The effect of a single early high-dose vitamin D supplement on fracture union in patients with hypovitaminosis D: a prospective randomised trial.

AIMS: To evaluate the effect of a single early high-dose vitamin D supplement on fracture union in patients with hypovitaminosis D and a long bone fracture. PATIENTS AND METHODS: Between July 2011 and August 2013, 113 adults with a long bone fracture were enrolled in a prospective randomised double-blind placebo-controlled trial. Their serum vitamin D levels were measured and a total of 100 patients were found to be vitamin D deficient (< 20 ng/ml) or insufficient (< 30 ng/mL). These were then randomised to receive a single dose of vitamin D3 orally (100 000 IU) within two weeks of injury (treatment group, n = 50) or a placebo (control group, n = 50). We recorded patient demographics, fracture location and treatment, vitamin D level, time to fracture union and complications, including vitamin D toxicity. Outcomes included union, nonunion or complication requiring an early, unplanned secondary procedure. Patients without an outcome at 15 months and no scheduled follow-up were considered lost to follow-up. The t-test and cross tabulations verified the adequacy of randomisation. An intention-to-treat analysis was carried out. RESULTS: In all, 100 (89%) patients had hypovitaminosis D. Both treatment and control groups had similar demographics and injury characteristics. The initial median vitamin D levels were 16 ng/mL (interquartile range 5 to 28) in both groups (p = 0.885). A total of 14 patients were lost to follow-up (seven from each group), two had fixation failure (one in each group) and one control group patient developed an infection. Overall, the nonunion rate was 4% (two per group). No patient showed signs of clinical toxicity from their supplement. CONCLUSIONS: Despite finding a high level of hypovitaminosis D, the rate of union was high and independent of supplementation with vitamin D3. Cite this article: Bone Joint J 2017;99-B:1520-5.

Osteogenic, stem cell and molecular characterisation of the human induced membrane from extremity bone defects.

OBJECTIVES: The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics. METHODS: Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student t-test (two tailed; p < 0.05 was considered significant). RESULTS: Average PMMA spacer in vivo time was 11.9 weeks (six to 18). Trabecular bone was present in 33.3% of the biomembrane specimens; bone presence did not correlate with spacer duration. Biomembrane morphology showed high vascularity and collagen content and positive staining for the key bone forming regulators, bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2). Positive differentiation of cultured biomembrane cells for osteogenesis was found in cells from patients with PMMA present for six to 17 weeks. Stem cell differentiation showed greater variability in pluripotency for osteogenic potential (70.0%) compared with chondrogenic or adipogenic potentials (100% and 90.0%, respectively). Significant upregulation of BMP2 and 6, numerous collagens, and bone gla protein was present in biomembrane compared with the cultured cell line. Biomembranes with longer resident PMMA spacer duration (vs those with shorter residence) showed significant upregulation of bone-related, stem cell, and vascular-related genes. CONCLUSION: The biomembrane technique is gaining favour in the management of complicated bone defects. Novel data on biological mechanisms provide improved understanding of the biomembrane's osteogenic potential and molecular properties.Cite this article: Dr H. E. Gruber. Osteogenic, stem cell and molecular characterisation of the human induced membrane from extremity bone defects. Bone Joint Res 2016;5:106-115. DOI: 10.1302/2046-3758.54.2000483.

Outcome after fixation of ankle fractures with an injury to the syndesmosis: the effect of the syndesmosis screw.

The purpose of this study was to compare the clinical and radiological outcome of patients with intact, broken and removed syndesmosis screws after Weber B or C ankle fracture with an associated injury to the syndesmosis. We hypothesised that there would be no difference. Of a possible 142 patients who fulfilled our inclusion criteria, 52 returned for clinical and radiological assessment at least one year after surgery. Of these, 27 had intact syndesmosis screws, ten had broken screws, and 15 had undergone elective removal of the screw. The mean American Orthopaedic Foot and Ankle Society ankle/hindfoot score was 83.07 (sd 13.59) in the intact screw group, 92.40 (sd 12.69) in the broken screw group, and 85.80 (sd 11.33) in the removed screw group (p = 0.0466). There was no difference in clinical outcome of patients with intact or removed syndesmotic screws. Paradoxically, patients with a broken syndesmosis screw had the best clinical outcome. Our data do not support the removal of intact or broken syndesmosis screws, and we caution against attributing post-operative ankle pain to breakage of the syndesmosis screw.

Indometacin as prophylaxis for heterotopic ossification after the operative treatment of fractures of the acetabulum.

Our study was designed to compare the effect of indometacin with that of a placebo in reducing the incidence of heterotopic ossification in a prospective, randomised trial. A total of 121 patients with displaced fractures of the acetabulum treated by operation through a Kocher-Langenbeck approach was randomised to receive either indometacin (75 mg) sustained release, or a placebo once daily for six weeks. The extent of heterotopic ossification was evaluated on plain radiographs three months after operation. Significant ossification of Brooker grade III to IV occurred in nine of 59 patients (15.2%) in the indometacin group and 12 of 62 (19.4%) receiving the placebo. We were unable to demonstrate a statistically significant reduction in the incidence of severe heterotopic ossification with the use of indometacin when compared with a placebo (p = 0.722). Based on these results we cannot recommend the routine use of indometacin for prophylaxis against heterotopic ossification after isolated fractures of the acetabulum.

[Magnetic resonance tomogography after cryotherapy of long bones in an animal model]. / Magnetresonanztomographie nach Kryoablation langer Röhrenknochen im Tiermodell.

PURPOSE: To describe the MR findings following cryoablation of long bones. MATERIALS AND METHOD: Cryoablation was performed in femoral and tibial bones of 24 sheep under general anesthesia. MRI of the treated and untreated contralateral bones was performed immediately thereafter and at 2, 4 and 6 months after the cryosurgical procedure. RESULTS: On the MRI performed immediately after cryotherapy, the lesions showed low signal intensities relative to the normal bone marrow on unenhanced T1- and T2-weighted images. At 2, 4 and 6 months after cryoablation, the lesions showed high signal intensities on STIR images, low signal intensities on T1-weighted and heterogeneous enhancement on contrast-enhanced T1-weighted MR images. The femoral lesions decreased in size from 31 +/- 3 mm immediately after the cryotherapy to 13 +/- 4 mm 6 month later and the tibial lesions from 29 +/- 7 mm to 19 +/- 4 mm. CONCLUSION: MRI shows bone marrow lesions immediately after cryotherapy and can easily monitor healing lesions. MR imaging is suitable for following cryotherapy.

Rate of perioperative complications in thermal ablation of bone: an animal trial.

INTRODUCTION: While only few data are available yet for radioablation of bone tissue, the occurrence of bone marrow embolisms during cryoablation has been documented. It was the aim of this study to assess perioperative complication rates of thermoablation in animals using state-of-the-art ablation probes. MATERIALS AND METHODS: Eight adult sheep were placed under general anaesthesia, and using a radioprobe, thermoablation was performed on the medial side of the head of the right tibia. In addition, freezing was performed with miniature cryoprobes on both femurs and the head of the left tibia. Haemodynamic monitoring and determination of blood gases and electrolytes were done intraoperatively. The animals were killed 1 week after surgery, and the ablation sites and lung tissue examined macroscopically and microscopically. RESULTS: None of the animals showed pathological changes in any of these parameters. Blood gases remained unremarkable throughout the operation. All eight animals showed an average drop in haemoglobin of 0.97 g/100 ml. Two animals showed fresh embolisms in the pulmonary vessels. CONCLUSION: Experimental thermoablation of bone tissue in large animals failed to show any significant perioperative complications following surgery. The lung embolisms which did occur were not clinically relevant. The use of mini-cryoprobes or radioprobes as alternative or complementary measures for treating pathologically altered bone tissue seems viable and does not involve any undue risks.

[Changes in stability after cryosurgical treatment of long tubular bones. An animal experiment study]. / Stabilitätsveränderungen nach kryochirurgischer Behandlung an langen Röhrenknochen. Eine tierexperimentelle Studie.

The incidence of spontaneous fractures after cryosurgical treatment is described in the literature. The purpose of this study in the sheep model was to analyze the possibility of minimizing the potential risk of bone failure using a new miniature cryoprobe with minimal tissue traumatism and exact control of the ablation. In each of 24 sheep ablations at the right femur and left tibia were performed by drilling. The ablation at the femur was restricted to an area of 2 cm(2) of only one cortical bone, whereas at the proximal tibia the whole tibial plateau was included. The opposite side, which was treated with analog drillings without cryoablation, served as control. The ultimate bending strength of the femur and the ultimate compression strength of the tibia were examined 2, 4, and 6 months after the operation. After 2 months there was a significant difference ( p<0.05) in the ultimate compression strength between the treated and untreated tibiae, whereas the ultimate bending strength of the treated femora tended to be lower. After 4 and 6 months the side treated with cryosurgery was only marginally weaker than the untreated side. Spontaneous fractures were not observed during the whole experimental period. The good controllability of the freezing procedure and the low iatrogenic weakening of the bone using a modern miniature cryoprobe minimizes the risk of pathological postoperative fractures. After ablation of larger bone sections, the treated extremity should be partially unloaded or managed by osteosynthesis for at least 3 months.

Cryosurgery in long bones with new miniature cryoprobe: an experimental in vivo study of the cryosurgical temperature field in sheep.

AIM: The aim of this in vivo study was to determine whether new miniature cryoprobes provide adequate tissue cooling in long bones by measuring the field of temperature under various conditions. METHODS: Freezings were performed in femoral and tibial bones of 10 sheep under general anaesthesia. Applying one cryoprobe, temperatures of -75 degrees C resp. -51 degrees C could be reached within 0.75 cm resp. 1.00 cm of the probe. RESULTS: Histological examinations revealed compact bone and marrow necroses along the isotherm in all 10 sheep. Using two cryoprobes simultaneously, a mean temperature decrease to -71 degrees C between the two cryoprobes was achieved thanks to the synergistic freezing effect. Looking at consecutive freezes, it was apparent that with similar cryoprobe end temperatures, the temperature dropped faster if the number of freezing cycles was increased. CONCLUSION: In conclusion, it was seen that despite its small diameter, the new miniature cryoprobe delivers adequate in vivo tissue cooling in long tubular bones. Employing the synergistic freezing effect by using two or more cryoprobes simultaneously, efficient in vivo freezing of larger bone segments is also possible. Thus, cryosurgery with the new miniature probes can provide a valuable complement to conventional resection of long tubular bones, and offers a viable alternative to surgical treatment of neoplastic diseases of the skeletal system.

[Detection of air embolism by a re-usable Doppler probe integrated in a central venous line--application in-vivo]. / Wiederverwendbare, in einen Zentralvenenkatheter integrierbare Dopplersonde zur Detektion von Luftembolien Anwendung in-vivo.

PROBLEM: Air embolism frequently occurs under neurosurgical operations performed in the sitting position. Recently we reported the idea of inserting a re-usable doppler probe into a blind-ending lumen of a central venous catheter (Schregel-Volk-Catheter, SVC). In vitro testing in a circulation model showed a high sensitivity: air bubbles as small as 0.5 microliter were reliably detected at a distance up to 4 cm from the tip of the SVC. METHOD: After approval by the local ethics committee pigs were anaesthetised and a cardiopulmonary bypass was connected. During the bypass period a 12 F SVC (Medex Medical, Germany) with one blind-ending lumen was positioned into the proximal vena cava cranialis or vena cava caudalis. An 8 MHz doppler probe (MTB Basler, Suisse) was introduced into the SVC and connected with the doppler device Multi-Dop T (DWL, Germany). Well defined air bubbles (3-6 microliter) were generated by a bubble generator and injected into the right femoral vein or the left vena jugularis interna. RESULTS: All bubbles were reliably detected by the re-usable doppler probe. Embolic events can be documented, counted and quantified by the Multi-Dop T. CONCLUSION: Using SVC's with a blind-ending lumen could improve and simplify the detection of air embolism. We see several advantages (e.g. sensitivity, costs) compared with established methods (precordial doppler, TEE) for detection of air embolism.

Bronchial inflammation in corticosteroid-sensitive and corticosteroid-resistant asthma at baseline and on oral corticosteroid treatment.

BACKGROUND: Pathophysiology of corticosteroid (CS)-resistant asthma remains incompletely understood. OBJECTIVE: To determine if failure of asthma to clinically improve with CS is due to a defective response of airway bronchial inflammation to these drugs. METHODS: Twenty-one asthmatics having a decreased baseline FEV1 that improved >or= 30% with inhaled beta2 agonist got bronchial biopsies before and at the end of an oral CS treatment (methylprednisolone 40 mg daily for 14 days). They were arbitrarily divided into two groups according to baseline FEV1 improvement following this treatment: >or= 23% designated as CS-sensitive (CSS) (n = 10) and < 15% as CS-resistant (CSR) (n = 11). RESULTS: Before oral CS, counts of bronchial mucosa inflammatory cells identified by immunohistochemistry (CD3, MBP, tryptase, CD68, neutrophil elastase and CD25 for lymphocytes, eosinophils, mast cells, macrophages, neutrophils and IL-2 receptors, respectively) were similar in CSS and CSR subjects. Oral CS decreased CD3+ cell counts (medians: 60-20 cells/mm(2); P = 0.014) and MBP+ cell counts (medians: 19-4 cells/mm(2); P = 0.03) in CSS asthmatics, but only tryptase+ cell counts in CSR asthmatics (medians: 30-18 cells/mm(2); P = 0.05). Few bronchial neutrophil elastase+ cells were observed and their counts were similar in the two groups of asthmatics before and when on oral CS (all medians: = 2 cells/mm(2)). CONCLUSIONS: These data show that, in these subjects with moderate to severe asthma, lymphocytes and eosinophils constitute most of the inflammatory cells infiltrating the bronchial mucosa. They also demonstrated that clinical impaired response to CS is associated with a persistent bronchial mucosa cellular infiltrate despite oral CS treatment. Additional studies are required to determine the role of this CS-resistant bronchial inflammation in the impaired asthma clinical response to these drugs.

Attitudes of orthopaedic trauma surgeons regarding current controversies in the management of pelvic and acetabular fractures.

A closed-ended questionnaire was mailed to all 363 active members of the Orthopaedic Trauma Association. It directed, toward practicing pelvic and acetabular surgeons, questions pertaining to practice demographics and preferred methods for detection and prevention of deep venous thrombosis (DVT), nerve injury, and heterotopic ossification (HO). Questionnaires were received from 226 surgeons (62 percent). Of the surgeons who responded, 181 (80 percent) perform pelvic-fracture and acetabular-fracture surgery; only questionnaires from this group were analyzed. Standard statistical methods were used to perform both univariate and multivariate analyses. Preoperative DVT screening was performed by 48 percent of the surgeons; ultrasound was the most commonly used modality (82 percent). Preoperative DVT prophylaxis was administered by 88 percent of those surveyed; the majority (78 percent) used sequential compression devices. Postoperative prophylaxis was used by 99 percent; the most commonly used modality was sequential compression devices. Analysis suggests that fellowship-trained surgeons and surgeons in practice for fewer than twenty years are more likely to use preoperative DVT prophylaxis. HO prophylaxis was administered by 88 percent; the most commonly used modality was indomethacin. Intraoperative nerve monitoring was performed by only 15 percent of the respondents. Most surgeons employed prophylactic measures to prevent DVT and HO. The wide variation in type of prophylaxis and reasons for use suggests that controversy will continue, and a standard of care for these conditions has yet to be defined. Very few surgeons use intraoperative nerve monitoring routinely.

The floating shoulder: clinical and functional results.

BACKGROUND: Displaced ipsilateral fractures of the clavicle and the glenoid neck are a complex injury pattern that is usually the result of high-energy trauma. The treatment of these injuries is controversial, as good results have been reported with both operative and nonoperative treatment. METHODS: Nineteen patients who had sustained a displaced fracture of the glenoid neck with an ipsilateral clavicular fracture or acromioclavicular separation (floating shoulder) were retrospectively evaluated. The treatment was nonoperative in twelve patients and operative in seven. At the time of final follow-up, standard radiographs were made and all patients were examined by a physical therapist and either a fellowship-trained shoulder surgeon or an orthopaedic traumatologist. In addition, each patient responded to three different validated objective functional outcome measures: the Short Form-36, the American Shoulder and Elbow Surgeons Shoulder Scale, and the Disabilities of the Arm, Shoulder and Hand Questionnaire. Isokinetic strength-testing was performed, and strength in internal and external rotation was compared with that of the uninvolved shoulder. The main outcome measures included fracture-healing, functional outcome, patient satisfaction, and muscular strength. RESULTS: With regard to range of motion, only the amount of forward flexion was found to be significantly greater in the operatively treated group (p = 0.03). The operatively treated shoulders were found to be weaker in external rotation at 300 degrees /sec and weaker in internal rotation at 180 degrees /sec. When normalized to hand dominance, however, the numbers were too small to identify any significant difference. There was no significant difference between groups with regard to the three functional outcome measures. CONCLUSIONS: Good results may be seen both with and without operative treatment. Therefore, we cannot universally recommend operative treatment for a double disruption of the superior suspensory shoulder complex. Treatment must be individualized for each patient.

Decreased capacity of asthmatic bronchial fibroblasts to degrade collagen.

The mechanisms of fibrillar collagen accumulation in asthmatic bronchi remain unclear, an imbalance between synthesis and degradation of collagen may be implicated in this process. The aim of this study was to compare the capacities of normal (BNF) and asthmatic (BAF) bronchial fibroblasts to degrade collagen. Metalloproteinases and their inhibitors were measured by ELISA, types I and III procollagen synthesis was determined by liquid RIA and, finally, zymography was used to assess the presence of active and latent forms of MMPs. The capacity of fibroblasts to degrade collagen coated onto latex beads was evaluated by flow cytometry. Our results showed that MMP-2 secretion was significantly higher in BNF when compared to BAF and this was confirmed by gelatin zymography. In BNF culture, TIMP-1 and MMP-1 secretions positively correlated with types I and III procollagen synthesis. However, in BAF, this correlation was negative. This suggests that a balance exists between collagen synthesis and degradation in BNF and that this balance is compromised in BAF. On the other hand, BAF did show significantly reduced capacity to degrade collagen when compared to that of BNF. This reduced phagocytic activity was not associated with a decrease in collagen receptor expression. This study establishes for the first time that a relationship exists between metalloproteinases enzyme dysregulation and the reduced capacity of asthmatic bronchial fibroblast to degrade collagen. These events may shed light on why accumulation of collagen can be observed in asthmatic airways.

A prospective evaluation of the clinical utility of the lower-extremity injury-severity scores.

BACKGROUND: High-energy trauma to the lower extremity presents challenges with regard to reconstruction and rehabilitation. Failed efforts at limb salvage are associated with increased patient mortality and high hospital costs. Lower-extremity injury-severity scoring systems were developed to assist the surgical team with the initial decision to amputate or salvage a limb. The purpose of the present study was to prospectively evaluate the clinical utility of five lower-extremity injury-severity scoring systems. METHODS: Five hundred and fifty-six high-energy lower-extremity injuries were prospectively evaluated with use of five injury-severity scoring systems for lower-extremity trauma designed to assist in the decision-making process for the care of patients with such injuries. Four hundred and seven limbs remained in the salvage pathway six months after the injury. The sensitivity, specificity, and area under the receiver operating characteristic curve were calculated for the Mangled Extremity Severity Score (MESS); the Limb Salvage Index (LSI); the Predictive Salvage Index (PSI); the Nerve Injury, Ischemia, Soft-Tissue Injury, Skeletal Injury, Shock, and Age of Patient Score (NISSSA); and the Hannover Fracture Scale-97 (HFS-97) for ischemic and nonischemic limbs. The scores were analyzed in two ways: including and excluding limbs that required immediate amputation. RESULTS: The analysis did not validate the clinical utility of any of the lower-extremity injury-severity scores. The high specificity of the scores in all of the patient subgroups did confirm that low scores could be used to predict limb-salvage potential. The converse, however, was not true. The low sensitivity of the indices failed to support the validity of the scores as predictors of amputation. CONCLUSIONS: Lower-extremity injury-severity scores at or above the amputation threshold should be cautiously used by a surgeon who must decide the fate of a lower extremity with a high-energy injury.

Characterization of patients with high-energy lower extremity trauma.

PURPOSE: (a) to report the demographic, socioeconomic, behavioral, social, and vocational characteristics of patients enrolled in a study to examine outcomes after high-energy lower extremity trauma (HELET) and to compare them with the general population; (b) to determine whether characteristics of patients undergoing limb salvage versus amputation after HELET are significantly different from each other. DESIGN AND STUDY POPULATION: A prospective study of 601 patients admitted with high-energy lower extremity trauma to eight Level I trauma centers. PROCEDURES: Patients were evaluated during the initial hospitalization. They are being followed up for 24 months postinjury. Study patients are compared with the general population by using census information, population survey data, and published norms. Characteristics of patients undergoing limb salvage versus amputation are also compared. RESULTS: Most patients were male (77 percent), white (72 percent), and between the ages of twenty and forty-five years (71 percent). Seventy percent graduated from high school (compared with 86 percent nationally) (p < 0.05). One fourth lived in households with incomes below the federal poverty line, compared with 16 percent nationally (p < 0.05). The percentage with no health insurance (38 percent) was also higher than in the general population (20 percent) (p < .05). The percentage of heavy drinkers was over two times higher than reported nationally (p < 0.01). Study patients were slightly more neurotic and extroverted and less open to new experiences. When patient characteristics were compared for those undergoing amputation versus limb salvage, no significant differences were found among any of the variables (p > 0.05). CONCLUSION: In conclusion, LEAP patients differ in important ways from the general population. However, the decision to amputate verus reconstruct does not appear to be significantly influenced by patient characteristics.

Induction of putative tumor-suppressing genes in Rat-1 fibroblasts by oncogenic Raf-1 as evidenced by robot-assisted complex hybridization.

The growth factor receptor-dependent protein kinase Raf-1 is activated by GTP-bound Ras, thereby activating the mitogen-activated protein kinase pathway. To study the role of Raf in transformation we transduced Rat-1 cells with a tetracycline-regulatable retroviral vector encoding the constitutively active oncogenic C-terminal fragment of the human Raf-1 protein. Using subtractive hybridization of mRNAs from induced and noninduced cells and robot-assisted screening by complex hybridization, Raf-induced genes with various different characteristics of induction were investigated. Among the strongly induced genes were those involved in carcinogenesis such as metalloproteinases 3, 10 and 13, cathepsin L, ornithine decarboxylase, and putative tumor-suppressing genes such as monocyte chemoattracting protein 1, interferon-induced protein 10, a recently identified 2'-5' oligoadenylate synthetase-like protein, and plasminogen activator inhibitor type 2. Other components of the plasminogen activator system were not induced. Plasminogen activator inhibitor type 2 is a down-regulator of the proteolytic cascade consisting of various metalloproteinases, some of which are induced by a carboxy-terminal Raf mutant (RafCT). In conclusion, RafCT induces factors which act in a conflicting manner in respect of carcinogenesis, especially within the proteolytic system of the extracellular matrix.

[Surgery of the external auditory canal in familial bilateral auditory canal atresia]. / Die Chirurgie des äusseren Gehörgangs bei familiärer bilateraler Gehörgangsatresie.

BACKGROUND: Inherited isolated bilateral atresia of the external auditory canal is rare. Ear canal surgery procedure is difficult. METHODS: Basing on a case report of a family with inherited isolated bilateral atresia of the external auditory canal in 4 cases the way of preoperative diagnostics including human genetics and our surgical concept is described. RESULTS: Resulting clinical findings showed complete epithelialization of the ear canal and ear drum with slight conductive hearing loss. CONCLUSIONS: Canaloplasty in atresia can be easily and successfully accomplished by our modified technique.

Failure of exchange reamed intramedullary nails for ununited femoral shaft fractures.

OBJECTIVE: To determine the effectiveness of exchange reamed nails for treatment of aseptic femoral delayed unions and nonunions. DESIGN: Retrospective chart review. PATIENTS: Nineteen patients admitted to the Carolinas Medical Center Level I trauma center from 1990 to 1996 for repair of femoral shaft fracture nonunion following contemporary locked nailing performed at least six months previously. These patients showed no radiographic evidence of progression of fracture healing for three months and had clinical symptoms of nonunion. INTERVENTION: Exchange reamed nails to treat ununited femoral shaft fracture. MAIN OUTCOME MEASUREMENTS: Radiographic and clinical evidence of union of the fracture or of the necessity for additional procedures. RESULTS: In 53 percent of the patients the secondary procedure resulted in fracture union, whereas in 47 percent, one or more additional procedures were required. Eight of the nine fractures that did not unite with exchange nailing united after a subsequent procedure (bone grafting, compression plating, or nail dynamization). Neither the type of nonunion, the location of the shaft fracture, the use of static versus dynamic cross-locking, nor the use of tobacco products was statistically predictive of the need for additional procedures. CONCLUSIONS: Reevaluation of routine exchange nailing as the recommended treatment for aseptic femoral delayed union or nonunion may be required. A significant number of patients who undergo reamed exchange nailing will require additional procedures to achieve fracture healing.

Eosinophil activation status and corticosteroid responsiveness in severe asthma.

BACKGROUND: Since eosinophils are implicated in asthma pathogenesis, we investigated whether these cells were activated in severe asthma. METHODS: Twenty-six asthmatics with different clinical responses to oral corticosteroid (CS), i.e. sensitive [change in forced expiratory volume in 1 s (DeltaFEV(1)) >/= 25% after oral methylprednisolone, 40 mg daily, for 14 days, n = 7], resistant (DeltaFEV(1) /= 20 mg oral prednisone daily for acceptable asthma control, n = 10), were studied. RESULTS: Calcium ionophore-induced leukotriene (LT) C(4) release of purified blood eosinophils was similar in the three groups. Cell incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced ionophore-induced LTC(4) release, and this effect was higher in CS-sensitive (5-fold) than in CS-resistant subjects (1.7-fold) (p = 0.02). CS treatment decreased blood eosinophil counts in these two groups of subjects (p