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Biomedical subjects

H T Aro

Publications and source records attributed to H T Aro.

At least 55 records · Page 3Linked to original sources

Incorporation and clinical results of large allografts of the extremities and pelvis.

The results of implantation of 37 large deep-frozen allografts with 29 osteoarticular grafts of the extremities and pelvis following the resection of malignant or aggressive benign bone tumors were evaluated at followup (mean, 6 years; range, 2.5-20 years). The patients had excellent or good results in 62% of all cases according to the Mankin-Waber functional rating score, and a corresponding rating of 81% in the Musculoskeletal Tumor Society Score. Benign versus malignant disease rated 83% and 76%, respectively, in the Musculoskeletal Tumor Society Score, and 67% and 46%, respectively, in the Mankin-Waber score. Radiological and nuclear medicine (single-photon emission computed tomography) studies and histological biopsies indicated that the incorporation, perfusion, and replacement with new bone was only partial and of a low degree. Late degenerative cartilage and sclerotic changes occurred in 20 of 29 cases with osteoarticular grafts. The best functional results were achieved with knee osteoarticular allografts (81%-88%) compared with modest results in the proximal humerus (69%) and hemipelvis (57%) according to the Musculoskeletal Tumor Society Score rating. Chemotherapy did not influence the union or infection rate of the allografts. In the 4 cases (11%) with infection, all grafts could be salvaged, but the functional results were only 63% in the Musculoskeletal Tumor Society Score. The overall complication rate was high (57%); graft-related complications occurred in 43%, including fatigue fractures in 27%. There were no cases of nonunion at the host graft junction. Clinical rejection did not occur. These clinical results may be improved in the future by new technology that uses bone substitutes, growth factors, and bone morphogenetic proteins.

Adult↗

A standardized experimental fracture in the mouse tibia.

The increased use of transgenic mice as experimental animals provides new opportunities to study the biology of fracture repair. We have developed a technique for the production of a standard closed experimental fracture in the mouse tibia. A 0.2 mm stainless-steel rod was introduced into the medullary cavity and the pre-nailed tibial shaft was fractured by an impact device, which resulted in a reproducible transverse or slightly oblique fracture pattern. The intramedullary rod maintained axial alignment, and the fractures united without displacement. On the basis of measurements of callus geometry, four-point bending tests, biochemical analyses, and quantitative histology, the progress of callus formation and remodeling occurred in a predictable sequence of healing phases. The ultimate bending loads of the fractures increased with time, reaching 74% of the strength of intact control tibias in 4 weeks. The stiffness values of the fractures returned to normal levels and, as determined radiographically, the fractures united by external callus in 4 weeks. Radiographically, callus size, cross-sectional callus area, and callus mass peaked at 2 weeks and decreased thereafter, indicating the start of external remodeling. Histologically, the amount of mesenchymal tissue was maximal at days 5 and 7. The callus cartilage area peaked at day 9; at its maximum, it accounted for 46% of the total callus area. Early periosteal formation of membranous new bone, followed by endochondral ossification, resulted in a linear increase of callus bone during the healing process. The healing sequence of the mouse tibial fracture was similar to that seen in the rat tibia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of axial dynamization on bone healing.

The effects of early dynamization (physiologic axial compression) on canine fracture healing at six weeks were studied. Bilateral transverse mid-tibial osteotomies were created and initially stabilized with a 2-mm gap using relatively rigid external fixators. Seven days after osteotomy, the telescoping mechanism of one of the fixators on each dog was released (dynamized), resulting in physiologic loading of the osteotomy, while the contralateral fixator remained locked as a rigid control. The dynamized osteotomy closed, and increased functional weight bearing resulted from 3 weeks on. Radiographically the amount of periosteal callus increased over time, but no difference in callus size was seen between the dynamized fractures and the controls. Torsional mechanical testing found the dynamized osteotomies to be significantly stiffer, and they tended to tolerate more maximum torque than the controls. Microscopic evaluation found no difference in the volume of the periosteal and endosteal calluses or in the tissues constituting them. However, a significantly greater proportion of the dynamized osteotomy gap was filled with new bone. These results suggest that dynamization in this delayed union model improved fracture healing by reducing fracture gap size and increasing weight bearing, not by altering the pathway of fracture healing.

Animals↗

Lisfranc joint injuries: trauma mechanisms and associated injuries.

A retrospective review of the roentgenograms of 750 patients treated in our institution for tarsometatarsal joint injuries or metatarsal fractures over a 10-year-period was performed. Injuries of the Lisfranc joint were found in 66 patients (9%). Twelve patients (19%) had a total dislocation, 47 patients (71%) a partial dislocation, and seven patients (11%) a subtle injury of the Lisfranc joint. Four main groups of trauma mechanisms were identified (low-energy injuries, falls from a height, direct crush injuries, and high-energy vehicular crashes). Lisfranc joint injuries caused by low-energy injuries (21 patients) were as frequent as those caused by high-energy vehicular crashes (22 patients). There was no apparent relationship between the mechanism of injury and the type of Lisfranc joint dislocation. All patients except three had associated metatarsal fractures, most commonly in the second metatarsal. The location of associated metatarsal fractures was different from that in patients with metatarsal fractures alone (p < 0.001). Fractures, dislocations, or fracture-dislocations of midtarsal bones (cuneiforms, cuboid, navicular) occurred in 26 patients (39%). Multiple metatarsal fractures and midtarsal bone injuries were more frequent in high-energy vehicular crashes than in low-energy injuries (p = 0.016 and p = 0.033, respectively). In 23 patients (35%), the treatment had been focused on multiple metatarsal fractures or midtarsal bone injuries without full appreciation of the concomitant Lisfranc joint incongruity. Increasing the knowledge of normal foot anatomy and the appreciation of the risk of Lisfranc joint injury even in seemingly trivial stumbling accidents obviously may improve the diagnosis and treatment of these potentially disabling injuries.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Cortical bone reactions at the interface of external fixation half-pins under different loading conditions.

The pin-bone interface is the weakest link in the mechanical stability of external skeletal fixation. In this investigation, a canine model was used to characterize the nature of cortical bone reactions at the pin-bone interface. Unilateral external fixators were applied to the tibiae of 61 dogs using six tapered cortical half-pins. The pins were inserted after predrilling both cortices, and pin insertion torque was measured. A transverse or oblique osteotomy was performed in each tibia and stabilized under different gap conditions. Unrestricted weight bearing was allowed immediately after surgery. Sequential functional evaluations of the animals and biweekly roentgenograms of the pin tracks were done. Pin removal torques were recorded at the time the animals were killed at different time periods. Pin tracks were analyzed using quantitative tetracycline histomorphometry and microradiography. The results showed that cortical bone undergoes extensive creeping substitution around external fixation half-pins. New bone accounted for approximately 43% of the intracortical space along the pin track, and cortical bone porosity showed a fourfold increase compared with intact bone value. This cortical bone remodeling resulted in a time-related decrease of pin removal torque (p < 0.001). In inherently unstable oblique osteotomies, and less in stable rigidly fixed transverse osteotomies, immediate postoperative weight bearing caused bone thread resorption and adverse cortical bone remodeling at the entry cortex of external fixation half-pins. The unicortical loosening of half-pins that became evident during the first month of fixation obviously represents a consequence of micromotion and local bone yielding failure caused by high dynamic stresses of the pin-bone interface. Effective precautions should be taken to reduce such stresses.

Animals↗

Clinical use of bone allografts.

Modern techniques of bone allograft surgery provide a treatment modality for management of difficult skeletal defects. In oncological limb-salvage surgery, allograft reconstructions permit re-establishment of skeletal continuity and function after a wide resection of bone tumour. Bone allografts are increasingly used in salvage of difficult bone stock deficiencies following failed total joint replacements. Union between the allograft and the host bone takes place slowly and the use of autogenous bone graft at the graft-host junction is recommended for induction of repair. Internal repair (revascularization and substitution of the original graft bone with new host bone) also progresses slowly and seems to be confined only to the superficial surface and the ends of the graft. Biomechanically, a massive allograft may serve a structural function in the absence of advanced revascularization and creeping substitution processes. Infection of an allograft is a disastrous complication, whereas non-union of the graft-host junction and fracture of the graft are amenable to surgical treatment. Osteochondral allografts tend to show gradual deterioration of the articular cartilage with time, necessitating occasionally late resurfacing arthroplasty. It is evident that there is more active immune response to osteochondral grafts than was thought previously. Bone allografts induce cell-mediated and antibody-mediated cytotoxicity specific for donor antigens similar to that seen after organ transplantations. Not only the basic mechanisms of bone allograft rejection but also the clinical features of bone allograft rejection are poorly characterized. Clinically, new non-invasive imaging techniques should be applied in determining the metabolic activity of bone in order to find the optimal loading of healing allografts. Although the clinical results of massive bone allografts are still not completely predictable, the method has proved to be a technically and biologically feasible alternative for non-biological skeletal reconstructions.

Arthroplasty↗

Gene expression at graft-host interfaces of cortical bone allografts and autografts.

The healing processes of autogenous and frozen allogeneic cortical bone grafts were compared in rats. Two unicortical defects created in the proximal metaphysis of the tibia were autografted or allografted with blocks of cortical bone. The biomechanical properties of the graft-host junction and the time-related changes of the expression of genes coding for Type I, II, III, and X collagens and osteonectin were determined at one, two, four, and eight weeks. The strength of the allograft-host bone union was lower than that of autografts at the early stage of incorporation but the difference diminished by eight weeks. Northern analysis of graft mRNAs demonstrated a strong expression of Type I collagen and osteonectin genes at the beginning of autograft incorporation. The allografts showed a lower expression of the corresponding genes at one and two weeks, but the difference diminished thereafter. The gene coding for Type III collagen showed a temporary expression at two weeks both in allografts and autografts, probably because of the formation of inflammatory fibrovascular stroma provided by the host bone at the graft-host interface. No expression of cartilage-specific Type II and Type X collagens were observed, demonstrating that the healing in both grafts proceeded through primary bone healing. Compared with cortical-cortical junctions of autografts, the graft-host interfaces of allografts exhibited a reduced osteoinductive process and a slower increase of union strength.

Animals↗

Regulation of extracellular matrix genes during fracture healing in mice.

The expression of several collagens, cartilage proteoglycan core protein (aggrecan), and osteonectin was investigated during healing of standardized fractures of the mouse tibia. Total RNA was extracted from fracture calluses and normal bone, and analyzed by Northern hybridization using specific cDNA probes. Based on the predominant fibrillar collagen type expressed, three phases of fracture healing were observed. Type III collagen expression characteristic for the inflammatory stage increased first, followed by Type II collagen expression indicative of the cartilaginous reparative phase, and by Type I collagen production, characteristic for the ossification and remodelling stages. Type IX collagen and aggrecan expression coincided with Type II collagen expression during the chondrogenesis. The mRNA for Type X collagen, a marker for hypertrophic chondrocytes during endochondral ossification, occurred somewhat later than that of other cartilage-specific genes. Osteonectin mRNA was present throughout the healing process and peaked during rapid new bone growth. This study confirms that the pattern of gene expression in the murine system is similar to, but somewhat faster than, other species analyzed (rat, rabbit, human).

Aggrecans↗

Biomechanics and biology of fracture repair under external fixation.

The major factors determining the mechanical milieu of a healing fracture under external fixation, and thereby the mechanism of union, are the rigidity of the selected fixation device, the fracture configuration, the accuracy of fracture reduction, and the amount of physiologic stresses dictated by functional activity and loading. Bone healing problems encountered in fractures stabilized externally merely reflect the severity of the local soft-tissue and periosteal injury and should not be attributed to the inherent features of the fixation modality. Although some surgeons have had reservations concerning the use of external fixation for fracture treatment, based mainly on concerns of pin-tract infection and fracture nonunion, much of the clinical experience and basic science research results have proven the reverse. Many of the potential benefits of external fixation, such as the change of fixation stiffness, are not yet fully appreciated. Additional research and well-organized clinical trials must be performed. Pin-tract problems can be controlled, but the surgeon using such a device must be familiar with the techniques and follow the established regimens during postoperative care. One common mistake is to assume that external fixators, especially those of the simpler unilateral configuration, are easy to use and do not require learning or mastering the surgical techniques until the time of application. Periodic examination and radiographic evaluations are also essential to adjust conditions of the fracture site. The importance of balancing the biomechanical properties and the biologic consequences of different external fixation modalities has been demonstrated. Understanding this knowledge and the techniques of application associated with external fixation is the prerequisite to successful treatment. Some of the basic biomechanical information related to external fixation and bone fracture union is still unknown. This lack should provide the impetus for surgeons, bioengineers, and medical scientists to continue collaborative basic and applied research. Furthermore, by recognizing the proper cell mediators and the physical means to stimulate these cellular elements, the bone fracture healing process may be modulated, regardless of the fixation technique. The result of such effort should provide new modalities to improve fracture management.

Animals↗

Bone-healing patterns affected by loading, fracture fragment stability, fracture type, and fracture site compression.

The major factors determining the mechanical milieu of a healing fracture are the rigidity of the selected fixation device, the fracture configuration, the accuracy of fracture reduction, and the amount and type of stresses occurring at the bone ends dictated by functional activity and loading at the fracture gap. Of the effects of these factors on fracture healing and remodeling in the canine tibia under unilateral external fixation, the two most significant factors in promoting periosteal callus formation were the amount of physiologic loading as dictated by the body weight and the presence of a significant fracture gap. Uniform axial loading and motion, performed at two or four weeks, did not increase callus formation but did reduce the existing fracture gap. The time-related diminution of periosteal callus (external remodeling) was related to the progress of cortical healing. Cortical reconstruction was fast in stable transverse fractures and delayed in unstable oblique fractures. Motion with loading tended to promote external callus maturation in secondary bone healing. Intracortical new bone formation and porosity were related to the healing pattern and not to the loading magnitude. Endosteal new bone formation showed a strong correlation with the presence of a fracture gap. In terms of torsional strength and energy absorption at failure, the fractures healing through a combination of primary and secondary bone union mechanisms showed the mechanical strength of the healing bone closest to intact bone.

Animals↗

Gene expression during bone repair.

Detailed understanding of the basic events in fracture healing constitutes a foundation for the development of new approaches to stimulate bone healing. Since the fracture healing process repeats, in an adult organism, several stages of skeletal growth in the same temporal order, it offers an interesting model for developmental regulation of cellular phenotypes and tissue-specific genes. Molecular biology has introduced new methods to study the regulatory phenomena during the process of fracture repair. Gene technology has also produced purified growth factors for research, which will help to understand their roles in fracture healing. This review summarizes data on the regulation of genes coding for extracellular matrix components and growth regulatory molecules during fracture healing. The information available focuses on the sequential expression of genes coding for collagens, proteoglycans, and some other matrix proteins during secondary (callus) healing. The temporal and spatial appearance of the different connective tissue components, mesenchyme, cartilage, and bone, are closely linked to the expression of genes coding for their characteristic constituents. Members of the transforming growth factor-beta superfamily, such as the bone morphogenetic proteins (BMP), are currently the most interesting ones among the factors that regulate chondrogenesis and osteogenesis. In the coming years, the availability of new cloned probes combined with sensitive analytical methods, as reviewed here, will add greatly to our understanding of the various aspects of gene expression during bone repair. This information should provide answers to some of the unresolved questions in fracture callus development.

Animals↗

Healing of microvascular free skin flaps in irradiated recipient tissue beds.

This laboratory study compared the biomechanical and biochemical healing of microvascular free skin flaps in irradiated and nonirradiated recipient areas. In the adult rat, the skin of the right groin region was exposed to a single fraction dose of 20 Gy, using a linear megavoltage accelerator. The left groin was shielded. One week after radiotherapy, the left femoral artery and vein were divided, and an anastomosis was created in situ at the site of the epigastric pedicle. The epigastric skin flap was crossed over to replace the central area of the irradiated skin in the contralateral right groin. The healing of the interface between the irradiated recipient skin and the transferred free epigastric flap was studied at 4 weeks. A comparison was made with the microvascular free flaps of nonirradiated control animals. An additional group of control animals was used to verify the retarding effect of the 20-Gy radiation dose on wound healing. In control animals, the single dose of 20 Gy decreased the tensile strength of standardized surgical wounds by 23% (p = 0.03). Clinical healing of the transferred microvascular free flaps between the irradiated and control recipient areas was comparable, and the flaps showed no significant differences in the mechanical incorporation. The biochemical assays of the DNA, RNA-ribose, total nitrogen, and hydroxyproline contents of the flap showed an increased concentration of proteins (total nitrogen) expressed per cell count (DNA) (25%, p = 0.04), reflecting the excessive accumulation of organic matrix and a relatively decreased number of cells in irradiated recipient tissues. We conclude that there are no major differences in the healing capacity of microvascular free skin flaps between irradiated and nonirradiated recipient areas.

Animals↗

Synovial fluid leukocytosis in bacterial arthritis vs. reactive arthritis and rheumatoid arthritis in the adult knee.

In this comparative analysis of laboratory data, we examined the characteristics of synovial fluid leukocytosis in eighty adult patients with bacterial arthritis, reactive arthritis or rheumatoid arthritis of the knee joint. Synovial fluid leukocyte count and the percentage of polymorphonuclear cells seemed to perform well as a discriminator between bacterial infection and acute flare of the underlying disease in patients with rheumatoid arthritis. In contrast, there were no definite difference in the intensity of synovial fluid leukocytosis between patients with bacterial arthritis caused by living bacteria and patients with reactive arthritis probably caused by bacterial antigens.

Adolescent↗

Minor axial shortening of the radius affects outcome of Colles' fracture treatment.

Functional disability after a Colles' fracture was correlated to the degree of axial shortening of the radius measured at the site of distal radioulnar joint. According to the sum of demerit points, the functional end result was unsatisfactory (fair or poor) in 4% of the patients with an acceptable anatomic result, in 25% of the patients with grade 1 shortening (corresponding to a shortening of 3 to 5 mm), and in 31% of the patients with grade 2 shortening (shortening of more than 5 mm). The results suggest that even a minor axial shortening of the radius, without concomitant malalignment of the articular surface, carries an increased risk of permanent disability.

Colles' Fracture↗

Healing patterns of transverse and oblique osteotomies in the canine tibia under external fixation.

Healing patterns were compared between transverse and 60 degrees oblique osteotomies in canine tibiae stabilized under external fixation. Under similar in vitro testing conditions (osteotomy ends in contact), the axial stiffness of the oblique osteotomy under external fixation was 45% of the paired transverse osteotomy. Under torsion and bending, the two sides exhibited similar fixation rigidity. The animals put significantly less weight on the oblique side than on the transverse side in the early phases of bone healing (p less than 0.05 for static and p = 0.024 for dynamic weight bearing). The osteotomy bending stiffness at 60 days (in vivo) and the torsional stiffness of osteotomy union measured after sacrifice at 90 days were significantly higher on the transverse side (p = 0.013 and p = 0.016, respectively). Intracortical new bone formation was significantly higher on the transverse side (p less than 0.01), indicating a difference in the rate of cortical healing and remodeling. The average pin removal torque was significantly lower on the oblique side (p less than 0.05), a sign of increased pin loosening. In the clinical situation, unstable oblique or spiral fractures should be protected from weight bearing even under stable external fixation due to the delayed recovery of bone union stiffness property as well as increased pin tract problems.

Animals↗

Macrophages in trauma-induced myositis ossificans.

The basic cellular mechanisms of different forms of myositis ossificans are poorly known. In the current experiment the nature of the early (24-168 h) inflammatory cell reaction preceding trauma-induced myositis ossificans was studied. New bone formation was induced in the vastus intermedius region of the rabbit quadriceps muscle by means of immobilization and daily passive mobilization. Before the start of treatment, a cell harvesting device (viscose cellulose sponge in a silastic tube) was implanted in the region of interest. The opposite intermedius muscle and a standardized surgical skin wound served as the control sites. The results showed a significantly prolonged invasion of macrophages into the ossifying intermedius muscle as compared with the control intermedius muscle. It is hypothesized that microinjury and subsequent muscle necrosis cause the invasion of macrophages, and these cells respond to the conditions of the traumatized muscle under passive mobilization by releasing osteogenic growth factors.

Animals↗

Internal remodeling of periosteal new bone during fracture healing.

A closed fracture model of the rat tibia was employed to study internal remodeling of periosteal new bone during fracture repair. Static histomorphometric parameters of osteoid surface (or perimeter) and eroded surface (resorption surface) were used as indicators of appositional bone formation and resorption of bone trabeculae, respectively. Intracortical remodeling at the fracture site was evaluated using quantitative tetracycline histology and microradiography. The extents of osteoid and eroded bone surfaces did not differ significantly in the periosteal woven new bone in the early phases of fracture healing. Later on, the periosteal new bone had significantly more osteoid surface than eroded surface (p less than 0.001). The number of osteoclasts also decreased significantly over time during fracture healing (p = 0.028). Cortical bone showed a continuous increase of porosity (p less than 0.01) between 1 and 6 weeks after fracture. These results suggest that there is a time-related change in the balance of periosteal bone formation and resorption during the progress of fracture repair. We hypothesize that this change was related to the restoration of bony continuity. Further studies are, however, needed to indicate the histomorphometric features of periosteal new bone in fracture nonunions.

Animals↗

Mechanical characteristics of an upper-extremity external fixator.

Static and fatigue tests of the small Orthofix unilateral external fixator frame and its main components were performed. The use of six pins increased torsional rigidity, but this configuration failed at lower bending loads when compared to the four-pin configuration, reflecting the uneven holding strength of the pin clamp on three pins. The ball joint maximum torsional resistance was reduced by 27.2%, and the maximum bending resistance was decreased by 35.2% after first failure loading of a fatigue test. The strength of the ball joint returned to the normal level after replacement of the cam and bushing with new components. The locking strength of the fixator body telescoping mechanism was high and did not change during repetitive failure loading. Hence, the fixator should be applied under the four-pin configuration, placing pins in the outer slots of the clamps as recommended by the manufacturer. The frame stability is governed by the performance of the ball joint, and its locking cam should be tightened periodically. If the ball joint locking position starts to migrate from its initial position, the cam and bushing should be replaced.

Arm↗