| 1. |
- Edsberg, Lennart
(författare)
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Natriuresis and the extracellular volume expansion by hypertonic saline
- 2003
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 113:1, s. 6-12
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Tidskriftsartikel (refereegranskat)abstract
- Background. The mechanisms governing the duration of the extracellular fluid volume (ECF) expansion as a result of intravenous infusion of hypertonic saline solution are poorly understood. We hypothesized that the duration is closely related to the sodium excretion. Materials and methods. Six conscious splenectomized ewes with a mean body weight of 30 kg were given an intravenous infusion of 4 ml kg(-1) of 7.5% saline solution on two occasions, one over a period of 5 min and another over a period of 20 min. Mass balance and volume kinetic calculations of the distribution and elimination of fluid were performed after repeated sampling of the plasma sodium concentration and the urinary excretion of water and sodium during 3 h. Results. On considering the addition of sodium to and its excretion from the body, the plasma sodium concentration indicated a 10% dilution of the extracellular space. The volume expansion decayed at an average rate of 20% of the volume expansion per hour, which, however, varied greatly in the animals, depending on their capacity to excrete sodium. After 1 h, increasing natriuresis promoted translocation. of water into the cells, which amounted to 25-35% of the total elimination. Computer simulations indicated that tripled natriuresis (up to approximately 750 mmol l(-1)) would increase the rate of elimination to 45% of the volume expansion per hour. Conclusion. The sodium excretion was inversely proportional to the duration of the extracellular volume expansion by 7.5% saline.
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| 2. |
- Abrahamsson, Pernilla, et al.
(författare)
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Outcome of microdialysis sampling on liver surface and parenchyma
- 2016
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 200:2, s. 480-487
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Tidskriftsartikel (refereegranskat)abstract
- Background: To investigate whether surface microdialysis (μD) sampling in probes covered by a plastic film, as compared to noncovered and to intraparenchymatous probes, would increase the technique's sensitivity for pathophysiologic events occurring in a liver ischemia-reperfusion model. Placement of μD probes in the parenchyma of an organ, as is conventionally done, may cause adverse effects, e.g., bleeding, possibly influencing outcome.Methods: A transient ischemia-reperfusion model of the liver was used in six anesthetized normoventilated pigs. μD probes were placed in the parenchyma and on the liver surface. Surface probes were either left uncovered or were covered by plastic film.Results: Lactate and glucose levels were significantly higher in plastic film covered probes than in uncovered surface probes throughout the ischemic period. Glycerol levels were significantly higher in plastic film covered probes than in uncovered surface probes at 30 and 45 min into ischemia.Conclusions: Covering the μD probe increases the sensibility of the μD–technique in monitoring an ischemic insult and reperfusion in the liver. These findings confirm that the principle of surface μD works, possibly replacing need of intraparenchymatous placement of μD probes. Surface μD seemingly allows, noninvasively from an organ's surface, via the extracellular compartment, assessment of intracellular metabolic events. The finding that covered surface μD probes allows detection of local metabolic changes earlier than do intraparenchymatous probes, merit further investigation focusing on μD probe design.
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| 3. |
- Acosta, Stefan, et al.
(författare)
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L-lactate after embolization of the superior mesenteric artery
- 2007
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Ingår i: Journal of Surgical Research. - Orlando, Fla. : Elsevier BV. - 1095-8673 .- 0022-4804. ; 143:2, s. 320-328
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Tidskriftsartikel (refereegranskat)abstract
- Background. Plasma markers for intestinal ischemia have not proven to be accurate. The value of L-lactate is unclear. Experimental models based on open surgery confound the effects of surgical trauma with that of ischemia. The aim was to create an endovascular model for acute superior mesenteric artery thromboembolism, and then to study L-lactate and lactate dehydrogenase (LD) activity in plasma and peritoneal fluid in pigs with extensive, high-grade intestinal ischemia. Materials and methods. Nine pigs underwent full superior mesenteric artery embolization with 4 h of intended intestinal ischemia, whereas six were control animals. Sampling of central venous and arterial blood was performed throughout the experiment, ending with laparotomy to collect peritoneal fluid and segmental intestinal biopsies. A pathologist, blinded to the performed interventions, graded the ischemic lesions. Results. There were no differences in plasma L-lactate (P = 0.61) or LD activity levels (P = 0.69), measured at different time points from baseline to end of study, between animals with extensive, high-grade intestinal ischemia and sham. Intraperitoneal L-Lactate (P = 0.005) and LD activity (P = 0.018) levels were elevated compared with sham. There were differences in grades of ischemia in the duodenum (P = 0.003), small intestine (P < 0.001), proximal (P < 0.001), and sigmoid (P = 0.032) colon between experimental animals and sham. The grade of small bowel ischemia (n = 15) correlated to intraperitoneal fluid L-lactate (r = 0.80; P < 0.001) and LD activity levels (r = 0.72; P = 0.003). Conclusions. This endovascular study in a porcine model showed that L-lactate and LD activity levels in peritoneal fluid, not in plasma, reflect intestinal ischemia. The study suggests that plasma L-lactate not is a useful early marker in patients with suspicion of intestinal ischemia. (c) 2007 Elsevier Inc. All rights reserved.
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| 4. |
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| 5. |
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| 6. |
- Angenete, Eva, 1972, et al.
(författare)
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uPA and PAI-1 in rectal cancer--relationship to radiotherapy and clinical outcome.
- 2009
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Ingår i: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 153:1, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is well known that the fibrinolytic system is of importance in inflammation, wound healing, and fibrosis development. However, it is also important in the process of tumor invasion and metastasis. We have investigated protein levels of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in rectal cancer and effects of radiotherapy, links to clinical outcome, and potential use as prognostic factors. MATERIALS AND METHODS: Ninety-one patients with rectal cancer were studied. Blood samples and biopsies were taken during surgery and assayed with enzyme-linked immunosorbent assay for uPA and PAI-1, and patients were followed prospectively (0-96 mo). RESULTS: Higher levels of uPA (P < 0.0001) and PAI-1 (P < 0.0001) were found in tumor compared with mucosa. Mucosa exposed to radiotherapy had higher levels of uPA (P < 0.0001) and of PAI-1 (P < 0.0001). Irradiated tumor tissue had higher levels of PAI-1 (P < 0.001). PAI-1 in tumor was correlated with T stage (P < 0.001) and N stage (P < 0.01). PAI-1 in plasma was higher in patients with synchronous distant metastases (P < 0.001). Cox regression was used to identify high levels of PAI-1 in tumor as an independent factor related to short disease-free survival (P < 0.01) and the ratio of uPA/PAI-1 to development of metastases (P < 0.01). CONCLUSIONS: There is a relationship between PAI-1 in plasma and rectal cancer metastases. PAI-1 in tumor tissue is correlated to histopathological data and to outcome of rectal cancer. If these findings can be confirmed in larger trials, there will be a possibility to use PAI-1 as a prognostic factor.
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| 7. |
- Asif, Sana, et al.
(författare)
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Oxygen-charged HTK-F6H8 emulsion reduces ischemia : reperfusion injury in kidneys from brain-dead pigs
- 2012
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 178:2, s. 959-967
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Tidskriftsartikel (refereegranskat)abstract
- Background:Prolonged cold ischemia is frequently associated with a greater risk of delayed graft function and enhanced graft failure. We hypothesized that media, combining a high oxygen-dissolving capacity with specific qualities of organ preservation solutions, would be more efficient in reducing immediate ischemia-reperfusion injury from organs stored long term compared with standard preservation media.Methods:Kidneys retrieved from brain-dead pigs were flushed using either cold histidine-tryptophan-ketoglutarate (HTK) or oxygen-precharged emulsion composed of 75% HTK and 25% perfluorohexyloctane. After 18 h of cold ischemia the kidneys were transplanted into allogeneic recipients and assessed for adenosine triphosphate content, morphology, and expression of genes related to hypoxia, environmental stress, inflammation, and apoptosis.Results:Compared with HTK-flushed kidneys, organs preserved using oxygen-precharged HTK-perfluorohexyloctane emulsion had increased elevated adenosine triphosphate content and a significantly lower gene expression of hypoxia inducible factor-1 alpha, vascular endothelial growth factor, interleukin-1 alpha, tumor necrosis factor-alpha, interferon-alpha, JNK-1, p38, cytochrome-c, Bax, caspase-8, and caspase-3 at all time points assessed. In contrast, the mRNA expression of Bcl-2 was significantly increased.Conclusions:The present study has demonstrated that in brain-dead pigs the perfusion of kidneys with oxygen-precharged HTK-perfluorohexyloctane emulsion results in significantly reduced inflammation, hypoxic injury, and apoptosis and cellular integrity and energy content are well maintained. Histologic examination revealed less tubular, vascular, and glomerular changes in the emulsion-perfused tissue compared with the HTK-perfused counterparts. The concept of perfusing organs with oxygen-precharged emulsion based on organ preservation media represents an efficient alternative for improved organ preservation.
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| 8. |
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| 9. |
- Bass, Gary Alan, 1979-, et al.
(författare)
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Admission Triage With Pain, Inspiratory Effort, Cough Score can Predict Critical Care Utilization and Length of Stay in Isolated Chest Wall Injury
- 2022
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Ingår i: Journal of Surgical Research. - : Academic Press. - 0022-4804 .- 1095-8673. ; 277, s. 310-318
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Damage to the thoracic cage is common in the injured patient, both when the injuries are confined to this single cavity and as part of the overall injury burden of a polytraumatized patient. In a subset of these patients, the severity of injury to the intrathoracic viscera is either underappreciated at admission or blossom over the following 48-72 h. The ability to promptly identify these patients and abrogate complications therefore requires triage of such at-risk patients to close monitoring in a critical care environment. At our institution, this triage hinges on the Pain, Inspiratory effort, Cough (PIC) score, which generates a composite unitless score from a nomogram which aggregates several variables-patient-reported Pain visual analog scale, Incentive spirometry effort, and the perceived adequacy of Cough. We thus sought to audit PIC's discriminant power in predicting intensive care unit (ICU) need.METHODS: This retrospective cohort study was performed at an urban, academic, level 1 trauma center. All isolated chest wall injuries (excluded any Abbreviated Injury Score >2 in head or abdomen) from January 2020 to June 2021 were identified in the local trauma registry. The electronic medical record was queried for standard demographics, admission PIC score, postadmission destination, ICU and hospital length of stay (LOS), and any unplanned admissions to the ICU. Chi-squared tests were used to determine differences between PIC score outcomes and the recursive partitioning method correlated admission PIC score to ICU LOS.RESULTS: Two hundred and thirty six isolated chest wall injury patients were identified, of whom 194 were included in the final analysis. The median age was 60 (interquartile range [IQR] 50-74) years, 63.1% were male, and the median (IQR) number of rib fractures was 3.0 (2.0-5.0). A cutoff PIC score of 7 or lower was associated with ICU admission (odds ratio [OR] 95% CI: 8.19 [3.39-22.55], P < 0.001 with a PPV = 41.4%, NPV = 91%), and with ICU admission for greater than 48 h [OR (95% CI): 26.86 (5.5-43.96), P < 0.001, with a PPV = 25.9%, NPV = 98.7%] but not anatomic injury severity score, hospital LOS or ICU, or the requirement for mechanical ventilation. The association between PIC score 7 or below and the presence of bilateral fractures, flail chest, or sternal fracture did not meet statistical significance. The accurate cut point of the PIC score to predict ICU admission over 48 h in our retrospective cohort was calculated as PIC ≤ 7 for P = 0.013 and PIC ≤ 6 for P = 0.001.CONCLUSIONS: Patients with isolated chest wall injuries require effective reproducible triage for ICU-level care. The PIC score appears to be a moderate discriminator of critical care need, per se, as judged by our recorded complication rate requiring critical care intervention. This vigilance may pay dividends in early detection and abrogation of respiratory failure emergencies. Furthermore, PIC score delineation for ICU need appears to be appropriate at 7 or less; this threshold can be used during admission triage to guide care.
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| 10. |
- Bauden, Monika, et al.
(författare)
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Novel anti-adhesive barrier Biobarrier reduces growth of colon cancer cells.
- 2014
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 191:1, s. 196-202
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Tidskriftsartikel (refereegranskat)abstract
- Postoperative peritoneal carcinomatosis together with adhesion formation are considered as two major clinical complications after resection of malignant abdominal tumors, jeopardizing the beneficial effect of the curative surgery. Biobarrier is a novel anti-adhesive barrier fulfilling the criteria for a good adhesion preventive agent, possessing biochemical properties that may enable it to function as a dual efficient device, reducing both adhesion and tumor development. This study aims to evaluate the effect of novel anti-adhesive device Biobarrier on intra-abdominal tumor progression.
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| 11. |
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| 12. |
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| 13. |
- Björnsson, Bergthor, et al.
(författare)
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Remote or Conventional Ischemic Preconditioning -Local Liver Metabolism in Rats Studied with Microdialysis
- 2012
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Ingår i: Journal of Surgical Research. - : Elsevier. - 0022-4804 .- 1095-8673. ; 176:1, s. 55-62
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Tidskriftsartikel (refereegranskat)abstract
- Background. Ischemic preconditioning (IPC) of the liver decreases liver injury secondary to ischemia and reperfusion. An attractive alternative to IPC is remote ischemic preconditioning (R-IPC), but these two methods have not previously been compared. Material and Methods. Eighty-seven rats were randomized into four groups: sham operated (n = 15), 1 h segmental ischemia (IRI, n = 24), preceeded by IPC (n = 24), or R-IPC (n = 24) (to the left hindleg). IPC and R-IPC were performed with 10 min ischemia and 10 min of reperfusion. Analyses of liver microdialysate (MD), serum transaminase levels, and liver histology were made. Results. Rats treated with IPC and R-IPC had significantly lower AST, 71.5 (19.6) IU/L respective 96.6 (12.4) at 4 h reperfusion than those subjected to IRI alone, 155 (20.9), P = 0.0004 and P = 0.04 respectively. IPC also had lower ALT levels, 41.6 (11.3) IU/L than had IRI 107.4 (15.5), P = 0.003. The MD glycerol was significantly higher during ischemia in the R-IPC = 759 (84) mu M] and the IRI = 732 (67)] groups than in the IPC 514 (70) group, P = 0.022 and P = 0.046 respectively. The MD glucose after ischemia was lower in the IPC group 7.1 (1.2) than in the IRI group 12.7 (1.6), P = 0.005. Preconditioning to the liver caused an direct increase in lactate, glucose and glycerol in the ischemic segment compared with the control segment an effect not seen in the R-IPC and IRI groups. Conclusions. IPC affects glucose metabolism in the rat liver, observed with MD. IPC reduces liver cell injury during ischemic and reperfusion in rats. R-IPC performed over the same length of time as IPC does not have the same effect as the latter on ALT levels and MD glycerol; this may suggest that R-IPC does not offer the same protection as IPC in this setting of rat liver IRI.
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| 14. |
- Bockhorn, Maximilian, et al.
(författare)
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VEGF is important for early liver regeneration after partial hepatectomy
- 2007
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 138:2, s. 291-299
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The aim of the study was to determine the role of Vascular Endothelial Growth Factor (VEGF) on the microvasculature and on angiogenetic gene expression after partial hepatectomy (PH) in the rat model.METHODS: To determine the effect of exogenous and endogenous VEGF after PH, rats were subjected to 70% PH and treated either with VEGF, anti-VEGF or NaCl. Postoperatively (3-168 h), vessel density (VD), vessel diameter (VDi), and intersinusoidal space, liver body weight ratio (LBR), hepatic proliferation and biochemical markers were assessed. To further elucidate the underlying molecular mechanisms hepatic gene expression was determined by customized cDNA arrays and quantitative RT-PCR.RESULTS:In the VEGF group, VD, VDi, and LBR were significantly increased compared with anti-VEGF or controls. Blockage of endogenous VEGF led to a marked increase of biochemical markers. Anti-VEGF almost completely suppressed and VEGF markedly enhanced hepatic proliferation in the first 24 h after surgery. This was associated with a modulation of cell cycle control genes (PC4, Gadd45a, Tis21/BTG2), v-jun, and CD14 by VEGF.CONCLUSIONS: VEGF plays an important role in liver regeneration and this may be due in part through its effects on neovascularization. Whether it may, when given therapeutically, represent a strategy to optimize liver regeneration in problematic patients needs to be clarified.
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| 15. |
- Brokelman, Walter J A, et al.
(författare)
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Decreased peritoneal tissue plasminogen activator during prolonged laparoscopic surgery.
- 2009
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Ingår i: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 151:1, s. 89-93
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Peritoneal fibrinolysis is crucial in the peritoneal healing processes and subsequent adhesion formation. During conventional surgery, the peritoneal fibrinolytic system is rapidly disturbed. Short-term laparoscopy does not seem to affect peritoneal fibrinolysis. The aim of the present study was to assess the effect of prolonged laparoscopic surgery on peritoneal fibrinolysis. METHODS: Twelve consecutive patients undergoing laparoscopic gastric bypass surgery for morbid obesity were included in the study. During the procedure, biopsies of the parietal peritoneum were taken at the start of the procedure and each 45 min afterward. Tissue samples were homogenized and tissue-type plasminogen activator (tPA) antigen, tPA activity, urokinase-type PA antigen, and plasminogen activating inhibitors type 1 antigen were measured using commercial assay techniques. RESULTS: Both tPA antigen and its activity progressively decreased during the procedure, reaching significant levels after 90 min of surgery. The levels of uPA antigen and plasminogen activating inhibitors antigen did not significantly change throughout the procedure. CONCLUSIONS: As for conventional surgery, prolonged laparoscopic surgery causes a decreased fibrinolytic activity in the peritoneum due to decreased tPA levels.
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| 16. |
- Caballero-Corbalán, José, et al.
(författare)
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Using HTK for Prolonged Pancreas Preservation Prior to Human Islet Isolation
- 2012
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 175:1, s. 163-168
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Tidskriftsartikel (refereegranskat)abstract
- Background. Histidine-tryptophan-ketoglutarate (HTK) has been established as an alternative to University-of-Wisconsin solution (UWS) for abdominal organ preservation, but data about HTK efficiency to preserve pancreata during prolonged cold ischemia time (CIT) are conflicting. In human islet transplantation, HTK provided similar isolation outcomes after short CIT. The present study aimed to investigate whether islets can be successfully isolated from HTK-preserved pancreata after prolonged CIT compared with UWS. Materials and Methods. Sixty-four human pancreata retrieved from donors meeting criteria for kidney donation were perfused utilizing either HTK or UWS and preserved for more or less than 10 h prior to islet isolation. Along with parameters related to isolation and islet quality assessment, the dry-to-wet weight ratio was evaluated. Results. Donor-and procurement-related factors did not vary between HTK- and UWS-perfused pancreata. The dry-to-wet weight ratio was lower in HTK-preserved pancreata indicated tissue edema (21.0% +/- 3.5% versus 24.8% +/- 2.0%, P = 0.007). Isolation-related variables differed between experimental groups after prolonged CIT with respect to purified packed tissue volume (9.1 +/- 5.0 versus 17.2 +/- 8.1 mu L/g, P = 0.004) and islet yield (1910 +/- 980 versus 3150 +/- 1420 IE/g, P = 0.012). Islet purity and survival after culture were similar after HTK or UWS perfusion. The preservation solution did not affect in vitro function and transplantability of isolated islets. Conclusions. Compared with UWS, HTK has similar efficiency to preserve human pancreata for subsequent islet isolation during <10 h CIT but seems to be limited for prolonged cold storage. (C) 2012 Elsevier Inc. All rights reserved.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Dillström, M., et al.
(författare)
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Patients' experience of acute unplanned surgical reoperation
- 2017
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 209, s. 199-205
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Tidskriftsartikel (refereegranskat)abstract
- Background Undergoing surgery always involves various risks of complications, often depending on the type of surgery. Because of complications, a second surgical intervention, a reoperation, must occasionally be done, which in turn often causes an extended hospital stay, a longer recovery phase, greater suffering for the patient, and higher health care costs. Even though complications after general surgery are relatively common, little is known regarding patient experience of a reoperation. Knowledge of this could impact on care models in the future. The aim of this study was to describe patients' experience of acute, unplanned reoperation during a planned hospital stay. Materials and methods A purposive sampling strategy was used, and 16 patients were included, all who had undergone acute unplanned reoperation during a planned hospital stay. Semi-structured interviews were used to collect data, and a content analysis with an inductive approach was used for data analysis. Results The analysis resulted in two main themes: (1) health professionals' importance, having its foundation in categories trust and information, and (2) reaction, based on the categories anxiety and sadness. Conclusions Unplanned reoperation caused psychological, social, and existential reactions. Health care professionals were perceived as important because good communication, accurate information, their presence, and creating feelings of confident and safe care were meaningful factors for the patients as they managed the situation. © 2016 Elsevier Inc.
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| 21. |
- Eguchi, Susumu, et al.
(författare)
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Loss and recovery of liver regeneration in rats with fulminant hepatic failure
- 1997
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Ingår i: Journal of Surgical Research. - 0022-4804 .- 1095-8673. ; 72:2, s. 112-122
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Tidskriftsartikel (refereegranskat)abstract
- We earlier described a model of fulminant hepatic failure (FHF) in the rat where partial hepatectomy is combined with induction of right liver lobes necrosis. After this procedure, lack of regenerative response in the residual viable liver tissue (omental lobes) was associated with elevated plasma hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-beta1) levels and delayed expression of HGF and c-met mRNA in the remnant liver. Here, we investigated whether syngeneic isolated hepatocytes transplanted in the spleen will prolong survival and facilitate liver regeneration in FHF rats. Inbred male Lewis rats were used. Group I rats (n = 46) received intrasplenic injection of 2 x 10(7) hepatocytes and 2 days later FHF was induced. Group II FHF rats (n = 46) received intrasplenic injection of saline. Rats undergoing partial hepatectomy of 68% (PH; n = 30) and a sham operation (SO; n = 30) served as controls. In 20 FHF rats (10 rats/group), survival time was determined. The remaining 72 FHF rats (36 rats/group) were used for physiologic studies (liver function and regeneration and plasma growth factor levels). In Group I rats survival was longer than that of Group II controls (73 +/- 22 hr vs. 33 +/- 9 hr; P < 0. 01). During the first 36 hr, Group I rats had lower blood ammonia, lactate, total bilirubin, PT, and PTT values, lower activity of liver enzymes, and higher monoethylglycinexylidide (MEGX) production than Group II rats. In Group I rats, livers increased in weight at a rate similar to that seen in PH controls and showed distinct mitotic and DNA synthetic activity (incorporation of bromodeoxyuridine and proliferation cell nuclear antigen expression). Plasma HGF and TGF-beta1 levels in these rats decreased and followed the pattern seen in PH rats; additionally, c-met expression in the remnant liver was accelerated. Hepatocyte transplantation prolonged survival in FHF rats and facilitated liver regeneration. Even though the remnant liver increased in weight four times reaching 30% of the original liver mass, the transplant-bearing rats expired due to inability of the regenerating liver to support the rat.
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| 22. |
- Ekelund, Mikael, et al.
(författare)
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Effects of total parenteral nutrition on rat enteric nervous system, intestinal morphology, and motility.
- 2005
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 124:2, s. 187-193
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Tidskriftsartikel (refereegranskat)abstract
- Total parenteral nutrition (TPN) is often crucial for patients not being able to feed enterally or having intestinal absorptive deficits. Enteral nutrition is, however, frequently regarded vital for maintaining functional and structural intestinal integrity. The aim of this study was to investigate possible effects of TPN on rat distal small intestine compared to enterally fed identically housed controls, regarding the enteric nervous system (ENS), motility in vitro, and morphology. This study shows that motor responses evoked by electrical stimulation or exposure to vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide-27 (PACAP-27), and nitric oxide (NO) donor were unchanged. By using immunohistochemistry, the numbers of submucous (P < 0.05) and myenteric (P < 0.05) nerve cells were found to increase, expressed as numbers per unit length. The percentage of neurons expressing VIP, PACAP-27, NO-synthase, and galanin remained unchanged, however. By in situ hybridization the number of submucous neurons expressing neuropeptide Y-mRNA was found to decrease (P < 0.05); the other populations were unaltered. Morphometry revealed an increased submucosal thickness (P < 0.05), while intestinal circumference markedly decreased (P < 0.0001) in TPN-treated rats. In conclusion, TPN treatment resulted in reduced intestinal circumference leading to condensation of enteric neurons. No marked changes in neurotransmitter expression of the enteric neurons or in motor activity were noted.
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| 23. |
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| 24. |
- Ewaldsson, Carl-Arne, et al.
(författare)
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Adrenergic drugs alter both the fluid kinetics and the hemodynamic responses to volume expansion in sheep
- 2006
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Ingår i: Journal of Surgical Research. - : Elsevier. - 0022-4804 .- 1095-8673. ; 131:1, s. 7-14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Plasma volume expansion is often performed during adrenergic therapy in the intensive care unit, but little is known about their combined effects.MATERIALS AND METHODS: The influence of three adrenergic drugs (50 microg/kg/min of dopamine, 0.1 microg/kg/min of isoprenaline, or 3 microg/kg/min of phenylephrine) on the relationship between plasma dilution (an index of volume expansion) and the central hemodynamic responses to volume loading with 24 ml/kg of 0.9% saline were evaluated in 6 adult sheep. Kinetic analysis was also applied to the data on plasma dilution and the urinary excretion measured during and after volume loading.RESULTS: The adrenergic agents markedly changed the baseline values for all hemodynamic parameters. The kinetic analysis showed that phenylephrine, which is an alpha-adrenergic receptor agonist, promoted renal excretion of infused fluid at the expense of fluid distribution to the periphery (P < 0.05 versus controls). Isoprenaline, which stimulates adrenergic beta-receptors, had the opposite effect. During volume expansion, cardiac atrial pressures increased by 25 to 90%, cardiac output by 13-80% and the arterial pressures by 2 to 22%. Plasma dilution during and after volume loading correlated, in a linear fashion, with these hemodynamic responses. The correlations were strong (r > 0.80) in the control and phenylephrine groups, but weaker in the dopamine and isoprenaline groups. Dopamine was associated with the most variable hemodynamic responses overall.CONCLUSIONS: Adrenergic drugs altered the hemodynamics at baseline (direct effects), changed the distribution and elimination of infused 0.9% saline (indirect effects) and, finally, modified most hemodynamic responses to plasma dilution (interaction effects).
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| 25. |
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| 26. |
- Falk, Peter, 1962, et al.
(författare)
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Studies of TGF-beta(1-3) in serosal fluid during abdominal surgery and their effect on in vitro human mesothelial cell proliferation.
- 2009
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Ingår i: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 154:2, s. 312-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increased transforming growth factor-beta (TGF-beta) levels are associated with fibrosis, affected cell proliferation, and postsurgical adhesion development, but the knowledge regarding TGF-beta response to the surgical trauma is limited. This study investigated TGF-beta(1-3) isoforms and fibrinolytical factors in peritoneal serosal fluid during abdominal surgery, together with the in vitro effect of TGF-beta(1-3) on human mesothelial cell proliferation. MATERIALS AND METHODS: Total as well as biologically active TGF-beta(1-3) and fibrinolytic factors: t-PA, uPA, and PAI-1 were measured in serosal fluid and plasma from 23 patients undergoing colorectal cancer surgery. In vitro proliferation of human primary mesothelial cell cultures upon TGF-beta(1-3) stimulation was also investigated. RESULTS: Total TGF-beta1 and TGF-beta2 levels were similar in serosal fluid and plasma while active fractions were increased in serosal fluid. In contrast, total fraction of TGF-beta3 was higher in serosal fluid compared with plasma, while levels of active fractions did not differ. Plasminogen activators (t-PA, uPA) were elevated while the inhibitor (PAI-1) was decreased in serosal fluid compared with plasma. The in vitro mesothelial cell proliferation studies revealed that high TGF-beta(1-3) concentrations decreased cell proliferation, while lower concentrations of TGF-beta1 increased mesothelial cell proliferation. CONCLUSIONS: This human study shows increased active TGF-beta levels in peritoneal serosal fluid, compared with plasma, during abdominal surgery and that TGF-beta1 at physiological concentrations increased human mesothelial cell proliferation in vitro. TGF-beta cytokines may be involved in postsurgical adhesion formation.
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| 27. |
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| 28. |
- Faria, Isabella, et al.
(författare)
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Gender-Based Discrimination Among Medical Students: A Cross-Sectional Study in Brazil
- 2023
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Ingår i: Journal of Surgical Research. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0022-4804 .- 1095-8673. ; 283, s. 102-109
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Gender-based discrimination (GBD) creates a hostile environment during medical school, affecting students personal life and academic performance. Little is known about how GBD affects the over 204,000 medical students in Brazil. This study aims to explore the patterns of GBD experienced by medical students in Brazil. Methods: This is a cross-sectional study using an anonymous, Portuguese survey dissemi-nated in June 2021 among Brazilian medical students. The survey was composed of 24 questions to collect data on GBD during medical school, formal methods for reporting GBD, and possible solutions for GBD. Results: Of 953 responses, 748 (78%) were cisgender women, 194 (20%) were cisgender men, and 11 (1%) were from gender minorities. 65% (616/942) of respondents reported experiencing GBD during medical school. Women students experienced GBD more than men (77% versus 22%; P < 0.001). On comparing GBD perpetrator roles, both women (82%, 470/574) and men (64%, 27/42) reported the highest rate of GBD by faculty members. The occurrence of GBD by location differed between women and men. Only 12% (115/953) of respondents reported knowing their institution had a reporting mechanism for GBD. Conclusions: Most respondents experienced GBD during medical school. Cisgender women experienced GBD more than cisgender men. Perpetrators and location of GBD differed for men and women. Finally, an alarming majority of students did not know how to formally report GBD in their schools. It is imperative to adopt broad policy changes to diminish the rate of GBD and its a consequential burden on medical students. 2022 Elsevier Inc. All rights reserved.
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| 29. |
- Ferreira, Julia, et al.
(författare)
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Evolution of Gender Disparities Among Brazilian Surgical, Anesthesia, and Obstetric Providers.
- 2022
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Ingår i: Journal of Surgical Research. - : Elsevier. - 0022-4804 .- 1095-8673. ; 275, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Since 2010, most graduating physicians in Brazil have been female, nevertheless gender disparities among surgical specialties still exist. This study aims to explore whether the increase in female physicians has translated to increased female representation among surgical specialties in Brazil.METHODS: Data on gender, years of practice, and specialty was extracted from Demografia Médica do Brasil, from 2015 to 2020. The percentage of women across 18 surgical, anesthesia, and obstetric (SAO) specialties and the relative increases in female representation during the study period were calculated.RESULTS: Of the 18 SAO specialties studied, 16 (88%) were predominantly male (>50%). Only obstetrics/gynecology and breast surgery showed a female predominance, with 58% and 52%, respectively. Urology, neurosurgery, and orthopedic surgery and traumatology were the three specialties with the largest presence of men - and the lowest absolute growth in the female workforce from 2015 to 2020.CONCLUSIONS: In Brazil, where significant gender disparities persist, women are still underrepresented in surgical specialties. Female presence is predominant in surgical specialties dedicated to the care of female patients, while it remains poor in those with male patient dominance. Over the last 5 y, the proportion of women working in SAO specialties has grown, but not as much as in nonsurgical specialties. Future studies should focus on investigating the causes of gender disparities in Brazil to understand and tackle the barriers to pursuing surgical specialties.
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| 30. |
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| 31. |
- Gerk, Ayla, et al.
(författare)
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Gender Discrimination, Career Aspirations, and Access to Mentorship Among Medical Students in Brazil.
- 2022
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Ingår i: Journal of Surgical Research. - : Elsevier. - 0022-4804 .- 1095-8673. ; 279, s. 702-711
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Gender-based discrimination (GBD) creates a hostile environment that can affect medical students. Mentorship has been recognized as a mitigating factor for GBD. We aimed to investigate the impacts of GBD on career selection and well-being of medical students in Brazil and to explore access to mentorship among these students.METHODS: A cross-sectional study was performed using an anonymous survey in Portuguese. The survey was distributed in June 2021 to students enrolled in Brazilian medical schools. It contained 24 questions, including demographics, episodes of GBD experienced by responders and their impact on professional and personal life, and mentorship access.RESULTS: Of 953 respondents, 748 (78%) were cisgender women, 194 (20%) cisgender men, and 11 nonbinary (1%). Sixty-six percent (625/953) of students reported experiencing GBD, with cisgender women and nonbinary being more likely to experience it than cisgender men (P < 0.001). Responders who experiences GBD report moderate to severe impact on career satisfaction (40%, 250/624), safety (68%, 427/624), self-confidence (68%, 426/624), well-being (57%, 357/625), and burnout (62%, 389/625). Cisgender women were more likely to report these effects than men counterparts (P < 0.01). Only 21% of respondents (201/953) had mentors in their medical schools.CONCLUSIONS: Our findings demonstrate that GBD is widespread among Brazilian medical students affecting their personal and professional lives, and most of them do not have access to a mentor. There is an urgent need to increase access to mentors who could mitigate the adverse effects of GBD and help develop a diverse and inclusive medical workforce.
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| 32. |
- Gessler, Bodil, et al.
(författare)
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Loop ileostomies in colorectal cancer patients-morbidity and risk factors for nonreversal.
- 2012
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Ingår i: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 178:2, s. 708-714
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In colorectal cancer patients, loop ileostomies are used to protect an anastomosis, in salvage surgery after a complication, and as a palliative measure. The aim of this study was to identify complications to the ileostomy, time until reversal, and risk factors for nonclosure or a permanent stoma. MATERIAL AND METHODS: Consecutive patients who received a loop ileostomy with the diagnosis of colorectal cancer at index surgery in four hospitals in Region Västra Götaland, Sweden, from January 1, 2007 until February 28, 2010 were retrospectively studied. Demography, events during index surgery, complications related to the ileostomy and technique, and complications during closure were registered. RESULTS: A total of 262 patients received a loop ileostomy. Loop iliostomies were constructed during emergency surgery in 15% of patients. Forty-three percent had complications related to the ileostomy; most common were high-volume output and leakage of stomal output. Morbidity after closure was high, at 28%, and mortality was 1%. Eighty-six percent had their stoma closed, median time 178 (3-700) d. Risk factors for nonreversal were postoperative complications to index surgery and advanced cancer disease. Eleven percent received a secondary stoma, and at the end of the study 23% had a permanent stoma. CONCLUSIONS: The morbidity related to loop ileostomies and loop ileostomy closure is considerable. One in five patients will have a permanent stoma, and our conclusion is that for emergency patients with advanced disease another type of stoma should be chosen, if possible, to reduce the morbidity.
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| 33. |
- Graf, W, et al.
(författare)
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The influence of early postoperative intraperitoneal chemotherapy on human wound healing.
- 1994
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 57:3, s. 394-400
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Tidskriftsartikel (refereegranskat)abstract
- Cell ingrowth, hydroxyproline accumulation, and mRNA expression of collagen I were measured in two polytetrafluoroethylene grafts implanted subcutaneously at the time of colorectal cancer surgery to evaluate the influence of early postoperative chemotherapy on human wound healing. Eleven patients treated with intraperitoneal 5-fluorouracil and intravenous folinic acid Days 1-6 after operation were compared with 15 patients who underwent surgery alone. At 1 week, chemotherapy-treated patients had accumulated less hydroxyproline (mean 0.35 +/- 0.33 micrograms/cm) compared with untreated patients (mean 0.73 +/- 0.37 micrograms/cm, P < 0.05). By 2 weeks, the hydroxyproline content had increased sixfold in the chemotherapy group (P < 0.01) and threefold in the nonchemotherapy group (P < 0.01) and there was no difference between the groups. Cell and connective tissue ingrowth and total RNA content did not differ between the groups at any point in time, but at 1 week the mRNA expression of collagen I was higher in the chemotherapy group (P < 0.05). These results indicate that collagen accumulation in human subjects is reduced during a short course of postoperative chemotherapy and normalizes after the end of treatment.
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| 34. |
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| 35. |
- Hansbrough, John F., et al.
(författare)
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Neutrophil activation and tissue neutrophil sequestration in a rat model of thermal injury
- 1996
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 61:1, s. 17-22
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil (PMN) deposition in tissues (leukosequestration) after shock may produce local tissue injury from proteases and oxygen intermediaries which are released from sequestered PMNs. We quantified leukosequestration in tissues in burned rats using two methods of analysis: 1), measurement of lung myeloperoxidase (MPO); 2), measurement of radiolabeled PMNs and erythrocytes deposited in multiple tissues. After tracheostomy and venous cannulation, rats received 17% TBSA full-thickness contact burns and were resuscitated with 20 cc intraperitoneal saline. Lung PMNs were estimated by measuring MPO in lung tissue. PMN influx into lung, liver, spleen, gut, skin, muscle, kidney, and brain was determined by removing (preburn) and differentially radiolabeling PMNs (111In) and erythrocytes (51Cr), reinfusing cells 4.5 hr postburn, and measuring tissue radioactivity 5 hr postburn. Tissue edema was measured by determining extravasation of 125I-labeled albumin in tissues. Peripheral blood PMNs were analyzed for intracellular H2O2 content utilizing a fluorescent dye which reacts with H2O2 coupled with analysis of cell fluorescence by flow cytometry. MPO was elevated in lungs 8 hr postburn (P < 0.05). PMN influx into lung tissues was confirmed by histologic examination. Radioisotope studies demonstrated significant (P < 0.05) leukosequestration into lung, gut, kidney, skin, and brain tissues at 5 hr postburn. Respiratory burst activity of peripheral blood PMNs was increased 5 hr postburn (P < 0.05). Flow cytometric analysis indicated that peripheral blood PMNs were capable of producing markedly increased H2O2 levels 5 hr postburn. Tissue edema, manifested by radiolabeled albumin influx, was not seen in any tissues. Since others have shown that sequestration of metabolically active PMNs may induce remote tissue injury, therapies which block postburn leukosequestration may be able to improve clinical outcomes by limiting remote tissue injury.
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| 36. |
- Hatchimonji, Justin S., et al.
(författare)
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Resuscitative Endovascular Balloon Occlusion of Aaorta Use in Nontrauma Emergency General Surgery : A Multi-institutional Experience
- 2020
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Ingår i: Journal of Surgical Research. - : Academic Press. - 0022-4804 .- 1095-8673. ; 256, s. 149-155
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to determine the current utilization patterns of resuscitative endovascular balloon occlusion of aorta (REBOA) for hemorrhage control in nontrauma patients.METHODS: Data on REBOA use in nontrauma emergency general surgery patients from six centers, 2014-2019, was pooled for analysis. We performed descriptive analyses using Fisher's exact, Student's t, chi-squared, or Mann-Whitney U tests as appropriate.RESULTS: Thirty-seven patients with acute hemorrhage from nontrauma sources were identified. REBOA placement was primarily performed by trauma attendings (20/37, 54%) and vascular attendings (13/37, 35%). In seven patients (19%), balloons were positioned prophylactically but never inflated. In 24 (65%) of 37 patients, REBOA was placed in the operating room. 28/37 balloons (76%) were advanced to zone 1, 8/37 (22%) were advanced to zone 3, and there was one REBOA use in the inferior vena cava. Most common indications were gastrointestinal and peripartum bleeding. In the 30 cases of balloon inflation, 24 of 30 (80%) resulted in improved hemodynamics. Eleven of 30 patients (37%) died before discharge. One patient developed a distal embolism, but there were no reports of limb loss. Twelve patients (40% of all REBOA inflations and 63% of survivors) were discharged to home.CONCLUSIONS: REBOA has been used in a range of acutely hemorrhaging emergency general surgery patients with low rates of access-related complications. Mortality is high in this patient population and further research is needed; however, appropriate patient selection and early use may improve survival in these life-threatening cases.
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| 37. |
- Hwaiz, Rundk, et al.
(författare)
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Rac1 signaling regulates sepsis-induced pathologic inflammation in the lung via attenuation of Mac-1 expression and CXC chemokine formation.
- 2013
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 183:2, s. 798-807
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Tidskriftsartikel (refereegranskat)abstract
- Excessive neutrophil recruitment is a major feature in septic lung damage although the signaling mechanisms behind pulmonary infiltration of neutrophils in sepsis remain elusive. In the present study, we hypothesized that Rac1 might play an important role in pulmonary neutrophil accumulation and tissue injury in abdominal sepsis. Male C57BL/6 mice were treated with Rac1 inhibitor NSC23766 (5 mg/kg) before cecal ligation and puncture (CLP). Bronchoalveolar lavage fluid and lung tissue were collected for the quantification of neutrophil recruitment and edema and CXC chemokine formation. Blood was collected for the determination of Mac-1 on neutrophils and proinflammatory compounds in plasma. Gene expression of CXC chemokines and tumor necrosis factor alpha was determined by quantitative reverse transcription-polymerase chain reaction in alveolar macrophages. Rac1 activity was increased in lungs from septic animals, and NSC23766 significantly decreased pulmonary activity of Rac1 induced by CLP. Administration of NSC23766 markedly reduced CLP-triggered neutrophil infiltration, edema formation, and tissue damage in the lung. Inhibition of Rac1 decreased CLP-induced neutrophil expression of Mac-1 and pulmonary formation of CXC chemokines. Moreover, NSC23766 abolished the sepsis-evoked elevation of messenger RNA levels of CXC chemokines and tumor necrosis factor alpha in alveolar macrophages. Rac1 inhibition decreased the CLP-induced increase in plasma levels of high mobility group protein B1 and interleukin 6, indicating a role of Rac1 in systemic inflammation. In conclusion, our results demonstrate that Rac1 signaling plays a key role in regulating pulmonary infiltration of neutrophils and tissue injury via regulation of chemokine production in the lung and Mac-1 expression on neutrophils in abdominal sepsis. Thus, targeting Rac1 activity might be a useful strategy to protect the lung in abdominal sepsis.
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| 38. |
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| 39. |
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| 40. |
- Johnson, Louis Banka, et al.
(författare)
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Combination of pre-operative radiotherapy and surgery suppresses local accumulation of collagen and TGF-beta 1 in rats
- 2006
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 133:2, s. 136-142
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Tidskriftsartikel (refereegranskat)abstract
- Background. The systemic and local tissue repair responses of radiation in combination with surgery are still unclear. We have studied the effect of fractionated pre-operative radiotherapy with or without subsequent laparotomy on collagen accumulation using a rodent model. Materials and methods. Thirty-two male Sprague-Dawley rats were divided into four groups (eight rats per group): 1) sham radiation and sham laparotomy (control); 2) sham radiation and laparotomy; 3) radiation and sham laparotomy; and 4) radiation followed by laparotomy. Expanded polytetrafluoroethylene (ePTFE) tubes were implanted subcutaneously in the abdominal wall in the radiotherapy field and on the back outside the radiotherapy field day 0. The abdomen (3 cm x 4 cm) was irradiated day 3 (10 Gy) and again day 7 (10 Gy). On day 10, implants were extirpated, laparotomy undertaken in groups 2 and 4 and new ePTFE tubes implanted subcutaneously. The second implants were extirpated on day 20. Implants were analyzed for hydroxyproline, total protein and transforming growth factor-ss 1 (TGF-ss 1) levels. Results. On day 10, hydroxyproline (P < 0.05) and TGF-ss 1 (P < 0.001) were lower in ePTFE tubes in irra-diated compared with non-irradiated rats. On day 20, the abdominal ePTFE hydroxyproline remained low (P < 0.001) in animals subjected to laparotomy and pre-operative irradiation while hydroxyproline levels of rats subjected to irradiation only were similar to controls. The effects of radiation on hydroxyproline were confined to the irradiated abdominal area. There was a positive correlation between hydroxyproline and TGF-ss 1 levels in the abdominal wall implant day 20 (r = 0.53, P < 0.005). Conclusion. A clinically relevant fractionated radiation scheme reduced subcutaneous collagen accumulation pre-operatively and profoundly within the radiation field post-operatively after laparotomy, possibly because of lowered TGF ss 1 levels. (c) 2006 Elsevier Inc. All rights reserved.
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| 41. |
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| 42. |
- Kiwanuka, Elizabeth, et al.
(författare)
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CCN2 is transiently expressed by keratinocytes during re-epithelialization and regulates keratinocyte migration in vitro by the ras-MEK-ERK signaling pathway
- 2013
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 185:2, s. E109-E119
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Tidskriftsartikel (refereegranskat)abstract
- Background: CCN2 (previously known as connective tissue growth factor) is a multifunctional matricellular protein that has numerous effects on cell life and cell interactions with the connective tissue. Although the importance of CCN2 for the fibrotic process in wound healing has been well studied, the involvement of CCN2 in keratinocyte function has not yet been explored. Therefore, the aim of the present study was to investigate the role of CCN2 in the epidermis during wound healing. Materials and methods: Immunohistochemistry was done on sections from full-thickness porcine wounds. The effect of CCN2 on the migration of cultured human keratinocytes exposed to scratch wounds, the effect on phosphorylation of extracellular signal-related kinases (ERK), and the effect of adding inhibitors to the ERK/ mitogen-activated protein kinase pathway to human keratinocytes were studied. Results: The CCN2 protein was transiently expressed in vivo at the leading keratinocyte edge during re-epithelialization of full-thickness porcine wounds. In vitro, exogenous addition of CCN2 to human keratinocyte cultures regulated keratinocyte migration and resulted in phosphorylation of ERK. The addition of inhibitors of ERK/mitogen-activated protein kinase counteracted the effect of CCN2 on migration. Conclusions: CCN2 was transiently expressed at the leading keratinocyte edge in vivo. The biologic importance of this was supported in vitro, because CCN2 regulated human keratinocyte migration through activation of the Ras-mitogen-activated protein kinase kinase-ERK signal transduction pathway.
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| 43. |
- Källskog, Örjan, et al.
(författare)
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Autoregulation of Islet Graft Blood Flow Follows the Implantation
- 2011
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 171:2, s. 865-870
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transplantation of pancreatic islets necessitates a revascularization, which is associated with a generalized graft vascular dysfunction, manifested, e.g., as a capillary hypertension, a decreased graft blood perfusion and graft hypoxia. Some of these changes can be due to impaired autoregulation of the newly formed vasculature in the islet grafts, and the aim of the present study was to further examine if this was the case. MATERIALS AND METHODS: We implanted 250 syngeneic islets under the renal capsule of rats and studied them 1 or 12-13 mo later. The blood perfusion of the whole kidney, renal cortex, and islet grafts were recorded in anesthetized animals with an ultrasound probe or laser-Doppler probes, respectively. The blood pressure in the kidneys was then gradually decreased by an adjustable clamp, during simultaneous measurement of blood flow values. RESULTS: The whole kidney, renal cortex, and islet grafts regulated their blood flow in concert with one another down to pressures of approximately 60 mmHg both 1 and 12-13 mo after implantation. However, the variability was greater at 1 mo. CONCLUSION: Islets transplanted under the renal capsule show similar autoregulatory properties with the kidney. It may be that the autoregulatory capacity of the renal interlobular arteries provides the underlying mechanism. This may be of importance for the good long-term survival of transplanted islets at this implantation site in experimental studies.
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| 44. |
- Laato, M, et al.
(författare)
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Epidermal growth factor (EGF) prevents methylprednisolone-induced inhibition of wound healing.
- 1989
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Ingår i: Journal of Surgical Research. - 0022-4804 .- 1095-8673. ; 47:4, s. 354-9
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Tidskriftsartikel (refereegranskat)abstract
- Subcutaneously implanted cylindrical hollow viscose cellulose sponges were used to study the effect of locally applied epidermal growth factor (EGF) on methylprednisolone-induced inhibition of granulation tissue formation in rats. In in vivo studies the sponges were treated immediately after implantation with a single injection of 2 mg (approximately 1.7 x 10(-3) M) of depot methylprednisolone or with its carrier solution only. Thereafter the implants were injected daily with 5 micrograms of EGF or with its carrier solution 0.1% albumin for 7 days. Methylprednisolone treatment decreased the accumulation of nucleic acids, collagen, and glycosaminoglycans in the developing granulation tissue. After daily injections of EGF the concentrations of these tissue components returned close to the control values. In cultures of rat granulation tissue fibroblasts, 10(-4) M and 10(-3)M methylprednisolone decreased collagen synthesis by 41 and 81% from the control level, respectively. In the presence of methylprednisolone EGF treatment could not increase collagen synthesis of fibroblasts. Methylprednisolone treatment resulted in a dose-dependent reduction in pro alpha 1(I) collagen mRNA levels, which was partially inhibited by low EGF concentrations (1 and 10 ng/ml). In the presence of methylprednisolone all concentrations of EGF increased fibronectin mRNA levels in a dose-dependent manner. It is concluded that EGF treatment can prevent the inhibitory effect of methylprednisolone on wound healing by stimulating fibroblast proliferation but does not stimulate collagen synthesis per cell.
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| 45. |
- Laschke, Matthias, et al.
(författare)
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Rho-Kinase Inhibitor Attenuates Cholestasis-Induced CXC Chemokine Formation, Leukocyte Recruitment, and Hepatocellular Damage in the Liver.
- 2010
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Ingår i: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 159, s. 666-673
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the present experimental study, we analyzed the role of Rho-kinase during obstructive cholestasis by studying the effect of the Rho-kinase inhibitor Y-27632 on hepatic CXC chemokine formation, leukocyte recruitment and hepatocellular damage. MATERIALS AND METHODS: C57BL/6 mice underwent bile duct ligation (BDL) to induce obstructive cholestasis. Mice were pretreated with Y-27632 (1 and 10mg/kg) or the vehicle PBS. Sham-operated animals served as controls. After 12h, hepatic accumulation of leukocytes and sinusoidal perfusion were determined using intravital fluorescence microscopy. Hepatocellular damage was monitored by measuring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). CXC chemokines in the liver were analyzed by ELISA. RESULTS: Administration of 10mg/kg of Y-27632 protected against cholestasis-induced hepatocellular damage indicated by a more than 87% reduction of ALT and AST in BDL mice. Moreover, this Rho-kinase inhibitor significantly decreased BDL-induced production of CXC chemokines by 44-83% and leukocyte recruitment by 60%. Finally, treatment with Y-27632 restored sinusoidal perfusion in cholestatic animals. CONCLUSIONS: Our findings indicate that the Rho-kinase signaling pathway plays a key role in the pathophysiology of cholestatic liver injury. Thus, targeting Rho-kinase activity may represent a new therapeutic approach in the treatment of inflammation and liver injury in cholestatic liver diseases.
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| 46. |
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| 47. |
- Lepistö, J, et al.
(författare)
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Effects of homodimeric isoforms of platelet-derived growth factor (PDGF-AA and PDGF-BB) on wound healing in rat.
- 1992
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Ingår i: Journal of Surgical Research. - 0022-4804 .- 1095-8673. ; 53:6, s. 596-601
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor (PDGF) has been suggested to have a significant role in wound healing. The present work was aimed at studying the effects of PDGF-AA and PDGF-BB homodimers on developing granulation tissue in rats. Subcutaneously implanted hollow cylindrical cellulose sponges were used as an inductive matrix for the ingrowth of granulation tissue. Fifty microliters of solutions containing 0, 5, 50, or 500 ng of PDGF-AA or PDGF-BB homodimers was injected daily into the sponges; 7 days after implantation the granulation tissue in the sponge cylinders was analyzed. Five hundred nanograms of PDGF-BB stimulated significantly the accumulation of collagen, indicated by the elevated hydroxyproline content of the sponge (+34%, P < 0.001). Similarly, the amounts of RNA-ribose, nitrogen, hexosamines, and uronic acids were significantly higher, reflecting a PDGF-BB-induced increase in the accumulation of RNA, protein, and glycosaminoglycans. Analyses of wound fluid showed no essential changes in the composition of different cell types after PDGF-BB-treatment. The PDGF-AA-treatment increased significantly the mean amount of RNA but there were no significant changes in other parameters. In vitro both PDGF-AA and PDGF-BB increased significantly the number of rat granulation tissue derived fibroblasts in culture at concentrations of 10 and 30 ng/ml. This proliferative effect resulted in a lowered level of protein synthesis per cell. To conclude, PDGF-BB accelerates granulation tissue formation both in vitro and in vivo, whereas PDGF-AA is effective in vitro but it is clearly less effective in vivo.
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| 48. |
- Lund, Tormod, et al.
(författare)
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Sustained Reversal of Diabetes Following Islet Transplantation to Striated Musculature in the Rat
- 2010
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 160:1, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is an increasing emphasis in the islet transplant community on the development of alternative sites for islet implantation. Striated musculature constitutes a potential alternative, which has been successfully employed in autotransplantation of parathyroid glands for decades. In the present study, a technique for intramuscular islet transplantation was developed and compared with intraportal islet transplantation in a syngeneic rat model. MATERIALS AND METHODS: Lewis rats were used. Pancreata were digested using Liberase. Islets were either transplanted into m. biceps femoris in a pearls-on-a-string fashion or intraportally, and the ability to reverse diabetes was compared. Eight weeks after transplantation an IVGTT was performed. Real-time quantitative RT-PCR was employed on muscle biopsies to investigate mRNA levels of cytokines in response to the transplant procedure. Explanted livers, muscles, and pancreata were harvested at the end of the experiment for histopathological analyses. RESULTS: 2000 IEQ repeatedly cured diabetic rats at the intraportal site, while 4000 IEQ was required at the intramuscular site. Time to reversal of diabetes, post-transplant weight development, and IVGTT curves did not differ between the groups. Normoglycemia was sustainable to the end of the study (>100 days) for all animals. The transplant procedure upregulated pro-inflammatory cytokines (IL-6 and IL-8) in striated muscle, and peri-islet fibrosis was observed in intramuscular grafts. CONCLUSIONS: Islet transplantation into striated musculature is feasible; however, in its present form the intramuscular site is less efficient compared with the liver in rats. The intramuscular site allows manipulation of the graft and implantation site prior to transplantation and may therefore have implications for islet transplantation in humans.
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| 49. |
- Lundberg, J., et al.
(författare)
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Liver parenchyma access and lesion marker via the endovascular route
- 2015
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 195:2, s. 488-494
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Tidskriftsartikel (refereegranskat)abstract
- Background Neoadjuvant chemotherapeutic regimens for metastatic colorectal cancer are now so effective that they can cause "vanishing" lesions. With new advances such as local ablation, intra-arterial treatments in bolus with pumps or with beads, and isolation of hepatic perfusion, the need for a working channel to the liver may be warranted, ideally reducing the risk of spreading neoplastic cells. Materials and methods The endovascular trans-vessel wall Extroducer device makes it possible to gain direct access to the liver parenchyma. The distal tip is then detached, to act as both a marker and a securing plug in the vessel defect. We used ex vivo and in vivo tests to evaluate the device as a working channel for local administration of substances to the parenchyma and as a marker for detection with both transabdominal and intraoperative ultrasonography. Results We could deploy the Extroducer device without any hemorrhagic or thromboembolic complications in vivo, and we were able to detect all markers ex vivo and in vivo using both transabdominal and intraoperative ultrasonography. Furthermore, we found that it is possible to administer substances to the liver parenchyma using the catheter. Conclusions The trans-vessel wall technique can be used to establish a working channel to the liver parenchyma for administration of any substance, such as chemotherapeutic agents or cells. The detached device can also be used as a marker for ultrasound-guided partial liver resection in "vanishing lesions." The technique should have a low risk of seeding of neoplastic cells. This study in large animals forms a strong basis for translation to clinical studies.
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| 50. |
- Macarak, Edward J., et al.
(författare)
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Trametinib prevents mesothelial-mesenchymal transition and ameliorates abdominal adhesion formation
- 2018
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Ingår i: Journal of Surgical Research. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0022-4804 .- 1095-8673. ; 227, s. 198-210
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intra-abdominal adhesions are a major cause of morbidity after abdominal or gynecologic surgery. However, knowledge about the pathogenic mechanism(s) is limited, and there are no effective treatments. Here, we investigated a mouse model of bowel adhesion formation and the effect(s) of an Federal Drug Administration-approved drug (trametinib) in preventing adhesion formation. Materials and methods: C57BL/6 mice were used to develop a consistent model of intra-abdominal adhesion formation by gentle cecal abrasion with mortality rates of <10%. Adhesion formation was analyzed histologically and immunochemically to characterize the expression of pro-fibrotic marker proteins seen in pathologic scaring and included alpha smooth muscle actin (alpha SMA) and fibronectin EDA (FNEDA) which arises from alternative splicing of the fibronectin messenger RNA resulting in different protein isoforms. Trichrome staining assessed collagen deposition. Quantitative polymerase chain reaction analysis of RNA isolated from adhesions by laser capture microscopy was carried out to assess pro-fibrotic gene expression. To block adhesion formation, trametinib was administered via a subcutaneous osmotic pump. Results: Adhesions were seen as early as post-operative day 1 with extensive adhesions being formed and vascularized by day 5. The expression of the FNEDA isoform occurred first with subsequent expression of alpha SMA and collagen. The drug trametinib was chosen for in vivo studies because it effectively blocked the mesothelial to mesenchymal transition of rat mesothelium. Trametinib, at the highest dose used (3 mg/kg/d), prevented adhesion formation while at lower doses, adhesions were usually limited, as evidenced by the presence of FNEDA isoform but not alpha SMA. Conclusions: Cecal abrasion in mice is a reliable model to study abdominal adhesions, which can be ameliorated using the MEK1/2 inhibitor trametinib. While blocking adhesion formation at the cell and molecular levels, trametinib, at the therapeutic doses utilized, did not impair the wound healing at the laparotomy site.
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