Shared phenotypic expression of osteoblasts and chondrocytes in fracture callus.

Endochondral ossification in fracture healing of rats at 4, 8, 11, 14, and 21 days was analyzed using immunological and molecular probes for markers of the chondrocyte and osteoblast phenotype. These markers were osteocalcin, type I and type II collagen, including the probes homologous to the alternatively spliced forms of alpha 1 type II collagen, type IIA and type IIB. Histologic examination was performed on serial sections of the same tissue blocks to correlate cellular morphology with the immunohistochemical and in situ hybridization findings. At the junction of the cartilaginous and osseous tissue, an overlap of phenotype and morphology was noted. At the 8-day time point, the cells with chondrocyte morphology expressed intracellular message for osteocalcin and type I collagen. Immunohistochemical analysis of these cells also demonstrated intracellular osteocalcin. However, high levels of the type IIA collagen mRNA, which has previously been associated with less differentiated mesenchymal precursor cells, were expressed in both chondrocytes and osteoblasts. At the later time point (21 days) there was a substantial decrease in the number of cells displaying shared phenotypic characteristics. In situ hybridization and immunohistochemistry have permitted identification of an overlapping or shared phenotype in osteoblasts and chondroblasts in fracture callus. The findings raise important questions regarding the possible plasticity of mesenchymal cell phenotypes within the dynamic environment of fracture healing. Additional examination of these issues will further define factors involved in origin, differentiation, and maturation of bone and cartilage cells.

Diminished uptake of 67Ga-citrate in a case of pseudarthrosis.

A 22-year-old man with pseudarthrosis and infection of the right hip was referred for a 67Ga-citrate scan. A striking decrease was seen in normal bone and soft-tissue uptake in the entire right leg compared with the normal limb. Aortic injection of 99mTc-labeled microspheres showed increased trapping in the region of the hip but contrast angiography was unremarkable. Despite clinical imporvement, 67Ga uptake by the right leg on a repeat scan did not return to normal. This case represents the first report of a "photon-deficient" body part on 67Ga scanning.

Distribution of 67-Ga following intravenous administration: effects of disodium edetate therapy.

Following intravenous administration of 67Ga-citrate to normal and abscessed rats, the colon content of 67Ga decreased with increasing oral doses of Na2EDTA. The effects observed, however, were not thought to be of potential clinical value.

Atriopeptin in the twin transfusion syndrome.

Atriopeptin, a peptide produced by mammalian atria that promotes diuresis, natriuresis, and vascular changes, was in much higher concentration in the recipient twin than in the donor in two cases of severe twin transfusion syndrome. This finding suggests a possible etiology for the changes seen in twin transfusion syndrome.

Effects of parathyroid hormone-related peptide on chick growth plate chondrocytes.

Parathyroid hormone-related peptide (PTHrP) and parathyroid hormone (PTH) have similar biological effects in vitro that are mediated through the PTH receptor. PTH receptors have been demonstrated in the zone of provisional calcification and the hypertrophic zone of the cartilaginous growth plate. The current study examined the biological effects of PTHrP on chick growth plate chondrocytes. Chondrocytes were exposed to varying doses of PTHrP for 24 h, and the incorporation of radioactive thymidine into DNA was used as an index of proliferation. A dose-dependent stimulation of proliferation was seen, with a maximal 27-fold increase at 50 nM PTHrP. A dose-dependent stimulation of cAMP was seen, with a maximal effect at a dose of 50 nM. Proteoglycan synthesis, measured by incorporation of radioactive sulfate, was stimulated, with a maximal effect of 65% at 1 nM. Collagen synthesis and alkaline phosphatase activity from both cellular and matrix vesicle sources decreased in a dose-dependent fashion, with a maximal inhibition of approximately 50% of the control value. The physiologic significance of the PTH and PTHrP-responsiveness of growth plate chondrocytes is uncertain at the present time. It is possible that PTH or PTHrP, or both, act as a systemic, developmental modulator of cellular proliferation and differentiation in the growth plate.

Changes in the expression of type-X collagen in the fibrocartilage of rat Achilles tendon attachment during development.

This study histologically and immunohistochemically demonstrated developmental changes in cell morphology and expression of type-X collagen in the attachment of the Achilles tendon to the calcaneus in the rat. Although the site of attachment in the mature rat showed a well organized, direct insertion that was composed of tendon, fibrocartilage, calcified fibrocartilage, and bone, this four-zone structure was not observed in the immature 1-week-old rat. Formation of fibrocartilage was observed at 2 weeks, together with the hypertrophy of chondrocytes and the appearance of the secondary center of ossification. Type-X collagen was not detected either in chondrocytes in the attachment area at 1 week or in hypertrophic chondrocytes at the attachment at 2 weeks. In the 3-week-old rat, the secondary center of ossification extended to the area of attachment and type-X collagen was detected both in cartilage spicules within the secondary center of ossification and in cells found at the attachment adjacent to the secondary center of ossification. A four-zone structure had been established by 6 weeks and remained through 20 weeks. After 6 weeks, type-X collagen was identified both in the attachment of the tendon and beneath the calcaneal fibrocartilage. Type-X collagen is produced by cells in transitional zones between calcified and noncalcified tissue, such as the interface between articular cartilage and subchondral bone. In these areas, the expression of this protein persists through maturity and is not transient.

Biomechanical evaluation of early fracture healing in normal and diabetic rats.

Diabetes mellitus has been shown to alter the properties of bone and impair fracture healing in both humans and animals. The objective of this study was to document changes in the structural and material properties of intact bone and bone with healed fractures in diabetic rats compared with nondiabetic controls after 3 and 4 weeks of healing. Rods were inserted in the right femurs of control rats and rats with streptozotocin-induced diabetes, and the femurs were fractured in a standardized procedure and then allowed to heal for 3 and 4 weeks. After death, all femurs were mechanically tested to failure in torsion. The degree of healing was quantified for each animal by normalizing mechanical parameters for the femur with a healed fracture with those for the intact contralateral femur. At both time points of healing, diabetic rats exhibited inferior healing compared with that of control animals in terms of failure torque, failure stress, structural stiffness, and material stiffness of the femur with the healed fracture relative to the intact contralateral femur (p < 0.05). Our results demonstrate that the recovery of structural and material strength in femurs with healed fractures in diabetic rats is delayed by at least 1 week compared with that in controls.

Use of an articulated external fixator for fractures of the tibial plafond.

We performed a prospective study of forty-nine displaced fractures of the tibial plafond in forty-eight patients managed, at three centers, with an articulated external fixator placed medially across the ankle joint. Forty ankles had interfragmental screw fixation of a reduced articular fracture, and fourteen ankles had bone-grafting. The average duration of external fixation was twelve weeks. All of the fractures healed (one after delayed bone-grafting). There were no infections in any of the operative or traumatic wounds over the tibia. Two wound infections over the fibula resolved with treatment. Eight patients were managed with antibiotics for a pin-site infection, and two patients had curettage and débridement of a pin site in the hindfoot after removal of the fixator. Thirty patients (thirty-one ankles) completed two-year data sheets at an average of thirty months after the injury. The average ankle score was 67 points. Twenty-one patients had grade-0 or 1 osteoarthrosis and nine had grade-2 or 3. One ankle had been treated with an arthrodesis. These data suggest that the prevalence of early complications associated with severe fractures of the tibial plafond and their treatment can be decreased with use of an articulated external fixator combined with limited internal fixation. We concluded that this technique of external fixation is a satisfactory technique for the treatment of these fractures.

Mechanical considerations for the syndesmosis screw. A cadaver study.

The purpose of this study was to examine the mechanical necessity of using a syndesmosis screw to supplement rigid internal fixation of the fibula and medial malleolus in the treatment of pronation-external rotation fractures. The legs of thirty embalmed and five fresh cadavera were dissected and mounted through the tibia to a frame so that multiple radiographs could be made with a constant relationship between the specimen and the x-ray apparatus. A standardized pronation-external rotation load was applied to the foot, and widening of the syndesmosis was studied on mortise radiographs that were made after each experimental step. On the basis of previous investigations, we developed a model for pronation-external rotation injuries that included disruption of the syndesmosis and interosseous membrane up to the level of the fibular fracture. Accordingly, multiple repaired fibular fractures could be simulated at several levels in the same specimen by incremental proximal division of the interosseous membrane. Specimens were separated into two groups. Group I consisted of thirteen specimens in which the deltoid ligament, syndesmosis, and interosseous membrane were serially sectioned in 1.5-centimeter increments. Group II (ten sections) was subjected to the same protocol, except that the deltoid ligament was kept intact until the final step. The five fresh specimens were sectioned in the same way as those in Group I. In Group I, since the simulated pronation-external rotation injury included a deltoid tear, rigid medial fixation was not possible; accordingly, there was rigid fibular fixation only.(ABSTRACT TRUNCATED AT 250 WORDS)

Tumor localization by tumor infiltrating lymphocytes labeled with indium-111 in patients with metastatic renal cell carcinoma, melanoma, and colorectal cancer.

BACKGROUND: Adoptive immunotherapy with autologous tumor infiltrating lymphocytes (TIL) is a promising approach for cancer bio-therapy. One issue, however, is whether such cells actually migrate to sites of tumor after intravenous infusion. There have been several reports of tumor uptake of radiolabeled TIL in patients with metastatic melanoma, but efforts to visualize tumor with radiolabeled TIL in other tumor types reportedly have been unsuccessful. METHODS: Eight patients with metastatic cancer (5 renal, 2 melanoma, 1 colon) received an intravenous infusion of 2 to 100 billion autologous TIL, including 50 million TIL which had been conjugated to 500 microCi Indium-111, co-administered with interleukin-2 (IL-2). One patient received 1 gm/m2 of cyclophosphamide one day prior to TIL; seven patients received interferon alpha 2b for 4 days prior to receiving TIL. Total body gamma camera imaging, including single photon emission computerized tomography (SPECT), was performed at 24 and 48 hours. RESULTS: All eight patients had demonstrable uptake of 111-Indium-labeled TIL into one or more known sites of tumor. There were no known sites of tumor which were not imaged. Metastatic sites imaged included bone, brain, mediastinal and perihilar lymph nodes, lung and liver parenchyma, abdominal periaortic nodes, and a pelvic mass. One patient served as a negative control in that the TIL scan was negative at a time when she had no evident disease, but a few weeks later had a positive TIL scan which lead to a diagnosis of axillary recurrence. CONCLUSION: Uptake of radiolabeled TIL, whether CD8+ or CD4+, by metastatic renal cell carcinoma and other carcinomas was similar to that previously reported in melanoma. Pretreatment with cyclophosphamide was not a prerequisite for imaging, and TIL uptake did not predict tumor response.

Gallium-67 imaging to localize urinary-tract infections.

To differeniate upper from lower-tract urinary infections, 73 patients were imaged with 67Ga citrate. Renal uptake of the radioisotope occurred in pyelonephritis (documented in 47 patients by ureteral cathieterization, bladder washout, or histology) with an accuracy of 86%. There were 15% false-positives and 13% false-negatives. 67Ga may prove to be a clinically valuable test in the diagnosis of pyelonephritis. Results are promptly available 24 hours after injection, and it is non-invasive test that can safely be repeated to follow recurrent infections.

Hindfoot pain treated by a leg-hindfoot orthosis. A case report.

This case report describes an orthotic management option for the treatment of persistent subtalar and ankle joint pain in a patient with rheumatoid arthritis. Orthotic design, principles of control, and methods of application are discussed in addition to the advantages and disadvantages of prefabricated and custom-formed orthotic devices.

Lower extremity compensations following anterior cruciate ligament reconstruction.

BACKGROUND AND PURPOSES: Several studies have demonstrated that patients with knee injury scored within a normal range during one-legged hop tests, yet showed quadriceps femoris muscle weakness with non-weight-bearing isokinetic testing. This study evaluated lower-extremity kinetics while subjects performed a single-leg vertical jump (VJ) and a lateral step-up (LSU) in an attempt to explain this phenomenon. SUBJECTS AND METHODS: Using a motion analysis and force platform system, hip, knee, and ankle extension moments of 20 subjects with anterior cruciate ligament (ACL) reconstructions and 20 matched subjects were measured while they performed an LSU and a VJ. RESULTS: An analysis of variance revealed that the knee extension moment of the ACL-reconstructed extremity was lower than that of the uninjured and matched extremities during the LSU, VJ take-off, and VJ landing. However, there was no difference in summated extension moment (hip + knee + ankle) among extremities during the LSU and VJ take-off. The summated extension moment of the ACL-reconstructed extremity during VJ landing was less than that of the uninvolved and matched extremities. CONCLUSION AND DISCUSSION: These results suggest that the hip or ankle extensors may compensate for the knee extension moment deficit. The decrease in summated extension moment in the ACL-reconstructed extremity during VJ landing represents inadequate attenuation of landing forces, which may expose the skeleton and joint structures to injury.

Atherosclerosis of the lower extremity and free-tissue reconstruction for limb salvage.

Atherosclerosis of the lower extremity frequently leads to limb-threatening ischemic soft-tissue wounds. Over the past 44 months, 30 selected patients with arterial disease documented by angiography were treated with combined vascular reconstruction and free-tissue transfer for limb salvage. Soft-tissue defects occurred on the plantar and dorsal surfaces of the foot and distal tibia with significant bone, tendon, or joint exposure. Thirteen patients had osteomyelitis. Eighteen patients underwent simultaneous soft-tissue and vascular reconstruction, while 12 patients underwent delayed soft-tissue reconstruction. The free-flap tissues included the rectus abdominis flap in 13, the latissimus dorsi flap in 7, the radial forearm flap in 5, the scapular flap in 3, and the omentum flap in 2. Autogenous venous bypass was performed to the popliteal segment in 6 patients and the infrapopliteal arteries in 18. Five patients had inadequate outflow for complete vascular reconstruction and were treated with proximal vein grafts directed into the free flap. Twenty-two patients (73 percent) had successful free-tissue transfer and bypass graft patency and were independent ambulators over the mean follow-up period of 22 months. Of the 8 unsuccessful reconstructions, 3 patients had early free-flap and graft failure. Five patients developed new areas of ischemic disease despite graft and flap patency. All 8 patients were treated with amputation; 7 never regained ambulation. The combined application of vascular and free-flap soft-tissue reconstruction for the threatened ischemic lower extremity has produced excellent functional results in the majority of our patients.

External fixation of tibial plafond fractures: is routine plating of the fibula necessary?

OBJECTIVES: To determine the advantages and disadvantages of plating an associated fibula fracture in tibial plafond fractures treated with external fixation that spans the ankle. STUDY DESIGN: Retrospective clinical review. METHODS: The incidence of treatment complications and the outcomes achieved were compared between two groups of patients with tibial plafond fractures and associated fractures of the fibula. Both groups were treated by a uniform technique of monolateral external fixation. One group, consisting of twenty-two patients with twenty-two fractures, had plate fixation of the distal fibula and the other group, thirty-one patients with thirty-two fractures, had no fibular fixation. RESULTS: The demographics of the two groups, including sex, fracture classification, and number of open fractures, were similar. The outcome of the two groups for radiographic arthrosis and clinical ankle score, measured at minimum two-year follow-up, showed no statistically significant difference. The total numbers of complications were not statistically different between the two groups (p = 0.15), but the types of complications varied. Group I had eight complications: five fibular wound infections, two fibular nonunions, and one angular nonunion. Group II had seven complications: six angular malunions and one tibial wound infection. CONCLUSION: Open reduction and internal fixation of the fibula fracture in tibial plafond fractures treated with external fixation that spans the ankle is associated with a significant rate of complications, and good clinical results may be obtained without fixing the fibula.

Guidelines for teaching the foot and ankle in an orthopaedic residency.

Orthopaedic graduate medical education includes evaluation and treatment of problems of the foot and ankle. The challenges of managed care, podiatry, and institutional resources have reshaped the way we educate orthopaedic residents as managers of disorders of the foot and ankle. The most useful tools acquired in residency will be those that establish a strong medical and surgical foundation in problems of the foot and ankle and foster lifelong adaptation of new knowledge and techniques.

Rank order analysis of tibial plafond fractures: does injury or reduction predict outcome?

We investigated the effects of severity of initial injury pattern and the quality of the articular reduction on outcome of displaced intra-articular distal tibial fractures, using a series of 25 patients who were treated with articulated external fixation and limited internal fixation, which provided a spectrum of reduction quality. Outcome was assessed by clinical ankle scores and radiographic arthrosis. The results demonstrate the rank order method to be a reliable means of stratifying severity of injury and quality of reduction. Neither injury nor reduction correlated with clinical ankle score. Reduction had a significant correlation with radiographic arthrosis. We conclude that the rank order method is useful in stratification of fracture patients, and that factors other than injury pattern and quality of articular reduction are important in determining outcome of patients with this severe articular injury.