Eric E. Johnson

The treatment of infected nonunions and segmental defects of the tibia by the methods of Ilizarov.

Circular external fixation using the Ilizarov apparatus combined with internal bone transport or compression-distraction techniques were used to treat 28 patients with infected nonunions or segmental bone loss of the tibia. There were 22 males and six females with an average age of 34 years (range, 17-58 years). Six of 28 patients had infected tibial nonunions associated with hemicircumferential bone loss. These tibiae were treated by anterior hemicircumferential corticotomy and partial bone fragment internal transport. Fifteen of the remaining 22 patients had an average of 4 cm of segmental bone loss (range, 2-7 cm). Seven patients without shortening or defect had infected nonunions associated with extensive diaphyseal sequestrae. These nonunions were treated by en bloc resection of the diaphyseal shaft and internal bone transport. All patients healed their infected extremities without the addition of cancellous bone graft, microvascular fibular, or soft-tissue grafting. Preoperative shortening was present in 13 of 28 patients. Regenerate new bone formation averaged 6 cm (range, 1.5-22 cm). Postoperative antibiotics were not administered in 21 of 28 patients. In seven patients, antibiotics were given for ten days after en bloc resection of the diaphyseal sequestrae. Equal limb length was maintained in 21 extremities, within 1 cm in five tibiae and less than 3 cm in two tibiae. Functional results were good to excellent in 21, fair in six, and poor in one. The application of Ilizarov techniques to diaphyseal infected nonunions and segmental defects is very encouraging. It may prove to be an excellent technique for future management of resistant diaphyseal infections of bone.

Microbial ferric iron reductases

Almost all organisms require iron for enzymes involved in essential cellular reactions. Aerobic microbes living at neutral or alkaline pH encounter poor iron availability due to the insolubility of ferric iron. Assimilatory ferric reductases are essential components of the iron assimilatory pathway that generate the more soluble ferrous iron, which is then incorporated into cellular proteins. Dissimilatory ferric reductases are essential terminal reductases of the iron respiratory pathway in iron-reducing bacteria. While our understanding of dissimilatory ferric reductases is still limited, it is clear that these enzymes are distinct from the assimilatory-type ferric reductases. Research over the last 10 years has revealed that most bacterial assimilatory ferric reductases are flavin reductases, which can serve several physiological roles. This article reviews the physiological function and structure of assimilatory and dissimilatory ferric reductases present in the Bacteria, Archaea and Yeast. Ferric reductases do not form a single family, but appear to be distinct enzymes suggesting that several independent strategies for iron reduction may have evolved.

Resistant nonunions and partial or complete segmental defects of long bones. Treatment with implants of a composite of human bone morphogenetic protein (BMP) and autolyzed, antigen-extracted, allogeneic (AAA) bone.

Twenty-five patients with resistant nonunions including partial or complete segmental defects were treated with a composite alloimplant of human bone morphogenetic protein (h-BMP) and autolyzed, antigen-free, allogeneic bone (AAA). The series consisted of 16 females and nine males; average age was 45 years. Preoperative symptoms averaged 30 months (range, five to 83 months); 22 of 25 patients had failed multiple attempts at electrical stimulation. Twenty-three of 25 patients had an average of three prior failed surgical attempts at union (range, one to ten). There were ten segmental defects with an average length of 4 cm (range, 2-9 cm). The composite implant was incorporated as an onlay in 15 extremities and as an inlay graft supported by internal fixation in ten extremities. Seven patients received supplementary autogeneic cancellous bone grafting. Average healing time was six months (range, three to 14 months). Average follow-up time was 21 months (range, five to 82 months). Functional results were rated as excellent, 14; good, five; and fair, five. One failed to unite because of a recurrent infection. Union was obtained in 24 of 25 patients. There were five failures of the original operation that required reoperations; union eventually occurred in four of five extremities by repeat composite grafting and replacement of the failed internal fixation. Bony union between host bone and the composite implant began at an average of eight weeks postoperatively. Present results indicate that h-BMP/AAA composite implants represent adjunctive treatment of difficult nonunions. The h-BMP/AAA composite implants may be implanted in either partial or complete segmental defects of long bones.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiographic analysis of tibial fracture malalignment following intramedullary nailing.

Intramedullary nailing of the tibia was performed on 145 tibiae (137 patients) for fracture or nonunion from 1985 to 1992. There were 133 cases available for radiographic analysis of postoperative tibial alignment. Of the 133 nailings, 16 (12%) were malaligned (12 acute fractures and 4 nonunion-malunions). Malalignment was defined as 5 degrees angulatory deformity in any plane. Malalignment was seen in 58% of proximal third fractures, 7% of middle third fractures, and 8% of distal third fractures. Of the malaligned fractures, 83% were either segmental or comminuted. Thirteen percent of the reamed tibiae were malaligned as compared with 9% of the unreamed tibiae. There was no relationship between nail insertion site and degree of angulation. The medial entrance angle averaged 9.5 degrees and contributed to a valgus deformity in 4 proximal third tibial fractures. The average anterior bow deformity of 5 proximal third fractures was 7 degrees (range, 5 degrees-12 degrees). Careful attention to operative technique and entrance angle, particularly with proximal third or comminuted fractures, is recommended to prevent angular deformity and malunion after tibial nailing. Proximal third tibial fractures may require a neutral or slightly lateral entrance angle to ensure a more anatomic reduction and centromedullary nail orientation to offset the tendency for valgus angulation.

Repair of segmental defects of the tibia with cancellous bone grafts augmented with human bone morphogenetic protein: a preliminary report

Human bone morphogenetic protein (hBMP) is a bone cell differentiation-inducing factor. Six patients with traumatic segmental three- to 17-cm tibial defects developed solid union by implantation of hBMP and autogeneic cancellous grafts and stabilization. There were no allergic, infectious, or surgical complications. If hBMP augmentation in biodegradable delivery systems can be established by a prospective, randomized, double-blind investigation, the incidence of successful bone graft operations for treatment of large segmental defects would be measurably improved.

Distal metaphyseal tibial nonunion. Deformity and bone loss treated by open reduction, internal fixation, and human bone morphogenetic protein (hBMP).

Four patients with severely deformed nonunions of the distal end of the tibia failed to respond to standard surgical methods and were successfully treated as follows: debridement of fibrous tissue, sequestrectomy, correction of angulatory deformities, internal stabilization, and implantation of human bone morphogenetic protein (hBMP). After resection of the sequestra, all four patients had significant bone defects of the anterior tibial cortex extending to the ankle joint. The average number of failed previous surgical procedures was 5.8. The average patient age was 35.3 years. The intervals of nonunion averaged 24.8 months. In two patients, the hBMP, including other low molecular weight bone matrix noncollagenous proteins (hBMP/NCP), was implanted across the fracture site in polylactic-polyglycollic acid strips (1 X 13 cm) as an onlay graft. In one patient, the BMP was implanted in the fracture gap in absorbable gelatin (No. 5 capsules). In another patient, the BMP/NCP was also implanted in the form of a composite of cortical allogeneic bone in addition to a capsule of BMP/NCP. In all four cases, alignment was restored and the bone ends were stabilized with internal fixation. Preoperatively, the ankle joints were ankylosed and painful. Healed fractures and functional ankle joints were observed in three of four patients at an average of 4.4 months. In one patient, the fracture healed but the joint remained ankylosed. Although a randomized double-blind consecutive series of matched cases is necessary to prove the efficacy of hBMP, implants of hBMP combined with skillful surgical treatment are under investigation in the interim as an alternative to amputation.

The contribution of the anterior talofibular ligament to ankle laxity.

The motion responses of thirty fresh-frozen cadaver tibiotalar joints were measured for applied anterior-posterior force, inversion-eversion moment, and internal-external rotary torque. The load-motion response curves obtained after sectioning the anterior talofibular ligament were compared with those for intact specimens in three positions of flexion of the ankle. Laxity of the intact ankle was shown to be dependent on flexion position; dorsiflexion was consistently the position of least laxity, reflecting the effects of talar geometry and its articulation with the tibiotalar syndesmosis. Section of the anterior talofibular ligament produced significant increases in laxity for all modes tested. Total anterior-posterior laxity increased by 4.3 millimeters in dorsiflexion, which was the position of maximum change. In contrast, the greatest increases in total inversion-eversion laxity (5.2 degrees) and total internal-external rotation laxity (10.8 degrees) were recorded in plantar flexion.

Bone morphogenetic protein augmentation grafting of resistant femoral nonunions. A preliminary report.

Twelve patients with intractable nonunions of the femoral diaphyseal or metaphyseal-diaphyseal shaft were successfully treated by a combination of internal fixation and implants of human bone morphogenetic protein (h-BMP). There was an average of 4.3 surgical procedures per patient attempting union prior to h-BMP implantation. Union was obtained in 11 of 12 patients and in one patient with a repeat stabilization and implantation of h-BMP. Four patients received autogeneic cancellous bone graft and four patients received allogeneic bone grafts. The BMP implant was prepared in the form of an aggregate of h-BMP and bone matrix water-insoluble noncollagenous proteins (h-BMP/iNCP). Fifty to 100 mg of h-BMP/iNCP was either implanted in the fracture gap in ultra thin gelatin capsules, or incorporated in a strip of polylactic/polyglycolic acid copolymer (PLA/PGA) and placed as an onlay across the fracture gap. The average time to union was 4.7 months. Further clinical investigations are planned as a series of matched cases with and without BMP augmentation in order to distinguish h-BMP effects from new or improved methods of fracture fixation combined with autogeneic cancellous bone grafts.

Human bone morphogenetic protein allografting for reconstruction of femoral nonunion.

A composite inductive allograft consisting of an allogeneic, autolysed, antigen-free cortical bone carrier lyophilized with partially purified human bone morphogenetic protein was implanted in 30 consecutive femoral reconstructions that resulted from failure of fracture healing. There were 24 atrophic shortened femoral nonunions, four equal length femoral nonunions, and two femoral malunions. There were 10 men and 20 women with an average age of 47 years (range, 28-75 years). Allogeneic, autolysed antigen-free cortical bone was used as a structural alloimplant and as a delivery system for partially purified human bone morphogenetic protein. The composite implant of human bone morphogenetic protein/allogeneic, autolysed antigen-free cortical bone was used in conjunction with one-stage lengthening of the extremity, restoration of mechanical axis and rotational alignment. In 26 of 30 femurs, the human bone morphogenetic protein/allogeneic autolysed antigen-free cortical bone consisted of an allogeneic cortical bone implant incorporated into a one-stage lengthening of atrophic femoral nonunion. In four patients with equal length femoral nonunions, the human bone morphogenetic protein/allogeneic, autolysed antigen-free implant was placed as an medial femoral shaft onlay graft. Internal remodeling of the implant occurred within 8 to 12 weeks after implantation. Lengthening defects greater than 2 cm were supplemented with intercalary autogeneic bone graft. Twenty-four femurs healed at an average of 6 months at an average followup of 55 months. Four of six plate fatigue failures were salvaged with repeat plating. Two patients were lost to followup. The human bone morphogenetic protein/allogeneic, autolysed antigen-free bone allograft is an excellent structural and delivery system that induces host bone formation and implant remodeling allowing salvage of difficult femoral nonunions.

Heterotopic ossification prophylaxis following operative treatment of acetabular fracture.

Eighty seven patients with 88 fractures were retrospectively reviewed to assess the effect of postoperative prophylaxis on the formation of heterotopic ossification (HO). Sixty eight patients with 69 acetabular fractures were followed for an average of 21 months (range, 3-98 months). The grade of HO was assessed using the Brooker classification system. Thirty four fractures had no prophylactic treatment, 30 were treated prophylactically with indomethacin, two with radiation therapy, and three with both indomethacin and radiation. Twenty (59%) of 34 untreated fractures developed HO, of which nine (26%) were Grade III or IV. Thirteen (43%) of 30 fractures treated with indomethacin developed HO, of which 5 (16%) were Grade III and none were Grade IV. Twenty one of 24 fractures were stabilized through the extended iliofemoral approach; 13 of these had no prophylaxis. Eleven of the 13 developed HO; eight were Grade III or IV (62%). Seven of eight fractures treated with indomethacin following the extended iliofemoral approach developed HO; one was Grade III (13%) and non Grade IV. There was no significant difference between 13 patients who were not treated prophylactically and 18 indomethacin treated patients stabilized through the Kocher-Langenbeck approach. Only one of 11 patients had HO (Grade I) following an ilioinguinal approach. Postoperative radiation therapy, with or without indomethacin, resulted in three patients with Grade 0 HO (all radiated 1-4 days post surgery), one with Grade II (radiated postoperative Day 8), and one with Grade III HO (significant delay in surgery with preoperative Grade III HO of the hip).(ABSTRACT TRUNCATED AT 250 WORDS)