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M Shea

Publications and source records attributed to M Shea.

At least 37 records · Page 2Linked to original sources
PubMed1993

Effects of combined prostaglandin and alendronate treatment on the histomorphometry and biomechanical properties of bone in ovariectomized rats.

Prostaglandin E2 (PGE2) has been shown to stimulate both bone resorption and formation in experimental animals, leading to augmentation of trabecular and cortical bone. The amino bisphosphonate alendronate (ALN) is a potent inhibitor of bone resorption. The objectives of this study were to examine if PGE2 stimulation of bone formation was dependent on bone resorption and if the bone accrued as a result of PGE2 treatment contributed to bone strength. The 48 female Sprague-Dawley rats were assigned to six groups as follows: five groups (8/group) were ovariectomized at the age of 6 months. One group was sacrificed 2 months later to establish baseline conditions, and four groups were treated for 25 days with (1) vehicle, (2) PGE2 at 3 mg/kg/day, (3) ALN sc at 0.8 micrograms/kg/day, and (4) PGE2 + ALN at the respective doses. The sixth group served as nonovariectomized untreated controls. Histomorphometric analysis of 6-10 microns thick tibial sections after in vivo fluorochrome double labeling showed that treatment with PGE2 alone increased endocortical mineral apposition rate and bone formation rate, stimulated production of bone trabeculae in the marrow cavity, and increased cortical porosity. Combined ALN + PGE2 treatment prevented the resorption induced by PGE2 but not the stimulation of bone formation on endocortical and periosteal surfaces and resulted in a significant increase in cortical thickness. Consistent with these observations, the femoral midshaft tested to failure in three-point bending showed a significant increase in strength in the PGE2 + ALN group (181 +/- 15 N) compared to time 0 controls (145 +/- 23 N) or to the ovariectomized vehicle-treated group (141 +/- 28 N).(ABSTRACT TRUNCATED AT 250 WORDS)

Alendronate↗
PubMed1993

Continuous alendronate treatment throughout growth, maturation, and aging in the rat results in increases in bone mass and mechanical properties.

Alendronate (4-amino-1-hydroxybutylidene bisphosphonate) is a novel amino bisphosphonate that is being developed for the treatment of osteolytic bone disorders such as osteoporosis. As part of a 2-year carcinogenicity study, we investigated the morphologic and biomechanical effects of long-term alendronate (ALN) therapy, given throughout skeletal growth, maturation, and aging, on rat vertebrae and femora. Three treatment groups, receiving either deionized water, low- (1.00 mg/kg), or high-dose (3.75 mg/kg) ALN, were given daily oral treatment for 105 weeks. Results from mechanical tests indicate that ALN therapy (in males) increased the vertebral ultimate compressive load by 96% in the high- and 51% in the low-dose groups when compared with controls. ALN similarly increased the male ultimate femoral bending load by 59% in the high- and 31% in the low-dose groups. Vertebrae and femora from female rats treated with both high- and low-dose ALN also failed at significantly higher loads than controls, but no differences were seen between low- and high-dose groups. Morphologic analysis of both male and female vertebrae revealed a dose-dependent increase in area fraction of bone. Rats receiving high-dose ALN had a greater area fraction of bone than those receiving low doses. Both groups were greater than controls. Thus, the administration of ALN resulted in increased femoral cortical bending load when compared with control animals, as well as increased vertebral ultimate compressive load commensurate with a dose-related preservation of vertebral bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Validation of continuous thermal measurement of cerebral blood flow by arterial pressure change.

A thermal measurement system to monitor cerebral blood flow (CBF) continuously from the cortical surface is evaluated in vivo. It has a temperature resolution of better than 0.001 degrees C (1 m degrees C) and can compensate for baseline temperature fluctuations in the brain tissue. A new approach has been developed to test the capability of monitoring dynamic CBF response. Transient CBF changes associated with changes in mean arterial blood pressure (MABP) caused by repeated bolus norepinephrine injections are used to examine the response of the measurement system in both the heated mode, sensitive to flow, and the unheated mode, sensitive only to temperature. Experiments on 13 rats demonstrate that changes in the MABP are closely correlated with those of temperature difference in the heated mode. Regression analysis shows a mean slope of 0.9 m degrees C/mm Hg in the heated mode, which is significantly different from zero (p < 0.002) and from the mean slope in the unheated mode (p < 0.002). This indicates that flow signal in the system output can be distinguished from the baseline thermal fluctuations. Thus, the system can be used to detect and study dynamic perfusion changes from the brain surface with minimal tissue damage. Furthermore, analysis of the data shows that the transient flow signal before autoregulation is linearly correlated with changes in MABP.

Animals↗
PubMed1993

Evidence that heterogeneity of cerebral blood flow does not involve vascular recruitment.

Recent studies indicate that blood flow to cerebral cortex is not homogeneous but may vary both spatially and temporally. In addition, some investigators have reported that capillaries and arterioles can be recruited to increase cerebral blood flow, an issue that is extremely controversial. The goal of this study was to determine whether recruitment of cerebral blood vessels is an important mechanism in spatial and temporal heterogeneity of cerebral blood flow. In seven anesthetized ventilated rats, different fluorescent tracers were injected 45 and 10 s before decapitation. In addition, [14C]iodoantipyrine also was injected 10 s before decapitation. After the brains were sectioned, fields in the cerebral cortex were examined microscopically for fluorescence and processed for measurement of cerebral blood flow with techniques of quantitative autoradiography and image analysis. With examination of 24 +/- 2 (SE) points in cerebral cortex of each rat, similar numbers of small blood vessels (< or = 10 microns) were counted that contained fluorescent tracers injected 45 and 10 s before decapitation (346 +/- 48 and 355 +/- 42 vessels/mm2, respectively; P > 0.05). Large blood vessels (20-60 microns; 73 +/- 6 vessels in each rat) contained both fluorescent tracers. In addition, adjacent regions of high and low blood flow contained similar numbers of small and large vessels. Our findings indicate that vascular recruitment is not an important mechanism in temporal or spatial heterogeneity of cerebral blood flow.

Animals↗
PubMed1993

The effects of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry, and bone strength in ovariectomized nonhuman primates.

This study examined the effect of 2 yr of treatment with the aminobisphosphonate alendronate (ALN) (0.05 or 0.25 mg/kg i.v. ALN every 2 wk) on estrogen deficiency bone loss and bone strength changes in ovariectomized (OVX) baboons (n = 7 per group) and the ALN mode of action at the tissue level. Biochemical markers of bone turnover increased in OVX animals and were maintained by ALN treatment at non-OVX levels (low dose) or below (high dose). 2 yr of treatment produced no cumulative effects on bone turnover markers. Histomorphometry showed a marked increase in cancellous bone remodeling in OVX animals. Activation frequency increased from 0.48 to 0.86 per yr (L5 vertebra), and the osteoid surfaces from 9 to 13.5% (P < 0.05). No changes were observed in eroded and osteoclast surfaces. ALN treatment decreased activation frequency and indices of bone formation to control levels (low dose) or below (high dose), did not change indices of mineralization, and increased bone mineral density (BMD) in the lumbar vertebrae (L2-L4) by 15% at 0.25 mg/kg (P < 0.05), relative to vehicle-treated animals. The mean strength of cancellous bone (L4) increased by 44% (low ALN dose) and 100% (high dose), compared with vehicle. The strength of individual bones correlated with the square of the L2-L4 BMD (r = 0.91, P < 0.0034). In conclusion, ALN treatment reversed the effects of ovariectomy on cancellous bone turnover and increased bone mass and bone strength in baboons.

Acid Phosphatase↗
PubMed1993

Effect of screw diameter, insertion technique, and bone cement augmentation of pedicular screw fixation strength.

This study investigated (1) the effect of screw diameter and insertion technique in lumbar vertebrae, and insertion site in the sacrum, on the axial pullout force and transverse bending stiffness of pedicle screws, and (2) the effect of bone cement augmentation using polymethylmethacrylate (PMMA) and the biodegradable composite, poly(propylene glycol-fumarate) on axial pullout force and transverse bending stiffness of pedicle screws inserted into lumbar vertebrae. The axial pullout force and transverse bending stiffness of a 6.25-mm Steffee screw and a 6-mm Kluger screw did not differ significantly in vertebral bodies of similar equivalent bone mineral density. The axial pullout force of Schanz screws was significantly increased with a 1-mm increase in screw diameter. However, there was no significant increase in transverse bending stiffness. In the sacrum, an approach through the S1 facet produced significantly higher axial pullout forces and transverse bending stiffness than the approach described by Harrington and Dickson. PMMA and a biodegradable composite bone cement poly(propylene glycol-fumarate) both increased the axial pullout force. PMMA also increased the transverse bending stiffness.

Biomechanical Phenomena↗
PubMed1993

Cervical injuries under flexion and compression loading.

Cervical spine segmental tests were performed to determine the specific patterns of initial cervical injury in response to loading just beyond the point of structural failure. Well-defined combinations of flexion rotation and compression translation were applied to segments with varying degrees of disc and facet degeneration. Twelve cervical spine specimens (from human cadavers ages 52-91 years), each consisting of three vertebrae (two motion segments) from the middle (C2-C5) or lower (C5-T1) regions, were subjected to pure flexion rotation (seven specimens) or to combined flexion rotation and axial compression translation (five specimens). Specimens were sectioned and dissected to determine the patterns of structural failure. Pure flexion, and combined flexion and compression produced similar patterns of injuries. The disc was the most commonly injured structure, with annular injuries noted in 8 of the 12 specimens, and with anterior herniation of the nucleus occurring in two specimens. Wedge fractures and posterior ligament injuries were noted in both specimen groups and with both modes of loading. We conclude that similar patterns of initial anterior bony compressive failure and posterior ligamentous failure can occur with both flexion and with combined flexion-compression, without axial or lateral rotation, at low rates of loading. Anterior cervical disc herniations were produced in both middle and lower cervical segments.

Aged↗
PubMed1992

Effects of 4-amino-1-hydroxybutylidene bisphosphonate on bone biomechanics in rats.

Bisphosphonates inhibit osteoclast-mediated bone resorption, but their effects on the mechanical behavior of bone remain uncertain. This study investigated the effects of 4-amino-1-hydroxybutylidene bisphosphonate (AHBuBP) on the biomechanical and morphologic properties of bone in ovariectomized rats. Sprague-Dawley rats (four groups, n = 6) were ovariectomized at 3 months of age. From 7 to 13 months, the groups received vehicle or 0.28, 2.8, or 28 micrograms/kg of AHBuBP twice weekly through subcutaneous injection. An additional group of control animals (n = 6) received neither surgery nor drug. We determined the stiffness, yield, and ultimate loads of the femoral midshaft, the sixth lumbar (L6) vertebra, and the femoral neck. Geometric properties of the cortical bone were measured from digitized images of the tibial diaphysis at the level of the synostosis. The area fraction of trabecular bone was determined through the midsagittal plane of the fifth lumbar (L5) vertebra. There were no significant differences in the structural properties of the femoral neck and midshaft, with the exception that the medium-dose group had a greater ultimate load than the vehicle group for the femoral midshaft in bending. Cross-sectional analysis of the tibia did not show significant differences in the inertial properties or area. Ovariectomy caused a significant reduction in the stiffness and ultimate load of L6 and in the area fraction of trabecular bone of L5.(ABSTRACT TRUNCATED AT 250 WORDS)

Alendronate↗
PubMed1992

In vitro hyperextension injuries in the human cadaveric cervical spine.

To investigate the relationship between the type of hyperextension injuries and the conditions producing them, nine cervical specimens (occiput to T1) were loaded to failure in tension at a fixed extension angle of 30 degrees. Under these loading conditions, specimens failed at average tensile loads and extension moments of 499 +/- 148 (SD) N and 4.0 +/- 3.1 Nm, respectively. Failure occurred at an average tensile displacement of 18.8 +/- 7.7 mm. The anterior longitudinal ligament ruptured and the intervertebral disc failed in at least one level in all specimens. In four specimens, the disc failed at an additional level, leaving the anterior longitudinal ligament intact at that site. With one exception, all injuries occurred in the lower cervical spine (C5-C6 and C6-C7), the region most often injured in vivo. The location of the injuries was associated with the degree of degeneration of the facet joints and the discs. The discs of the lower cervical spine were significantly more degenerated than those at the C2-C3 level. In addition, the degree of disc degeneration in the noninjured discs was significantly less than in the injured discs. These data help quantify the threshold of injury and the patterns of tissue damage resulting from hypertension loading of the cervical spine.

Aged↗
PubMed1992

A biomechanical study of the fatigue characteristics of thoracolumbar fixation implants in a calf spine model.

Clinical failures of internal fixation implants for the treatment of the thoracolumbar spine are generally attributed to fatigue. Few studies, however, have characterized changes in fixation rigidity with time or subjected spine-implant fixation constructs to fatigue loading until failure. Fatigue characteristics of five dorsally applied spinal fixation implants were determined using lumbosacral calf spines, with an L3 vertebrectomy, loaded cyclically in combined compression (maximum 605 N) and flexion (maximum 16 Nm) for up to 100,000 cycles. Displacement transducers monitored motion at the site of instability and at the segment above the implants. Flexibility and strain at these segments were then calculated. A one-way analysis of variance showed that there were no significant differences in flexibility of the five fixation constructs (P greater than .05). A multiple Bonferroni test revealed that the AO and Kluger fixateur interne and Steffee plates, with fixation at L2 and L4, allowed significantly more strain (P less than .01) across the site of instability than did Harrington rods and Luque plates with fixation at L1, L2, L4, and L5. There were no significant differences between fixation constructs in initial strain above the implants. After 10,000 cycles, however, there were significant increases in strain across the segment above the Luque and Harrington implants (P less than .05). Failure of the AO Schanz screw occurred in three of six constructs at a mean of 73,300 cycles. The Steffee screws failed in four of five constructs at a mean of 20,800 cycles. The rods of the Kluger fixateur interne broke in four of five constructs at a mean of 47,800 cycles, and one screw slipped at 11,000 cycles. There were no metal failures in the Harrington or Luque implants.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cyclosporine in the treatment of nonmicrobial inflammatory ophthalmic disease.

Eighteen patients with severe, progressive nonmicrobial inflammatory ophthalmic disease (including five with intermediate uveitis, four with sympathetic ophthalmia and three with serpiginous choroiditis) that had not responded to conventional therapy were treated with cyclosporine. Three of the four patients with sympathetic ophthalmia responded quickly and maximally, and the fourth showed partial improvement. One patient, with several corneal graft failures in the right eye, started cyclosporine therapy after undergoing left corneal transplantation; at the last follow-up visit the graft had been clear for almost 3 years. The response was inconsistent in patients with other types of eye disease. In general, the drug was well tolerated; however, two patients stopped treatment because of unpleasant side effects. No serious or irreversible complications developed. The results suggest that cyclosporine therapy is useful in the treatment of sympathetic ophthalmia and in high-risk corneal transplantation.

Adolescent↗
PubMed1991

Physical and mechanical properties of calf lumbosacral trabecular bone.

The physical and mechanical properties of calf lumbar and sacral trabecular bone were determined and compared with those of human trabecular bone. The mean tissue density (1.66 +/- 0.12 g cm-3), equivalent mineral density (169 +/- 36 mg cm-3), apparent density (453 +/- 89 mg cm-3), ash density (194 +/- 59 mg cm-3), ash content (0.6 +/- 0.05%), compressive strength (7.1 +/- 3.0 MPa) and compressive modulus (173 +/- 97 MPa) of calf trabecular bone are similar to those of young human. There were moderate, positive linear correlations between apparent density and equivalent mineral density, ash density, and compressive strength; and between compressive strength and equivalent mineral density (R2 ranging from 0.35 to 0.48, p less than 0.001). Apparent density, ash density, and equivalent mineral density did not differ significantly in different regions. In contrast to humans, the compressive strength increased from posterior, near the facet, to the anterior vertebral body. These comparisons of physical and mechanical properties, as well as anatomical comparisons by others, indicate that the calf spine is a good model of the young non-osteoporotic human spine and thus useful for the testing of spinal instrumentation.

Animals↗
PubMed1991

Variations of stiffness and strength along the human cervical spine.

The load-displacement response and strength of the mid (C2-C5) and lower (C5-T1) cervical regions were determined for combinations of sagittal loads, in vitro. In unpaired t-test comparisons, the mid cervical region was significantly stiffer in compression and extension than the lower region. In tests to failure, failure in six out of seven mid cervical specimens resulted from flexion alone, while combined compression-flexion was required to fail five of the eight lower cervical specimens. Post-test dissections revealed no regional differences in the pattern of failure. In addition to sagittal tests, the load-displacement responses of three-vertebrae cervical specimens were measured with the upper body axially rotated with respect to the lower body. The effect of this pre-torsion was to diminish the zone of low slope near zero load for axial, shear, and flexion motion. Three of the four axially rotated specimens failed in flexion without added compression. These controlled load-displacement measurements of cervical spine specimens describe for the first time the continuous flexion-compression response up to failure, and suggest that consideration of the biomechanics of three apparently distinct mobile regions of the cervical spine (C1-C2, C2-C5, C5-T1) may facilitate the interpretation of hazardous conditions and the diagnosis of injury. These data also provide basic information for the in vitro investigation of passive cervical spine protection such as helmets and head-rests, suggesting that the head should be kept in a non-rotated position to reduce risk of injury.

Biomechanical Phenomena↗
PubMed1991

Three-dimensional load displacement properties of posterior lumbar fixation.

Pedicular fixation devices for the posterior treatment of segmental spinal instability are thought to offer enhanced stabilization compared with sublaminar wire systems, while avoiding the immobilization of multiple normal motion segments. We compared the performance of three dissimilar stabilization systems: the Hartshill rectangle, the Acromed/Steffee interpedicular screw and plate, and the Synthes/Dick fixateur interne. Human cadaveric lumbosacral specimens were first tested intact, then after a laminectomy and a facetectomy at the L3/L4 level, and finally after the fixation devices were sequentially attached. Constructs spanning two to four vertebral levels were compared for stabilization of the resected lumbar spine segments. When tested in compression, the Acromed/Steffee system with pedicular screws at L2-L5 allowed significantly less intersegmental distraction than the Synthes/Dick construct with screws at L2 and L5 only, and less than the intact and the destabilized uninstrumented spine. When sagittally rotated, the Acromed/Steffee construct with screws at L2-L5, or at L2 and L5, allowed significantly less distraction than the intact or destabilized segments, and the construct with screws at L2 through L5 allowed less distraction than the Synthes/Dick constructs with screws at L3/L4 or L2/L5. With the exception of the Acromed/Steffee system with screws at four levels, there were no significant differences in distraction allowed between the Synthes/Dick and Acromed/Steffee constructs, or between the multisegment and single segment constructs. There were no significant differences in stiffness across levels L3/L4 with the various implants. Results indicate that the use of posterior spine constructs significantly augment the stability of posterior segmental defects. Pedicular fixation immediately cephalad and caudad to the defect provided stable fixation in this application.

Bone Plates↗
PubMed1991

Importance of bone mineral density in instrumented spine fusions.

The effect of equivalent mineral density on pedicular screw fixation strength was investigated. The equivalent mineral density of human vertebral bodies was correlated highly with the pullout force of Kluger screws (r2 = 0.61, P less than 0.02). A moderate to high correlation existed between density and vertical force (r2 = 0.42 for Kluger screws, r2 = 0.55 for Steffee screws, P less than 0.02). In calf vertebral bodies of higher density (146 +/- 14 mg/cc), the forces were significantly higher than in the human vertebral bodies (P less than 0.05). Human lumbosacral spines were instrumented with three different fixators: Steffee plates, AO fixateur interne, and Kluger fixateur interne. Of five specimens with a mean density of 88 +/- 11 mg/cc, one screw loosened. More than one screw loosened in six specimens with a mean density of 63 +/- 12 mg/cc, and no screw loosened in four specimens with a mean density of 114 +/- 38 mg/cc. Measurement of equivalent mineral density correlates with the fixation strength of the intrapedicular screws in vitro and should be considered in patients with signs of osteopenia before using pedicular screws for spinal fusions. It is also concluded that calf spines are a good model for testing implants because they tend to focus failure processes in the implant rather than in the implant-bone interface.

Aged↗
PubMed1991

Importance of freezing time when iodoantipyrine is used for measurement of cerebral blood flow.

The goal of the present study was to determine effects of delay of freezing of the brain on distribution of [14C]iodoantipyrine in the brain. Blood flow to parietal cerebral cortex (CBF) and choroid plexus was measured with the indicator fractionation technique and quantitative autoradiography. After injection of iodoantipyrine, each rat was decapitated, and the head was immersed in chlorodifluoromethane (-40 degrees C). The brain was removed from the skull after it was frozen. In some rats, heads were immersed immediately after decapitation, and CBF was markedly heterogeneous. In another group, heads were frozen 3 min after decapitation. In this case, CBF was uniform in its distribution. Average CBF was similar in groups with immediate and delayed freezing (90-104 ml.min-1 x 100 g-1). In contrast, delays in freezing decreased blood flow to choroid plexus from 551 +/- 115 to 261 +/- 48 ml.min-1 x 100 g-1. Our findings indicate that immediate freezing of the brain after decapitation is necessary to prevent diffusion of iodoantipyrine from regions of high blood flow to regions of lower blood flow and underestimations of blood flow in regions with high blood flow.

Animals↗
PubMed1990

Diagnosis and control of neonatal losses in sheep.

Perinatal mortality is affected by a variety of management factors and disease processes that create significant losses for the sheep industry. Annual production losses prior to weaning include roughly 15% to 20% of the lamb crop. The majority of these perinatal losses occur during the prenatal, natal, and early postnatal periods, with the predominant wave of mortality occurring during the first several days following birth. Causes of perinatal mortality may vary between flocks and between geographic areas; however, four dominant categories of lamb loss consistently surface: (1) abortions; (2) hypothermia, starvation, and exposure; (3) pneumonia; and (4) stillbirth and dystocia. They account for roughly 50% to 75% of all documented perinatal losses. Veterinarians and producers need to work together to document the type of losses that occur in a given flock and then design economic prevention programs that address these problems. In most cases, traditional prevention programs will need to be replaced by a comprehensive management scheme addressing nutrition, genetics, housing, marketing, lambing husbandry, and labor.

Abortion, Veterinary↗