A comparison of short- and long-term intravenous antibiotic therapy in the postoperative management of adult osteomyelitis.

The current standard recommendation for antibiotic therapy in the management of chronic osteomyelitis is intravenous treatment for six weeks. We have compared this regime with short-term intravenous therapy followed by oral dosage. A total of 93 patients, with chronic osteomyelitis, underwent single-stage, aggressive surgical debridement and appropriate soft-tissue coverage. Culture-specific intravenous antibiotics were given for five to seven days, followed by oral therapy for six weeks. During surgery, the scar, including the sinus track, was excised en bloc. We used a high-speed, saline-cooled burr to remove necrotic bone, and osseous laser Doppler flowmetry to ensure that the remaining bone was viable. Infected nonunions (Cierny stage-IV osteomyelitis) were stabilised by internal fixation. In 38 patients management of dead space required antibiotic-impregnated polymethylmethacrylate beads, which were exchanged for an autogenous bone graft at six weeks. Free-tissue transfer often facilitated soft-tissue coverage. These 93 patients were compared with 22 consecutive patients treated previously who had the same surgical management, but received culture-specific intravenous antibiotics for six weeks. Of the 93 patients, 80 healed without further intervention. Of the 31 Cierny-IV lesions, 27 healed without another operation, and four fractures required additional bone grafts. No more wound drainage was needed. Treatment was successful in 91% of patients, regardless of the organism involved. There was no difference in outcome in terms of these variables when the series were compared. We conclude that the long-term administration of intravenous antibiotics is not necessary to achieve a high rate of clinical resolution of wound drainage for adult patients with chronic osteomyelitis.

Interobserver variation in the AO/OTA fracture classification system for pilon fractures: is there a problem?

OBJECTIVES: To evaluate the interobserver variation for the AO/OTA fracture classification system: region forty-three-pilon fractures. METHODS: One senior attending, two fellows (one trauma, one foot and ankle), one junior orthopaedic resident, and one experienced research coordinator independently classified eighty-four sets of radiographs. The evaluator was blinded as to treatment and functional outcome. The radiographs initially used to manage the patients were evaluated; no special radiographs or standardized radiographic techniques were used. The kappa statistic, Williams index, and SAV statistic were calculated. RESULTS: Using the SAV statistic to quantify rater agreement beyond that expected by chance alone, the average chance-adjusted agreement among the raters was 0.57 for fracture type, 0.43 for group, and 0.41 for subgroup. This is equivalent to moderate agreement (0.41 to 0.60). The kappa statistic was used to determine whether there was difficulty with any specific category of the AO type classification among raters for selecting fracture type (A, B, C). Kappa values were 0.49 for type A, 0.58 for type B, 0.57 for type C, all of which were considered adequate. CONCLUSION: These data are similar to others reported for interobserver agreement with the AO/OTA fracture classification and other classification systems. The issue of individual judgement in taking a continuous variable (fracture pattern) and compartmentalizing it into a dichotomous variable (fracture classification system) is highlighted by these data. Determination of fracture types alone (type A, B, or C) would seem to be sufficient for clinical research where fracture severity should be reported as a variable.

Evaluation of new plate designs for symphysis pubis internal fixation.

The purpose of this study was to evaluate and compare biplanar and other newly designed plates used for pubic symphysis internal fixation to other standard plates. Our data demonstrate that neither of the newly designed symphyseal plates, curved (Zimmer four-hole plate with either two or four 4.5-mm cortical screws) nor the biplanar (Zimmer six-hole plate with four 4.5-mm cortical screws in one plane and two 4.5-mm cortical screws in another) significantly reduce motion more than the other plates tested (Synthes two-hole 4.5-mm dynamic compression plate with two 6.5-mm cancellous screws and six-hole 3.5-mm reconstruction plate with four 3.5-mm cortical screws). All of the plate constructs were able to restore motion to nearly that of the intact symphysis pubis and sacroiliac joint. In summary, using the anteroposterior compression disruption pattern and model, the disrupted symphysis does gap under load but has no effect on sacroiliac joint gapping. It does permit increase in relative flexion angles between the wings of the pelvis. All of the plate systems tested restore normal gap motion at the symphysis and normal sacroiliac joint flexion.

Healing of a segmental defect in the rat femur with use of an extract from a cultured human osteosarcoma cell-line (Saos-2). A preliminary report.

Devitalized extracts from cultured human osteosarcoma cells (Saos-2) can induce ectopic bone formation. The ability of an extract from Saos-2 cells to stimulate healing of an operatively created four-millimeter defect in the femoral diaphyses of rats was compared with that of collagen and that of autogenous bone graft. Forty adult rats were randomized into four groups of ten each. In Group 1 (controls), no material was placed in the defect; in Group 2, the defect was filled with pure bovine collagen; in Group 3, it was filled with autogenous graft obtained by morseling of the resected segment of the femur; and in Group 4, it was filled with ten milligrams of extract from Saos-2 cells that was mixed with an equal amount of bovine collagen. Five rats from each group were killed at four weeks and the remaining five, at eight weeks. Each femoral defect was analyzed radiographically and histologically for osseous healing. There was no evidence of healing at either four or eight weeks in Groups 1 and 2. Although there was some new-bone formation in Group 3, none of the defects had united at eight weeks. There was early, almost complete union in all five four-week specimens in Group 4 and complete healing of the defect in four of the five rats assessed at eight weeks. The Saos-2 cell extract was found to be the most effective agent, promoting union by mature lamellar bone within eight weeks.

Superoxide dismutase attenuates effects of platelet-activating factor on gastric microcirculation.

This study examined the effect of Cu-Zn superoxide dismutase (SOD) on platelet-activating factor (PAF)-induced alterations of the gastric microcirculation. In separate experiments using an ex vivo canine gastric segment, changes in vascular resistance, filtration, and circulating neutrophil counts were measured during intra-arterial infusion of PAF (0.12 to 150 nM, n = 6) alone and with SOD (10 U/ml, n = 5). PAF produced dose-related increases in vascular resistance and filtration. SOD pretreatment attenuated changes in these measurements in response to 9 and 38 nM PAF. PAF also produced dose-related increases in the difference between arterial and venous neutrophil counts across the gastric segment. SOD significantly reduced this neutrophil flux at 0.5, 2, 9, and 38 nM PAF. Our results suggest that PAF causes both mucosal ischemia due to increased vascular resistance and microvascular injury as evidenced by increased filtration, as well as enhanced neutrophil adhesion to the microvasculature. The protective effects of SOD suggest that these responses to PAF involve the generation of oxygen-derived free radicals. In addition, these responses to PAF appear to be dependent upon circulating neutrophils.

The mechanism of bone induction and bone healing by human osteosarcoma cell extracts.

Saos-2 cultured human osteosarcoma cells contain an extractable bone inducing agent that can induce heterotopic bone in the muscle of Nu/Nu mice. A semipurified GuHCl extract of Saos-2 cells also can promote healing and complete bony union in otherwise non-healing surgically induced defects of rat femur. Northern blot analyses indicate expression of mRNAs for bone morphogenetic proteins (BMP)-1, 2, 3, 4, 6 and transforming growth factor beta (TGF beta) in Saos-2 cells, and BMP-2, 3, 4, 5, 7 and TGF beta in nonosteoinductive U20S human osteosarcoma cells. Saos-2 cells exceeded U20S cells in expression levels of BMP-1, 3, 4 and TGF beta, whereas U20S cells expressed higher levels of BMP-2, 6 and also expressed trace amounts of BMP-5 and 7 not seen in Saos-2 cells. The authors hypothesize that Saos-2 cells contain an optimal admixture of known bone growth factors plus possible other unknown components that, acting alone or in combination with bone morphogenetic protein and/or TGF beta, can induce bone. Although bone inducing agent-induced heterotopic bones have half lives of only a few weeks, the reparative bone induced by bone inducing agent in femoral defects gives every indication of being permanent and self-sustaining. This suggests a fundamental difference between heterotopic and orthotopic osteoprogenitor cells with those involved in orthotopic bone repair more closely resembling the committed or determined osteoprogenitor cells of marrow as described by Friedenstein.

Subcapital fractures of the femoral neck: prevalence and cause of radiographic appearance simulating pathologic fracture.

OBJECTIVE: Subcapital fractures of the femoral neck are common in elderly persons who have osteoporosis. Occasionally, radiographs of the hip in these patients show a radiolucency in the superolateral, subcapital region of the femoral neck that mimics the features of a pathologic fracture. Our purpose was to determine the prevalence of this finding and the anatomic variations of fracture alignment that cause this appearance. MATERIALS AND METHODS: All subcapital nonpathologic hip fractures (n = 111) that occurred at our institution during a 5-year period were reviewed. Radiographs were available in 100 of these cases. Review of intraoperative biopsy specimens, available in 69 patients, revealed no evidence of neoplasm in any case. In the other patients, follow-up radiographs, clinical evaluation, and pathology reports were used to exclude neoplastic involvement. Preoperative radiographs were analyzed for the presence of findings suggesting a pathologic fracture. Fracture configuration was classified by using the Garden staging system. Cadaveric femurs (n = 6) were fractured and studied radiographically. RESULTS: Seventeen (17%) of the 100 subcapital fractures had a radiographic appearance similar to that of a pathologic fracture. This finding occurred only with Garden stage III fractures (n = 7, 32% of Garden stage III fractures) or Garden stage IV fractures (n = 10, 24% of Garden stage IV fractures). Study of the cadaveric femoral specimens showed that the radiographic appearance simulating a pathologic fracture was primarily caused by external rotation of the distal fracture fragment and was accentuated by displacement between fracture fragments. CONCLUSION: The radiographic appearance of subcapital fractures of the femoral neck unrelated to neoplasm is often similar to that of pathologic fractures. This appearance is caused primarily by rotation of the fracture fragments, and the finding is accentuated by displacement. Recognition of the appearance of subcapital hip fractures mimicking pathologic fractures and knowledge of the cause of this finding are important for prescribing appropriate treatment.

Neutrophils accumulate and contribute to skeletal muscle dysfunction after ischemia-reperfusion.

Skeletal muscles subjected to ischemia and then reperfusion develop contractile dysfunction for reasons that are unclear. We found that rats pretreated with vinblastine 4 days before study had decreased numbers of blood neutrophils and increased gastrocnemius muscle function after ischemia (3h) and reperfusion (4 h) compared with untreated rats or rats treated 4 days before study with saline. By comparison, rats pretreated with vinblastine or saline 1 day before study had increased blood neutrophils and decreased gastrocnemius muscle contractile function after ischemia-reperfusion compared with untreated rats. In addition, numbers of neutrophils in gastrocnemius muscles paralleled numbers of blood neutrophils and correlated with gastrocnemius muscle edema and contractile function after ischemia and reperfusion. The results indicate that neutrophils accumulate and may play an important role in the genesis of skeletal muscle contractile dysfunction after ischemia-reperfusion.

Xanthine oxidase-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle.

We hypothesized that xanthine oxidase (XO)-derived hydrogen peroxide (H2O2) contributes to ischemic skeletal muscle injury during reperfusion. We found that after ischemia (3 h) and then reperfusion (4 h) rat gastrocnemius muscles had decreased contractile function following direct stimulation. Three lines of investigation suggested that XO-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle. First, treatment with dimethylthiurea (DMTU), a highly permeant O2 metabolite scavenger, but not urea, just before reperfusion improved muscle function in legs subjected to ischemia and then reperfusion. Second, gastrocnemius muscles from rats fed tungsten or allopurinol had negligible XO activities and increased muscle function after ischemia and reperfusion. Third, as assessed by measurement of skeletal muscle catalase activity in the presence of aminotriazole, H2O2 was measured during reperfusion of ischemic muscles from untreated or urea-treated rats but not during reperfusion of muscles from rats treated with DMTU, tungsten, or allopurinol.