Corpus callosotomy: a palliative therapeutic technique may help identify resectable epileptogenic foci.

Corpus callosotomy has a long history as a palliative treatment for intractable epilepsy. Identification of a single epileptogenic zone is critical to performing successful resective surgery. We describe three patients in which corpus callosotomy allowed recognition of unapparent seizure foci, leading to subsequent successful resection. We retrospectively reviewed our epilepsy surgery database from 2003 to 2005 for children who had a prior callosotomy and were candidates for focal resection. All underwent magnetic resonance imaging and scalp video electroencephalograph monitoring, and two had magnetoencephalography, electrocorticography and/or intracranial video electroencephalograph monitoring. The children were 8 and 9 years old, and seizure onset varied from early infancy to early childhood. One child had a history of head trauma preceding seizure onset, one had a large intracerebral infarct and dysplastic cortex in the contralateral frontal lobe, and the other had an anterior temporal lobe resection without improvement in seizure frequency. After medical management failed, callosotomy was performed with the expectation of decreasing the seizure types affecting both hemispheres. Following transection of the callosal fibers, a single focus was recognized and resected, with resultant dramatic improvement in seizure control. In medically refractory epilepsy, where rapid secondary bisynchrony is suspected but the electroencephalograph is non-localizing, callosotomy should be considered as a means of treating generalized seizure types, but may also assist in identifying potentially operable seizure foci. Study limitations include its retrospective nature and cohort size. The findings, however, suggest the need for prospective, systematic, well-controlled studies of the use of corpus callostomy in this intractable patient population.     

Effect of Graft Size, Angle, and Intergraft Distance on Dense Packing in Hair Transplant

BACKGROUND: The maximum number of hair grafts that can be safely implanted in 1 cm2 is still debatable. To our knowledge, no previous report has addressed this issue in three dimensions, taking into account the size, the angle of the graft, and the intergraft distance. OBJECTIVES: To study the effect of the size and angle of the graft and the intergraft distance on dense packing. METHODS: Using a mathematical formula (the maximum number of hair grafts in 1 cm2 = 33 * cosine), the volume of the recipient area and the volume of the hair graft are calculated, assuming that the surface area of the recipient area is 1 cm2, the diameter of the hair graft is 1 mm, and the intergraft distance is 1.5 mm laterally and 1 mm anteriorly and posteriorly. RESULTS: The maximum number of hair grafts that could be implanted in 1 cm2 at a 90 angle in relation to the skin surface is 33 grafts, at a 60 angle is 28 grafts, and at a 30 angle is 16 grafts. CONCLUSION: The maximum number of hair grafts that can be implanted in any given recipient area depends on the graft size, the angle or direction of these grafts, and the intergraft distance. Where more space is allowed between the grafts, and the more acute the angle, the fewer hair grafts that can be implanted.     

The use of 19F spectroscopy and diffusion-weighted MRI to evaluate differences in gene-dependent enzyme prodrug therapies.

To evaluate noninvasive measures of gene expression and tumor response in a gene-dependent enzyme prodrug therapy (GDEPT), a bifunctional fusion gene between Saccharomyces cerevisiae cytosine deaminase (CD) and Haemophilus influenzae uracil phosphoribosyltransferase (UPRT) was constructed. CD deaminates 5-fluorocytosine (5FC) to 5-fluorouracil (5FU), and UPRT subsequently converts 5FU to fluorouridine monophosphate, and both of these reactions can be monitored noninvasively in vitro and in vivo using 19F magnetic resonance spectroscopy (MRS). Following transient transfection the CD-UPRT fusion protein exhibited both UPRT and CD enzymatic activities as documented by 19F MRS. In addition, an increase in CD activity and thermal stability was witnessed for the fusion protein compared to native CD. Stable expression of CD-UPRT in 9L glioma cells increased both 5FC and 5FU sensitivity in vitro compared to CD-expressing and wild-type 9L cells. Noninvasive 19F MRS of both CD and UPRT gene function in vivo demonstrated that in animals bearing CD-expressing tumors there was limited conversion of 5FC to 5FU with no measurable accumulation of cytotoxic fluorinated nucleotides (F-nucs). In contrast, CD-UPRT-expressing tumors had increased CD gene activity with a threefold higher intratumoral accumulation of 5FU and significant generation of F-nucs. Finally, CD-UPRT yielded increased efficacy in an orthotopic animal model of high-grade glioma. More importantly, early changes in cellular water mobility, which are felt to reflect cellular death, as measured by diffusion-weighted MRI, were predictive of both durable response and increased animal survival. These results demonstrate the increased efficacy of the CD-UPRT GDEPT compared to CD alone both biochemically and in a preclinical model and validate both 19F MRS and diffusion-weighted MRI as tools to assess gene function and therapeutic efficacy.     

Postoperative splinting for isolated digital nerve injuries in the hand.

Digital nerve injuries in the hand are common and can result in significant impairment and functional restriction. Despite this, there is relatively little literature, particularly with respect to postoperative rehabilitation. Splinting after repair, purported to protect the repaired nerve from excessive stretch is still commonly used. Recent cadaveric studies indicate postoperative rehabilitation is not necessary with resection up to 2.5mm. A randomized controlled trial was therefore undertaken to determine whether splinting after isolated 5th degree digital nerve transection is in fact necessary. Twenty-six subjects were recruited over a two-year period and randomized to either three weeks of hand-based splinting or free active motion. ANCOVA indicated no differences in sensibility at six months between the two groups. Subjects also reported their greatest functional limitations were because of hyperesthesia. Although this study is underpowered, these limited results suggest splinting may not be required postoperatively.     

Similar motion of a hand-held object may trigger nonsimilar grip force adjustments.

The tight coupling between load (L) and grip (G) forces during voluntary manipulation of a hand-held object is well established. The current study is to examine grip-load force coupling when motion of the hand with an object was either self-generated (voluntary) or externally generated. Subjects performed similar cyclic movements of different loads at various frequencies with three types of manipulations: 1) voluntary oscillation, 2) oscillating the right arm via the pulley system by the left leg (self-driven oscillation), and 3) oscillating the arm via the pulley system by another person (other-driven oscillation). During the self-generated movements: 1) the grip forces were larger and 2) grip-load force modulation was more pronounced than in the externally generated movements. The G-L adjustments are not completely determined by the mechanics of object motion; nonmechanical factors related to movement performance, for instance perceptual factors, may affect the G-L coupling.     

Executive functions and adaptive functioning in young adult attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is associated with impairments in occupational, social, and educational functioning in adults. This study examined relations of adaptive impairment to ADHD symptom domains (inattentive-disorganized and hyperactive-impulsive) and to deficits in executive functioning (EF) in 195 well-characterized adults (105 ADHD, 90 non-ADHD, between ages 18 and 37). Participants completed a battery of EF measures as well as assessments of adaptive functioning. Confirmatory factor analyses were used to validate latent factors for adaptive functioning and EF. In a measurement model, weaker EF was associated with poorer adaptive functioning (r = -.30). When multi-informant composite variables for current inattentive-disorganized and hyperactive-impulsive ADHD symptoms were included in the structural model, EF no longer predicted adaptive functioning. While both symptom composites were similarly related to EF (inattentive-disorganized r = .36; hyperactive-impulsive r = .29), inattentive-disorganized symptoms accounted for more variance in adaptive functioning (67.2% vs. 3.6%). Furthermore, for retrospectively reported childhood symptoms of ADHD, only the inattentive-disorganized symptom domain was related to EF or adaptive impairment. These results suggest that, in adults with ADHD, inattentive-disorganized symptoms may be the primary contributor to key aspects of poorer adaptive function and may be the behavioral path through which EF deficits lead to adaptive impairment.     

Secretory immunoglobulin‐A reactivity following increases in workload intensity using the Defined Intensity Stressor Simulation (DISS)

Previous work suggests that secretory immunoglobulin‐A (S‐IgA) reactivity is inversely related to the perceived demands of the stressor. The Defined Intensity Stressor Simulation (DISS) comprises eight stressor modules, and allows for the manipulation of stress either through increasing the number of modules, or increasing the workload of the modules. The current study assessed the effect of increasing the workload of four modules upon S‐IgA reactivity and perceived demands. Participants (N = 14) attended three sessions on consecutive days where they provided a timed saliva sample immediately before and after 5 min on the DISS at low, medium and high workload. Following each session participants recorded their perceptions of the task with regard to workload and levels of stress and arousal. Perceived workload and stress, but not arousal, increased in accordance with increases in workload, however, differential S‐IgA reactivity was observed. Low workload resulted in a slight increase in S‐IgA secretion; medium workload elicited significant up‐regulation, while down‐regulation of S‐IgA occurred following high workload. As DISS is analogous to a variety of working environments it is suggested that the observed S‐IgA reactivity is indicative of how individuals react to multi‐tasking environments when faced with increases in objective or perceived workload demands. As S‐IgA levels are related to protection from illness, down‐regulation of S‐IgA in those who perceive greater demands may lead to greater vulnerability to ill‐health. Copyright © 2005 John Wiley & Sons, Ltd.