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Biomedical subjects

C T Brighton

Publications and source records attributed to C T Brighton.

At least 91 records · Page 5Linked to original sources

Temporal course of bone formation in response to constant direct current stimulation.

Reactive, post-traumatic bone formation in response to intramedullary insertion of a polytetrafluorethylene-coated, 28 gauge stainless steel wire was compared with the sequential bone formation seen in response to an identical intramedullary stainless steel cathode delivering 20 microA constant direct current. Animals were studied at days 1, 2, 3, 4, 5, 7, 9, 11, 14, 17, and 21 after wire insertion. Point count analysis revealed progressive bone formation beginning as early as day 3 on the constant direct current-stimulated side, progressing steadily through day 21. Control tibia, however, began to show bone formation on day 5 with peaking at day 9 and subsequent bone resorption. The osteogenic response at the 20 microA cathode was statistically elevated above that seen at the control on days 11, 17, and 21.

Animals↗

Amelioration of oxygen-induced osteoporosis in the in vitro fetal rat tibia with a capacitively coupled electrical field.

Near-term fetal rat tibiae were grown in M.E.M. Eagle/NCTC 135/15% newborn calf serum in 5% carbon dioxide and 5, 10, 21, 35, 60, and 90% oxygen for 3, 7, 10, and 14 days. Linear growth of the explants, as measured from macrophotographs of the explants at day zero and each of the days above, was greatest in the lower oxygen concentrations and least in the higher oxygen concentrations. Breaking strengths of the tibial diaphyses were significantly reduced in those explants grown in 60 and 90% oxygen. When the fetal rat tibiae were grown in 60% oxygen for 7 days and were subjected to a capacitively coupled electrical signal (sine wave, 60 kHz, 10 V peak-to-peak output signal; current density and field in the culture dish calculated to be 5.2 microA/cm2 and 0.32 mV/cm, respectively), the breaking strengths and middiaphyseal widths were statistically significantly greater than control tibiae grown in 60% oxygen alone. It is concluded that an appropriate capacitively coupled electrical field can inhibit an oxygen-induced osteoporosis in an in vitro mammalian long bone model.

Animals↗

Fracture healing in the rabbit fibula when subjected to various capacitively coupled electrical fields.

The effect of capacitively coupled electrical stimulation on the healing of midshaft transverse osteotomies of the rabbit fibula is assessed roentgenographically, mechanically, and histologically. The results show that a dose-response curve for capacitive coupling and fracture healing exists and that a 220 mV, 250 microA, 60 kHz applied electrical signal (0.33 V/cm internal electric field) is the most effective signal for fracture stimulation in this model.

Animals↗

Prevention and treatment of sciatic denervation disuse osteoporosis in the rat tibia with capacitively coupled electrical stimulation.

Osteoporosis in the sciatic-denervated rat tibia was both prevented and reversed with a capacitively coupled electrical field. In both the prevention of the development of osteoporosis and the reversal of a previously established osteoporosis, a statistically significant enhancement of wet weight, dry weight, ashed weight, ultimate strength, cortical area, cortical thickness, and a concomitant decrease in cortical porosity occurred in the stimulated, denervated tibiae of the experimental animals compared with the nonstimulated, denervated tibiae of the control animals. These effects exhibited dose-response characteristics. A 60 kHz symmetrical sinewave signal was effective in preventing osteoporosis at a range of 5-10 peak-to-peak, and it was effective in reversing osteoporosis at 10 V peak-to-peak. Reversal of a well-established osteoporosis in laboratory animals has not been reported previously. Continued investigation into the use of a capacitively coupled electrical field in the prevention and treatment of osteoporosis seems warranted from these studies.

Animals↗

Calcium flux and endogenous calcium content in isolated mammalian growth-plate chondrocytes, hyaline-cartilage chondrocytes, and hepatocytes.

The role of chondrocyte mitochondria in endochondral ossification has been the subject of intensive investigation and controversy. The purpose of this study was to quantitate the endogenous calcium content and the maximum capacity for calcium accumulation and release in isolated mammalian growth-plate chondrocytes and hyaline-cartilage chondrocytes. The results indicated that the mitochondria of the isolated growth-plate and hyaline-cartilage chondrocytes possess a greater endogenous calcium content, a greater capacity for calcium accumulation, and a larger labile Ca+2 pool than do the mitochondria of hepatocytes. Growth-plate and hyaline-cartilage mitochondria had an endogenous calcium content of 908 and 142 nanomoles of Ca+2 per milligram of mitochondrial protein. The growth-plate mitochondria had a maximum calcium capacity of 5249 nanomoles of Ca+2 per milligram of mitochondrial protein. In comparison, the mitochondria of hepatocytes had a much smaller endogenous-calcium content and a smaller maximum Ca+2 capacity: twenty-one and 3262 nanomoles of Ca+2 per milligram of mitochondrial protein, respectively. The mitochondrial labile-calcium pool in both growth-plate and hyaline-cartilage chondrocytes was twofold greater than that in the mitochondria of hepatocytes. Chondrocyte mitochondria released approximately 2400 nanomoles of Ca+2 per milligram of mitochondrial protein, whereas hepatocyte mitochondria released 1200 nanomoles of Ca+2 per milligram. These results suggest that the chondrocyte mitochondria are specialized for calcium transport and are important in the calcification of the extracellular matrix of the growth plate.

Animals↗

Treatment of recalcitrant non-union with a capacitively coupled electrical field. A preliminary report.

Twenty-two well established non-unions in twenty patients were treated with a capacitively coupled electrical signal (sine wave, sixty kilohertz, five volts peak to peak) that was applied non-invasively through stainless-steel capacitor plates placed on the skin surface overlying the approximate site of the non-union. The average age of the eleven female and nine male patients in this series was 38.4 years, and the average duration of the twenty-two non-unions was 3.3 years. Seventeen of the non-unions were labeled recalcitrant, meaning that they had failed to heal after either previous bone-grafting or another type of electrical stimulation, or both. Five of the non-unions had not been previously treated. Seventeen (77.3 per cent) of the non-unions achieved solid osseous union after an average of 22.5 weeks of treatment with capacitive coupling. The results in this small series were not affected by the non-union being recalcitrant, by the fact that one patient bore full weight on the extremity in a cast, by the presence of osteomyelitis, or by the presence of remaining metallic internal-fixation devices in the bone. Since capacitive coupling is non-invasive, involves portable equipment, allows full weight-bearing on the lower extremity in a cast, is easy to apply, and does not require precise localization of the capacitor plates, it has distinct advantages over other methods of treating non-union with electricity.

Adolescent↗

Direct current stimulation of bone production in the pony: observations with a diaphyseal osteotomy model.

Electrically induced osteogenesis exhibits a dose response curve and can induce bone formation in the absence of trauma and in nonunions. Electrically induced osteogenesis, using direct electric current (DC) in a third metacarpal diaphyseal osteotomy model, in conjunction with internal fixation and postoperative loading, was investigated. Twelve young adult ponies of mixed sex were divided into 2 treatment groups (A and B) of 3 stimulated and 3 controls each and evaluated, using a specifically designed procedure. Stimulated ponies in both groups were given 20 microA of DC via an implanted bone growth stimulator (BGS); group A ponies were stimulated for 60 days and group B ponies for 120 days. Biocompatibility of the BGS was excellent in all ponies. Radiographically, there was more advanced healing with better vascular development in the ponies stimulated for 60 days compared with controls, but no discernible difference was seen at 120 days. Nuclear medical bone imaging revealed a peak uptake at 4 weeks in stimulated groups and the uptake decreased after 8 weeks. Radiopharmaceutical uptake in stimulated ponies was consistently below control uptake throughout the study. Mean specific gravity (SG) of specimens prepared for testing materials properties for group A and B controls were 2.044 +/- 0.119 and 1.939 +/- 0.065, respectively. The SG for group A and group B stimulated were 1.992 +/- 0.049 and 1.876 +/- 0.031, respectively. The SG of specimens obtained from metacarpi of age-matched control ponies was 2.194 +/- 0.166. The ultimate bending strengths and the flexural moduli of elasticity in 60-day control ponies and stimulated ponies were 57 +/- 8.4, 59 +/- 23.9 MN/m2 and 89 +/- 3.5, 106 +/- 6.5 MN/m2 and in 120-day control ponies and stimulated ponies were 13 +/- 1.0, 13 +/- 3.2 GN/m2 and 13 +/- 2.89, 15 +/- 0.577 GN/m2, respectively. Sixty-day samples and 120-day samples had pending strengths (SU) of 25% and 50% that of unfractured cortex, respectively. These findings indicate that 20 microA of DC stimulation on a diaphyseal osteotomy model may not stimulate sufficient bone production to affect the mechanical properties of the bone. Therefore, based on our research, clinical use of BGS in fresh fracture management cannot be recommended.

Animals↗

Direct current stimulation of bone production in the horse: preliminary study with a "gap healing" model.

The effect of a 20-microA direct-current implantable bone growth stimulator (BGS) on bone production with a "gap healing" model in the horse was evaluated. The right and left 4th metatarsal bones (Mt-4) were used in 7 adult horses to create the "gap healing" model. A 4-mm section of the Mt-4 bone was resected bilaterally in each horse. The BGS was surgically placed into the 7 left Mt-4 defects. The 7 right Mt-4 defects served as controls. Six horses survived the 16-week experimental period. Signs of pain, decreased range of limb motion, or lameness was not observed in any animal during the 16 weeks. None of the animals showed complete healing radiographically. Four stimulated sites showed less periosteal reaction and 2 showed greater reaction than the 6 controls. The greatest amount of periosteal reaction or bone resorption was seen around the screws and plates in both groups. Uptakes of 99mTc-MDP in counts/pixel for control sites and stimulated sites were 7.90 and 8.25 in the "gap defect" and 5.19 and 5.06 in the areas adjacent to the gap defect. The ratio of uptake between the gap defect and adjacent area was 1.5 and 1.58 respectively. Biocompatability of the BGS was excellent; however, 1 horse had a broken cathode wire 5 cm from the generator capsule at 6 weeks. All polyethylene cathode sheaths were fluid filled at 16 weeks. The average mineralization rates were 1.57 +/- 0.34, 1.71 +/- 0.28 mm/day and bone formation activity was 0.0182 +/- 0.171, and 0.0168 +/- 0.0149 mm2/day for control limbs and stimulated limbs, respectively. There was no significant difference between groups in any of the histomorphometric values measured. Direct current (20 microA) did not increase bone production in this experiment. Methods to objectively evaluate electrically induced osteogenesis and a "gap defect" model for BGS research on the horse are discussed. The results provide a basis for additional research on electrical stimulation of fractures in the horse and for dose-response studies.

Animals↗

Electrical stimulation in the treatment of osteonecrosis of the femoral head--a 1-year follow-up.

To date, there is no completely satisfactory method for the treatment of osteonecrosis of the femoral head. "Conservative" management leads to a high failure rate, and surgical results have been inconsistent and disappointing. The study described in this article seeks to evaluate the role of electrical stimulation in conjunction with decompression and bone grafting. A total of 82 hips have been included to date, of which 42 with a minimum follow-up of 1 year have been evaluated. Pain relief and improved function have been noted in the majority of hips operated on, both with and without electrical stimulation. Careful radiologic assessment using a comprehensive new method of evaluation has shown some degree of progression in the majority of cases, however. No effects of electrical stimulation per se have been demonstrated to date. It must be emphasized that this is a preliminary report with a minimum follow-up of 1 year. Final conclusions await the completion of the study, when all patients have been followed for a minimum of 3 years.

Adult↗

Treatment of sciatic denervation disuse osteoporosis in the rat tibia with capacitively coupled electrical stimulation. Dose response and duty cycle.

We determined the dose-response characteristics of a low-voltage, high-frequency, capacitively coupled electrical signal that reverses an established osteoporosis in a rat tibial model with sciatic neurectomy. The electrical signals were delivered by means of stainless-steel gel-coated electrodes. In the first part of the study, the shape (sine wave) and frequency (sixty kilohertz) of the signal were kept constant while the voltage was varied from 0.01 to ten volts, peak to peak. Control osteoporotic and sham osteoporotic animals showed a mean loss of tibial ash weight of 19 and 17 per cent, respectively, twenty-eight days after sciatic neurectomy plus twelve days of no treatment using sham electrodes. Rats that were subjected to 0.25, 0.50, 1.0, 2.5, and 5.0 volts, peak to peak, for twelve days beginning on the twenty-eighth day after sciatic neurectomy all showed mean losses of tibial ash weight that were significantly less than those of the controls. The rats that had a 0.5-volt peak-to-peak signal showed the least mean loss of tibial ash weight (only 6 per cent). We concluded that a capacitively coupled electrical signal, delivered through gel-coated electrodes, can largely reverse an established disuse osteoporosis due to neurectomy in the rat tibia. In the second part of the study, the duty cycles of a sine-wave, sixty-kilohertz, 0.5-volt peak-to-peak signal were varied (12.5, 50, and 100 per cent on), and the wet, dry, and ash weights were determined and compared with those of unstimulated osteoporotic controls. Only the 100 per cent duty-cycle signal was effective in reversing the loss of bone mass in the neurectomized tibiae.

Animals↗

Biosynthesis of a disulphide-bonded short-chain collagen by calf growth-plate cartilage.

Collagen biosynthesis by organ cultures of the hypertrophic zone of calf growth-plate cartilage was studied. It was found that this tissue devotes a large portion of its biosynthetic commitment towards production of a collagen molecule comprising short collagen chains. This collagen is similar to short-chain collagens synthesized by chick-embryo tibiotarsus, rabbit growth-plate cartilage and chick chondrocytes grown in three-dimensional gels. However, in contrast with the collagen synthesized in these three systems, the short-chain collagen synthesized by calf growth-plate hypertrophic cartilage is stabilized by disulphide bonds localized within the pepsin-resistant triple-helical collagenous domains of these molecules.

Animals↗

Zonal analysis of cytoplasmic components of articular cartilage chondrocytes.

The cytoplasmic components of chondrocytes in the various zones of articular cartilage of the medial femoral condyle of adult male New Zealand white rabbits were quantitated from electron micrographs. A progressive increase in the content of endoplasmic reticulum, Golgi apparatus, mitochondria, and electrondense bodies (presumed to be lysosomes) from the tangential zone through the top half of the calcified zone was observed. These organelles then showed a decrease in content in the bottom half of the calcified zone. This was associated with an even greater increase in content of holes in the cytoplasm at that level, providing clear evidence of cellular swelling. Based on these quantitative morphologic studies, it is concluded that the chondrocytes in all zones of articular cartilage are metabolically active, but those cells in the calcified zone show signs of degeneration. The ultimate fate of the chondrocytes in the bottom of the calcified zone is not clear from this study.

Animals↗

In vitro growth of bovine articular cartilage chondrocytes in various capacitively coupled electrical fields.

Isolated articular cartilage chondrocytes from 1- to 3-week-old male Holstein calf knee joints were formed into pellets containing 4 X 10(6) isolated cells and were grown in tissue culture medium (minimum essential medium/NCTC 135) containing either 1 or 10% newborn calf serum (NBCS) in plastic Petri dishes in 5% CO2 and air at 37 degrees C in saturation humidity. On the 4th postisolation day either [35S]sulfate or [3H]thymidine was added to the medium, and the pellets were exposed for 24 h to capacitively coupled electrical fields (10, 100, 250, and 1,000 V peak-to-peak, 60 kHz, sine wave signals). The pellets were then harvested, dialyzed, hydrolyzed, and assayed for DNA, protein, [35S]sulfate incorporation, and [3H]thymidine incorporation. Results indicated that at 250 V peak-to-peak there was a statistically significant increase in [35S]sulfate in 1% NBCS and a statistically significant increase in [3H]thymidine in 10% NBCS. At potentials above or below 250 V no changes were noted. Thus, articular cartilage chondrocytes grown in pellet form can be stimulated to increase glycosaminoglycan synthesis or to increase cell proliferation by an appropriate capacitively coupled electrical field. The importance of the serum concentration in the medium in evaluation of biosynthesis in vitro is noted.

Animals↗

Sequential changes in the mechanical properties of viable articular cartilage stored in vitro.

Viable articular cartilage from the medial femoral condyles of rabbits was stored in vitro in tissue culture medium with various additives and the same site of each specimen was mechanically tested sequentially throughout a 12-day storage period. Indentation testing was performed with instantaneous and sustained loads. Preservation of sustained-load carrying capacity was observed in the condyles stored with additives, indicating maintenance of an intact cartilage matrix. However, initial testing with small sustained loads (preload) showed changes not observed at higher load levels. The changes noted at small sustained initial loads may reflect alterations in cartilage surface structure and may be an early indicator of its mechanical integrity. Chondrocyte viability and proteoglycan content, as measured by 35S incorporation and hexosamine concentration, were unchanged in comparison to fresh articular cartilage.

Animals↗

Characterization of growth plate mitochondria.

The growth plate chondrocyte plays a central role in growth plate function. The purpose of this study was to characterize the respiratory and calcium transport properties of isolated mammalian growth plate chondrocytes and mitochondria obtained from these cells and to quantitate the mitochondrial weight and volume fraction in each zone of the growth plate. A new method was developed for isolation of mitochondria from chondrocyte suspensions. Isolated chondrocyte mitochondria demonstrated an eightfold increase in oxygen consumption in response to calcium and a two- to threefold increase in oxygen consumption in response to adenosine diphosphate. Similar responses were observed in chondrocytes treated with digitonin. The mitochondrial protein content of the growth plate and hyaline cartilage chondrocytes is significantly less than hepatocytes. Conversely, the chondrocyte mitochondrial cytochrome aa3 content is similar to mitochondria from a wide variety of sources. A zonal analysis of the growth plate demonstrates an increase in the mitochondrial weight (protein) fraction from the reserve to the hypertrophic zone whereas the mitochondrial volume fraction decreases from the reserve to the hypertrophic zone. The findings of this study emphasize the dependence of chondrocytes on glycolysis as a prime energy source and support the concept that chondrocyte mitochondria have become specialized in the process of matrix calcification.

Animals↗

Prognostic factors in nonunion of the tibia: an evaluation of 185 cases treated with constant direct current.

The present series represents a retrospective clinical study of 185 cases of nonunion of the tibia. The severity of the injury was important in the development of the nonunion. Primary closure of open injuries was noted to be dangerous and resulted in high incidence of infection, 27 of 37 cases. The distal third of the tibia was the most frequent site of the nonunion. One of the most striking findings in this study was a high incidence (92.4%) of patients presenting with initial delay to weight bearing of greater than 6 weeks. The authors feel that this is a definite contributory factor in the development of nonunion of the tibia.

Adult↗