Identification and functional characterization of a novel F5 mutation (Ala512Val, FVB onn ) associated with activated protein C resistance.

UNLABELLED: Essentials Activated protein C (APC) resistance is a prevalent risk factor for venous thrombosis. A novel missense mutation (Ala512Val - FVBonn ) was characterized in vitro and in silico. FVBonn is a new cause of APC resistance and venous thrombosis. FVBonn expresses additionally enhanced procoagulant activity in the absence of APC. SUMMARY: Background Activated protein C (APC) resistance is a prevalent risk factor for venous thrombosis. This phenotype is most commonly associated with the factor V Arg506Gln mutation (FV Leiden), which impairs the APC-mediated inactivation of both activated FV (FVa) and activated FVIII (FVIIIa). Objectives Here, we report the identification and characterization of a novel FV mutation (Ala512Val, FVBonn ) in six patients with APC resistance and venous thrombosis or recurrent abortions. Methods FVBonn was expressed in a recombinant system and compared with recombinant wild-type (WT) FV and FV Leiden in several functional assays. Results FVBonn conferred APC resistance to FV-depleted plasma, both in the activated partial thromboplastin time (APTT)-based test (APC sensitivity ratio [APCsr] of 1.98 for FVBonn versus 4.31 for WT FV and 1.59 for FV Leiden) and in the thrombin generation-based test (normalized APCsr of 5.41 for FVBonn versus 1.00 for WT FV and 8.99 for FV Leiden). The APC-mediated inactivation of FVaBonn was slower than that of WT FVa (mainly because of delayed cleavage at Arg506), but was greatly stimulated by protein S. The APC cofactor activity of FVBonn in FVIIIa inactivation was ~ 24% lower than that of WT FV. In line with these findings, an in silico analysis showed that the Ala512Val mutation is located in the same loop as the Arg506 APC cleavage site and might hamper its interaction with APC. Moreover, FVBonn was more procoagulant than WT FV and FV Leiden in the absence of APC, because of an increased activation rate and, possibly, an enhanced interaction with activated FX. Conclusions FVBonn induces hypercoagulability via a combination of increased activation/procoagulant activity, decreased susceptibility to APC-mediated inactivation, and slightly reduced APC cofactor activity.

Volar plating of AO C3 distal radius fractures: biomechanical evaluation of locking screw and locking smooth peg configurations.

PURPOSE: The goal of this study was to determine whether locking screws or smooth locking pegs optimize fixation of AO C3 intra-articular distal radius fractures. A secondary goal was to determine which combinations of locking screws and smooth locking pegs influence construct stability. METHODS: In anatomic radius models, AO C3 intra-articular distal radius fractures were fixed using volar locking plates. For the first part, 16 specimens were randomized to receive either 2 locking screws or 2 smooth locking pegs in each of the 3 pairs of holes in the plate. For the second part, 30 specimens were randomized to receive any 4 combinations of locking screws and smooth locking pegs in each of the 3 pairs of holes. Axial loading to failure was applied. RESULTS: Constructs consisting of 4 smooth locking pegs within the lunate fragment were significantly weaker than constructs with 4 locking screws (means 626 N vs 981 N, respectively). Constructs with smooth locking pegs in the ulnar positions of the lunate fragment were weaker than with locking screws in these positions (means 737 N vs 977 N, respectively). Locking screws in the subchondral position of the lunate fragment were stronger than smooth locking pegs in these positions (means 1,227 N vs 934 N, respectively) and any other combination (means 1,227 N vs 942 N, respectively). CONCLUSIONS: Use of locking screws as opposed to smooth locking pegs for AO C3 intra-articular distal radius fractures, particularly subchondral and in the ulnar side of the lunate fragment, optimizes construct stability. This may have implications on postoperative rehabilitation protocols and may limit costs related to use of volar locking plates.

Simulation of nasal flow by lattice Boltzmann methods.

The lattice Boltzmann method is used to calculate the incompressible, viscous flow of air through a model of a nasal cavity, used in experiments. Computations are performed for steady flows at the inspiration and expiration phase of nose breathing. Computed pressure distributions and friction coefficients compare well with Navier-Stokes solutions from a finite-volume method on structured, curvilinear grids. The comparison with conventional Navier-Stokes solvers shows several advantages of the lattice Boltzmann method in particular for bio-medical flow problems. These are the fast grid generation, the simple, granular algorithm, suited for efficient parallelization and the high flexibility for implementing complex boundary conditions and additional transport equations. Lattice Boltzmann methods are therefore efficient candidates for fast flow predictions in the frame of computer-aided rhino-surgery.

Indirect reduction and percutaneous fixation versus open reduction and internal fixation for displaced intra-articular fractures of the distal radius: a randomised, controlled trial.

A total of 179 adult patients with displaced intra-articular fractures of the distal radius was randomised to receive indirect percutaneous reduction and external fixation (n = 88) or open reduction and internal fixation (n = 91). Patients were followed up for two years. During the first year the upper limb musculoskeletal function assessment score, the SF-36 bodily pain sub-scale score, the overall Jebsen score, pinch strength and grip strength improved significantly in all patients. There was no statistically significant difference in the radiological restoration of anatomical features or the range of movement between the groups. During the period of two years, patients who underwent indirect reduction and percutaneous fixation had a more rapid return of function and a better functional outcome than those who underwent open reduction and internal fixation, provided that the intra-articular step and gap deformity were minimised.

The contribution of MD-PhD training to academic orthopaedic faculties.

UNLABELLED: Little is known about the distribution of research-trained physicians across the various specialties. To document the extent to which MD-PhD programs are a source of research-trained faculty for orthopaedic departments, this study examined the specialty choices of graduates of the Medical Scientist Training Program (MSTP) from 1964 to 1994. The MSTP, a combined MD-PhD program supported by the National Institute of General Medical Sciences, (NIGMS), produces roughly 25% of all MD-PhDs in the US. METHODS: Copies of the appendices from training grant applications containing information on MSTP graduates were obtained from the NIGMS. Also, a questionnaire was mailed to 116 university-affiliated orthopaedic surgery departments asking how many faculty were MD's, PhDs or MD-PhDs. RESULTS: Records were obtained for all MST programs. Information on postdoctoral training and/or a current position was reported for 1615 graduates who earned both MD and PhD. Of these graduates, 277 chose non-clinical paths. The other 1338 entered a residency or internship. Of these, 593 were still in residency training, 566 were academic faculty members and 130 were in private practice. In the records, 12 (0.9%) were listed as orthopaedic surgical residents (6) or faculty (6). At this time, all 12 have completed training, and 11 are in academic practice. Eighty-three departments replied to the questionnaire. In that sample of 1761 faculty positions, 1478 were MDs, 217 were PhDs and 36 (2.0%) were MD-PhDs. CONCLUSION: Despite robust support of MD-PhD programs, the number of dual degree recipients on orthopaedic faculties is small when compared to the relative size of the specialty. Other sources of research-trained staff should perhaps be developed.

Autograft replacements for the scapholunate ligament: a biomechanical comparison of hand-based autografts.

An ideal replacement for the scapholunate ligament (SLL) has not been found. The carpometacarpal bone-ligament-bone complex at the base of the second and third metacarpal is proposed as a replacement for the SLL in this study. A cadaveric study of matched SLL, second metacarpal-trapezoid ligament, third metacarpal-capitate ligament, and dorsal periosteal retinaculum was performed. Stiffness and strength were obtained from fresh-frozen specimens tested to failure with a hydraulic distractor. The second metacarpal-trapezoid ligament and the third metacarpal-capitate ligament most closely approximated the stiffness and strength of the SLL. The dorsal periosteal retinaculum was significantly less stiff and was significantly weaker than the SLL. This study indicates that the second or third carpometacarpal ligaments are grafts that approximate the mechanical properties of the SLL.

Successful infiltration of the flexor tendon sheath.

Twenty cadaveric fingers and five thumbs were injected through a midaxial approach, a palmar approach superficial to the flexor tendon, and a palmar approach deep to the tendon, to assess the ability of these approaches to infiltrate the flexor tendon sheath successfully. With care to observe proper positioning of the needle, we were able to achieve essentially equivalent success in infiltration with most of these approaches. However, the midaxial approach to the thumb flexor sheath was unsuccessful.

Early "simple" release of posttraumatic elbow contracture associated with heterotopic ossification.

"Simple" elbow release in the setting of heterotopic ossification is defined as excision of ectopic bone and removal of restricting soft tissues without associated articular procedures. In the past, such procedures were postponed until bone scans were quiescent, serum alkaline phosphatase was normal, and the ectopic bone was mature. Postoperative management sometimes included radiation therapy, prolonged nonsteroidal anti-inflammatory agents, and intensive physiotherapy. We believe that delayed treatment beyond the time of fracture healing is unnecessary to obtain results comparable to those of previous studies. Similarly, we propose that radiation therapy is not necessary after excision of heterotopic ossification. Fourteen patients (15 elbows) were prospectively managed with early excision of posttraumatic heterotopic ossification, immediate postoperative mobilization, and a 5-day course of indomethacin. The average time from injury to release was 23 weeks. The mean preoperative arc of flexion/extension was 43 degrees; that of pronation/supination was 79 degrees. After 2 years, the corresponding values were 120 degrees and 152 degrees. Cubital tunnel syndrome, present in 5 patients, resolved after surgery. Three postoperative complications occurred in 2 patients. There were no recurrent contractures or loss of motion.

Intra-articular fractures of the distal aspect of the radius.

Intra-articular distal radius fractures are a heterogeneous group of injuries with different fracture patterns. The existing classification systems are helpful for describing the fractures but not for assessing their stability or for deciding which surgical approach to use. Patients who have a fracture with at least 1.0 mm of displacement of the articular surface may benefit from open surgical treatment. Improved diagnostic imaging with CT is helpful for fracture classification and surgical planning. The options for surgical treatment include limited open reduction and internal fixation, arthroscopically assisted internal fixation, and open reduction and internal fixation. The surgical approach is determined on the basis of the initial displacement of the fracture. Patients who have a displaced fracture of the volar rim may benefit from a volar approach; those who have a dorsally displaced fracture, from a dorsal approach; and those who have an impacted fracture such as a die-punch fracture, from a dorsal approach that provides better visualization of the articular surface. The long-term functional outcome is determined in part by the severity of the fracture as defined by the amount of comminution, the initial severity of displacement, and the number of fracture fragments. The accuracy of the reconstruction of the articular surface, with the goal of establishing congruency to within 1.0 mm, is also important in order to minimize the risk of late osteoarthrosis. Of all of the extra-articular parameters, restoration of the length of the radius is the most important for enhancing recovery of motion and grip strength and for preventing problems involving the distal radioulnar joint--the so-called forgotten joint in distal radial fractures.

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

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

Biomechanical analysis of capitate shortening with capitate hamate fusion in the treatment of Kienböck's disease.

The biomechanical effects of surgical treatment options for Kienböck's disease have been compared. However, no study has included a direct analysis of capitate shortening along with capitate-hamate fusion (CSCHF). To investigate the biomechanical effects of CSCHF, a cadaver model of the upper extremity was used to determine radiocarpal articular pressure changes resulting from this procedure using pressure-sensitive film. Ten specimens were tested by placing each in an apparatus that applied load across the radiocarpal joint through the wrist flexor and extensor tendons. Testing was performed in 3 wrist positions (ulnar deviation, radial deviation, and neutral) combined with 3 forearm positions (pronation, supination, and neutral) and neutral flexion/extension. Radioscaphoid, radiolunate, and mean contact pressures in the entire radiocarpal joint were determined for each of the 9 wrist positions, both intact and after surgery. The radioscaphoid mean pressure increased in 6 of 9 positions and was unchanged in 3 positions. The radiolunate mean pressure decreased in 9 of 9 positions. The radiocarpal mean pressure increased in 2 of 9 positions and was unchanged in 7 positions. These data suggests that CSCHF increases radioscaphoid mean pressure, decreases radiolunate mean pressure, and has little effect on radiocarpal mean pressure.

Intrafocal (Kapandji) pinning of distal radius fractures with and without external fixation.

Seventy-three patients were treated with either intrafocal pinning (Kapandji technique) alone or in combination with external fixation between 1988 and 1993 for extra-articular fractures of the distal radius (with or without a nondisplaced extension into the radiocarpal articular surface) with inadequate alignment after initial closed reduction. Sixty-one patients were available for follow-up examination at an average of 34 months (range, 24-71 months). The average age was 52 years (range, 16-84 years). Thirty-three of the patients were female. The patients all had dorsally displaced extra-articular fractures, although 56% had a nondisplaced extension of the fracture into the radiocarpal joint and 46% had a nondisplaced fracture extending into the distal radioulnar joint. The patients were separated into groups based on age, degree of comminution, and whether external fixation was also used. In the older patients, range of motion, grip strength, and pain relief were significantly better when external fixation was used, even when only 1 cortex of the radius demonstrated comminution. In the younger patients, good results in terms of range of motion, grip strength, and pain relief were obtained when percutaneous intrafocal pins were used alone in patients with comminution of only 1 surface of the radius (<50% of the metaphyseal diameter). When > or = 2 sides of the radial metaphysis were comminuted, the patients with external fixation had better results than those without external fixation. Although the correction of palmar tilt and radial tilt did result in better functional results, the restoration of radial length had the most significant effect on range of motion and grip strength.

Two-, four-, and six-strand zone II flexor tendon repairs: an in situ biomechanical comparison using a cadaver model.

A dynamic in vitro model of zone II flexor tendon repair was used to compare gliding resistance, gap formation, and ultimate strength of the 2-, 4-, and 6-strand repair techniques. Each of 12 hands was mounted to a loading frame with 3 flexor tendons attached to individual pneumatic cylinders. A spring attached to a pin through the distal end of each digit provided a 1.25-kg resistance force. The force required to flex each proximal interphalangeal joint to 90 degrees was determined. Following this, the tendons were sectioned and each was repaired using a different technique so that each specimen acted as its own control. The 2- and 4-strand core sutures were placed using a suture interlock technique with radial and ulnar grasping purchase of the tendon on each side of the transverse part of the repair. Each repair was accomplished using a single core stitch with the knot buried between the tendon ends. The 4-strand repair involved an additional horizontal mattress suture with the knot buried. Repair of the dorsal side of the tendon was performed followed by core suture placement. The palmar portion of the peripheral locking suture was completed after core suture placement. Following repair, each hand was remounted on the frame and cycled 1,000 times. After cyclic loading, the resulting gap between the repaired ends of each tendon was measured, the tendons were removed from the hand, and each was loaded to failure in tension. All tendon repairs showed a small, but not statistically significant, increase in gliding resistance after reconstruction. The 2-strand repair had significantly greater gap formation after cyclic loading (mean gap, 2.75 mm) than either the 4-strand (0.30 mm) or 6-strand (0.31 mm) repair. The tensile strength of the 6-strand repair (mean, 78.7 N) was significantly greater than either the 4-strand (means, 43.0 N) or 2-strand (mean, 33.9 N) repair.

Self-tapping versus standard tapped titanium screw fixation in the upper extremity.

Most screws used in fracture fixation necessitate a separate step for tapping of the screw hole. Titanium screw systems have been developed in which the screws can be inserted directly after a drill hole is made. These self-tapping screws thereby eliminate an operative step. A retrospective study was conducted that evaluated all wrist and hand procedures performed between January 1992 and December 1994 by 1 surgeon using screw fixation. The results of 39 cases treated with standard tapped titanium screws were compared with 28 cases treated with self-tapping titanium screws. Nearly identical union and complication rates were obtained in each group. Comparable results can be obtained with self-tapping screw fixation, which limits the number of instruments needed, eliminates an operative step, and thereby may diminish operative risk and shorten operative time.

MR imaging of clinically suspected scaphoid fractures.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of MR imaging in revealing occult fractures in patients with clinically suspected acute scaphoid fractures who have normal or equivocal findings on radiographs. SUBJECTS AND METHODS: Thirty-six patients underwent MR imaging within 7 days of wrist injury. All had physical findings suggestive of scaphoid fracture. Coronal T1-weighted, short inversion time inversion recovery, and either T2-weighted or proton density-weighted fast spin-echo sequences with fat suppression were used. Follow-up radiographs were obtained at least 2 weeks after MR imaging whenever possible. All imaging studies were reviewed by two musculoskeletal radiologists. RESULTS: MR imaging revealed 22 occult fractures in 20 patients. Thirteen of these 22 fractures were in the scaphoid bone, and nine were in the distal radius. On MR images, 16 patients had no evidence of fracture. Follow-up radiographs were available in 14 of the 20 patients who had occult fracture revealed by MR imaging. Eleven of the 13 occult fractures of the scaphoid bone were followed up (two were lost to follow-up), and 10 of the 11 showed signs of healing. Five of the nine lesions of the distal radius were followed up, and three of these showed evidence of healing fracture. Three patients without MR evidence of a fracture had follow-up radiographs that showed no fracture. Three patients had findings consistent with bone contusion on MR images; in two patients, the contusion was associated with other fractures, and in one patient, the contusion was isolated. CONCLUSION: MR imaging can reveal occult wrist fractures when findings on radiographs are normal or equivocal.

Failure of cast immobilization for thumb ulnar collateral ligament avulsion fractures.

To determine if small avulsion fractures of the thumb ulnar collateral ligament (UCL) with minimal (< or = 2.0 mm) displacement can successfully be treated by cast immobilization, the authors reviewed 9 patients with minimally displaced fractures initially treated by casting. Despite immobilization within an average of 2 days of the initial injury (range, 0-6 days), a minimum of 6 weeks of immobilization in a cast, and adequate rehabilitation, all 9 patients had persistent thumb pain, especially with activities requiring strong pinch. After undergoing open reduction and internal fixation, the patients had relief of thumb pain and pinch strength improved from 36% of the contralateral side to 89% (p < .01). Grip strength increased from 77% to 93% (p < .05), but the ranges of motion of the thumb metacarpophalangeal and interphalangeal joints were not significantly altered. Minimally displaced UCL avulsion fractures frequently have significant rotation that prevents successful fracture healing even with prompt cast immobilization.

Consistency of AO fracture classification for the distal radius.

We sought to quantify agreement by different assessors of the AO classification for distal fractures of the radius. Thirty radiographs of acute distal radial fractures were evaluated by 36 assessors of varying clinical experience. Our findings suggest that AO 'type' and the presence or absence of articular displacement are measured with high consistency when classification of distal radial fractures is undertaken by experienced observers. Assessors at all experience levels had difficulty agreeing on AO 'group' and especially AO 'subgroup'. To categorize distal radial fractures according to joint displacement and AO type is simple and reproducible. Our study examined only whether distal radial fractures could be consistently classified according to the AO system. Validation of the classification as a predictor of outcome will require a prospective clinical study.

Primary fusion of fracture dislocations of central carpometacarpal joints.

Six patients with dislocations or fracture dislocations of at least the second and third carpometacarpal joints are presented. Closed reduction was attempted in all cases. Two dislocations with minimal periarticular fractures were stable and were treated with cast immobilization. Four fracture dislocations were unstable and were treated with primary arthrodesis of the injured joints. One patient was lost to followup and the other 5 were observed for an average of 24 months. Establishment of a stable or rigid central carpometacarpal joint produced an excellent result in 4 patients and a satisfactory result in 1 patient.

Fibro-osseous pseudotumor of the distal phalanx.

Recurrent soft-tissue digital masses with osseous components frequently result in diagnostic and treatment dilemmas. We discuss a case of a recurrent fibro-osseous pseudotumor of the digit, review specific diagnostic and histological features, and recommend treatment.