CM101-mediated recovery of walking ability in adult mice paralyzed by spinal cord injury

CM101, an antiangiogenic polysaccharide derived from group B streptococcus, was administered by i.v. injection 1 hr post-spinal-cord crush injury in an effort to prevent inflammatory angiogenesis and gliosis (scarring) in a mouse model. We postulated that gliosis would sterically prevent the reestablishment of neuronal connectivity; thus, treatment with CM101 was repeated every other day for five more infusions for the purpose of facilitating regeneration of neuronal function. Twenty-five of 26 mice treated with CM101 survived 28 days after surgery, and 24 of 26 recovered walking ability within 2–12 days. Only 6 of 14 mice in the control groups survived 24 hr after spinal cord injury, and none recovered function in paralyzed limbs. MRI analysis of injured untreated and treated animals showed that CM101 reduced the area of damage at the site of spinal cord compression, which was corroborated by histological analysis of spinal cord sections from treated and control animals. Electrophysiologic measurements on isolated central nervous system and neurons in culture showed that CM101 protected axons from Wallerian degeneration; reversed γ-aminobutyrate-mediated depolarization occurring in traumatized neurons; and improved recovery of neuronal conductivity of isolated central nervous system in culture.

A common muscarinic pathway for diapause recovery in the distantly related nematode species Caenorhabditis elegans and Ancylostoma caninum

Converging TGF-β and insulin-like neuroendocrine signaling pathways regulate whether Caenorhabditis elegans develops reproductively or arrests at the dauer larval stage. We examined whether neurotransmitters act in the dauer entry or recovery pathways. Muscarinic agonists promote recovery from dauer arrest induced by pheromone as well as by mutations in the TGF-β pathway. Dauer recovery in these animals is inhibited by the muscarinic antagonist atropine. Muscarinic agonists do not induce dauer recovery of either daf-2 or age-1 mutant animals, which have defects in the insulin-like signaling pathway. These data suggest that a metabotropic acetylcholine signaling pathway activates an insulin-like signal during C. elegans dauer recovery. Analogous and perhaps homologous cholinergic regulation of mammalian insulin release by the autonomic nervous system has been noted. In the parasitic nematode Ancylostoma caninum, the dauer larval stage is the infective stage, and recovery to the reproductive stage normally is induced by host factors. Muscarinic agonists also induce and atropine potently inhibits in vitro recovery of A. caninum dauer arrest. We suggest that host or parasite insulin-like signals may regulate recovery of A. caninum and could be potential targets for antihelminthic drugs.

A case of central nervous system vasculitis related to an episode of Guillain-Barrè syndrome

The authors report their knowledge about an uncommon case of isolated vasculitis, restricted to the left sylvian artery during an auto-immune Guillain-Barrè syndrome (GBS), sustained by cytomegalovirus (CMV). An acute cardiopulmonary failure requiring a ventilator and vasopressor support manifested, notwithstanding plasma exchanging and immune-modulating therapy. An IgM-enriched formula administration coincided with a rapid amelioration of GBS and vasculitis to a complete recovery the next month after her discharge to a rehabilitation centre.

Long-term functional recovery from age-induced spatial memory impairments by nerve growth factor gene transfer to the rat basal forebrain.

Nerve growth factor (NGF) stimulates functional recovery from cognitive impairments associated with aging, either when administered as a purified protein or by means of gene transfer to the basal forebrain. Because gene transfer procedures need to be tested in long-term experimental paradigms to assess their in vivo efficiency, we have used ex vivo experimental gene therapy to provide local delivery of NGF to the aged rat brain over a period of 2.5 months by transplanting immortalized central nervous system-derived neural stem cells genetically engineered to secrete NGF. By grafting them at two independent locations in the basal forebrain, medial septum and nucleus basalis magnocellularis, we show that functional recovery as assessed in the Morris water maze can be achieved by neurotrophic stimulation of any of these cholinergic cell groups. Moreover, the cholinergic neurons in the grafted regions showed a hypertrophic response resulting in a reversal of the age-associated atrophy seen in the learning-impaired aged control rats. Long-term expression of the transgene lead to an increased NGF tissue content (as determined by NGF-ELISA) in the transplanted regions up to at least 10 weeks after grafting. We conclude that the gene transfer procedure used here is efficient to provide the brain with a long-lasting local supply of exogenous NGF, induces long-term functional recovery of cognitive functions, and that independent trophic stimulation of the medial septum or nucleus basalis magnocellularis has similar consequences at the behavioral level.

Avoiding Extinction: An Evaluation of Short-Term Recovery Recommendations for the Endangered Rio Grande Silvery Minnow

The endangered Rio Grande silvery minnow (Hybognathus amarus; RGSM) is nearing extinction and requires immediate recovery actions. In a draft report to the Middle Rio Grande Program, a Program Advisory Panel (PAP) recommended 34 short-term recovery measures to be implemented within the next five years, and 21 long-term recovery actions. However, these recommendations need further analysis to determine if and how the actions could be implemented. This project evaluated short-term recommendations provided by the PAP to identify the most effective and rank the relative importance of the actions. These recommendations were divided into 7 recovery categories: population augmentation (5 recommendations); hydrologic regimen (4 recommendations); physical habitat (3 recommendations); biological component of habitat (2 recommendations); population monitoring (6 recommendations); monitoring, analysis, and modeling (12 recommendations); and information and planning (2 recommendations). Each recommendation was evaluated for its potential to produce anticipated recovery progress for the RGSM based on assessments of the degree of feasibility, cost effectiveness, and associated potential consequences if fully implemented. In addition, other alternatives in a range of options were also considered where applicable. In each case, recommendations were evaluated from on-site visits, interviews with researchers and resource managers, and literature review. Based on the research findings, three major groupings of the recovery categories were identified: natural aspects of recovery, program aspects of recovery, and emergency measures. At least one recovery category within each major grouping was considered important by the respondents, which indicates that each grouping is of high importance in relation to the situation at hand. However, actions within each grouping have varying priorities given constraints on available resources, time, and budget. An integrated approach that accounts for the complexity of the river system and the species itself was considered the best approach to avoid extinction while ensuring long-term sustainability. Results of these analyses were provided directly to the PAP for their review, and it is anticipated that project results could advance implementation of the most appropriate immediate recovery actions needed to prevent extinction of the RGSM.

The white gene and locomotor recovery from anoxia in Drosophila melanogaster

Locomotor recovery from anoxia is complicated and little is known about the molecular and cellular mechanisms regulating anoxic recovery in Drosophila. For this thesis I established a protocol for large-scale analysis of locomotor activity in adult flies with exposure to a transient anoxia. Using this protocol I observed that wild-type Canton-S flies recovered faster and more consistently from anoxia than the white-eyed mutant w1118, which carries a null allele of w1118 in an isogenic genetic background. Both Canton-S and w1118 are commonly used controls in the Drosophila community. Genetic analysis including serial backcrossing, RNAi knockdown, w+ duplication to Y chromosome as well as gene mutation revealed a strong association between the white gene and the timing of locomotor recovery. I also found that the locomotor recovery phenotype is independent of white-associated eye pigmentation, that heterozygous w+ allele was haplo-insufficient to induce fast and consistent locomotor recovery from anoxia in female flies, and that mini-white is insufficient to promote fast and consistent locomotor recovery. Moreover, locomotor recovery was delayed in flies with RNAi knockdown of white in subsets of serotonin neurons in the central nervous system. I further demonstrated that mutations of phosphodiesterase genes (PDE) displayed wild-type-like fast and consistent locomotor recovery, and that locomotor recovery was light-sensitive in the night in w1118. The delayed locomotor recovery and the light sensitivity were eliminated in PDE mutants that were dual-specific or cyclic guanosine monophosphate (cGMP)-specific. Up-regulation of cGMP using multiple approaches including PDE mutation, sildenafil feeding or specific expression of an atypical soluble guanylyl cyclase (Gyc88E) was sufficient to suppress w-RNAi induced delay of locomotor recovery. Taken together, these data strongly support the hypothesis that White transports cGMP and promotes fast and consistent locomotor recovery from anoxia.

Emergency care systems demonstration projects. Volume 2: the emergency care system. Final report.

National Highway Safety Bureau, Washington, D.C.

Dade County Trauma Task Force: a multi-system comparative analysis.

National Highway Traffic Safety Administration, Washington, D.C.

Regulatory strategies for construction site erosion control programs : forms, costs, and cost recovery mechanisms : contractor assistance for the cost of financing regulatory programs /

"December, 1980."

Sensory hypersensitivity occurs soon after whiplash injury and is associated with poor recovery

Hypersensitivity to a variety of sensory Stimuli is a feature of persistent whiplash associated disorders (WAD). However, little is known about sensory disturbances from the time Of injury until transition to either recovery or symptom persistence. Quantitative sensory testing (pressure and thermal pain thresholds, the brachial plexus provocation test), the sympathetic vasoconstrictor reflex and psychological distress (GHQ-28) were prospectively measured in 76 whiplash Subjects within 1 month of injury and then 2, 3 and 6 months post-injury. Subjects were classified at 6 months post-injury using scores on the Neck Disability Index: recovered (30). Sensory and sympathetic nervous system tests were also measured in 20 control subjects. All whiplash groups demonstrated local mechanical hyperalgesia in the cervica spine at 1 month post-injury. This hyperalgesia persisted in those with moderate/severe symptoms at 6 months but resolved by 2 months in those who had recovered or reported persistent mild symptoms. Only those with persistent moderate/severe symptoms at 6 months demonstrated generalised hypersensitivity to all sensory tests. These changes Occurred within 1 month of injury and remained Unchanged throughout the Study period. Whilst no significant group differences were evident for the sympathetic vasoconstrictor response, the moderate/severe group showed a tendency for diminished sympathetic reactivity. GHQ-28 scores of the moderate/severe group were higher than those of the other two groups. The differences in GHQ-28 did not impact on any of the sensory measures. These findings suggest that those with persistent moderate/severe symptoms at 6 months display, soon after injury, generalised hypersensitivity suggestive of changes in central pain processing mechanisms. This phenomenon did not Occur in those who recover or those with persistent mild symptoms. (C) 2003 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.

A proposed new classification system for whiplash associated disorders - implications for assessment and management

The development of chronic symptoms following whiplash injury is common and contributes substantially to costs associated with this condition. The currently used Quebec Task Force classification system of whiplash associated disorders is primarily based on the severity of signs and symptoms following injury and its usefulness has been questioned. Recent evidence is emerging that demonstrates differences in physical and psychological impairments between individuals who recover from the injury and those who develop persistent pain and disability. Motor dysfunction, local cervical mechanical hyperalgesia and psychological distress are present soon after injury in all whiplash injured persons irrespective of recovery. In contrast those individuals who develop persistent moderate/severe pain and disability show a more complex picture, characterized by additional impairments of widespread sensory hypersensitivity indicative of underlying disturbances in central pain processing as well as acute posttraumatic stress reaction, with these changes present from soon after injury. Based on this heterogeneity a new classification system is proposed that takes into account measurable disturbances in motor, sensory and psychological dysfunction. The implications for the management of this condition are discussed. (C) 2004 Elsevier Ltd. All rights reserved.

An evaluation of different models of water recovery in flotation

Water recovery is one of the key parameters in flotation modelling for the purposes of plant design and process control, as it determines the circulating flow and residence time in the individual process units in the plant and has a significant effect on entrainment and froth recovery. This paper reviews some of the water recovery models available in the literature, including both empirical and fundamental models. The selected models are tested using the data obtained from the experimental work conducted in an Outokumpu 3 m(3) tank cell at the Xstrata Mt Isa copper concentrator. It is found that all the models fit the experimental data reasonably well for a given flotation system. However, the empirical models are either unable to distinguish the effect of different cell operating conditions or required to determine the empirical model parameters to be derived in an existing flotation system. The model developed by [Neethling, SJ., Lee, H.T., Cilliers, J.J., 2003, Simple relationships for predicting the recovery of liquid from flowing foams and froths. Minerals Engineering 16, 1123-1130] is based on fundamental understanding of the froth structure and transfer of the water in the froth. It describes the water recovery as a function of the cell operating conditions and the froth properties which can all be determined on-line. Hence, the fundamental model can be used for process control purposes in practice. By incorporating additional models to relate the air recovery and surface bubble size directly to the cell operating conditions, the fundamental model can also be used for prediction purposes. (C) 2005 Elsevier Ltd. All rights reserved.

Error recovery in a hospital pharmacy

A field study was performed in a hospital pharmacy aimed at identifying positive and negative influences on the process of detection of and further recovery from initial errors or other failures, thus avoiding negative consequences. Confidential reports and follow-up interviews provided data on 31 near-miss incidents involving such recovery processes. Analysis revealed that organizational culture with regard to following procedures needed reinforcement, that some procedures could be improved, that building in extra checks was worthwhile and that supporting unplanned recovery was essential for problems not covered by procedures. Guidance is given on how performance in recovery could be measured. A case is made for supporting recovery as an addition to prevention-based safety methods.