Persistent behavioral impairment caused by embryonic methylphenidate exposure in zebrafish.

As more adults take the stimulant medication methylphenidate to treat attention deficit hyperactivity disorder (ADHD) residual type, the risk arises with regard to exposure during early development if people taking the medication become pregnant. We studied the neurobehavioral effects of methylphenidate in zebrafish. Zebrafish offer cellular reporter systems, continuous visual access and molecular interventions such as morpholinos to help determine critical mechanisms underlying neurobehavioral teratogenicity. Previously, we had seen that persisting neurobehavioral impairment in zebrafish with developmental chlorpyrifos exposure was associated with disturbed dopamine systems. Because methylphenidate is an indirect dopamine agonist, it was thought that it might also cause persistent behavioral impairment after developmental exposure. Zebrafish embryos were exposed to the ADHD stimulant medication methylphenidate 0-5 days post fertilization (12.5-50mg/l). They were tested for long-term behavioral effects as adults. Methylphenidate exposure (50mg/l) caused significant increases in dopamine, norepinepherine and serotonin on day 6 but not day 30 after fertilization. In the novel tank diving test of predatory avoidance developmental methylphenidate (50mg/l) caused a significant reduction in the normal diving response. In the three-chamber spatial learning task early developmental methylphenidate (50mg/l) caused a significant impairment in choice accuracy. These data show that early developmental exposure of zebrafish to methylphenidate causes a long-term impairment in neurobehavioral plasticity. The identification of these functional deficits in zebrafish enables further studies with this model to determine how molecular and cellular mechanisms are disturbed to arrive at this compromised state.

Quantifying deficits in the 3D force capabilities of a digit caused by selective paralysis: application to the thumb with simulated low ulnar nerve palsy.

We present the development of a vision-feedback method to characterize how selective paralysis distorts the three-dimensional (3D) volume representing digit-tip force production capability and its application to healthy individuals producing thumb-tip force with and without simulated low ulnar nerve palsy (LUNP). Subjects produced maximal static voluntary force spanning the transverse, sagittal and frontal planes of the thumb (16, 15 and 10 subjects, respectively). Subjects produced thumb-tip force tasks in guided and self-selected directions. The envelope (convex hull) of extreme forces in each plane approximated that cross-section of the 3D volume of force capability. Some subjects repeated the tasks with a temporary ulnar nerve block applied at the wrist to simulate complete acute LUNP. Three geometric properties of the force convex hull characterized each cross-section's shape: the ratios of its principal moments of inertia (RPMIs), the orientation of its principal axis (OPA), and its centroid location. Our results show that force production in the thumb's sagittal plane may be a reproducible and objective test to grade motor impairment in LUNP: paired t-tests of the larger RPMI in this plane best distinguished the nerve-blocked cases from the control cases in the guided task (p = 0.012), and Discriminant Analysis of the centroid location for the self-selected task in this plane correctly classified 94.7% of subjects into the control and ulnar nerve-blocked groups. We show that our method measures and detects changes in a digit's force production capabilities. Towards a clinical test of motor impairment in LUNP, this biomechanical study dictates which 3D thumb-tip forces to measure (those in the sagittal plane) and how to measure them (using the self-selected task).

The fundamental thumb-tip force vectors produced by the muscles of the thumb.

A rigorous description of the magnitude and direction of the 3D force vector each thumb muscle produces at the thumb-tip is necessary to understand the biomechanical consequences to pinch of a variety of paralyses and surgical procedures (such as tendon transfers). In this study, we characterized the 3D force vector each muscle produces at the thumb-tip, and investigated if these thumb-tip force vectors scaled linearly with tendon tension. In 13 cadaver specimens, we measured the output 3D thumb-tip force vector produced by each tendon acting on the thumb, plus two common tendon transfers, as a function of input tendon tension. After fixing the hand to a rigid frame, we mounted the thumb by configuring it in standardized key or opposition pinch posture and coupling the thumb-tip to a rigidly held 6 degree-of-freedom force/torque sensor. Linear actuators applied tension to the distal tendons of the four extrinsic thumb muscles, and to six Nylon cords reproducing the lines of action of (i) the four intrinsic thumb muscles and (ii) two alternative tendon transfers commonly used to restore thumb opposition following low median nerve palsy. Each computer-controlled linear actuator ramped tendon tension from zero to 1/3 of predicted maximal muscle force expected at each tendon, and back to zero, while we measured the 3D force vector at the thumb-tip. In test/re-test trials, we saw thumb-tip force vectors were quite sensitive to mounting procedure, but also sensitive to variations in the seating of joint surfaces. We found that: (i) some thumb-tip force vectors act in unexpected directions (e.g., the opponens force vector is parallel to the distal phalanx), (ii) the two tendon transfers produced patently different force vectors, and (iii) for most muscles, thumb-tip force vectors do not scale linearly with tendon tension--likely due to load-dependent viscoelastic tendon paths, joint seating and/or bone motion. Our 3D force vector data provide the first quantitative reference descriptions of the thumb-tip force vectors produced by all thumb muscles and two tendon transfers. We conclude that it may not be realistic to assume in biomechanical models that thumb-tip force vectors scale linearly with tendon tensions, and that our data suggest the thumb may act as a "floating digit" affected by load-dependent trapezium motion.

Failure of a retinacular flap to prevent dorsal wrist pain after titanium Pi plate fixation of distal radius fractures.

Patients with distal radius fractures that had been treated with a dorsal Pi plate and retinacular flap covering the transverse limb of the Pi plate were evaluated clinically and radiographically. Nine of 20 patients (45%) required plate removal for dorsal wrist pain. Three of the remaining 11 who retained the plate had dorsal tenderness over the wrist extensors. There were no differences evident between the 2 groups in plate size, position, or number of screws used. In addition there were no significant differences between the groups in either radial height or inclination. The palmar tilt did show a trend toward statistical significance: those patients who required plate removal had an average of 4.1 degrees of dorsal tilt, patients whose plate was not removed averaged 2.8 degrees of palmar tilt. Our results show that the retinacular flap covering the distal transverse limb of the Pi plate did not prevent the occurrence of dorsal wrist pain. Dorsal wrist pain remained a problem with dorsal plating of distal radius fractures.