The effectiveness of the anti-CD11d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage.

We have previously reported that administration of a CD11d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI. In contrast to its effects in the clip-compression model, the CD11d mAb treatment did not improve forelimb function nor did it significantly reduce MPO levels in the hemi-contused cord. To determine if the disparate results using the CD11d mAb were due to the biomechanical nature of the cord injury (compression SCI versus contusion SCI) or to the spinal level of the injury (12th thoracic level versus cervical) we further evaluated the CD11d mAb treatment after a T12 contusion SCI. In contrast to the T12 clip compression SCI, the CD11d mAb treatment did not improve locomotor recovery or significantly reduce MPO levels after T12 contusion SCI. Lesion analyses revealed increased levels of hemorrhage after contusion SCI compared to clip-compression SCI. SCI that is accompanied by increased intraspinal hemorrhage would be predicted to be refractory to the CD11d mAb therapy as this approach targets leukocyte diapedesis through the intact vasculature. These results suggest that the disparate results of the anti-CD11d treatment in contusion and clip-compression models of SCI are due to the different pathophysiological mechanisms that dominate these two types of spinal cord injuries.

An analysis of ideal and actual time to surgery after traumatic spinal cord injury in Canada.

STUDY DESIGN: Retrospective analysis of a prospective registry and surgeon survey. OBJECTIVES: To identify surgeon opinion on ideal practice regarding the timing of decompression/stabilization for spinal cord injury and actual practice. Discrepancies in surgical timing and barriers to ideal timing of surgery were explored. SETTING: Canada. METHODS: Patients from the Rick Hansen Spinal Cord Registry (RHSCIR, 2004-2014) were reviewed to determine actual timing of surgical management. Following data collection, a survey was distributed to Canadian surgeons, asking for perceived to be the optimal and actual timings of surgery. Discrepancies between actual data and surgeon survey responses were then compared using χ2 tests and logistic regression. RESULTS: The majority of injury patterns identified in the registry were treated operatively. ASIA Impairment Scale (AIS) C/D injuries were treated surgically less frequently in the RHSCIR data and surgeon survey (odds ratio (OR)= 0.39 and 0.26). Significant disparities between what surgeons identified as ideal, actual current practice and RHSCIR data were demonstrated. A great majority of surgeons (93.0%) believed surgery under 24 h was ideal for cervical AIS A/B injuries and 91.0% for thoracic AIS A/B/C/D injuries. Definitive surgical management within 24 h was actually accomplished in 39.0% of cervical and 45.0% of thoracic cases. CONCLUSION: Ideal surgical timing for traumatic spinal cord injury (tSCI) within 24 h of injury was identified, but not accomplished. Discrepancies between the opinions on the optimal and actual timing of surgery in tSCI patients suggest the need for strategies for knowledge translation and reduction of administrative barriers to early surgery.

The differential effects of norepinephrine and dopamine on cerebrospinal fluid pressure and spinal cord perfusion pressure after acute human spinal cord injury.

STUDY DESIGN: Prospective vasopressor cross-over interventional studyObjectives:To examine how two vasopressors used in acute traumatic spinal cord injury (SCI) affect intrathecal cerebrospinal fluid pressure and the corresponding spinal cord perfusion pressure (SCPP). SETTING: Vancouver, British Columbia, Canada. METHODS: Acute SCI patients over the age of 17 with cervical or thoracic ASIA Impairment Scale (AIS). A, B or C injuries were enrolled in this study. Two vasopressors, norepinephrine and dopamine, were evaluated in a 'crossover procedure' to directly compare their effect on the intrathecal pressure (ITP). The vasopressor cross-over procedures were performed in the intensive care unit where ITP, mean arterial pressure (MAP) and heart rate were being continuously measured. The SCPP was calculated as the difference between MAP and ITP. RESULTS: A total of 11 patients were enrolled and included in our analysis. There were 6 patients with AIS A, 3 with AIS B and 2 with AIS C injuries at baseline. We performed 24 cross-over interventions in these 11 patients. There was no difference in MAP with the use of norepinephrine versus dopamine (84±1 mm Hg for both; P=0.33). Conversely, ITP was significantly lower with the use of norepinephrine than with dopamine (17±1 mm Hg vs 20±1 mm Hg, respectively, P<0.001). This decrease in ITP with norepinephrine resulted in an increased SCPP during the norepinephrine infusion when compared with dopamine (67±1 mm Hg vs 65±1 mm Hg respectively, P=0.0049). CONCLUSION: Norepinephrine was able to maintain MAP with a lower ITP and a correspondingly higher SCPP as compared with dopamine in this study. These results suggest that norepinephrine may be preferable to dopamine if vasopressor support is required post SCI to maintain elevated MAPs in accordance with published guidelines.

Perspectives on strategies and challenges in the conversation about stem cells for spinal cord injury.

STUDY DESIGN: Qualitative study. OBJECTIVE: To examine how trusted communication between individuals with spinal cord injury (ISCIs) and physicians who care for ISCIs is affected by the discussion of advances in stem cell research and interventions locally and abroad. SETTING: Canada and the United States (US). METHODS: Semi-structured interviews with ISCIs and physicians. A thematic analysis approach was applied to more than 12 h of data to derive prominent themes and describe relationships between them. RESULTS: A convergence of factors involving transparency impact trusted communication between ISCIs and physicians about stem cells and spinal cord injury (SCI). ISCIs expressed that trusted communication is strengthened when physicians exhibit caring, attentive and positive attitudes that are underpinned by domain-specific knowledge and scholarship. Perceived reluctance to communicate or lack of knowledge poses significant challenges. Physicians also emphasised the importance of transparency for trusted communication but expressed that the still limited clinical reality of treatment choices for SCI and the pressures imposed by external resources are significant stressors that complicate the communication landscape. Both groups cited the range and variable quality of information sources, and the difficulty associated with navigating them, as priorities for action that would remediate these tensions. CONCLUSIONS: (1) Epistemic transparency should be privileged over silence. (2) A new generation of innovations in research and clinical trial dissemination about stem cells for SCI is needed to remedy the perceived inadequacies of existing information content and accessibility.

Developing a spinal cord injury research strategy using a structured process of evidence review and stakeholder dialogue. Part III: outcomes.

STUDY DESIGN: Focus Group. OBJECTIVES: To develop a unified, regional spinal cord injury (SCI) research strategy for Australia and New Zealand. SETTING: Australia. METHODS: A 1-day structured stakeholder dialogue was convened in 2013 in Melbourne, Australia, by the National Trauma Research Institute in collaboration with the SCI Network of Australia and New Zealand. Twenty-three experts participated, representing local and international research, clinical, consumer, advocacy, government policy and funding perspectives. Preparatory work synthesised evidence and articulated draft principles and options as a starting point for discussion. RESULTS: A regional SCI research strategy was proposed, whose objectives can be summarised under four themes. (1) Collaborative networks and strategic partnerships to increase efficiency, reduce duplication, build capacity and optimise research funding. (2) Research priority setting and coordination to manage competing studies. (3) Mechanisms for greater consumer engagement in research. (4) Resources and infrastructure to further develop SCI data registries, evaluate research translation and assess alignment of research strategy with stakeholder interests. These are consistent with contemporary international SCI research strategy development activities. CONCLUSION: This first step in a regional SCI research strategy has articulated objectives for further development by the wider SCI research community. The initiative has also reinforced the importance of coordinated, collective action in optimising outcomes following SCI.

Structural biomarkers in the cerebrospinal fluid within 24 h after a traumatic spinal cord injury: a descriptive analysis of 16 subjects.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To characterize the cerebrospinal fluid (CSF) concentrations of glial fibrillary acidic protein, neuron specific enolase (NSE), S-100ß, tau and neurofilament heavy chain (NFH) within 24 h of an acute traumatic spinal cord injury (SCI), and to correlate these concentrations with the baseline severity of neurologic impairment as graded by the American Spinal Injury Association impairment scale (AIS). METHODS: A lumbar puncture was performed to obtain CSF from 16 acute traumatic SCI patients within 24 h post injury. Neurological examinations were performed within 24 h of injury and again at 6 or 12 months post injury. The correlations between the CSF concentrations and initial AIS were calculated by using Pearson correlation coefficients. In addition, an independent Student's t-test was used to test for differences in CSF concentrations between patients of different AIS grades. RESULTS: The CSF NSE concentrations were significantly correlated with the baseline neurologic impairment being either 'motor complete' (AIS A, B) or 'motor incomplete' (AIS C, D) (r=0.520, P<0.05). The mean S-100ß concentration in motor complete patients was significantly higher compared with motor incomplete patients; 377.2 µg l(-1) (s.d.±523 µg l(-1)) vs 57.1 µg l(-1) (s.d.±56 µg l(-1)) (P<0.05), respectively. Lastly, the mean NFH concentration in motor complete patients was significantly higher compared with motor incomplete patient, 11 813 ng l(-1) (s.d.±16 195 ng l(-1)) vs 1446.8 ng l(-1) (s.d.±1533 ng l(-1)), (P<0.05), respectively. CONCLUSION: In this study we identified differences in the structural CSF biomarkers NSE, S-100ß and NFH between motor complete and motor incomplete SCI patients. Our data showed no clear differences in any of the protein concentrations between the different AIS grades.

Combinatorial treatment of acute spinal cord injury with ghrelin, ibuprofen, C16, and ketogenic diet does not result in improved histologic or functional outcome.

Because of the complex, multifaceted nature of spinal cord injury (SCI), it is widely believed that a combination of approaches will be superior to individual treatments. Therefore, we employed a rat model of cervical SCI to evaluate the combination of four noninvasive treatments that individually have been reported to be effective for acute SCI during clinically relevant therapeutic time windows. These treatments included ghrelin, ibuprofen, C16, and ketogenic diet (KD). These were selected not only because of their previously reported efficacy in SCI models but also for their potentially different mechanisms of action. The administration of ghrelin, ibuprofen, C16, and KD several hours to days postinjury was based on previous observations by others that each treatment had profound effects on the pathophysiology and functional outcome following SCI. Here we showed that, with the exception of a modest improvement in performance on the Montoya staircase test at 8-10 weeks postinjury, the combinatorial treatment with ghrelin, ibuprofen, C16, and KD did not result in any significant improvements in the rearing test, grooming test, or horizontal ladder. Histologic analysis of the spinal cords did not reveal any significant differences in tissue sparing between treatment and control groups. Although single approaches of ghrelin, ibuprofen, C16, and KD have been reported to be beneficial after SCI, our results show that the combination of the four interventions did not confer significant functional or histological improvements in a cervical model of SCI. Possible interactions among the treatments may have negated their beneficial effects, emphasizing the challenges that have to be addressed when considering combinatorial drug therapies for SCI.

Dissociations in the meaning of risk between health-care professionals and individuals with spinal cord injury.

OBJECTIVE: Risks have been a central concern in stem cell research overall, and in clinical trials of individuals with spinal cord injury (ISCIs) in particular. We sought to elucidate how two important stakeholder groups-health-care professionals (HCPs) and ISCIs-view and value both the physical and non-physical risks of stem cell interventions. SETTING: The study was conducted in Canada, and included participants from both Canada and the United States America. STUDY DESIGN: We used semi-structured interviews to gain perspectives on risk from HCPs and ISCIs. METHODS: We applied a constant comparative analytic strategy to derive themes from the discourse collected through the interviews. RESULTS: We identified three major themes about risk from 12 HCP and 24 ISCI participants: focus, rationale and approach. The salient components of the themes differed: HCPs focus on the physical causes of risks, and the ISCIs on their downstream consequences as well as on non-physical risks; HCPs are concerned about evidence, and ISCIs about experience; and HCPs approach risk narrowly, whereas the approach of ISCIs is more broad and contextualized. CONCLUSION: Although major themes were common to the two stakeholder groups, the components of the themes were dissociable and illustrate differences in what HCPs and ISCIs worry about, why they worry and how they approach their worries. We draw upon these findings to make recommendations for improving risk communication and informed consent for stem cell research for spinal cord injury.

A prospective evaluation of hemodynamic management in acute spinal cord injury patients.

STUDY DESIGN: Prospective observational study of acute spinal cord-injured (SCI) patients. OBJECTIVES: To determine how effectively mean arterial blood pressure (MAP) and spinal cord perfusion pressure (SCPP) are maintained at target levels in acute SCI patients. SETTING: Single-institution study at a Canadian level-one trauma center. METHODS: Twenty-one individuals with cervical or thoracic SCI were enrolled within 48 h of injury. A lumbar intrathecal drain was inserted for monitoring intrathecal cerebrospinal fluid pressure (ITP). The MAP was monitored concurrently with ITP, and the SCPP was calculated. Data was recorded hourly from the time of first assessment until at least the end of the 5th day post injury. RESULTS: All subjects had at least one recorded episode with a MAP below 80 mm Hg, and 81% had at least one episode with a MAP below 70 mm Hg. On average, subjects with cervical injuries had 18.4% of their pressure recordings below 80 mm Hg. Subjects with thoracic cord injuries had on average 35.9% of their MAP recordings <80 mm Hg. CONCLUSION: It is common practice to establish MAP targets for optimizing cord perfusion in acute SCI. This study suggests that even in an acute SCI referral center, when prospectively scrutinized, the actual MAP may frequently fall below the intended targets. Such results raise awareness of the vigilance that must be kept in the hemodynamic management of these patients, and the potential discrepancy between routinely setting target MAP according to 'practice guidelines' and actually achieving them.

Expression of inflammatory cytokines following acute spinal cord injury in a rodent model.

Many therapies that have been developed for acute spinal cord injury (SCI) either influence or are influenced by posttraumatic inflammation. Many such therapies have reportedly produced promising neurologic benefits in animal models of SCI, but demonstrating convincing efficacy in human clinical trials has remained elusive. This discrepancy may be related in part to differences in the inflammatory response to SCI between human patients and the widely studied rodent models. Our objectives were, therefore, to establish the time course of inflammatory cytokine release in the spinal cord of rats after a thoracic contusion, to determine whether the cytokine release was injury dependent, and to correlate these findings with those that we have recently reported for the cerebrospinal fluid (CSF) of human SCI patients. After rodent SCI, GRO (the rat equivalent of IL-8), IL-6, IL-1α, IL-1ß, IL-13, MCP-1, MIP1α, RANTES, and TNFα were elevated within the spinal cord, whereas IL-12p70 was decreased. In human SCI, IL-6, IL-8, and MCP-1 were also elevated within the cerebrospinal fluid but at later times than those observed in the rodent spinal cord. IL-6, IL-8, and MCP-1 were released in an injury-dependent manner in both the rodent model of SCI and the human condition. In this regard, similar patterns of expression were observed for a number of inflammatory cytokines after SCI in rodent spinal cords and in human CSF. Such proteins may therefore have potential utility as biomarkers and surrogate outcome measures for evaluating biological response to therapeutic interventions.

The Rick Hansen Spinal Cord Injury Registry (RHSCIR): a national patient-registry.

STUDY DESIGN: Development of a prospective patient registry. OBJECTIVE: To develop a patient registry for persons with traumatic spinal cord injuries (SCI), which can be used to answer research questions and improve patient outcomes. SETTING: Nine provinces in Canada. METHODS: The Rick Hansen Spinal Cord Injury Registry (RHSCIR) is part of the Translational Research Program of the Rick Hansen Institute. The launch of RHSCIR in 2004 heralded the initiation of the first nation-wide SCI patient registry within Canada. Currently, RHSCIR is being implemented in 14 cities located in 9 provinces, and there are over 1500 individuals who have sustained an acute traumatic SCI registered to date. Data are captured from the pre-hospital, acute and rehabilitation phases of care, and participants are followed in the community at 1, 2, 5 and then every 5 years post-injury. RESULTS: During the development of RHSCIR, there were many challenges that were overcome in selecting data elements, establishing the governance structure, and creating a patient privacy and confidentiality framework across multiple provincial jurisdictions. The benefits of implementing a national registry are now being realized. The collection of an internationally standardized set of clinical information is helping inform clinicians of beneficial interventions and encouraging a shift towards evidence-based practices. Furthermore, through RHSCIR, a network is forming amongst SCI clinicians and researchers, which is fostering new collaborations and the launch of multi-center clinical trials. CONCLUSIONS: For networks that are establishing SCI registries, the experiences and lessons learned in the development of RHSCIR may provide useful insights and guidance.

Systematic review: occupational physical activity and low back pain.

BACKGROUND: Although various occupational physical activities are suspected of contributing to low back pain (LBP), causal relationships have not been confirmed, complicating adjudication of work injuries, return to work instructions and preventive efforts. AIMS: To summarize eight systematic review (SR) reports that examined evidence supporting causal relationships between bending/twisting, awkward postures, sitting, standing/walking, carrying, pushing/pulling, lifting and manual handling/assisting patients and LBP. METHODS: A literature search was conducted to identify eligible studies. Methodological quality was assessed using a modified Newcastle-Ottawa Scale (NOS). Levels of evidence supporting factors for causation were examined using a Bradford Hill framework. Results were presented in eight SR reports, each focused on one or more related physical activities. This study summarizes findings from those reports and offers clinicians an overview. RESULTS: Collectively, the eight SR reports included 99 studies. None found strong evidence supporting a causal relationship between any occupational physical activity considered and LBP. Conflicting evidence was found between LBP and bending, twisting, lifting or pushing/pulling, but only for statistical association, not causation. Strong evidence against a causal relationship was found between LBP and manual handling/assisting patients, awkward postures, carrying, sitting, standing or walking. CONCLUSIONS: Although occupational physical activities are suspected of causing LBP, findings from the eight SR reports did not support this hypothesis. This may be related to insufficient or poor quality scientific literature, as well as the difficulty of establishing causation of LBP. These population-level findings do not preclude the possibility that individuals may attribute their LBP to specific occupational physical activities.

Stem cell clinical trials for spinal cord injury: readiness, reluctance, redefinition.

A wealth of scientific and clinical research has focused on the use of stem cells as a potential therapy for spinal cord injury (SCI), culminating most recently in the initiation of clinical trials. However, with the urgency that scientists and clinicians have undertaken to move forward with novel therapies for this devastating injury, the perspectives of stakeholders who live with a SCI have been left behind. Translational research in this rapidly growing field therefore overlooks a critically important viewpoint. We address this concern with a qualitative study of the perspectives on experimental stem cell treatments from individuals who have actually suffered a spinal cord injury. Using focus groups and interviews, we engaged individuals with thoracic and cervical SCIs at sub-acute and chronic stages post-injury. We found four major themes that inform the progression of stem cell research to clinical trials: 'readiness', 'the here and now', 'wait and see', and 'informed hope'. Taken together, the data suggest a profound difference related to target timing of stem cell clinical trials and the perspectives about timing from those who are the end-beneficiaries of therapy. To bridge this gap, we conclude with a number of considerations for the timing disparity of trials and recommendations for improving informed consent.

Radioisotope synoviorthesis with Holmium-166-chitosan complex in haemophilic arthropathy.

Radiosynoviorthesis is a safe and easy method for synovectomy in haemophilic arthropathy. Various agents have been used in radiosynoviorthesis, especially newly developed agent Holmium-166-chitosan complex has good clinical outcome. This study analysed clinical results and radiologic evaluation of radioisotope synoviorthesis using Holmium-166-chitosan complex in haemophilic arthropathy. From March 2001 to December 2003, 58 radiosynoviorthesis were performed in 53 haemophiliacs. The average age at procedure was 13.8 years. The Arnold and Hilgartner stage of the patients was from I to IV. Holmium-166-chitosan complex was injected in 31 ankle joints, 19 elbow joints and 8 knee joints. Average follow-up was 33 months since primary procedure. The range of motion of each joint, frequency of intra-articular bleeding and factor dose used were analysed for clinical assessment. There was no significant improvement of range of motion in affected joints. After procedure, the average frequency of bleeding of the elbow joint has decreased from 3.76 to 0.47 times per month, the knee joint from 5.87 to 1.12 times per month, and the ankle joint from 3.62 to 0.73 times per month respectively (P < 0.05). After treatment, the average coagulation factor dose injected was significantly decreased to 779.3 units per month from 2814.8 units per month before treatment (P < 0.001). Radioisotope synoviorthesis with Holmium-166-chitosan complex in haemophilic arthropathy is a very safe and simple procedure with the expectation of a satisfactory outcome without serious complication. It has excellent bleeding control effect on target joint and the need for substitution of coagulation factor concentrate can be reduced.

A systematic review of the evidence supporting a role for vasopressor support in acute SCI.

STUDY DESIGN: A systematic review of clinical and preclinical literature. OBJECTIVE: To critically evaluate the evidence supporting a role for vasopressor support in the management of acute spinal cord injury and to provide updated recommendations regarding the appropriate clinical application of this therapeutic modality. BACKGROUND: Only few clinical studies exist examining the role of arterial pressure and vasopressors in the context of spinal cord trauma. METHODS: Medical literature was searched from the earlier available date to July 2009 and 32 articles (animal and human literature) answering the following four questions were studied: what patient groups benefit from vasopressor support, which is the optimal hypertensive drug regimen, which is the optimal duration of the treatment and which is the optimal arterial blood pressure. Outcome measures used were the incidence of patients needing vasopressors, the increase of arterial blood pressure and neurologic improvement. RESULTS: Patients with complete cervical cord injuries required vasopressors more frequently than either incomplete injuries or thoracic/lumbar cord injuries (P<0.001). There was no statistical difference in neurologic improvement between patients on vasopressor support with a mean arterial pressure (MAP) of less than 85 mm Hg and those with MAP less than 90 mm Hg. Duration of treatment is often recommended between 5 and 7 days although this is not supported by high-level evidence and no single vasopressor appeared superior over the variety used in clinical treatment. CONCLUSION: There is currently no gold standard on vasopressor support. Based on non-randomized human studies, complete cervical cord injuries require vasopressors more frequently than other spinal cord injuries.

Orthostatic hypotension in the first month following acute spinal cord injury.

STUDY DESIGN: Retrospective data analysis. OBJECTIVES: To determine prevalence of orthostatic hypotension (OH) in patients with spinal cord injury (SCI) during the acute rehabilitation period. SETTING: Quaternary care spinal unit, Vancouver General Hospital, British Columbia, Canada. METHODS: Eighty-nine patients with acute SCI stratified by neurological level (cervical, 55 (62%); upper thoracic, 12 (13%); lower thoracic, 22 (25%)), and graded by American Spinal Injury Association standards. Non-invasive measurement of systolic and diastolic blood pressure and heart rate were made at baseline and 3 min following an orthostatic challenge test administered during the first month after SCI. RESULTS: Patients with cervical or upper thoracic motor complete SCI more frequently experienced OH (P<0.01). OH persisted during the first month following SCI in 74% of cervical and only 20% of upper thoracic motor complete SCI patients. CONCLUSION: Patients with cervical and upper thoracic motor complete SCI are more likely to experience persistent OH than those with lower level or motor incomplete SCI during the first month of rehabilitation.

Molecular cloning of kpcA gene encoding a Kex2p-like endoprotease from Aspergillus nidulans.

We cloned and sequenced a gene, kpcA (Kex2p-like proprotein convertase A), from a genomic library of Aspergillus nidulans. The kpcA gene encodes an 820-residue protein, named KpcA, which contains a putative subtilisin-like catalytic domain (residues 136-466) homologous to that of the subtilisin serine protease family. KpcA shows 56, 73, and 47% amino acid identities with Saccharomyces cerevisiae Kex2p, Aspergillus niger KexB, and mouse furin within the subtilisin-like catalytic domain, respectively. The sequences around the proposed active site Asp, His, and Ser residues of KpcA are similar to those of other Kex2p family members. The KpcA mRNA transcript with an expected size of approximately 2.8 kb was detected in A. nidulans. The substrate specificity of KpcA, expressed in CHO cells, is similar to that of A. niger KexB and yeast Kex2p. We conclude that KpcA is a resident Kex2p-like proprotein that processes endoprotease in A. nidulans.

Spinal cord regeneration: from gene to transplants.

The past 20 years has seen the emergence of many exciting and promising experimental therapeutic strategies to promote regeneration of the injured spinal cord in laboratory animals. A greater understanding of the pathophysiologic mechanisms that contribute to the initial and secondary cord injury may facilitate the development of neuroprotective strategies that preserve axonal function and prevent apoptotic cell death, thus optimizing neurologic function. Neurotrophic factors have been used to augment the poor intrinsic regenerative capacity of central nervous system neurons, and the need for sophisticated delivery of such trophic agents has stimulated the application of gene therapy in this context. In addition to augmenting the neuronal capacity to regenerate axons, many researchers are developing strategies to overcome the inhibitory environment into which these axons must grow. Characterizing the inhibitory elements of the glial scar at the site of injury and of myelin in the distal tracts is therefore a focus of intense scientific interest. To this effect, a number of strategies have also been developed to bridge the injury site and facilitate axonal growth across the lesion with a variety of cellular substrates. These include fetal tissue transplants, stem cells, Schwann cells, and olfactory ensheathing cells. With the collaboration of basic scientists and clinicians, it is hoped that these experimental strategies coupled with a greater understanding of the neurobiology of spinal cord injury will be translatable to the clinical setting in the near future.

[People's way to fight the epidemic diseases in the early Choson period].

Epidemic diseases in the early Choson period were big problems to the people and society. However, the weapons to the epidemic diseases were very limited at that time. There were few drugs and well-trained practitioners for people. Most people could only depend on religious means and simple folklore medicine including inhalation of specific flavor. People tried to overcome or prevent the epidemics by praying, sorcery, ornaments, runaway and isolation. In most cases, the epidemic diseases came with or broke out from the famine, severe labour (especially in civil engineering) imposed by the ruling class. The epidemics of that time are thought to be typhoid fever, epidemic typhus, or similar febrile diseases.

[History of the Korean medical journals (1945-1995) - principally on the basic science journals].

The development of Korean medical journals is summarized as the following: 1) Until the early 1960s there were not basic medical journals except Journal of the Korean Society for Microbiology (first issued in the year of 1958), so researchers of basic medical science had difficulty in publishing their articles. 2) Many of the basic medical journals made their first appearance around the mid-1960s, but the progress was not striking until the mid-1980s. 3) From the mid-1980s most of the journals rapidly developed in the aspect of quality as well as quantity. The increase in the number of issues per year and articles per an issue, and the increment of the articles written in English are remarkably found. The increase in the number of researchers, appropriate education and training, improvement of the research facilities, the growth of research fund, and increment of the international academic exchange are thought to be the main factors of such development. Besides those factors, the devotion of the editors of the journals played the important role.