth into 28 calvarial defects was measured. After exposure of the calvaria in seven animals, four defects of 10 mm in diameter were created. In each animal, one defect was treated with a 10-mm disc of porous hydroxyapatite alone (Interpore 500, Interpore International), and a second defect was covered with an expanded polytetrafluoroethylene membrane (Gore-Tex OV-6) secured by four 3-mm microscrews (Luhr Microsystem, Howe-Medica Inc.). The third defect combined an implanted hydroxyapatite disc covered by an expanded polytetrafluoroethylene membrane, whereas the fourth defect served as an untreated control. Histology and histomorphometry were performed on undecalcified specimens harvested at 6 weeks after surgery. In both hydroxyapatite groups, the bone growth into the inorganic matrix provided complete osseous union in all specimens, and the amount of fibrosis was significantly lower (p < 0.02) in comparison with the control. Unexpectedly, there was significant osteoclastic resorption of the hydroxyapatite matrix (35.1 percent decrease) with simultaneous bone deposition and remodeling. The addition of an expanded polytetrafluoroethylene membrane covering the hydroxyapatite implant provided an insignificant advantage in bone growth (27.3 percent versus 28.3 percent, respectively). Finally, the expanded polytetrafluoroethylene membrane alone afforded no qualitative advantage secondary to intrusion of brain and dura into the defect as well as displacement of the membrane inward during appositional growth, leading to incomplete healing of the defect with thinning of the surrounding cranial bone. Unique in this maturing model was morphologic evidence of complete union at the calvaria-hydroxyapatite interface in all specimens as well as active remodeling of the hydroxyapatite matrix. The results of this study suggest that porous hydroxyapatite may be a suitable bone substitute in maturing calvarial bone defects, achieving superior osseous integration and volumetric bone gain while undergoing concurrent resorption and remodeling.
Assuntos
Durapatita , Membranas Artificiais , Politetrafluoretileno , Próteses e Implantes , Crânio/cirurgia , Animais , Animais Recém-Nascidos , Regeneração Óssea , Osseointegração , Porosidade , Crânio/crescimento & desenvolvimento , Crânio/patologia , SuínosRESUMO
Since the initial employment of magnetic resonance imaging (MRI) to diagnose meniscal tears, a characteristic low-signal intensity, triangular-shaped structure has been interpreted as representing the entire meniscus. The difficulty in diagnosing meniscocapsular separations with MRI has brought attention to our lack of understanding of the appearance on MRI of the outer third of the meniscus and the meniscocapsular junction. We correlated MRIs of the meniscus in cadaver knees with histological sections and found that the low-signal, wedge-shaped structure corresponds only to the avascular (white) zone of the meniscus, whereas the high-signal zone peripheral to it corresponds to the vascularized (red) zone.
Assuntos
Meniscos Tibiais/anatomia & histologia , Adulto , Humanos , Imageamento por Ressonância Magnética , Meniscos Tibiais/irrigação sanguíneaRESUMO
The novel aminosterol, squalamine, inhibits angiogenesis and tumor growth in multiple animal models. This effect is mediated, at least in part, by blocking mitogen-induced proliferation and migration of endothelial cells, thus preventing neovascularization of the tumor. Squalamine has no observable effect on unstimulated endothelial cells, is not directly cytotoxic to tumor cells, does not alter mitogen production by tumor cells, and has no obvious effects on the growth of newborn vertebrates. Squalamine was also found to have remarkable effects on the primitive vascular bed of the chick chorioallantoic membrane, which has striking similarities to tumor capillaries. Squalamine may thus be well suited for treatment of tumors and other diseases characterized by neovascularization in humans.
Assuntos
Anticarcinógenos/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Animais , Divisão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Embrião de Galinha/efeitos dos fármacos , Colestanóis/farmacologia , Colágeno , Córnea , Neovascularização da Córnea/prevenção & controle , Combinação de Medicamentos , Fatores de Crescimento Endotelial/metabolismo , Fatores de Crescimento Endotelial/farmacologia , Endotélio Vascular/efeitos dos fármacos , Neoplasias Oculares/prevenção & controle , Fator 2 de Crescimento de Fibroblastos/farmacologia , Glioma/tratamento farmacológico , Glioma/patologia , Laminina , Linfocinas/efeitos dos fármacos , Linfocinas/metabolismo , Linfocinas/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteoglicanas , Coelhos , Ratos , Ratos Endogâmicos F344 , Transplante Heterólogo , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
BACKGROUND: Calcitriol therapy is the mainstay of therapy for the treatment of secondary hyperparathyroidism. Oral administration of calcitriol is necessary in CAPD patients, but no studies have directly compared different routes of administration in this patient population. METHODS: To determine if the peak serum calcitriol level (pulse therapy) is more important than the total delivered dose, we randomized CAPD patients with mild to moderate secondary hyperparathyroidism to receive either pulse (3.0 microg twice a week, n = 10) or daily (0.75 microg a day, n = 8) oral calcitriol in comparable weekly doses. The main comparison was the rate of decline of serum intact parathyroid hormone (PTH) levels to reach the desired end-point of 100 pg/ml. The patients were dialysed with low-calcium dialysate and received only calcium-containing phosphate binders. RESULTS: Pharmacokinetic analysis after a single dose of 3.0 microg (pulse) vs 0.75 microg (daily) revealed 1,25(OH)2-vitamin D levels to be higher in the pulse group at 3 and 6 h, but equivalent by 12 h. The area under the curve for 1 week of daily and 1 week of pulse therapy was equal. The patients in the 2 arms had equivalent basal serum levels of PTH (pulse = 562 +/- 291 vs daily = 454 +/- 113 pg/ml), calcium (pulse = 2.32 +/- 0.20 vs daily = 2.32 +/- 0.12 mmol/l) and phosphorus (pulse = 1.32 +/- 0.52 vs daily = 1.35 +/- 0.26 mmol/l). The time required for the PTH to decrease to 100 pg/ml and the rate of decline in PTH were similar (time: pulse = 14.2 +/- 6.8 weeks, daily = 12.2 +/- 7 weeks; rate: pulse = 7.4 +/- 4.2 vs daily = 8.4 +/- 4.2% PTH/week; P = NS). The serum calcium increased similarly in both groups. Hypercalcaemia (> 2.9 mmol/l) was rare (pulse = 3, daily = 2 episodes). CONCLUSIONS: This study demonstrates that pulse and daily calcitriol are similarly effective and safe for the treatment of mild to moderate secondary hyperparathyroidism in CAPD patients despite higher peak levels of 1,25(OH)2-vitamin D with pulse therapy.
Assuntos
Calcitriol/administração & dosagem , Diálise Peritoneal Ambulatorial Contínua , Adulto , Idoso , Calcitriol/efeitos adversos , Calcitriol/uso terapêutico , Cálcio/sangue , Feminino , Humanos , Hiperparatireoidismo/tratamento farmacológico , Hiperparatireoidismo/etiologia , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Hormônio Paratireóideo/sangue , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
A 2-year-old child with fibrodysplasia ossificans progressiva underwent a muscle biopsy of a very early lesion, and had findings that showed the earliest stage ever seen in the histopathology of fibrodysplasia ossificans progressiva. This very early stage consisted of intense perivascular lymphocytic infiltration into normal appearing skeletal muscle. A nearly identical histopathologic sequence was noted in a cat with phenotypic features similar to those of fibrodysplasia ossificans progressiva in humans. These new findings represent the earliest documented changes that have ever been noted in fibrodysplasia ossificans progressiva, and provide further histopathologic support for the recent discovery that lymphocytes may play a role in the pathogenesis of heterotopic ossification in fibrodysplasia ossificans progressiva.