Esophageal injury from thoracic pedicle screw placement in a polytrauma patient: a case report and literature review.

The authors present a case report illustrating a visceral complication that may occur as result of thoracic pedicle screw placement. The case describes the previously unreported occurrence of esophageal impingement secondary to anterior vertebral body perforation by a pedicle screw at the third thoracic vertebra. This case highlights the challenge of thoracic pedicle screw placement and the importance of preoperatively measuring the maximum anterior-posterior dimension of the vertebral body.

Growth factor modulation of distraction osteogenesis in a segmental defect model.

A model was established in 39 dogs to investigate the growth factor modulation of regenerate bone in distraction osteogenesis. A segment of the diaphysis of the radius was resected unilaterally. An osteotomy was made proximal to the segmental defect to create a transport segment. A monolateral external fixator was applied. After a latency period, the segment was transported across the defect. One week after the transport assembly contacted the distal pin clamp, an ipsilateral osteotomy of the proximal ulna was performed. In 20 dogs, transforming growth factor-beta was injected into the regenerate bone halfway through the transport period. Four dogs were sacrificed before docking, when the regenerate bone was still immature. In specimens harvested halfway through the transport period, evidence was found of intramembranous ossification during distraction. In specimens harvested after the transport assembly contacted the distal pin clamp, evidence was found that the mature regenerate formed by endochondral ossification. Therefore, a combined mechanism of ossification is proposed for this segmental defect model that includes mechanical stimulus for bone differentiation. The one-time administration of transforming growth factor-beta retarded the formation of a stable, united regenerate. It is concluded that transforming growth factor-beta caused an effect opposite to that which was desired.

Evaluation of recombinant human bone morphogenetic protein-2 as a bone-graft substitute in a canine segmental defect model.

A study was performed in dogs to evaluate the dose-response characteristics and effectiveness of recombinant human bone morphogenetic protein-2 with a collagen sponge carrier in a segmental defect model. Twenty-seven dogs underwent bilateral radial osteotomies with creation of a 2.5-cm diaphyseal defect. All received autogenous cancellous bone graft in one defect and a collagen implant in the other. These implants contained recombinant human bone morphogenetic protein-2 at the following doses: group 1 at 0 microg (three dogs, 0 microg/ml total implant volume), group 2 at 150 microg (three dogs, 50 microg/ml), group 3 at 600 ,g (three dogs, 200 microg/ml), group 4 at 2,400 microg (three dogs, 800 microg/ml), group 5 at 0 microg (five dogs, 0 microg/ml), group 6 at 150 microg (five dogs, 200 microg/ml), and group 7 at 600 microg (five dogs, 50 microg/ml). The defects were stabilized with external fixators. The dogs in groups 1-4 were killed at 12 weeks postoperatively, and those in groups 5-7 were killed at 24 weeks postoperatively except for one dog in group 7, which was killed at 48 weeks. Evaluation included monthly radiographs, biomechanical testing, and nondemineralized histology. All 27 radii with autogenous cancellous bone graft and all 19 implants treated with recombinant human bone morphogenetic protein-2 achieved radiographic and histologic union and gross stability. The eight radii treated with collagen carrier alone went on to radiographic and histologic nonunion and were grossly unstable at death. A dose-dependent occurrence of cyst-like bone voids was noted radiographically and histologically. Biomechanical performance tended to be better at the lowest dose studied at 12 weeks, and all three doses performed better than the placebo (p < 0.05) at 12 and 24 weeks. By 24 weeks, radiolucent areas corresponding to histologic bone voids persisted radiographically, although there was evidence of early bone remodeling. This remodeling progressed to 48 weeks in the single animal followed to this time point, although bone voids remained. These radiologic findings were confirmed histologically. Recombinant human bone morphogenetic protein-2 in a collagen sponge carrier has significant osteoinductive activity in this canine segmental defect model. A dose-response relationship is evident, with heterotopic bone and cyst-like void formation at higher doses and a minimum effective dose of 0-150 microg. At 12 and 24 weeks postoperatively, biomechanical parameters achieved by defects treated with recombinant human bone morphogenetic protein-2 were comparable with those of autograft controls and were significantly stronger than those of the placebo (p < 0.05).

Bovine-derived bone protein as a bone graft substitute in a canine segmental defect model.

OBJECTIVES: To evaluate the efficacy of a bone graft substitute in healing of a segmental defect of a weight-bearing long bone. DESIGN: An established canine model was used to perform a blinded, prospective, randomized study of the performance of bone graft substitute implants. This performance was compared with that of an accepted treatment modality (autograft) in a paired fashion. SETTING: An accredited animal research facility. SUBJECTS AND INTERVENTION: Twenty-eight dogs underwent bilateral radial osteotomies with creation of a 2.5-centimeter defect. On one side, the defect in every dog was filled with autogenous cancellous bone graft (ABG). Contralateral defects received, in a blinded, randomized fashion, cylindrical implants of demineralized bone matrix (DBM) allograft or DBM plus a constant dose (3.0 milligrams) of bovine-derived bone protein (DBM + BP). The defects were stabilized by external fixation. Subjects underwent monthly radiographs and were killed at six, twelve, or twenty-four weeks. Regenerate bone was studied by biomechanical testing and histology. Six animals were studied to determine the dose-response characteristics of the protein preparation. Three received implants containing 0.3 milligram of BP (group 1) and three received 1.0 milligram of BP (group 2). These animals were killed at twelve weeks of follow-up. RESULTS: All twenty-eight ABG radii (100 percent) progressed to radiographic union, as did thirteen of thirteen (100 percent) DBM + BP radii compared with only four of fifteen (27 percent) of DBM radii. The difference between union rates was statistically significant (p < 0.05). Mean values for most biomechanical parameters of DBM + BP radii exceeded those of their contralateral ABG controls at twelve and twenty-four weeks, whereas those for DBM implants did not. Histology revealed microscopic evidence of normal bone healing in all ABG and DBM + BP radii, whereas most DBM radii demonstrated nonunions. In the dose-response arm of the study, six of six ABG radii (100 percent) achieved union; zero of three (0 percent) of group 1 and two of three (67 percent) of group 2 radii achieved grossly stable unions. Biomechanical testing was consistent with radiographic results, indicating that the 3.0-milligram dose was the most effective of those studied. CONCLUSIONS: The DBM + BP composite implants were more effective at healing critical-sized segmental defects than DBM alone in this canine model when a 3.0-milligram per implant dose of BP was used. Biomechanical and histologic properties of the regenerated bone formed by DBM + BP implants was comparable to that of cancellous autograft.

Evaluation of bovine-derived bone protein with a natural coral carrier as a bone-graft substitute in a canine segmental defect model.

The efficacy of a bone-graft substitute (bovine-derived bone protein in a carrier of natural coral) in the healing of a segmental defect of a weight-bearing long bone was evaluated. Twenty dogs, divided into two groups, underwent bilateral radial osteotomies with creation of a 2.5 cm defect. On one side of each dog, the defect was filled with autogenous cancellous bone graft. Contralateral defects received, in a blinded randomized fashion, cylindrical implants consisting of natural coral (calcium carbonate) or calcium carbonate enhanced with a standard dose of bovine-derived bone protein (3.0 mg/implant; 0.68 mg bone protein/cm3). The limbs were stabilized with external fixators, and all animals underwent monthly radiographs. They were killed at 12 (group 1) or 24 (group 2) weeks, and regenerated bone was studied by biomechanical testing and histology. Radiographic union developed in all 20 radii with autogenous cancellous bone grafts and in all 10 of the radii with the composite implants. None of the radii with implants of calcium carbonate alone showed radiographic evidence of union. This represented a statistically significant difference between implant types. In addition, calcium carbonate implants both with and without bone protein demonstrated radiographic evidence of near total resorption of the radiodense carrier by 12 weeks. This resorption facilitated radiographic evaluation of healing. Mean values for biomechanical parameters of radii with the composite implants exceeded those for the contralateral controls at 12 and 24 weeks; the difference was statistically significant at 12 weeks. Histology revealed scant residual calcium carbonate carrier at either time in the defects with calcium carbonate implants; however, a moderate amount was present in defects with the composite implants. In these specimens, the residual carrier was completely surrounded by newly formed bone that may have insulated the calcium carbonate from further degradation. The present study used a carrier of granular calcium carbonate reconstituted with bovine type-I collagen to deliver an osteoinductive protein to the defect site. This carrier is of nonhuman origin (eliminating the risk of disease transmission or antigenicity) and resorbs rapidly. In this model, bovine-derived bone protein in a natural coral carrier performed consistently better than the gold standard autogenous cancellous bone graft in terms of the amount of bone formation and strength of the healed defect. This may have implications for removal of hardware or resumption of weight-bearing in certain clinical situations. These data also indicate that coralline calcium carbonate alone represents a poor option as a bone-graft substitute in this critical-sized segmental defect model.

Porous ceramics as bone graft substitutes in long bone defects: a biomechanical, histological, and radiographic analysis.

Three porous ceramic bone graft materials were compared with regard to their ability to heal a 2.5 cm defect created surgically in a bilateral canine radius model. The ceramic materials were analyzed at 12 and 24 weeks after surgery and included tricalcium phosphate, hydroxyapatite, and collagen hydroxyapatite, which contained a mixture of 35% tricalcium phosphate and 65% hydroxyapatite with added collagen. Each material was evaluated alone and with added bone marrow aspirate. All the implants were compared with a graft of autogenous cancellous bone in the contralateral radius. Biomechanical testing and radiographic evaluation revealed that the addition of bone marrow aspirate was essential for tricalcium phosphate and hydroxyapatite to achieve results comparable with those of cancellous bone. Collagen hydroxyapatite performed well without the addition of bone marrow, although the addition of marrow did have a positive effect. Further qualitative radiographic and histological analysis demonstrated that tricalcium phosphate was the only ceramic that showed any sign of degradation at 24 weeks. This observed degradation proved to be an important factor in evaluating radiographs because the radiodensity of collagen hydroxyapatite and hydroxyapatite interfered with the determination of radiographic union. At 24 weeks, tricalcium phosphate with bone marrow was the material that performed most like cancellous bone. In this study, the biomechanical and radiographic parameters of tricalcium phosphate with bone marrow were roughly comparable with those of cancellous bone at 12 and 24 weeks. Tricalcium phosphate was the only implant that showed significant evidence of degradation at 24 weeks by both histological and radiographic evaluations, and this degradation took place only after a degree of mechanical competence necessary for weight-bearing was achieved.

Chromosome telomere integrity of human solid neoplasms.

Eukaryotic chromosomes contain specialized structures at the termini called telomeres. This region of DNA is required for replication and stability of the chromosome. Telomere reduction can contribute to genetic instability and has been described in certain malignancies (e.g., colon, leukemia, giant cell tumor of bone). To determine whether telomere reduction is a generalized phenomenon in malignancies, the telomere integrity of genomic DNA isolated from tumor cells was determined from 39 individuals with 15 different malignancies categorized as musculoskeletal, epithelial, cranial, or other, and peripheral blood leukocytes from the same patient, when possible, or age-matched controls. Significant telomere reduction occurred randomly across histopathologic groups including giant cell tumor of bone, glioblastoma, colon cancer, and Wilms' tumor while telomere elongation occurred in chordoma. The other remaining 10 malignancies do not show significant differences in telomere lengths compared with controls.

Evaluation of ground cortical autograft as a bone graft material in a new canine bilateral segmental long bone defect model.

The recent orthopaedic literature reflects a growing number of bone graft substitutes and osteogenic growth factors under investigation in a number of animal models. We attempted to establish a well-controlled, large animal model of a segmental defect in a weight-bearing long bone by developing a bilateral diaphyseal radial defect model in the canine. We also evaluated the effectiveness of ground cortical autograft as a graft material. Twenty-three adult mongrel dogs underwent bilateral radial osteotomies with creation of a 2.0-2.5-cm diaphyseal defect on each side. All dogs received cancellous autograft (CAN) on one side, nine received no graft material (DEF) on the opposite side, and 14 received morselized cortical autograft (CORT) on the opposite side. Radii were stabilized by external fixation. Animals were followed radiographically at 6-week intervals to evaluate the healing process. Thirteen dogs were sacrificed at short-term follow-up (8-12 weeks postsurgery) and 10 at long-term (16-24 weeks). Biomechanical torsion testing to failure and histological evaluation were performed on each defect. All CAN radii achieved union (100%) while only one of nine DEF radii (11%) and none of 14 (0%) of CORT radii achieved union. Statistically significant differences in biomechanical parameters between both test groups and their corresponding autograft control radii were found. Histology revealed fibrous nonunions in the DEF and CORT radii. These results demonstrate that the bilateral canine radial defect model represents a consistent and reproducible model for bone healing of segmental defects in weight-bearing long bones and that ground cortical autograft is an ineffective graft material.

Effects on pulmonary physiology of reamed femoral intramedullary nailing in an open-chest sheep model.

We have recently developed an open-chest sheep model to monitor and study the effects of major orthopedic procedures on pulmonary physiology. In this pilot study, we focused on reamed intramedullary femoral nailing in animals without pulmonary injury. Details of the model are described herein. The control group consisted of sheep that underwent thoracotomy and invasive monitoring only, while the study group also underwent femoral osteotomy, reaming, and intramedullary nailing. Baseline, postthoracotomy, and post-reaming/nailing values were recorded for mean pulmonary arterial pressure, central venous pressure, left arterial pressure, dynamic compliance, arterial blood gas, mixed venous O2, cardiac index, and mean arterial pressure so that hemodynamic and oxygen transport data could be calculated. Postprocedure values were recorded at hourly intervals for 4 h. A physiologically stable, reproducible model was created. No statistically significant differences were found between the control and experimental groups, indicating no adverse effect of femoral reaming/nailing. In one animal, using echocardiography, pulmonary embolization was documented while reaming and inserting the intramedullary nail. Reamed femoral intramedullary nailing is not detrimental to sheep with otherwise normal lungs. This finding suggests that femoral reaming and nailing in trauma patients without associated pulmonary injuries and otherwise normal lungs may be carried out without risk of inducing significant respiratory complications.

Cytogenetic, telomere, and telomerase studies in five surgically managed lumbosacral chordomas.

Lumbosacral chordomas are rare skeletal sarcomas of the spine that originate from the remnant notochord. The understanding of this human cancer is limited to observations of its clinical behavior and its embryonic link. Thus, we performed chromosome and molecular analyses from five surgically harvested chordomas in an effort to document genetic and biochemical abnormalities which might aid in understanding the tumor biology of this understudied neoplasm. Cytogenetic analysis of the five chordomas revealed normal results in four patients and random abnormalities in only one tumor cell in the 100 cells studied from the fifth patient. A repeat telomeric probe (TTAGGG)50 was hybridized to genomic DNA isolated from chordoma cells (and HeLa cells) and digested with HinfI. The tumor DNA was paired with leukocyte DNA from age-matched controls and revealed telomere elongation in four of the four chordoma patients studied with molecular genetic techniques. Conversely, telomere length reduction has been reported during in vitro senescence of human fibroblasts, giant cell tumor of bone, colon cancer, intracranial tumors, childhood leukemia, Wilms tumor, and in HeLa cells. Telomerase activity (telomerase is required to maintain telomere integrity) was also determined by visualizing the extension of radioactive telomeric repeats on DNA sequencing gels. The telomeric fragments were assembled during incubation of the cytoplasmic extract containing telomerase. Telomerase activity was observed in HeLa (positive control and commercially available cell line), giant cell tumor of bone (positive control tumor cells from living patients), and in chordoma cells from one of the two chordoma patients (but to a lesser degree compared with HeLa). As expected, the chordoma patients' fibroblasts exhibited no telomerase activity.

Telomerase activity and oncogenesis in giant cell tumor of bone.

BACKGROUND: Benign giant cell tumor of bone (GCT) is a primary skeletal neoplasm with an unpredictable pattern of biologic aggressiveness and cytogenetic findings characterized by telomeric associations and telomeric reduction. The role of maintaining telomeric integrity is performed by telomerase. To determine if telomerase activity is present, cell extracts from fibroblasts and tumor cells from five patients with GCT were analyzed and compared with HeLa (a positive control cell line). METHODS: Telomerase activity was detected by visualizing the extension of radioactive telomeric repeats on DNA sequencing gels. Telomere reduction was assessed using southern blot analyses of the restriction enzyme Hinf I digested DNA with a radio-labeled telomere probe. RESULTS: Telomerase or telomerase-like activity was detected in the cell extracts from HeLa and tumor cells. However, GCT telomerase activity varied and was less than that observed in HeLa, but no activity was detected from fibroblasts. In addition, telomere reduction was seen in DNA isolated from both HeLa and GCT but not in fibroblasts or age-matched controls. CONCLUSION: Telomere reduction and telomerase activity may be oncogenic sustaining events required to maintain the transformed phenotype seen in GCT.

Tubular adenoma of the main pancreatic duct.

We report a case of tubular adenoma of the duct of Wirsung with focal villous changes. To our knowledge, this is the 13th reported case of this uncommon neoplasm and the first with a primarily tubular histologic pattern. The patient presented with abdominal pain and diarrhea and was found on endoscopic retrograde cholangiopancreaticography to have a mass in the head of the pancreas, which was confirmed by endoscopic ultrasound. Clinical and pathological features of the 12 previously reported cases are reviewed. Intraoperative testing failed to rule out adenocarcinoma which, in addition to difficulties presented by local anatomic relationships of the tumor, supports wide surgical resection as the preferred surgical solution.

Erectile and copulatory dysfunction in chronically diabetic BB/WOR rats.

The pituitary-testicular axis, penile reflexes, and copulatory behavior were studied in male BB diabetic rats from 10 to 40 wk of diabetes. Serum testosterone was diminished from 18 to 28 wk of diabetes, and the responses to human chorionic gonadotropin stimulation were blunted. Serum luteinizing hormone (LH) in diabetic rats did not differ from that of the control rats before or after LH-releasing hormone stimulation. Serum follicle-stimulating hormone and prolactin levels were also similar to controls. After 26 wk of diabetes, androgen-sensitive reproductive accessory organs were significantly reduced in size. This also was true for the androgen-sensitive bulbocavernosus and ischiocavernosus muscles. Penile reflexes in these animals from 20 to 32 wk of diabetes were consistently reduced in number and demonstrated prolonged latency. Copulatory behavior was evaluated in these animals at 25 and 28 wk of diabetes and revealed a reduced number of BB diabetic rats showing normal behavior at 25 wk of diabetes. At 28 wk of diabetes, mount latency, intromission latency, ejaculatory latency, and the postejaculatory interval were all prolonged compared with controls. In addition, the number of diabetic animals showing normal behavior was reduced compared with controls. These studies demonstrate that chronically BB diabetic rats develop diminished testosterone and erectile dysfunction that precedes ejaculatory dysfunction in a similar fashion as impotence in diabetic men. We suggest that further studies in this animal model may be critical to the better understanding and treatment of impotence in diabetic men.

Comparison of sorbinil and ponalrestat (Statil) diminution of proteinuria in the BB rat.

Diabetic nephropathy leading to kidney failure is a major complication of type I (insulin-dependent) diabetes mellitus and is associated with progressive proteinuria. In the present 6-month study, effects of two structurally dissimilar aldose reductase inhibitors (sorbinil and ponalrestat or Statil) were examined on prevention of proteinuria in insulin-dependent spontaneously diabetic BB rats and compared with age-matched BB resistant controls. Prior to aldose reductase inhibitor treatment, all diabetic BB rats exhibited hyperglycemia (> 300 mg/dl), glycosuria (> 2,000 mg/dl) and 24-hour urinary protein excretion ranging from 5.01 to 11.23 mg/day. After daily administration of ponalrestat (20 mg/kg) for 3 months, 24-hour urinary protein excretion was 11.53 +/- 1.76 mg/day in ponalrestat-treated rats, despite persistence of hyperglycemia (444 +/- 31 mg/dl) and glycosuria (> 2,000 mg/dl); by contrast, urinary protein excretion was 17.76 +/- 2.59 mg/day in the control group of untreated BB diabetic rats. Ponalrestat initially protected against excretion of an array of urinary proteins having molecular weights between 30,000 and 100,000 daltons. These effects sustained throughout the 4th month of treatment, tended to change toward valves in control rats by the 5th month. At the end of 6 months, ponalrestat-treated diabetic rats excreted 18.73 +/- 3.20 mg/day of protein, similar to valves in untreated BB diabetic rats; both demonstrated a 4-fold increase in urinary protein excretion when compared to age-matched BB resistant controls. Proteinuria was attributed to an increase in albumin and an array of proteins having molecular weights between 30,000 and 100,000 daltons.(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrent acute pancreatitis as a complication of cystic fibrosis: report of one case treated surgically.

We present the case of a young woman previously diagnosed with cystic fibrosis (CF) manifested primarily by respiratory symptoms and pancreatic exocrine insufficiency. Only 0.5% of these patients suffer from episodes of recurrent acute pancreatitis, the majority of which respond to conservative treatment. In this case, recurrent episodes of acute pancreatitis made it necessary to perform a surgical pancreatic drainage procedure.

Reversal of proteinuria by sorbinil, an aldose reductase inhibitor in spontaneously diabetic (BB) rats.

Sorbinil, an aldose reductase inhibitor, was examined as a therapeutic agent to arrest and/or reverse proteinuria in 'type 1' insulin-dependent BB rats having spontaneous diabetes mellitus. Prior to sorbinil treatment, diabetic rats exhibited hyperglycemia and increased urinary excretion of urobilinogen, glucose and protein. To assess proteinuria, 24-hour urine samples were analyzed for both total protein and individual components between 30,000 and 100,000 daltons. Daily oral administration of sorbinil (20 mg/kg body weight) was initiated and the aforementioned parameters reevaluated after 1, 2 and 4 months. Results indicated that after 1 month of sorbinil treatment, urobilinogen was normalized in all diabetic BB rats (n = 12), whereas urinary protein excretion was either diminished (67%) or remained constant (16%), despite persistence of hyperglycemia and glycosuria. These therapeutic effects were sustained after 2 months of sorbinil treatment. After 4 months, protein excretion was normalized (6.56 +/- 3.34 mg/24 h), despite persistence of hyperglycemia and glycosuria (n = 12); in marked contrast, 6 untreated rats continued to exhibit proteinuria (17.76 +/- 2.59 mg/day). Sorbinil diminished albumin and a series of urinary proteins between 30,000 and 100,000 daltons, suggesting that sorbinil may represent a therapeutic approach to manage diabetic nephropathy as indicated by diminution of proteinuria.