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Reliable predictive accident models (PAMs) (also referred to as safety performance functions (SPFs)) are essential to design and maintain safe road networks however, ongoing changes in road and vehicle design coupled with road safety initiatives, mean that these models can quickly become dated. Unfortunately, because the fitting of sophisticated PAMs including a wide range of explanatory variables is not a trivial task, available models tend to be based on data collected many years ago and seem unlikely to give reliable estimates of current accidents. Large, expensive studies to produce new models are likely to be, at best, only a temporary solution. This paper thus seeks to develop a practical and efficient methodology to allow currently available PAMs to be updated to give unbiased estimates of accident frequencies at any point in time. Two principal issues are examined: the extent to which the temporal transferability of predictive accident models varies with model complexity; and the practicality and efficiency of two alternative updating strategies. The models used to illustrate these issues are the suites of models developed for rural dual and single carriageway roads in the UK. These are widely used in several software packages in spite of being based on data collected during the 1980s and early 1990s. It was found that increased model complexity by no means ensures better temporal transferability and that calibration of the models using a scale factor can be a practical alternative to fitting new models.

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BACKGROUND: Historical reports indicate that active rewarming with extracorporeal membrane oxygenation (ECMO) can salvage a patient after hypothermic cardiac arrest. We created a protocol that includes ECMO for extreme hypothermia to guide rewarming of the hypothermic patient. METHODS: A retrospective review of the ECMO rewarming protocol (2004-2006) was conducted. RESULTS: The active rewarming protocol is a flowchart that is available on our hospital intranet and can be accessed in the trauma bay. A severely hypothermic patient triggers the activation of a TRAUMA ONE-OP ECMO response. During the 2-year period, there were 5 activations of the system and 4 children were placed on ECMO. Two of the 4 were dramatically salvaged and eventually discharged neurologically intact. All 5 children were found pulseless at the scene before transport. The average time from the injury occurrence to arrival was 94 minutes (range, 41-181 minutes). Mean cardiopulmonary resuscitation time was 78.2 minutes (range, 37-152 minutes). The mean core temperature on arrival was 25.4 degrees C (range, 20.4 degrees C-28.6 degrees C). The average time from arrival to ECMO cannulation was 25.5 minutes (range, 16-37 minutes). CONCLUSION: A preemptive strategy for the severely hypothermic patient provides an organized approach and prompt response. Expeditious rewarming can make the difference in an opportunity for survival.

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The objective of this study was to determine levels of DNA fragmentation in blood leukocytes and parietal cortex from guinea pigs following repeated low-level exposure to the chemical warfare nerve agent (CWNA) sarin. Guinea pigs were injected (s.c.) once a day for 10 days with saline, or 0.1, 0.2, or 0.4 LD50 (50% mean lethal dose) sarin dissolved in sterile physiological saline. Blood and parietal cortex was collected after injection at 0, 3, and 17 days recovery and evaluated for DNA fragmentation using single-cell gel electrophoresis (Comet assay). Cells were imaged using comet analysis software and three parameters of DNA fragmentation measured: tail length, percent DNA in the tail, and tail moment arm. Repeated low-dose exposure to sarin produced a dose-dependent response in leukocytes at 0 and 3 days post-exposure. There was a significant increase in all measures of DNA fragmentation at 0.2 and 0.4 LD50, but not at 0.1 LD50. There was no significant increase in DNA fragmentation in any of the groups at 17 days post-exposure. Sarin did not produce a systematic dose-dependent response in parietal cortex at any of the time points. However, significant increases in DNA fragmentation at 0.1 and 0.4 LD50 were observed at 0 and 3 days post-exposure. All measures of DNA fragmentation in both leukocytes and neurons returned to control levels by 17 days post-exposure, indicating a small and non-persistent increase in DNA fragmentation following repeated low-level exposure to sarin.

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PURPOSE: To determine the effect of scleral fixation ring placement in induction of astigmatism by topographic analysis. METHODS: Baseline measurements were used in human eyes from the Utah Lions Eye Bank. In two control eyes, the effect of placing and replacing the eye in the holder was determined. In nine eyes, the effect of placing a 14-mm ring 2.0-mm from the limbus and an 18-mm ring 4.0-mm from the limbus, both in line with and between the rectus muscles, was determined. Induced astigmatism (IA) was determined by Alpins' vector analysis method. RESULTS: Control eyes had a mean variation of 0.26 +/- 0.18 diopters (D) (range, 0.07-0.65). The study eyes had a mean IA of 1.55 D with statistically significant differences noted when comparing 14-mm rings (0.92 +/- 2.00 D) versus 18-mm rings in line with the rectus (3.02 +/- 1.49 D; p = 0.02), with 18-mm rings in line with the rectus muscles (3.02 +/- 1.46 D) versus between the muscles (1.37 +/- 1.14 D; p = 0.03), and all measurements with the 14-mm ring (1.0 +/- 1.49 D) versus the 18-mm ring (2.14 +/- 1.51 D; p = 0.04.). CONCLUSIONS: Significant IA can occur with placement of fixation rings, especially when suture placement is near the insertions of the rectus muscles.

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OBJECTIVE: To determine factors associated with the occurrence of pneumonia after intracranial surgery in dogs. STUDY DESIGN: Retrospective cohort study. Animals-Forty-nine client-owned dogs. METHODS: The medical records of 49 dogs with space-occupying intracranial disease that underwent craniotomy were reviewed. Development of pneumonia after surgery was considered highly likely in 12 dogs (affected dogs) based on clinical signs, including acute dyspnea or coughing in association with typical radiographic findings or abnormal transtracheal wash results. Pneumonia was confirmed in 6 dogs based on necropsy findings. Affected dogs were compared with 37 dogs that did not develop pneumonia (unaffected dogs) subsequent to intracranial surgery. Based on the medical records of affected dogs, determinations were made regarding time between development of pneumonia and surgery, surgical procedure, intracranial lesion type, and intracranial lesion location. Risk factors examined for both affected and unaffected dogs included level of consciousness, body position during the postoperative recovery period, duration of anesthesia, occurrence of vomiting or regurgitation, presence of seizures, cranial nerve deficiencies, and the presence of megaesophagus before and after surgery. We also compared the feeding protocol after surgery for each group. RESULTS: Pneumonia typically occurred within the first week after surgery (median, 6.5 days); however, this was variable (range, 1-96 days). Of the factors that were present within 24 hours before the clinical signs of pneumonia, vomiting or regurgitation and megaesophagus were found to be significant risk factors. Dogs that vomited or regurgitated were 2.71 times more likely to develop pneumonia than dogs that did not. Vomiting or regurgitation occurred in 63% of the dogs that developed pneumonia in this cohort. Dogs with megaesophagus were 9.25 times more likely to develop pneumonia than dogs without megaesophagus. Seven dogs with pneumonia died. Five of these 7 dogs appeared to have died as a direct sequel to pneumonia. CONCLUSION: Dogs undergoing craniectomies for space-occupying intracranial disease may be at higher risk for development of pneumonia due to several factors, including vomiting, regurgitation, and megaesophagus.

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Baclofen is a muscle relaxant used in both adults and children with neuromuscular disorders to control spasticity. In children, relatively few cases of overdose have been previously reported. We report two cases of baclofen overdose occurring in two siblings. One sibling with cerebral palsy was being treated with baclofen at the time of overdose. Both cases presented with severe respiratory depression requiring mechanical ventilation. Serum baclofen concentrations from both children were significantly elevated. We also review the published literature on baclofen overdose in children and adolescents. These cases emphasize the importance of warning parents about the potential toxicity of baclofen when prescribing the drug to a family member.

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BACKGROUND: Development of lung preservation solutions typically requires whole-organ models which are animal and labor intensive. These models rely on physiologic rather than biochemical endpoints, making accurate comparison of the relative efficacy of individual solution components difficult. We hypothesized that lung slices could be used to assess preservation of biochemical function during cold storage. MATERIALS AND METHODS: Whole rat lungs were precision cut into slices with a thickness of 500 microm and preserved at 4 degrees C in the following solutions: University of Wisconsin (UW), Euro-Collins (EC), low-potassium-dextran (LPD), Kyoto (K), normal saline (NS), or a novel lung preservation solution (NPS) developed using this model. Lung biochemical function was assessed by ATP content (etamol ATP/mg wet wt) and capacity for protein synthesis (cpm/mg protein) immediately following slicing (0 h) and at 6, 12, 18, and 24 h of cold storage. Six slices were assayed at each time point for each solution. The data were analyzed using analysis of variance and are presented as means +/- SD. RESULTS: ATP content was significantly higher in the lung slices stored in NPS compared with all other solutions at each time point (P < 0.0001). Protein synthesis was significantly higher in the lung slices stored in NPS compared with all other solutions at 6, 12, and 18 h of preservation (P < 0.05). CONCLUSIONS: This lung slice model allows the rapid and efficient screening of lung preservation solutions and their components using quantifiable biochemical endpoints. Using this model, we have developed a novel solution that improves the biochemical preservation of lung slices during cold storage.

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OBJECTIVE: Inflammatory cytokines, particularly tumor necrosis factor, contribute to myocardial dysfunction after ischemia-reperfusion injury. Aprotinin may improve outcomes in cardiac surgery through suppression of inflammatory mediators. We hypothesized that aprotinin may exert its beneficial effects through suppression of tumor necrosis factor alpha. METHODS: Adult rat hearts were precision cut into slices with a thickness of 200 microm and stored in crystalloid cardioplegic solution alone or with one of the following additions: aprotinin or tumor necrosis factor alpha, aprotinin plus tumor necrosis factor alpha, a monoclonal antibody to tumor necrosis factor alpha, or a polyclonal antibody to the tumor necrosis factor alpha receptor. Myocardial biochemical function was assessed by adenosine triphosphate content and capacity for protein synthesis immediately after slicing (0 hours) and after 2, 4, and 6 hours of storage at 4 degrees C. The content of tumor necrosis factor alpha was measured by an enzyme-linked immunosorbent assay. Six slices were assayed at each time point for each solution. The data were analyzed by analysis of variance and are expressed as the mean +/- standard deviation. RESULTS: When stored in cardioplegic solution containing aprotinin, the heart slices demonstrated (1) an increase in adenosine triphosphate content and protein synthesis (P <.0001), (2) a decrease in intramyocardial generation of tumor necrosis factor alpha (P

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BACKGROUND: Development of myocardial preservation solutions requires the use of whole organ models which are animal and labor intensive. These models rely on physiologic rather than biochemical endpoints, making accurate comparison of the relative efficacy of individual solution components difficult. We hypothesized that myocardial slices could be used to assess preservation of biochemical function during cold storage. MATERIALS AND METHODS: Whole rat hearts were precision cut into slices with a thickness of 200 microm and preserved at 4 degrees C in one of the following solutions: Columbia University (CU), University of Wisconsin (UW), D5 0.2% normal saline with 20 meq/l KCL (QNS), normal saline (NS), or a novel cardiac preservation solution (NPS) developed using this model. Myocardial biochemical function was assessed by ATP content (etamoles ATP/mg wet weight) and capacity for protein synthesis (counts per minute (cpm)/mg protein) immediately following slicing (0 hours), and at 6, 12, 18, and 24 hours of cold storage. Six slices were assayed at each time point for each solution. The data were analyzed using analysis of variance and are presented as the mean +/- standard deviation. RESULTS: ATP content was higher in the heart slices stored in the NPS compared to all other solutions at 6, 12, 18 and 24 hours of cold storage (p < 0.05). Capacity for protein synthesis was higher in the heart slices stored in the NPS compared to all other solutions at 6, 12, and 18 hours of cold storage (p < 0.05). CONCLUSIONS This myocardial slice model allows the rapid and efficient screening of cardiac preservation solutions and their components using quantifiable biochemical endpoints. Using this model, we have developed a novel preservation solution which improves the biochemical function of myocardial slices during cold storage.

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Taxol-induced peripheral neuropathy is a commonly-occurring side-effect in the treatment of cancer patients with taxoteres or taxanes. Taxol is known to induce apoptosis in a number of tumor cells. This report documents that, similar to proliferating cells, taxol induces apoptosis in NGF-differentiated PC12 cells, as assessed by exogenous FITC-annexin-V binding and nuclear fragmentation. It is shown that PC12 cells that stably overexpress Bcl-2 are protected against the toxic effect of taxol, as evidenced by the XTT assay and by a decreased fraction of propididum iodide positive cells in a dye exclusion test. Also the number of annexin-V-positive cells and the number of fragmented nuclei are lower in the Bcl-2 transfected cells. The effect is similar to the protective effect of Bcl-2 against NGF deprivation in differentiated PC12 cells. Although taxol forced both wild-type and Bcl-2-overexpressing cells into a mitotic state, only in Bcl-2-overexpressing cells did this lead to the appearance of metabolically active, multi-nucleated cells. This suggests that Bcl-2 is able to induce an alternative escape pathway, downstream of the G2/M block, in taxol-treated differentiated PC12 cells.

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Bcl-2 is a gene with clear anti-apoptotic properties in neurodegenerative conditions. One of the earliest hallmarks of degeneration in neuronal cell cultures is the loss of neurite morphology. Therefore the effect of Bcl-2 on neuronal morphology and microtubule stability was studied in nerve growth factor differentiated PC12 cells. Microtubule dynamics were modulated using the microtubule stabilizer taxol and the microtubule destabilizer, okadaic acid, a protein phosphatase inhibitor. It was shown that Bcl-2 protects against both taxol- and okadaic acid induced neurite retraction. Bcl-2 overexpression also significantly reduced the increased ratio of acetylated tubulin over total tubulin induced by taxol treatment. Interestingly, Bcl-2 attenuates the decrease of the same ratio after exposure to okadaic acid, suggesting that Bcl-2 is able to normalize the level of acetylated tubulin. In addition, cell death and nuclear fragmentation, induced by okadaic acid, were reduced in Bcl-2 overexpressing cells. This protection is either downstream or independent of tau phosphorylation as quantitative immunocytochemistry with AT8 showed that Bcl-2 did not modify the level of tau phosphorylation. The data suggest that the protective effect of Bcl-2 on the neuronal cytoskeleton is probably linked to changes in the post-translational modification of tubulin.

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OBJECTIVE: To determine the prevalence of various clinical signs in dogs with brain tumors. DESIGN: Retrospective study. ANIMALS: 97 dogs with brain tumors. PROCEDURE: Medical records were reviewed for signalment, tumor type and location, and clinical signs. RESULTS: 33 breeds were represented; Golden Retrievers were most commonly affected. Most dogs were older (median age, 9 years); 95% of dogs were > or = 5 years old. Seventy-six percent of dogs had tumors in the supratentorial region. Seizures were the most common clinical sign at initial examination, with lower prevalence for circling, ataxia, and head tilt. Meningioma was the most common tumor. CONCLUSIONS AND CLINICAL RELEVANCE: Brain tumors develop most often in dogs > or = 5 years old and are uncommon in dogs < 5 years old. Seizures are a common clinical sign, and a brain tumor should be considered in dogs that have their first seizure after they are 4 years old.

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This report addresses the relation between Bcl-2 and mitochondrial membrane potential (DeltaPsi(m)) in apoptotic cell death. Rat pheochromocytoma (PC12) cells are differentiated into neuron-like cells with nerve growth factor (NGF). It is known that Bcl-2 can attenuate apoptosis induced by deprivation of neurotrophic factor. The protective effect of Bcl-2 has been correlated with preservation of DeltaPsi(m). Protonophores, such as carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), collapse the proton gradient across the mitochondrial inner membrane, resulting in a complete abolition of the mitochondrial membrane potential. Based on the analysis of morphology, of phosphatidylserine exposure and of nuclear fragmentation we conclude that FCCP induces apoptosis in PC12 cells, which can be prevented by overexpression of Bcl-2. To determine whether the cytoprotective effect of Bcl-2 is due to stabilization of DeltaPsi(m), we investigated the effect of Bcl-2 on changes in DeltaPsi(m), induced by FCCP in PC12 cells. We showed that treatment with FCCP induced a reduction in DeltaPsi(m), as assessed with the lipophilic cationic membrane potential-sensitive dye JC-1, and that Bcl-2 protects against FCCP-induced changes in NGF differentiated PC12 cells. Our data indicate that Bcl-2 protects against FCCP-induced cell death by stabilizing DeltaPsi(m).

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As military medicine continues its adoption of managed care economic principles, the leadership of our military treatment facilities (MTFs) need a clear and simple rationale for making resource allocation decisions. The leadership body of an MTF needs to be cognizant of the role of readiness when making such decisions. This article provides a simple resourcing decision model that includes "readiness" as a decision-making factor.

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The specificity of protein kinases has been shown to be influenced by residues near the phosphoaccepting amino acid. To examine the determinants for platelet-derived growth factor receptor (PDGFR) tyrosine kinase specificity, a peptide library with three degenerate positions N-terminal to tyrosine was constructed. After reaction with PDGFR, the most abundant phosphopeptides were isolated by immunoaffinity chromatography on a column containing monoclonal anti-phosphotyrosine antibody. Further separation of bound phosphopeptides with reverse-phase HPLC led to the identification of three optimal substrates for PDGFR: Ala-Ala-Asn-Ile-Thr-Tyr-Ala-Ala-Arg-Arg-Gly, Ala-Ala-Asn-Arg-Thr-Tyr-Ala-Ala-Arg-Arg-Gly and Ala-Ala-Leu-Ile-Thr-Tyr-Ala-Ala-Arg-Arg-Gly, where underlined residues are in the degenerate positions of the peptide library. Kinetic analyses of the three individual peptides (synthesized separately) showed these peptides to be among the best reported substrates for PDGFR. Our results expand the range of amino acid residues that have been shown to serve as recognition elements for receptor tyrosine kinases.

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Families and surrogates sometimes use religious themes to justify their insistence on aggressive end-of-life care. Their hope that "God will work a miracle" can halt negotiations with health care professionals and lead to litigation. The possibility of "re-imagining" religious themes, to broaden their scope and present a wider vision of the Christian tradition, may offer a solution.

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Self-injury is increasingly linked to traumatic childhood experiences, and is identified in this paper as a means by which some trauma survivors cope with post-traumatic effects. It is proposed that self-injury serves a number of functions, organized here into four categories: re-enactment of the original trauma, expression of feelings and needs, reorganization of the self, and management of dissociative process.

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Responding effectively to trauma survivors who engage in self-injury can be challenging, even for experienced therapists. This paper outlines therapeutic goals and appropriate clinical responses, including remaining present at and open to communication about disclosures of self-injury, helping clients to intervene in their own process of self-injury, and working with clients to resolve underlying issues. Alternatives to self-injury are discussed and cautions are offered about common therapeutic responses likely to be particularly unhelpful.

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The management of a high-output pancreatic fistula is often difficult, and can be even more challenging in the pediatric patient. Octreotide acetate (OA) (Sandostatin, Sandoz, East Hanover, NJ) has served to facilitate the treatment of this difficult problem, but experience has been limited to adults. Somatostatin is a hormone that decreases the production of pancreatic exocrine and endocrine secretions. The use of the long-acting somatostatin analogue, OA, has reduced pancreatic fistula output and facilitated resolution of pancreatic fistulae in adults. This report summarizes the IV use of OA and external drainage in the complete resolution of high-output traumatic pancreatic fistulae in three pediatric patients. The treatment was well tolerated without side effects, and resulted in a dramatic decrease in the amount of fistula drainage within the first 24 to 48 h. OA can be safely administered IV (5-10 µg/kg per day) and is valuable in the management of traumatic pancreatic fistula in children.

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Recent literature pertinent to adult survivors suggests that childhood sexual abuse is a serious problem, and that disclosure is on the rise. The aftereffects of childhood sexual abuse can cause dysfunction in various aspects of the survivor's physical and mental health. Understanding the traumagenic dynamics of childhood sexual abuse and its aftereffects provides direction for the nurse therapist during both the client's disclosure and intervention planning. This knowledge assists the therapist in promoting mental health and healing, as well as providing comfort for the therapist. The nurse therapist's reactions to the client's disclosure can affect the way the client feels about disclosure and the therapeutic relationship. If a negative message is conveyed to the survivor at the time of disclosure, the feelings of betrayal, stigmatization, and powerlessness that the survivor experienced as a child will be replicated. This can damage the therapeutic relationship and delay the healing process. When disclosure is received and acted upon in a sensitive, therapeutic manner, the survivor is empowered and can enter with the nurse therapist into an effective therapeutic alliance. Nurse therapists should gain awareness of the types of emotional responses that can be engendered in the health professional during disclosure. Awareness of these emotional reactions can lead to the identification of coping strategies useful to both the therapist and the adult survivor. Coping strategies useful to the therapist include maintaining adequate boundaries, understanding oneself and one's responses to sexual-abuse issues, utilizing ongoing consultation or supervision, and preventing burnout.(ABSTRACT TRUNCATED AT 250 WORDS)

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