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Introduction: Operations in trauma patients represent a second insult and the extent of the surgical procedures influences the magnitude of the inflammatory response. Our hypothesis was that a reamer-irrigator-aspirator (RIA) system would cause a lesser inflammatory response than traditional reaming (TR)., Materials and Methods: Coagulation, fibrinolysis and cytokine responses were studied in Norwegian landrace pigs during and after intramedullary nailing (IMN) with two different reaming systems using ELISA and chromogenic peptide substrate assays. The TR (n=8) and the RIA (n=7) reaming systems were compared to a control group (n=7). The animals were followed for 72 h. Arterial, mixed venous and femoral vein blood were withdrawn simultaneously peroperatively and until 2 h after the nail was inserted for demonstration of local, pulmonary and systemic activation of the cascade systems. At 6 h, 24 h, 48 h and 72 h postoperatively arterial blood samples were withdrawn., Results: Significantly procedure-related increased levels were found for thrombin-antithrombin (TAT) and tissue plasminogen activator (t-PA) in the TR group and TAT in the RIA group. The local and the pulmonary activation of coagulation and fibrinolysis were more pronounced in the TR than in the RIA group, the difference reached significance for plasminogen activator inhibitor-1 (PAI-1) (arterial blood). The cytokine response, mainly represented by IL-6 increase, was more pronounced in the TR than the RIA group, and was significant for IL-6 in femoral vein blood. The arterial levels of IL-6 exceeded the mixed venous levels indicating an additional pulmonary activation of IL-6. Two animals in the TR group, who died of pulmonary embolism (PE) prior to planned study end point, had a more pronounced response compared to the rest of the TR group., Conclusion: A procedure-related coagulation and fibrinolytic response was demonstrated in both reaming groups, with more pronounced response in the TR than in the RIA group. Elevated levels of cytokines were demonstrated related to reaming and nailing, with significantly higher IL-6 levels in the TR than in the RIA group., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Introduction: Intramedullary orthopaedic procedures may increase the intramedullary pressure (IMP) and thereby cause intravasation of bone marrow contents. In recent studies by the authors the reamer-irrigator-aspirator (RIA) has been demonstrated to reduce IMP and coagulation-, fibrinolysis- and cytokine responses, but did not prove any significant difference in cardiopulmonary function parameters or numbers of emboli when compared to a traditional reaming (TR) system. The correlations between IMP increase, regardless type of reamer, and inflammatory- and coagulation responses, pulmonary embolization, and cardiopulmonary alterations have, however, not previously been analyzed in this material. Our hypothesis was that a lower IMP would result in reduced occurrence of pulmonary embolization, reduced inflammatory-and coagulation responses, as well as reduced cardiopulmonary alterations., Materials and Methods: Twenty-eight young Norwegian landrace pigs were exposed to femoral intramedullary reaming, with either the TR (n = 10) or the RIA (n = 10) system, or used as controls (n = 8). IMP was recorded during reaming and nailing. Serial blood samples for demonstration of coagulation-, fibrinolysis-, and cytokine activation were withdrawn peroperatively and until 72 hours post nail insertion. Circulatory and pulmonary effects were monitored peroperatively and until two hours postoperatively. The animals were sacrificed 72 hours post nail insertion and lung tissue biopsies were harvested and examined for lung emboli., Results and Conclusions: A strong correlation between increased IMP and increased coagulation-and cytokine responses was found. The number of emboli was not significantly correlated to IMP, but was strongly correlated to changes in the coagulation- and cytokine responses. No clinical relevant correlations were observed between increased IMP or numbers of lung emboli and changes in hemodynamic- or pulmonary function parameters. A correlation between coagulation activation and cytokine activation was observed. This study confirms the connection between increased IMP, increased coagulation activation and the magnitude of pulmonary emboli in a model evaluating the effects of intramedullary reaming of intact pig femora. In this model, the lowering of IMP during reaming, as obtained with RIA, reduced the magnitude of and the effects of bone marrow extravasation., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Aim: Bilirubin overload caused by haemolysis of transfused blood and breakdown of extravasated blood constitutes an important causative factor of jaundice in trauma patients. Intravenous infusions of large amounts of unconjugated bilirubin (UCB) block biliary phospholipid secretion and produce canalicular membrane lesions in pigs, putatively because of enhanced cytotoxicity of bile. Severe intrahepatic cholestasis is the functional end result. The aim of the study was to investigate whether bilirubin ditaurate (BDT) overload, which also inhibits biliary phospholipid secretion, also induces intrahepatic cholestasis., Methods: Six pigs were infused with 2.8 g of BDT for 150 min. Six control pigs were infused with albumin sham solution for 150 min. Bile samples were analysed for bile acid- and phospholipid-secretion rates. Bile and serum samples were analysed for bilirubin concentration. Liver biopsies were obtained for scanning electron microscopic studies (SEM)., Results: Biliary bile acid secretion fell by 7.7% and biliary phospholipid secretion rate fell by 88% after BDT infusion. Thus, infusion of BDT for 150 min did not cause intrahepatic cholestasis. SEM showed some variability in the size of canalicular membrane microvilli, but no evidence of gross destruction., Conclusion: BDT overload markedly lowers biliary phospholipid secretion. In contrast to UCB, BDT does not induce canalicular membrane damage nor cause intrahepatic cholestasis. Sustained, marked inhibition of phospholipid secretion does therefore not adequately explain UCB-induced cholestasis. Accumulation of UCB in the canalicular membrane may be the important factor in the pathogenesis of canalicular membrane lesions and intrahepatic cholestasis during UCB overload.

Objective: Insulin and adiponectin exert important effects on the vasculature. We wanted to explore whether the eNOS inhibitor asymmetric dimethylarginine (ADMA) contribute to their effects., Methods: Human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (HCAECs) were incubated with growth medium in the presence or absence of tumor necrosis factor-alpha (TNFalpha), D-glucose, insulin or adiponectin. Further, cells exposed to TNFalpha for 24h were co-stimulated with insulin or adiponectin for additional 24h. Concentrations of ADMA in conditioned media and activity of dimethylarginine dimethylaminohydrolase (DDAH) in cell lysates were determined., Results: The dose-dependent TNFalpha-induced ADMA accumulation was significantly inhibited when co-stimulated with insulin or adiponectin in both cell lines (p<0.01 for all), accompanied by significant increases in DDAH activity in all conditions. Insulin alone resulted in a significant, but inversely dose-dependent accumulation of ADMA as compared to control cells in both cell lines, accompanied by increased DDAH activity. Adiponectin alone tended, dose-dependently to decrease ADMA, but without an increase of DDAH activity., Conclusion: The results indicate that ADMA accumulation in human cultured endothelial cells is influenced by both insulin and adiponectin, and both mediators counteract the TNFalpha-induced accumulation of ADMA through the DDAH pathway.

Objective: The purpose of the present study was to compare the efficacy of intracoronary and intravenous injection of autologous progenitor cells for homing to the acutely infarcted but reperfused myocardium in pigs., Methods: Myocardial infarction was induced in 11 anesthetized pigs by 60-min balloon inflation in the mid LAD. After balloon deflation, reperfusion was verified and autologous CD31(+) progenitor cells, or bone marrow mononuclear cells, labeled with PKH67, were injected either intracoronarily (n=6) or intravenously (n=3). By autopsy, 4-5 days after induction of infarction, tissue from the heart and other organs was obtained for fluorescence microscopy., Results: In the heart, PKH(+) cells were detected throughout the reperfused infarcted myocardium, and the number of PKH(+) cells was significantly higher after intracoronary than after intravenous injection (3.2+/-0.55 vs. 0.33+/-0.17 cells/high-power field/10(6) cells injected, P=.01). Few PKH(+) cells were detected in the spleen, lung, mesenteric lymph node, and bone marrow. In an additional animal with a coil placed in the mid LAD, progenitor cells were not detected in the infarcted myocardium or in the normal myocardium., Conclusion: Autologous mononuclear and CD31(+) cells from bone marrow accumulated in the infarcted myocardium when injected intracoronarily or intravenously after established reperfusion, and the accumulation of cells was significantly greater after intracoronary injection than after intravenous injection. Accumulation of PKH(+) cells did not appear in the normal myocardium or in the nonreperfused infarcted myocardium. PKH(+) cells were detected in spleen, lung, and bone marrow but to a lesser degree than in the infarcted myocardium.

Background: Increased intramedullary pressure in the femoral cavity causes intravasation of bone marrow content to the circulation which may lead to occlusion of pulmonary vessels and cardiorespiratory dysfunction. A one-step reamer-irrigator-aspirator (RIA) technique has been developed to reduce the intramedullary pressure (IMP) during the reaming procedure. This study was design to compare IMP with a standard reaming technique with IMP during reaming with the RIA system with a hypothesis that the RIA system would involve lower pressures., Material and Method: In a randomised study in 19 Norwegian landrace pigs reamed intramedullary nailing was performed with two different reamer devices. Nine animals were operated with a traditional reamer and 10 animals with RIA. One animal in the RIA group was excluded due to a perioperative femoral fracture, and three animals in the traditional group were excluded due to a perforation of the distal medial femoral cortex. The intramedullary pressure was registrated with a transducer-tipped pressure monitoring catheter during reaming., Results: There was a significantly higher intramedullary pressure (P<0.05) during reaming in the traditional reamer group (mean 188+/-38 mmHg) than in the RIA group (mean 33+/-8 mmHg). Intramedullary pressures recorded before surgery, at the opening of the femoral cavity with an awl, by insertion of a guide wire, at insertion of the intramedullary nail, and 10 min after nail insertion showed no significant differences between the groups., Conclusion: The use of a one-step reamer-irrigator-aspirator technique in the pig femur induced less intramedullary pressure increase than the use of a traditional reamer.

Fat embolism (FE) and fat embolism syndrome (FES) are controversial topics, particularly regarding their clinical relevance and their independency as a clinical syndrome. FE describes the presence of fat globules within the microcirculation. FES on the other hand, is a clinical syndrome characterized by the presence of FE with the manifestation of an identifiable clinical pattern of signs and symptoms. Both experimental and clinical studies have demonstrated the occurrence and the possible harmful effects of FE. For instance, FE involving the lungs can result in adult respiratory distress syndrome (ARDS). The effects of FE are certainly mechanical, leading to capillary congestion, but are also highly likely to be of a proinflammatory and prothrombotic nature. The demarcation of FES against ARDS is mainly demonstrated by the single organ involvement of ARDS, exclusively influencing the lungs, whereas FES has a multiorgan effect with pulmonary, skin and, neurological manifestations. This article is a review of the pathophysiological mechanisms of FE and the clinical occurrence and influence of FE and FES.

Background: Fibrinolysis in blood is mainly reflected by the activities of tissue plasminogen activator (tPA) and of plasminogen activator inhibitor-1 (PAI-1). The effect of myocardial ischemia on their activities in the coronary circulation is, however, not established., Objectives: With an improved experimental model, we therefore examined the effect of a brief period of myocardial ischemia on their activities. Furthermore, the consequences of repeated periods of ischemia, mimicking the situations in patients with unstable angina, were investigated., Methods: In six anesthetized pigs, we occluded the distal left anterior descending coronary artery (LAD) four times for 10 min with 40 min intervals and determined the activities of tPA and PAI-1 in arterial and coronary venous blood. By simultaneously recording LAD flow, we could estimate cardiac release of these factors at baseline conditions and during reperfusion., Results: Neither net cardiac release of PAI-1 nor alterations in plasma PAI-1 levels were demonstrated during the experiment. However, a significant net release of tPA activity of 10.4 +/- 3.2 IU mL(-1) (P < 0.005) was recorded during baseline conditions. During reperfusion following the first period of ischemia, the cardiac release of tPA activity increased to a peak of 103 +/- 30-fold baseline release, but declined progressively after repeated periods of ischemia. After the fourth period, tPA release did not exceed an estimated baseline accumulation during ischemia and early reperfusion., Conclusions: In this porcine model, a substantial local increase in fibrinolytic capacity was observed after brief periods of ischemia, but declined subsequently by repeated periods of ischemia.

Objective: The aims of our study were to determine the basal platelet activation state in women with preeclampsia compared with normotensive pregnant women and nonpregnant women and to investigate the platelet reactivity on in vitro stimulation with adenosine diphosphate or thrombin receptor activation peptide., Study Design: Platelet expression of CD61 (fibrinogen receptor), CD42a (von Willebrand factor receptor), CD62P (P-selectin), CD63 (Glycoprotein 53), and PAC-1 binding (activated fibrinogen receptor) were determined in 20 pairs of women with preeclampsia/normotensive pregnant women and in 12 nonpregnant women, with the use of flow cytometry., Results: Basal platelet expression of CD61, CD42a and CD62P, and adenosine diphosphate-stimulated CD62P expression were increased in women with preeclampsia compared with normotensive pregnant women. Platelets from women with preeclampsia and normotensive pregnant women differed from platelets from nonpregnant women by expressing higher basal CD63 levels and being more responsive to in vitro agonist stimulation, which was demonstrated by increased expression of CD61, CD62P, and CD63., Conclusion: This study supports the notion that platelets are important in the pathophysiologic condition of preeclampsia.

In a randomized trial on the effect of dalteparin for 5 weeks after HRS we evaluated hemostatic variables in plasma sampled before and 1, 6 and 35 days postoperatively. In 218 patients we found that prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT), d-dimer and fibrinogen were significantly higher on day 35 as compared with baseline values in the placebo group (P < 0.001 for all). The same pattern was found in the dalteparin group, but with significantly lower values for F1 + 2, TAT and d-dimer. In patients in the placebo group with venographically proven deep vein thrombosis (DVT) on day 35 (33%), significantly higher values were found for F1 + 2, TAT and d-dimer than in patients without DVT. Patients in the highest quartile of d-dimer (>2850 ng mL-1) had an odds ratio for the presence of DVT of 24.0 when compared with patients in the lowest quartile (<1625 ng mL-1). It is concluded that a substantial hypercoagulability is sustained until day 35 after HRS, significantly reduced with prolonged administration of dalteparin.

The cysteinyl leukotrienes (cysLTs) and the peptide hormone endothelin (ET)-1 are potent bronchoconstrictor substances, and these mediators are also claimed to be implicated in the development of eosinophilic airway inflammation. In the present study, we have investigated the effect of the cysLT1 receptor antagonist montelukaston the development of an eosinophilic airway inflammation 24 h after intratracheal Sephadex (SDX) provocation in rats. Furthermore, the effect of montelukast treatment on the generation of ET-1 and other pro-inflammatory mediators has been studied. The inflammatory response was significantly reduced in the animals receiving SDX + montelukast compared to animals receiving solely SDX, as evaluated by a decrease in bronchoalveolar lavage fluid total cell count (10.3 +/- 1.2 vs. 18.5 +/- 1.8 x 10(4) ml(-1), P<0.001), number of eosinophils (299.7 +/- 43.8 vs. 577.6 +/- 46.6 x 10(2) ml(-1), P<0.001), and lymphocytes (116.8 +/- 20 vs. 222.0 +/- 34.8 x 10(2) ml(-1), P<0.05), as well as the degree of tissue inflammation (P<0.05). Montelukast also inhibited the increase in the concentration of the pro-inflammatory mediators ET-1 (28.5 +/- 75 vs. 40.9 +/- 7.3 x pg ml(-1), P<0.05) and interferon (IFN)-gamma (4.3 +/- 2.2 vs. 15.6+/-8.7 x pg ml(-1), P<0.05), but not tumor necrosis factor-gamma or interleukin-8. In summary, treatment with the cysLT1 receptor antagonist montelukast reduced the inflammatory response during development of an eosinophilic airway inflammation, possibly by inhibiting the release of pro-inflammatory mediators like ET-1 and IFN-gamma.

The objectives of this cephalometric study were to assess long-term changes in the soft tissue profile following mandibular advancement surgery and to investigate the relationship between soft tissue and hard tissue movements. The sample consisted of 61 patients treated consecutively for mandibular retrognathism with orthodontic therapy combined with bilateral sagittal split osteotomy and rigid fixation. Lateral cephalograms were taken on 6 occasions: immediately before surgery, immediately after surgery, 2 and 6 months after surgery, and 1 and 3 years after surgery. Postsurgical changes in the upper and the lower lips and the mentolabial fold were more pronounced among low-angle cases compared with high-angle cases. In accordance with other studies, the soft tissue chin and the mentolabial fold were generally found to follow their underlying skeletal structures in a 1:1 ratio. Because of the strong influence skeletal relapse has on soft tissue profile changes, alternative ratios of soft tissue-to-hard tissue movement that accounted for mean relapse were also generated. It is suggested that if a more realistic long-term prediction of the postsurgical soft tissue profile is desirable, then ratios incorporating mean relapse should be used rather than estimates based on a 1:1 relationship.

The objective of this cephalometric study was to compare skeletal stability and the time course of postoperative changes in high-angle and low-angle Class II patients after mandibular advancement surgery. The subjects were 61 consecutive mandibular retrognathism patients whose treatment included bilateral sagittal split osteotomy and rigid fixation. The patients were divided according to the preoperative mandibular plane angle; the 20 patients with the lowest mandibular plane angle (20.8 degrees +/- 4.9 degrees ) constituted the low-angle group, while the 20 cases with the highest mandibular plane angle (43.0 degrees +/- 4.0 degrees ) represented the high-angle group. Lateral cephalograms were taken on 6 occasions: immediately before surgery, immediately after surgery, 2 and 6 months after surgery, and 1 and 3 years after surgery. Results demonstrated that the high-angle and low-angle groups had different patterns of surgical and postoperative changes. High-angle patients were associated with both a higher frequency and a greater magnitude of horizontal relapse. While 95% of the total relapse took place during the first 2 months after surgery in the low-angle group, high-angle patients demonstrated a more continuous relapse pattern, with a significant proportion (38%) occurring late in the follow-up period. Possible reasons for the different postsurgical response are discussed.

Background: Pathogenesis of obstructive sleep apnoea (OSA) is complex and not yet fully understood. Several factors contribute to OSA severity. Obesity is believed to play an important role. Nevertheless, not all OSA patients are obese. Therefore, the different features that cause nocturnal upper airway obstruction in obese and non-obese OSA patients could be expected., Purpose: To investigate the different components of cervico-craniofacial skeletal and upper airway soft tissue morphology among obese OSA, non-obese OSA patients and the controls., Patients: One hundred male OSA patients were classified into two groups on the basis of body mass index (BMI) as obese (BMI > or = 30 kg/m2) and non-obese (BMI < 30 kg/m2). Consequently, 57 obese and 43 non-obese OSA patients were examined and compared with a control group of 36 healthy males., Study Design: A comprehensive cephalometric analysis of cervico-craniofacial skeletal and upper airway soft tissue morphology was performed. Sixty-eight cephalometric variables were compared among the three groups by one way analysis of variance with Bonferroni's test., Results: Both OSA groups had aberrations of cervico-craniofacial skeletal as well as upper airway soft tissue morphology when compared with the controls. These anatomic deviations were confined to cervico-craniofacial skeletal structures in the non-obese OSA patients, whereas the obese OSA patients had more abnormalities in the upper airway soft tissue morphology, head posture and position of the hyoid bone., Conclusion: The findings imply that there should be different treatment regimens for the two subgroups of OSA patients. Cephalometric analysis together with various considerations of BMI is highly recommended as one of the most important tools in diagnosis and treatment planning for OSA patients.

Increased nitrogen monoxide (NO) concentrations change leukocyte function under a multitude of experimental conditions. NO inhalation is an experimental treatment for lung failure and exposes leukocytes to increased NO concentrations during passage through the lungs. To investigate whether short-term NO inhalation induces lasting changes in the function of circulating human leukocytes, venous blood samples were drawn from eight healthy male volunteers before and at the end of a 35-min period of breathing 40 ppm NO in 30% O(2). The leukocytes in the samples were subsequently analyzed for NO-induced changes in expression of cell surface molecules, generation of reactive oxygen species (ROS), and cytokine production by flow cytometry and ELISA techniques. The results were (1) NO inhalation changed neither the baseline nor the Escherichia coli lipopolysaccharide (LPS)-induced expression of the cell adhesion molecules CD11a, CD11b, CD11c, and CD62L (l-selectin) on neutrophilic granulocytes (PMN) or monocytes (Mo). The expression of CD14 and HLA-DR was also unchanged. (2) The generation of ROS in response to activation with phorbol myristate acetate increased in PMN after NO inhalation; an increase in Mo did not reach significance. (3) Baseline and LPS-stimulated production of IL-1beta decreased after NO inhalation, while the LPS-stimulated production of TNF-alpha increased. No changes in IL-6 production were detected., (Copyright 2000 Academic Press.)

1178 patients with mandibular prognathism and/or asymmetry, in some cases combined with maxillary retrognathism, were treated by extraoral horizontal or oblique ramus osteotomy during the period from 1939 to 1989. The described percutaneous retromandibular approach is a simple, rapid and reliable technique which can usually be performed under local anaesthesia. Very few complications, particularly neurological, were observed. These aspects justify consideration of this technique when indications for a simple, straight set-back procedure of the mandible exist, and there is no tendency to bite-opening. However, the method demands intermaxillary fixation for 6-9 weeks postoperatively.

Vascularized fibular bone grafts have advantages over other bone grafts in the restoration of the contour and function of defective mandibles. The fibular graft can be tailored to fit even major mandibular defects; in combination with preformed temporomandibular joint prostheses total mandibular reconstruction can be performed in a single procedure. The fibular transplant is considered ideal for the insertion of implants to support dental suprastructures to obtain maximal oral rehabilitation. We have used fibular grafts in eight cases for primary or secondary reconstruction of a variety of mandibular defects resulting from cancer, chronic osteomyelitis or gunshot injuries. The results have been most encouraging with respect to function and cosmetic appearance. There have been no transplant failures and minimal donor site complications.