| 1. |
- Lepsenyi, Mattias, et al.
(författare)
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Self-expanding metal stents in malignant colonic obstruction: experiences from Sweden.
- 2011
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acute surgery in the management of malignant colonic obstruction is associated with high morbidity and mortality. The use of self-expanding metal stents (SEMS) is an alternative method of decompressing colonic obstruction. SEMS may allow time to optimize the patient and to perform preoperative staging, converting acute surgery into elective. SEMS is also proposed as palliative treatment in patients with contraindications to open surgery. Aim: To review our experience of SEMS focusing on clinical outcome and complications. The method used was a review of 75 consecutive trials at SEMS on 71 patients based on stent-protocols and patient charts. FINDINGS: SEMS was used for palliation in 64 (85%) cases and as a bridge to surgery in 11 (15%) cases. The majority of obstructions, 53 (71%) cases, were located in the recto-sigmoid. Technical success was achieved in 65 (87%) cases and clinical decompression was achieved in 60 (80%) cases. Reasons for technical failure were inability to cannulate the stricture in 5 (7%) cases and suboptimal SEMS placement in 3 (4%) cases. Complications included 4 (5%) procedure-related bowel perforations of which 2 (3%) patients died in junction to post operative complications. Three cases of bleeding after SEMS occurred, none of which needed invasive treatment. Five of the SEMS occluded. Two cases of stent erosion were diagnosed at the time of surgery. Average survival after palliative SEMS treatment was 6 months. CONCLUSION: Our results correspond well to previously published data and we conclude that SEMS is a relatively safe and effective method of treating malignant colonic obstruction although the risk of SEMS-related perforations has to be taken into account.
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| 2. |
- Wang, Yongzhi, et al.
(författare)
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DYNAMIC CHANGES IN THROMBIN GENERATION IN ABDOMINAL SEPSIS IN MICE.
- 2014
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Ingår i: Shock. - 1540-0514. ; 42:4, s. 343-349
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT-Systemic inflammatory response syndrome and severe infections are associated with major derangements in the coagulation system. The purpose of this study was to examine the dynamic alterations in thrombin generation in abdominal sepsis. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in C57/Bl6 mice. CLP caused a systemic inflammatory response with neutrophil recruitment and tissue damage in the lung as well as thrombocytopenia and leukocytopenia. Thrombin generation, coagulation factors, lung histology and myeloperoxidase (MPO) activity was determined 1h, 3h, 6h and 24h after induction of CLP. It was found that thrombin generation was increased 1h after CLP and that thrombin generation started to decrease at 3h and was markedly reduced 6h and 24h after CLP induction. Platelet poor plasma from healthy mice could completely reverse the inhibitory effect of CLP on thrombin generation, suggesting that sepsis caused a decrease in the levels of plasma factors regulating thrombin generation in septic animals. Indeed, it was found that CLP markedly decreased plasma levels of prothrombin, factor V and factor X at 6h and 24h. Moreover, we observed that CLP increased plasma levels of activated protein C at 6h, which returned to baseline levels 24h after CLP induction. Finally, pretreatment with imipenem/cilastatin attenuated the CLP-evoked decrease in thrombin generation and consumption of prothrombin 24h after CLP induction. Our novel findings suggest that thrombin generation is initially increased and later decreased in abdominal sepsis. Sepsis-induced reduction in thrombin generation is correlated to changes in the plasma levels of coagulation factors and activated protein C. These findings help explain the dynamic changes in global hemostasis in abdominal sepsis.
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| 3. |
- Zhang, Su, et al.
(författare)
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NFAT regulates neutrophil recruitment, systemic inflammation and T-cell dysfunction in abdominal sepsis.
- 2014
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Ingår i: Infection and Immunity. - 1098-5522. ; 82:8, s. 3275-3288
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Tidskriftsartikel (refereegranskat)abstract
- The signaling mechanisms regulating neutrophil recruitment, systemic inflammation and T-cell dysfunction in polymicrobial sepsis are not clear. This study explored the potential involvement of the calcium/calcineurin-dependent transcription factor, nuclear factor of activated T-cells (NFAT) in abdominal sepsis. Cecal ligation and puncture (CLP) triggered NFAT-dependent transcriptional activity in the lung, spleen, liver and aorta in NFAT-luciferase reporter mice. Treatment with the NFAT inhibitor A-285222 prior to CLP completely prevented sepsis-induced NFAT activation in all these organs. Inhibition of NFAT activity reduced sepsis-induced formation of CXCL1, CXCL2 and CXCL5 chemokines and edema as well as neutrophil infiltration in the lung. Notably, NFAT inhibition efficiently reduced the CLP-evoked increases in HMBG1, IL-6 and CXCL5 levels in plasma. Moreover, administration of A-285222 restored sepsis-induced T-cell dysfunction, as evidenced by markedly decreased apoptosis and restored proliferative capacity of CD4 T-cells. Along these lines, treatment with A-285222 restored IFN-γ and IL-4 levels in the spleen, which were markedly reduced in septic mice. CLP-induced formation of regulatory T-cells (CD4(+)CD25(+)Foxp3(+)) in the spleen was also abolished in A-285222-treated animals. Altogether, these novel findings suggest that NFAT is a powerful regulator of pathological inflammation and T-cell immune dysfunction in abdominal sepsis. Thus, our data suggest that NFAT signaling might be a useful target to protect against respiratory failure and immunosuppression in patients with sepsis.
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| 4. |
- Hartman Magnusson, Hannes, et al.
(författare)
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P-selectin mediates neutrophil rolling and recruitment in acute pancreatitis
- 2012
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 99, s. 246-255
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Tidskriftsartikel (refereegranskat)abstract
- Background: The adhesive mechanisms regulating leucocyte-endothelium interactions in the pancreas remain elusive, but selectins may play a role. This study examined the molecular mechanisms mediating leucocyte rolling along the endothelium in the pancreas and the therapeutic potential of targeting the rolling adhesive interaction in acute pancreatitis (AP). Methods: Pancreatitis was induced by retrograde infusion of 5 per cent sodium taurocholate into the pancreatic duct, repeated intraperitoneal administration of caerulein (50 μg/kg) or intraperitoneal administration of L-arginine (4 g/kg) in C57BL/6 mice. A control and a monoclonal antibody against P-selectin were administered before and after induction of AP. Serum and tissue were sampled to assess the severity of pancreatitis, and intravital microscopy was used to study leucocyte rolling. Results: Taurocholate infusion into the pancreatic duct increased the serum level of trypsinogen, trypsinogen activation, pancreatic neutrophil infiltration, macrophage inflammatory protein (MIP) 2 formation and tissue damage. Immunoneutralization of P-selectin decreased the taurocholate-induced increase in serum trypsinogen (median (range) 17·35 (12·20- 30·00) versus 1·55 (0·60-15·70) μg/l; P = 0·017), neutrophil accumulation (4·00 (0·75-4·00) versus 0·63 (0-3·25); P = 0·002) and tissue damage, but had no effect on MIP-2 production (14·08 (1·68-33·38) versus 3·70 (0·55-51·80) pg/mg; P = 0·195) or serum trypsinogen activating peptide level (1·10 (0·60-1·60) versus 0·45 (0-1·80) μg/l; P = 0·069). Intravital fluorescence microscopy revealed that anti-P-selectin antibody inhibited leucocyte rolling completely in postcapillary venules of the inflamed pancreas. Conclusion: Inhibition of P-selectin protected against pancreatic tissue injury in experimental pancreatitis. Targeting P-selectin may be an effective strategy to ameliorate inflammation in AP. © 2011 British Journal of Surgery Society Ltd.
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| 5. |
- Hwaiz, Rundk, et al.
(författare)
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Rac1 regulates platelet shedding of CD40L in abdominal sepsis.
- 2014
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Ingår i: Laboratory Investigation. - : Elsevier BV. - 1530-0307 .- 0023-6837. ; 94:9, s. 1054-1063
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Tidskriftsartikel (refereegranskat)abstract
- Matrix metalloproteinase-9 (MMP-9) regulates platelet shedding of CD40L in abdominal sepsis. However, the signaling mechanisms controlling sepsis-induced shedding of CD40L from activated platelets remain elusive. Rac1 has been reported to regulate diverse functions in platelets; we hypothesized herein that Rac1 might regulate platelet shedding of CD40L in sepsis. The specific Rac1 inhibitor NSC23766 (N6-[2-[[4-(diethylamino)-1-methylbutyl] amino]-6-methyl-4-pyrimidinyl]-2 methyl-4, 6-quinolinediamine trihydrochloride) was administered to mice undergoing cecal ligation and puncture (CLP). Levels of CD40L and MMP-9 in plasma, platelets, and neutrophils were determined by use of ELISA, western blot, and confocal microscopy. Platelet depletion abolished the CLP-induced increase in plasma levels of CD40L. Rac1 activity was significantly increased in platelets from septic animals. Administration of NSC23766 abolished the CLP-induced enhancement of soluble CD40L levels in the plasma. Moreover, Rac1 inhibition completely inhibited proteinase-activated receptor-4-induced surface mobilization and secretion of CD40L in isolated platelets. CLP significantly increased plasma levels of MMP-9 and Rac1 activity in neutrophils. Treatment with NSC23766 markedly attenuated MMP-9 levels in the plasma from septic mice. In addition, Rac1 inhibition abolished chemokine-induced secretion of MMP-9 from isolated neutrophils. Finally, platelet shedding of CD40L was significantly reduced in response to stimulation with supernatants from activated MMP-9-deficient neutrophils compared with supernatants from wild-type neutrophils, indicating a direct role of neutrophil-derived MMP-9 in regulating platelet shedding of CD40L. Our novel data suggest that sepsis-induced platelet shedding of CD40L is dependent on Rac1 signaling. Rac1 controls surface mobilization of CD40L on activated platelets and MMP-9 secretion from neutrophils. Thus, our findings indicate that targeting Rac1 signaling might be a useful way to control pathologic elevations of CD40L in the systemic circulation in abdominal sepsis.Laboratory Investigation advance online publication, 21 July 2014; doi:10.1038/labinvest.2014.92.
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| 6. |
- Swahn, Fredrik, et al.
(författare)
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Endoscopic retrograde cholangiopancreatography with rendezvous cannulation reduces pancreatic injury
- 2013
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 19:36, s. 6026-6034
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To examine whether rendezvous endoscopic retrograde cholangiopancreatography (ERCP) is associated with less pancreatic damage, measured as leakage of proenzymes, than conventional ERCP. METHODS: Patients (n = 122) with symptomatic gallstone disease, intact papilla and no ongoing inflammation, were prospectively enrolled in this case-control designed study. Eighty-one patients were subjected to laparoscopic cholecystectomy and if intraoperative cholangiography suggested common bile duct stones (CBDS), rendezvous ERCP was performed intraoperatively (n = 40). Patients with a negative cholangiogram constituted the control group (n = 41). Another 41 patients with CBDS, not subjected to surgery, underwent conventional ERCP. Pancreatic proenzymes, procarboxypeptidase B and trypsinogen-2 levels in plasma, were analysed at 0, 4, 8 and 24 h. The proenzymes were determined in-house with a double-antibody enzyme linked immunosorbent assay. Pancreatic amylase was measured by an enzymatic colourimetric modular analyser with the manufacturer's reagents. All samples were blinded at analysis. RESULTS: Post ERCP pancreatitis (PEP) occurred in 3/41 (7%) of the patients cannulated with conventional ERCP and none in the rendezvous group. Increased serum levels indicating pancreatic leakage were significantly higher in the conventional ERCP group compared with the rendezvous ERCP group regarding pancreatic amylase levels in the 4- and 8-h samples (P = 0.0015; P = 0.03), procarboxypeptidase B in the 4- and 8-h samples (P < 0.0001; P < 0.0001) and trypsinogen-2 in the 24-hour samples (P = 0.03). No differences in these markers were observed in patients treated with rendezvous cannulation technique compared with patients that underwent cholecystectomy alone (control group). Post procedural concentrations of pancreatic amylase and procarboxypeptidase B were significantly correlated with pancreatic duct cannulation and opacification. CONCLUSION: Rendezvous ERCP reduces pancreatic enzyme leakage compared with conventional ERCP cannulation technique. Thus, laparo-endoscopic technique can be recommended with the ambition to minimise the risk for post ERCP pancreatitis. (C) 2013 Baishideng. All rights reserved.
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| 7. |
- Thorlacius, Henrik, et al.
(författare)
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Cystic neuroendocrine tumor in the pancreas detected by endoscopic ultrasound and fine-needle aspiration: a case report.
- 2014
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 7:Aug 9
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic neuroendocrine tumors are typically solid neoplasms but in very rare cases present as cystic lesions. The diagnosis of cystic tumors in the pancreas is extremely difficult and the use of endoscopic ultrasound and fine-needle aspiration might be helpful in the work-up of patients with cystic neuroendocrine tumors in the pancreas.
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| 8. |
- Zhang, Songen, et al.
(författare)
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Geranylgeranyl transferase regulates streptococcal m1 protein-induced CXC chemokine formation and neutrophil recruitment in the lung.
- 2013
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Ingår i: Shock. - 1540-0514. ; 39:3, s. 293-298
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Streptococcal toxic shock syndrome is most frequently associated with Streptococcus pyogenes of the M1 serotype. Simvastatin protects against M1 protein-induced acute lung damage, although downstream mechanisms remain elusive. Herein, we hypothesized that geranylgeranylation might regulate proinflammatory effects in M1 protein-induced lung injury. Male C57BL/6 mice received the geranylgeranyl transferase inhibitor, GGTI-2133, before M1 protein injection. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema, and CXC chemokine formation. Mac-1 expression on neutrophils was quantified by use of flow cytometry. Quantitative reverse transcriptase-polymerase chain reaction was used to determine gene expression of CXC chemokines in alveolar macrophages. GGTI-2133 reduced M1 protein-provoked infiltration of neutrophils, edema, and tissue injury in the lung. Inhibition of geranylgeranyl transferase had no effect on M1 protein-evoked upregulation of Mac-1 on neutrophils. However, geranylgeranyl transferase inhibition completely inhibited pulmonary formation of CXC chemokines in mice exposed to M1 protein. Notably, GGTI-2133 abolished M1 protein-induced gene expression of CXC chemokines in alveolar macrophages. These novel findings indicate that geranylgeranyl transferase is an important regulator of neutrophil recruitment and CXC chemokine production in the lung. Thus, targeting geranylgeranyl transferase might be a potent way to ameliorate streptococcal M1 protein-triggered acute lung injury.
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| 9. |
- Zhang, Su, et al.
(författare)
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STREPTOCOCCAL M1 PROTEIN-INDUCED LUNG INJURY IS INDEPENDENT OF PLATELETS IN MICE.
- 2011
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Ingår i: Shock. - 1540-0514. ; Jul 1, s. 86-91
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes of the M1 serotype is frequently associated with severe streptococcal infections. M1 protein challenge can cause widespread microthrombosis, suggesting a role of platelets in streptococcal sepsis. Herein, we hypothesized that platelets may play a role in M1 protein-induced lung inflammation and injury. M1 protein was injected intravenously in C57Bl/6 mice. For platelet and neutrophil depletion, an anti-GP1balpha antibody and an anti-Gr-1 antibody, respectively, were administered prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for analysis of neutrophil infiltration, edema and macrophage inflammatory protein-2 (MIP-2) formation. Blood was collected for analysis of membrane-activated complex-1 (Mac-1) and CD40 ligand (CD40L) expression on neutrophils and platelets as well as soluble CD40L in plasma. M1 protein caused significant pulmonary damage characterized by neutrophil infiltration, increased formation of edema and MIP-2 in the lung as well as enhanced Mac-1 expression on neutrophils. However, M1 protein challenge had no effect on platelet surface expression of CD40L or soluble CD40L levels in plasma. Interestingly, platelet depletion had no influence on M1 protein-induced neutrophil recruitment, MIP-2 production and tissue damage in the lung or Mac-1 expression on neutrophils. Moreover, we observed that M1 protein could bind to neutrophils but not to platelets. On the other hand, neutrophil depletion abolished M1 protein-induced edema formation and tissue damage in the lung. Our data suggest that neutrophils but not platelets are involved in the pathophysiology of M1 protein-provoked pulmonary damage. Thus, neutrophils may constitute a key target in infections caused by Streptococcus pyogenes of the M1 serotype.
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| 10. |
- Zhang, Songen, et al.
(författare)
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Streptococcal M1 protein triggers farnesyltransferase-dependent formation of CXC chemokines in alveolar macrophages and neutrophil infiltration in the lung.
- 2012
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Ingår i: Infection and Immunity. - 1098-5522. ; 80:11, s. 3952-3959
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Tidskriftsartikel (refereegranskat)abstract
- M1 serotype of Streptococcus pyogenes plays an important role in streptococcal toxic shock syndrome. Simvastatin, a HMG-CoA reductase inhibitor, has been shown to inhibit streptococcal M1 protein-induced acute lung damage although downstream mechanisms remain elusive. Protein isoprenylation, such as farnesylation and geranylgeranylation, has been suggested to regulate anti-inflammatory effects exerted by statins. Herein, we examined the effect of a farnesyltransferase inhibitor (FTI-277) on M1 protein-triggered lung inflammation. Male C57BL/6 mice were treated with FTI-277 prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema and CXC chemokine formation. Flow cytometry was used to determine Mac-1 expression on neutrophils. Gene expression of CXC chemokines was determined in alveolar macrophages by using quantitative RT-PCR. We found that administration of FTI-277 markedly decreased M1 protein-induced accumulation of neutrophils, edema formation and tissue damage in the lung. Notably, inhibition of farnesyltransferase abolished M1 protein-evoked production of CXC chemokines in the lung and gene expression of CXC chemokines in alveolar macrophages. Moreover, FTI-277 completely inhibited chemokine-induced neutrophil migration in vitro. However, farnesyltransferase inhibition had no effect on M1 protein-induced expression of Mac-1 on neutrophils. Our findings suggest that farnesyltransferase is a potent regulator of CXC chemokine formation in alveolar macrophages and that inhibition of farnesyltransferase not only reduces neutrophil recruitment but also attenuates acute lung injury provoked by streptococcal M1 protein. We conclude that farnesyltransferase activity is a potential target in order to attenuate acute lung damage in streptococcal infections.
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