The accuracy of FAST in relation to grade of solid organ injuries: a retrospective analysis of 226 trauma patients with liver or splenic lesion

BACKGROUND: This study investigated the role of a negative FAST in the diagnostic and therapeutic algorithm of multiply injured patients with liver or splenic lesions. METHODS: A retrospective analysis of 226 multiply injured patients with liver or splenic lesions treated at Bern University Hospital, Switzerland. RESULTS: FAST failed to detect free fluid or organ lesions in 45 of 226 patients with spleen or liver injuries (sensitivity 80.1%). Overall specificity was 99.5%. The positive and negative predictive values were 99.4% and 83.3%. The overall likelihood ratios for a positive and negative FAST were 160.2 and 0.2. Grade III-V organ lesions were detected more frequently than grade I and II lesions. Without the additional diagnostic accuracy of a CT scan, the mean ISS of the FAST-false-negative patients would be significantly underestimated and 7 previously unsuspected intra-abdominal injuries would have been missed. CONCLUSION: FAST is an expedient tool for the primary assessment of polytraumatized patients to rule out high grade intra-abdominal injuries. However, the low overall diagnostic sensitivity of FAST may lead to underestimated injury patterns and delayed complications may occur. Hence, in hemodynamically stable patients with abdominal trauma, an early CT scan should be considered and one must be aware of the potential shortcomings of a "negative FAST".

Model based experimental investigation on Powered Gait Orthosis (PGO)

Research on rehabilitation showed that appropriate and repetitive mechanical movements can help spinal cord injured individuals to restore their functional standing and walking. The objective of this paper was to achieve appropriate and repetitive joint movements and approximately normal gait through the PGO by replicating normal walking, and to minimize the energy consumption for both patients and the device. A model based experimental investigative approach is presented in this dissertation. First, a human model was created in Ideas and human walking was simulated in Adams. The main feature of this model was the foot ground contact model, which had distributed contact points along the foot and varied viscoelasticity. The model was validated by comparison of simulated results of normal walking and measured ones from the literature. It was used to simulate current PGO walking to investigate the real causes of poor function of the current PGO, even though it had joint movements close to normal walking. The direct cause was one leg moving at a time, which resulted in short step length and no clearance after toe off. It can not be solved by simply adding power on both hip joints. In order to find a better answer, a PGO mechanism model was used to investigate different walking mechanisms by locking or releasing some joints. A trade-off between energy consumption, control complexity and standing position was found. Finally a foot release PGO virtual model was created and simulated and only foot release mechanism was developed into a prototype. Both the release mechanism and the design of foot release were validated through the experiment by adding the foot release on the current PGO. This demonstrated an advancement in improving functional aspects of the current PGO even without a whole physical model of foot release PGO for comparison.

Magnetic resonance imaging for diagnosis and assessment of cartilage defect repairs

Clinical magnetic resonance imaging (MRI) is the method of choice for the non-invasive evaluation of articular cartilage defects and the follow-up of cartilage repair procedures. The use of cartilage-sensitive sequences and a high spatial-resolution technique enables the evaluation of cartilage morphology even in the early stages of disease, as well as assessment of cartilage repair. Sequences that offer high contrast between articular cartilage and adjacent structures, such as the fat-suppressed, 3-dimensional, spoiled gradient-echo sequence and the fast spin-echo sequence, are accurate and reliable for evaluating intrachondral lesions and surface defects of articular cartilage. These sequences can also be performed together in reasonable examination times. In addition to morphology, new MRI techniques provide insight into the biochemical composition of articular cartilage and cartilage repair tissue. These techniques enable the diagnosis of early cartilage degeneration and help to monitor the effect and outcome of various surgical and non-surgical cartilage repair therapies.

The role of purinergic signaling in the liver and in transplantation: effects of extracellular nucleotides on hepatic graft vascular injury, rejection and metabolism

Extracellular nucleotides (e.g. ATP, UTP, ADP) are released by activated endothelium, leukocytes and platelets within the injured vasculature and bind specific cell-surface type-2 purinergic (P2) receptors. This process drives vascular inflammation and thrombosis within grafted organs. Importantly, there are also vascular ectonucleotidases i.e. ectoenzymes that hydrolyze extracellular nucleotides in the blood to generate nucleosides (viz. adenosine). Endothelial cell NTPDase1/CD39 has been shown to critically modulate levels of circulating nucleotides. This process tends to limit the activation of platelet and leukocyte expressed P2 receptors and also generates adenosine to reverse inflammatory events. This vascular protective CD39 activity is rapidly inhibited by oxidative reactions, such as is observed with liver ischemia reperfusion injury. In this review, we chiefly address the impact of these signaling cascades following liver transplantation. Interestingly, the hepatic vasculature, hepatocytes and all non-parenchymal cell types express several components co-ordinating the purinergic signaling response. With hepatic and vascular dysfunction, we note heightened P2- expression and alterations in ectonucleotidase expression and function that may predispose to progression of disease. In addition to documented impacts upon the vasculature during engraftment, extracellular nucleotides also have direct influences upon liver function and bile flow (both under physiological and pathological states). We have recently shown that alterations in purinergic signaling mediated by altered CD39 expression have major impacts upon hepatic metabolism, repair mechanisms, regeneration and associated immune responses. Future clinical applications in transplantation might involve new therapeutic modalities using soluble recombinant forms of CD39, altering expression of this ectonucleotidase by drugs and/or using small molecules to inhibit deleterious P2-mediated signaling while augmenting beneficial adenosine-mediated effects within the transplanted liver.

Virtopsy -- noninvasive detection of occult bone lesions in postmortem MRI: additional information for traffic accident reconstruction

In traffic accidents with pedestrians, cyclists or motorcyclists, patterned impact injuries as well as marks on clothes can be matched to the injury-causing vehicle structure in order to reconstruct the accident and identify the vehicle which has hit the person. Therefore, the differentiation of the primary impact injuries from other injuries is of great importance. Impact injuries can be identified on the external injuries of the skin, the injured subcutaneous and fat tissue, as well as the fractured bones. Another sign of impact is a bone bruise. The bone bruise, or occult bone lesion, means a bleeding in the subcortical bone marrow, which is presumed to be the result of micro-fractures of the medullar trabeculae. The aim of this study was to prove that bleeding in the subcortical bone marrow of the deceased can be detected using the postmortem noninvasive magnetic resonance imaging. This is demonstrated in five accident cases, four involving pedestrians and one a cyclist, where bone bruises were detected in different bones as a sign of impact occurring in the same location as the external and soft tissue impact injuries.

Improving outcome after stroke: overcoming the translational roadblock

Stroke poses a massive burden of disease, yet we have few effective therapies. The paucity of therapeutic options stands contrary to intensive research efforts. The failure of these past investments demands a thorough re-examination of the pathophysiology of ischaemic brain injury. Several critical areas hold the key to overcoming the translational roadblock: (1) vascular occlusion: current recanalization strategies have limited effectiveness and may have serious side effects; (2) complexity of stroke pathobiology: therapy must acknowledge the 'Janus-faced' nature of many stroke targets and must identify endogenous neuroprotective and repair mechanisms; (3) inflammation and brain-immune-system interaction: inflammation contributes to lesion expansion, but is also instrumental in lesion containment and repair; stroke outcome is modulated by the interaction of the injured brain with the immune system; (4) regeneration: the potential of the brain for reorganization, plasticity and repair after injury is much greater than previously thought; (5) confounding factors, long-term outcome and predictive modelling. These 5 areas are linked on all levels and therefore need to be tackled by an integrative approach and innovative therapeutic strategies.

Students Helping Students

A Montana Tech student was injured and his home needed to be made wheelchair accessible. Highlands College Construction Technology students designed and constructed an exterior ramp leading to the house as well as interior ramps between levels inside the house.

Razor Thin Win: The 1972 Constitution Ballot, Campaign, Ratification & the Courts -- Mae Nan (Robinson) Ellingson & Mick McKeon “In the Crucible of Change”

Beyond the challenge of crafting a new state Constitution that empowered the people and modernized and opened up state and local government in Montana, the Constitutional Convention delegates, as they signed the final document, looked forward to the arduous task of getting it ratified by the electorate in a short ten week period between the end of the convention on March 24 and the ratification election of June 6, 1972. While all 100 delegates signed the draft Constitution, not all supported its adoption. But the planning about how to get it adopted went back to the actions of the Convention itself, which carefully crafted a ballot that kept “hot political issues” from potentially killing the entire document at the polls. As a result, three side issues were presented to the electorate on the ballot. People could vote for or against those side issues and still vote to ratify the entire document. Thus, the questions of legalizing gambling, having a unicameral legislature and retaining the death penalty were placed separately on the ballot (gambling passed, as did the retention of the death penalty, but the concept of a one-house legislature was defeated). Once the ballot structure was set, delegates who supported the new Constitution organized a grassroots, locally focused effort to secure ratification – thought hampered by a MT Supreme Court decision on April 28 that they could not expend $45,000 in public monies that they had set aside for voter education. They cobbled together about $10,000 of private money and did battle with the established political forces, led by the MT Farm Bureau, MT Stockgrowers’ Assn. and MT Contractors Assn., on the question of passage. Narrow passage of the main document led to an issue over certification and a Montana Supreme Court case challenging the ratification vote. After a 3-2 State Supreme Court victory, supporters of the Constitution then had to defend the election results again before the federal courts, also a successful effort. Montana finally had a new progressive State Constitution that empowered the people, but the path to it was not clear and simple and the win was razor thin. The story of that razor thin win is discussed in this chapter by the two youngest delegates to the 1972 Constitutional Convention, Mae Nan Ellingson of Missoula and Mick McKeon, then of Anaconda. Both recognized “Super Lawyers in their later professional practices were also significant players in the Constitutional Convention itself and actively participated in its campaign for ratification. As such, their recollections of the effort provide an insider’s perspective of the struggle to change Montana for the better through the creation and adoption of a new progressive state Constitution “In the Crucible of Change.” Mae Nan (Robinson) Ellingson was born Mae Nan Windham in Mineral Wells, TX and graduated from Mineral Wells High School in 1965 and Weatherford College in Weatherford, TX in 1967. Mae Nan was the youngest delegate at the 1972 Convention from Missoula. She moved to Missoula in 1967 and received her BA in Political Science with Honors from the University of MT in 1970. She was a young widow known by her late husband’s surname of Robinson while attending UM graduate school under the tutelage of noted Professor Ellis Waldron when he persuaded her to run for the Constitutional Convention. Coming in a surprising second in the delegate competition in Missoula County she was named one of the Convention’s “Ten Outstanding Constitutional Convention Delegates,” an impressive feat at such a young age. She was 24 at the time, the youngest person to serve at the ConCon, and one of 19 women out of 100 delegates. In the decade before the Convention, there were never more than three women Legislators in any session, usually one or two. She was a member of the American Association of University Women, a Pi Sigma Alpha political science honorary, and a Phi Alpha Theta historical honorary. At the Convention, she led proposals for the state's bill of rights, particularly related to equal rights for women. For years, Ellingson kept a copy of the preamble to the Constitution hanging in her office; while all the delegates had a chance to vote on the wording, she and delegate Bob Campbell are credited with the language in the preamble. During the convention, she had an opportunity that opened the door to her later career as an attorney. A convention delegate suggested to her that she should go to law school. Several offered to help, but at the time she couldn't go to school. Her mom had died in Texas, and she ended up with a younger brother and sister to raise in Missoula. She got a job teaching, but about a year later, intrigued with the idea of pursuing the law as a career, she called the man back to ask about the offer. Eventually another delegate, Dave Drum of Billings, sponsored her tuition at the UM School of Law. After receiving her JD with Honors (including the Law Review and Moot Court) from the UM Law School Ellingson worked for the Missoula city attorney's office for six years (1977-83), and she took on landmark projects. During her tenure, Missoula became the first city to issue open space bonds, a project that introduced her to Dorsey & Whitney. The city secured its first easement on Mount Sentinel, and it created the trail along the riverfront with a mix of playing fields and natural vegetation. She also helped develop a sign ordinance for the city of Missoula. She ended up working as bond counsel for Dorsey & Whitney, and she opened up the firm's full-fledged Missoula office after commuting a couple of years to its Great Falls office. She was a partner at Dorsey Whitney, working there from 1983 until her retirement in 2012. The area of law she practiced there is a narrow specialty - it requires knowledge of constitutional law, state and local government law, and a slice of federal tax law - but for Ellingson it meant working on great public projects – schools, sewer systems, libraries, swimming pools, ire trucks. At the state level, she helped form the Montana Municipal Insurance Authority, a pooled insurance group for cities. She's shaped MT’s tax increment law, and she was a fixture in the MT Legislature when they were debating equal rights. As a bond lawyer, though, Ellingson considers her most important work for the state to be setting up the Intercap Program that allowed local governments to borrow money from the state at a low interest rate. She has been a frequent speaker at the League of Cities and Towns, the Montana Association of Counties, and the Rural Water Users Association workshops on topics related to municipal finance, as well as workshops sponsored by the DNRC, the Water and Sewer Agencies Coordination Team, and the Montana State University Local Government Center. In 2002, she received an outstanding service award from the Montana Rural Water Users Association. In addition to being considered an expert on Montana state and constitutional law, local government law and local government finance, she is a frequent teacher at the National Association of Bond Lawyers (NABL) Fundamentals of Municipal Bond Law Seminar and the NABL Bond Attorney’s Workshop. For over 30 years Mae Nan has participated in the drafting of legislation in Montana for state and local finance matters. She has served on the Board of Directors of NABL, as Chairman of its Education Committee, was elected as an initial fellow in 1995 to the American College of Bond Counsel, and was recognized as a Super Lawyer in the Rocky Mountain West. Mae Nan was admitted to practice before the MT and US Supreme Courts, was named one of “America’s Leading Business Lawyers” by Chambers USA (Rank 1), a Mountain States Super Lawyer in 2007 and is listed in Best Lawyers in America; she is a member and former Board Member of NABL, a Fellow of the American College of Bond Counsel and a member of the Board of Visitors of the UM Law School. Mae Nan is also a philanthropist who serves on boards and applies her intelligence to many organizations, such as the Missoula Art Museum. [Much of this biography was drawn from a retirement story in the Missoulian and the Dorsey Whitney web site.] Mick McKeon, born in Anaconda in 1946, is a 4th generation Montanan whose family roots in this state go back to the 1870’s. In 1968 he graduated from Notre Dame with a BA in Communications and received a Juris Doctorate degree from the University of Montana Law School in 1971. Right after graduating from law school, Mick was persuaded by his father, longtime State Senator Luke McKeon, and his uncle, Phillips County Attorney Willis McKeon, to run for delegate to Montana’s Constitutional Convention and was elected to represent Deer Lodge, Philipsburg, Powell, and part of Missoula Counties. Along with a coalition of delegates from Butte and Anaconda, he fought through the new Constitution to eliminate the legal strangle hold, often called “the copper collar,” that corporate interests -- the Anaconda Company and its business & political allies -- had over state government for nearly 100 years. The New York Times called Montana’s Constitutional Convention a “prairie revolution.” After helping secure the ratification of the new Constitution, Mick began his practice of law in Anaconda where he engaged in general practice for nearly 20 years. Moving to Butte in 1991, Mick focused has practice in personal injury law, representing victims of negligence and corporate wrongdoing in both Montana district courts and federal court. As such, he participated in some of the largest cases in the history of the state. In 1992 he and his then law partner Rick Anderson obtained a federal court verdict of $11.5 million -- the largest verdict in MT for many years. Mick’s efforts on behalf of injured victims have been recognized by many legal organizations and societies. Recently, Mick was invited to become a member of the International Academy of Trial Lawyers - 600 of the top lawyers in the world. Rated as an American Super Lawyer, he has continuously been named one of the Best Lawyers in America, and an International Assn. of Trial Lawyers top 100 Trial Lawyer. In 2005, he was placed as one of Montana’s top 4 Plaintiff’s lawyers by Law Dragon. Mick is certified as a civil trial specialist by the National Board of Trial Advocacy and has the highest rating possible from Martindale-Hubble. Mick was awarded the Montana Trial Lawyers Public Service Award and provided pro bono assistance to needy clients for his entire career. Mick’s law practice, which he now shares with his son Michael, is limited to representing individuals who have been injured in accidents, concentrating on cases against insurance companies, corporations, medical providers and hospitals. Mick resides in Butte with his wife Carol, a Butte native. Mick, Carol, Michael and another son, Matthew, who graduated from Dartmouth College and was recently admitted to the Montana bar, enjoy as much of their time together in Butte and at their place on Flathead Lake.

Tissue neogenesis and STRO-1 expression in immature and mature articular cartilage

This study determined the potential for neotissue formation and the role of STRO-1+ cells in immature versus mature articular cartilage. Cartilage explants from immature and mature bovine knee joints were cultured for up to 12 weeks and stained with safranin-O, for type II collagen and STRO-1. Bovine chondrocyte pellet cultures and murine knee joints at the age of 2 weeks and 3 months, and surgically injured cartilage, were analyzed for changes in STRO-1 expression patterns. Results show that immature explants contained more STRO-1+ cells than mature explants. After 8 weeks in culture, immature explants showed STRO-1+ cell proliferation and newly formed tissue, which contained glycosaminoglycan and type II collagen. Mature cartilage explants showed only minimal cell expansion and neotissue formation. Pellet cultures with chondrocytes from immature cartilage showed increased glycosaminoglycan synthesis and STRO-1+ staining, as compared to pellets with mature chondrocytes. The frequency of STRO-1+ cells in murine knee joints significantly declined with joint maturation. Following surgical injury, immature explants had higher potential for tissue repair than mature explants. In conclusion, these findings suggest that the high percentage of STRO-1+ cells in immature cartilage changes with joint maturation. STRO-1+ cells have the potential to form new cartilage spontaneously and after tissue injury. (c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Are there risk factors in alpine skiing? A controlled multicentre survey of 1278 skiers

OBJECTIVE: To analyse risk factors in alpine skiing. DESIGN: A controlled multicentre survey of injured and non-injured alpine skiers. SETTING: One tertiary and two secondary trauma centres in Bern, Switzerland. PATIENTS AND METHODS: All injured skiers admitted from November 2007 to April 2008 were analysed using a completed questionnaire incorporating 15 parameters. The same questionnaire was distributed to non-injured controls. Multiple logistic regression was performed. Patterns of combined risk factors were calculated by inference trees. A total of 782 patients and 496 controls were interviewed. RESULTS: Parameters that were significant for the patients were: high readiness for risk (p = 0.0365, OR 1.84, 95% CI 1.04 to 3.27); low readiness for speed (p = 0.0008, OR 0.29, 95% CI 0.14 to 0.60); no aggressive behaviour on slopes (p<0.0001, OR 0.19, 95% CI 0.09 to 0.37); new skiing equipment (p = 0.0228, OR 59, 95% CI 0.37 to 0.93); warm-up performed (p = 0.0015, OR 1.79, 95% CI 1.25 to 2.57); old snow compared with fresh snow (p = 0.0155, OR 0.31, 95% CI 0.12 to 0.80); old snow compared with artificial snow (p = 0.0037, OR 0.21, 95% CI 0.07 to 0.60); powder snow compared with slushy snow (p = 0.0035, OR 0.25, 95% CI 0.10 to 0.63); drug consumption (p = 0.0044, OR 5.92, 95% CI 1.74 to 20.11); and alcohol abstinence (p<0.0001, OR 0.14, 95% CI 0.05 to 0.34). Three groups at risk were detected: (1) warm-up 3-12 min, visual analogue scale (VAS)(speed) >4 and bad weather/visibility; (2) VAS(speed) 4-7, icy slopes and not wearing a helmet; (3) warm-up >12 min and new skiing equipment. CONCLUSIONS: Low speed, high readiness for risk, new skiing equipment, old and powder snow, and drug consumption are significant risk factors when skiing. Future work should aim to identify more precisely specific groups at risk and develop recommendations--for example, a snow weather index at valley stations.

Immune response deviation and enhanced expression of chemokine receptor CCR4 in TBI patients due to unknown serum factors

BACKGROUND: Severe brain trauma leads to an activation of the immune system. To this date, neither the exact perturbation of the specific immune reaction induced by the traumatic brain injury (TBI), nor the interactions leading to the infiltration of peripheral immune cells into the brain are fully understood. PATIENTS AND METHODS: Serum was collected from 17 patients with TBI and a long bone fracture, 24 patients with an isolated long bone fracture and from healthy individuals. The effect of the serum on normal human monocytes and T-lymphocytes was tested in vitro by assessing proliferation and expression of surface markers, chemokine receptors and cytokines. RESULTS: Serum collected from patients with a TBI and a long bone fracture increased the expression of the chemokine receptor CCR4 in monocytes when compared to patients with an isolated long bone fracture. Extending this comparison to T-lymphocytes, the serum from TBI patients induced lower proliferation rates and decreased expression of the pro-inflammatory cytokine TNF-alpha, while simultaneously increasing the secretion of immune-modulatory cytokines (IL-4, IL-10 and TGF-beta) (p<0.05). CONCLUSION: Patients with a TBI release currently unknown soluble factors into the circulating blood that up regulate expression of chemokine receptor CCR4 in peripheral blood monocytes whilst concurrently inducing expression of immunosuppressive cytokines by activated T-lymphocytes.

The role of admission blood glucose in outcome prediction of surviving patients with multiple injuries

BACKGROUND: Recent literature demonstrates hyperglycemia to be common in patients with trauma and associated with poor outcome in patients with traumatic brain injury and critically ill patients. The goal of this study was to analyze the impact of admission blood glucose on the outcome of surviving patients with multiple injuries. METHODS: Patients' charts (age >16) admitted to the emergency room of the University Hospital of Berne, Switzerland, between January 1, 2002, and December 31, 2004, with an Injury Severity Score >or=17 and more than one severely injured organ system were reviewed retrospectively. Outcome measurements included morbidity, intensive care unit, and hospital length of stay. RESULTS: The inclusion criteria were met by 555 patients, of which 108 (19.5%) patients died. After multiple regression analysis, admission blood glucose proved to be an independent predictor of posttraumatic morbidity (p < 0.0001), intensive care unit, and hospital length of stay (p < 0.0001), despite intensified insulin therapy on the intensive care unit. CONCLUSIONS: In this population of patients with multiple injuries, hyperglycemia on admission was strongly associated with increased morbidity, especially infections, prolonged intensive care unit, and hospital length of stay independent of injury severity, gender, age, and various biochemical parameters.

Admission blood glucose is an independent predictive factor for hospital mortality in polytraumatised patients

PURPOSE: The goal of this study was to analyse a possible association of admission blood glucose with hospital mortality of polytraumatised patients and to develop an outcome prediction model for this patient group. METHODS: The outcome of adult polytraumatised patients admitted to the University Hospital of Berne, Switzerland, between 2002 and 2004 with an ISS > or = 17, and more than one severely injured organ system was retrospectively analysed. RESULTS: The inclusion criteria were met by 555 patients, of which 108 (19.5%) died. Hyperglycaemia proved to be an independent predictor for hospital mortality (P < 0.0001), following multiple regression analysis. After inclusion of admission blood glucose, the calculated mortality prediction model performed better than currently described models (P < 0.0001, AUC 0.924). CONCLUSION: In this retrospective, single-centre study in polytraumatised patients, admission blood glucose proved to be an independent predictor of hospital mortality following regression analysis controlling for age, gender, injury severity and other laboratory parameters. A reliable admission blood glucose-based mortality prediction model for polytraumatised patients could be established. This observation may be helpful in improving the precision of future outcome prediction models for polytraumatised patients. These observations warrant further prospective evaluation.

Urokinase plasminogen activator released by alveolar epithelial cells modulates alveolar epithelial repair in vitro

Intra-alveolar fibrin is formed following lung injury and inflammation and may contribute to the development of pulmonary fibrosis. Fibrin turnover is altered in patients with pulmonary fibrosis, resulting in intra-alveolar fibrin accumulation, mainly due to decreased fibrinolysis. Alveolar type II epithelial cells (AEC) repair the injured alveolar epithelium by migrating over the provisional fibrin matrix. We hypothesized that repairing alveolar epithelial cells modulate the underlying fibrin matrix by release of fibrinolytic activity, and that the degree of fibrinolysis modulates alveolar epithelial repair on fibrin. To test this hypothesis we studied alveolar epithelial wound repair in vitro using a modified epithelial wound repair model with human A549 alveolar epithelial cells cultured on a fibrin matrix. In presence of the inflammatory cytokine interleukin-1beta, wounds increase by 800% in 24 hours mainly due to detachment of the cells, whereas in serum-free medium wound areas decreases by 22.4 +/- 5.2% (p < 0.01). Increased levels of D-dimer, FDP and uPA in the cell supernatant of IL-1beta-stimulated A549 epithelial cells indicate activation of fibrinolysis by activation of the plasmin system. In presence of low concentrations of fibrinolysis inhibitors, including specific blocking anti-uPA antibodies, alveolar epithelial repair in vitro was improved, whereas in presence of high concentrations of fibrinolysis inhibitors, a decrease was observed mainly due to decreased spreading and migration of cells. These findings suggest the existence of a fibrinolytic optimum at which alveolar epithelial repair in vitro is most efficient. In conclusion, uPA released by AEC alters alveolar epithelial repair in vitro by modulating the underlying fibrin matrix.