Search

Purpose: To evaluate the current utilization trends of practicing surgeons performing and lateral extra-articular augmentation (LEA) at the time of primary anterior cruciate ligament reconstruction (ACLR)., Methods: The survey was distributed via e-mail in August 2023 to members of the Arthroscopy Association of North America who identified as knee surgeons and was available online on the Arthroscopy Association of North America website from January to September 2023. The 18-question survey was designed regarding surgeons' surgical utilization patterns of LEA during ACLR. Survey questions were created based on prior published research and recommendations regarding indications for LEA, as well as surgeon factors that have been shown to influence operative decision-making. Data were analyzed by surgeon geographics, procedure preferences, patient-based decision factors, surgeon-based decision factors, and surgeon age., Results: The survey was completed by 165 sports medicine surgeons who identified as arthroscopic knee surgeons. Majority practice types included private practice (42.1%), academic centers (26.8%), and hospital systems (20.7%). Surgeon age was 50.36 years (range, 33-77 years). In total, 6.8% perform <20 ACLRs per year, 30.2% perform 20 to 40, 26.5% perform 40 to 60, 10.5% perform 60 to 80, and 25.9% perform >80 per year. Of the surgeons, 79.4% conduct LEA, with the modified Lemaire being the most common technique (43.5%), followed by other lateral extra-articular tenodesis (LET) techniques (42.0%) and anterolateral ligament reconstruction (ALL) (27.5%). Some surgeons (14.5%) use more than 1 technique. High-volume (>60 ACLR/year) surgeons were more likely to perform LEA (23.1% vs 10.0%, P = .061) and more likely to perform anterolateral ligament reconstruction (32.2% vs 16.5%, P = .034). Younger surgeons (age <50) were more likely to use the modified Lemaire (44.4% vs 24.3%, P = .014). Decision-making to perform LEA weighted highly on patient hyperlaxity, pivot-shift severity, knee hyperextension, sport type, and age, respectively. The most reported surgeon-related factor influencing LEA utilization was training bias (38.9%)., Conclusions: Most orthopaedic surgeons with diverse geographics, demographics, practice setting, and ACLR volume perform LEA. Younger surgeons perform more frequently LEA, and surgeons admit to training bias in decision-making. Patient factors highly impacting utilization of LEA are hyperlaxity, pivot-shift severity, knee hyperextension, sport, and age., Clinical Relevance: LEA procedures for ACLR have become increasingly utilized in populations at high risk for rerupture. However, there is not currently a clear standard of care with regard to LEA procedure type or indications for augmentation., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Background: Melanoma is increasing worldwide, with incidence rates of invasive melanoma and melanoma in situ (MIS) varying by country., Objective: To provide updated invasive melanoma and MIS incidence and mortality trends in Iceland and explore differences among sex and rurality., Methods: In this whole-population study using the Icelandic Cancer Registry, patients diagnosed with invasive melanoma or MIS between 1957 and 2021 were included. Sex-specific world standardized incidence (WSR) and mortality rates were assessed by rurality. Joinpoint analysis was used to calculate trends using annual per cent change (APC)., Results: Invasive melanoma incidence rates increased from 0.66 to 7.0 (men) and 1.6 to 11.0 (women) per 100,000 person-years, and from 0.2 to 4.0 and 0.9 to 9.5 per 100,000 person-years for MIS in men and women, respectively, with a statistically significant linear trend (p = 0.001). WSR peaked in both men and women (10.7, 17.9 per 100,000 person-years) between 2002 and 2006 and has since been trending down. Between 1991 and 2005, the rise in invasive melanoma occurred more frequently in urban regions. Between 2003 and 2005, joinpoint analysis demonstrated a downtrend in invasive melanoma in men and women (-0.29, -0.73; p < 0.05). For MIS, the WSR peaked at 12.4 per 100,000 person-years in women between 1997 and 2001 before down-trending to 4.2. In recent years (2017-2021), the WSR has been steadily increasing in women with an APC of 1.43. Melanoma-specific mortality has decreased since 2012 (-0.07; p < 0.05)., Conclusions: Declining invasive melanoma incidence and mortality rates in conjunction with the recent rise in MIS may reflect the impact of Iceland's sun safety and anti-sunbed educational campaigns, federal regulation of sunbeds and earlier melanoma detection in urban areas., (© 2024 European Academy of Dermatology and Venereology.)

Background: Impact of Merkel cell polyomavirus (MCPyV) associated Merkel cell carcinoma (MCC) has not been assessed in the Icelandic population, nor in a whole population elsewhere., Objectives: The primary objective was to assess trends in the incidence of MCC in Iceland and the association with MCPyV. Secondary objectives aimed to analyze MCC outcomes., Methods: In this retrospective cohort study, patients diagnosed with MCC between 1981 and 2021 were identified from the Icelandic Cancer Registry. Patients were separated into 2 groups based on MCPyV immunochemistry staining. Age-standardized incidence was calculated and Joinpoint analysis was used to assess incidence trends. A Cox proportional hazards model was used to assess survival differences between the 2 groups., Results: Overall incidence of MCC increased from 0.015 to 0.26 per 100,000 persons, though the incidence of MCPyV positive cases recently decreased while negative cases increased. MCPyV negative tumors were associated with sun exposure ( P  < .01), a history of keratinocyte carcinoma, smaller tumor size, and lower overall survival., Limitations: Even with population-level data, comprehensively investigating associations with MCC is difficult due to its rarity., Conclusion: MCPyV negative MCC tumors were associated with lower survival despite smaller tumor size. Thus, MCPyV status could be an important prognostic biomarker., Competing Interests: None disclosed., (© 2024 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Primary central nervous system post-transplant lymphoproliferative disease (PCNS-PTLD) is a rare subset of post-transplant lymphoproliferative disorder (PTLD) isolated to the CNS without nodal or extra-nodal organ involvement [1,2]. PCNS-PTLD occurs primarily in patients following either solid organ transplants or hematopoietic stem cell transplants and tends to be monomorphic DLBCL. The development of PCNS-PTLD is commonly associated with EBV infection [3]. Many intracranial pathologies can resemble the imaging appearance of PCNS-PTLD, including primary CNS lymphoma, glial tumors, metastatic disease, and intracranial abscesses. The purpose of this systematic review is to identify the most common imaging characteristics of PCNS-PTLD. Our review included 97 sources that describe the imaging appearance of PCNS-PTLD. Based on our review, PCNS-PTLD lesions are typically multifocal, ring-enhancing and diffusion-restricting. PCNS-PTLD lesions typically demonstrate focal FDG avidity. Despite advancement in medical imaging, PCNS-PTLD remains a diagnostic challenge due to its rare incidence. Limited data is available on advanced imaging with regards to PTLD, but techniques including DCE-MRI and fMRI demonstrate promising results that may help further delineate PCNS-PTLD., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

As direct mediators between plants and soil, roots play an important role in metabolic responses to environmental stresses such as drought, yet these responses are vastly uncharacterized on a plant-specific level, especially for co-occurring species. Here, we aim to examine the effects of drought on root metabolic profiles and carbon allocation pathways of three tropical rainforest species by combining cutting-edge metabolomic and imaging technologies in an in situ position-specific 13 C-pyruvate root-labeling experiment. Further, washed (rhizosphere-depleted) and unwashed roots were examined to test the impact of microbial presence on root metabolic pathways. Drought had a species-specific impact on the metabolic profiles and spatial distribution in Piper sp. and Hibiscus rosa sinensis roots, signifying different defense mechanisms; Piper sp. enhanced root structural defense via recalcitrant compounds including lignin, while H. rosa sinensis enhanced biochemical defense via secretion of antioxidants and fatty acids. In contrast, Clitoria fairchildiana , a legume tree, was not influenced as much by drought but rather by rhizosphere presence where carbohydrate storage was enhanced, indicating a close association with symbiotic microbes. This study demonstrates how multiple techniques can be combined to identify how plants cope with drought through different drought-tolerance strategies and the consequences of such changes on below-ground organic matter composition.

Importance: Emergency research is challenging to do well as it involves time sensitive interventions in unstable patients. There is limited time to obtain informed consent from the patient or their legally authorized representative (LAR). Such research is permitted under exception from informed consent (EFIC) if specific criteria are met, including notification after enrollment. Some question whether the risks of EFIC outweighs its benefits. To date, there is limited empiric information about time to notification (TTN) and rates of withdrawal in such trials., Objective: To describe variation in TTN and rates of withdrawal among that patients enrolled in EFIC trials over a twelve-year period., Design: We performed post hoc descriptive analyses of data from five trials conducted under EFIC., Setting: Emergency medical services and receiving hospitals participating in the Resuscitation Outcomes Consortium in the United States and Canada., Participants: Patients with out-of-hospital cardiac arrest or life-threatening traumatic injury., Exposures: Notification strategies were specified at each site before initiation of enrollment by a local institutional review board. We monitored TTN within each site centrally throughout each study's enrollment period., Outcomes: TTN was defined as time from randomization to first-reported notification of patient or LAR of enrollment. Withdrawal was defined as patient or LAR opt out of ongoing participation at the time of notification., Results: Of 35,442 patients enrolled in five trials, 33,805 had cardiac arrest; and 1636 had traumatic injury. TTN varied overall and by patient outcome. Among those with cardiac arrest, TTN ranged from median (5%ile, 95%ile) of 6 (1,27) days to 28 (2, 53) days across sites. 0.3% of notified patients with cardiac arrest withdrew. Among those with traumatic injury, TTN ranged from 0 (0, 5) days to 36 (5, 68) days across sites. 7.7% of notified patients with traumatic injury withdrew., Conclusions and Relevance: There is large variation in TTN in trials conducted under EFIC for emergency research. This may be due to several factors. It may or may not be modifiable. Overall rates of withdrawal are low, which suggests current practices related to EFIC are acceptable to those who have participated in emergency research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Purpose of Review: Urologic chronic pelvic pain syndrome (UCPPS) is a chronic, noncyclic pain condition which can lead to significant patient morbidity and disability. It is defined by pain in the pelvic region, lasting for greater than 3 to 6 months, with no readily identifiable disease process. The aim of this review is to provide a comprehensive update of diagnosis and treatment of UCPPS., Recent Findings: UCPPS encompasses chronic pelvic pain syndrome or chronic prostatitis (CP/CPPS) in men and interstitial cystitis or painful bladder syndrome (IC/PBS) in women. Underlying inflammatory, immunologic, and neuropathic components have been implicated in the pathogenesis of UCPPS. For optimal patient management, an individualized and multimodal approach is recommended. Medical management and physical therapy are the mainstays of treatment. Injection therapy may offer additional relief in medically refractory patients. Further minimally invasive management may include spinal cord and peripheral nerve stimulation, though evidence supporting efficacy is limited.

Purpose of Review: This comprehensive review of current concepts in the management of vertebral compression fractures is a manuscript of vertebral augmentation literature of risk factors, clinical presentation, and management. The objective of this review is to compare outcomes between multiple augmentation techniques and ongoing discussions of effectiveness of vertebral augmentation procedures., Recent Findings: Vertebral compression fractures (VCFs) are a prevalent disease affecting approximately 1.5 million US adults annually. VCFs can cause severe physical limitations, including back pain, functional disability, and progressive kyphosis of the thoracic spine that ultimately results in decreased appetite, poor nutrition, impaired pulmonary function, and spinal cord compression with motor and sensory deficits. The deconditioning that affects patients with vertebral compression fractures leads to mortality at a far higher rate than age-matched controls. The management of vertebral compression fractures has been extensively discussed with opponents arguing in favor or restricting conservative management and against augmentation, while proponents argue in favor of augmentation. The literature is well established in reference to the effects on mortality when patients undergo treatment with vertebral augmentation; in over a million patients with vertebral compression fractures treated with vertebral augmentation as compared with patients treated with non-surgical management, the patients receiving augmentation performed well with a decrease in morbidity and mortality. Summary of the literature review shows that understanding the risk factors, appropriate clinical evaluation, and management strategies are crucial. Analysis of the evidence shows, based on level I and II studies, balloon kyphoplasty had significantly better and vertebroplasty tended to have better pain reduction compared with non-surgical management. In addition, balloon kyphoplasty tended to have better height restoration than vertebroplasty.

Postoperative cognitive dysfunction (POCD) is defined as a prolonged cognitive function impairment that occurs within weeks to months of a surgical procedure. It is especially prevalent in the elderly population, leading to increased morbidity and mortality. As anaesthetic and surgical care continues to improve and become increasingly safer, a significantly greater number of older patients have elective surgical procedures today, yet this comes with an increased POCD risk as they go through the perioperative phases. Although the pathophysiology behind the development of POCD is still under investigation, current causative mechanisms include the mode of anaesthesia administered, anaesthetic used, cerebral hypoperfusion, hyperventilation and neuroinflammation. These findings lend an insight into the importance of being cognisant of the higher likelihood of POCD in at-risk patients, including the elderly, and taking precautions to include preoperative and postoperative cognitive testing, careful monitoring during anaesthesia, blood pressure control and early treatment of postoperative complications as they arise. In this review, we provide an update on the current understanding of the pathophysiology leading to POCD, identifying risk factors, prevention and treatment strategies, with a specific focus on the elderly population., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (© Copyright 2019 by Turkish Anaesthesiology and Intensive Care Society.)

Purpose of Review: Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system that can lead to severe physical, cognitive, and neurological deficits that often manifest in young adults. Central neuropathic pain is a common presenting symptom, often prompting patients to seek treatment with opioids, NSAIDS, antiepileptics, and antidepressants despite minimal effectiveness and alarming side-effect profiles. Additionally, spasticity occurs in more than 80% of MS patients and is an important consideration for further study in treatment., Recent Findings: Related to inconsistencies in pain presentation and clinical reporting, current studies continue to investigate clinical patient presentation to define chronic pain characteristics to optimize treatment plans. Although often neuropathic in origin, the complex nature of such pain necessitates a multimodal approach for adequate treatment. While psychiatric comorbidities typically remain unchanged in their severity over time, physical conditions may lead to worsening chronic pain long-term, often due to decreased quality of life. The prevalence of neuropathic pain is ~ 86% in patients with multiple sclerosis and most commonly presents as extremity pain, trigeminal neuralgia, back pain, or headaches. As MS symptoms are frequently unremitting and poorly responsive to conventional medical management, recent attention has been given to novel interventions for management of pain. Among these, medicinal cannabis therapy, targeted physical therapy, and neuromodulation offer promising results. In this review, we provide a comprehensive update of the current perspective of MS pathophysiology, symptomatology, and treatment.

Objective: To compare three variants of a culturally relevant and theoretically based message to determine the most influential risk-framing approach for improving intention to place dental sealants for preschool children., Design and Sample: A convenience sample of adult, American Indian participants (n = 89) attending a community health fair were assigned to view a gain-framed, loss-framed, or mix-framed dental sealant message., Measures: We compared participants' scores on a 46-item survey to determine the relative effect of the frame assignment on seven indices of behavior change., Results: The mean difference in participants' stage-of-change scores (x = 1.17, n = 89, SD = 1.90) demonstrated a significant improvement for all groups after watching the dental sealant message t88  = 5.81, p < .0001, 95% CI [0.77-1.57]. Self-efficacy was the only construct for which we detected a statistically significant difference as a function of frame assignment. Overall, the mix-framed message resulted in the highest scores. The gain-framed message was the least influential on four constructs. This finding is in contrast to findings that gain-framed oral health messages are most influential (Gallagher & Updegraff, 2012; O'Keefe & Jensen, 2007)., Conclusions: Community advisory board members determined to use the mix-framed approach in an oral health social marketing campaign with a rural, American Indian audience., (© 2015 Wiley Periodicals, Inc.)

Estimates of emissions for processes and point sources at petroleum refineries and chemical plants provide the foundation for many other environmental evaluations and policy decisions. The most commonly used method, based on emission factors, results in unreliable estimates. More information regarding the actual emissions within a facility is necessary to provide a foundation for improving emission factors and prioritizing which emission factors most need improvement. Identification of which emission factors both perform poorly and introduce the largest error is needed to provide such a prioritization. To address this need, benzene and volatile organic compound (VOC) emissions within a major chemical plant/refinery were measured and compared with emission factor estimates. The results of this study indicate estimated emissions were never higher and commonly lower than the measured emissions. At one source location, VOC emissions were found to be largely representative of those measured (i.e., the catalytic reformer), but more often, emissions were significantly underestimated (e.g., up to 448 times greater than estimated at a floating roof tank). The sources with both the largest relative error between the estimate and the measurement and the largest magnitude of emissions in this study were a wastewater treatment process, an aromatics concentration unit and benzene extraction unit process area, and two sets of tanks (sets 7 and 8). Emission factors for these sources are priorities for further evaluation and improvement in this chemical plant/refinery. This study presents empirical data that demonstrate the need to validate and improve emission factors. Emission factors needing improvement are prioritized by identifying those that are weak models and introduce the largest error in magnitude of emissions. The results can also be used to prioritize evaluations of the emissions sources and controls, and any operational conditions or erroneous assumptions that may be contributing to the error.

Endoglin is a transforming growth factor β (TGF-β) coreceptor that serves as a prognostic, diagnostic and therapeutic vascular target in human cancer. A number of endoglin ectodomain-targeting antibodies (Abs) can effectively suppress both normal and tumor-associated angiogenesis, but their molecular actions remain poorly characterized. Here we define a key mechanism for TRACON105 (TRC105), a humanized monoclonal Ab in clinical trials for treatment of advanced or metastatic tumors. TRC105, along with several other endoglin Abs tested, enhance endoglin shedding through direct coupling of endoglin and the membrane-type 1 matrix metalloproteinase (MMP)-14 at the cell surface to release the antiangiogenic factor, soluble endoglin (sEng). In addition to this coupling process, endoglin shedding is further amplified by increased MMP-14 expression that requires TRC105 concentration-dependent c-Jun N-terminal kinase (JNK) activation. There were also notable counterbalancing effects on canonical Smad signaling in which TRC105 abrogated both the steady-state and TGF-β-induced Smad1/5/8 activation while augmenting Smad2/3 activation. Interestingly, TRC105-induced sEng and aberrant Smad signaling resulted in an excessive migratory response through enhanced stress fiber formation and disruption of endothelial cell-cell junctions. Collectively, our study defines endoglin shedding and deregulated TGF-β signaling during migration as major mechanisms by which TRC105 inhibits angiogenesis.

Objectives/hypothesis: To determine the resorption rate and biocompatibility characteristics of novel cross-linked hydrogel ventilation tubes and varied formulations of polyester ventilation tubes in a Chinchilla model., Study Design: Animal Study., Methods: Three cross-linked glycosaminoglycan hydrogel ventilation tubes fabricated by cross-linking thiol-modified chondroitin sulfate or thiol-modified carboxymethylated hyaluronic acid, four different polyester ventilation tubes (poly L-lactide [PLA], 50/50 poly D,L-lactide-co-glycolide [PLGA], and silver-impregnated versions of PLA and PLGA tubes) were placed into the tympanic membranes of chinchillas. Commercially available fluoroplastic ventilation tubes were placed in the contralateral ear of each animal to serve as a control. Integrity of the tubes was assessed by weekly otoscopy. Biocompatibility was assessed by auditory brainstem response, by otoscopic and histologic examination of the tympanic membrane at the tube site., Results: The hydrogel tubes had very short resorption times that expanded and enlarged the myringotomy site. PLGA and silver-coated PLGA tubes maintained their integrity in the tympanic membrane for similar durations of 18.9 ± 6.4 days and 21.0 ± 6.0 days, respectively. The silver-coated PLGA tubes had lower neutrophil and fibrosis scores than PLGA tubes. PLA tubes demonstrated equivalent findings to commercially available nonresorbable tubes with respect to otoscopic findings, auditory brainstem response thresholds, and histologic inflammatory scores., Conclusions: Resorbable polyester pressure equalization tubes demonstrate predictable resorption behavior and similar biocompatibility characteristics when compared with nonresorbable tubes. Silver modification may confer some stability to PLGA tubes. Hydrogel tubes have very short resorption times, tend to enlarge the myringotomy site, and show greater inflammatory changes., (Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.)

Efforts to develop trauma systems in the United States followed the publication of the landmark article, "Accidental Death and Disability: The Neglected Disease of Modern Society," by the National Academy of Sciences (1966) and have resulted in the implementation of a system of care for the seriously injured in most states and within the US military. In 2007, Hoyt and Coimbra published an article detailing the history, organization, and future directions of trauma systems within the United States. This article provides an update of the developments that have occurred in trauma systems in system verification and regionalization., (Published by Elsevier Inc.)

Background: In a previous retrospective study, we demonstrated that pelvic radiographs (PXRs) in the evaluation of blunt trauma patients undergoing abdominal computed tomographic (CT) scanning have limited utility in the absence of hemodynamic instability and significant physical findings. The purpose of this study was to prospectively validate an algorithm defining indications for PXR in blunt trauma patients in the emergency department., Methods: We performed a prospective observational study of consecutive blunt trauma patients over 6 months at a single Level 1 trauma center. The trauma faculty agreed to implement an algorithm of obtaining PXRs in patients undergoing abdominal CT scanning only if a specific set of criteria were met: systolic blood pressure <90 mm Hg, hemoglobin <8 mg/dL, a drop in Hgb of more than 3 mg/dL while in the trauma bay, or significant physical examination findings. The algorithm could be overridden at the discretion of the attending physician., Results: Nine hundred ninety-five consecutive blunt trauma patients whose evaluation was to include an abdominal CT scan were included in the study. Only 54 patients (6%) received a PXR. Fifty-six indications for PXR were provided: 35 (63%) severe pelvic pain, 14 (25%) proximal fractures, 3 (5%) hip dislocations, and only 4 (7%) had unexplained hypotension. No adverse events or delays in care occurred such as hypotension in the CT scanner or a delay in contacting interventional radiology, blood transfusion, or application of a pelvic binder. The algorithm selected PXR for patients who were more likely to have a pelvic fracture (33% vs. 4.5%, p < 0.001), hip dislocation (7.4% vs. 0.1%, p < 0.001), femur fracture (22.2% vs. 2.7%, p < 0.001), and to require blood transfusion (11.1% vs. 1.9%, p < 0.001). Implementation of this algorithm resulted in a decrease in charges of >$226,000 in 6 months., Conclusion: When objective evaluation of the abdomen is to be obtained via CT scanning, PXR in the emergency department is obsolete in the absence of hemodynamic instability and significant physical examination findings. Implementation of a selective algorithm in this patient population can result in significant cost savings without adverse patient outcomes.

Increased use of thoracic CT (TCT) in diagnosis of blunt traumatic injury has identified many injuries previously undetected on screening chest x-ray (CXR), termed "occult injury". The optimal management of occult rib fractures, pneumothoraces (PTX), hemothoraces (HTX), and pulmonary contusions is uncertain. Our objective was to determine the current management and clinical outcome of these occult blunt thoracic injuries. A retrospective review identified patients with blunt thoracic trauma who underwent both CXR and TCT over a 2-year period at a Level I urban trauma center. Patients with acute rib fractures, PTX, HTX, or pulmonary contusion on TCT were included. Patient groups analyzed included: (1) no injury (normal CXR, normal TCT, n=1337); (2) occult injury (normal CXR, abnormal TCT, n=205); and (3) overt injury (abnormal CXR, abnormal TCT, n=227). Patients with overt injury required significantly more mechanical ventilation and had greater mortality than either occult or no injury patients. Occult and no injury patients had similar ventilator needs and mortality, but occult injury patients remained hospitalized longer. No patient with isolated occult thoracic injury required intubation or tube thoracostomy. Occult injuries, diagnosed by TCT only, have minimal clinical consequences but attract increased hospital resources.

Background: Targeting Signal Transducer and Activator of Transcription 3 (STAT3) signaling is an attractive therapeutic approach for most types of human cancers with constitutively activated STAT3. A novel small molecular STAT3 inhibitor, FLLL32 was specifically designed from dietary agent, curcumin to inhibit constitutive STAT3 signaling in multiple myeloma, glioblastoma, liver cancer, and colorectal cancer cells., Results: FLLL32 was found to be a potent inhibitor of STAT3 phosphorylation, STAT3 DNA binding activity, and the expression of STAT3 downstream target genes in vitro, leading to the inhibition of cell proliferation as well as the induction of Caspase-3 and PARP cleavages in human multiple myeloma, glioblastoma, liver cancer, and colorectal cancer cell lines. However, FLLL32 exhibited little inhibition on some tyrosine kinases containing SH2 or both SH2 and SH3 domains, and other protein and lipid kinases using a kinase profile assay. FLLL32 was also more potent than four previously reported JAK2 and STAT3 inhibitors as well as curcumin to inhibit cell viability in these cancer cells. Furthermore, FLLL32 selectively inhibited the induction of STAT3 phosphorylation by Interleukin-6 but not STAT1 phosphorylation by IFN-γ., Conclusion: Our findings indicate that FLLL32 exhibits potent inhibitory activity to STAT3 and has potential for targeting multiple myeloma, glioblastoma, liver cancer, and colorectal cancer cells expressing constitutive STAT3 signaling.

Objective: To compare the outcomes of Medicare beneficiaries who underwent bariatric surgery within 18 months before and after implementation of the national coverage determination (NCD) for bariatric surgery., Design: Analysis of the University HealthSystem Consortium database from October 1, 2004, through September 31, 2007., Setting: A total of 102 academic medical centers and approximately 150 of their affiliated hospitals, representing more than 90% of the nation's nonprofit academic medical centers., Patients: Medicare and Medicaid patients who underwent bariatric surgery to treat morbid obesity., Main Outcome Measures: Demographics, length of stay, 30-day readmission, morbidity, observed-to-expected mortality ratio, and costs., Results: A total of 3196 bariatric procedures were performed before and 3068 after the NCD. After the implementation of the NCD, the volume of gastric banding doubled and the proportion of laparoscopic gastric bypass increased from 60.0% to 77.2%. Patients who underwent bariatric surgery after the NCD benefited from a shorter length of stay (3.5 vs 3.1 days, P < .001) and lower overall complication rates (12.2% vs 10.0%, P < .001), with no significant differences in the in-hospital mortality rates (0.28% vs 0.20%). Among Medicare patients, there was a 29.3% reduction in the number of bariatric procedures performed within the first 2 quarters after the NCD. However, the number of procedures returned to baseline volume within 1 year and exceeded baseline volume after 2 years of the NCD., Conclusion: The bariatric surgery NCD resulted in improved outcomes for Medicare beneficiaries without limiting access to care for individuals with medical disability.

Twenty-five to 30 per cent of hypotensive trauma patients require an emergent surgery, however, we have no reliable means to quickly determine that need. Our goal was to determine, via retrospective review, parameters available within minutes of arrival that predict the need for emergent surgery to control hemorrhage in hypotensive trauma patients. Inclusion criterion was initial systolic blood pressure (SBP) < 90 mm Hg in the emergency department (ED). Patients who were dead on arrival or underwent ED thoracotomy were excluded. Emergent surgery was defined as sternotomy, thoracotomy, laparotomy, or major neck vascular repair on day of admission. Potential clinical predictors were analyzed in a binary logistic regression model. Six hundred and thirty-nine hypotensive patients were identified and 193 excluded, leaving 446 with a mean age of 33 +/- 19 years and Injury Severity Score of 22 +/- 17. Thirty-two per cent suffered penetrating trauma, 30 per cent needed emergent surgery, and 19 per cent died. Independent predictors were: prolonged extrication (odds ratio (OR) 2.3), no loss of consciousness (OR 2.8), intubation (OR 1.7), central line placement (OR 1.7), and blood transfusion (OR 2.1, all P < 0.05). We concluded that hypotensive trauma patients without head injuries who require prolonged extrication, intubation, central venous access, and blood transfusion in the ED are more likely to need emergent surgery.

A nasogastric tube (NGT) is commonly used in the postoperative period after esophagectomy for decompression of the gastric conduit. The aim of this study was to evaluate the safety of a minimally invasive esophagectomy without the use of NGT decompression. We performed a retrospective review of 124 patients who underwent minimally invasive esophagectomy. Ninety-eight patients had an NGT placed for postoperative decompression and 26 patients did not. The main outcome measure was postoperative complications in regard to the gastric conduit and esophageal anastomosis. There were 96 males with a mean age of 65 +/- 11 years. Three (3%) of 98 patients with operative NGT placement developed postoperative complications directly related to the NGT, which included perforation of the gastric conduit (n = 1) and perforation of the anastomosis (n = 2). In the 26 patients without operative NGT decompression, one patient (3.8%) had distention of the gastric conduit requiring placement of a NGT under fluoroscopic guidance on postoperative Day 1. There was no significant difference in the leak rate between the groups with NGT decompression compared with the group without NGT decompression (9.2 vs 7.7%, respectively). In conclusion, the use of NGT decompression during minimally invasive esophagectomy can be safely omitted. In cases with postoperative gastric conduit distention, an NGT can be safely placed under fluoroscopic guidance.

The purpose of this study was to identify the utility of thoracic computed tomography (TCT) in blunt trauma patients with a normal admission chest radiograph (CXR). A retrospective study was performed of 200 consecutive blunt trauma patients who received both CXR and TCT. One hundred and forty-three patients had a normal screening CXR; 36 of these patients (25%) had an abnormal TCT. TCT changed the management in only nine of these patients (6%): two required serial CXR for occult pneumothorax, four received additional imaging of the spine, and three were admitted to a monitored bed. Fifty-seven patients had an abnormal initial CXR. Of these, 41 (81%) had an abnormal TCT. TCT changed management in 21 (37%) of these patients: two aortic injuries identified, 12 aortic injuries excluded, two chest tubes placed, one patient taken to the Operating Room, and four patients required further diagnostic evaluation. TCT was significantly more likely to alter management in patients with an abnormal admission CXR (6% vs 37%, P < 0.001). TCT is of limited utility in patients with a normal admission CXR. A diagnostic strategy of obtaining TCT only in patients with abnormal CXR or high-risk mechanism of injury can result in significant cost savings without adversely affecting patient outcomes.

Objectives: To review the outcomes of 104 consecutive minimally invasive esophagectomy (MIE) procedures for the treatment of benign and malignant esophageal disease., Summary Background Data: Although minimally invasive surgical approaches to esophagectomy have been reported since 1992, MIE is still considered investigational at most institutions., Methods: This prospective study evaluates 104 MIE procedures performed between August 1998 and September 2007. Main outcome measures include operative techniques, operative times, blood loss, length of stay, conversion rates, morbidities, and mortalities., Results: Indications for surgery were esophageal cancer (n = 80), Barrett esophagus with high-grade dysplasia (n = 6), recalcitrant stricture (n = 8), gastrointestinal stromal tumor (n = 3), and gastric cardia cancer (n = 7). Surgical approaches included thoracoscopic/laparoscopic esophagectomy with a cervical anastomosis (n = 47), minimally invasive Ivor Lewis esophagectomy (n = 51), laparoscopic hand-assisted blunt transhiatal esophagectomy (n = 5), and laparoscopic proximal gastrectomy (n = 1). There were 77 males. The mean age was 65 years. Three patients (2.9%) required conversion to a laparotomy. The median ICU and hospital stays were 2 and 8 days, respectively. Major complications occurred in 12.5% of patients and minor complications in 15.4% of patients. The incidence of leak was 9.6% and of anastomotic stricture was 26%. The 30-day mortality was 1.9% with an in-hospital mortality of 2.9%. The mean number of lymph nodes retrieved was 13.8., Conclusions: Minimally invasive esophagectomy is feasible with a low conversion rate, acceptable morbidity, and low mortality. Our preferred operative approach is the laparoscopic\thoracoscopic Ivor Lewis resection, which provides a tension-free intrathoracic anastomosis.

The objective of this study was to determine whether tube thoracostomy can be safely avoided in a subset of patients with blunt occult pneumothorax. A retrospective review was performed. Management without tube thoracostomy was attempted for 59 occult pneumothoraces and was successful in 51 (86%). Observation was successful in 16 of 20 occult pneumothoraces (80%) exposed to positive pressure ventilation within 72 hours of admission. Eight delayed tube thoracostomies were required an average of 19.7 hours post admission. Patients who failed observant management had more significant physiologic derangement on admission (revised trauma score 6.96 vs 7.66, P = 0.04), were more likely to have significant multisystem trauma (88% vs 37%, P = 0.007), but were not more likely to require positive pressure ventilation (PPV) (50% vs 31%, P = 0.31). This study demonstrates that a subset of patients with blunt occult pneumothorax requiring positive pressure ventilation may be safely managed without tube thoracostomy.

Background: Identifying risk factors for the development of post-traumatic stress disorder (PTSD) is important for understanding and ultimately preventing the disorder. This study assessed pain shortly after traumatic injury (i.e. peritraumatic pain) as a risk factor for PTSD., Method: Participants (n=115) were patients admitted to a Level 1 Surgical Trauma Center. Admission to this service reflected a severe physical injury requiring specialized, emergent trauma care. Participants completed a pain questionnaire within 48 h of traumatic injury and a PTSD diagnostic module 4 and 8 months later., Results: Peritraumatic pain was associated with an increased risk of PTSD, even after controlling for a number of other significant risk factors other than acute stress disorder symptoms. An increase of 0.5 s.d. from the mean in a 0-10 pain rating scale 24-48 h after injury was associated with an increased odds of PTSD at 4 months by more than fivefold, and at 8 months by almost sevenfold. A single item regarding amount of pain at the time of hospital admission correctly classified 65% of participants., Conclusions: If these findings are replicated in other samples, high levels of peritraumatic pain could be used to identify individuals at elevated risk for PTSD following traumatic injury.

ApoAI is the major protein component of the high-density lipoprotein (HDL) that has been a hot subject of interests because of its anti-atherogenic properties. ApoAI/prebeta-HDL is the most effective acceptors specifically for free cholesterol in human plasma and serves as the precursor of HDL particles. Here we report a complete backbone assignment of human apoAI on a 38 kDa prebetaHDL (Lp1-AI) particle.

ApoAI is the major protein component of the high-density lipoprotein (HDL) that has been a hot subject of interests because of its anti-atherogenic properties. Lipid-free apoAI specifically binds to phospholipids, triggering HDL formation. Here we report a complete backbone assignment and nearly complete sidechain assignment of a C-terminal 24-residue truncation mutant of mouse apoAI, apoAI(1-216), in its lipid-free form.

Background: The purpose of this study is to describe practice patterns and outcomes of posttraumatic retrievable inferior vena caval filters (R-IVCF)., Methods: A retrospective review of R-IVCFs placed during 2004 at 21 participating centers with follow up to July 1, 2005 was performed. Primary outcomes included major complications (migration, pulmonary embolism [PE], and symptomatic caval occlusion) and reasons for failure to retrieve., Results: Of 446 patients (69% male, 92% blunt trauma) receiving R-IVCFs, 76% for prophylactic indications and 79% were placed by interventional radiology. Excluding 33 deaths, 152 were Gunter-Tulip (G-T), 224 Recovery (R), and 37 Optease (Opt). Placement occurred 6 +/- 8 days after admission and retrieval at 50 +/- 61 days. Follow up after discharge (5.7 +/- 4.3 months) was reported in 51%. Only 22% of R-IVCFs were retrieved. Of 115 patients in whom retrieval was attempted, retrieval failed as a result of technical issues in 15 patients (10% of G-T, 14% of R, 27% of Opt) and because of significant residual thrombus within the filter in 10 patients (6% of G-T, 4% of R, 46% Opt). The primary reason R-IVCFs were not removed was because of loss to follow up (31%), which was sixfold higher (6% to 44%, p = 0.001) when the service placing the R-IVCF was not directly responsible for follow up. Complications did not correlate with mechanism, injury severity, service placing the R-IVCF, trauma volume, use of anticoagulation, age, or sex. Three cases of migration were recorded (all among R, 1.3%), two breakthrough PE (G-T 0.6% and R 0.4%) and six symptomatic caval occlusions (G-T 0, R 1%, Opt 11%) (p < 0.05 Opt versus both G-T and R)., Conclusion: Most R-IVCFs are not retrieved. The service placing the R-IVCF should be responsible for follow up. The Optease was associated with the greatest incidence of residual thrombus and symptomatic caval occlusion. The practice patterns of R-IVCF placement and retrieval should be re-examined.

Background: This study reports prevalence and comorbidity of five DSM-III-R diagnoses (alcohol abuse, alcohol dependence, drug abuse, major depressive episode, and generalized anxiety disorder) among American Indian and Canadian First Nations parents/caretakers of children aged 10-12 years from the Northern Midwest United States and Canada. Lifetime prevalence rates were compared to adults in the National Comorbidity Survey (NCS) and Southwest and Northern Plains cultures from the AI-SUPERPFP study., Method: Native interviewers used computer-assisted personal interviews to administer the University of Michigan Composite International Diagnostic Interview (UM-CIDI) to 861 tribally enrolled parents and caretakers (625 females; 236 males) of 741 tribally enrolled children aged 10-12 years. Fathers/male caretakers ranged in age from 21 years to 68 years with an average age of 41 years; mothers/female caretakers ranged in age from 17 years to 77 years with an average of 39 years., Results: About three-fourths (74.6%) of the adults met lifetime criteria for one of the five disorders; approximately one-third (31.6%) met lifetime criteria for two or more of the five disorders. Prevalence of the substance use disorders was higher than those in the general population (NCS); prevalence of internalizing disorders (major depressive disorder and generalized anxiety disorder) was very similar to those in the general population. Prevalence rates for alcohol abuse among the Northern Midwest adults were higher than those reported for Southwest and Northern Plains Tribes, but rates of alcohol dependency were very similar across cultures., Conclusions: The higher prevalence rates for some mental disorders found for the Northern Midwest are discussed in terms of potential method variance. The Northern Midwest results reflect unique patterns of psychiatric disorders in the ubiquity of substance abuse disorders and the co-occurrence of substance abuse disorders with internalizing disorders. Reducing lifetime occurrences of substance abuse disorders would have an enormous positive impact on the mental health of this population.

Reason for Performing Study: The relationship between fatigue and stride and/or muscle stiffness requires further study., Objective: To measure stride parameters in horses undergoing fatigue associated with running at submaximal speeds both on a treadmill and in an endurance ride., Hypothesis: Stride frequencies and estimates of hindlimb stiffness would be decreased in fatigued horses., Methods: Horses were fatigued using 2 paradigms: run to exhaustion at a treadmill (4.5 m/sec, 6% incline) and finishing an 80 km endurance ride. Videos were digitised before and after fatigue and analysed for stride parameters: hind limb length, stride frequency, time of contact, step length, duty factor and stride length., Results: In fatigued horses, stride durations were 5% longer (P = 0.007) resulting in lower stride frequencies (P = 0.016) and longer stride lengths (P = 0.006). The time of contacts (tc) for stance phase were not different (P = 0.108) nor was duty factor (tc/stride period, P = 0.457). Step length (speed x tc) and hindlimb lengths were also not different (P = 0.104, P = 0.8). For endurance horses, stride data for nonfatigued horses were consistent with data extrapolated to 4.5 m/sec from nonfatigued horses on the treadmill. Endurance horses slowed (P = 0.002) during the race from 4.55 to 4.03 m/sec and stride lengths were shorter. Despite a slower speed, other stride parameters were unchanged. Hindlimb length was shorter in fatigued horses., Conclusion: Horses fatigued on a treadmill and during the natural course of an endurance ride responded differently, biomechanically. On the treadmill, where speed is constrained, stride frequencies decreased and stride lengths increased. During one endurance ride, stride frequencies were the same, although speeds were substantially reduced. Limb length was shorter in fatigued endurance horses. It remains to be determined if these changes in mechanics are advantageous or disadvantageous in terms of energetics or injury. Further examination of endurance rides is also warranted.

Reasons for Performing Study: Although there have been reports of oxygen consumption measurements of horses running on the level and incline, there are no measurements during decline locomotion. This may be due, in part, to the potential for muscle damage produced by eccentric contractions. In man, running on a 10% decline, VO2 decreased by 35% and stride frequency (SF) decreased by 3% when compared to level locomotion., Hypothesis: The rate of O2 consumption and SF would be decreased in horses on a 10% decline when compared to the level., Methods: Six horses (average 467 +/- 68 kg) were acclimated to trotting on the level and decline prior to data collection. VO2 under moderate conditions was measured (using open flow respirometry) during trotting between 2.25 and 4.0 m/sec (at 0.25 m/sec increments) on a treadmill on the level and declined 10%. Stride frequencies were counted manually., Results: VO2 decreased (P<0.009) on the decline by an average of 45% (range 42-47%), and SF was 2.7% slower. The speed at which the minimum Cost of Transport occurs on the decline was faster than on the level. SF was reduced on the decline. No evidence of muscle soreness was noted in response to the downhill running., Conclusions and Potential Relevance: Downhill trotting, eccentric exercise, can be done safely in the horse and requires almost half the energetic costs as trotting on the level. It is not known whether this is the optimum downhill gradient or if the horse adjusts its preferred speed to accommodate downhill trotting.

Purpose: To develop and validate an ultrasensitive and specific hybridization-based enzyme-linked immunosorbent assay method for quantification of two phosphorothioate oligonucleotides (PS ODNs) (G3139 and GTI-2040) in biological fluids., Methods: This assay was based on hybridization of analytes to the biotin-labeled capture ODNs followed by ligation with digoxigenin-labeled detection ODN. The bound duplex was then detected by anti-digoxigenin-alkaline phosphatase using Attophos (Promega, Madison, WI, USA) as substrate. S1 nuclease and major factors such as the hybridization temperature, concentration of capture probe, and the use of detergent were evaluated toward assay sensitivity, selectivity, and accuracy., Results: The method is selective to the parent drugs with minimal cross-reactivity (<6%) with 3'-end deletion oligomers for both G3139 and GTI-2040. A linear range of 0.05 to 10 nM (r2 > 0.99) was observed for GTI-2040 in a variety of biological matrices. For both G3139 and GTI-2040, the within-day precision and accuracy values were found to be <20% and 90-110%, respectively; the between-day precision and accuracy were determined to be <20% and 90-120%. Addition of S1 nuclease combined with washing step greatly improved the assay linearity and selectivity. The utility of this assay was demonstrated by simultaneous determination of GTI-2040 in plasma and its intracellular levels in treated acute myeloid leukemia patients., Conclusions: The validated hybridization enzyme-linked immunosorbent assay method is specific for quantitation of PS ODNs in biological samples to picomolar level. This method provides a powerful technique to evaluate plasma pharmacokinetics and intracellular uptake of PS ODNs in patients and shows its utility in clinical evaluations.

The criteria used to diagnose recurrent airway obstruction (RAO) in affected horses include demonstration of reversible lower airway obstruction and greater than 25% neutrophils in bronchoalveolar lavage fluid (BALF). Additional objective laboratory tests are needed to improve diagnostic accuracy and to monitor response to treatment. The goal of this study was to determine if neutrophil chemoattractant activity of BALF could be measured by using a previously described, rapid, multiwell colorimetric assay for chemotaxis. In this assay, neutrophils that have migrated through a membrane filter are collected into the bottom well of a disposable chemotaxis-cell migration chamber. The number of viable cells collected in the bottom well is quantified by measurement of the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenol tetrazolium bromide (MTT), which is reduced by dehydrogenase in mitochondria of live cells. The number of migrating cells corresponds to the amount of MTT reduced, which is measured with an enzyme-linked immunosorbent assay plate reader. Fourteen adult horses were enrolled in this study, 7 of which had owner histories consistent with RAO. Each horse was sedated, a bronchoalveolar lavage tube was passed, and saline was infused and immediately aspirated. An aliquot of BALF was used for differential cell count, and BALF supernatant was harvested to assess neutrophil chemoattractant activity. Normal control horses and RAO-affected horses were distinguished according to clinical signs and percent neutrophils in BALF. Neutrophil chemoattractant activity of BALF was significantly greater in RAO-affected horses (P = 0.001) compared with control horses. This assay may be useful in future studies for monitoring response to therapy in RAOaffected horses.

Purpose: Down-regulation of Bcl-2 by the antisense G3139, currently under clinical evaluations, could restore chemosensitivity in otherwise resistant malignant cells. To date, the mechanism of intracellular accumulation of G3139 following in vivo administration remains to be elucidated. This study aimed to assess whether detectable intracellular concentrations of G3139 are achievable in vivo and how these relate to Bcl-2 down-regulation., Experimental Design: Cellular uptake of G3139 was studied in leukemia myeloid cell lines and blasts collected from treated patients using a newly developed, novel, and highly sensitive ELISA-based assay. Real-time reverse transcription-PCR was used to quantify Bcl-2 mRNA changes in treated cells., Results: The assay was fully validated and showed a limit of quantification of 50 pmol/L. When exposed to 0.33 to 10 mumol/L G3139, K562 cells exhibited intracellular concentrations in the range of 2.1 to 11.4 pmol/mg protein. When G3139 was delivered with cationic lipids, a 10- to 25-fold increase of the intracellular concentrations was observed. There was an accumulation of G3139 in the nuclei, and the ratio of nucleus to cytoplasm was increased 7-fold by cationic lipids. Intracellular concentrations of G3139 were correlated with Bcl-2 mRNA down-regulation. Robust intracellular concentrations of G3139 were achieved in vivo in bone marrow (range, 3.4-40.6 pmol/mg protein) and peripheral blood mononuclear cells (range, 0.47-19.4 pmol/mg protein) from acute myeloid leukemia patients treated with G3139., Conclusions: This is the first evidence that measurable intracellular levels of G3139 are achievable in vivo in acute myeloid leukemia patients and that Bcl-2 down-regulation is likely to depend on the achievable intracellular concentrations rather than on plasma concentrations.

Reason for Performing Study: It is well known that adding a load to a horse's back increases its energetic costs of locomotion, but the magnitude of increase obtained by loading the most distal portion of limb has not been measured., Objectives: To measure oxygen consumption in horses with mass added to the back and hooves. Because such mass distribution alters inertial parameters of the limbs, kinematic measurements were made to quantify the magnitude of change in limb movement., Methods: Steady-state oxygen consumption was measured in 6 horses with a load of 2.4 kg. The load was either carried on the back or distributed equally between the 4 limbs. Modified bell boots kept the mass at the level of P3. Horses trotted on a treadmill at speeds ranging from 2 to 5 m/sec (in 0.5 m/sec increments). High-speed (250 Hz) digital images were recorded in a sagittal plane and the positions of retroreflective markers located on standard positions on the limbs were digitised for kinematic analysis., Results: Loading of the distal limbs produced a 6.7% increase in metabolic rate, an order of magnitude higher than when the mass was added over the back. Although the stride period was 2% longer in horses with loads on the distal limbs, time of contact and duty factor were not different. Distal limb loading increased the range of motion in hind- but not forelimbs., Conclusions: The costs of swinging the limbs in the horse are considerable and the addition of weights to the distal limb can have a profound effect on not only the energetics of locomotion but also the kinematics, at least in the hindlimb., Potential Relevance: The use of weighted shoes, intended to increase animation of the gait, increases the metabolic effort of performance horses a disproportionate amount. The additional mass also increases the joint range of motion and, potentially, the likelihood of injury.

Several atypical presentations of gallbladder carcinoma have been reported, but one of the rarest is intraluminal hemorrhage. We report a case of carcinoma of the gallbladder disclosed by an emergency cholecystectomy, performed for acute cholecystitis caused by a hemocholecyst. The diagnostic approaches and characteristics of a hemocholecyst associated with carcinoma of the gallbladder are discussed.

Pancreatic tissue homogenate induces a powerful pathophysiologic response sufficient to produce lethal shock in a rat. However, limited progress has been made in the biochemical characterization of these pancreas-derived active factors or their mechanisms of action. It has been shown that the pancreas is a major source of these shock-inducing factors and that they are generated by pancreatic proteinases. Porcine pancreas was homogenized and the filtered homogenate was subjected to organic extraction both before and after incubation for 2.5 h at 37 degrees C. The aqueous and lipid extracts of pancreatic homogenates were collected and analyzed for their ability to activate human neutrophils and to induce lethal shock in the rat. Neutrophil activation, a presumed hallmark of shock, was determined by chemiluminescence and myeloperoxidase (MPO) release. Only the intact homogenate and lipid extracts stimulated the neutrophils, and the aqueous extracts proved to be inactive. Neutrophils exhibited enhanced cellular activation when exposed to substimulatory levels of either formyl-methionyl-leucyl-phenylalanine (FMLP) or platelet-activating factor (PAF) followed by substimulatory levels of the lipid extracts, but not by the aqueous extracts. Both the lipid and aqueous extracts induced dramatic decreases in heart rate and blood pressure when injected in the rat, often resulting in lethal shock. In all cases, incubation of the homogenates at 37 degrees C enhanced the potency of the extracts. Our results demonstrated that the pancreas-derived homogenate and lipid factors were capable of inducing both neutrophil activation and shock. These results support the hypothesis that shock is produced via neutrophils that have been activated by inflammatory components. However, the shock-inducing factors in the aqueous extracts (i.e., hydrophilic fraction of the homogenate) apparently function via a pathway independent of neutrophil activation. This is the first evidence that there are both hydrophobic and hydrophilic factors generated in tissue homogenates capable of inducing shock, and that these different chemical classes of factors appear to function via separate mechanisms.

We hypothesised that trotters during an extended trot have lower energetic costs of locomotion (CT) than horses not bred for this behaviour. VO2 was measured as a function of speed in 7 Arabian horses (3 trained to extend their trotting speeds) and in 2 horses, of similar mass, bred to trot (Hackney). Both oxygen consumption and CT increased with speed and there was, contrary to our hypothesis, no difference between breeds. In Arabians at 6.5 m/s, CT had increased 25% above the CT at 5.0 m/s (normal transition speed). For Hackneys at 6.8 m/s, the CT was almost 35% higher. Stride frequencies increased linearly in all horses up to 5.0 m/s. At the canter at 5.0 m/s, the frequency increased 9% to 111 strides/min, but then increased minimally with speed. In the Hackneys and the Arabians that extended the trot, stride frequencies were approximately 102 and did not increase with speed. Stride length (SL) increased linearly with speed in both trotting and cantering horses, and cantering SL were lower than trotting (at 5.0 m/s, SL for trotting = 3.04 m and for cantering SL = 2.68 m). There were no differences between breeds in stride frequency or stride length. Extending the trot can have profound energetic requirements that could limit athletic performance and may lead to increased concussive impact on the limbs.

Net joint powers and energies have been described in walking horses during the swing phase of the stride in the fore- and hindlimb (Clayton et al. 2001). During trotting, swing phase net joint powers have been described in the forelimb but not in the hindlimb. The effects of velocity on power profiles and energy patterns are important in relation to locomotor energetics. The objective of this study was to evaluate velocity-dependent changes in hindlimb net energy profiles of the swing phase during trotting. Inverse dynamic analysis was used to calculate net joint energies at the hindlimb joints of 6 horses trotting overground at velocities ranging from 2.27-5.17 m/s. At all velocities, there was net energy generation at the hip and tarsus and net energy absorption at the stifle, fetlock and coffin joints. Velocity-dependent bursts of energy generation at the hip actively protracted the limb in early swing and initiated retraction in late swing. Synchronous with the bursts of energy generation at the hip were velocity-dependent bursts of energy absorption across the stifle that acted to control flexion in early swing and extension in late swing. The distal limb was raised and lowered by velocity-dependent bursts of energy generation that flexed the tarsus in early swing and extended it in late swing. The energy bursts in early swing increased linearly with velocity, whereas the energy bursts in late swing increased as a function of the square or cube of velocity. The results contribute to understanding the mechanisms used to accelerate and decelerate the limbs more rapidly as velocity increases, which is an important consideration in racing and sporting performance.

The objective was to understand how the stance-phase kinematics of the hindlimb of trotting horses change with speed under 3 conditions (level, loaded and incline), to compare our results with the predictions of the spring-mass model and to help focus our future studies of muscle function. Video recordings were made of 5 Arabian horses trotting on a treadmill. Five consecutive strides were digitised and averaged for each trial. The angle-time diagrams were qualitatively similar to those reported previously. As speed increases, the range of motion of the hindlimb increases, as predicted by the spring-mass model. This is the result of increased range of motion in the coxofemoral and tarsal joints. The hindlimb does not 'land short-take off long'. When trotting up an incline, the hindlimb undergoes a greater range of motion because of increased retraction resulting from increased extension of the coxofemoral joint. At hoof contact on an incline, the 3 proximal joints are more flexed than on the level. Carrying a load had no effect on kinematics. These results suggest that there may be larger changes in strain with speed in muscles acting at the coxofemoral and tarsal joints than at the femorotibial joint, and that locomotion up an incline will change muscle strain more than carrying a load.

Study Objective: We evaluate the ability of paramedic rapid sequence intubation (RSI) to facilitate intubation of patients with severe head injuries in an urban out-of-hospital system., Methods: Adult patients with head injuries were prospectively enrolled over a 1-year period by using the following inclusion criteria: Glasgow Coma Scale score of 3 to 8, transport time of greater than 10 minutes, and inability to intubate without RSI. Midazolam and succinylcholine were administered before laryngoscopy, and rocuronium was given after tube placement was confirmed by means of capnometry, syringe aspiration, and pulse oximetry. The Combitube was used as a salvage airway device. Outcome measures included intubation success rates, preintubation and postintubation oxygen saturation values, arrival arterial blood gas values, and total out-of-hospital times for patients intubated en route versus on scene., Results: Of 114 enrolled patients, 96 (84.2%) underwent successful endotracheal intubation, and 17 (14.9%) underwent Combitube intubation, with only 1 (0.9%) airway failure. There were no unrecognized esophageal intubations. On arrival at the trauma center, median oxygen saturation was 99%, mean arrival PO2 was 307 mm Hg, and mean arrival PCO2 was 35.8 mm Hg. Total out-of-hospital times were higher when RSI was performed on scene (26 versus 13 minutes)., Conclusion: Paramedics can use RSI protocols that include neuromuscular blocking and sedative agents to facilitate intubation of patients with head injuries.