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Inhaled epoprostenol is a selective pulmonary vasodilator that has shown a potentially broad number of applications in the management of critically ill patients. To date, the vast majority of the literature with regard to efficacy, indications for use, and adverse effects of inhaled epoprostenol is focused on use of this agent in critical care settings, with relatively little literature describing use of inhaled epoprostenol in the Emergency Department. This retrospective review sought to examine instances in which inhaled epoprostenol was administered in the Emergency Department of a tertiary-care, Level I trauma center following implementation of a clinical pathway for administration of this medication for cases of refractory hypoxemia, RV dysfunction, and refractory hypoxemia. Primary outcomes were monitoring for adverse effects (i.e. hypotension), trend in FiO2 requirement over time, and clinical indication for initiation of inhaled epoprostenol.An automated review was performed to query cases in which inhaled epoprostenol had been initiated in the Emergency Department following adoption of the inhaled epoprostenol clinical pathway. Cases were excluded if the medication was initiated in the prehospital setting, ordered but not administered, or administered for a period of1 h. Vital signs and co-administration of vasopressors were followed before and following epoprostenol administration to assess for change over time. Clinical indication of epoprostenol administration was assessed via manual chart review.Inhaled epoprostenol was administered in 20 instances, with 15 cases ultimately meeting inclusion criteria. There were no cases of clinically significant hypotension (MAP65) in any of the cases in which inhaled epoprostenol was administered in the Emergency Department, and mean vasopressor requirement did not increase over time. A majority of patients saw a reduction in FiO2 requirement following administration of inhaled epoprostenol. The most common indication for initiation of inhaled epoprostenol based on manual chart review was pulmonary embolism.In this review of cases in which inhaled epoprostenol was administered following adoption of a clinical pathway for medication administration, there were no cases of hypotension or other adverse effects that appear to be attributable to medication administration. Pulmonary embolism and refractory hypoxemia were the most common noted indications for administration of inhaled epoprostenol. Further research is warranted regarding development of clinical protocols for administration of inhaled pulmonary vasodilators in the Emergency Department setting.

Facilitation is a global phenomenon that occurs when one species promotes the growth, survival, or reproduction of another species, mostly in stressful environments. However, the importance of facilitation by shrubs in maintaining plant community diversity is not well evaluated in the Himalayas, especially for the richness and conservation of medicinal and human-valued species. Therefore, we aimed to explore the facilitative role of a dwarf shrub species, Berberis angulosa, in maintaining plant composition and richness of human-valued species in the Langtang valley of Nepal's Himalayas. We censused plant species in open patches and beneath Berberis during monsoon and post-monsoon (dry) seasons at three elevations. Total species richness and richness of human-valued species were significantly higher inside the Berberis canopy than in gaps; the former being 39% and the latter 46% greater under shrubs than in open sites. Facilitation by Berberis shrubs promoted plant community diversity irrespective of season and elevation; however, higher differences in mean species richness for both total plant species and human-valued species during the dry season and at high elevation indicated increased facilitation intensity under more stressful conditions. The facilitative effect of Berberis shrubs increased, combining both seasons, overall plant diversity by 19% (total=105), and human-valued species by 16% (total=56). Our results show the importance of facilitation by nurse shrubs in structuring plant communities and protecting medicinal and socio-ecologically important plants, thus enriching ecosystem services in the Himalayas. These results suggest nurse plant species should be incorporated into conservation policies and management strategies for effective biodiversity conservation and sustainability, especially in the face of climate change.

BACKGROUND CONTEXT Patient-centered goal setting is an important component of behavioral interventions for chronic pain. Limited data exist on the relationship between goal attainment during cognitive-behavioral based physical therapy (CBPT) and pain-related outcomes. PURPOSE The purpose of this study was to examine the relationship between CBPT goal attainment and pain-related outcomes in a cohort of patients who completed a 6-week telephone-based CBPT intervention after lumbar spine surgery. STUDY DESIGN/SETTING Secondary analysis from a randomized trial comparing postoperative CBPT and an education program. The primary results of the trial showed superiority of CBPT in an intervention completers only analysis. PATIENT SAMPLE This study included 108 participants (mean ± SD age = 63.5 ± 11.3 years, 54 [50%] female, 92 [85%] White) who completed the CBPT intervention were included. OUTCOME MEASURES Six and 12-month outcomes included physical function (PROMIS), pain interference (PROMIS), and back and leg pain intensity (Brief Pain Inventory). Methods At each session, CBPT participants used goal attainment scaling (GAS) to set goals and report goal attainment from the previous session. The number and type of goals and percentage of goals met were recorded. A GAS t-score for achievement of goals across all sessions was computed for each patient. Patients were grouped as high or low goal attainment based on a GAS t-score of 50, which indicates goals were met as expected. Outcome differences between groups at each follow-up time point were examined using linear regression analyses controlling for baseline outcome score. Alpha was set at the 0.05 level for statistical significance. Results Participants set a median of 3 goals (range: 1 to 6) at each CBPT session. The most common goals were related to participating in a physical/recreational activity (36%), adopting a cognitive or behavioral strategy (28%), exercising (11%), or performing activities of daily living (11%). The least common goals related to social activities (2%). Forty-six (43%) participants met criteria for high goal attainment (mean % goals met = 87% compared to 64% in the low goal attainment group, p Conclusions The attainment of personalized goals within a CBPT intervention was an important factor related to improvements in physical functioning after spine surgery. Implementing a structured process for setting personalized goals and tracking goal attainment may be an essential aspect of a biopsychosocial approach for addressing functional impairment following surgery. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Summary Introduction Germline-inactivating DICER1 mutations are responsible of a familial tumour susceptibility syndrome with an increased risk of tumours, mainly pleuropulmonary blastoma (PPB). DICER1 mutations also cause a range of other tumours, some of them in urogenital organs (cystic nephroma [CN], ovarian sex cord-stromal tumours, bladder and cervix embryonal rhabdomyosarcoma [ERMS]). Objective The aim was to clarify the range of urogenital phenotypes associated with DICER1 mutations and to give practical course of action to paediatric urologist that are exposed to DICER1-related conditions. Study design A literature review was performed. Pertinent papers focused on urogenital diseases associated with DICER1 mutations were reviewed. Results Seventy per cent of CN have a DICER1 germline mutation. The majority of them (80%) have PPB. Like PPB, CN could undergo a malignant progression to a primitive sarcoma. Some rare cases of Wilms tumours were reported. Regarding gonadal manifestations, sex-cord stromal neoplasia of the ovary, especially Sertoli–Leydig cell tumour (SLCT), is the most frequent tumour associated with DICER1 germline mutation. Germline DICER1 mutations also predispose to uterine cervix and bladder ERMS. Discussion The presence of unusual tumours suggesting DICER1 mutations may alert clinicians. The first step is to obtain a complete familial history. The variable clinical presentation and the modest penetrance raise concerns about the appropriateness of genetic testing to patients and their relatives. The education of DICER1 mutations carriers about tumour-related symptoms is consensual. In the first 5 years of life, a yearly chest X-ray and abdominal ultrasound are recommended. Conclusion The presence of a CN, ovarian SLCT or urogenital ERMS in a child should alert the clinician to the possibility of DICER1 mutation and the associated risk of PPB. Individuals with one of the typical DICER1 conditions should be offered DICER1 analysis. Despite the low penetrance, a genetic counselling and testing should be offered to the family of the affected child.

The paper reports on how a child protection agency capitalized on the knowledge acquired at the Improving Educational Outcomes for Children in Care conference to launch the development of a long term strategy to promote educational success for the children in its care. After attending the conference a team from the agency completed a review of current agency strategies and an analysis of the presentations given by practitioners and researchers. As a result the team was able to identify immediate steps that will be taken. It also found that a number of themes ran through the presentations that will become the pillars underpinning the development of a long term plan. The themes are: the importance of transitions; a commitment to strong collaboration between the child welfare and education systems; enhanced educational support for children in care; the cultivation of an expectation of success; the importance of caregiver involvement; and the creation of a culture of education.

Background: The aim of this study was to assess if F-18-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)-CT scanning could minimise the time non-responding patients were exposed to erlotinib (Tarceva (R)). Methods: Patients were selected for clinical factors that would predict response to erlotinib. A FDG PET-CT and diagnostic contrast-enhanced (traditional) CT scan were carried out at baseline, and then a FDG PET-CT at 6 weeks and a traditional CT at 12 weeks were repeated. The primary end-point was rate of early progression in patients after 6 weeks, of which a minimum 12 out of 35 were required to make the study worthwhile. The responses at 6 (PET-CT) and 12 weeks (traditional CT) were compared and correlated with symptomatic response at both these time points. Results: Forty seven patients were recruited with 38 and 33 patients assessable by FDG PET-CT at 6 weeks and traditional CT at 12 weeks, respectively. There was good correlation between Partial response (PR) at both time points and all 10 patients who had a PR at 12 weeks had a PR at 6 weeks. Of the 13 patients with progressive disease (PD) at 12 weeks, seven had PD at 6 weeks and could have had their treatment stopped early. No evaluable patient with stable disease (SD) (8/38) or PD (9/38) on FDG PET-CT at 6 weeks went on to have a later response. Symptomatic response at 6 or 12 weeks did not correlate well with objective response on scanning at either time point. Conclusions: The primary end-point of this study was met as >12 (15/38) patients could have stopped treatment early on the basis of the FDG PET-CT scan result. A FDG PET-CT evaluable response of SD or PD at 6 weeks does predict future lack of response. No correlation was found between response and symptomatic response at either 6 or 12 weeks. (C) 2011 Elsevier Ltd. All rights reserved.

A 20% mineral filled polypropylene homopolymer (Hifax XM2 U16 from LyondellBasell Industries) was studied. Correlation between experimental impact tests of components and tensile tests on specimens with simulations in ANSYS and LS-DYNA were conducted. The main goal of these tests was to evaluate the validity of elasto-plastic strain rate sensitive constitutive models implemented in both codes. Initially, strain localisation or necking phenomena were studied by simulating quasi-static tensile tests in ANSYS. An iterative method was used to match experimental force-displacement curves and so obtain true stress-strain curves as input for finite element analysis programs. Subsequently, the experimental impact testing of parts manufactured from the mineral filled polypropylene was simulated in ANSYS and LS-DYNA. It was found that the viscoplastic strain rate sensitive Perzyna's model compared well with test results from force-time and velocity-time curves but did not adequately describe the high force levels developed, particularly at the start of the tests. Additional sensitivity analyses in terms of element type, contact stiffness and mesh density were also carried out. Yield stress rate dependency was evaluated using the material model MAT 24 in LS-DYNA and, in addition, yield stress and elastic modulus rate dependency was evaluated with MAT 19. Both models offered very similar results. An initial attempt to simulate failure was also carried out with MAT 24.

Summary Introduction Prader–Willi syndrome (PWS) is a rare (1:20.000) genetic condition affecting both males and females. Among other features, in boys, the syndrome is characterized by cryptorchidism in 86–100% of cases, hypogonadism, delayed puberty and infertility. The aim of the present study is to appraise the results of orchidopexy in this selected population of children. Study design A follow-up study of children with PWS treated for undescended testes at a single institution over a 20-year period was performed. Patients were identified from a National PWS registry and reviewed at a special follow-up clinic. Data were collected from electronic and hard copies records and reported as median (range). Results Thirty-three children (1–17 years) were identified. Co-morbidities were present in 22 (66%) and 15 (45%) were on growth-hormone therapy. Six patients (19%) had normal testes palpable in the scrotum; twenty-seven (81%) had undescended testes and required orchidopexy. Thirteen (48%) underwent a bilateral procedure for a total of 40 procedures. A 2-stage Fowler-Stephens orchidopexy was required in 2 (7%) testes. At surgery hypotrophic testes were documented in 6 (22%) patients. Age at orchidopexy was 1.4 years (0.5–5.5). Age at F U was 7.2 years (1.7–17). Length of follow-up is 3.5 years (0.4–14). At follow-up 16 (40%) testes were of normal size and palpable in the scrotum; 7 (17.5%) testes required redo-orchidopexy. All patients (6/33) over 16 years of age that had testosterone levels tested had values below normal limits after successful orchidopexy. Conclusions This study evaluates the results of orchidopexy in a large population of children with PWS. At follow-up, only 40% of testes were of normal size and in the scrotum. This information should be taken into consideration for patients' management and pre-operative parents' counseling. Findings at follow-up (40 testes) Number (%) Normal testes in scrotum 16 (40) Hypotrophic testes in scrotum 8 (20) Testes in inguinal canal 10 (25) Non-palpable testes 4 (10) Atrophic testes in scrotum 2 (5) Redo-orchidopexy 7 (17.5)

Native Monterey pine ( Pinus radiata D. Don) stands on the Monterey peninsula have been significantly modified by natural and anthropogenic disturbances. The exclusion of fire and the introduction of pitch canker (caused by Fusarium circinatum Nirenberg & O’Donnell) created a need for the examination of these changing ecosystems with respect to regeneration, especially as these stands reach mature ages. We established 210 plots on 35 transects distributed throughout five stands in order to describe the current stand structure and quantify the extent and condition of regeneration. The results indicated that Monterey pine seedling establishment varies throughout the peninsula depending on percent canopy cover, duff and litter depth, and percent shrub cover while seedling growth is influenced by percent shrub cover. Canopy cover was also found to inversely influence shrub cover. Our study highlights the importance of understory removal to increase Monterey pine regeneration and seedling growth as canopy cover decreases, especially in areas where coast live oak ( Quercus agrifolia Nee) and poison-oak ( Toxicodendron diversilobum E. Greene) are abundant.

Summary Introduction Posterior urethral valves (PUV) are among the most common urological causes of chronic kidney disease (CKD) in childhood. Recently, genomic imbalances have been cited as potential risk factors for altered kidney function and have been associated with CKD. The phenotypic effects of a copy number variant (CNV) in boys with PUV are unknown. Here, it was hypothesised that the progression to early renal failure in PUV patients may be influenced by genetic aberrations. Objective To assess the relationship between CNVs and renal outcomes. Patients and methods Between September 2012 and July 2015, 45 children with PUV were recruited to evaluate the presence of CNVs in their DNA. The patients' medical records were retrospectively reviewed. The criteria for outcomes of renal function included: assessments of the nadir serum creatinine in the first year of life, the estimated glomerular filtration rate at 1 and 5 years, and the requirement for renal replacement. Results Thirteen CNVs were identified in 12 boys (29% of the cohort). Microarray analysis revealed two pathogenic CNVs (well-established CNVs known to be associated with genetic disease) and 11 of unknown significance (CNVs with insufficient current available evidence for unequivocal determination of clinical significance), including genes that have been previously implicated in kidney diseases and urogenital disorders. The median follow-up was 10.2 years (range 3–17.5) in the group of patients with CNV compared with 5.8 years (range 1–16.6) in those CNV−. The nadir creatinine values were significantly higher in boys with CNVs than in those without CNVs (57.5 μmol/L (range 23–215) and 28 μmol/L (range 18–155), respectively (P = 0.05) (Figure). Boys CNV+ had a worse prognosis, with a higher incidence of Stage-V CKD compared with the control group (33% with CNVs vs. 9% in CNV−, P = 0.06) at a median age of 22 months (range 8 months–16 years). Four (33%) patients CNV+ underwent renal transplantation. Discussion The role of CNVs in the deterioration of renal function remains unknown. It can be hypothesised that CNVs could be a contributing factor or may serve as an accelerant for the progression to renal failure. Conclusion The CNVs >100 Kb were significantly associated with early onset renal failure in children with PUV. Prenatal detection of CNV could help to identify foetuses at high risk of severe renal impairment in cases of suspected PUV, especially in cases without oligohydramnios or severe pulmonary hypoplasia. These preliminary results should be confirmed in a larger cohort of patients. Download : Download high-res image (121KB) Download : Download full-size image Summary Figure . Box plot graphic representation of nadir of creatinine value during the first year of life according to the presence of CNV (CNV+) or the absence of CNV (CNV−).

The syntheses and biological activities for anilides derived from 2-phenyl-2-(dodecyl-2H-tetrazol-5-yl)acetic acid are described. Evidence is provided that one of these compounds, (+)- 8b , stereoselectively inhibits ACAT in vitro and possesses superior efficacy in vivo compared to (−)- 8b or the recemic mixture (±)- 8b .

The identification of tetrazole benzamide and nicotinamide derivatives as new structural classes of potent ACAT inhibitors is described. The ensuing structure-activity relationship (SAR) studies revealed that retroamide 8c and 7q possesses comparable in vitro potency and efficacy to that of the fatty acid anilide, CI-976 ( 1 ).

Atherosclerotic lesion development was assessed in the thoracic aorta and chronically denuded iliac-femoral artery of hypercholesterolemic New Zealand White rabbits using inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which have previously been shown to possess varying degrees of hepatoselectivity in rats. Atorvastatin, previously known as CI-981 (2.5 mg/kg), PD135022 (1.0 mg/kg), simvastatin (2.5 mg/kg), lovastatin (2.5 mg/kg), PD134965 (1.0 mg/kg), pravastatin (2.5 mg/kg) and BMY22089 (2.5 mg/kg) were added to a 0.5% cholesterol, 3% peanut, 3% coconut oil diet and fed for 8 weeks. Although reductions in plasma total cholesterol of 27% to 60%, VLDL-cholesterol of 31% to 71% and plasma total cholesterol exposure of 37% to 43% were obtained, no correlation between these parameters and vascular lipid content, lesion size or monocyte-macrophage content was noted. Iliac-femoral lipid content was unchanged; however, atorvastatin and simvastatin significantly reduced the cholesterol content of the thoracic aorta by 45%-62%. Atorvastatin and PD135022 reduced the size of the iliac-femoral lesion by 67% and monocyte-macrophage content by 72%. Simvastatin, lovastatin and PD134965 decreased the monocyte-macrophage content; however, lesion size was unchanged. Pravastatin and BMY22089 had no effect on lesion size or content. No compound significantly reduced the extent of thoracic aortic lesions. We concluded that changes in plasma lipids and lipoproteins noted with the various HMG-CoA reductase inhibitors did not account for the beneficial effect on atherosclerotic lesion development. The antiatherosclerotic potential of the HMG-CoA reductase inhibitors was compound-specific and clearly not a class effect.

An understanding of spinal mechanics is necessary for the treatment of athletic injuries. Recognizing and isolating the mechanism of injury through noninvasive techniques will lead to specific treatment for that injury. Because the prevention of physical injury is the goal of all health care professionals, the authors hope that the information will be helpful.

Purpose The management of exstrophy-epispadias has changed markedly over the past thirty years, and long-term outcomes for different approaches of closure are not known. We have evaluated the outcomes and complications seen in all patients with exstrophy-epispadias complex managed at our institution over the past thirty years. Material and methods A retrospective notes review of all patients treated for exstrophy-epispadias complex was carried out. Basic patient demographics were recorded, as were details of all operations, complications, continence and renal function. Continence rates for patients with classic bladder exstrophy were calculated. Patients were divided into three groups on the basis of their date of birth (1975-1985, 1985-1995 and 1995-2005). Results A total of 62 patients with exstrophy-epispadias complex were treated at RCH from 1975-2005. The majority of these patients were treated from 1985-2005 (53), using the Kelly soft tissue mobilisation principle. The majority of patients had classic bladder exstrophy (42). Patients typically undergo a large number of operations in the management of classic bladder exstrophy and for complications of surgery. Complications remain commonplace, but a small number of patients had no complications. Most patients have normal renal function, but with attempts to achieve continence, more patients have some degree of renal impairment (25% of patients born 1995-2005). Continence without catheterisation is uncommon in patients with classic bladder exstrophy aged under 10 (25%), but continence improves dramatically in patients aged between 10 and 20 with 53% of patients in this age range being continent without catheterisation and a further 25% continent with catheterisation. Conclusions Bladder exstrophy remains a challenging condition to treat effectively. Complications are common, and continence is uncommon in the first decade of life. Secondary operations to improve bladder capacity and reconstruct the bladder neck have allowed the majority of patients to achieve continence in adolescence and early adult life.

Results Patients reported significant improvement in all outcome measures except for SRS mental health: SF-36 MCS (mean=2.80; p

Introduction ASD is associated with the highest subspecialty complication rate pseudoarthrosis accounting for the majority. Not long after its introduction, BMP use in ASD surgery increased in an attempt to reduce pseudoarthrosis rates. However, as BMP use has increased, scrutiny has been paid to previous studies showing low complication rates Methods This study is an analysis of complications following ASD surgery for BMP or no BMP (NOBMP). Data analyzed was from a multicenter, prospective, consecutive dataset. Inclusion criteria: Age >=18 years • ASD surgery (scoliosis >=20 degrees, sagittal vertical axis (SVA) >=5cm, pelvic tilt (PT) >=25 degrees, or thoracic kyphosis (TK)>=60 degrees) •

Purpose of study: Increased fracture rates among osteoporotic patients in proximity to instrumentation and prosthetic joint replacements is well documented in the literature. The authors have recently described burst fractures of the caudal end-instrumented lumbar vertebrae in adult patients treated with an instrumented fusion for scoliosis. The purpose of this study was to describe traumatic sacral spondylolisthesis (TSS), which is a newly recognized complication resulting from the surgical management of adult deformity after instrumentation to the sacrum, and to suggest possible treatment options. Methods used: Review of four patients with symptomatic spinal deformities and osteoporosis who were treated with surgical intervention. Each patient subsequently developed an insufficiency fracture and olisthesis of S1. of findings: Four patients averaging 60 years of age (range, 36 to 78 years) underwent a combined anterior and posterior spinal fusion to the sacrum averaging 9 levels (range, 3 to 13). Preoperative diagnoses included degenerative spondylolisthesis (n=2), degenerative scoliosis (n=1) and Charcot spine (n=1). Insufficiency fractures of the sacrum resulting in a traumatic S1 spondylolisthesis was documented an average of 7 weeks postoperatively in these patients (range, 5 to 12). Minor trauma resulting from a fall was documented in two patients. Two patients did not have a clear history of significant trauma associated with the onset of symptoms. Anterior olisthesis of the proximal S1 fragment varied from 20% to 100%. Three patients did not progress, and one patient with a 40% olisthesis progressed to a spondyloptosis. Intermittent urinary incontinence with urgency as a result of high-grade stenosis was identified in a patient with traumatic spondyloptosis. All patients had significant pain. One patient presented with the hallmark clinical posture of a high-grade spondylolisthesis. The two patients with spondyloptosis elected surgical intervention. One of these patients developed incontinence and underwent decompression, partial reduction and extension of the fusion to the ilium. Another patient underwent extension of the fusion to the ilium without reduction. The remaining two patients were treated nonoperatively. All patients demonstrated clinical improvement at most recent follow-up. Relationship between findings and existing knowledge: Combined anterior and posterior fusion may create stress risers at adjacent levels. In the osteoporotic patient this may result in insufficiency fractures. Sacral insufficiency fractures as a consequence of spinal instrumentation have not been previously described. These fractures may present with painful instability and symptoms of neurologic compression similar to that seen in high-grade developmental spondyloptosis. Overall significance of findings: In the osteoporotic patient preoperative consideration should be given to constructs that are shorter and that preserve a distal buffer zone between the lowest instrumented vertebrae and the sacrum. In addition, decreasing the stiffness of the constructs may help to decrease the magnitude of stress transferred to the adjacent vertebral levels or the sacrum. Developing a plan of treatment for a patient with TSS of S1 must take into consideration the degree of displacement, neurologic symptoms and the general health and goals of the patient. Nonsurgical treatment is appropriate for patients who cannot tolerate a significant spinal reconstruction to the ilium or the potential significant blood loss that could result from disimpaction and realignment of the fracture. Nonoperative care consisting of an extended period of bedrest has resulted in acceptable outcome. However, the risks of prolonged bed rest in the elderly is not benign. Surgical intervention to perform reduction and stabilization is an attractive, definitive option for patients who are physiologically robust. The benefit of surgical repair is the ability to decompress the neural elements and achieve rapid mobilization. Disclosures: No disclosures. Conflict of interest: No conflicts.

Purpose of study: The effect(s) of steroid administration on second-pathway mediators associated with inflammation and repair after spinal cord injury have not been well characterized. CNTF, an interlekin-6 superfamily protein associated with neuronal repair and regeneration is one such mediator. We hypothesized that methylprednisolone (MP) administration is a standard model of ASCI would inhibit CNTF expression at the site of injury. Methods used: Sprague-Dawley rats (n=24) were randomly divided into MP-treated and control groups. Paraplegia after lower thoracic laminectomy was achieved using a standardized weight drop technique. MP rats were treated with a human dose equivalent MP continuous infusion for 23 hours. Spinal cords were harvested at variable timed intervals from both groups and prepared for histologic/immunohistochemical evaluation. of findings: Representative stained spinal cord sections prepared with a specific CNTF antibody (24 hours post ASCI); MP-treated and CTNF + neurons are not observed; control section demonstrates significant CNTF+ staining. At both 0 and 8 hours after injury, the MP-treated group and the control group demonstrated negative CNTF staining. At 24 and 48 hours, respectively, a consistent staining trend was appreciated. The control group exhibited a positive CNTF reaction, whereas the MP group did not. Relationship between findings and existing knowledge: In the present experiment, MP treatment in a model of ASCI led to histologically evident inhibition of CNTF in spinal cord tissue by immunohistochemistry 24 to 48 hours after injury. Overall significance of findings: The known role of CNTF as a neuronal repair and regenerative cytokine supports future studies to evaluate MP dosing regimens that inhibit spinal cord edema while optimizing CNTF expression. Disclosures: No disclosures. Conflict of interest: No conflicts.

This paper presents information and opinion on the characteristics of part-time traineesand the working of the scheme over the past 11 years. Data have been of variable quality and it is perhaps too early to assess properly the outcome of part-time training schemes. Nevertheless such evaluation is necessary and will only be possible if suitable data are collected systematically and thoroughly, starting now.

The activities of the first two years of an Area Ethical Committee are described and analysed. Sixty-one research projects have been considered, of which 55 have been approved.

Having read the report on the ethics of research in a Teaching Area, published by a working group of the Northern Regional Health Authority, it was decided to collate and evaluate the clinical research proposals in a multi-district non-teaching Area. Despite the measures taken to examine research proposals, the results of the evaluation showed that at least one investigation had evaded ethical review altogether, and the fate of half the research was not readily available. Revised control measures are under consideration.

Fifty-two children were inadvertently given B.C.G. vaccination by subcutaneous instead of intradermal injection. Two of these children received excessive doses. There were no immediate untoward reactions. The children have been followed up for 3 years. Two developed cold abscesses and one a large discharging ulcer, all of which resolved. Administrative procedures were amended and the doctor concerned was the subject of a disciplinary inquiry.

Having identified deficiencies in the system for the ethical control of clinical research in Durham, the task of improving the system was tackled. Considerable help was derived from drawing on the experience of the Medical Research Council's Clinical Research Centre at Northwick Park Hospital. In Durham, effort is to be concentrated from seven ethical committees into one, using standard forms for initial appraisal and subsequent monitoring of clinical research projects.