RESUMO
We have shown that osteoblastic cells derived from trabecular bone explants of osteoporotic subjects (OP cells) exhibited an altered alkaline phosphatase (ALP) response to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] compared to control (CON) cells. Our hypothesis that OP cells have other intrinsic abnormalities was investigated using our cell models representing two different stages of differentiation. OP and CON cells were cultured in the absence (-DEX) or presence (+DEX) of 10 nM dexamethasone (DEX) in 10% fetal calf serum (FCS) prior to exposure to serum-free medium containing 1 nM of PTH and/or 17-beta estradiol (E2). Both OP and CON cells responded to DEX with a two-fold increase in basal ALP activity. While E2 or PTH+E2 had no effect on OP cells, both treatments inhibited ALP activity in CON cells (p<0.05). OP and CON cells grown in DEX also expressed PTH-stimulated adenylate cyclase (AC) activities higher than those of (-DEX) cells. OP+DEX cells, however, exhibited activities which were 8-fold higher than those of CON+DEX cells (p<0.001). In OP+DEX cells, E2 stimulated basal AC activity (p<0.05) but did not affect PTH-stimulated activity. In contrast, in CON+DEX cells, E2 had no effect on basal activity but inhibited PTH-stimulated AC activity (p<0.001). Osteocalcin production was 4-fold lower in OP+DEX cells compared to OP-DEX and CON cells (p<0.05) while osteocalcin mRNA levels were significantly lower in OP+DEX and CON+/-DEX cells compared to OP-DEX cells (p<0.05). E2 did not affect osteocalcin protein or mRNA levels in either OP or CON cells. No differences in mRNA levels were found for estrogen receptor-alpha (ER-a) in OP+/-DEX cells whereas these levels were significantly higher in CON+DEX compared to CON-DEX cells (p<0.05). These results indicate that DEX amplified the differences between OP and CON cells and confirm the presence of intrinsic osteoblastic abnormalities in patients with osteoporosis that persist in culture.
Assuntos
Dexametasona/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteoporose/patologia , Adenilil Ciclases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/metabolismo , Calcitriol/farmacologia , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Estradiol/farmacologia , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoblastos/enzimologia , Osteocalcina/genética , Osteocalcina/metabolismo , Osteoporose/enzimologia , Osteoporose/genética , Hormônio Paratireóideo/farmacologia , Fenótipo , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Receptor Tipo 1 de Hormônio Paratireóideo/genética , Receptor Tipo 1 de Hormônio Paratireóideo/metabolismo , Fatores de TempoRESUMO
We compared the effects of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and its analog, 1alpha,25-dihydroxy-16-ene-vitamin D3 [1alpha,25(OH)2-16-ene-D3], as well as their interactions with 17-beta estradiol (E2) on osteoblastic function in our human normal (HOB) and osteosarcoma SaOS-2 cell models representing two different stages of differentiation, the more differentiated HOB+DEX cells and SaOS+DEX cells, and the corresponding less differentiated HOB-DEX and SaOS-DEX cells. The differential effects of 1alpha,25(OH)2D3 and 1alpha,25(OH)2-16-ene-D3 and the modulation by E2 on ALP activity in HOB-DEX and HOB+DEX cells were small but significant. The most significant effects were seen in SaOS+DEX cells, in which 1alpha,25(OH)2-16-ene-D3 was 100-fold more potent than 1alpha,25(OH)2D3, the maximal enhancement being exerted at 0.1 nM and 10 nM, respectively. E2 enhanced the stimulatory effects of both compounds, with ALP being increased 2-fold at 0.1 nM (p<0.001). Osteocalcin (OC) production in HOB-DEX cells was stimulated 1.3 to 1.4-fold by 1alpha,25(OH)2D3 and 1alpha,25(OH)2-16-ene-D3 at a concentration of 0.01 nM, with E2 inhibiting the effect of 1alpha,25(OH)2-16-ene-D3. In SaOS-DEX and SaOS+DEX cells, 1alpha,25(OH)2D3 and 1alpha,25(OH)2-16-ene-D3 stimulated OC production 1.6-fold at 0.1 nM with E2 slightly enhancing the effect of 1alpha,25(OH)2D3. Western blot analysis of 1alpha,25(OH)2D3 receptor (VDR) levels showed that in SaOS+DEX cells, the effect of 1alpha,25(OH)2D3 was larger than that of 1alpha,25(OH)2-16-ene-D3. These results show that 1alpha,25(OH)2-16-ene-D3 is biologically active in human osteoblasts.
Assuntos
Neoplasias Ósseas/patologia , Calcitriol/farmacologia , Estradiol/farmacologia , Osteoblastos/efeitos dos fármacos , Osteossarcoma/patologia , Adulto , Fosfatase Alcalina/metabolismo , Western Blotting , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Masculino , Osteocalcina/biossíntese , Células Tumorais CultivadasRESUMO
To better understand the cutaneous immune response to Treponema pallidum, we performed an immunohistologic study of skin biopsies from a total of 11 patients with secondary syphilis; biopsies from five persons infected with HIV-1 were included in the analysis to assess at the tissue level the impact of concomitant HIV-1 infection on disease expression. In all of the biopsies, staining for HLA-DR, a marker for cellular activation, was observed among infiltrating leukocytes, dermal vascular endothelial cells, and keratinocytes. Infiltrating mononuclear cells stained positively for CD4 or CD8, with CD4+ cells always being in the majority. Surprisingly, most of the CD4+ cells had histiocytic, rather than lymphocytic, morphologic characteristics. Immunostaining for CD14 confirmed that these cells were monocytic in origin, whereas immunostaining for CD3 revealed that the lymphocytes were predominantly CD8+ cytotoxic T cells. B cells were not detected despite the presence of variable numbers of plasma cells in all specimens. By immunofluorescence, all of the specimens demonstrated perivascular deposition of immunoglobulins, complement, or fibrinogen; linear staining at the dermal-epidermal junction also was observed in most of the specimens. No differences in immunocytochemical or immunofluorescence staining patterns were observed between the specimens from patients who were HIV positive and patients who were HIV negative. In addition to providing a more precise definition of the infiltrating cells in syphilitic lesions, our results, taken as a whole, indicate that cellular immune processes are largely responsible for the development of cutaneous manifestations during syphilitic infection and that coinfection with HIV-1 has little discernible effect on the cutaneous response to T. pallidum.
Assuntos
Infecções por HIV/virologia , HIV-1 , Sífilis Cutânea/patologia , Adulto , Biópsia , Complexo CD3/análise , Antígenos CD4/análise , Antígenos CD8/análise , Feminino , Infecções por HIV/complicações , Infecções por HIV/metabolismo , Humanos , Imuno-Histoquímica , Receptores de Lipopolissacarídeos/análise , Masculino , Pessoa de Meia-Idade , Pele/química , Pele/patologia , Sífilis Cutânea/complicações , Sífilis Cutânea/metabolismoRESUMO
We previously developed two models of human osteoblasts with distinct differentiation stages using cells derived from iliac crest trabecular bone explants cultured long term in the presence (HOB + DEX) and absence (HOB - DEX) of 10 nM dexamethasone (DEX) (Wong et al., J Bone Miner Res 1990;5:803). Using these models from 36 subjects aged 41-80 years, we examined the effects of 17 beta-estradiol (E2) on cell proliferation, osteocalcin (OC) production, alkaline phosphatase (ALP) and basal and parathyroid hormone (PTH)-stimulated adenylate cyclase activities, as well as the steady-state mRNA levels of ALP, collagen type I(COLL), OC, and receptors for E2 (ER) and PTH (PTHr). E2 alone had no effect on [3H]thymidine uptake in (HOB - DEX) cells but appeared to stimulate the uptake in (HOB + DEX) cells in a dose-dependent manner, with maximum effect at 10(-10)M (p < 0.05). However, in the presence of 10(-6)M PTH, E2 inhibited the uptake in (HOB - DEX) cells (ANOVA, KW = 18.95, p < 0.005) but stimulated the uptake in (HOB + DEX) cells (KW = 13.52, p < 0.025). E2 decreased the amount of osteocalcin in culture media from both (HOB - DEX) and (HOB + DEX) cells (p < 0.05). PTH alone or E2, alone or in combination with 10(-9)M PTH, had no effect on ALP activity in (HOB - DEX) cells. In contrast, in (HOB + DEX) cells, E2 + PTH but not E2 alone, had biphasic effects on ALP activity, with maximum stimulation observed at 10(-11) and 10(-10)M E2, and a return to basal levels at 10(-9)M E2. E2 decreased basal adenylate cyclase activities in a dose-dependent manner in (HOB + DEX) but not (HOB - DEX) cells (KW = 13.48, p < 0.05). In (HOB + DEX) cells, E2 had biphasic effects on PTH-stimulated adenylate cyclase activity, with significant stimulation observed at 10(-10)M (p < 0.05). While E2 had no significant effect on osteoblastic marker mRNA levels in (HOB - DEX) cells, it decreased osteocalcin and stimulated PTHr mRNA levels in (HOB + DEX) cells. Thus, in our human osteoblastic cell models, estrogen regulated metabolic function largely in the more differentiated cells, by modifying the effects of PTH.
Assuntos
Dexametasona/farmacologia , Estradiol/farmacologia , Glucocorticoides/farmacologia , Osteoblastos/metabolismo , Hormônio Paratireóideo/farmacologia , Adenilil Ciclases/genética , Adenilil Ciclases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Análise de Variância , Northern Blotting , Divisão Celular/efeitos dos fármacos , Células Cultivadas , DNA/biossíntese , Relação Dose-Resposta a Droga , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteocalcina/biossíntese , Osteocalcina/genética , RNA Mensageiro/metabolismo , RadioimunoensaioRESUMO
Thoracolumbar burst fractures are a major cause of disability; however, there are few studies on the functional outcome of patients with this injury. The purpose of this study is to evaluate the functional outcome of patients with thoracolumbar burst fractures using a generic and a condition-specific health status survey. The SF-36 survey (generic) and the Roland scale (condition-specific) were administered to 24 patients who had a minimum of 2 years follow-up after a thoracolumbar burst fracture without neurologic deficit. The average SF-36 score was 65% (compared to 45% for dialysis and 66% for diabetes) and the Roland score was 65% (compared to 58% for low back pain). Of the patients, 33% were able to return to their previous employment, but only 8% were able to return to their pre-injury level of sports. There was a strong correlation (r = 0.71) between the Roland scale and the SF-36 pain scale. There were poor correlations between the Roland scale and residual kyphosis (r = 0.003), and between the SF-36 pain scale and residual kyphosis (r = 0.10). There was no significant difference in the functional outcome of those patients treated operatively versus nonoperatively.
Assuntos
Vértebras Lombares/lesões , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Adulto , Feminino , Nível de Saúde , Humanos , Escala de Gravidade do Ferimento , Cifose/etiologia , Tempo de Internação , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Fraturas da Coluna Vertebral/complicações , Vértebras Torácicas/cirurgia , Resultado do TratamentoRESUMO
Pseudohypoparathyroidism (PHP) is characterized by a lack of response to parathyroid hormone (PTH); however, normal skeletal responsiveness to PTH in some patients with PHP type Ia was previously suggested on the basis of clinical observations. To test this hypothesis, we measured cyclic adenosine monophosphate (cAMP) production in response to various agonists in bone-derived osteoblast-like (OBL) cells from trabecular explants obtained from an iliac crest biopsy of a 25-year-old woman with PHP. The patient was proved to have PHP type Ia on the basis of Albright's hereditary osteodystrophy and decreased activity of stimulatory guanine nucleotide-binding protein (Gs) in erythrocytes. Responsiveness of the patient's OBL cells was compared with OBL cells from eight subjects aged 18-39 years who had no evidence of metabolic bone disease. OBL cells from the patient responded to the following agonists (expressed in multiples of elevation of cAMP, stimulated/basal, mean +/- SE, n = 3): PTH, 3.8 +/- 0.3; forskolin, 8.2 +/- 0.2; and cholera toxin, 56.8 +/- 10.0. These responses were not significantly different from those of control OBL cells: PTH, 4.5 +/- 1.1 (range 2.4-7.5); forskolin, 7.7 +/- 1.4; and cholera toxin, 57.9 +/- 16.2. The normal cholera toxin response indicated the presence of functional Gs. Bone cells from patients with PHP type Ia may exhibit a normal PTH receptor-coupled adenylyl cyclase system in vitro despite clinical evidence of impaired hormone-responsive adenylyl cyclase in other tissues, including the kidney. Skeletal responsiveness to PTH may explain the long periods of spontaneous normocalcemia observed in this patient.
Assuntos
Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Hormônio Paratireóideo/farmacologia , Pseudo-Hipoparatireoidismo/metabolismo , Adenilil Ciclases/metabolismo , Adolescente , Adulto , Fosfatase Alcalina/metabolismo , Osso e Ossos/patologia , Células Cultivadas , AMP Cíclico/biossíntese , Feminino , Humanos , Masculino , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteocalcina/biossíntese , Pseudo-Hipoparatireoidismo/classificação , Pseudo-Hipoparatireoidismo/patologiaRESUMO
STUDY DESIGN: This study reports the experience with four patients regarding a modified anterior approach to the cervicothoracic junction. OBJECTIVES: This technique was evaluated with respect to extent of exposure, ease of technique, and postoperative morbidity. SUMMARY OF BACKGROUND DATA: Previously reported anterior approaches to the cervicothoracic junction have described either full sternotomy resection of the left sternoclavicular junction or osteotomy of the clavicle. A simplified approach was chosen using a partial sternotomy, which has not been described previously for approaches to the spine. METHODS: Four patients with metastatic disease, in the region of the cervicothoracic junction, required decompression and stabilization for palliation of symptoms. An anterior approach was required for decompression. A standard cervical approach was combined with a partial median sternotomy and transverse osteotomy through the synostosis between the manubrium and body of the sternum. In three patients, the left innominate vein was divided. Decompression and anterior stabilization were followed by posterior stabilization at an interval of 4 to 7 days. RESULTS: This procedure was simple to perform, requiring little additional operative time for opening or closure. It provided excellent exposure from C3-T4. There was no associated morbidity related to the division of the manubrium or innominate vein. CONCLUSION: Partial sternotomy combined with a standard cervical incision provides excellent exposure to the cervicothoracic junction from C3-T4. It is technically simple to perform and avoids the risk of injury to subclavian vessels inherent in resection of the clavicle or sternoclavicular junction. There is no additional morbidity associated with this approach.
Assuntos
Vértebras Cervicais/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgia , Humanos , Articulações/cirurgia , Imageamento por Ressonância Magnética , Métodos , Neoplasias da Coluna Vertebral/diagnóstico , Neoplasias da Coluna Vertebral/secundárioRESUMO
We have examined bone cells derived from iliac crest trabecular explants of 30 patients with idiopathic osteoporosis and 45 control subjects in order to determine whether intrinsic abnormalities in osteoblast function may contribute to the decreased bone formation observed in this disease. Bone cells isolated from all subjects expressed several in vitro characteristics of the osteoblast phenotype including adenylate cyclase responsiveness to parathyroid hormone (PTH) and prostaglandin E1 (PGE1), basal and 1,25(OH)2D3-stimulated alkaline phosphatase activity and osteocalcin production. Results were compared amongst three subject groups; young controls less than 40 years old, older controls over 40 years old, and osteoporotics. Osteoporotic cells were found in general to be fully active in vitro. There were no differences between osteoporotic and control cells in their basal levels of adenylate cyclase, or alkaline phosphatase, in their growth rates, or cell morphology. The cyclic AMP (cAMP) response to PTH was significantly lower in osteoporotic cells (71%, p < 0.01) and older control cells (64%, p < 0.005) relative to the response in cells from younger controls, suggesting that the decreased responsiveness in osteoporotic cells was due to subject age rather than the osteoporotic state. At the same time, the cAMP responses to PGE1 and cholera toxin were similar in cells from all three subject groups. The response to forskolin was reduced to about 40% in osteoporotic cells compared with controls, but this was not mirrored by similar differences in the responses to PTH, PGE1 or cholera toxin, suggesting that the availability of catalytic subunits is not rate-limiting in these cells. 1,25(OH)2D3-stimulated osteocalcin production was 220% higher in osteoporotics than in older controls, but the numbers tested were small and the difference did not reach significance. The one significant abnormality we observed in osteoporotic cells was in alkaline phosphatase activity: 1,25(OH)2D3-stimulated alkaline phosphatase activity was twofold higher in osteoporotics than in younger (p < 0.05), older (p < 0.05) and pooled controls (p < 0.025). The significance of this finding is unknown, but we postulate that it may reflect an intrinsic abnormality in osteoblast function in patients with idiopathic osteoporosis.
Assuntos
Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoporose/metabolismo , Osteoporose/patologia , Adolescente , Adulto , Fosfatase Alcalina/metabolismo , Calcitriol/metabolismo , Células Cultivadas , AMP Cíclico/metabolismo , Feminino , Humanos , Masculino , Osteocalcina/metabolismo , Hormônio Paratireóideo/farmacologia , Valores de ReferênciaRESUMO
A young girl had tibial osteotomies at age 14 for genu valgum and then had recurrent tibial cysts over a number of years. Hypocalcemia and hyperphosphatemia were first noted at age 21. The diagnosis of pseudohypoparathyroidism was made at age 28, when elevated plasma PTH was detected. Clinical and biochemical features, including a PTH response test and assay of RBC Gs, established the diagnosis of pseudohypoparathyroidism type 1b. Failure to suppress plasma PTH with vitamin D therapy led to an exacerbation of her cystic bone disease; there were widespread lytic lesions radiologically, most of which took up [99mTc]diphosphonate on bone scan. Microradioscopy revealed evidence of resorption of phalangeal tufts. Bone biopsy showed osteitis fibrosa cystica. During an orthopedic procedure, trabecular bone fragments were taken from her right humerus, and bone-derived cells cultured using an explant technique. The cultured cells were osteoblast-like in morphology, fully responsive to PTH, cholera toxin, forskolin, and PGE1 in vitro, and had an alkaline phosphatase and osteocalcin response to 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Following this examination of skeletal responsiveness, attempts were made to suppress the elevated plasma PTH levels and symptomatic bone disease by optimizing therapy with oral 1,25-(OH)2D3. When bone pain associated with the cystic bone disease failed to resolve, the patient underwent total parathyroidectomy, following which the bone pain gradually resolved. This is the first direct demonstration of PTH responsiveness in cultured bone cells in the syndrome of pseudohypoparathyroidism with osteitis fibrosa cystica.
Assuntos
Osso e Ossos/efeitos dos fármacos , Osteíte Fibrosa Cística/metabolismo , Osteoblastos/efeitos dos fármacos , Hormônio Paratireóideo/farmacologia , Pseudo-Hipoparatireoidismo/metabolismo , Adenilil Ciclases/metabolismo , Adulto , Osso e Ossos/citologia , Osso e Ossos/metabolismo , Células Cultivadas , Feminino , Humanos , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Hormônio Paratireóideo/metabolismo , SíndromeAssuntos
Neoplasias da Medula Espinal/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgia , Diagnóstico por Imagem , Seguimentos , Humanos , Exame Neurológico , Complicações Pós-Operatórias/diagnóstico , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/secundário , Neoplasias da Coluna Vertebral/diagnóstico , Neoplasias da Coluna Vertebral/secundário , Vértebras Torácicas/patologiaRESUMO
A total of 33 patients with renal cell carcinoma metastatic to the spine underwent spinal decompression over a 5-year period; 20 were operated on for neurologic dysfunction, and the remainder for pain alone. Surgery was performed anteriorly in 21, posteriorly in 9, and combined in 3 cases. The surgical approach was determined by the preoperative anatomic localization of the tumor. Of these patients 88% had fusions with instrumentation and polymethylmethacrylate; 88% of patients had partial or complete relief of pain; and 64% of bedridden patients subsequently were able to walk. Neurologic function improved in 60% of patients with a neurologic deficit; however, only 36% of incontinent patients regained bladder control. Survival averaged 8.0 +/- 1.5 months. Survival correlated with the degree of neurologic dysfunction and the presence of other known metastases. Recurrent cord compression developed in 49% of patients, usually at the same level; 9 of these 16 patients had repeat decompression, with similar operative results as the primary procedure in terms of pain and neurologic function. Blood loss was variable but often significant. Preoperative embolization appeared to be beneficial. Precise tumor localization preoperatively directing the surgical approach and better patient selection would likely improve results and decrease morbidity. Good palliation appeared to be achieved in regards to both pain relief and improved neurologic function.
Assuntos
Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Cuidados Paliativos , Neoplasias da Coluna Vertebral/secundário , Cimentos Ósseos/uso terapêutico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Masculino , Metilmetacrilato , Metilmetacrilatos/uso terapêutico , Pessoa de Meia-Idade , Fusão Vertebral , Neoplasias da Coluna Vertebral/mortalidade , Neoplasias da Coluna Vertebral/cirurgia , Taxa de SobrevidaRESUMO
Bone cells derived from human trabecular explants display osteoblastic features. We examined the modulation of alkaline phosphatase activity and cAMP production as the result of exposing trabecular explants to physiologic concentrations of dexamethasone for 4 weeks during cellular outgrowth and subculture. Cells treated with dexamethasone were observed to grow generally more slowly than control cells. Cells appeared larger and more polygonal, and staining for alkaline phosphatase was more intense in the dexamethasone-exposed cultures. There was a progressive increase in cellular PTH responsiveness with increasing duration of exposure of cells to dexamethasone. Cells grown for 6 weeks in 3 x 10(-8) M dexamethasone had a 10-fold increase in PTH-stimulated cyclic AMP accumulation. Dexamethasone-treated cells also had a significantly increased alkaline phosphatase activity. 1,25-(OH)2D3-stimulated alkaline phosphatase activity was increased approximately 20-fold. cAMP responses were significantly increased to PTH (21.7-fold), PGE1 (2.67-fold), and forskolin (4.81-fold), but not to cholera toxin. Dexamethasone-treated cells also had a mean decrease in 1,25-(OH)2D3-stimulated osteocalcin production to 26.2% of control values (p less than 0.001). Hydrocortisone treatment gave rise to similar effects but of smaller magnitude than those of dexamethasone. Testosterone did not have a significant effect on alkaline phosphatase activity or cAMP production. Skin fibroblasts showed a significant enhancement of alkaline phosphatase activity in response to dexamethasone, but of a much smaller magnitude than in bone cells. The phenotypic changes induced by long-term culture in dexamethasone are consistent with the promotion of a more differentiated osteoblastic phenotype.
Assuntos
Osso e Ossos/efeitos dos fármacos , Dexametasona/farmacologia , Adenilil Ciclases/metabolismo , Fosfatase Alcalina/metabolismo , Osso e Ossos/citologia , Osso e Ossos/metabolismo , Contagem de Células/efeitos dos fármacos , Células Cultivadas , AMP Cíclico/metabolismo , Humanos , Hidrocortisona/farmacologia , Osteoblastos/efeitos dos fármacos , Osteocalcina/metabolismo , Hormônio Paratireóideo/metabolismo , Ligação Proteica , Testosterona/farmacologia , Fatores de TempoRESUMO
Lytic metastatic lesions from breast, prostate, and other cancers often develop on the endosteal surface of a long bone without penetrating the cortical wall. Current clinical guidelines for determining the fracture risk associated with these endosteal defects do not account for the structural consequences of the lesion. We undertook a combined experimental and analytical study of the structural consequences of the lesions with the ultimate goal of providing improved fracture risk guidelines. Endosteal defects of variable length and involving a variable amount of the cortical wall were created with an expanding reamer in canine femurs. The contralateral femur served as a control. The femurs were tested to failure in four point bending. The geometry of the experimental defects was determined from radiographs and CT. Finite element models of the canine femurs were then used to examine geometric and material parameters in both four point bending and in torsion. The experimental data demonstrate a linear relation between bone strength and amount of cortical wall remaining: % intact strength = 99.6 x remaining wall thickness - 2.0, R2 = 0.769, standard deviation of regression = 11.57. Four of five data points from the linear finite element models were within the 95% confidence intervals for the experimental data. Experimental and finite element data suggest that the minimum wall thickness is the most critical geometric parameter for predicting the structural consequences of endosteal defects. The length of the defect along the bones' long axis has little effect on bone strength. The anelastic behavior of bone does not need to be represented in finite element models of simple endosteal defects because the defects do not cause significant stress concentrations. However, reduction in the modulus of bone along the border of a defect (due to osteolytic changes) can significantly reduce bone strength. These results indicate that the minimum wall thickness should be determined when clinically evaluating an endosteal defect. The results also suggest that information on bone porosity around metastatic lesions should be considered when making estimates of bone strength.
Assuntos
Neoplasias Ósseas/secundário , Osso e Ossos/patologia , Fraturas do Fêmur/patologia , Neoplasias Femorais/patologia , Animais , Neoplasias Ósseas/patologia , Neoplasias da Mama/patologia , Modelos Animais de Doenças , Cães , Fraturas Espontâneas/patologia , Fraturas de Estresse/patologia , Humanos , Neoplasias Experimentais/patologiaRESUMO
Metastatic lesions due to renal cell carcinoma are frequently hypervascular. This study reports the results of preoperative embolization of skeletal metastases from hypernephroma. Reported for the first time in the English literature is the use of this technique for preoperative devascularization of metastatic lesions to the spine in eight patients. Effective devascularization was achieved in all peripheral lesions. Blood loss for peripheral lesions averaged 940 cc and compared favorably to 20 nonembolized cases, in whom average blood loss was 1975 cc. Spinal embolization requires careful identification and preservation of any segmental arteries that supply the anterior spinal artery. Effective spinal devascularization was achieved in six of eight patients. In two patients significant bleeding occurred as a result of incomplete embolization. This series supports the growing evidence for the efficacy and safety of selective arterial embolization in the preoperative control of hemostasis in patients with metastatic hypernephroma. Embolization of spinal metastases, although technically demanding, has been effective in devascularizing these lesions without serious neurologic complications.
Assuntos
Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/terapia , Embolização Terapêutica , Neoplasias Renais/terapia , Embolização Terapêutica/efeitos adversos , Feminino , Hemorragia/epidemiologia , Humanos , Pessoa de Meia-IdadeRESUMO
Surgical strategies for the treatment of symptomatic spinal metastases must take into account both decompression of the spinal cord and stabilization of the spinal column. A method is described for securing spinal stabilization in patients who have undergone surgical decompression for symptomatic spinal metastases by an anterior approach. The fixation device used is a tailor-made prosthesis consisting of a U-shaped stainless steel plate permitting screw fixation to secure axial and rotational stability with an interposed methyl methacrylate strut to provide axial strength and support. The device has been used successfully in 51 patients who have undergone anterior decompression procedures for symptomatic spinal metastases.
Assuntos
Dispositivos de Fixação Ortopédica , Compressão da Medula Espinal/cirurgia , Neoplasias da Coluna Vertebral/secundário , Coluna Vertebral/cirurgia , Idoso , Placas Ósseas , Parafusos Ósseos , Feminino , Humanos , Masculino , Métodos , Próteses e Implantes , Compressão da Medula Espinal/etiologia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/cirurgiaRESUMO
The purpose of this investigation was to measure the reduction in bone strength resulting from drill holes in diaphyseal bone and to compare this with finite element and theoretical predictions for stresses in a tubular structure. Fifty-two pairs of canine femora were tested to failure in four-point bending. One bone of each pair was used as the control; the other femora had holes of variable size drilled in the lateral cortex. At a ratio of drill hole diameter to bone diameter of 0.2, the bone retained only 62% of its expected strength. A linear regression between the area fraction (the ratio of the cross-sectional area of the drilled specimen to the control specimen) and the percentage of expected strength yielded a strong positive correlation (R2 = 0.79). The average cross-sectional properties were used as the basis for linear orthotropic and nonlinear elastic-plastic finite element models of idealized geometry. The linear models proved insufficient for prediction of failure loads. The nonlinear models, which accounted for both material plasticity and the stress concentration effects of the defect, yielded good correspondence with the experimental data. While the influence of irregular borders and adaptive remodeling of the bone adjacent to the defect requires further investigation, our results suggest the possibility of prediction of fracture risk based on geometric properties of metastatic lesions. Prophylactic fixation remains a matter of clinical judgement based on the functional demands and expected strength of the affected bones.
Assuntos
Neoplasias Ósseas/fisiopatologia , Fraturas Ósseas/fisiopatologia , Metástase Neoplásica/fisiopatologia , Estresse Mecânico , Animais , Fenômenos Biomecânicos , Neoplasias Ósseas/complicações , Cães , Fraturas Ósseas/etiologiaRESUMO
Clinical and standard radiographic evaluation of patients with lumbosacral radicular symptoms may, on occasion, fail to delineate a cause. This study retrospectively reviews 62 patients who had undergone nerve root infiltration (NRI) and assesses the accuracy and indications for this diagnostic study. Surgical exploration of patients with a Group 1 response (typical pain reproduced by needle placement and then relieved by NRI) confirmed local root pathology in all. Exclusive of patients with arachnoiditis, a Group 1 response showed 85% accuracy in identifying a single symptomatic root. A Group 2 response (typical pain reproduced by needle placement but not relieved by local anesthesia) indicated multiple root involvement. Patients with a Group 3 or Group 4 response (typical pain not reproduced by needle insertion, with or without relief of pain by local anesthesia) were seldom relieved of radicular pain. NRI was most useful in investigation of patients with radicular symptoms in whom other investigations were 1) normal, 2) showed multiple level involvement, or 3) were difficult to interpret because of previous surgery.
Assuntos
Dor nas Costas/diagnóstico , Raízes Nervosas Espinhais/diagnóstico por imagem , Dor nas Costas/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Radiografia , Raízes Nervosas Espinhais/cirurgiaRESUMO
Management of patients with symptomatic spinal metastasis is designed to (1) relieve pain, and (2) restore or preserve neurologic function. The surgical strategy must include provisions for decompression of the dural sac and nerve roots, and stabilization of the spinal column. The optimal surgical approach, whether from in front or from behind is determined by a number of factors including (1) tumour location, (2) spinal level, (3) fixation factors, (4) patient debility.
Assuntos
Compressão da Medula Espinal/cirurgia , Neoplasias da Coluna Vertebral/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Métodos , Pessoa de Meia-Idade , Compressão da Medula Espinal/etiologia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/cirurgiaRESUMO
We performed quantitative computed tomography in vitro on the first and third lumbar vertebrae in human cadavera using a dibasic potassium phosphate phantom for calibration. The quantitative computed-tomography numbers exhibited a significant positive correlation (R2 = 0.89, p less than 0.0001) with direct measurements of the apparent density of the vertebral trabecular bone. We also conducted uniaxial compression tests to failure of the vertebral bodies after removal of the posterior elements, and found that vertebral compressive strength was also correlated at a high level of significance (R2 = 0.82, p less than 0.0001) with direct measurement of the trabecular apparent density. These findings suggested the possibility that the quantitative computed-tomography values might be directly predictive of vertebral compressive strength. However, when we correlated the quantitative computed-tomography values directly with vertebral compressive strength, the results (R2 = 0.46, p less than 0.061) were suggestive but not quite significant. All vertebral bodies failed by compression of the end-plate, suggesting only a modest structural role for the cortical shell under these loading conditions. This was confirmed by comparing the compressive load to failure of twenty additional pairs of vertebrae that were tested with and without an intact vertebral cortex. Removal of the cortex was associated with approximately 10 per cent reduction in vertebral load to failure.