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Biomedical subjects

G I Anderson

Publications and source records attributed to G I Anderson.

At least 19 recordsLinked to original sources

Inhibition of leukotriene function can modulate particulate-induced changes in bone cell differentiation and activity.

Aseptic loosening remains the major problem facing arthroplasty longevity with particulates from component materials touted as the cause of periprosthetic osteolysis. Proposed mechanisms in aseptic bone loss include: increased resorption, increased differentiation of osteoclasts (and/or macrophages locally), and decreased osteoblastic bone formation. Leukotrienes participate in osteoclastic bone resorption. We investigated inhibiting leukotrienes synthesis, using ICI 230487, to ameliorate the effects of particulates on osteoclast pit formation and also assessed the effects of alendronate, a bisphosphonate, on pit formation. Three particulates were used: ultra high molecular weight polyethylene (UHMWPE), polymethylmethacrylate (PMMA) and hydroxyapatite (HA). Osteoclast resorption was increased with UHMWPE, PMMA, and HA particles. Interventions with alendronate and ICI 230487 reduced particulate-induced osteoclast resorption. Both ICI 230487 and alendronate reduced osteoclast numbers at higher doses. To assess the effect of particulates on osteoclast and macrophage differentiation, mouse bone marrow was cultured and stained for tartrate resistant acid phosphatase colonies (TRAP+, osteoclasts) and nonspecific esterase positive colonies (NSE+, macrophage precursors). Particulates increased both TRAP+ and NSE+ colony formation. These increases were inhibited by ICI 230487. Particulates also inhibited osteoblast function assessed by the development of mineralized nodules and alkaline phosphatase positive (AP+) colony area. ICI 230487 partly protected osteoblast function from this particulate effect. Blockade of leukotriene production may prove a useful therapeutic intervention for particulate-induced aseptic loosening by inhibiting resorptive activity, reducing the pro-inflammatory cell populations induced and recruited by these particulates, as well as ameliorating the negative effects of inflammatory mediators on osteoblast function.

Animals↗

The effect of partial vs. full hydroxyapatite coating on periprosthetic bone quality around the canine madreporic femoral stem.

While hydroxyapatite coatings have been shown to enhance osseointegration of metal prostheses, the optimal extent of the coating over the femoral stem component remains unclear. In this study, we investigated the effect of the application of hydroxyapatite to the proximal half of the femoral stem vs. full hydroxyapatite coating on the madreporic-surfaced femoral stems in a canine model over time. Total hip arthroplasties were performed on 22 dogs. Fifteen had half-HA coated stems, and seven had fully HA coated stems. The dogs were followed for 3 weeks, 3 months, or 1 year postoperatively. Micromotion near the femoral component was assessed at three levels along the medial aspect of the stems. Percent bone apposition, trabecular strut width, connectivity index, and cortical porosity measurements were performed at five levels and in four quadrants about the femoral stems. Micromotion was greater adjacent to the half-coated stems at 3 weeks postoperatively only. There was a trend to decreased micromotion from proximal to distal in both stem types. Both designs fixed proximally and tended to load share laterally more than in the other three quadrants. Fully HA coated stems induced greater percent bone apposition, wider trabecular struts, and more connectivity compared to half-HA coated stems.

Animals↗

Femoral bone blood flow after reaming and intramedullary canal preparation: a canine study using laser Doppler flowmetry.

This study was conducted to determine the effect of intramedullary reaming and canal preparation on bone blood flow in the proximal femur. Thirty-five adult dogs were randomly assigned to have their intramedullary canals prepared after reaming in the following manner: group 1, ream only; group 2, lavage; group 3, methylmethacrylate cement introduction; group 4, cement pressurization after placing a cement restrictor; group 5, lavage then cement introduction; and group 6, lavage then cement pressurization. Bone blood flow was measured at both metaphyseal and diaphyseal sites by using laser Doppler flowmetry before reaming, after reaming, after lavage, after cementing, and at 6 weeks after the procedure just before euthanasia. Reaming significantly decreased bone blood flow in the diaphysis (P = .046) but not in the metaphysis. Cement introduction and cement pressurization both significantly decreased bone blood flow in the metaphysis (P = .035, P = .004) and diaphysis (P = .007, P = .029). Pressurization of cement had a significantly greater relative effect than cement introduction alone in the diaphysis (P = .006) but not in the metaphysis. Lavage had no effect on bone perfusion. Bone blood flow was significantly increased at 6 weeks after the initial procedure in both the metaphysis (P = .049) and the diaphysis (P = .004). The results suggest that reaming decreases diaphyseal cortical but not metaphyseal bone blood flow significantly, whereas lavage has no effect. Cement introduction with or without pressurization has a significant detrimental effect on metaphyseal and diaphyseal blood flow. These findings have implications for intramedullary nailing and for canal preparation when performing arthroplasty.

Animals↗

Pulmonary and systemic fat embolization after medullary canal pressurization: a hemodynamic and histologic investigation in the dog.

BACKGROUND: The potential to produce fat embolism may be important in determining the ideal method and timing of fracture treatment in patients with preexisting lung injury. METHODS: Four dogs underwent femoral and tibial canal reaming and pressurization. Blood gas samples were analyzed, and pulmonary arterial pressure was monitored at 1 and 72 hours. Animals were killed 72 hours postoperatively, and the lungs, kidneys, and brain were examined histologically and compared with equivalent specimens from four control dogs that had not undergone femoral and tibial canal reaming and pressurization. RESULTS: Postmortem, intravascular fat persisted for 72 hours after induction of pulmonary fat embolism. Mean PaO2 was unchanged from baseline at 72 hours after canal pressurization. Canal pressurization caused a sustained increase in pulmonary arterial pressure (p=0.02) for 1 hour after canal pressurization. The mean pulmonary edema score at 72 hours was 29+/-3. Only a scant polymorph infiltrate (zero to two polymorphs per high-power field) was present at any time. No hyaline membranes were seen at any time. The percentage area occupied by intravascular fat in the lungs was 0.0214+/-0.0058 at 72 hours. No signs of ischemia or inflammation were seen in either the cerebral or the renal specimens. CONCLUSION: This study is the first to show that intravascular fat persists in the lungs, kidneys, and brain for 72 hours after canal pressurization and, by itself, does not cause pathologic evidence of acute inflammation.

Animals↗

The role of methylmethacrylate monomer in the formation and haemodynamic outcome of pulmonary fat emboli.

We examined the roles of methylmethacrylate (MMA) monomer and cementing technique in the formation, and haemodynamic outcome, of pulmonary fat emboli. The preparation of the femoral canal and the cementing technique were studied in four groups of adult dogs as follows: control (no preparation); lavage; cement pressurisation; and cement pressurisation after lavage. We measured the intramedullary pressure, pulmonary artery pressure (PAP), pulmonary capillary wedge pressure and bilateral femoral vein levels of triglyceride, cholesterol and MMA monomer at rest and after reaming, lavage, and cementing. Femoral vein triglyceride and cholesterol levels did not vary significantly from resting levels despite significant elevations in intramedullary pressure with reaming, lavage and cementing (p = 0.001). PAP was seen to rise significantly with reaming (p = 0.0038), lavage (p = 0.0031), cementing (p = 0.0024) and cementing after lavage (p = 0.0028) while the pulmonary capillary wedge pressure remained unchanged. MMA monomer was detected in femoral vein samples when cement pressurisation was used. Intramedullary lavage before cementing had no significant effect on the MMA level. Haemodynamic evidence of pulmonary embolism was noted with reaming and intramedullary canal preparation, irrespective of the presence of MMA monomer. We found no relationship between MMA monomer level and intramedullary pressure, PAP or pulmonary capillary wedge pressure. Our findings suggest that the presence of MMA monomer in femoral venous blood has no effect on the formation of fat emboli or their pulmonary haemodynamic outcome during cemented hip arthroplasty.

Animals↗

Effect of stainless steel and titanium low-contact dynamic compression plate application on the vascularity and mechanical properties of cortical bone after fracture.

OBJECTIVES: Comparison of the effect of stainless steel and titanium low-contact dynamic compression plate application on the vascularity and mechanical properties of cortical bone after fracture. DESIGN: Randomized, prospective. SETTING: Orthopaedic research laboratory. ANIMALS: Ten large (greater than twenty-five kilogram) adult dogs. INTERVENTION: A short, midshaft spiral tibial fracture was created, followed by lag screw fixation and neutralization with an eight-hole, 3.5-millimeter, low-contact dynamic compression plate (LCDCP) made of either 316L stainless steel (n = five) or commercially pure titanium (n = five). After surgery, animals were kept with unrestricted weight-bearing in individual stalls for ten weeks. MAIN OUTCOME MEASUREMENTS: Cortical bone blood flow was assessed by laser Doppler flowmetry using a standard metalshafted probe (Periflux Pf303, Perimed, Jarfalla, Sweden) applied through holes in the custom-made LCDCPs at five sites. Bone blood flow was determined at four times: (a) prefracture, (b) postfracture, (c) postplating, and (d) ten weeks postplating. After the dogs were killed, the implant was removed and both the treated tibia and contralateral tibia were tested for bending stiffness and load to failure. RESULTS: Fracture creation decreased cortical perfusion in both groups at the fracture site (p = 0.02). The application of neither stainless steel nor titanium LCDCPs further decreased cortical bone blood flow after fracture creation. However, at ten weeks postplating, cortical perfusion significantly increased compared with acute postplating levels in the stainless steel (p = 0.003) and titanium (p = 0.001) groups. Cortical bone blood flow ten weeks postplating was not significantly different between the titanium group and the stainless steel group. Biomechanical tests performed on the tibiae with the plates removed did not reveal any differences in bending stiffness nor load required to cause failure between the two groups. CONCLUSIONS: Both titanium and stainless steel LCDCPs were equally effective in allowing revascularization, and neither provided a significant advantage in biomechanical properties of fracture healing at ten weeks.

Analysis of Variance↗

Plasminogen activator system in osteoclasts.

To determine which genes of the plasminogen activator (PA) system were expressed in osteoclasts, RNA extracted from microisolated mouse osteoclasts was used as template for reverse transcribed polymerase chain reaction (RT-PCR) with gene-specific primer pairs. Using this approach, the expression of RNAs for tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor-1, plasminogen activator inhibitor-2, protease nexin, and urokinase receptor isoform 1 (uPAR1) were detected in mouse osteoclasts. The expression of uPAR RNA in osteoclasts was confirmed by in situ hybridization with a uPAR1 probe. RNA encoding the uPAR isoform 2 was not detected in mouse osteoclasts, but a novel unspliced uPAR RNA variant was detected in these cells. The novel uPAR variant and uPAR1 RNA were also detected in mouse calvarial osteoblasts, kidney, muscle, and the mouse macrophage cell line J774A.1 by RT-PCR. The presence of RNAs for most of the components of the PA system in osteoclasts suggests that it may have a functional role in this cell type.

Animals↗

Pulmonary effects of fixation of a fracture with a plate compared with intramedullary nailing. A canine model of fat embolism and fracture fixation.

UNLABELLED: Fat-embolism syndrome and pulmonary dysfunction may develop in multiply injured patients who have a fracture of a long bone. Although early fixation of a fracture is beneficial, intramedullary nailing may exacerbate pulmonary dysfunction by causing additional embolization of marrow fat. We examined the pulmonary effects of the timing and method of fixation of a fracture in a canine fat-embolism model. Fat embolism was induced in forty-one adult dogs by reaming the ipsilateral femur and tibia followed by pressurization of the intramedullary canal. The animals were divided into a control group of eight dogs that had induction of fat embolism alone and an experimental group of thirty-three dogs that had induction of fat embolism and internal fixation of a transverse fracture of the middle of the contralateral femoral shaft. In the control group, four dogs each were killed four hours and twenty-four hours after induction of fat embolism. In the experimental group, a femoral fracture was created and fixation was performed four hours after embolic showering in fifteen animals and twenty-four hours after embolization in eighteen animals. The two experimental groups were subdivided according to the method of fixation of the fracture: eleven dogs each had application of a plate, nailing without reaming, and nailing with reaming. The pulmonary arterial pressure and the alveolar-arterial gradient were measured preoperatively, during induction of fat embolism, and as long as one hour after fixation of the fracture but before the animal was killed. The lungs, brain, and kidneys were examined for pathological and physiological evidence of intravascular fat. The intravascular fat persisted for twenty-four hours after induction of pulmonary fat embolism. Pulmonary arterial pressure remained elevated at four hours after the embolic showering, before creation and fixation of the fracture. By twenty-four hours after the induction of fat embolism, pulmonary arterial pressure had returned to the baseline level. Neither the creation nor the fixation of the fracture affected pulmonary arterial pressure. In the animals that had fixation of a fracture four hours after embolization, both nailing with reaming and nailing without reaming produced alveolar-arterial gradients that were higher than the baseline values, whereas fixation with a plate did not change the alveolar-arterial gradient significantly from the baseline value. In addition, the alveolar-arterial gradients in the animals that had nailing with reaming and nailing without reaming four hours after embolization were, respectively, four and 3.5 times higher than that in the animals that had fixation of the femur with a plate. In the animals that had fixation twenty-four hours after embolization, none of the methods for fixation affected the alveolar-arterial gradient. The amount of embolic fat in the lungs, brain, and kidneys was not affected by fixation of the fracture when it was performed at either the four-hour or the twenty-four-hour time-interval. Scores for pulmonary edema were increased by fixation of the fracture, but there was no difference among the scores associated with the three methods of fixation. CLINICAL RELEVANCE: The findings of the present study indicated that the amount of intravascular fat persisting in the lungs, kidneys, and brain twenty-four hours after pressurization of the intramedullary canal is not affected by the method of fixation of the fracture. Fixation of a fracture is associated with minimum evidence of acute inflammation and has no effect on pulmonary artery pressure. The development of pulmonary dysfunction from fat emboli depends on other factors, not just on the presence of fat in pulmonary vessels. It appears that the method of fracture fixation has little influence on the outcome of treatment.

Animals↗

Assessment of the relationship between standard probe and implantable fiber measurements of cortical bone blood flow: a canine study.

Laser Doppler flowmetry (LDF) has been used to assess cortical bone blood flow in various clinical situations, such as osteomyelitis and osteonecrosis. Standard metal-sheathed probes containing optical fibers, applied to cortical bone for perfusion measurements, require direct exposure of the bone surface for each measurement, making nonanesthetized assessments over time impractical. Implantable optical fibers offer a noninvasive method for evaluating cortical bone perfusion without repeated surgical exposure of the bone after initial surgical implantation of the fibers. In vitro studies have shown the reliability of laser Doppler (LD) fibers compared with those of the standard probe. This investigation studied the relationship between measurements of cortical bone perfusion obtained by implanted optical (LD) fibers and standard (LDF) probes in vivo. Midshaft tibial fractures were created in the right hindlimb of 11 adult, large (>25 kg) dogs and stabilized by low contact-dynamic compression plate fixation. Cortical bone blood flow was measured by LDF using standard probes and implantable fibers at five sites along the tibia prefracture, postfracture, immediately postplate application, and at 10 weeks postplating, immediately prior to euthanasia. The implantable fibers were secured onto the cortical bone via the plate and led through a percutaneous exit site. Histological examination of the inguinal and popliteal lymph nodes and soft tissue surrounding the fibers revealed mild inflammation. No significant correlation of blood flow assessed by the implantable fibers and standard probe occurred immediately postfracture (r < 0. 13, p > 0.62). However, a statistically significant correlation was seen postplate application at one of the measurement sites in the distal fracture fragment (r = 0.78, P < 0.003). The fibers remained intact and functional until an average of 3 weeks at which time they either fractured or were removed by the animals. This is the first in vivo study assessing the reliability of implantable fibers for the measurement of cortical bone blood flow. Further modification of the fibers will be necessary to improve their longevity and durability for assessment of cortical bone blood flow.

Animals↗

A Madreporic-surfaced femoral component in a canine total hip arthroplasty model: bone remodelling response at 6 and 24 months.

OBJECTIVE: To evaluate the bone-remodelling response at 6 and 24 months after total hip arthroplasty around a two-thirds Madreporic-surfaced femoral component in a canine model. DESIGN: A research study in dogs. Statistical analysis was by multivariate analysis of variance. SETTING: A musculoskeletal research laboratory in a university teaching hospital. MATERIAL: Ten mature mixed-breed dogs. INTERVENTION: Unilateral implantation of total hip arthroplasty in the right femur with a Madreporic-surfaced prosthesis. Studies were conducted at 6 months in five dogs and at 24 months in five dogs. In each case, the nonoperated femur was the study control. MAIN OUTCOME MEASURES: Fluorescence microscopy analysis on comparable sections at four levels of the femora, percent porosity computed by image analysis, cortical atrophy. RESULTS: Cancellous hypertrophy was most prominent at the junction of the beaded and smooth portions of the femoral stem. At 6 months the cortex demonstrated atrophy predominant in the anteromedial quadrant. Active bone turnover was present within the interstices of the prosthesis at 6 and 24 months. No significant cortical bone loss occurred between 6 and 24 months. Stress transfer to the bone-prosthesis interface and endosteal cortical "cancellization" appear to be linked phenomena.

Animals↗

A study of micromotion and appositional bone growth to a canine madreporic-surfaced femoral component.

A canine total hip arthroplasty model was used to examine micromotion and bone apposition to a proximally two-thirds madreporic-surfaced femoral prosthesis. Micromotion was also measured following initial press-fit implantation into canine cadaveric femora. After initial press-fit fixation and either 6 or 24 months of biologic fixation, micromotion was less than 23 microns in the proximal and midstem regions, a magnitude consistent with bone apposition. Bone apposition was greatest near the junction of the madreporic and smooth surfaces and was not significantly different between 6 and 24 months (51% at 6 months and 47% at 24 months). The quality of the interface tissue appears to be conductive to long-term fixation.

Animals↗

Fracture disease and related contractures.

Fracture disease and the complications of immobilization are described. The pathogenesis of the disease is discussed. The clinical implications of immobilization are outlined, and physical therapy modalities are reviewed. Also included is a summary of quadriceps contracture management.

Animals↗

Polyethylene synovitis following canine total hip arthroplasty. Histomorphometric analysis.

The synovial membrane response to polyethylene wear debris was analyzed in canine total hip arthroplasties (THA). Fifty-four THAs were performed in healthy, mature dogs. None of the arthroplasties demonstrated clinical or radiographic signs of loosening. Synovial membrane biopsies were harvested 4 (n = 13), 6 (n = 5), 8 (n = 8), 12 (n = 15), and 24 (n = 6) months after surgery and were scored for inflammation, polyethylene (PE) wear debris, histiocyte density, and membrane thickness. The amount of PE wear debris tended to increase with time. However, the inflammatory changes within the joint capsule and synovial membrane did not progress, and the total thickness of the alveolar and surface layers decreased (P = .008). It appears that the amount of wear debris at 2 years in canine hip arthroplasties, without evidence of loosening, is well tolerated by the joint capsule.

Animals↗

Soft-tissue blood flow after segmental osteotomy of the canine tibia.

The response of soft-tissue blood flow to a segmental osteotomy of the canine tibial diaphysis was investigated. Forty-three dogs underwent unilateral tibial osteotomies to create a 2.5-cm avascular diaphyseal segment, which was then rigidly stabilized with a plate. Blood flow measurements of the limbs that underwent surgery and control limbs were made using cerium 141 microspheres. One month after surgery, blood flow to the caudal musculature was increased 1.4-fold and at 2 and 3 months was twofold the value of the control side. The cranial musculature blood flow was 2.4-fold the control value at 1 month and 1.4-fold the control value at 2 and 3 months. Skin blood flow was significantly elevated at 1 month after surgery (p less than 0.0277), but by 2 and 3 months, skin flow had decreased to 1.4-fold and 1.3-fold of control values (p = 0.22). Bone marrow and cortical blood flows were still significantly elevated at 3 months after surgery. Muscle blood flow remains markedly elevated 3 months after surgery. This study demonstrates the importance of soft-tissue blood flow to the process of revascularization, remodeling, and incorporation of avascular cortical bone.

Animals↗

A comparison of the effects of skin coverage and muscle flap coverage on the early strength of union at the site of osteotomy after devascularization of a segment of canine tibia.

A study was done to compare the effects of coverage with skin and those of coverage with a muscle flap on the early return of strength at the site of an osteotomy after interposition of a devascularized segmental autogenous graft, two centimeters long, from a canine tibia. The bone was fixed with a plate. Thirty-two animals were randomized into two groups, one of which was treated with skin coverage and the other of which was treated with muscle flap coverage. Half of the animals from each group were killed at eight weeks and half, at twelve weeks postoperatively. The tibiae were tested to failure in four-point bending. Failure occurred primarily through the site of the distal osteotomy. Maximum bending load (p = 0.0002) and energy absorbed to failure (p less than 0.02) increased significantly between eight and twelve weeks postoperatively in the group in which a muscle flap had been used for coverage. Bending stiffness was significantly greater at eight weeks in the group in which a muscle flap had been used for coverage than in the group in which skin had been used (p less than 0.03). Maximum bending load was also significantly increased at twelve weeks in the group in which a muscle flap had been used compared with the group in which skin had been used (p less than 0.05).

Animals↗

Synovitis subsequent to total-hip arthroplasty with and without hydroxyapatite coatings: a study in dogs.

OBJECTIVE: To establish whether hydroxyapatite (HA) coatings applied to metal total-hip-replacement components increased synovitis in the coxofemoral joint of dogs. Study Design-An in vivo research trial and histologic study. ANIMALS: Twenty-three large, mixed-breed dogs. METHODS: Arthroplasty components were implanted with HA on neither stem nor cup, or with HA applied to either the femoral component or with both stem and cup having HA applied in 23 dogs. Synovial inflammation was scored 3, 6, and 12 months after surgery. Synovial membrane thickness; polyethylene particulate load; fibrin exudate; membrane edema; mitotic index; giant-cell, mononuclear histiocyte, lymphocyte, and polymorph number; and collagen degeneration were scored and statistical analyses performed. RESULTS: Operated-side synovial thickness was greatly increased relative to control. Fibrin deposition, intramembranous edema, and collagen degeneration were similar within each time interval among the various component groups. The majority of inflammatory scores among the groups were unchanged. In this 12-month study, the presence of HA coatings appear not to have a marked impact on the development of synovial inflammation. CONCLUSIONS: HA-coated components do appear to contribute somewhat to the inflammatory load within the periprosthetic environment, but this effect is not marked. CLINICAL RELEVANCE: The major advantage of HA addition to arthroplasty components is enhanced osteoconductivity around metallic surfaces. The slight increase in particulate load seen in the presence of HA coatings may contribute to the development of aseptic loosening of arthroplasty components, but is unlikely to be the major causative factor.

Animals↗

Rectal resection in the dog. A new surgical approach and the evaluation of its effect on fecal continence.

Thirteen healthy mixed breed dogs (6 female and 7 male) underwent rectal transection and resection of 0 to 6 cm using a dorsal approach. Rectoanal sphincter pressure studies were performed preoperatively and 6 weeks after surgery using a double balloon manometer device. Sphincter pressure profiles were altered in the 6 cm resection dogs. Clinical observations of defecation and degree of continence were made over a 10 week period postoperatively. The transection only and 4 cm resection dogs defecated normally. All dogs in the 6 cm resection group involving the peritoneal reflection were incontinent but retained some normal posturing behavior. Surgical complications included minor infection in two dogs, rectocutaneous fecal leakage in four dogs, breakdown of the anastomotic site in four dogs, and incontinence in all of the dogs that underwent 6 cm resections. Barium enemas were performed on the rectums postmortem to ascertain the degree of stricturing induced by the surgery. The index of stenosis measured did not correlate well with the extent of straining in each group. Histopathologic findings on dogs in the transection only and 4 cm resection groups without dehiscence showed mild granulomatous proctitis with normal myenteric plexi seen. Dogs suffering dehiscence had suppurative proctitis, necrosis, and obliteration of the myenteric plexi.

Anastomosis, Surgical↗

The treatment of chronic sinusitis in six cats by ethmoid conchal curettage and autogenous fat graft sinus ablation.

Six cats with chronic recurrent rhinitis and frontal sinusitis were treated by surgical ablation of their frontal sinuses by the implantation of autogenous fat grafts and curettage of the remaining ethmoid conchae. Deep nasal bacterial cultures and skull radiographs were performed before surgery. Excellent results were achieved in four of six cats and there was significant improvement in two of six cats. Median follow-up time was 15 months. Subcutaneous emphysema over the temporal area was managed by needle aspiration and bandaging. Frontal sinus ablation with autogenous fat graft in combination with ethmoid conchal curettage appears to be an effective treatment for chronic sinusitis in cats.

Adipose Tissue↗