Conventional versus epineural sleeve neurorrhaphy technique: functional and histomorphometric analysis

Three methods of nerve repair involving the epineural sleeve technique were compared with conventional nerve repair using the rat sciatic nerve transection model in four groups. In group 1, the sciatic nerve was repaired using the conventional epineural technique by placing four sutures. In groups 2, 3, and 4, the epineural sleeve technique was combined with two sutures, fibrin glue, and two sutures with fibrin glue, respectively. Functional recovery was evaluated using walking track analysis, limb circumference, and the severity of toe contracture. Diameter of the sciatic nerve fibers, total number of myelinated fibers, diameter of the myelin sheath, and the axon-to-fiber diameter ratio were measured at 12 weeks. The results showed better functional recovery as well as a higher number of myelinated fibers in groups using the epineural sleeve technique compared with conventional technique ( < 0.05). The addition of fibrin glue, however, did not make any significant difference. The epineural sleeve technique was found to be superior when compared with conventional nerve repair, providing faster functional recovery and improved nerve regeneration.     

Advances in composite tissue allograft transplantation as related to the hand and upper extremity

The clinical transplantation of composite tissue allografts (CTA) such as human hand or larynx is stimulating discussions among surgeons at national and international forums on the indications, ethical aspects, toxic effects of immunosuppression, and functional results of the first reported cases of unilateral and bilateral hand transplantation. This Clinical Perspective article presents the latest advances in clinical and experimental research related to the field of CTAs. The article presents the historic aspects of CTA, a broad view of the current state of composite tissue transplantation, the mechanism of allograft rejection, current experimental and clinical protocols, and, finally, the future prospects of the standard use of CTAs. It is clear that there is a substantial demand for routine use of CTAs but the treatment protocols need to be optimized and the functional outcomes need to be improved.     

Dehydroepiandrosterone as an enhancer of functional recovery following crush injury to rat sciatic nerve

This study was designed to investigate the effect of dehydroepiandrosterone (DHEA) on the recovery of the rat sciatic nerve following crush injury. A standard hemostat system was used to create the injury, with a length of 1.5 mm in three groups of 18 animals each. In group I, the crush injury was applied without any treatment. In groups II and III, vehicle (ethylene glycol) and DHEA solutions were injected subepineurally 30 min following the crush injury. Sciatic function index (SFI), toe contracture measurement, gastrocinemius muscle weight, total number of myelinated fibers, fiber diameters, myelin thickness, and axon/fiber cross-sectional ratio were measured at 3, 6, and 12 weeks. The SFI values in the DHEA group showed a faster return to normal values confirmed at 3 and 6 weeks (P < 0.05). The number of myelinated fibers and fiber diameters at 6 and 12 weeks were significantly higher in the DHEA group (P < 0.05). In this study, the subepineural injection of DHEA following crush injury was found to enhance functional recovery of the rat sciatic nerve.     

Late effects of TNF-alpha-induced inflammation on the microcirculation of cremaster muscle flaps under intravital microscopy

In order to understand the microcirculatory changes and regulatory mechanisms governing passage of neutrophils from the vascular bed to the interstitial tissue during ischemia/reperfusion (I/R) injury, a key component of this injury, tumor necrosis factor-alpha (TNF-alpha)-induced inflammation was analyzed. Twenty-four Sprague-Dawley rats were divided into four groups, containing six animals in each. The effect of TNF-alpha-induced inflammation was studied at two different time points, early sequential and late. In the early-effect Groups 1 and 2, animals were given TNF-alpha and vehicle, respectively. Microcirculatory changes were recorded for 6 hr continuously. In the late-effect Groups 3 and 4, following TNF-alpha injection and vehicle, microcirculatory changes were measured 16 hr later. In the early-effect groups, the number of rolling and adhering leukocytes was increased immediately following TNF-alpha injection and remained elevated for the first 3 hr (p<0.05). The number of transmigrated leukocytes remained significantly increased throughout the first 6 hr (p<0.05) and returned to normal at 16 hr. In delayed-effect groups, a second peak in the number of rolling leukocytes was noted at 16 hr (p<0.05). The numbers of rolling and adhering lymphocytes, although remained at the baseline for the first 6 hr, was increased 2- and 1.5-fold at 16 hr, respectively (p<0.05). The number of perfused capillaries gradually decreased over time in the TNF-alpha-induced inflammation groups. A vasodilatory response was noted at the third and fourth order arterioles within the first 3 hr of measurement (p<0.05), but returned to normal afterward. The detrimental effects of TNF-alpha-induced inflammation during I/R injury could be prolonged up to 16 hr at the microcirculatory level of the muscle flaps.     

Polyglutamine-induced ion channels: a possible mechanism for the neurotoxicity of Huntington and other CAG repeat diseases

CAG repeats resulting in long polyglutamine tracts have been implicated in the pathogenesis of at least eight neurodegenerative diseases including Huntington. Expression of polyglutamine repeats is required for disease and increasing length of the repeats leads to earlier onset of illness (anticipation). Expression of polyglutamine repeats in cultured neurons leads to deposition of intracellular aggregates resembling those found in amyloid diseases, and to neurotoxicity. We report here that polyglutamine can induce large (19-220 pS), long-lived, (lifetime = 6 sec), non-selective (P(cation) = P(anion)) ion channels in planar phospholipid bilayer membranes, and that channel formation is enhanced by acidic pH. We propose that channel formation may be a mechanism of cellular toxicity in Huntington and other CAG repeat disease.     

Further evidence of association between behavioral inhibition and social anxiety in children

OBJECTIVE: The authors sought to examine psychopathological correlates of behavioral inhibition in young offspring of parents with panic disorder and/or major depression. METHOD: Behavioral inhibition, determined by using standard laboratory observations, was assessed in four groups of children (age 2-6 years): 129 children of parents with both panic disorder and major depression, 22 children of parents with panic disorder alone, 49 children of parents with major depression alone, and 84 comparison children of parents with neither panic disorder nor major depression. Psychopathology in children > or =5 years was compared between children with behavioral inhibition (N=64) and without (N=152). RESULTS: Social anxiety disorder (social phobia or avoidant disorder) was significantly more likely to be found in the children with behavioral inhibition (17%) than in those without (5%). Noninhibited children were significantly more likely than inhibited children to have disruptive behavior disorders (20% versus 6%, respectively) and had higher scores on the attention problems scale of the Child Behavior Checklist (mean=52.1 versus 50.8). CONCLUSIONS: This study adds to the growing literature suggesting an association between behavioral inhibition and social anxiety disorder and an inverse relationship between inhibition and disruptive behavior disorders.     

Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder

BACKGROUND: We report on a controlled trial of a mixed amphetamine salts compound (Adderall, dextroamphetamine sulfate, dextro-, levoamphetamine sulfate, dextroamphetamine aspartate, levoamphetamine aspartate, and dextroamphetamine saccharate) in the treatment of adult attention-deficit/hyperactivity disorder (ADHD). METHODS: This was a 7-week, randomized, double-blind, placebo-controlled, crossover study of Adderall in 27 well-characterized adults satisfying full DSM-IV criteria for ADHD of childhood onset and persistent symptoms into adulthood. Medication was titrated up to 30 mg twice a day. Outcome measures included the ADHD Rating Scale and the Clinical Global Impression Score. Comorbid psychiatric disorders were assessed to test for potential effects on treatment outcome. RESULTS: Treatment with Adderall at an average oral dose of 54 mg (administered in 2 daily doses) was effective and well tolerated. Drug-specific improvement in ADHD symptoms was highly significant overall (42% decrease on the ADHD Rating Scale, P<.001), and sufficiently robust to be detectable in a parallel groups comparison restricted to the first 3 weeks of the protocol (P<.001). The percentage of subjects who improved (reduction in the ADHD rating scale of > or =30%) was significantly higher with Adderall treatment than with a placebo (70% vs 7%; P =.001). CONCLUSIONS: Adderall was effective and well tolerated in the short-term treatment of adults with ADHD. More work is needed to evaluate the long-term effects of Adderall, or other amphetamine compounds, in the treatment of adults with ADHD.     

Reconstitution of apo-superoxide dismutase by nitric oxide-induced copper transfer from metallothioneins

Little is known about copper transfer from Cu-metallothionein (Cu-MT) to various target proteins, such as apo-SOD, and the potential role of redox mechanisms in this transfer. We studied Cu transfer from Cu-MT to apo/Zn-SOD in a cell-free model system and found that Cu(5)-MT and Cu(10)-MT were able to reconstitute SOD activity only in the presence of a nitric oxide donor, (Z)-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium++ +-1,2-diolate (NOC-15). The percentage of reconstitution by Cu(5)-MT and Cu(10)-MT was 34 and 83%, respectively, compared with that reconstituted by free Cu alone. A Cu chelation assay using bathocuproine disulfonate (BCS) showed that NOC-15 induced release of free Cu from Cu(10)-MT but not from Cu(5)-MT. The transfer of Cu from Cu-MT to apo/Zn-SOD was not accompanied by enhanced Cu-dependent generation of ascorbate radicals or hydroxyl radicals as measured by EPR spectroscopy. We found a 70% decrease in the number of 2,2'-dithiodipyridine titratable SH groups on MT after incubation with NOC-15. Overall, our results suggest that Cu-MT could potentially function in a nitric oxide-dependent pathway for the delivery of Cu to apo-SOD in copper-challenged cells.