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Biomedical subjects

A J Weiland

Publications and source records attributed to A J Weiland.

At least 19 recordsLinked to original sources

Vascularized growth-plate transplantation: a comparative study in the rat.

The purpose of this study was to evaluate the influence of hormonal milieu on endochondral growth. This was achieved by transplanting hind limbs of juvenile rats to syngeneic adult rats. Because there is no potential for rejection, the limb can be transplanted between animals of different ages, to study the influence of hormonal maturity on stimulation and cessation of physeal growth and maturation. Tibial length and the histologic appearance of the physis were recorded. Whole vascularized hind-limb transplantation in syngeneic Lewis rats was used. Group 1: Thirty-five transplants between animals of the same age (three weeks old) were performed (isochronografts). Group 2: In 35 procedures, the age of the donor was three weeks old and of the recipient, 15 weeks (heterochronografts). In the first two study groups, the transplanted limb was placed on the dorsal flank of the recipient animal without nerve reconstruction. Controls were the contralateral hind limb of the donor animal. Because the limb was transplanted with loss of femoral and sciatic nerve supply to the dorsal flank position, the effects of denervation and lack of weight bearing were also evaluated. Group 3: Thirty-five limbs in three-week-old animals were transposed to the dorsal flank position, after severing the femoral and sciatic nerves. Analysis of variance of tibial length was used to compare study groups. Limbs transplanted to older animals (heterochronografts--Group 2) achieved the greatest length, 91 percent of normal, and significantly more when compared to Groups 1 (84 percent) and 3 (83 percent) (p less than .005). Growth of the limb was adversely affected by limb position and denervation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Pre-formed vascularized bone grafts using polyethelyne chambers.

Previous work has shown that corticocancellous bone chips placed in a titanium chamber with an arteriovenous vascular pedicle will result in a pre-formed vascularized bone graft. The present study was designed to determine whether these grafts can be transferred as an island or free vascularized bone graft, and to examine the material properties of these grafts. Thirty-two male, New Zealand white rabbits were divided into four groups based on the time of sacrifice following the initial chamber implantation. Injected molded cylindrical polyethelyne chambers, measuring 22 mm long and with an 8-mm inner diameter, were used. Corticocancellous bone chips were placed in the chambers and each chamber was implanted in the mid-thigh, with saphenous vessels running through the chamber. The chambers were implanted into the right and left thigh of each animal. To test the hypothesis of the possibility of transferring this graft as an island or free vascularized graft, ligation of the distal vascular pedicle on one side was achieved at re-exploration at 3, 6, 9, and 12 weeks. The contralateral side served as a control in which the vascular pedicle was not ligated. In the controls, bony bridging between the corticocancellous bone chips was observed after 7 weeks. A solid bone graft was present within the chamber by 10 weeks. However, histomorphometric evaluation indicated significant bone resorption. By 13 weeks, resorption progressed to the point where only small islands of bone remained. Ligation of the distal vessels resulted in thrombosis of the vessels within the chamber. Necrosis of newly-formed bone was observed in the area adjacent to the vascular thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Vascularized bone grafts to the upper extremity. Indications and technique.

Massive autogenous bone grafts with an intact vascular pedicle decrease the time to bony union and immobilization required for treatment of segmental bony defects. These techniques have been shown to be effective in treatment of segmental defects of more than 6 cm after trauma or tumor resection in relatively avascular beds. Additionally, in the upper extremity, the free vascularized bone graft is in the developmental phase for employment in the reconstruction of epiphyseal arrest and congenital radial club hand. There are disadvantages to free vascularized bone transfers compared with conventional techniques. For example, a free vascularized fibular transfer requires a team skilled in microvascular technique, a long operative time (6 to 10 hours), and the sacrifice of a major vessel to the lower extremity. If the anastomosis fails, however, the free vascularized fibula will act as a conventional bone graft, thereby minimizing adverse effects. We think that by proper patient selection, appropriate evaluation and preparation of the bony defect, meticulous microvascular anastomosis, and correct fixation and immobilization of the graft a good outcome can be achieved in those patients with large bony defects that defy the use of conventional methods.

Adolescent

The microvasculature of the triangular fibrocartilage complex: its clinical significance.

The microvascular anatomy of the triangular fibrocartilage complex was investigated in 10 cadaver specimens by histology and tissue clearing (Spalteholz) techniques. It was found that the triangular fibrocartilage of the wrist is supplied by small vessels that penetrate the triangular fibrocartilage complex in a radial fashion from the palmar, ulnar, and dorsal attachments of the joint capsule and supply the peripheral 10% to 40%. The inner (horizontal) portion is avascular, and no vessels cross the radial attachment of the triangular fibrocartilage complex. The results of this study suggest that tears in the periphery of the triangular fibrocartilage complex may have sufficient blood supply to mount a reparative response and, in theory, can be repaired. However, tears that occur in the center and along the radial attachment do not have immediate access to a blood supply and are not likely to heal.

Cartilage, Articular

Relative antigenicity of components of a vascularized limb allograft.

At present, the transplantation of vascularized limb-tissue allografts can be achieved only with generalized host immunosuppression, which results in significant systemic toxicity, thereby precluding their clinical use. A better understanding of the immunogenic mechanisms of these allografts may permit less toxic and thus clinically applicable means of host immunosuppression. In this study, individual vascularized limb tissues (skin, subcutaneous tissue, muscle, bone, and blood vessels) and a whole limb were transplanted microsurgically across a strong histocompatibility barrier in rats. The respective cell-mediated and humoral immune responses generated in the hosts were determined by means of mixed lymphocyte cultures by radioactive 51Cr release assays and compared. No single tissue predominated in the elicited immune response. Rather, the various tissue components interacted with the host immune system in a complex but predictable pattern with differing timing and intensity. Surprisingly, the whole-limb allograft elicited less immune response than did allografts of its individual components. The data presented here also serve as a foundation for further elucidation of the immunogenic mechanisms of vascularized limb-tissue allografts.

Animals

Vascularized muscle allografts and the role of cyclosporine.

This study examined the fate of vascularized muscle allografts using a genetically defined rat model. Its purposes were (1) to analyze the histologic/immunologic responses, (2) to study the effect of cyclosporine on graft survival, and (3) to examine the possibility of inducing tolerance. In rats differing at a major histocompatibility locus, vascularized gastrocnemius muscle transplants were performed based on the sural branches of the femoral artery and vein. Forty-two animals studied were divided into three groups: Group 1, allografts, was treated without cyclosporine; Group 2, allografts, was administered continuous cyclosporine; and Group 3, allografts, was administered cyclosporine for 6 weeks only. Evaluation consisted of gross examination, H&E histology, and immunologic studies (MLC, CML, and complement-dependent 51Cr lysis assay). Lytic units (LU) were derived from the assays and served as the indicator of immune response. Group 1 animals had uniform rejection with intense cell-mediated response (LU 23 to 47) and low humoral response. Group 2 animals had viable allografts throughout with suppressed lytic unit values of 0 to 9 initially, which rose to 14 to 29 at 6 weeks despite continuous cyclosporine treatment. Group 3 animals showed rejection similar to the untreated animals. Autografts were performed as controls and survived indefinitely. Analysis of variance was significant at p less than 0.05. Using a reliable rat model for vascularized muscle allografts, we found that in transplantation across a major histocompatibility barrier, the initial immune response was primarily cell-mediated. Cyclosporine suppressed rejection only when given continuously, and short-term cyclosporine treatment did not induce a tolerant state. These data should be useful for future studies of vascularized muscle allografts.

Animals

Immunologic and ultrastructural changes during early rejection of vascularized bone allografts.

This investigation evaluated ultrastructural changes during the earliest phase of immunologic rejection of vascularized bone allografts in a genetically defined rat model. These results were correlated with the cell-mediated and humoral immunologic responses during this time period. Employing a model for heterotopic allograft transplantation, 33 rats divided into four categories were evaluated. Group I consisted of ungrafted (naive) Lewis and Brown Norway rats; group II consisted of Lewis-to-Lewis vascularized bone isografts; group III consisted of Lewis-to-Brown Norway vascularized bone allografts; and group IV consisted of Lewis-to-Brown Norway vascularized bone allografts in rats receiving cyclosporine (10 mg/kg/day). Experimental animals were sacrificed at 3, 5, and 7 days. Immunologic analysis was performed using a cell-mediated lymphocytotoxicity assay and a complement-dependent cytotoxic antibody assay. The results of this study show that rejection of vascularized bone allografts appears as early as 3 days postoperatively, with osteocytes and vascular endothelium being the first elements affected. This early rejection is probably a manifestation of the humoral response. All changes secondary to rejection were arrested by cyclosporine.

Animals

Vascularized bone allografts: in vitro assessment of cell-mediated and humoral responses.

The immunologic consequences of transplantation of vascularized bone allografts have not been previously characterized. In this study, knee allografts, both vascularized and nonvascularized, were transplanted from Lewis rats to Brown Norway rats across a strong histocompatibility barrier. A total of 66 transplants and 8 control animals were evaluated. The vascularized knee grafts consisted of 1 cm of proximal tibia and distal femur with a minimal muscular cuff isolated on the femoral vessels, and these were transplanted to a heterotopic, subcutaneous position on the abdominal wall of the recipient rat. Nonvascularized allografts (identical but without anastomoses) were transplanted for comparison. The cell-mediated response was measured by lymphocytotoxicity assay, and the humoral response was measured by cytotoxic antibody assay, both employing 51Cr-labeled target cells. The timing and intensity of the immune response differed according to the type of graft. The vascularized bone allografts generated significant cell-mediated and humoral responses as early as 5 days posttransplant. A significant humoral response in nonvascularized bone allografts was not apparent until day 14, while cell-mediated response in these grafts was variable. These findings were correlated with the histologic appearance of the grafted tissue. Cyclosporine, which was administered to one group of vascularized bone allografts, resulted in the suppression of both types of immune responses. The histologic appearance of this group resembled that of isografts transplanted as controls. The clinical application of vascularized bone allografts may offer significant advantages over nonvascularized allografts in the reconstruction of massive bone defects. Complications such as nonunion, fracture, and collapse of articular segments seen in nonvascularized allograft transplantation may be avoided by preservation of the blood supply to the graft. Characterization of the immune response to vascularized bone allografts may subsequently allow the manipulation of the host and/or graft tissue and promote graft incorporation.

Analysis of Variance

Radial shortening for Kienböck disease.

The cases of twenty-nine consecutive patients (thirty wrists) who had radial shortening for the treatment of stages I through IIIB Kienböck disease were reviewed to assess the results of this procedure. Thirteen patients (45 per cent) had a history of trauma, and all thirty wrists had a negative ulnar variance (average, 2.8 millimeters) on radiographs. All wrists were re-examined after an average follow-up of 3.8 years (minimum, two years). At that time, the pain had decreased in 87 per cent of the wrists. Extension of the wrist had improved an average of 32 per cent; flexion, 27 per cent; radial deviation, 30 per cent; ulnar deviation, 41 per cent; and grip strength on the affected side, 49 per cent. Analysis of the radiographs by computer digitization showed no significant changes in the amount of collapse of the lunate at the latest follow-up. In two wrists, there were complications at follow-up (excessive shortening of the radius and non-union of the radial osteotomy). Radial shortening is an effective treatment for Kienböck disease in wrists that do not have degenerative changes in adjacent carpal joints. Pain, range of motion, and strength can be expected to improve, but the radiographic appearance of the lunate changes little, if any.

Adolescent

Scapholunate dissociation in the skeletally immature carpus.

A case of scapholunate dissociation with a dorsal carpal instability pattern is described in a skeletally immature 13-year-old male. The malrotation of the scaphoid was treated by soft tissue reconstruction, with use of a dorsal capsulodesis to provide a dorsal restraint to excessive palmar flexion of the scaphoid. In the skeletally immature carpus, isolated ligamentous injuries are less frequently recognized than epiphyseal injuries. To avoid interference with the successful conclusion of carpal growth, soft tissue reconstruction of deranged carpal relationships is preferable to intercarpal arthrodesis in the skeletally immature patient.

Adolescent

Quantifying the effect of ischemia on epiphyseal growth in an extremity replant model.

Warm ischemia (21 degrees C) of 0, 2, 4, 6, or 8 hours was produced in a modified hindlimb preparation of 35 10-week-old Lewis rats by amputation. Subsequent microvascular anastomoses of each hindlimb to a syngeneic animal was done after which fluorochrome bone labels were administered 5 minutes after operation and on day 14 after operation. Epiphyseal plate growth (that between bone labels) was analyzed histomorphometrically and statistically. Epiphyseal plate growth was found to have a linear inverse relationship to ischemia time with a correlation coefficient (r) of -0.653 and high statistical significance (p less than 0.001). Overgrowth occurred at all ischemic periods except 8 hours, and vascular pedicle patency decreased as ischemia time progressed.

Anastomosis, Surgical

Role of free vascularized bone grafts in the experimentally-induced ischemic necrosis of the femoral head.

In 15 mongrel adult dogs, an ischemic necrosis of the femoral head was produced, following the technique described by Gartsman and colleagues. Five weeks later, a 6- to 8-cm long rib graft was harvested with its vascular bundle and transferred into the previously induced ischemic femoral head. Microsurgical anastomoses were performed for revascularizing the rib graft. Dogs were studied using scintigraphy, blood flow measurements, roentgenograms, angiograms, and histology at four, eight and 12 weeks after grafting. New bone and vascular formation was exhibited throughout the study, as demonstrated by a highly positive scintigraphic activity and the formation of numerous arterial terminal branches arising from the rib graft circulation which entered the femoral head and reached the subchondral plate. The formerly necrotic femoral head bone exhibited osteoblastic activity, viable osteocytes, and well-populated bone marrow. The rib graft was also incorporated into the femoral head. These results suggest that a vascularized bone graft is able to repair a femoral head necrosis, and may be considered a rational approach for clinical purposes.

Anastomosis, Surgical

Inability of donor total body irradiation to prolong survival of vascularized bone allografts: experimental study in the rat.

At the present time, the toxic side effects of recipient immunosuppression cannot be justified for human non-vital organ transplantation. Total body irradiation has proven effective in ablating various bone-marrow-derived and endothelial immunocompetent cellular populations, which are responsible for immune rejection against donor tissues. Irradiation at a dose of 10 Gy was given to donor rats six days prior to heterotopic transplantation of vascularized bone allografts to host animals. Another group of recipient rats also received a short-term (sixth to fourteenth day after grafting), low dose of cyclosporine. Total body irradiation was able merely to delay rejection of grafts across a strong histocompatibility barrier for one to two weeks, when compared to nonirradiated allografts. The combination of donor irradiation plus cyclosporine did not delay the immune response, and the rejection score was similar to that observed for control allografts. Consequently, allograft viability was quickly impaired, leading to irreversible bone damage. This study suggest that 10 Gy of donor total body irradiation delivered six days prior to grafting cannot circumvent the immune rejection in a vascularized allograft of bone across a strong histocompatibility barrier.

Animals

Study of growth kinetics and morphology in limbs transplanted between animals of different ages.

The influence of age and maturity on longitudinal skeletal growth was studied using heterotopic limb transplantation with microvascular anastomoses between syngeneic male Lewis rats of different ages. Longitudinal growth of the tibia and growth plate morphology were compared after transplantation between isochronografts (juvenile-to-juvenile and adult-to-adult), heterochronografts (juvenile-to-adult), and unoperated limbs. Four animals comprised each experimental group, except for the juvenile-to-adult heterochronograft group, which had six animals. Limbs were measured at 2-week intervals until sacrifice at 7 weeks. All transplanted limbs demonstrated significant longitudinal growth with maintenance of growth plate morphology and columnar organization. Despite being subjected to an adult hormonal environment, the juvenile tibias transplanted into adult hosts grew 12.0 +/- 1 mm--not significantly different from the unoperated juvenile controls, which grew 12.2 +/- 1 mm. Adult isochronografts showed continued growth of 3.1 mm, which was not significantly different from the unoperated control. Juvenile isochronografts demonstrated decreased growth when compared to unoperated limbs. Maintenance of growth in juvenile limbs transplanted to adults suggests a permissive effect of the hormonal milieu and that ultimate skeletal length is primarily determined by factors inherent in each physis. The use of vascularized transplantation of limbs in syngeneic animals of different ages offers a unique method of altering the hormonal and maturational milieu of the growth plate.

Age Factors

The effects of different schedules of total-body irradiation in heterotopic vascularized bone transplantation. An experimental study in the Lewis rat.

To evaluate the effects of irradiation on heterotopically placed vascularized knee isografts, a single dose of 10 Gy of total-body irradiation was given to Lewis donor rats. Irradiation was delivered either 2 or 6 days prior to harvesting or subsequent transplantation, and evaluated at 1, 2, and 4 weeks after grafting. Irradiation caused endothelial depopulation of the graft artery, although vascular pedicle patency was maintained throughout the study. Bone graft viability and mineralization were normal. Dramatic changes in the bone marrow were seen that included an increase of its fat content (P less than 0.001), and a concomitant decrease in bone marrow-derived immunocompetent cells. These changes were more prominent in recipients of grafts from day -6 irradiated donor rats. Total-body irradiation did not prejudice the use of vascularized bone grafts, and exhibited an associated immunosuppresant effect over the vascular endothelium and bone marrow. This may be a further rational conditioning procedure to avoid recipient manipulation in vascularized bone allotransplantation.

Animals

Vascularized fibular grafts in the treatment of congenital pseudarthrosis of the tibia.

Free vascularized fibular bone grafts were used in nineteen children, seen consecutively, who had congenital pseudarthrosis of the tibia. The average age was 5.1 years (range, 1.4 to 11.4 years). Sixteen of the patients had been treated with electrical stimulation for at least one year, and the tibia had not united. All but four patients had had at least one previous operative procedure. At an average follow-up of 6.3 years (range, 2.0 to 11.0 years), eighteen (95 per cent) of the nineteen pseudarthroses had healed. The leg-length discrepancy averaged 1.6 centimeters (range, 0 to 4.0 centimeters), but ten tibiae had residual or progressive valgus or anteroposterior malalignment despite bracing. There was minimum morbidity at the donor site.

Bone Transplantation

Unconstrained shoulder arthroplasty. A five-year average follow-up study.

A series of 42 total shoulder arthroplasties and four humeral hemiarthroplasties were performed with either the English-McNab or Neer prosthesis. Retrospective follow-up study averaged five years with a three-year minimum. Preoperative diagnoses included rheumatoid arthritis, osteoarthritis, posttraumatic arthritis, rotator cuff arthropathy, avascular necrosis, failed prosthesis, and congenital dislocation. Postoperatively, pain improved in 94% of shoulders, and active range of motion improved an average of 42 degrees in abduction and 47 degrees in forward flexion. Rotator cuff lesions were correlated with poorer postoperative function. Complications developed in four shoulders (9%) and consisted of humeral component protrusions (two shoulders), loosened prosthesis (one shoulder), and unrecognized, preoperative tuberculous infection (one shoulder). Fifteen glenoid components (36%) and six humeral components (13%) developed lucent lines roentgenographically, but only one glenoid component developed migration.

Adult