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Philippe Koninckx – One of the best experts on this subject based on the ideXlab platform.

  • The impact of the learning curve on Adhesion Formation in a laparoscopic mouse model
    Fertility and sterility, 2011
    Co-Authors: Roberta Corona, Carlos Roger Molinas, Maria Mercedes Binda, Jasper Verguts, Ron Schonman, Philippe Koninckx
    Abstract:

    Objective To evaluate the impact of surgeon training on Adhesion Formation in a laparoscopic mouse model. Laparoscopic surgery and bowel manipulation was demonstrated to enhance postoperative Adhesion Formation. Design Prospective randomized, controlled trial. Setting University laboratory research center. Animal(s) 200 BALB/c and 200 Swiss female mice. Intervention(s) Adhesions were induced by opposing bipolar lesions and 60 minutes of pneumoperitoneum. Each surgeon operated on 80 mice (40 Swiss and 40 BALB/c), the only variable thus being his/her increasing experience. Some surgeons were already experienced gynecologists, others were starting their training. Main Outcome Measure(s) End points were the duration of surgery while performing the lesions. The Adhesion Formation was scored quantitatively (proportion and total) and qualitatively (extent, type, and tenacity) after 7 days. Result(s) With training, duration of surgery and Adhesion Formation decreased exponentially for all surgeons, whether experienced or not. Experienced surgeons had initially a shorter duration of surgery, less Adhesion Formation, and less de novo Adhesions than inexperienced surgeons. Conclusion(s) These data suggest that laparoscopic skills improve with training, leading to a decrease in the duration of surgery and Formation of Adhesions. Therefore completion of a standardized learning curve should be mandatory when initiating Adhesion Formation studies both in laboratory or clinical setting.

  • Effect of upper abdomen tissue manipulation on Adhesion Formation between injured areas in a laparoscopic mouse model.
    Journal of minimally invasive gynecology, 2009
    Co-Authors: Ron Schonman, Roberta Corona, Adriana Bastidas, Carlo De Cicco, Philippe Koninckx
    Abstract:

    Study Objective: These experiments were designed to examine the effect of manipulation during surgery as a cofactor in Adhesion Formation at trauma sites. Design: Randomized, controlled trial. Canadian Task Force Classification-class 1. Setting: University laboratory research center. Subjects: A standardized laparoscopic mouse model (Balb\c mice 9-10 weeks old) for Adhesion Formation after opposing bipolar lesions and 60 minutes of carbon-dioxide pneumoperitoneum. In this model Adhesions are known to decrease after the addition of 3% of oxygen, dexamethasone, or both. In addition, Adhesions decrease with experience (i.e., with a decreasing amount of manipulation during the learning curve). Interventions: A factorial design was used to evaluate the effects of dexamethasone and of adding 3% of oxygen on manip- ulation-enhanced Adhesion Formation during a learning curve. Blocks of 4 animals were thus randomized as controls (carbon- dioxide pneumoperitoneum only) or received an additional 3% of oxygen, dexamethasone, or both. In a second experiment, the effects of manipulation on Adhesion Formation were quantified. In a third experiment we evaluated whether dexamethasone had a specific effect on manipulation-enhanced Adhesion Formation. Measurements and Main Results: Qualitative and quantitative Adhesion scoring 7 days after the intervention. The first ex- periment confirmedthat AdhesionFormation decreasedduringthelearning curve(p ,.0001)andafter theadditionofdexameth- asone whether assessed asthe total Adhesion score (p ,.0001 and p 5.0009, respectively) or aquantitative score (p ,.0001 and p ,.0001, respectively). The second experiment showed that Adhesion Formation increased by standardized touching and grasping of omentum and bowels (proportion score p 5.0059 and p 5.0003, respectively) and this effect increased with duration of touching (p 5.0301). In the third experiment, dexamethasone was confirmed to decreased Adhesion Formation (p 5.0001) but this effect was not specific for manipulation-enhanced Adhesion Formation. Conclusion: Manipulation of intraperitoneal organs in the upper abdomen enhances Adhesion Formation at trauma sites, confirming that the peritoneal cavity is a cofactor in Adhesion Formation. Dexamethasone decreases Adhesion Formation but

  • Adhesion Formation and interanimal variability in a laparoscopic mouse model varies with strains
    Fertility and sterility, 2005
    Co-Authors: Carlos Roger Molinas, Maria Mercedes Binda, Rudi Campo, Philippe Koninckx
    Abstract:

    Adhesion Formation after laparoscopic surgery was evaluated in mice of different strains. More Adhesions were observed in Swiss, NMRI, and BALB/c mice, with less interanimal variability in BALB/c mice. These data point to genetics effects on Adhesion Formation, which open new insights in its pathogenesis and indicate the importance of a careful strain selection for animal studies.

Carlos Roger Molinas – One of the best experts on this subject based on the ideXlab platform.

  • The impact of the learning curve on Adhesion Formation in a laparoscopic mouse model
    Fertility and sterility, 2011
    Co-Authors: Roberta Corona, Carlos Roger Molinas, Maria Mercedes Binda, Jasper Verguts, Ron Schonman, Philippe Koninckx
    Abstract:

    Objective To evaluate the impact of surgeon training on Adhesion Formation in a laparoscopic mouse model. Laparoscopic surgery and bowel manipulation was demonstrated to enhance postoperative Adhesion Formation. Design Prospective randomized, controlled trial. Setting University laboratory research center. Animal(s) 200 BALB/c and 200 Swiss female mice. Intervention(s) Adhesions were induced by opposing bipolar lesions and 60 minutes of pneumoperitoneum. Each surgeon operated on 80 mice (40 Swiss and 40 BALB/c), the only variable thus being his/her increasing experience. Some surgeons were already experienced gynecologists, others were starting their training. Main Outcome Measure(s) End points were the duration of surgery while performing the lesions. The Adhesion Formation was scored quantitatively (proportion and total) and qualitatively (extent, type, and tenacity) after 7 days. Result(s) With training, duration of surgery and Adhesion Formation decreased exponentially for all surgeons, whether experienced or not. Experienced surgeons had initially a shorter duration of surgery, less Adhesion Formation, and less de novo Adhesions than inexperienced surgeons. Conclusion(s) These data suggest that laparoscopic skills improve with training, leading to a decrease in the duration of surgery and Formation of Adhesions. Therefore completion of a standardized learning curve should be mandatory when initiating Adhesion Formation studies both in laboratory or clinical setting.

  • Angiogenic factors in peritoneal Adhesion Formation
    Gynecological Surgery, 2006
    Co-Authors: Carlos Roger Molinas, Maria Mercedes Binda, Philippe Robert Koninckx
    Abstract:

    Abdominal surgery is considered as the leading cause of peritoneal Adhesions and almost universally as adhesiogenic. Peritoneal injury at the time of surgery initiates an inflammatory reaction determining fibrin deposition on the wound surface. Depending on the balance between the different components of the plasminogen system, this fibrin can be either lysed, leading to normal peritoneal healing, or organised, serving as a scaffold for fibroblast ingrowth, extracellular matrix deposition and angiogenesis, leading to Adhesion Formation. The mechanism underlying the predisposition to form Adhesions in some patients and in some specific anatomic sites and not in others after similar surgical procedures remains unknown. In spite of the many attempts proposed over the years for reducing the incidence of Adhesion Formation, peritoneal Adhesions remain a major clinical problem, inducing intestinal obstruction, pelvic pain, female infertility and difficulties at the time of re-operation. The available evidence indicates that understanding the Adhesion Formation process at the molecular level is essential for developing successful strategies for preventing Adhesions. Fortunately, the advancement in molecular biology during the last years has led to the identification of many molecules with the potential of regulating inflammatory and immune responses, tissue remodelling and angiogenesis, key events in peritoneal healing and Adhesion Formation. This review focuses on the role of angiogenesis and angiogenic factors in peritoneal Adhesion Formation.

  • Adhesion Formation and interanimal variability in a laparoscopic mouse model varies with strains
    Fertility and sterility, 2005
    Co-Authors: Carlos Roger Molinas, Maria Mercedes Binda, Rudi Campo, Philippe Koninckx
    Abstract:

    Adhesion Formation after laparoscopic surgery was evaluated in mice of different strains. More Adhesions were observed in Swiss, NMRI, and BALB/c mice, with less interanimal variability in BALB/c mice. These data point to genetics effects on Adhesion Formation, which open new insights in its pathogenesis and indicate the importance of a careful strain selection for animal studies.

Gere S Dizerega – One of the best experts on this subject based on the ideXlab platform.

  • Reduction of Post-Surgical Adhesion Formation with Tranilast
    The Journal of surgical research, 2007
    Co-Authors: Kevin Cooper, Gere S Dizerega, Janel Young, Scott Wadsworth, Helen Cui, Kathleen E. Rodgers
    Abstract:

    Background Preclinical studies using the rabbit sidewall and double uterine horn models were used to assess time and dose response of tranilast delivered via subcutaneous pump, p.o., or as an intraperitoneal bolus in viscoelastic gels as well as an intraperitoneal biodegradable poly(p-dioxanone) fiber in reducing Adhesions compared to vehicle controls. Materials and methods New Zealand white rabbits underwent laparotomy followed by: 1) uterine horn abrasion and peripheral devascularization or 2) cecal abrasion and sidewall deperitonealization. Tranilast treatment using various vehicles and dosages was compared to vehicle alone versus no treatment. Animals were euthanized after 7 to 21 days. Adhesion Formation was assessed by two independent observers. Results There were reductions in Adhesion Formation when drug was delivered topically, but oral drug alone was not effective. When tranilast was given preoperatively, oral drug added to the Adhesion reduction of intraperitoneal administered drug. Tranilast in a viscoelastic carrier as well as in a biodegradable fiber was effective at reducing Adhesions in the double uterine horn model. The slow release of tranilast from a biodegradable rod produced overall the best results. There were no safety issues. Conclusion Tranilast was effective in reducing Adhesions when given in a variety of vehicles in different rabbit models of Adhesion Formation. Overall, the sustained intraperitoneal delivery of tranilast from biodegradable fibers was the most suitable for clinical testing.

  • Reduction of Adhesion Formation in rabbits by intraperitoneal administration of lazaroid formulations.
    Human reproduction (Oxford England), 1998
    Co-Authors: Kathleen E. Rodgers, Wefki Girgis, Joseph D. Campeau, K St Amand, Gere S Dizerega
    Abstract:

    Adhesion Formation is a major source of postoperative morbidity and mortality. In this study, the ability of a variety of lazaroid formulations [the antioxidant 21-aminosteroid PNU74006F (tirilazad) and the non-steroidal 2-methylaminochroman derivative PNU83,836E] to reduce i.p. Adhesion Formation in three rabbit models was examined. In initial studies, PNU83836E was administered via Alzet miniosmotic pump to the site of injury. In the sidewall and double uterine horn models, PNU83,836E was administered via Alzet miniosmotic pump for the entire postoperative interval. In the sidewall model, there was a dose-dependent reduction in the area of the sidewall injury that was involved in Adhesions. In the double uterine horn model, PNU83,836E was administered via Alzet miniosmotic pump to the area of injury for 1, 2, 3 or 7 days. Administration for as little as 24 h after surgery significantly reduced the extent of Adhesion Formation and the reduction was increased if it was administered for longer. Further studies were conducted in which various lazaroid formulations were administered as a bolus at the end of surgery. In both the sidewall and double uterine horn models, administration of either PNU83,386E (in citrate buffer) or PNU74006F (in cyclodextrin or lipid emulsion vehicles) at the end of surgery reduced Adhesion Formation. Administration of a bolus of PNU74006F 10 min prior to initiation of surgery with or without additional treatment at the end of surgery further increased its efficacy in the reduction of Adhesion Formation. Administration of a minimum of 1.5 mg before and after surgery (3 mg total) was required for maximal efficacy. These studies demonstrate that pre- and postoperative administration of either a steroidal (PNU74006F) or non-steroidal (PNU83,836E) lazaroid intraperitoneally reduced the Formation and reFormation of postoperative Adhesions in three animal models.

  • Reduction of Adhesion Formation by Intraperitoneal Administration of Various Anti-Inflammatory Agents
    Journal of investigative surgery : the official journal of the Academy of Surgical Research, 1998
    Co-Authors: Kathleen E. Rodgers, Wefki Girgis, Joseph D. Campeau, K St Amand, Gere S Dizerega
    Abstract:

    Adhesion Formation is a major source of postoperative morbidity and mortality. Therefore, the reduction of postoperative Adhesion Formation would be of clinical benefit. Various modalities have been shown to reduce Adhesion Formation, including fibrinolytic enzymes, nonsteroidal anti-inflammatory drugs, and barriers that reduce the apposition of sites of potential Adhesion Formation. In this report, the ability of three compounds with different mechanisms of action, all-trans-retinoic acid, quinacrine, and dipyridamole, to reduce the Formation of intraperitoneal Adhesions was examined in two rabbit models. In the sidewall model, the medicaments were administered via an Alzet miniosmotic pump for the entire postoperative interval. With all three agents, there was a reduction in the area of the sidewall injury that was involved in Adhesions to the cecum and the bowel at both doses tested. In the same model, quinacrine also reduced the area of the sidewall injury that was involved in Adhesions to the cecum and the bowel. At the higher concentrations of quinacrine, there was a deposition and walling off of the quinacrine at the site of delivery. In the double uterine horn model (DUH), the medicaments were administered via an Alzet miniosmotic pump to the area of injury for either 1, 2, 3, or 7 days. Administration of all three compounds for as little as 24 h after surgery significantly reduced the extent of Adhesion Formation. However, there was a further reduction in the amount of Adhesion when the retinoic acid or dipyridamole was administered for 72 h postoperatively. However, when the quinacrine was administered for longer times postoperatively, the amount of Adhesion reduction observed was less. These studies demonstrate that postoperative administration of retinoic acid, quinacrine, or dipyridamole to the site of injury reduced the Formation of postoperative Adhesions in two animal models.

Maria Mercedes Binda – One of the best experts on this subject based on the ideXlab platform.

  • The impact of the learning curve on Adhesion Formation in a laparoscopic mouse model
    Fertility and sterility, 2011
    Co-Authors: Roberta Corona, Carlos Roger Molinas, Maria Mercedes Binda, Jasper Verguts, Ron Schonman, Philippe Koninckx
    Abstract:

    Objective To evaluate the impact of surgeon training on Adhesion Formation in a laparoscopic mouse model. Laparoscopic surgery and bowel manipulation was demonstrated to enhance postoperative Adhesion Formation. Design Prospective randomized, controlled trial. Setting University laboratory research center. Animal(s) 200 BALB/c and 200 Swiss female mice. Intervention(s) Adhesions were induced by opposing bipolar lesions and 60 minutes of pneumoperitoneum. Each surgeon operated on 80 mice (40 Swiss and 40 BALB/c), the only variable thus being his/her increasing experience. Some surgeons were already experienced gynecologists, others were starting their training. Main Outcome Measure(s) End points were the duration of surgery while performing the lesions. The Adhesion Formation was scored quantitatively (proportion and total) and qualitatively (extent, type, and tenacity) after 7 days. Result(s) With training, duration of surgery and Adhesion Formation decreased exponentially for all surgeons, whether experienced or not. Experienced surgeons had initially a shorter duration of surgery, less Adhesion Formation, and less de novo Adhesions than inexperienced surgeons. Conclusion(s) These data suggest that laparoscopic skills improve with training, leading to a decrease in the duration of surgery and Formation of Adhesions. Therefore completion of a standardized learning curve should be mandatory when initiating Adhesion Formation studies both in laboratory or clinical setting.

  • Angiogenic factors in peritoneal Adhesion Formation
    Gynecological Surgery, 2006
    Co-Authors: Carlos Roger Molinas, Maria Mercedes Binda, Philippe Robert Koninckx
    Abstract:

    Abdominal surgery is considered as the leading cause of peritoneal Adhesions and almost universally as adhesiogenic. Peritoneal injury at the time of surgery initiates an inflammatory reaction determining fibrin deposition on the wound surface. Depending on the balance between the different components of the plasminogen system, this fibrin can be either lysed, leading to normal peritoneal healing, or organised, serving as a scaffold for fibroblast ingrowth, extracellular matrix deposition and angiogenesis, leading to Adhesion Formation. The mechanism underlying the predisposition to form Adhesions in some patients and in some specific anatomic sites and not in others after similar surgical procedures remains unknown. In spite of the many attempts proposed over the years for reducing the incidence of Adhesion Formation, peritoneal Adhesions remain a major clinical problem, inducing intestinal obstruction, pelvic pain, female infertility and difficulties at the time of re-operation. The available evidence indicates that understanding the Adhesion Formation process at the molecular level is essential for developing successful strategies for preventing Adhesions. Fortunately, the advancement in molecular biology during the last years has led to the identification of many molecules with the potential of regulating inflammatory and immune responses, tissue remodelling and angiogenesis, key events in peritoneal healing and Adhesion Formation. This review focuses on the role of angiogenesis and angiogenic factors in peritoneal Adhesion Formation.

  • Adhesion Formation and interanimal variability in a laparoscopic mouse model varies with strains
    Fertility and sterility, 2005
    Co-Authors: Carlos Roger Molinas, Maria Mercedes Binda, Rudi Campo, Philippe Koninckx
    Abstract:

    Adhesion Formation after laparoscopic surgery was evaluated in mice of different strains. More Adhesions were observed in Swiss, NMRI, and BALB/c mice, with less interanimal variability in BALB/c mice. These data point to genetics effects on Adhesion Formation, which open new insights in its pathogenesis and indicate the importance of a careful strain selection for animal studies.

Joel Rosenbloom – One of the best experts on this subject based on the ideXlab platform.

  • Trametinib prevents mesothelial-mesenchymal transition and ameliorates abdominal Adhesion Formation.
    The Journal of surgical research, 2018
    Co-Authors: Edward J. Macarak, Christine E. Lotto, Deepika Koganti, Xiaoling Jin, Peter J. Wermuth, Anna-karin Olsson, Matthew Montgomery, Joel Rosenbloom
    Abstract:

    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 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 αSMA 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 αSMA. 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.