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.

The DeltauvrB mutations in the Ames strains of Salmonella span 15 to 119 genes.

The DeltauvrB mutations present in strains of Salmonella enterica Typhimurium used commonly in the Salmonella (Ames) mutagenicity assay were isolated independently for at least five different his mutants. These deletions all involved the galactose operon, biotin operon, nucleotide-excision-repair uvrB gene, and chlorate-resistance genes. Beyond this, the size of the deletions and the number and type of genes deleted have remained unknown for nearly 30 years. Here, we have used genomic hybridization to a Typhimurium microarray to characterize these five DeltauvrB deletions. The number of genes (and amount of DNA) deleted due to the DeltauvrB mutations are 15 (16kb) each in TA97 and TA104, 47 (50kb) in TA100, 87 (96kb) in TA1537, and 119 (125kb) in TA98, accounting for 0.3, 0.3, 1.0, 1.9, and 2.6% of the genome, respectively. In addition, TA97 and TA104 contain an identical three-gene deletion elsewhere in their genomes, and, most remarkably, TA104 contains a 282-gene amplification, representing 7% of the genome. Missing genes include mfdA and mdaA, encoding a multi-drug translocase and a major nitroreductase, respectively, both absent in TA98; dps, encoding a DNA-binding protein absent in TA1537 and TA98; and dinG, encoding a lexA-regulated repair enzyme, absent in three DeltauvrB lineages. Genes involved in molybdenum cofactor biosynthesis and a number of ORFs of unknown functions are missing in all DeltauvrB strains investigated. Studies in DeltauvrB strains of Escherichia coli have found that the enhanced mutagenesis of some base analogues was due to the deletion of genes involved in molybdenum cofactor biosynthesis rather than to deletion of uvrB. These discoveries do not diminish the value of the data generated in the Ames strains. However, absence of genes other than uvrB may account for the enhanced mutagenicity of some compounds in DeltauvrB Ames strains. In general, microarrays will be useful for characterizing the extent and nature of deletion and amplification mutations.

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.

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.

Intraoperative fluoroscopy to evaluate fracture reduction and hardware placement during acetabular surgery.

OBJECTIVES: To evaluate use of intraoperative fluoroscopy during acetabular surgery to determine fracture reduction and accurate placement of screws. DESIGN: Retrospective. SETTING: Level I trauma center. PARTICIPANTS: Thirty patients with thirty-two acetabular fractures. INTERVENTION: Patients were evaluated with fluoroscopy during surgery to assess fracture reduction and screw placement. Anterior-posterior (AP), oblique, and lateral pelvic fluoroscopic images were obtained intraoperatively. Postoperative radiographs were used to verify fluoroscopic findings; computed tomography (CT) scans were used as the control to assess intraarticular screw placement. MAIN OUTCOME MEASUREMENTS: Radiographic and clinical assessment of fracture reduction and screw placement. RESULTS: Intraoperative fluoroscopy confirmed the extra-articular position of all screws evaluated. Postoperative CT scans confirmed the extra-articular placement of all screws assessed by fluoroscopy. Quality of reduction using intraoperative fluoroscopic images had a 100 percent correlation with reduction on final radiographs. One patient, with two screws placed without fluoroscopic evaluation, had intra-articular placement requiring revision surgery. CONCLUSIONS: Intraoperative fluoroscopy is effective in evaluating both acetabular fracture reduction and hardware placement.

Pulmonary gas exchange during intramedullary fixation of femoral shaft fractures.

BACKGROUND: This study was undertaken to determine if the alveolar dead space fraction (Vd/Vt) or the alveolar-arterial oxygen gradient (A-a DO2) increased during intramedullary fixation of femoral shaft fractures. METHODS: Fifty hemodynamically stable patients with femur fractures were prospectively enrolled. Three serial measurements of Vd/Vt and A-a DO2 were obtained immediately before femoral nailing (Pre), 30 minutes after nailing (+30), and 120 minutes after nailing (+120). Vd/Vt was determined by simultaneously measuring PaCO2 and the steady-state end-tidal CO2 (PetCO2), where Vd/Vt = (1 - PetCO2/PaCO2). RESULTS: Vd/Vt before nailing was 0.09 +/- 0.09 (mean +/- SD); at +30 and +120, Vd/Vt was 0.10 +/- 0.06 and 0.08 +/- 0.07, respectively (p > 0.2; paired t test, both time points). A-a DO2 before nailing was 84 +/- 85 mm Hg, and it did not change significantly at +30 (89 +/- 69 mm Hg; p = 0.51 vs. Pre; paired t-test) or at +120 (51 +/- 45 mm Hg). No difference in data was found with analysis by fracture classification or number of reamer passes. Vd/Vt and A-a DO2, however, were both significantly increased in patients with lung contusion (n = 6) before nailing, but neither measurement increased after nailing. One patient developed fat embolism (Vd/Vt of 0.35 at Pre and 0.31 at +120), and another patient experienced postoperative pulmonary thromboembolism (Vd/Vt increased from 0.06 at Pre to 0.17 at +120). CONCLUSION: The process of femoral nailing does not cause enough pulmonary embolization to alter pulmonary gas exchange as measured by Vd/Vt and A-a DO2. If Vd/Vt is increased preoperatively, the likelihood of subsequent pulmonary dysfunction secondary to either preoperative lung injury or fat embolism is increased.

Efficacy of surgical wound drainage in orthopaedic trauma patients: a randomized prospective trial.

OBJECTIVE: To study the efficacy of closed suction drainage in clean nonemergent surgical fracture fixation or bone grafting on the extremities or pelvis. DESIGN: A prospective randomized trial. SETTING: The orthopaedic trauma service of a Level I trauma hospital. PATIENTS: Patients were older than age eighteen years and undergoing clean nonemergent surgical fracture fixation or bone grafting procedures on the extremities (excluding hands and feet) or pelvis. INTERVENTION: The application of a surgical drain. MAIN OUTCOME MEASUREMENTS: Wound drainage, edema, hematoma and erythema, dehiscence, infection, and need for surgery or readmission were followed for six weeks. A univariate analysis with Student's t test for continuous variables and chi-squared analysis for all categorical data were used, with a p value of < or = 0.05 considered statistically significant. RESULTS: A total of 202 patients were randomized to 102 patients with no drain and 100 patients with a drain. There was no significant difference between the groups with regard to injury severity, systemic disease, age, body weight, physical status, or estimated blood loss. There was no significant difference between the drain and no-drain groups in any of the parameters evaluated. CONCLUSION: There is no significant difference between drained and nondrained wounds in clean, nonurgent orthopaedic trauma surgery. It appears that drainage systems can be safely eliminated in this group.

Does bacteremia occur during high pressure lavage of contaminated wounds?

The risk of bacteremia secondary to high pressure lavage of contaminated wounds was assessed. Twenty canines were divided randomly into four treatment groups. A 10-cm incision was made over the left shoulder of each dog. The deltoideus muscle was disrupted and traumatized. Groups A and B (n = 8) had wound contamination with 1.4 x 10(9) Staphylococcus aureus followed 75 minutes later by high pressure lavage or bulb syringe irrigation, respectively. Groups C and D (n = 2) had no contamination, followed by the same treatment. Bacterial counts were obtained before and after wound irrigation. Blood cultures were obtained before, during, and 15 minutes after irrigation. Positive control cultures were obtained during injection of bacteria into the antecubital vein. A detectable bacteremia did not occur during or after high pressure lavage or bulb syringe irrigation of acute contaminated wounds but did occur in 18 of 20 positive controls. Bacterial levels were reduced by an average of 70% +/- 10% by high pressure lavage and 44% +/- 50% by bulb irrigation. Reduction of wound bacteria was achieved more consistently with high pressure lavage than with bulb syringe irrigation.

Effects of surgical approaches for acetabular fractures with associated gluteal vascular injury.

OBJECTIVES: To examine the viability of the abductor muscles following extensile exposures to the acetabulum in the presence of superior gluteal artery (SGA) or vein (SGV) injury. DESIGN: In vivo animal study. INTERVENTION: Twenty-two dogs underwent either an extensile or combined two-incision acetabular approach; either the SGA, the SGV, or no vessel was ligated. MAIN OUTCOME MEASUREMENTS: Blood flow to the affected gluteal region was evaluated by angiography, laser Doppler flowmetry, and fluorescent microspheres, and histologic and wet weight analyses were performed on the abductor muscles. RESULTS: Complete ischemic necrosis of the abductor muscles did not occur in any specimen; however, there were statistically significant reductions in immediate postoperative gluteal muscle perfusion (-47 percent, p < 0.01), loss of abductor muscle mass (-41 percent, p < 0.001), and histologic evidence of moderate to severe necrosis in five of seven specimens with extensile exposures and SGA ligation (p = 0.01). Extensile exposure and SGV ligation also caused a significant loss of muscle mass (-25 percent, p < 0.02), with moderate to severe necrosis occurring in four of seven specimens (p < 0.04). Dogs with SGA ligation undergoing the two-incision approach had no significant changes in muscle mass (-3 percent) or perfusion. Moderate to severe necrosis occurred in only one of four specimens. CONCLUSIONS: This study fails to support the hypothesis that extensile approaches to complex acetabular fractures eliminate abductor collateral circulation when performed in the presence of SGA injury.

Incidence of sciatic nerve injury in operatively treated acetabular fractures without somatosensory evoked potential monitoring.

OBJECTIVE: The authors investigated the incidence of sciatic nerve injury associated with the operative repair of acetabular fractures without somatosensory evoked potential (SSEP) monitoring. DESIGN: Retrospective case review of prospectively documented pre- and postoperative physical examinations. SETTING: A level I trauma hospital. PATIENTS: All the cases were reviewed of patients with open reduction and internal fixation of acetabular fractures who underwent posterior or extensile approaches (129) performed by the three senior authors from January 1991 through March 1995. INTERVENTION: Intraoperative SSEP monitoring was not used during any of the procedures. The procedures included sixty-five Kocher-Langenbeck approaches, thirty-four combined Kocher-Langenbeck and iliofemoral approaches, four extended iliofemoral approaches, and four triradiate approaches. RESULTS: One case of iatrogenic nerve injury resulted in a sensory deficit. No patient suffered an exacerbation of a preexisting nerve injury. CONCLUSION: The results of this study indicate that open reduction and internal fixation of acetabular fractures, using current techniques with visualization and protection of the sciatic nerve, can reduce the incidence of neurologic injury to a negligible level. There does not appear to be justification for the addition of SSEP or electromyograph modalities to the operative routine of experienced surgeons.

Putative intestinal estrogen receptor: evidence for regional differences.

Previously we demonstrated that 17 beta-estradiol (E2) stimulates intestinal calcium absorption and enhances uptake of calcium by intestinal mucosal cells in vitro, and that the latter contains estrogen receptor (ER)-like proteins and mRNAs. The current study was undertaken to further characterize the putative intestinal ERs using RT-PCR analysis, Western blot analysis, Southern blot analysis, ligand binding assays and gel shift assays. RT-PCR analysis using primers directed at the terminal end of the A/B domain of the uterine ER confirmed our previous finding that intestinal ER mRNAs are present throughout the intestine, with the exception that the duodenum lacked the amplified region. Western blot analysis, using ER-715 antibody, detected the expected 68- to 70-kDa ER protein and additional 58-, 46- and 41-kDa proteins in the uterus and colon, while duodenal extract contained only a faint 46-kDa and strong 28-kDa protein bands. Southern blot analysis performed on enzyme-digested genomic DNAs demonstrated the presence of ER-like sequences in genomic DNA from the uterus, duodenum and colon. However, enzyme restriction maps of genomic DNAs from intestinal segments were different from the map for uterine genomic DNA digested with similar enzymes. In ligand binding assays, 125I-labeled E2 bound specifically to 46-kDa protein in duodenal, colonic and uterine extracts and the binding was competitively inhibited by excess cold E2. Gel mobility shift assays using 32P-labeled vitellogenin derived ERE demonstrated that jejunal, colonic and uterine ER protein contain the classical DNA binding domain. In addition, ERE bound in a specific fashion to sites in genomic DNAs from the uterus, colon and jejunum. In contrast, protein extracts and genomic DNAs from the duodenum failed to bind to 32P-labeled ERE and, consequently, appear to be devoid of the classical DNA binding domain. These findings establish the presence of ER-like proteins and genes in intestinal mucosal cells of rats and suggest that the duodenum contains a variant ER gene that encodes a variant ER protein.

Management of humeral nonunion after the failure of locking intramedullary nails.

We reviewed 21 cases of humeral nonunion following the failure of "locking" humeral nails. The nails had been inserted as the primary operative procedure following humeral fracture in fifteen cases or after the failure of closed treatment in six cases. Reconstruction after the failure of these implants was complicated by poor bone stock and difficulty in achieving union. Although technically difficult, open reduction and internal fixation with plating and bone grafting (successful in nine of nine cases) was more consistent than exchange nailing (successful in four of 10 cases) in achieving union (p = 0.01). Two patients refused further surgical intervention. The degree of bone loss associated with a loose nail, the lack of success of exchange nailing, and the insertion site morbidity associated with humeral nail removal differentiate these nonunions from similar lower extremity problems. The degree of bone loss following failed locking nailing of the humerus is a major concern, and exchange nailing alone may not be an acceptable option to deal with this problem.

Intramedullary nailing of humeral shaft fractures.

Twenty-one patients with 22 acute traumatic fractures of the humeral diaphysis were treated either with the True/Flex intramedullary rod or the Russell-Taylor rod. Follow-up is provided on 20 fractures. Indications for fixation on all but 3 patients was either multiple fractures, associated chest or abdominal trauma, vascular interruption, or open fracture. The series included 4 open fractures. Time to union averaged 7.6 weeks, with two nonunions, both in open fractures. Two isolated preoperative radial nerve palsies resolved fully; four brachial plexus injuries had a more complex recovery. No iatrogenic nerve damage was encountered. Excluding those patients with brachial plexus deficits, shoulder range of motion returned reliably. Impingement with a rod prominence was noted in 1 fracture. Functionally, all of the fractures, aside from those associated with a brachial plexus injury, had a normal or only mildly limiting result as reported by the patient. Additionally, eight humeral nonunions were treated with a reamed Russell-Taylor humeral nail with supplemental iliac crest bone graft at the time of nailing in 3 patients. Five of these 8 patients went on to union.

Is computed tomography useful after simple posterior hip dislocation?

Recent articles and textbooks of orthopaedic traumatology recommend routine computed tomography (CT) scans after successful reduction of simple posterior hip dislocations. This is based on the belief that CT, even in cases with concentric reductions, may identify fractures or intraarticular loose bodies not apparent on standard radiographs. This study was conducted to assess the usefulness of CT after concentric reduction of simple posterior hip dislocations. The hospital database was searched for all traumatic hip dislocations in the past 4 years. Charts and radiographs were reviewed, and only patients with simple posterior hip dislocations (no acetabular or femoral head fractures) and a concentric reduction identified on plain radiographs were included. Twenty-three patients who met these criteria and had subsequent CT scans to evaluate the hip joint were identified. CT scans confirmed the concentric reduction in all patients. Three small occult fractures were identified, and no occult intraarticular loose bodies were found. CT findings did not alter the treatment plan for any of the patients studied. In this small group of patients, CT scanning was not useful after concentric reduction by plain radiography of simple posterior hip dislocations.

Iatrogenic posterior interosseous nerve injury: is transosseous static locked nailing of the radius feasible?

To assess the risk of injury to the posterior interosseous nerve (PIN) in transosseous locked nailing of the radius, the relationship of the PIN to the surgical zone was studied in five pairs of fresh frozen adult cadaver arms. A static locked intramedullary nail was inserted in each radius using the recommended surgical technique. A formal dissection of the radial nerve and its branches was then performed to document the relationship of the PIN to the radial head in neutral, pronation, and supination also was measured. In no specimens was the PIN injured by the screw insertion. However, in two specimens (right and left arm of the same donor) the PIN was 1 mm and 2 mm, respectively, from the screw insertion site. The average shortest distance from the PIN to the screw was 11.3 mm. As measured along the mid-shaft of the radius, the average distance from the radial head to the PIN was 36.2 mm in 90 degrees supination, 46.7 mm in neutral, and 56.9 mm in 90 degrees pronation. Transosseous static locked nailing of the radius is feasible, but the surgeon and patient must be aware of the risk of possible injury to the PIN. To minimize this risk, we suggest that the proximal locking screw should be inserted from a direct lateral entry at < 30 mm from the radial head with the forearm in neutral rotation.

Interferon-gamma priming effects in the activation and deactivation of ISGF3 in K562 cells.

ISGF3 is a major protein factor which mediates the transcriptional activation of interferon-inducible genes. ISGF3 is composed of two subunits, ISGF3 gamma and ISGF3 alpha, which are stimulated by interferon-gamma (IFN-gamma) and interferon-alpha (IFN-alpha), respectively. In this paper, the effect of pretreatment of IFN-gamma on the response of K562 cells to IFN-alpha, termed "gamma-priming," is examined. Using techniques of gene transfection and mobility shift assay, we studied the gamma-priming effects on the kinetics of appearance and disappearance of (i) the protein product of a luciferase reporter gene driven by an IFN-inducible promoter and (ii) the binding of ISGF3 to the interferon-stimulated response element. We found that exposure of cells to IFN-gamma prior to IFN-alpha greatly increased both the levels and the rate of ISGF3 binding activity during the early phase of IFN-alpha treatment and caused the amount of ISGF3 bound to the interferon-stimulated response element to decrease more rapidly with time during the later phase. Such effects were reflected also on the kinetics of expression of the interferon-inducible luciferase gene induced by IFN-alpha. In order to understand the basis of these gamma-priming effects, we use an in vitro reconstitution method to examine the kinetics of the subcomponents of ISGF3 in response to different IFN treatments in K562 cells. It was found that gamma-priming not only increased the levels of ISGF3 gamma, but it also stimulated both the rates of rise and fall of the activated alpha-component of ISGF3. A molecular model is proposed to explain these findings.

Evidence for estrogen receptor-linked calcium transport in the intestine.

Intestinal calcium malabsorption in postmenopausal osteoporotic women is often linked indirectly to decreased serum 1,25(OH)2 vitamin D or to intestinal resistance to its action, rather than directly to the low circulating estrogen that results following menopause. The studies presented indicate that the intestinal mucosal cells of rats contain estrogen receptor immunoreactivity, express the mRNA for estrogen receptors, and respond directly to 17 beta-estradiol with enhanced calcium transport that is suppressed by gene transcription and protein synthesis inhibitors. These findings suggest that estrogen has a physiological role in the regulation of intestinal calcium absorption and that its deficiency in postmenopausal osteoporosis, and following therapeutic oophorectomy, may result directly in calcium malabsorption that is believed to be an important factor in the bone loss that occurs in these conditions.

A novel interferon-inducible domain: structural and functional analysis of the human interferon regulatory factor 1 gene promoter.

We have cloned and functionally characterized the human interferon regulatory factor 1 (IRF-1) gene promoter. The promoter contains a CpG island, with several GC boxes, a CAAT box, but no TATA box. IRF-1 mRNA is strongly induced by gamma interferon (IFN-gamma) but more weakly and transiently by IFN-alpha. There are several putative kappa B motifs and numerous AA(G/A)G(G/T)A and GAAANN motifs throughout the promoter. The IRF-1 promoter is not autoregulated by the IRF-1 gene product. IFN inducibility of the promoter was studied with 5' deletion mutants linked to a heterologous reporter gene. Gel mobility shift assays were used to show IFN-inducible factor binding to the IRF-1 promoter. These studies showed that IFN inducibility is conferred by a novel imperfect inverted-repeat arrangement of two GAAANN motifs within a domain, 130 nucleotides upstream of transcription initiation. This inverted repeat binds a factor upon induction with IFN and can confer IFN inducibility on a heterologous promoter. Conversely, point mutations of the inverted repeat are not IFN inducible when linked to the same heterologous promoter.

Human interferon regulatory factor 1: intron-exon organization.

Interferon (IFN) regulatory factor 1 (IRF-1) is a transcriptional regulatory protein that mediates the transcriptional activation of the IFN-alpha and IFN-beta genes by viruses and IFNs. To characterize the mechanisms that govern the level of IRF-1 in cells, we isolated the IRF-1 gene and characterized the structure of its intronic and exonic domains and of its regulatory promoter region. A human placental genomic library was screened with an IRF-1 cDNA probe, and two clones that contained the IRF-1 gene and its 5' regulatory region were obtained. We used these clones to determine the complete nucleotide sequence for the IRF-1 gene, finding that the IRF-1 gene spanned 7.72 kb of DNA and included 10 exons and 9 introns. When the deduced amino acid sequences were compared among different species, the most conserved exons were exons 2, 3, and 4, in which the putative DNA binding domain for the IRF-1 protein is located.