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R J McBroom

Publications and source records attributed to R J McBroom.

17 recordsLinked to original sources
PubMed2005

Long-term culture in dexamethasone unmasks an abnormal phenotype in osteoblasts isolated from osteoporotic subjects.

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.

Adenylyl Cyclases↗
PubMed2001

The biological activities of 1alpha,25-dihydroxyvitamin D3 and its synthetic analog 1alpha,25-dihydroxy-16-ene-vitamin D3 in normal human osteoblastic cells and human osteosarcoma SaOS-2 cells are modulated by 17-beta estradiol and dependent on stage of differentiation.

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.

Adult↗
PubMed1996

Positive interaction between 17 beta-Estradiol and parathyroid hormone in normal human osteoblasts cultured long term in the presence of dexamethasone.

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.

Adenylyl Cyclases↗
PubMed1996

Functional outcome of thoracolumbar burst fractures without neurological deficit.

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.

Adult↗
PubMed1995

Age-dependent expression of osteoblastic phenotypic markers in normal human osteoblasts cultured long-term in the presence of dexamethasone.

We have previously shown that osteoblasts derived from trabecular bone explants and cultured long term in 10 nM dexamethasone ((HOB + DEX) cells) exhibited properties consistent with a more differentiated phenotype compared with those grown in the absence of dexamethasone ((HOB-DEX) cells). To characterize these two cell models further, we measured the steady-state mRNA levels of the phenotypic markers alkaline phosphatase (ALP), collagen type I (COLL) and osteocalcin (OC), OC production, and the activities of ALP and parathyroid hormone (PTH)-stimulated adenylate cyclase. These findings were then correlated with the age and sex of the bone donors. Long-term culture in dexamethasone significantly increased ALP and OC mRNA levels and the activities of ALP and PTH-stimulated adenylate cyclase but not OC production, in (HOB + DEX) compared with (HOB-DEX) cells (p < 0.05). When the data were examined with respect to the age of the bone donor, age-dependent differences in the expression and responses to dexamethasone were apparent. ALP and PTH-stimulated adenylate cyclase activities decreased with increasing age of the bone donor in (HOB-DEX) and (HOB + DEX) cells (p < 0.05). There were no significant correlations between phenotypic marker mRNA levels and bone donor age in (HOB-DEX) and ((HOB + DEX) cells. All age-dependent decreases in ALP and PTH-stimulated cyclase activities were enhanced in the (HOB + DEX) cells. However, when the data were examined according to the sex of the bone donor, there were no differences in mRNA levels, OC production, or ALP and cyclase activities between cells from male and female donors. These results indicate an age dependence in the expression of osteoblastic markers in human bone cells at different stages of differentiation: thus osteoblastic cultures derived from older donors are likely to contain fewer osteoprogenitor cells, lower levels of glucocorticoid receptors or represent more differentiated osteoblasts compared with those derived from younger donors.

Adenylyl Cyclases↗
PubMed1992

Ipsilateral fractures of the distal radius and scaphoid treated by Herbert screw and external skeletal fixation. A report of two cases.

Two patients with comminuted, displaced fractures of the distal radius associated with ipsilateral, undisplaced scaphoid fractures were treated by internal fixation of the scaphoid fracture with a Herbert screw in association with external fixation of the distal radial fracture. One of the patients had a limited open reduction of the distal radius combined with bone grafting. Both patients had satisfactory results. Internal fixation of the scaphoid is indicated if distraction is applied to the carpus to treat an associated fracture of the distal radius, even if the scaphoid fracture is undisplaced.

Accidental Falls↗
PubMed1991

Surgical management of metastatic renal carcinoma of the spine.

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.

Bone Cements↗
PubMed1989

Structural consequences of endosteal metastatic lesions in long bones.

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.

Animals↗
PubMed1989

Preoperative embolization in the treatment of osseous metastases from renal cell carcinoma.

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.

Bone Neoplasms↗
PubMed1988

Strength reductions from metastatic cortical defects in long bones.

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.

Animals↗
PubMed1988

Nerve root infiltration in the diagnosis of radicular pain.

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.

Back Pain↗
PubMed1988

Spinal fixation after anterior decompression for symptomatic spinal metastasis.

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.

Aged↗
PubMed1987

Anterior versus posterior decompression for symptomatic spinal metastasis.

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.

Adult↗
PubMed1985

Prediction of vertebral body compressive fracture using quantitative computed tomography.

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.

Aged↗
PubMed1979

Acetabular reinforcement in total hip replacement.

In conclusion, based on our experimental and clinical material and analysis of failures, we recommend wire mesh reinforcement and bone graft for patients with mild to moderate protrusio. If the floor is strong but the pillars deficient, then the Eichler ring alone is the best implant. The combined system of wire mesh and Eichler ring should be used in cases of protrusion with a large deficiency of the acetabular floor and for protrusio with pillar weakness. Furthermore a bone graft should be used to reinforce the acetabular floor in addition to any prosthetic device.

Acetabulum↗