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ABSTRACT: Botulinum neurotoxin-A (BoNTA) is a potent neurotoxin used to alter muscle tone to manage spasticity and to provide tendon bioprotection; however, the appropriate dose and injection volume to administer is not defined. Male mice (n = 120) received BoNTA injections into one gastrocnemius with either a constant volume (10 µl) with a variable dose (1, 3, 6 U/kg) or a constant dose (3 U/kg) in a variable volume (2.5, 5, 10, 20, 30 µl). Electromyographic (EMG) examination, muscle force generation (MFG), and wet muscle mass were measured in the ipsilateral and contralateral limbs at 1, 2, 4, or 12 weeks post-injection. MFG and EMG responses decreased to approximately 40% of contralateral after a 1 U/kg injection and 0% of contralateral by 3 and 6 U/kg injection at 1 week after injection. Neuromuscular blockade was greatest with a 10 µl injection volume. MFG, EMG examination, and wet muscle mass reached contralateral values 12 weeks after injection for all injection doses and volumes tested. Effective injection doses and volumes were identified for producing full and partial neuromuscular blockade in the mouse gastrocnemius. These findings have important clinical implications in the intramuscular administration of BoNTA to manage muscle tone.
Journal of Orthopaedic Research 04/2011; 29(11):1764-70. · 2.81 Impact Factor
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ABSTRACT: The management of peripheral nerve injuries with segmental defects is a challenge to both patient and surgeon. Repairs under tension have a poor prognosis; sensory nerve allografts have donor site morbidity and suboptimal motor recovery, but remain the gold standard. The development of conduit-based repair strategies has evolved and these are promising for sensory nerves and short defects; however, no conduit filler is clinically available that improves motor recovery equivalent to sensory autografts. In this study, motor recovery using keratin-based hydrogel filler was compared with that for sensory nerve autografts and empty conduits.
Fifty-four mice were randomized into 3 treatment groups: empty conduit, sural nerve autograft, and keratin hydrogel-filled conduit. Animals were followed for 6 weeks, 3 months, and 6 months. Outcomes included compound motor action potential (CMAP), nerve area, myelinated axon number and density, and myelinated axon diameter.
Neuromuscular recovery with keratin was greater than with empty conduits in most outcome measures. Nerves that regenerated through the keratin hydrogel had lower conduction delays, greater amplitudes, more myelinated axons, and larger axons than nerves that regenerated through empty conduits. Sensory nerve autografts and keratin hydrogel were statistically equivalent in CMAP measurements at 6 months. Moreover, keratin-filled conduits demonstrated greater axon density and larger average axon diameter than both empty conduits and autograft at 6 months.
In a mouse tibial nerve model, keratin hydrogels significantly improved electrophysiological recovery, compared with empty conduits and sensory nerve autografts, at an early time point of regeneration. Keratin hydrogels also produce long-term electrical and histological results superior to empty conduits and equivalent to sensory nerve autografts.
The Journal of hand surgery 12/2008; 33(9):1541-7. · 1.33 Impact Factor
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Jianjun Ma,
Jian Shen, Jeffrey P Garrett,
Cassandra A Lee,
Zhongyu Li,
Gamal A Elsaidi,
Andrew Ritting,
Jeffrey Hick,
Kim H Tan,
Thomas L Smith,
Beth P Smith,
L Andrew Koman
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ABSTRACT: Neuromuscular junction destabilization following nerve injury contributes to irreversible functional impairment. Myogenic Regulatory Factors (MRF's) including myoblast determination factor (MyoD), MRF-4, Myogenin, and myogenic factors-5 (myf-5), and Growth-associated protein 43 KDa (GAP43) regulate gene expression of nicotinic acetylcholine receptor (nAChR) subunits (alpha, beta, delta, gamma, and epsilon). We hypothesized that nerve injury induces altered gene expression of MRF's, nAChRs, and GAP-43 in the skeletal muscle which destabilize neuromuscular junctions. The tibial nerve was transected in 42 juvenile male Sprague-Dawley rats. Denervated and contralateral control gastrocnemius m. mRNA for nAChR subunits, MRF's, and GAP-43 were determined by real time reverse transcription polymerase chain reaction (real time RT-PCR). After transection, muscle mass decreased for 1 year with a nadir of 75% at 3 months. Alpha, gamma, and epsilon subunit genes increased by 3 and peaked at 7 days before returning to control levels (P < 0.05). Beta subunits and GAP-43 tended to increase. Delta subunits peaked at 3 days returning to control levels by 30 days. By one month, most of the nAChR subunits had returned to control levels. Alpha, beta, gamma, and delta subunit expression remained significantly lower than control up to 1 year later (P < 0.05). MRF4, Myogenin, and MyoD expression paralleled that of alpha, gamma, and epsilon nAChR subunits (P < 0.05). Gene expression of nAChR alpha, gamma, delta and epsilon subunits was biphasic in the first month after nerve injury, similar to that of MRF's. nAChR subunits and MRF's may play a critical role in neuromuscular junction stability.
Journal of Orthopaedic Research 11/2007; 25(11):1498-505. · 2.81 Impact Factor
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ABSTRACT: Previous cadaveric data show that disruption of the triangular fibrocartilage complex (TFCC) at the wrist allows 0.5 to 3.0 mm of proximal radius migration. Anatomic studies have documented the presence of superficial and deep fibers of both the palmar and the dorsal distal radioulnar joint (DRUJ) ligaments. The aim of this study was to determine the contribution of the superficial and deep fibers of the DRUJ ligaments to longitudinal forearm stability as measured by ulnar-positive variance.
Eight fresh-frozen cadaver specimens were included in this study. Each specimen was secured with external fixation clamps to a sequential loading frame with the elbow in 90 degrees of flexion and the forearm and wrist in neutral pronation supination, neutral ulnar-radial deviation, and neutral volar-dorsal angulation. The radial head was resected and a force gauge was applied to the proximal radius. The peripheral TFCC was identified through an incision between the fifth and sixth extensor compartments and the dorsal capsulotomy of the DRUJ capsule. After baseline measurement sequential transection of the superficial and deep fibers of the TFCC was performed. Before and after each step load application and removal were performed by attaching an 88.90-N weight to the end of a force gauge and via longitudinal traction on the proximal part of the radius, and ulnar variance was measured with wrist fluoroscopy.
Transection of the superficial TFCC fibers resulted in radius migration of 0.70 mm. This migration, however, was not significantly different from that observed at baseline. After both the superficial and deep TFCC fibers were transected the radius migrated proximately with load. This change of ulnar variance was significantly greater than that observed at baseline or after transection of only the superficial TFCC fibers.
Traumatic injury to the TFCC with radiographic evidence of ulnar-positive variance may be an indication of disruption of the deep TFCC fibers.
The Journal Of Hand Surgery 12/2005; 30(6):1172-7. · 1.35 Impact Factor
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ABSTRACT: Although several factors have been related to the development of digital stiffness after external fixation of distal radius fractures, distraction can be considered one of the most important. This study determined a threshold for distraction during external fixation of distal radius fractures and documented the effect of distraction of the wrist on metacarpophalangeal (MCP) joint motion.
Eight fresh-frozen cadaveric forearms were mounted on a testing frame and the flexor digitorum superficialis (FDS) tendon of each finger was pulled individually until a 90 degrees flexion at the MCP joint was generated. A load cell was used to record the force applied on the tendons. Tendon displacement was calculated by using a linear potentiometer. Sequential distraction across the wrist was applied through a distraction outrigger on the external fixator and was measured both on the external fixator in millimeters and on fluoroscopic images. Finger motion was captured by using a 2-dimensional motion tracking system. The experiment was repeated at different levels of wrist distraction (increments of 2 mm to a maximum of 14 mm).
There was a significant difference in the effect of distraction on the individual fingers. For the index finger the load required for the FDS to produce a 90 degrees flexion at the MCP joint was increased linearly between 0 and 8 mm of wrist distraction. For the other fingers a threshold of distraction was found. A significant increase in the load was noticed after 5 mm of wrist distraction.
More than 5 mm of wrist distraction increases the load required for the FDS to generate MCP joint flexion for the middle, ring, and small fingers. For the index finger, however, as much as 2 mm of wrist distraction significantly increases the load required for flexion at the MCP joint.
The Journal Of Hand Surgery 08/2005; 30(4):773-9. · 1.35 Impact Factor
