Serotonergic interhemispheric asymmetry: Neurochemical and pharmaco-EEG evidence

1. Postmortem neurochemical investigations revealed interhemispheric asymmetry in the mediofrontal region of human brain. Significantly higher right hemisphere serotonin metabolite (5HIAA) content as well as increased maximal imipramine binding (IB) were found in the right hemisphere than in the left side.

2. IB did not show a gender difference in the mediofrontal area. However, women had higher IB in the right orbital frontal cortex than did men.

3. In vivo pharmaco-EEG results tend to support the postmortem neurochemical data. Intravenous chlorimipramine resulted in an asymmetric topographic distribution of the P300 auditory evoked potential, peak amplitudes were shifted to the right hemisphere.     

Outcomes and presurgery correlates of lumbar discectomy in Utah Workers' Compensation patients

Background contextLumbar discectomy is the most common type of back surgery performed in the United States. Outcomes after this procedure can be variable and it appears that Workers' Compensation patients might be at increased risk for poor outcomes.PurposeTo examine long-term multidimensional outcomes of lumbar discectomy within a cohort of Workers' Compensation patients from Utah and identify presurgical biopsychosocial factors related to poor outcomes.Study design/settingA retrospective cohort study consisting of a review of presurgical medical records and assessment of patient outcomes via a telephone survey. Outcomes were assessed at least 2 years postsurgery.Patient sampleA consecutive sample of 271 workers from Utah who underwent lumbar discectomy from 1994 to 1999. A total of 134 patients were surveyed at the time of follow-up.Outcome measuresPatient satisfaction, Roland-Morris Disability Questionnaire, SF-36v2, and Stauffer-Coventry Index.MethodsA retrospective review of presurgical biopsychosocial variables and outcome assessment via telephone survey was conducted.ResultsWork disability rate for the cohort was 12.7% (17/134). Analysis of patient satisfaction, back pain-related dysfunction, and the Short-Form Health Survey-36 subscales indicated approximately 25% of patients experienced poor outcomes. Older age, number of comorbid health conditions, assigned case manager, litigation, and time delay from injury to surgery were consistently statistically significant predictors (p<.05) of poor outcomes.ConclusionsResults of this study suggest that compensated back surgery patients are at greater risk for poor lumbar discectomy outcomes than noncompensation patients. Presurgery correlates of poor outcomes may be useful in identifying high-risk compensation patients.     

Framework for interactive million-neuron simulation.

SUMMARY: Large simulations have become increasingly complex in many fields, tending to incorporate scale-dependent modeling and algorithms and wide-ranging physical influences. This scale of simulation sophistication has not yet been matched in neuroscience. The authors describe a framework aimed at enabling natural interaction with complex simulations: their configuration, initial conditions, monitoring, and analysis. The architecture is built on three cornerstone components: active probes, adaptive data capture, and visual interface. The resulting synthesis will enable interactive exploration of live simulations running on supercomputing platforms.     

Chemical Stability of an Admixture Combining Ziconotide and Bupivacaine During Simulated Intrathecal Administration

Objective. To determine the stability of an admixture combining ziconotide with bupivacaine hydrochloride during simulated intrathecal infusion under laboratory conditions at 37°. Materials and Methods. An admixture containing ziconotide (25 µg/mL) and bupivacaine hydrochloride (5 mg/mL) was stored in SynchroMed® II pumps at 37° and in control vials at either 37° or 5°. Using high‐performance liquid chromatography, drug concentrations were determined from samples obtained at varying intervals during the 30‐day study. Results. After 30 days, pump ziconotide and bupivacaine hydrochloride concentrations measured an average of 86.9% and 99.4% of their initial concentrations, respectively. Control vials displayed similar degradation rates for both drugs. Statistical evaluation of the ziconotide 95% confidence interval indicated that the ziconotide concentration would meet or exceed 90% and 80% of initial concentration for 22 days and 45 days, respectively. Conclusions. An admixture containing 25 µg/mL ziconotide and 5 mg/mL bupivacaine hydrochloride was 90% stable for 22 days and 80% stable for 45 days (extrapolated) in SynchroMed® II infusion pumps.     

Smoking delays chondrogenesis in a mouse model of closed tibial fracture healing.

Smoking delays the healing process and increases morbidity associated with many common musculoskeletal disorders, including long bone fracture. In the current study, a murine model of tibial fracture healing was used to test the hypothesis that smoking delays chondrogenesis after fracture. Mice were divided into two groups, a nonsmoking control group and a group exposed to cigarette smoke for 1 month prior to surgical tibial fracture. Mice were euthanized at 7, 14, and 28 days after surgery. The outcomes measured were immunohistochemical staining for type II collagen protein expression as a marker of cartilage matrix and proliferating cell nuclear antigen (PCNA) staining to measure proliferation at the site of injury. Toluidine blue staining and histomorphometry were used to quantify areas of cartilaginous and noncartilaginous fracture callus. Radiographs were analyzed for evidence of remodeling after injury. At day 7 after injury, mice exposed to cigarette smoke had a smaller fracture callus with less cartilage matrix compared to controls. Proliferation was present at high levels in both groups at this time point, but proliferating cells had a more immature morphology in the smoking group. At day 14, chondrogenesis was more active in smokers compared to controls, while a higher percentage of bone was present in the control animals. At day 28, X-ray analysis revealed a larger fracture callus remaining in the smoking animals. Together, these findings show that the chondrogenic phase of tibial fracture healing is delayed by smoking. This study represents, to our knowledge, the first analysis of molecular and cellular mechanisms of healing in a smoking mouse fracture model.     

Feline Immunodeficiency Virus Neuropathogenesis: From Cats to Calcium

Invasion of human immunodeficiency virus (HIV) into the central and peripheral nervous system produces a wide range of neurological symptoms, which continue to persist even with adequate therapeutic suppression of the systemic viremia. The development of therapies designed to prevent the neurological complications of HIV require a detailed understanding of the mechanisms of virus penetration into the nervous system, infection, and subsequent neuropathogenesis. These processes, however, are difficult to study in humans. The identification of animal lentiviruses similar to HIV has provided useful models of HIV infection that have greatly facilitated these efforts. This review summarizes contributions made from in vitro and in vivo studies on the infectious and pathological interactions of feline immunodeficiency virus (FIV) with the nervous system. In vivo studies on FIV have provided insights into the natural progression of CNS disease as well as the contribution of various risk factors. In vitro studies have contributed to our understanding of immune cell trafficking, CNS infection and neuropathogenesis. Together, these studies have made unique contributions to our understanding of (1) lentiviral interactions at the blood–cerebrospinal fluid (CSF) barrier within the choroid plexus, (2) early FIV invasion and pathogenesis in the brain, and (3) lentiviral effects on intracellular calcium deregulation and neuronal dysfunction. The ability to combine in vitro and in vivo studies on FIV offers enormous potential to explore neuropathogenic mechanisms and generate information necessary for the development of effective therapeutic interventions.     

Reversible reorganisation of the motor cortical representation of the hand in cervical dystonia.

Previous work has suggested that there may be a widespread disturbance of motor control mechanisms in patients with cervical dystonia. In the present study, we used transcranial magnetic stimulation to investigate the topography of the corticomotor projection to the abductor pollicis brevis (APB) muscle in 10 subjects with idiopathic torticollis. Threshold-adjusted stimuli were delivered at multiple scalp sites during a low-level voluntary contraction of the APB, and maps were generated of motor evoked potential amplitude versus scalp site. The cortical maps for the APB on the side opposite to the direction of head rotation were displaced laterally or posteriorly in all subjects and reverted to a more normal position after botulinum toxin injection of the cervical muscles in 5 subjects. The findings point to a reversible reorganisation of the corticomotor representation of the hand on the same side as the sternocleidomastoid (SCM) muscle that is involved in producing the dystonia. These results provide further evidence for the involvement of cortical centres and for a more widespread abnormality of motor control mechanisms in focal dystonia. The findings also support the notion that head turning is chiefly mediated by the hemisphere ipsilateral to the direction of the head rotation by means of a corticomotor projection to the contralateral SCM.     

Vascular injury during anterior lumbar surgery.

BACKGROUND CONTEXT: With the number of anterior lumbar procedures expected to increase significantly over the next few years, it is important for spine surgeons to have a good understanding about the incidence of vascular complications during these operations. PURPOSE: To determine the incidence of vascular injury in 1,315 consecutive cases undergoing anterior lumbar surgery at various levels from L2 to S1. STUDY DESIGN/SETTING: Patients undergoing anterior lumbar surgery were studied. PATIENT SAMPLE: A total of 1,310 consecutive patients undergoing 1,315 anterior lumbar procedures between August 1997 and December 2002 were included in the study. OUTCOME MEASURES: All patients were evaluated for incidence of vascular injury during and immediately after surgery. METHOD: A concurrent database was maintained on all these cases. All the patients had distal pulse evaluation preoperatively. Patients with venous injuries were further analyzed to determine location and extent of injury, amount of blood loss, completion of the procedure and postoperative sequelae. Patients with pulse deficits or evidence of ischemia during or immediately after surgery were further analyzed in particular in relation to demographic, preoperative variables and management. RESULTS: Six patients were identified as having left iliac artery thrombosis (0.45%), and 19 had major vein lacerations (1.4%). CONCLUSION: This study shows that the incidence of vascular injury is relatively low (25 in 1,315 or 1.9%). Because only five of these patients experienced significant sequelae from the approach, it appears that anterior lumbar surgery is quite safe, although it must be carried out with utmost respect for the vessels to avoid possible catastrophic outcomes.     

Intrinsic nerves in the mammalian colon: confirmation of a plexus at the circular muscle-submucosal interface

Slow waves in the small intestine seem to arise in plexuses of neurites with interstitial cells of Cajal. In the colon, slow waves appear to arise at the circular muscle - submucosal interface. We therefore sought a plexus at this surface in the colon in the cat, dog, ferret, opossum, rabbit, rat, guinea-pig and man. Segments from all levels of the colon were stained by the Champy-Maillet osmic acid-zinc iodide method and cut into serial 25 micron sections in the plane of the muscle layers. A dense network of neurites with abundant interstitial cells of Cajal was found at the circular muscle - submucosal interface in all species except rabbit. Neurites in this plexus appeared to arise from the deep plexus of the submucosa (Schabadasch's or Henle's plexus). It was not found in the small intestine and stomach. A similar plexus was found in the interstices of the myenteric plexus in the colon. Interstitial cells of Cajal in both plexuses were positive for the NADH-diaphorase stain, but not for silver impregnation. The possible roles of the plexuses of neurites and interstitial cells of Cajal at the circular muscle - submucosal interface and at the plane of the myenteric plexus in the generation of rhythmic activity in the colon are discussed.