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Experimental models were created in rat fibula to represent impaired bone healing so that biological deficiencies that cause bone repair to fail or to be delayed may be investigated. These models consist of a 4-mm-long segmental defect, created in rat fibula by osteotomy, and fitted with a 7-mm-long tubular specimen of demineralized bone matrix (DBM) over the cut ends of the fibula. The experiments in this study involved various modifications of the DBM scaffold designed to reduce its osteoinductive activity: steam sterilization (sDBM), ethylene oxide sterilization (eoDBM), trypsin digestion (tDBM), and guanidine hydrochloride extraction (gDBM). Bone healing was evaluated by bending rigidity of the fibula and mineral content of the repair site at 7 weeks post-surgery. The sDBM scaffolds resorbed completely by 7 weeks and hence this model was a nonhealing negative control. Rigidities in the unmodified DBM and tDBM groups were comparable, whereas in the gDBM and eoDBM groups it was significantly reduced. Histologically, in the 4-mm defects repaired with unmodified DBM, direct and endochondral bone formation in the scaffold and the defect resulted in a neocortex consisting of woven and lamellar bone uniting the broken bone by 7 weeks post-surgery. We conclude that the eoDBM and gDBM groups represent failure or delay of the bone repair process when compared with the unmodified DBM group in which the process is analogous to normal bone healing.

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The present study is a retrospective review of the treatment of 12 humeral shaft nonunions by using an intramedullary allograft with compression plating. The average age of the patients was 61 years (range, 36-82 years). Eight cases involved the proximal shaft, 3 cases were at the mid-diaphyseal level, and 1 case was at the distal one third. Follow-up averaged 30 months (range, 12-96 months). Ten patients (83%) went on to uneventful healing at an average of 3 months after surgery. Two failures involving patients with multiple medical conditions occurred secondary to reinjury. Two cases of postoperative radial nerve neuropraxia involved the posterior approach to the humerus. Each resolved with no long-term residual morbidity. One patient developed postoperative adhesive capsulitis of the shoulder that resolved with nonoperative treatment. We feel that a fibular allograft, along with compression plating, can give satisfactory results for humeral shaft nonunions. This technique can be especially helpful in proximal humeral nonunions and in nonunions involving osteoporotic bone. Patients with multiple medical problems at risk for refalls should be protected until complete healing has occurred.

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Bone repair models in animals may be considered relevant to human fracture healing to the extent that the sequence of events in the repair process in the model reflect the human fracture healing sequence. In the present study, the relevance of a recently developed segmental defect model in rat fibula to human fracture healing was investigated by evaluating temporal progression of rigidity of the fibula, mineral content of the repair site, and histological changes. In this model, a surgically created 2-mm-long defect was grafted with a 5-mm-long tubular specimen of demineralized bone matrix (DBM) by inserting it over the cut ends of the fibula. The temporal increase in rigidity of the healing fibula demonstrated a pattern similar to biomechanical healing curves measured in human fracture healing. This pattern was characterized by a short phase of rapidly rising rigidity during weeks 4-7 after surgery, associated with a sharp increase in the mineral content of the repair tissue. This was preceded by a phase of nearly zero rigidity and followed by a phase of slow rate of increase approaching a plateau. Histologically, chondroblastic and osteoblastic blastema originating from extraskeletal and subperiosteal (near fibula-graft junction) regions, infiltrated the DBM graft during the first 2 weeks. The DBM graft assumed the role of a "bridging callus." By weeks 6-8, most of the DBM was converted to new woven and trabecular bone with maximal osteoblastic activity and minimal endochondral ossification. Medullary callus formation started with direct new bone formation adjacent to the cortical and endosteal surfaces in the defect and undifferentiated cells in the center of the defect at 3 weeks. The usual bone repair process in rodents was altered by the presence of the DBM graft to recapitulate the sequential stages of human fracture healing, including the formation of a medullary callus, union with woven and lamellar bone, and recreation of the medullary canal.

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The present study investigated the effect of dietary supplementation of selenomethionine on pulmonary metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Mice were assigned to four groups of 15 each. They were fed a basal AIN93G diet and the basal diet supplemented with 2.5 ppm or 5 ppm selenium as selenomethionine or with 2.5 ppm selenium as selenite for two weeks before and after the intravenous injection of 0.5 x 10(5) tumor cells. At necropsy, the number and size of tumors that developed in the lungs were determined. The number of mice that had > or = 11 tumors was 13, 8, 8, and 6 (p < 0.02 compared with the control), and the median number of lung tumors was 64, 14, 12 (p < 0.05 compared with the control), and 8 (p < 0.01 compared with the control) in the control group and the groups with 2.5 ppm and 5 ppm selenium as selenomethionine and 2.5 ppm selenium as selenite. Dietary supplementation of selenomethionine decreased tumor cross-sectional area and tumor volume compared with the controls. At the same dietary level, selenite had a greater inhibitory effect on tumor size than selenomethionine. These results demonstrate that dietary supplementation of selenomethionine reduced experimental metastasis of melanoma cells in mice and inhibited the growth of metastatic tumors that formed in the lungs. It is concluded that selenomethionine is an active form of selenium that reduces experimental metastasis.

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We investigated the effect of dietary supplementation with isoflavones on pulmonary metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Mice were fed a basal AIN-93G diet or the basal diet supplemented with the isoflavones genistein and daidzein at 113 micromol/kg, 225 micromol/kg, 450 micromol/kg, or 900 micromol/kg for 2 wk before and after the intravenous injection of 0.5 x 10(5) melanoma cells. At necropsy, the number and size of tumors that formed in the lungs were determined. The number of mice that had >15 lung tumors was 17 in the control group, and 16, 15, 13, and 10 in the groups fed isoflavones at 113 micromol/kg, 225 micromol/kg, 450 micromol/kg and 900 micromol/kg, respectively. The latter two were significantly different from the control (P

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Morbidity resulting from the toxicity of chemotherapeutic drugs suggests that novel approaches are worthy of investigation. Development of the use of low intensity magnetic fields as an adjuvant to current treatment regimens to prevent metastatic disease may prove to be efficacious. Using a cell culture model, we have developed a magnetic field (MF) treatment that offers the possibility of lowering the therapeutic dose of these drugs and thereby reducing morbidity. Our studies have found that a low intensity (approximately 2 gauss) MF signal and a relatively low dose (0.1 microg/ml) of Adriamycin (ADR) inhibited proliferation of human osteosarcoma cells by 82%, whereas the MF and ADR acting individually caused only 19% and 44% inhibition, respectively.

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Epidemiologic survey data were used to examine relationships between alcohol use and abuse and the physical and mental health status of elderly public housing residents (weighted n = 865) and to determine the influence that drinking behavior had on mortality. Residents with a current alcohol disorder (4%) were more likely to rate their physical health as fair/poor but had fewer major medical illnesses, functional impairments, and other current psychiatric disorders. Individuals with a current or past alcohol disorder (22%) were more likely than others to die (odds ratio [OR] = 7.5) during the 28-month follow-up period. In multivariate analyses, women with a past alcohol disorder were more likely than lifetime abstainers to die (OR = 21.9). Drinking behavior was not predictive of death in men. The high prevalence of alcohol disorder and its strong influence on mortality in this predominantly African-American female population demonstrate the need for programs designed to prevent and treat alcoholism in public housing developments for the elderly.

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Hyperparathyroidism is commonly seen in patients with end-stage renal disease and less commonly in the primary form. The skeletal manifestations of hyperparathyroidism are the same in both forms and are well described in the literature. We treated a patient from each category. Multiple bony lesions and pathologic fractures were observed. The clinical presentations and radiologic and histologic findings confirmed the diagnosis of hyperparathyroidism and osteitis fibrosa cystica in both patients. Subtotal excisions of the parathyroid glands were done in both patients. Appropriate treatment of the bony lesions and pathologic fractures resulted in healing. Histologic evaluation of the bony lesions indicated an osteoblastic or healing response. The reversal of the histologic pattern in just 5 days and 16 days after parathyroidectomy was noted. In treating such patients, physicians should consider parathyroidectomy as an aid in the overall management of patients.

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The present study investigated the effect of dietary supplementation of flaxseed, the richest source of lignans, on experimental metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Mice were fed a basal diet or the basal diet supplemented with 2.5, 5 or 10% flaxseed for 2 weeks before and after the intravenous injection of 0.75 x 10(5) melanoma cells. At necropsy, the number of tumors that developed in the lungs was counted, the cross-sectional area of tumors was measured and the volumes of tumors were calculated. The median number of tumors in mice fed the 2.5, 5 and 10% flaxseed-supplemented diets was 32, 54 and 63% lower than that of the controls, respectively. The addition of flaxseed to the diet also caused a dose-dependent decrease in the tumor cross-sectional area and the tumor volume. These results provide the first experimental evidence that flaxseed reduces metastasis and inhibits the growth of the metastatic secondary tumors in animals. It is concluded that flaxseed may be a useful nutritional adjuvant to prevent metastasis in cancer patients.

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We evaluated 242 consecutive fractures of the clavicle in adults which had been treated conservatively. Of these, 66 (27%) were originally in the middle third of the clavicle and had been completely displaced. We reviewed 52 of these patients at a mean of 38 months after injury. Eight of the 52 fractures (15%) had developed nonunion, and 16 patients (31%) reported unsatisfactory results. Thirteen patients had mild to moderate residual pain and 15 had some evidence of brachial plexus irritation. Of the 28 who had cosmetic complaints, only 11 considered accepting corrective surgery. No patient had significant impairment of range of movement or shoulder strength as a result of the injury. We found that initial shortening at the fracture of > or = 20 mm had a highly significant association with nonunion (p < 0.0001) and the chance of an unsatisfactory result. Final shortening of 20 mm or more was associated with an unsatisfactory result, but not with nonunion. No other patient variable, treatment factor, or fracture characteristic had a significant effect on outcome. We now recommend open reduction and internal fixation of severely displaced fractures of the middle third of the clavicle in adult patients.

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Tumor-specific chromosomal abnormalities have been identified in several histologic subtypes of sarcomas. Characterization of recurrent chromosomal abnormalities has provided direction for molecular investigations of pathogenetically important genes. Cytogenetic reports of osteosarcoma, the most common primary malignant bone tumor, are relatively rare. In this study, 73 osteosarcoma specimens from 51 patients were cytogenetically analyzed following short-term culture. Clonal chromosomal abnormalities were detected in 47 and included one haploid specimen, 18 near-diploid specimens, 17 near-triploid, 8 near-tetraploid, 1 near-hexaploid, and 2 specimens with multiple clones of different ploidy levels. Examination of the present data and previously published data (111 clonally abnormal osteosarcoma specimens) reveals that chromosomal bands or regions 1p11-13, 1q10-12, 1q21-22, 11p15, 12p13, 17p12-13, 19q13, and 22q11-13 are most frequently rearranged and the most common numerical abnormalities are +1, -9, -10, -13, and -17. Partial or complete loss of the long arm of chromosome 6 also was seen in all cases of the present study and all previously published cases describing structural abnormalities of 6q. Parosteal osteosarcoma, a prognostically favorable osteosarcoma subtype, was characterized by the presence of a ring chromosome accompanied by no or few other abnormalities. Complex karyotypes were seen nearly exclusively in the high-grade lesions. These findings indicate that specific chromosomal bands and/or regions are nonrandomly involved in osteosarcoma and may provide useful clinical information.

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The purpose of the present study was to determine the effect of dietary supplementation of soybean protein isolate (SPI) on experimental metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Four groups of mice were fed a basal AIN-93G diet or the basal diet supplemented with 10%, 15%, or 20% SPI for two weeks before and after the intravenous injection of 0.75 x 10(5) cells. At necropsy the number of tumors that developed in the lungs and their cross-sectional area were determined, and tumor volume was calculated. In the control group, 12 of the 15 mice had > or = 11 lung tumors. In contrast, only 3 or 4 of the 15 mice fed the SPI diets had > or = 11 tumors. The incidence of metastasis was 93%, 60%, 53%, and 53%, and the median number of lung tumors was 53, 2, 2, and 1 in mice fed the basal, 10%, 15%, and 20% SPI diets, respectively. Tumor cross-sectional area and tumor volume of SPI groups were significantly decreased compared with the controls. These results demonstrate that dietary supplementation of SPI reduced pulmonary metastasis of B16BL6 cells in mice and inhibited the growth of tumors that developed in the lungs. It is concluded that soybeans may be a useful adjuvant for preventing metastatic diseases in cancer patients.

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The purpose of the present study was to determine the effect of dietary supplementation of selenite on experimental pulmonary metastasis of B16BL6 murine melanoma cells in C57BL/6 mice by means of an intravenous injection model. Three groups of mice were fed a basal AIN-93G diet containing 0.1 ppm selenium (control group) or the basal diet supplemented with 2 or 4 ppm selenium as selenite (experimental groups). Mice were fed the diet for two weeks before and after the intravenous injection of 0.75 x 10(5) viable tumor cells. At necropsy the number of tumors that developed in the lungs and their cross-sectional area were determined, and tumor volume was calculated. In the control group, 12 of the 15 mice had > or = 1 lung tumors. In contrast, only 4 of the 15 mice in each of the selenite-supplemented groups had > or = 11 tumors. The incidence of metastasis in mice fed the control and the 2- and 4-ppm selenium diets was 93%, 73%, and 53%, respectively. The median number of lung tumors was 53, 1, and 1 in mice fed the basal and the 2- and 4-ppm selenium diets, respectively. Tumor cross-sectional area and tumor volume were significantly decreased in selenite-supplemented groups. These results demonstrate that dietary supplementation of selenite reduced pulmonary metastasis of B16BL6 melanoma cells in C57BL/6 mice and also inhibited the growth of the metastatic tumors that developed in the lungs. It is concluded that selenite may be a useful adjuvant to prevent metastatic diseases in cancer patients.

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Early studies had indicated that tissue repair is initially associated with a lower than normal serum pH that later becomes more alkaline. To determine how tissue pH may affect skeletal healing and mineralization, we used a rat skeletal repair model consisting of a long bone segmental defect grafted with acid-demineralized bone matrix (DBM), a biomaterial possessing both osteoinductive and osteoconductive repair properties. In this study, femoral and tibial diaphyses from young adult Sprague Dawley rats were cut into cylinders approximately 0.5 cm in length, demineralized in acid, perforated to accommodate a needle-type combination pH microelectrode, and grafted around a 0.3-cm-long diaphyseal fibula defect. The pH of repair tissues was recorded at various time intervals up to 28 days postgrafting. Healing and mineralization were monitored histologically and by the ash and calcium content of repair tissues. During the early healing phase, tissue pH was lower than normal serum pH, presumably because of an accumulation of acidic metabolites in tissue fluids. Subsequent pH increases to more alkaline values were accompanied by a rapid mineral deposition phase and a later phase characterized by a slow, gradual increase in tissue calcium content. The results of this study support previous observations suggesting that the pH of repair tissue fluids may play a regulatory role in the healing and mineralization of bone.

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Malignant neoplasms of the geriatric skeleton are either primary or metastatic in nature. The vast majority are metastatic to the skeleton from carcinomas. Rarely, a primary skeletal malignancy, usually a chondrosarcoma or a malignant fibrous histiocytoma, develops in the geriatric patient. This article discusses the presentation, evaluation, and management of these patients. Illustrative cases are presented.

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Fat embolization syndrome is a well-known complication associated with total hip arthroplasty. It is believed to be caused by high intramedullary pressures that occur during cement pressurization and femoral stem placement. Fat embolization syndrome has also been reported with intramedullary reaming and placement of an intramedullary alignment guide during total knee arthroplasty. To our knowledge, there have not been previous reports of fatal fat emboli as a result of uncemented hip arthroplasty. The purpose of this case report is to describe a fatality due to fat embolization following a noncemented bipolar arthroplasty.

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