Enhanced release of elastase is not concomitant with increased secretion of granulocyte-activating cytokines in whole blood from patients with sepsis

Die Diskussion am Ende des Artikels wurde gelöscht (§137l UrhG).Background The proteolytic enzyme elastase released by granulocytes (polymorphonuclear leukocytes [PMN]) in high concentrations during sepsis causes degradation of essential plasma proteins, endothelial damage, and tissue edema. This may result in organ dysfunction and organ failure during sepsis, since increased elastase plasma levels correlate with the mortality rate of patients with sepsis. In vitro studies demonstrated a regulatory role of inflammatory cytokines (tumor necrosis factor-{alpha} [TNF-{alpha}], interleukin 1β [IL-1β], IL-8]) upregulatingprotease release by PMN. In this light, the interactions between cytokine release by macrophages and altered elastase secretion during sepsis remain to be determined. Methods An ex vivo model consisting of lipopolysaccharide stimulation of human whole blood as a relevant physiological milieu was used. Heparinized blood was obtained from 20 patients with sepsis syndrome (APACHE II [Acute Physiology and Chronic Health Evaluation II] score 28.5±1.2 points [mean±SD]) on days 0 through 3, 5, 7, and 10 after sepsis diagnosis and from 20 control patients without infection. Blood was incubated with lipopolysaccharide (1 mg/L) for 8 hours. Plasma levels of elastase, TNF-{alpha}, IL-1β, and IL-8 were determined using enzyme-linked immunosorbent assay or bioassay (TNF-{alpha}), respectively. Results Elastase plasma levels in whole blood from patients with sepsis were increased up to 188% (P<.01) above normal, while the release of TNF-{alpha} (-87%), IL-1 β (-91%), and IL-8 (-51%) was markedly (P<.01) decreased compared with control patients. Neutralization of TNF-{alpha} or IL-1β did not attenuate the increased release of elastase. Conclusions These data indicate an increased release of elastase by PMN despite a reduced secretion of PMNactivating cytokines. Although priming effects of TNF-{alpha}, IL-1β, and IL-8 on protease secretion in vivo cannot be excluded completely, other mediators or mechanisms may be involved in the upregulation of detrimental protease release during sepsis

Die "bio-logische” Stabilisierung der subtrochantären Femurfraktur mit einer Kondylenplatte

Zusammenfassung: Operationsziel: Indirekte Reposition von subtrochantären Frakturen über die Ligamentotaxis ohne chirurgische Traumatisierung der Frakturzone (keine devaskularisierten Fragmente!) und übungsstabile Osteosynthese mit einer Kondylenplatte. Indikationen: Geschlossene und offene subtrochantäre Trümmerfrakturen des Femurs, insbesondere bei Beteiligung der Schenkelhalsbasis. Kontraindikationen: Keine, außer bei polytraumatisierten Patienten mit lebensbedrohlichen Verletzungen. Operationstechnik: Osteosynthese mit einer Kondylenplatte. Kapsulotomie, um die korrekte Position der Klinge zu prüfen. Reposition der Fraktur an den Schaft der Kondylenplatte unter Kontrolle von Länge, Rotation und Achse, aber ohne anatomische Reposition der einzelnen Fragmente. Kompression der Fraktur, falls möglich, mit dem Spanngerät. Weiterbehandlung: Frühe funktionelle Nachbehandlung mit 15 kg Teilbelastung ab zweitem postoperativen Tag. Ergebnisse: Von 1992 bis 1995 wurden 25 Patienten mit subtrochantärer Femurfraktur (Typ A: n=10; Typ B: n=8; Typ C: n=7 [nach AO-Klassifikation]; vier offene Frakturen) mit Kondylenplatte behandelt. Operationszeit: im Mittel 1,9 Stunden; intraoperativer Blutverlust: durchschnittlich 1300 ml. Normale Frakturheilung: 24/25 Patienten. Komplikationen: Infektpseudarthrose: n=1. Konsolidation der Fraktur nach mehrfachen Débridements und Reosteosynthese mit Wellenplatte. Achsenfehlstellungen: n=3 (Varus: n=2; Verkürzung: n=1; intertrochantäre Korrekturosteotomie: n=1). Entfernung der Platte wegen chronischer Trochanterirritation: n=

The Role of Surgical Hip Dislocation in the Treatment of Acetabular and Femoral Head Fractures

Abstract : Background and Purpose: : Surgical hip dislocation by trochanteric flip osteotomy facilitates access to acetabular and femoral head fractures. Furthermore, it allows evaluation of cartilage damage and vascularity of the femoral head. In this study the potential benefits of this procedure for improved fracture management and for prognostic assessment were investigated. Patients and Methods: : From July 1997 to October 1999, 20 selected patients with displaced acetabular fractures (n = 12), femoral head fractures (n = 7), or combined injuries (n = 1) were included. Inclusion criteria for acetabular fractures were either displaced posterior wall fragments with cranial extension or complex acetabular fractures involving a displaced transverse fracture line. Open reduction and fixation of either complex acetabular fractures or femoral head fractures were carried out through Kocher-Langenbeck approach, trochanteric flip osteotomy, and complete surgical hip dislocation. Additionally, the extent of cartilage destruction and femoral head perfusion were assessed. Results: : Anatomic reduction (≤ 1 mm displacement) of acetabular fractures was achieved in 69% of patients and good reduction (≤ 3 mm) in 31%. In patients with acetabular fractures, severe cartilage destruction of the acetabulum was found in 38% and of the femoral head in 15%, while patients with isolated femoral head fractures revealed severe cartilage damage of the femoral head in 57%. Arterial bleeding from the femoral head, tested by drilling, was observed in all patients. Secondary dislocation of the trochanteric osteotomy occurred in one patient and made refixation necessary. Patients were reexamined at least 2 years after intervention. 77% of patients with acetabular fractures and all patients with femoral head fractures showed good or excellent results after 32.6 ± 6.1 months according to the functional score of D'Aubigné & Postel. Conclusion: : Surgical hip dislocation allows adequate reconstruction of complex acetabular and femoral head fractures and intraoperative evaluation of local cartilage damage and femoral head perfusio

Discerning the spatio-temporal disease patterns of surgically induced OA mouse models

Osteoarthritis (OA) is the most common cause of disability in ageing societies, with no effective therapies available to date. Two preclinical models are widely used to validate novel OA interventions (MCL-MM and DMM). Our aim is to discern disease dynamics in these models to provide a clear timeline in which various pathological changes occur. OA was surgically induced in mice by destabilisation of the medial meniscus. Analysis of OA progression revealed that the intensity and duration of chondrocyte loss and cartilage lesion formation were significantly different in MCL-MM vs DMM. Firstly, apoptosis was seen prior to week two and was narrowly restricted to the weight bearing area. Four weeks post injury the magnitude of apoptosis led to a 40–60% reduction of chondrocytes in the non-calcified zone. Secondly, the progression of cell loss preceded the structural changes of the cartilage spatio-temporally. Lastly, while proteoglycan loss was similar in both models, collagen type II degradation only occurred more prominently in MCL-MM. Dynamics of chondrocyte loss and lesion formation in preclinical models has important implications for validating new therapeutic strategies. Our work could be helpful in assessing the feasibility and expected response of the DMM- and the MCL-MM models to chondrocyte mediated therapies

Influence of Injury Pattern on Incidence andSeverity of Posttraumatic InflammatoryComplications in Severely Injured Patients

Background:: Severe trauma causes systemic inflammatory response syndrome (SIRS) which may lead to multiple organ dysfunction syndrome (MODS) or multiple organ failure (MOF). The aim of this study was to evaluate the influence of the injury pattern on the incidence and severity of SIRS, sepsis, MODS, and mortality. Methods:: A total of 1,273 patients with an injury severity score (ISS) of ≥ 9 points and survival of more than 3 days were included in this retrospective study. Outcome parameters were various grades of SIRS, sepsis, MODS, and mortality. Results:: Severe non-infectious SIRS occurred in 23%, sepsis in 14%, and severe MODS in 14% of the patients. Serious (abbreviated injury scale (AIS) ≥ 3 points) head injury and the ISS represented the most potent risk factors for severe SIRS. As estimated by multivariate logistic regression analysis, the presence of severe extremity and pelvic injuries, the ISS, and the male gender were found to be independent risk factors for sepsis. Severe injuries of the abdomen were associated with an increased risk for sepsis in the univariate analysis. Severe injuries to the head or abdomen, the ISS, and the male gender represented independent risk factors for the development of severe MODS. Regarding the late (> 3 days after trauma) hospital mortality, severe head injury, the ISS, and the patient's age were independent risk factors. Conclusions:: Head injury predominantly determines the incidence of non-infectious systemic inflammation, MOF, and late hospital mortality of patients with severe trauma. Skeletal or abdominal injuries represent relevant risk factors for septic complications. Thus, the incidence of posttraumatic, life-threatening inflammatory complications is related with certain injury patterns in addition to the gender and the severity of traum

SLCV–a supervised learning—computer vision combined strategy for automated muscle fibre detection in cross-sectional images

Muscle fibre cross-sectional area (CSA) is an important biomedical measure used to determine the structural composition of skeletal muscle, and it is relevant for tackling research questions in many different fields of research. To date, time consuming and tedious manual delineation of muscle fibres is often used to determine the CSA. Few methods are able to automatically detect muscle fibres in muscle fibre cross-sections to quantify CSA due to challenges posed by variation of brightness and noise in the staining images. In this paper, we introduce the supervised learning-computer vision combined pipeline (SLCV), a robust semi-automatic pipeline for muscle fibre detection, which combines supervised learning (SL) with computer vision (CV). SLCV is adaptable to different staining methods and is quickly and intuitively tunable by the user. We are the first to perform an error analysis with respect to cell count and area, based on which we compare SLCV to the best purely CV-based pipeline in order to identify the contribution of SL and CV steps to muscle fibre detection. Our results obtained on 27 fluorescence-stained cross-sectional images of varying staining quality suggest that combining SL and CV performs significantly better than both SL-based and CV-based methods with regards to both the cell separation- and the area reconstruction error. Furthermore, applying SLCV to our test set images yielded fibre detection results of very high quality, with average sensitivity values of 0.93 or higher on different cluster sizes and an average Dice similarity coefficient of 0.9778

Health Demands Moderate the Link Between Willpower Beliefs and Physical Activity in Patients with Knee Osteoarthritis

Background Regular physical activity (PA) was found to alleviate pain and improve functioning among patients with osteoarthritis of the knee (OAK). Heightened health demands due to OAK severity, body mass index (BMI), and depressive symptoms may require self-regulatory strategies to engage in more PA. Research on willpower—the capacity to exert self-control—suggests that believing that willpower is a nonlimited rather than a limited resource predicts effective self-regulation specifically when demands are high. The present study examines the association of OAK patients’ willpower beliefs with their daily PA as a function of health demands. Methods To identify the moderating role of OAK severity (WOMAC), BMI, and depressive symptoms (CES-D) on the link between willpower beliefs and objectively assessed PA over a 7-day period, baseline data of a registered randomized controlled trial with 243 patients (Mage = 65.47 years, SD = 0.49) were examined in secondary analyses. Results Moderation analyses revealed that overall positive associations of willpower beliefs with PA were further qualified by OAK severity, BMI, and depressive symptoms. When patients faced less health demands, believing that willpower is nonlimited was associated with more PA. When health demands were higher, willpower beliefs were not associated with PA. Conclusion OAK patients’ willpower beliefs were associated with PA. However, facing more health demands seemed to erase this beneficial link. Improving willpower beliefs by way of intervention may help to shed more light on predictive direction and ways to overcome barriers to regular physical activity