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Biomedical subjects

T M Murray

Publications and source records attributed to T M Murray.

At least 19 recordsLinked to original sources
PubMed1995

Hockey helmets, face masks, and injurious behavior.

OBJECTIVE: To educate physicians about factors that contribute to injurious behaviors in ice hockey and to propose that the medical community play a role in advocating change within the sport. METHODS: A review of relevant literature on the topic was conducted, with information drawn from scientific journal publications, conference proceeding, theses, and newspaper publications. RESULTS: The introduction of mandatory head and facial protection has been effective in virtually eliminating ocular, facial, and dental injuries in youth hockey, but it has also been problematically linked with an increase in catastrophic spinal injuries. Players adopt a false sense of security when donning the equipment, leading them to take excessive and unwarranted risks because of the protection they are supposedly afforded. The addition of these protective devices has also altered how officials perceive game situations, leading them to be more lenient in administering penalties. The net result has been an increase in illegal and injurious behaviors, such as checking from behind. CONCLUSION: Physician advocacy may play an important role in effecting change within the sport.

Athletic Injuries↗
PubMed1991

Dexamethasone-treated ROS 17/2.8 rat osteosarcoma cells are responsive to human carboxylterminal parathyroid hormone peptide hPTH (53-84): stimulation of alkaline phosphatase.

We tested the effects of various parathyroid hormone (PTH) peptides on alkaline phosphatase (ALP) activity in the osteoblastic cell line ROS 17/2.8. In dexamethasone-treated ROS 17/2.8 cells there was a dose-related increase in ALP activity due to treatment with hPTH (53-84). ALP activity was stimulated by 10 nM hPTH (53-84) by a mean of 1.51 +/- 0.07-fold (P less than 0.001) in nine experiments, whereas the same dose of bPTH (1-34) and bPTH (1-84) inhibited enzyme activity to 0.36 +/- 0.02-fold (P less than 0.001) and 0.37 +/- 0.03-fold (P less than 0.001), respectively. Significant stimulation of ALP activity occurred with doses of hPTH (53-84) as low as 0.01 nM. There was no stimulation of enzyme activity by hPTH (53-84) in the absence of dexamethasone; the maximum ALP response to hPTH (53-84) occurred between 96 and 144 hours, and no significant effect was seen at time periods less than 96 hours. The optimum dose of dexamethasone required to enable the response to hPTH (53-84) was 10 nM. Carboxylterminal PTH fragments had a specific stimulatory effect on ALP activity in dexamethasone-treated ROS 17/2.8 cells, but the aminoterminal PTH effect appeared to be dominant, as the equimolar combination of bPTH (1-34) and hPTH (53-84) resulted in inhibition of ALP activity. Thus, in order for the effects of carboxylterminal fragments to be manifest, the cells would have to be stimulated under conditions in which the aminoterminal receptor is unoccupied; this could occur under some in vivo conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1990

Long-term effects of physiologic concentrations of dexamethasone on human bone-derived cells.

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.

Adenylyl Cyclases↗
PubMed1990

Fluoride-induced fractures: relation to osteogenic effect.

The possible effects of fluoride in inducing fractures were studied in 61 patients treated with sodium fluoride (NaF), 40-60 mg daily in combination with calcium and vitamin D. Nine patients developed the fluoride-(F) related lower extremity pain syndrome. Four other patients had stress fractures associated with trauma. Seven of the 61 patients had 10 upper femur fractures of which 5 were stress fractures. The bone mineral mass of the central skeleton including the hips was measured by neutron activation and the results expressed as a calcium bone index (CaBI) which normalizes the results to that of young adults of the same body size (normal range 0.75-1.2). At the time of hip fracture, 4 patients with a minimal increase in bone mass (mean delta CaBI 0.01) had 4 femur fractures and 3 patients with a marked increase (mean delta CaBI 0.24) had 6. The 7 patients with upper femur fractures at 4 years had a significantly higher bone fluoride retention, 30 mg/g Ca compared with 23.9 mg/g Ca for the other 54 (p less than 0.02) and were older, 73.1 versus 64.2 years (p less than 0.01). Using all 61 fluoride-treated patients, femur fractures/patient were significantly correlated to bone fluoride (p less than 0.05) and to age (p less than 0.05). By partial correlation, only the correlation between hip fractures/patient and bone fluoride remained significant after controlling for the effect of age (p less than 0.05). These results suggest that fluoride therapy may be implicated in the pathogenesis of hip fractures which may occur in treated patients despite a rapid, marked increase in bone mass. The lower extremity pain syndrome is not frequently associated with stress fractures in this study.

Aged↗
PubMed1990

Fluoride treatment of postmenopausal osteoporosis: age, renal function, and other clinical factors in the osteogenic response.

We report on 61 women with postmenopausal osteoporosis who were treated with either plain sodium fluoride (NaF) capsules or enteric-coated NaF tablets for 4 years, in whom possible therapeutic and toxic effects were monitored. In these patients there was a mean increase in axial bone mineral mass, assessed by neutron activation analysis, of 26.2% +/- 2.4% (SEM) during the 4 years. This corresponds to a decrease in the bone deficit (compared with reference values) of 48.6%. The response was linear over 4 years. The main predictors of the osteogenic response were bone fluoride (r = 0.52, p less than 0.01), serum fluoride (r = 0.50, p less than 0.01), and age (0.39, p less than 0.01). Patients over 65 years of age achieved higher bone fluoride (F) levels and a significantly greater increase in bone mineral than younger patients (32.8 vs. 17.9%, p less than 0.01), associated with an age-related decline in renal function; serum fluoride was significantly and negatively correlated to creatinine clearance (r = -0.52, p less than 0.01). Although the effect of NaF on fracture rate could not be assessed in this uncontrolled study, the major factors associated with the occurrence of new vertebral fractures were the number of vertebral fractures and the bone mineral mass at the beginning of therapy. There was no correlation between vertebral fracture rate and serum or bone fluoride or other parameters of the osteogenic response, but patients who did not experience new vertebral fractures achieved a normal bone mineral content sooner than those who had new fractures during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

The long-term treatment of steroid osteoporosis with fluoride.

Twenty-two patients with steroid-induced osteoporosis were studied retrospectively to assess the effects on bone mass of fluoride therapy over 4 years. Thirteen of 19 patients with miscellaneous disorders and 2 with Cushing's syndrome received 1 g calcium/day, 50,000 IU vitamin D (D) weekly, and 40-60 mg/day sodium fluoride (F). Six patients with miscellaneous disorders and one with Cushing's syndrome received only Ca and vitamin D. The mean (+/- SD) cumulative dose of prednisone for fluoride-treated patients at the beginning of the study was 42 +/- 25 g, and for those patients treated with only Ca and vitamin D, 45 +/- 47 g, and during the study the cumulative dose was comparable in both groups. The bone mineral mass of the central skeleton was measured by neutron activation analysis and the results expressed as the calcium bone index (CaBI) which normalizes the results to that of young adults of the same body size (normal range 0.75-1.2). In the 13 patients with miscellaneous disorders treated with fluoride, the mean +/- SD CaBI rose from 0.65 +/- .03 to 0.75 +/- .03 after 3 years p less than 0.001) and to 0.81 +/- .11 at 4 years. Patients without fluoride had an initial mean CaBI of 0.70 +/- .08 and it was not significantly changed over 3 years, 0.68 +/- .09 and 4 years, 0.71 +/- .09. The rise in CaBI in fluoride-treated patients with steroid-induced osteoporosis including Cushing's syndrome was comparable to that of 61 patients with postmenopausal osteoporosis treated with fluoride.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Bone mineral mass associated with postmenopausal vertebral deformities.

Vertebral morphometry on thoracic and lumbar spine radiographs and bone mass measurements were carried out on 215 patients investigated for postmenopausal osteoporosis. Bone mineral mass was measured on the central third of the skeleton by neutron activation analysis and the result, normalized for body size, expressed as a calcium bone index (CaBI). The normal CaBI value for females (20-40 years) is 0.97 (0.11) with a lower limit for these young, normal women, of 0.75. Vertebral compression deformity was defined as a mean height more than 15% lower than adjacent normal vertebrae. Thoracic and lumbar anterior wedge deformities and central compression were defined as anterior/posterior (A/P) or mid/posterior (M/P) height ratios of less than 0.75. For the 129 patients without vertebral deformities, the mean CaBI was 0.80 (0.12) (1 SD) and 32% of these patients had CaBI values below the normal young adult range (CaBI less than 0.75). In 20 patients, vertebral deformities were limited to 1 or 2 mid-thoracic vertebrae, and the mean CaBI values for these 20 patients was 0.81 (0.15), equal to that for patients without any vertebral deformity. For the remaining 67 patients, (i.e., patients with one or more vertebral deformities involving at least one distal thoracic or one lumbar vertebra) the mean CaBI value was 0.66 (0.10), 17% below the value for patients without vertebral deformities. Low CaBI values (CaBI less than 0.75) were observed in 87% of these patients, consistent with the diagnosis of osteoporotic fractures. Based on our CaBI results, however, mid-thoracic deformity was not associated with significant osteopenia and is not, therefore, diagnostic of osteoporotic fracture.

Adult↗
PubMed1989

Calcium and protein kinase C enhance parathyroid hormone- and forskolin-stimulated adenylate cyclase in ROS 17/2.8 cells.

Both parathyroid hormone (PTH)- and forskolin-stimulated adenylate cyclase activities in ROS 17/2.8 cells are enhanced by increasing the medium concentrations of CaCl2 from 10(-5) M to 3 x 10(-3) M. The ED50 for CaCl2 for both PTH- and forskolin-stimulated activities are similar. The tumor-promoting phorbol ester phorbol 12-myristate 13-acetate (PMA), a known activator of protein kinase C, also enhanced both PTH- and forskolin-stimulated adenylate cyclase. This action of PMA is specific for protein kinase C as phorbol esters that are not activators of protein kinase C had no effect on the system. The combined effects of PMA and CaCl2 were more than additive. The separate and combined effects of PMA and CaCl2 changed the rate of activation of the enzyme (Vmax) but did not modify the ED50 for PTH or for forskolin. PMA and CaCl2 both enhanced the potentiating effect of submaximal dose of forskolin on PTH-stimulated adenylate cyclase. It is concluded that calcium and PMA enhance PTH-sensitive adenylate cyclase and increase the production of cAMP by a mechanism that appears to involve the catalytic subunit of the enzyme and probably its interaction with a guanine nucleotide regulatory protein.

Adenylyl Cyclases↗
PubMed1989

Calcium modulation of the parathyroid hormone-sensitive adenylate cyclase in ROS 17/2.8 cells: effects of N-(6-aminohexyl-5-Cl-naphthalene sulfonamide) (W-7) and trifluoperazine (TFP).

The calcium modulation of the cyclic 3',5'-adenosine monophosphate (cAMP) response to parathyroid hormone (PTH) was studied in a clonal osteosarcoma cell line ROS 17/2.8. CaCl2 was found to stimulate the PTH-sensitive cAMP response of intact cells. At the maximal concentration of 1 mM CaCl2, the maximum response to PTH was increased, but the ED50 for PTH and the time course of maximal cAMP production were not affected. Verapamil blunted, while the cation ionophore A23187 enhanced, the stimulatory effect of CaCl2. Trifluoperazine (TFP) and N-(6-aminohexyl-5-Cl-naphthalene sulfonamide) (W-7) inhibited the stimulatory effect of CaCl2. In membranes prepared in the presence of 0.1 mM CaCl2, a biphasic effect of CaCl2 was demonstrated: stimulation at concentrations of 60-100 microM, and an inhibition above 200 microM, when adenylate cyclase was assayed in the presence of 200 microM EGTA. Addition of exogenous calmodulin to membranes prepared in the presence of EGTA did not have any effect on the PTH-sensitive adenylate cyclase activity, suggesting that endogenous calmodulin was not effectively stripped from the membranes by EGTA treatment. It is concluded that Ca2+ has both a stimulatory and an inhibitory role in modulating PTH-sensitive adenylate cyclase in ROS 17/2.8 cells by as yet unknown mechanisms, and that the involvement of endogenous calmodulin is implicated.

Adenylyl Cyclases↗
PubMed1989

Human parathyroid hormone carboxyterminal peptide (53-84) stimulates alkaline phosphatase activity in dexamethasone-treated rat osteosarcoma cells in vitro.

Previous studies in our laboratory have demonstrated relatively large numbers of cell surface binding sites for the carboxylterminal (53-84) region of PTH on ROS 17/2.8 rat osteosarcoma cells, a clonal osteoblast-like cell line. In order to gain insight into the significance of these carboxylterminal binding sites, we studied the effect of intact bovine PTH (1-84), its aminoterminal fragment bovine PTH (1-34), and the human PTH carboxylterminal fragment (53-84) on alkaline phosphatase activity in dexamethasone-treated rat osteosarcoma (ROS) 17/2.8 cells. While bovine PTH (1-84) and its aminoterminal 1-34 fragment inhibited alkaline phosphatase activity, we saw a dose-related stimulation of activity by human PTH (53-84), with maximal stimulation occurring after 120 hours, at a concentration of 10(-8) M. The effect was not seen in dexamethasone-untreated cells. To our knowledge, this is the first published demonstration of biological activity of this carboxylterminal PTH peptide, previously thought to be inactive. It is likely that dexamethasone caused differentiation of cells to a type more sensitive to human PTH (53-84). Further studies are necessary to elucidate the physiological significance of these findings.

Alkaline Phosphatase↗
PubMed1988

The effect of fluoride on bone histology in postmenopausal osteoporosis depends on adequate fluoride absorption and retention.

Forty-one women with idiopathic postmenopausal osteoporosis have been followed for 2 years after initiation of sodium fluoride at 40-50 mg/day, given together with a daily calcium supplement of 1 gram and vitamin D2, at 50,000 IU weekly. Histological and histomorphometric analyses were done on bone biopsies taken prior to and after 1 year of treatment (mean 1.25 +/- 0.35 years). Thirty patients (74%) developed the histological fluoride effect of hyperosteoidosis, while the remaining 11 patients (26%) had no change from pretreatment biopsies. Hyperosteoidosis was based on increased values for osteoid volume and/or thickened osteoid with greater than 3 lamellar bands. Based on previously reported findings, this histological evidence of hypersoteoidosis within 12-18 months of initiation of therapy provides a useful predictor of ultimate satisfactory fluoride response in terms of bone mineral accretion. No increases in bone mass (measured by neutron activation analysis) were observed at the time of the posttreatment biopsy but, according to this previous work, increases are anticipated over a further 2-3 years of treatment. Factors affecting the development of hyperosteoidosis were analyzed. Hyperosteoidosis was associated with a significantly higher dose of sodium fluoride and a significantly higher level of bone fluoride retention but without significant increase in fasting serum fluoride. Results suggest that fluoride retention depends not only on fluoride dose but also on body size, renal function, and intestinal absorptions of calcium and fluoride. There were no differences in the initial investigations between patients with and without hyperosteoidosis, with respect to age, years of postmenopause, estrogen use, initial biochemistry, or initial bone histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1987

The effect of exercise on bone mass of osteoporotic patients on fluoride treatment.

The study was conducted in order to determine the effect of exercise on osteoporotic patients with a mean age of 65 years. The majority of these patients had been on sodium fluoride for at least 2 years. Thirty-eight patients were assigned to either the hospital or home group. Nineteen were in the former group, which performed the 1 hour exercise twice weekly in the Hospital. The patients in the latter group were taught the exercises and were expected to continue them at home. The exercise protocol consisted of muscle-strengthening and aerobic activities. Bone mineral mass was determined by neutron activation analysis, which measured total calcium in the trunk and pelvis. It is expressed as a calcium bone index (CaBI), with a normal range of 0.75 to 1.2. The level of physical performance was determined by calculating the maximum oxygen uptake, VO2max, attained by a graded exercise test on the treadmill. Calcium bone index and VO2max were obtained before and after the 12.5 month study. Prior to the study, the hospital and home groups had low calcium bone index values (0.68 and 0.66 respectively). Both groups showed a significant increase in calcium bone index (p less than 0.001 for the hospital group, p less than 0.01 for the home group) after the study. When compared to the home group the hospital group was found to have a significantly higher post-study calcium bone index value (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Periosteal resorption and periosteal neostosis: comparison of normal subjects and renal failure patients on chronic ambulatory peritoneal dialysis using MOP-3 image analysis system and a grading method.

This is the first known attempt to quantitate periosteal resorption (PR) and perisoteal neostosis (PN) by a semi-automatic image analysis system (Zeiss MOP-3). The normal ranges and errors for PR were found to be similar to those of a previous study using a measuring magnifier. The findings in chronic renal failure patients showed that MOP-3 measurements were actually diagnostically slightly less sensitive than the results by a simple grading method. Comparison with plasma-immunoreactive parathyroid hormone (iPTH) concentrations showed that while the latter had a higher sensitivity for detection of hyperparathyroidism, the radiologic parameters nevertheless showed abnormal PR in 12% of the observations where iPTH was normal. Both PR and PN correlated significantly with iPTH (r = 0.55 and 0.30 respectively, P less than 0.01).

Adult↗
PubMed1986

Regional migratory osteoporosis of the lower extremities with vertebral osteoporosis.

Regional migratory osteoporosis is a disorder of unknown etiology, characterized by successive episodes of joint pain, accompanied by localized osteoporosis. The disorder affects the lower limbs, usually the region of the foot, knee, or hip, and each episode usually lasts several months and is followed by spontaneous recovery. This disorder has not previously been reported to cause episodes of vertebral osteoporosis. We describe three patients in whom regional osteoporosis, involving the lower limbs, was associated with simultaneous vertebral osteoporosis indistinguishable from idiopathic osteoporosis. These cases suggest that this disorder might be responsible for some cases of apparent idiopathic spinal osteoporosis.

Adult↗
PubMed1986

The effect of vitamin D on bone in vivo.

The linear rate of bone mineral apposition (BMAR) was measured in vitamin D-deficient and vitamin D-sufficient adult rats before and during treatment with either 25-hydroxyvitamin D3 (25OHD3), 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], or 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3]. Dietary vitamin D restriction caused a fall in BMAR which began after 1 week and fell progressively to a value of 35-50% of control values by 4 weeks. The fall in BMAR was related to a fall in the serum concentrations of 25(OH)D3 and 24,25-(OH)2D3, without a fall in the 1,25-(OH)2D3 concentration. Dietary supplementation of the D-deficient animals with either 25OHD3 or 24,25-(OH)2D3 at doses of 200 ng/day restored BMAR. If vitamin D-deficient animals were thyroparathyroid-ectomized before supplementation with vitamin D metabolites, 24,25-(OH)2D3 administration was without effect on BMAR. The combined administration of PTH and 24,25-(OH)2D3 to such animals led to a restoration of the BMAR to normal. In vitamin D-sufficient animals, parathyroidectomy led to a 50% reduction in BMAR, which could be restored by treatment with PTH alone but not with 24,25-(OH)2D3. Simultaneous treatment of these animals with PTH and 24,25-(OH)2D3 led to a greater than normal increase in BMAR (130% of control) in these animals. These data support the concept that 24,25-(OH)2D3 has a role in the regulation of bone formation and/or mineralization, and demonstrate the interrelation between the effects of PTH and 24,25-(OH)2D3 on bone.

24,25-Dihydroxyvitamin D 3↗