Spontaneous disc degeneration in the baboon model: magnetic resonance imaging and histopathologic correlation.

Degenerative disc disease is a major source of disability in humans. The baboon model is an excellent natural disease model to study comparable human disease, because baboons are relatively large (adult males 20-26 kg, adult females 12-17 kg), long-lived (30-45 years), well defined, easy to use, and closely related to humans. Published investigations with plain radiographs of disc degeneration in baboons indicated vertebral anatomy and changes that were remarkably similar to those seen in humans, and it would be valuable to determine if magnetic resonance imaging (MRI) and histopathologic evaluation would be useful methods for studying the model, as MRI allows multi-planar visualization of tissues without the use of intravenous contrast and it is superior for evaluating disc hydration, annulus tears, and herniations. The thoracolumbar junctions from 47 randomly selected baboons, ranging in age from 2 weeks to 34 years, were evaluated with MRI and histopathology. Excellent correlation with MRI was observed for changes in disc desiccation, height, and age (P < 0.001). The pathologic analysis demonstrated P values of < 0.001 when comparing histopathology with age and MRI results. All severely degenerated discs seen by MRI were in baboons 14 years of age or older.

TP53 overexpression in radiation-induced osteosarcoma of the rabbit mandible.

The objective of this study was to investigate the incidence of overexpression of TP53 (formerly known as p53) in osteosarcomas occurring after treatment of rabbit mandibles with high-dose external-beam radiation. As part of a protocol investigating hyperbaric oxygen treatment for osteoradionecrosis, 102 female New Zealand-White rabbits underwent mandibular radiation treatments with a total dose of 64 Gy in 20 treatment fractions. Twelve animals died during irradiation, leaving 90 animals at risk for tumor development. These animals were divided into one control group and 12 other groups each treated with different schedules of postirradiation hyperbaric oxygen. All animals were sacrificed after the hyperbaric oxygen treatment, approximately 8 months after completion of irradiation. Seventeen of the 90 animals that survived after irradiation developed high-grade osteosarcomas, for a 19% incidence of malignancy. Tumor sizes ranged from 1-4 cm. Immunohistochemistry staining of the 17 tumors detected a 59% overall incidence of TP53 overexpression. There was no correlation between the intensity of hyperbaric oxygen treatment and development of osteosarcoma. The high incidence and short interval of development of osteosarcoma suggest that the study animals may have had a genetic predisposition to radiation-induced osteosarcoma. Additionally, our data provide further evidence that TP53 mutations may play an important role in radiation-induced osteosarcoma.

"Mandibular and facial reconstruction" rehabilitation of the head and neck cancer patient.

Cancer surgery and its reconstruction today can result in functional and cosmetically supportive results for most patients. Today's better understanding of malignant tumor kinetics has evolved preservative and precision extirpative surgery which has on one hand enhanced cure rates and on the other hand has preserved function and appearance in such patients. Today's reconstructive techniques have a sound basis in wound healing and bone regeneration science so as to be predictable and long lasting. We now consistently reconstruct cancer patients with minimal complications and without adding undue deformity and disability. Within just the past ten years the additional advancement of osseointegrated implants has taken functional results related to chewing force and efficiency to a higher level. These implants provide for an optimal return of eating ability to closely match those with natural dentitions. Such implants have also been taken a step further with their application to facial unit restorations. Today facial units with the excellent tissue color and consistency matches made possible by available elastic materials are worn with confidence and comfort by those who require them. The messy and ineffectual adhesives of the past have been discarded. At the time of this writing the hope for the immediate future is the availability of recombinant human BMP. As the next anticipated advance in complete cancer reconstruction it has the potential to regenerate physiologically normal bone without bone grafting. The reduction in morbidity and operating room time would be an enormous step forward, as would the applicability of reconstruction to more people at a reduced cost.

Surgical correction of severe vaginal introital stenosis in female baboons (Papio sp.) infected with simian agent 8.

Simian agent 8 (SA8) is a neurotropic, endemic alphaherpesvirus in Papio sp. Lesions associated with simian agent 8 infections usually involve the genitalia of sexually mature baboons. In females, secondary bacterial infections may lead to scarring of the vulva and perineum, with resulting vaginal obstruction. Affected baboons are poor breeders and often develop urinary tract infections due to retention of urine in the vagina. Reconstructive vaginal surgery was performed on seven baboons with vaginal obstruction. Four weeks before surgery, 50 mg of Depo-Provera was administered intramuscularly to each animal to arrest the estrous cycle, reduce swelling, and allow adequate surgical exposure of the vagina. Ventral and circular incisions were made around the constricted vagina. The peripheral skin was excised to break down the underlying connective tissue, allowing access to the vaginal mucosa. Healthy vaginal tissue was then opposed to the incised skin edges with 3-0 Vicryl in an interrupted pattern. Once healed, the vaginas remained patent, allowing normal mating and urination. Nine months after surgery, five baboons had healthy infants, and pregnancy was confirmed in the other two animals. The described procedure may allow female baboons previously infertile and at risk of urinary tract infections to be returned to a healthy reproductive state.

Total reconstruction of the temporomandibular joint with cryogenically preserved allograft mandibular condyle, meniscus, and fossa in the adult goat.

OBJECTIVE: The purpose of this study was to determine the feasibility of total temporomandibular joint reconstruction with the use of cryogenically preserved allograft mandibular condyle, disk, and fossa in the adult goat. STUDY DESIGN: This study consisted of an experimental group of 10 adult goats that underwent total resection of their temporomandibular joints. These animals were immediately reconstructed with cryogenically preserved mandibular condyles, disks, and fossa. These allograft were harvested from 10 donor animals matched to the recipient animal with respect to age, sex, and head dimensions. These grafts were harvested and stored at -185 degrees C for several months before implantation. At 2 years after surgery, the animals were killed. They were evaluated, clinically, radiographically, and histologically. RESULTS: Fifty percent of the eight surviving animals had a normal clinically functional joint with an intact superior joint space and viable articular surfaces. CONCLUSION: The authors conclude that this temporomandibular joint reconstruction technique is feasible in the adult goat model and is deserving of further research.

Balloon angioplasty with stent implantation in experimental coarctation of the aorta.

BACKGROUND: Balloon angioplasty of coarctation of the aorta is an effective method of treatment but is complicated by tearing of the aortic intima, formation of aneurysms, and restenosis. Stent placement at the time of balloon dilation could prevent restenosis and could also prevent progression of intimal tears to aneurysms. The purpose of this study was to evaluate the feasibility of balloon dilation and implantation of balloon-expandable stents in an experimental model of coarctation and to examine the effect of stent placement at the site of surgically created stenosis. METHODS AND RESULTS: Coarctation of the aorta was surgically produced in 11 juvenile swine. Simultaneous coarctation angioplasty and stent implantation was performed in 10 animals 34 +/- 7.8 days after surgery. Repeat catheterization was performed 59 +/- 6 days after stent implantation. Five animals underwent reexpansion of stents with subsequent follow-up catheterization. Aortic specimens were examined by light microscopy and scanning electron microscopy. Coarctation angioplasty with stent implantation was successful in all, with an increase in coarctation diameter from 46 +/- 8.5% to 90 +/- 12.2% of proximal aortic diameter (P = .0001). Systolic pressure gradient decreased from 32 +/- 19.8 to 0.5 +/- 2.8 mm Hg (P < .001). All stents were patent at follow-up catheterization, with no evidence of intraluminal thrombosis. Reexpansion in five animals increased the stent diameter from a mean of 77.4 +/- 12.1% to 93 +/- 11.0% of proximal aortic diameter (P = .02). Gross examination of aortic specimens demonstrated formation of neointima over the stent wherever the stent struts were in contact with the aortic wall. The stent occupied a subintimal position and produced minimal compression of the underlying media. Medial compression was noted immediately beneath stent struts, but there was no evidence of intimal or medial dissection. CONCLUSIONS: Balloon angioplasty with simultaneous implantation of balloon-expandable stents is effective in relieving aortic obstruction in experimental coarctation. Reexpansion of the rigid stent can be performed in an area of surgical aortotomy and coarctation without significant intimal or medial injury. Stent implantation may be useful in preventing restenosis and aneurysm formation after angioplasty of coarctation.

Re-expansion of balloon-expandable stents after growth.

OBJECTIVES: The purpose of this study was to evaluate the feasibility of re-expansion of balloon expandable intravascular stents and to examine the gross and histologic effects of re-expansion on vascular integrity. BACKGROUND: Intravascular stents have been used successfully as an adjunct to balloon dilation of congenital pulmonary artery branch stenosis and postoperative stenosis of the pulmonary arteries in children. However, use of rigid stents in children could result in development of relative stenosis at the site of stent implantation with subsequent growth of the child. METHODS: Stainless steel "iliac" stents were placed in the thoracic aorta of 10 normal juvenile swine by a transcatheter technique. Angiography and re-expansion were performed at a mean of 11 weeks (n = 9) and again at 18 weeks (n = 5). After euthanasia, the aortic specimens were removed for gross and histologic examination. RESULTS: Stents were successfully implanted in 10 swine. Re-expansion was successfully performed in each animal at 11 weeks and at 18 weeks. Aortic growth produced a relative constriction of the aorta of 20% +/- 10% (mean +/- SD) at the site of stent implantation at both 11 and 18 weeks. Re-expansion produced a significant increase in mean stent diameter from 10.1 +/- 1 mm to 12.3 +/- 1.2 mm at 11 weeks and from 11.2 +/- 0.7 to 13.5 +/- 1.1 mm at 18 weeks after implantation (p < 0.001). Balloon dilation produced a relative increase in stent diameter of 21% +/- 7% at 11 weeks and 18% +/- 4% at 18 weeks. Stent re-expansion was accompanied by plastic deformation of the neointima without neointimal dissection. Where neointima was thick, there was no evidence of neointimal abrasion, but where neointima was thin, areas of localized neointimal abrasion were observed with focal fibrin and platelet adherence to the stent struts. There was no evidence of medial or adventitial hemorrhage or dissection produced by re-expansion. CONCLUSIONS: Re-expansion of intravascular stents is feasible after growth in juvenile swine without significant injury to neointima, media or adventitia. The results of this study support careful and selective use of intravascular stents as an adjunct to balloon dilation of congenital stenoses in children.

Intermittent gastric dilatation after gastropexy in a dog.

Gastroperitoneal adhesions, which developed after tube gastrostomy in a 3-year-old dog, caused an inverted L configuration of the pyloric antrum and duodenum, resulting in periodic episodes of gastric dilatation. The dog had undergone tube gastrostomy for treatment of gastric dilatation/volvulus, but gastropexy adhesions broke down 27 months later, necessitating a second pexy procedure. Adhesions then developed, constricting gastric outflow and trapping gas in the stomach and proximal duodenum. When the ventral row of adhesions was surgically dissected, the angle between the pyloric antrum and the duodenum was straightened, facilitating flow of digesta. Gastropexy rarely causes the degree of adhesion formation and the complications reported in this dog.

Cardiopulmonary reference standards in the pregnant sheep (Ovis aries): a comparative study of ovine and human physiology in obstetrics.

1. Complete blood counts, respiratory rate, tidal volume, arterial and mixed venous blood gases; heart rate, cardiac output, and arterial, pulmonary artery, central venous and pulmonary wedge pressures were determined in 10 pregnant adult sheep of 42.7-65.7 kg body weight. 2. Arithmetic means, standard deviations, and coefficients of variation were calculated to develop reference values; in addition, the 95% confidence limits for ranges were established. 3. Comparison of derived data with that from non-pregnant sheep shows changes similar to those seen when examining pregnant and non-pregnant humans. 4. These results indicate the pregnant sheep is an acceptable model for human obstetrical research.

Relationship of oxygen dose to angiogenesis induction in irradiated tissue.

This study was accomplished in an irradiated rabbit model to assess the angiogenic properties of normobaric oxygen and hyperbaric oxygen as compared with air-breathing controls. Results indicated that normobaric oxygen had no angiogenic properties above normal revascularization of irradiated tissue than did air-breathing controls (p = 0.89). Hyperbaric oxygen demonstrated an eight- to ninefold increased vascular density over both normobaric oxygen and air-breathing controls (p = 0.001). Irradiated tissue develops a hypovascular-hypocellular-hypoxic tissue that does not revascularize spontaneously. Results failed to demonstrate an angiogenic effect of normobaric oxygen. It is suggested that oxygen in this sense is a drug requiring hyperbaric pressures to generate therapeutic effects on chronically hypovascular irradiated tissue.

Cryogenically preserved adult and juvenile goat mandibular condylar transplantation.

Loss of a functional temporomandibular joint (TMJ) has long been a clinical challenge in both children and adults. Although reconstruction to date has been performed with various prosthetic devices or autogenous costochondral grafts, these procedures have a potential for complications and morbidity. Our studies were performed to determine the feasibility of healing, growth, and long-term function of TMJ reconstruction techniques with cryogenically preserved mandibular allografts in the goat model. This species was chosen because the surgical anatomy and biomechanics of the goat TMJ are very similar to those of the human TMJ. The positive results of the studies and their relevance will be described.

Evaluation of Gore-Tex graft material in the repair of right ventricular outflow tract defect.

Following right ventriculotomy, Gore-Tex PTFE vascular grafts were placed in eight neutered male, 6- to 8-week-old, 8- to 12-kg pigs. Ten to 14 months after surgery each pig was evaluated by right heart catheterization. The swine were sacrificed and the hearts were evaluated grossly and microscopically. Comparison of the mean derived cardiovascular hemodynamic parameters in this group with published data on swine and humans indicated normal cardiovascular physiology. Since there was no gradient across the patched areas, it appears that the patches had no adverse effects on the cardiovascular system of growing pigs over an approximately 1-year time period. In addition, the Gore-Tex appeared to be satisfactory for the repair of right ventricular outflow enlargement. Its relative ease of handling, configuration, and lack of aneurysm formation were advantages over other available materials. However, focal calcification and chronic inflammatory reaction did indicate the possibility of long-term prosthetic failure.

Simulated nasoalveolar palatal defects: a canine model to study bone grafts.

A simple, surgical technique to create a simulated nasoalveolar palatal defect in the canine is described. The procedure has been performed in 60 canines, and we have not experienced closure of the created clefts. The surgically created clefts had to fulfill five criteria: (1) bilateral maxillary alveolar clefts had to exist in each research animal; (2) each cleft had to have a 1-cm bony width; (3) a demonstrable oronasal communication had to be present; (4) each cleft had to be lined by healthy epithelialized mucosa; (5) there had to be functional teeth adjacent to each side of every cleft.

Glutaraldehyde-fixed bovine pericardium for right ventricular outflow enlargement.

Right ventricular outflow tract enlargement using glutaraldehyde-fixed bovine pericardium was evaluated experimentally using the pig model. Twelve piglets (8-16 kg) underwent closure of surgically created, longitudinal right ventriculotomies using premeasured, round, bovine pericardial patches. Half of the animals had pulmonary artery banding to increase right sided pressures. The animals were studied an average of 5.1 months following surgery. Cardiac catheterization was performed on eight animals. Pressure measurements revealed no gradient across any outflow patch, and angiography showed no stenosis or dilatation. There was marked right ventricular hypertension in the banded animals. The hearts from all twelve animals were examined grossly and microscopically. There was endothelialization of all patches with no aneurysm formation. Measurements revealed that most patches had become oval shaped. There was no difference in patch size changes between banded and non-banded animals. The patches showed no significant size change in the longitudinal plane (average from 20.8 mm to 20.3 mm, 6.3% change); however, there was a significant decrease in the transverse size (20.8 mm to 17.3 mm, 16.0%) (p less than 0.001). The change in patch size was probably due to reshaping to conform to the longitudinal ventriculotomy and caused no narrowing. In this study, glutaraldehyde-fixed bovine pericardium appeared to be satisfactory for right ventricular outflow enlargement. Favorable qualities include ease of handling, hemostasis, and no aneurysm formation.

Preliminary observations on the effects of hyperbaric oxygen therapy on western diamondback rattlesnake (Crotalus atrox) venom poisoning in the rabbit model.

Intermittent hyperbaric oxygen therapy has been shown to reduce skeletal muscle necrosis in a compartment syndrome animal model. To study whether intermittent exposure to hyperbaric oxygen augments antivenin therapy in reducing muscle necrosis, we injected sublethal doses of Western Diamondback rattlesnake (Crotalus atrox) venom intramuscularly into the hind legs of New Zealand White rabbits. In this pilot study, the animals were divided into three treatment groups. The first group received one vial of antivenin intravenously, the second group received one vial of antivenin intravenously plus three hyperbaric oxygen treatments, and the third group received no treatments. There were no statistically significant differences among the groups. These preliminary observations suggest that muscle necrosis secondary to Crotalus atrox venom poisoning is not significantly altered either by Antivenin [Crotalidae] Polyvalent at the dose level we used or in combination with intermittent hyperbaric oxygen treatments in this rabbit model.

Cardiovascular hemodynamics in the swine following long-term placement of prosthetic grafts post right ventriculotomy.

1. Heart rate, cardiac output and arterial, pulmonary artery, central venous and pulmonary wedge pressures were measured in eight neutered male pigs of an average of 14 months of age and 145.0-231.0 kg body weight. 2. These measurements were made 10-16 months after right ventriculotomy and placement of Gore-Tex PTFE Vascular Grafts. 3. Arithmetic means, standard deviations and coefficients of variation were calculated and the 95% confidence limits for ranges were established. 4. Comparison of derived data with that from published data on swine and on humans indicated normal cardiovascular hemodynamics in this group. 5. In addition, there was no gradient across the patched area. 6. It appears, therefore, that these patches had no adverse effects on the cardiovascular system of growing pigs.

Transplantation of cryogenically preserved mandibular condyles in the adult and juvenile goat.

Loss of a functional temporomandibular joint (TMJ), due to various causes including tumor resection, joint disease such as osteonecrosis, and injury or trauma, has long been a clinical challenge in both children and adults. It may be a significant problem facing physicians during another war. While reconstruction to date has been performed with various prosthetic devices or autogenous costochondral grafts, these procedures have a potential for complications and morbidity. This procedure could adversely delay the return of military members to a combat unit, or affect their ability to serve as functional members of society. Our studies were performed to determine the feasibility of TMJ reconstruction techniques, healing, and long-term function and growth using cryogenically preserved mandibular allografts in the goat. This species was chosen because the surgical anatomy and biomechanics of the goat TMJ are very similar to that of the human. The positive results of the studies and their relevance to future military medical readiness and civilian medicine will be described.

Sucralfate inhibition of tumor cell implantation in the murine urinary bladder.

Superficial transitional cell carcinoma of the bladder has a 50 to 70% recurrence rate. Recurrences may be related to tumor cell implantation during transurethral resection which disrupts the glycosaminoglycan layer of the bladder. This study demonstrated decreased tumor formation in murine bladders which were pre-treated with sucralfate, a synthetic glycosaminoglycan, prior to tumor cell instillation. These results suggest a possible role for sucralfate as a glycosaminoglycan supplement.