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Biomedical subjects

M Lind

Publications and source records attributed to M Lind.

At least 37 records · Page 2Linked to original sources

Resorption of hydroxyapatite and fluorapatite ceramic coatings on weight-bearing implants: a quantitative and morphological study in dogs.

Resorption (defined as loss of ceramic coating because of cellular activity or dissolution) of ceramic coatings is a matter of concern for the long-term performance of ceramic-coated implants. A new fluorine-containing coating, fluorapatite (FA), has been shown to be more stable than hydroxyapatite (HA) in unloaded models. In a weight-bearing model in trabecular bone, we evaluated loss (defined as reduction of coating irrespective of type of mechanism) of HA and FA coatings during 25 weeks of implantation. Eight mature dogs had HA- or FA-coated implants inserted bilaterally into the weight-bearing region of the medial femoral condyle. Quantified loss of ceramic coating was estimated at the light microscopic level using stereological methods. The experiment showed significant loss of both types of coatings. However, no statistical difference in loss of ceramic coating was found regarding surface area implant coverage, volume, and thickness (p = 0.77, p = 0.13, p = 0.56, p = 0.23, respectively). Completely resorbed HA coating was replaced by 36 +/- 6.0% (range: 26-42) bone in direct contact with the implant surface compared with 29 +/- 16.0% (range: 12-59) for FA (p = 0.40), suggesting that the implant was firmly fixed despite loss of the ceramic coating. Transmission electron microscopy in combination with electron energy spectroscopy and electron spectroscopic imaging showed that osteclast-like cells, osteocytes, macrophage-like cells, and fibroblasts had phagocytosed calcium-containing fragments, indicating cell-mediated resorption of the ceramic coating.

Animals↗

Porous-coated versus grit-blasted surface texture of hydroxyapatite-coated implants during controlled micromotion: mechanical and histomorphometric results.

Hydroxyapatite (HA)-coated implants with porous-coated and grit-blasted surface textures were inserted bilaterally in a paired design into the medial femoral condyles of eight dogs for 16 weeks. The implants were weight-loaded and initially subjected to controlled micromotion of 500 microm during each gait cycle. Histology revealed that five implants in each group had bony anchorage, and the remaining implants were surrounded by fibrous tissue. Push-out testing showed no difference in shear stiffness and strength, while energy absorption for porous-coated implants was increased significantly by threefold. The HA coating delaminated on grit-blasted implants during push-out testing, whereas porous-coated implants predominantly failed at the HA-tissue interface. Coverage, surface area, volume, and thickness of the HA coating were significantly reduced in vivo for porous-coated and grit-blasted implants. In conclusion, a plasma-sprayed porous-coated implant surface seems to give better fixation not only of the HA-coating to the implant surface but also of the implant to the surrounding tissues in comparison to a grit-blasted implant surface. The HA coating was reduced more on fibrous-anchored than on bony-anchored implants, suggesting that micromotion accelerates resorption of HA. Resorbed HA coating was replaced by more bone on porous-coated implants than on grit-blasted implants, which suggests that fixation of porous-coated implants will be durable.

Animals↗

Volume-referent bone turnover estimated from the interlabel area fraction after sequential labeling.

In the compact bony otic capsule remodeling is low, and bone remodeling units are distributed centrifugally in relation to inner ear tissues and spaces. Fluorochrome-labeled bone remodeling units are scarce, abortive, and tortuous with no uniform direction of movement. This study presents a method for the estimation of volume-referent bone turnover based on measurements of the fractional area between labels after sequential labeling with osteofluorochromes. The applicability of this method is tested against a classical quantification method in undecalcified cortical specimens from the canine humerus, where both methods can be used. The estimate of bone turnover derived from the new sequential labeling in eight dogs is 7.4% (SEM 2.1%) per year and the classic estimate derived from calculations of the formative osteonal area and the formative period yields 6.9% (SEM 2.1%) per year. Agreement is sufficient to justify future measurements of absolute bone turnover in sequentially labeled perilabyrinthine bone.

Animals↗

Randomized comparison of progenitor-cell mobilization using chemotherapy, stem-cell factor, and filgrastim or chemotherapy plus filgrastim alone in patients with ovarian cancer.

PURPOSE: This was the first randomized study to investigate the efficacy of peripheral-blood progenitor cell (PBPC) mobilization using stem-cell factor (SCF) in combination with filgrastim (G-CSF) following chemotherapy compared with filgrastim alone following chemotherapy. PATIENTS AND METHODS: Forty-eight patients with ovarian cancer were treated with cyclophosphamide and randomized to receive filgrastim 5 microg/kg alone or filgrastim 5 microg/kg plus SCF. The dose of SCF was cohort-dependent (5, 10, 15, and 20 microg/kg), with 12 patients in each cohort, nine of whom received SCF plus filgrastim and the remaining three patients who received filgrastim alone. On recovery from the WBC nadir, patients underwent a single apheresis. RESULTS: SCF in combination with filgrastim following chemotherapy enhanced the mobilization of progenitor cells compared with that produced by filgrastim alone following chemotherapy. This enhancement was dose-dependent for colony-forming unit-granulocyte-macrophage (CFU-GM), burst-forming unit-erythrocyte (BFU-E), and CD34+ cells in both the peripheral blood and apheresis product. In the apheresis product, threefold to fivefold increases in median CD34+ and progenitor cell yields were obtained in patients treated with SCF 20 microg/kg plus filgrastim compared with yields obtained in patients treated with filgrastim alone. Peripheral blood values of CFU-GM, BFU-E, and CD34+ cells per milliliter remained above defined threshold levels longer with higher doses of SCF. The higher doses of SCF offer a greater window of opportunity in which to perform the apheresis to achieve high yields. CONCLUSION: SCF (15 or 20 microg/kg) in combination with filgrastim following chemotherapy is an effective way of increasing progenitor cell yields compared with filgrastim alone following chemotherapy.

Adult↗

Effects of particulate debris on macrophage-dependent fibroblast stimulation in coculture.

The interactions between the different cell types in periprosthetic tissue are still unclear. We used a non-contact coculture model to investigate the effects of polymethylmethacrylate (PMMA) particles and human macrophage-derived soluble mediators on fibroblast activation. Macrophages were either exposed or not exposed to phagocytosable PMMA particles, but fibroblasts were not. Increasing numbers of macrophages were tested in cocultures in which the fibroblast cell number was held constant and cultures of macrophages alone were used for comparison of cytokine release. We used the release of interleukin-1 beta (IL-1beta), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha), lysosomal enzyme and metalloproteinase activity to assess the cultivation of macrophages and fibroblasts. In cocultures, IL-6 release was increased 100-fold for both unchallenged and particle-challenged cultures when compared with macrophage cultures alone. Furthermore, particle-challenged cocultures had threefold higher IL-6 levels than unchallenged cocultures. Release of TNF-alpha was similar in cocultures and in macrophage cultures. IL-1beta release in cocultures was independent of the macrophage-fibroblast ratio. Lysosomal enzyme activity and metalloproteinase activity were increased in cocultures. Our data show that macrophages and fibroblasts in coculture significantly increase the release of IL-6 and to a less degree other inflammatory mediators; particle exposure accentuates this effect. This suggests that macrophage accumulation in fibrous tissue may lead to elevated IL-6 levels that are much higher than those caused by particle activation of macrophages alone. This macrophage-fibroblast interaction represents a novel concept for the initiation and maintenance of the inflammatory process in periprosthetic membranes.

Coculture Techniques↗

In vitro, in vivo, and tissue retrieval studies on particulate debris.

The biologic effects of wear debris are an important factor limiting the longevity of total joint replacements. In vivo, in vitro, and tissue retrieval studies have underlined a central role for the macrophage in the etiology of loosening and periprosthetic osteolysis. Wear particles from the materials used for total joint replacement activate macrophages to secrete proinflammatory factors. Complex interactions between macrophages and other cells stimulate bone resorption and suppress bone formation at the prosthetic interface. To improve the long term outcome of joint replacements, future research must find innovative approaches to minimize the production and biologic effects of wear debris.

Animals↗

Growth factor stimulation of bone healing. Effects on osteoblasts, osteomies, and implants fixation.

Bone tissue has been shown to contain numerous cell-to-cell signalling peptides called growth factors. These growth factors are thought to have important regulating effects for bone remodeling and bone healing, due to their potent effects on bone cell metabolism. In vivo studies over the last half decade have demonstrated that growth factors candidates for future clinical use in orthopedic surgery. In numerous clinical situations enhanced bone formation and bone healing could lead to improved results of surgical procedures. This thesis describes the most important bone growth factors and their actions in vitro and in vivo. In vitro investigations of growth factor effects on osteoblast chemotaxis and metabolism are described as well as in vivo studies with growth factor stimulation of fracture healing and bone healing to prosthetic-like implants. In vitro results: Several growth factors exhibited chemotactic effects towards human osteoblasts. TGF-beta 1 and PDGF-BB had the strongest chemotactic effects, whereas PDGF-AA, IGF-1, and IGF-2 had less but significant chemotactic effects towards human osteoblasts. TGF-beta 1 exhibited the highest chemotactic potency with maximal activity at 100 pg/mL, whereas the other growth factors had maximal effects at 10-100 ng/mL. BMP-2 was found to have chemotactic effects toward human osteoblasts, human bone marrow osteoprogenitor cells, and U2-OS osteosarcoma cells. BMP-4 and BMP-6 were without any chemotactic effects towards these celltypes. Human bone marrow osteoprogenitor cells were the most responsive celltype to BMP-2 stimulation. Growth factor combinations resulted in synergic stimulative effects on different metabolic functions on human osteoblasts. Combinations with TGF-beta 1 and PDGF-BB strongly stimulated proliferation and chemotaxis. Combinations with TGF-beta 1, PDGF-BB and BMP-2 strongly stimulated an osteoblast differentiation parameter (alkaline phosphatase activity). The different growth factor combinations had no effect on collagen synthesis in human osteoblasts. In vivo results: Continuous application of 1 and 10 micrograms natural TGF-beta to a plated tibial osteotomy in rabbits increased mechanical bending strength and callus formation at 6 weeks observation. Diaphyseal cortical bone remodeling was not affected by the local growth factor application. In a dog model with unloaded implants surrounded by a gap, 0.3 microgram rhTGF-beta 1 adsorbed to gritblasted tricalcium phosphate coated implants, was able to enhance mechanical fixation, bone ingrowth and gap bone formation. 3.0 micrograms rhTGF-beta 1 had less but significant stimulative effect. In a weight-loaded model, 0.3 microgram rhTGF-beta 1, adsorbed to gritblasted tricalcium phosphate coated implants, was able to enhance bone ingrowth, without enhancement of mechanical fixation. In the unloaded model, 0.3 microgram rhTGF-beta 1, adsorbed to gritblasted hydroxyapatite coated implants, was able to enhance bone ingrowth, without enhancement of mechanical fixation. 3.0 micrograms rhTGF-beta 1 had no stimulative effects. The establishment of a biological implant fixation concept with growth factor absorbed to ceramic coatings of implants was successful. These data are promising for a possible future clinical usage of growth factors, especially for enhancement of bone healing to cementless prosthetic components.

Animals↗

CD19-selected B lymphocytes synthesize, secrete and migrate in the presence of IL-8. TNF-alpha and gammaIP-10 are also B lymphocyte migratory factors.

B lymphocytes are responsible for antigen uptake and presentation, as well as antibody production. These reactions require close cell-to-cell contact between B lymphocytes and monocytes. In this study we demonstrate that interleukin 8 (IL-8), gamma-immune protein 10 (gammaIP-10) and tumour necrosis factor alpha (TNF-alpha) all induce a significant chemokinetic response of human B lymphocytes. Among the cytokines tested, rIL-8 was the strongest B lymphocyte migratory factor with a migratory index (MI) of 2.03+/-0.32, (P<0.002), followed by rTNF-alpha (MI=1.89+/-0.17, P<0.001) and rgammaIP-10 (MI=1.63+/-0.17, P<0.001). We did not observe B lymphocyte migration towards rIL-1alpha, rIL-2, rIL-4, rIL-10, interferon gamma (rINF-gamma) or transforming growth factor beta (rTGF-beta). Furthermore, we report that human B lymphocytes have a constitutive IL-8 mRNA expression and protein secretion in vitro. Resting as well as stimulated B lymphocytes secrete on average 1.5 ng IL-8/ml medium/24 h (2x10(6) B lymphocytes). Our data indicate a possible mechanism by which B lymphocytes make contact with other cells, during immuno-inflammatory processes.

Antigens, CD19↗

Hydroxyapatite and fluorapatite coatings for fixation of weight loaded implants.

Survivor analysis of total hip replacement recently has shown disappointing results in younger patients. To improve this, ceramic coatings have been applied to prostheses for cementless use. A new fluorine containing coating, fluorapatite, has been shown to increase bone ingrowth compared with hydroxyapatite in unloaded models. In a weight loaded model, the effects of hydroxyapatite and fluorapatite coated implants on implant fixation and bone ingrowth were evaluated. Eight hydroxyapatite and fluorapatite coated implants with porous surface were inserted into the medial femoral condyles of 8 mature dogs in a paired design. The implants initially were surrounded by a gap communicating with the joint space and were loaded during each gait cycle. After 25 weeks, no differences in pushout data or bone ingrowth between hydroxyapatite and fluorapatite coated implants were found. An important finding was the absence of foreign body reaction in the bone. Neither hydroxyapatite nor fluorapatite coatings delaminated during implantation or as a result of the pushout test. Bone repair activity remained in the initial gap zone, but most of the bone was of the lamellar type. No difference in bone remodeling between the hydroxyapatite and fluorapatite coated implants was found in the initial gap zone. Microprobe analysis showed no increase in fluorine content around the fluorapatite coated implants. The hydroxyapatite and fluorapatite coatings seem efficacious after a 25-week implantation period under weight loaded conditions.

Animals↗

Resorption of hydroxyapatite and fluorapatite coatings in man. An experimental study in trabecular bone.

The clinical use of hydroxyapatite (HA) coating is controversial especially in regard to the long-term performance of the coating and the effects of resorption. In each of 15 consenting patients we inserted two implants, coated with either HA or fluorapatite (FA) into the iliac crest. They were harvested at a mean of 13.6 +/- 0.6 months after surgery. Histological examination showed that bone ongrowth on the HA-coated implants was significantly greater (29%) than that on the FA-coated implants. When bone was present on the coating surface the HA coating was significantly thicker than the FA coating. When bone marrow was present, the HA coating was significantly thinner than the FA coating. The reduction in coating thickness when covered by bone or bone marrow was 23.1 +/- 9.7 microm for HA and 5.1 +/- 1.7 microm for FA (p < 0.01) suggesting that FA is more stable than HA against resorption by bone marrow. The findings suggest that in man the osteoconductive properties of HA coating are superior to those of FA. Resorption rates for both coatings were approximately 20% of the coating thickness per year. Bone ongrowth appears to protect against resorption whereas bone marrow seems to accelerate resorption. No adverse reaction was seen in the surrounding bone.

Apatites↗

Improved fixation of porous-coated versus grit-blasted surface texture of hydroxyapatite-coated implants in dogs.

We inserted, in 8 dogs, implants with either porous-coated or grit-blasted titanium surface and coated with hydroxyapatite (HA) into trabecular bone in the proximal humerus, using a 1 mm gap model. After 25 weeks, push-out tests showed that energy absorption for porous-coated implants was twice that of grit-blasted implants, whereas shear stiffness was reduced by one fifth, indicating a stronger fixation of porous-coated implants. Macroscopically, all grit-blasted implants had delamination of the HA coating, whereas porous implants failed mostly at the HA-tissue interface. Porous-coated implants had 47% bone ingrowth and grit-blasted implants 70% (p = 0.02), however, no difference in absolute surface area was found. Part of the HA coating was resorbed during the implantation period as regards volume and thickness. HA coverage was more reduced on porous-coated than on grit-blasted implants (p = 0.01). No foreign-body reaction or osteolysis was seen. An important finding was that one fifth of the surface with complete resorption of HA coating was replaced by newly formed bone.

Animals↗

Transforming growth factor-beta 1 enhances bone healing to unloaded tricalcium phosphate coated implants: an experimental study in dogs.

Growth of bone into cementless prosthetic components is compromised after revision of failed joint prostheses and by osteoporosis, gaps, and micromotion. We studied the effects of recombinant human transforming growth factor-beta 1 adsorbed on ceramic coated implants on the improvement of mechanical fixation and bone growth on the implant. Unloaded cylindrical grit-blasted titanium alloy implants were inserted bilaterally into both the medial and lateral femoral condyles of 10 skeletally mature mongrel dogs. The implants measured 10 mm in length and 6 mm in diameter and were initially surrounded by a 2 mm gap. One implant had an uncoated titanium surface and three implants were coated with tricalcium phosphate and 0, 0.3, or 3.0 micrograms of recombinant human transforming growth factor-beta 1. The dogs were killed at 6 weeks. Mechanical testing showed a 3-fold increase in fixation for the 0.3 microgram dose of recombinant human transforming growth factor-beta 1 and a 2-fold increase for the 3.0 micrograms dose. Histological analysis of bone growth on the implant demonstrated that maximal stimulation occurred with the 0.3 microgram dose, but bone volume in the gap was maximally stimulated by the 3.0 micrograms dose and increased 2-fold over control values. The majority of tricalcium phosphate was resorbed after the 6-week observation period. This study suggests that recombinant human transforming growth factor-beta 1 adsorbed onto implants coated with tricalcium phosphate ceramic can enhance mechanical fixation and bone growth on the implant. The use of transforming growth factor-beta 1 on ceramic coated prosthetic components may help to improve the functional outcome of cementless total joint replacements.

Animals↗

The relationship between tumour glutathione concentration, glutathione S-transferase isoenzyme expression and response to single agent carboplatin in epithelial ovarian cancer patients.

There is evidence to suggest that glutathione (GSH) and glutathione-S-transferases (GST) are important factors in determining sensitivity to cytotoxic drugs in vitro and in preclinical in vivo model systems. To define the relationship between tumour GSH concentration, GST isoenzyme expression and response to carboplatin in epithelial ovarian cancer (EOC), tumour samples from 39 patients with assessable disease after primary surgery were analyzed for GSH content and GST expression. Response was assessed after completing six courses of single agent carboplatin therapy. GSH was measured by high performance liquid chromatography (HPLC) in fresh tumour samples taken at primary laparatomy. GST isoenzyme expression was assessed by immunohistochemistry of fixed tumour material using antibodies specific for pi, alpha and mu classes. GST isoenzyme expression was defined as positive if the staining intensity was strong and more than 10% of tumour cells were involved. The mean GSH concentrations were: 8351 +/- 4496, 7211 +/- 5026, 6559 +/- 4573 and 3758 +/- 1885 (nmol g-1 tissue dry weight mean +/- s.d.) for tumours from patients who subsequently achieved a complete response (CR, n = 18), partial response (PR, n = 10) or who had static disease (SD, n = 7) or progressive disease (PD, n = 4) respectively. There was no relationship between GSH concentration and response (ANOVA, P = 0.32). There were also no relationship between GST isoenzyme expression and response (P Fisher's exact test 0.51-0.55 and chi-squared test 0.98-0.99). In conclusion, there was no association between the concentration of GSH or expression of GST isoenzymes and response to single agent carboplatin in primary previously untreated EOC.

Antineoplastic Agents↗

Transforming growth factor-beta stimulates bone ongrowth. Hydroxyapatite-coated implants studied in dogs.

Unloaded cylindrical grit-blasted titanium (Ti-6A-4V) implants (6 x 10 mm) coated with hydroxyapatite ceramic were inserted into the proximal part of the humerus of 20 skeletally mature Labrador dogs. The implants were initially surrounded by a 2 mm gap. In 10 dogs, HA-coated implants without growth factor were inserted in one humerus and implants with 0.3 microgram rhTGF-beta 1 adsorbed onto the HA coating were inserted in the contralateral humerus. In another group of 10 dogs, a dose of 3.0 micrograms rhTGF-beta 1 was tested in a similar design. All dogs were killed at 6 weeks after treatment. Results were evaluated by histomorphometry and mechanical push-out testing. Bone ongrowth was increased by one third, using the 0.3 mg rhTGF-beta 1 stimulation. Bone volume in the gap and mechanical testing showed no statistically significant differences between control and rhTGF-beta 1 stimulated implants. RhTGF-beta 1 only moderately enhanced bone ongrowth to hydroxyapatite-coated implants.

Alloys↗

Growth factors: possible new clinical tools. A review.

Bone tissue contains numerous cell-to-cell signaling peptides called growth factors with potent effects on bone cell metabolism. In vivo studies over the last 5 years have demonstrated that growth factors can stimulate bone formation and bone healing and these results have made them candidates for use in orthopedic surgery. In numerous clinical conditions enhanced bone formation and bone healing could improve the results of surgery; clinical trials using growth factors to stimulate bone formation in spinal surgery, and to stimulate healing of bone defects, have been initiated. Growth factors for clinical use will become commercially available in the near future. This review describes the main growth factors and their actions in vitro and in vivo in relation to bone tissue and bone healing. Possible areas for clinical use are also discussed.

Animals↗

The effect of polar projection on the perception of euclidean structure from motion.

The aim of the present study was to examine whether euclidean structure could be recovered from apparent motion sequences under polar projection. In Experiment 1, length judgments of two sides of a simulated triangle rotating in depth did not reveal effects of type of projection, polar or parallel, on the perception of euclidean structure. However, there was a significant correlation between simulated and produced slants. The results also indicated that absolute depth judgments could not be accounted for by a random mechanism suggested by Todd and Bressan (1990). Experiments 2 and 3, in which a continuous dot surface was substituted for the triangle, showed that polar projection information from a relatively large visual angle, 17.40 degrees, as compared with a small visual angle, 4.35 degrees, facilitated discrimination of depth. Produced height:width ratios were consistently related to simulated shape, although the depth dimension was underestimated. Finally, Experiment 4 showed significant correlations between simulated and produced height:width ratios that could be accounted for only by an analysis in which X and Y velocities were treated independently. As in previous experiments, the variation in the depth dimension was underestimated. It was concluded that the visual system utilizes the additional information that is available in polar projection when recovering structure from motion, but that for different reasons the perceived structure does not become euclidean. These reasons are discussed briefly.

Adult↗

Perceiving motion and rigid structure from optic flow: a combined weak-perspective and polar-perspective approach.

Structure-from-motion algorithms based on weak-perspective projection have many interesting properties and could serve as a basis for a model of human perception of motion and structure from motion (M&SFM). There is some psychophysical evidence, however, that points to discrepancies between what can be accomplished with these algorithms and the performance of human subjects in certain M&SFM tasks. In light of this evidence, this paper presents a mechanism that both takes advantage of all the possibilities offered by a weak-perspective approach and behaves in a manner that is in close correspondence with human performance in M&SFM tasks. It consists of a novel weak-perspective-based method operating at small visual angles and a complementary, perspective-projection-based method operating at larger visual angles.

Algorithms↗