orabase and Peritoneal-Diseases

Intra-peritoneal adhesions are frequent following abdominal surgery and are the most common cause of small bowel obstructions. A hyaluronic acid/carboxymethylcellulose (HA/CMC) film adhesion barrier has been shown to reduce adhesion formation in abdominal surgery. An HA/CMC powder formulation was developed for application during laparoscopic procedures.. This was an exploratory, prospective, randomised, single-blind, parallel-group, Phase IIIb, multicentre study conducted at 15 hospitals in France to assess the safety of HA/CMC powder versus no adhesion barrier following laparoscopic colorectal surgery. Subjects ≥18 years of age who were scheduled for colorectal laparoscopy (Mangram contamination class I‒III) within 8 weeks of selection were eligible, regardless of aetiology. Participants were randomised 1:1 to the HA/CMC powder or no adhesion barrier group using a centralised randomisation list. Patients assigned to HA/CMC powder received a single application of 1 to 10 g on adhesion-prone areas. In the no adhesion barrier group, no adhesion barrier or placebo was applied. The primary safety assessments were the incidence of adverse events, serious adverse events, and surgical site infections (SSIs) for 30 days following surgery. Between-group comparisons were made using Fisher's exact test.. Of those randomised to the HA/CMC powder (n = 105) or no adhesion barrier (n = 104) groups, one patient in each group discontinued prior to the study end (one death in each group). Adverse events were more frequent in the HA/CMC powder group versus the no adhesion barrier group (63% vs. 39%; P <0.001), as were serious adverse events (28% vs. 11%; P <0.001). There were no statistically significant differences between the HA/CMC powder group and the no adhesion barrier group in SSIs (21% vs. 14%; P = 0.216) and serious SSIs (12% vs. 9%; P = 0.38), or in the most frequent serious SSIs of pelvic abscess (5% and 2%; significance not tested), anastomotic fistula (3% and 4%), and peritonitis (2% and 3%).. This exploratory study found significantly higher rates of adverse events and serious adverse events in the HA/CMC powder group compared with the no adhesion barrier group in laparoscopic colorectal resection.. ClinicalTrials.gov NCT00813397. Registered 19 December 2008.

Topics: Abscess; Adult; Aged; Carboxymethylcellulose Sodium; Colon; Female; Fistula; France; Humans; Hyaluronic Acid; Laparoscopy; Male; Middle Aged; Peritoneal Diseases; Peritonitis; Powders; Prospective Studies; Rectum; Risk Assessment; Risk Factors; Single-Blind Method; Surgical Wound Infection; Time Factors; Tissue Adhesions; Treatment Outcome

To evaluate the efficacy of hyaluronate/carboxymethylcellulose (HA/CMC) membrane and melatonin separately and in combination in reducing adhesion reformation following adhesiolysis of surgically induced adhesions in a rat uterine horn adhesion model.. A randomized, prospective study was carried out in a university animal laboratory. Ninety-eight female Sprague-Dawley albino rats were operated on. Following infliction of standard lesions, all the animals underwent second operations after one week. In all the animals, there were dense and vascular adhesions only between the uterine horns. These adhesions were lysed. Following the completion of adhesiolysis, the animals were randomized before closure of the abdomen to one of four groups (melatonin, HA/CMC membrane, combination of melatonin and HA/CMC membrane, control group). Seven days after the second surgery, the third operations were carried out and adhesions were scored. The main outcome measures were type, tenacity, and extent of adhesions. Total adhesion scores were determined.. Adhesion scores in the melatonin and HA/CMC membrane groups were similar, and significantly lower than those in the control group (P < 0.001). Adhesion scores in the combination group were lower than those in the other three groups (P < 0.001).. Melatonin and HA/CMC membrane are both effective separately in preventing adhesion reformation following adhesiolysis, but in combination they are significantly more beneficial.

Topics: Administration, Topical; Animals; Carboxymethylcellulose Sodium; Combined Modality Therapy; Disease Models, Animal; Female; Free Radical Scavengers; Hyaluronic Acid; Melatonin; Membranes, Artificial; Peritoneal Diseases; Postoperative Complications; Prospective Studies; Random Allocation; Rats; Rats, Sprague-Dawley; Tissue Adhesions; Treatment Outcome; Uterine Diseases; Uterus

Postoperative abdominal adhesions are associated with significant morbidity and mortality, placing a substantial burden on healthcare systems worldwide. Development of a bioresorbable membrane containing up to 23 percent glycerol and chemically modified sodium hyaluronate/carboxymethylcellulose offers ease of handling and has been shown to provide significant postoperative adhesion prevention in animals. This study was designed to assess the safety of glycerol hyaluronate/carboxymethylcellulose and to evaluate its efficacy in reducing the incidence, extent, and severity of postoperative adhesion development in surgical patients.. Twelve centers enrolled 120 patients with ulcerative colitis or familial polyposis who were scheduled for a restorative proctocolectomy and ileal pouch-anal anastomosis with diverting loop ileostomy. Before surgical closure, patients were randomized to no anti-adhesion treatment (control) or treatment with glycerol hyaluronate/carboxymethylcellulose membrane under the midline incision. At ileostomy closure, laparoscopy was used to evaluate the incidence, extent, and severity of adhesion formation to the midline incision.. Data were analyzed using the intent-to-treat population. Treatment with glycerol hyaluronate/carboxymethylcellulose resulted in 19 of 58 patients (33 percent) with no adhesions compared with 6 of 60 adhesion-free patients (10 percent) in the no treatment control group (P = 0.002). The mean extent of postoperative adhesions to the midline incision was significantly lower among patients treated with glycerol hyaluronate/carboxymethylcellulose compared with patients in the control group (P < 0.001). The severity of postoperative adhesions to the midline incision was significantly less with glycerol hyaluronate/carboxymethylcellulose than with control (P < 0.001). Adverse events were similar between treatment and no treatment control groups with the exception of abscess and incisional wound complications were more frequently observed with glycerol hyaluronate/carboxymethylcellulose.. Glycerol hyaluronate/carboxymethylcellulose was shown to effectively reduce adhesions to the midline incision and adhesions between the omentum and small bowel after abdominal surgery. Safety profiles for the treatment and no treatment control groups were similar with the exception of more infection complications associated with glycerol hyaluronate/carboxymethylcellulose use. Animal models did not predict these complications.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Aged; Aged, 80 and over; Biocompatible Materials; Carboxymethylcellulose Sodium; Colonic Pouches; Female; Glycerol; Humans; Hyaluronic Acid; Ileostomy; Male; Membranes, Artificial; Middle Aged; Peritoneal Diseases; Proctocolectomy, Restorative; Prospective Studies; Severity of Illness Index; Single-Blind Method; Tissue Adhesions; Treatment Outcome

To evaluate the efficacy of a hyaluronate-carboxymethylcellulose (HA-CMC) barrier for prevention of pelvic adhesion formation in women undergoing primary cytoreductive surgery with radical oophorectomy for locally advanced epithelial cancer.. Between 3/1/01 and 3/1/02, all patients undergoing primary surgery for locally advanced FIGO Stage III-IV epithelial ovarian cancer were prospectively offered study enrollment. Radical oophorectomy (en bloc rectosigmoid colectomy) with total pelvic peritonectomy was performed as clinically indicated. Intestinal continuity was reestablished via stapled anastomosis following complete cytoreduction of pelvic disease. The entire pelvic peritoneal defect was covered with subdivided sheets of HA-CMC (6.5 cm x 5.0 cm) using a 'quilting' technique. The abdominal wall incision site was not treated with adhesion preventive measures. At second-look surgery, four-quadrant pelvic (treated area) and abdominal wall (untreated internal control) adhesion scores were assigned using a previously validated scoring system. Statistical analysis for differences in mean pelvic and abdominal wall adhesion scores was performed using Student's t test.. Fourteen patients satisfied all inclusion criteria. Abdominal wall adhesions were noted in 92.9% of patients. In the pelvis, the dorsal peritoneal surfaces were the most common sites of adhesion formation (42.9%). Overall, the mean pelvic (treated) adhesion score was statistically significantly lower (0.91, SD +/- 1.04) than the mean abdominal wall (untreated control) score (5.56, SD +/- 4.55, P = 0.02). There were no instances of intestinal anastomotic leak, and no peri-operative complications directly attributable to HA-CMC were observed.. Placement of a HA-CMC barrier is associated with a significant reduction in the extent and density of pelvic adhesion formation following radical oophorectomy and pelvic peritonectomy for locally advanced epithelial ovarian cancer.

Topics: Abdominal Wall; Aged; Carboxymethylcellulose Sodium; Female; Humans; Hyaluronic Acid; Membranes, Artificial; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Ovariectomy; Peritoneal Diseases; Prospective Studies; Tissue Adhesions

To evaluate efficacy and safety of IP administration of high-molecular-weight carboxymethylcellulose (HMW CMC) for the prevention of postoperative intra-abdominal adhesions in ponies.. 10 ponies.. A 1% solution of HMW CMC was instilled intra-abdominally prior to surgery in 5 ponies, whereas 5 control ponies did not receive HMW CMC. Postoperative adhesions were induced by use of a bowel-abrasion method comprising laparotomy, typhlotomy, and abrasion of jejunal serosa at multiple sites with placement of 3 sutures at each site. Day of surgery was day 0. After surgery, ponies were monitored, and hematologic, serum biochemical, and peritoneal fluid analyses were performed on days 1, 2, 3, 5, 7, and 10. On day 10, ponies were euthanatized. Intra-abdominal adhesions were recorded, and tissue samples were collected for histologic examination.. A significantly greater number of adhesions, number of multiple adhesions, and mean incidence of adhesions were identified in control ponies, compared with CMC-treated ponies. Mean peritoneal fluid WBC count on day 7 and serum fibrinogen concentrations on days 5 and 7 were significantly higher in control ponies, compared with CMC-treated ponies. Results of serum biochemical analyses did not differ significantly between the 2 groups.. Intra-abdominal use of 1% HMW CMC during surgery was effective for preventing postoperative adhesions in ponies. Use of HMW CMC did not have detrimental effects on wound healing, intra-abdominal defenses, or patient health. A 1% solution of HMW CMC may be used routinely during abdominal surgery of horses for prevention of postoperative adhesions.

Topics: Abdomen; Animals; Carboxymethylcellulose Sodium; Female; Horse Diseases; Horses; Male; Molecular Weight; Peritoneal Diseases; Postoperative Complications; Solutions; Tissue Adhesions

Adhesion formation that occurred after alkali-induced injury of the cecum was used as a novel adhesion model in rats, and it was compared with that of a common adhesion model after abrading the cecum. Using the novel adhesion model, inhibition of adhesion formation by a chymase inhibitor, Suc-Val-Pro-PheP(OPh)2, and by sodium hyaluronate/carboxymethylcellulose (Seprafilm) was evaluated, and their mechanisms were assessed. The degree of adhesion formation was more severe and more stable in the alkali-induced injury model than in the abrasion-induced injury model. Both the chymase inhibitor and Seprafilm showed significant attenuation of the degree of adhesion 14 days after alkali-induced injury. Chymase activity in the cecum was significantly increased after alkali-induced injury, but it was significantly attenuated by the chymase inhibitor and Seprafilm. Myeloperoxidase and transforming-growth factor (TGF)-β levels were significantly increased after alkali-induced injury, but they were attenuated by both the chymase inhibitor and Seprafilm. At the level of the adhesions, the numbers of both chymase-positive cells and TGF-β-positive cells were significantly increased, but their numbers were reduced by the chymase inhibitor and Seprafilm. In conclusion, a chymase inhibitor attenuated the degree of adhesions to the same degree as Seprafilm in a novel peritoneal adhesion model that was more severe and more stable than the common adhesion model, and not only the chymase inhibitor, but also Seprafilm reduced the chymase increase at the adhesions.

Topics: Animals; Carboxymethylcellulose Sodium; Cecum; Chymases; Disease Models, Animal; Gene Expression; Hyaluronic Acid; Male; Peritoneal Diseases; Peroxidase; Protease Inhibitors; Rats; Rats, Sprague-Dawley; Tissue Adhesives; Transforming Growth Factor beta

To evaluate macro and microscopically the adhesions developed after using the anti-adherence compound sodium hyaluronate and carboxymethylcellulose (SH-CBMC) gel and to determine the volume of the adhesions using a stereological estimation.. The study was experimental, random, comparative, and prospective. The subjects of the study were male Wistar rats divided in three groups (n = 10). Group I (control) included rats with no peritoneal injury. Group II rats had a 2 cm diameter injury created bilaterally in the parietal peritoneum at 3 cm from the abdominal midline with electrocautery coated with physiological solution. Group III rats were given the same injuries and coated with SH-CBMC gel. All groups were followed up postoperatively for 30 days, after which a laparotomy was performed to macroscopically determine the presence and type of adhesions. Experimental models were euthanized with anesthetic overdose and biopsies were taken for histopathological examination and stereological estimate of the volume of adhesions.. Macroscopic adhesions were 20% less prevalent in Group III compared to Group II, which presented 40% more multiple and firm adhesions, unlike in Group III, in which they were unique and lax. There was a statistically significant decrease in the presence and number of adhesions in rats treated with SH-CBMC gel. Inflammatory infiltrate was significantly lower in rats treated with SH-CBMC gel, but there were no differences in connective tissue, fibrosis, and angiogenesis among groups. There was no statistical difference in the overall volume of adhesions among the treatment groups.. SH-CBMC gel reduces macroscopic presence and number of adhesions and the severity of the inflammatory infiltrate.

Topics: Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Gels; Hyaluronic Acid; Laparotomy; Male; Peritoneal Diseases; Peritoneum; Prospective Studies; Random Allocation; Rats; Rats, Wistar; Tissue Adhesions

Abdominal operations are followed by adhesions, a prevalent cause of abdominal pain, and the most frequent cause for bowel obstruction and secondary female infertility. This rat study addresses adhesion prevention capability of Adept(®), Interceed(®), Seprafilm(®), and a novel device, 4DryField(®) PH which is provided as powder and generates its effect as gel.. Sixty-eight male Lewis rats had cecal abrasion and creation of an equally sized abdominal wall defect, and were grouped randomly: A control group without treatment (n=10); two groups treated with 4DryField(®) PH using premixed gel (n=15) or in-situ gel technique (n=16); one group each was treated with Seprafilm(®) (n=8), Interceed(®) (n=9), or Adept(®) (n=10). Sacrifice was on day 7 to evaluate incidence, quality, and quantity of adhesions, as expressed via adhesion reduction rate (AR). Histologic specimens were evaluated. Statistical analyses used ANOVA and unpaired t-tests.. 4DryField(®) PH significantly reduced incidence and severity of adhesions both as premixed gel (AR: 85.2%) and as in-situ made gel (AR: 100%), a comparison between these two application techniques showed no differences in efficacy. Seprafilm(®) did not reduce incidence but severity of adhesions significantly (AR: 53.5%). With Interceed(®) (AR: 3.7%) and Adept(®) (AR: 16.1%) no significant adhesion-reduction was achieved. Except for inflammatory response with Interceed(®), histopathology showed good tissue compatibility of all other devices.. 4DryField(®) PH and Seprafilm(®) showed significant adhesion prevention capabilities. 4DryField(®) PH achieved the highest adhesion prevention effectiveness without restrictions concerning mode of application and compatibility and, thus, is a promising strategy to prevent abdominal adhesions.

Topics: Animals; Carboxymethylcellulose Sodium; Hyaluronic Acid; Male; Membranes, Artificial; Peritoneal Diseases; Postoperative Complications; Random Allocation; Rats; Rats, Inbred Lew; Tissue Adhesions

We aimed to evaluate the effects of the barrier agent sodium carboxymethyl cellulose (SCMC) with and without dexamethasone for the prevention of postoperative adhesion formation in a rat model of postoperative peritoneal adhesion. A total of 160 three-month old male and female Wistar rats underwent a laparotomy, and adhesions were induced by ileocecal abrasion. Rats were randomly assigned to 4 groups (n=40 each): group A, untreated; group B, treated with SCMC only; group C1, treated with SCMC + 3 mg dexamethasone, and group C2, treated with SCMC + 8 mg dexamethasone. After 12 days, adhesion formation and histopathological changes were compared. In groups A, B, C1, and C2, the mortality rates were 10, 5, 5, and 5%, respectively. In groups C1 and C2, the adhesions were filmy and easy to dissect and were milder compared with those in groups A and B. The total adhesion score in group C1 (3.38±0.49) was significantly lower than that of group B (6.01±0.57; P<0.01) or group A (8.01±0.67; P<0.05). There was no significant difference in adhesion formation between groups C1 and C2. Compared with groups A and B, groups C1 and C2 exhibited milder histopathological changes. SCMC in combination with dexamethasone can prevent adhesion formation and is a better barrier agent than SCMC alone. The safety and feasibility of SCMC in combination with dexamethasone to prevent adhesion formation after abdominal surgery warrants further clinical study.

Topics: Animals; Carboxymethylcellulose Sodium; Dexamethasone; Disease Models, Animal; Drug Therapy, Combination; Female; Laparotomy; Male; Peritoneal Diseases; Peritoneum; Postoperative Complications; Random Allocation; Rats, Wistar; Tissue Adhesions

We aimed to compare the effectiveness of linezolid in preventing intraperitoneal adhesions with hyaluronic acid + carboxymethylcellulose (Seprafilm).. Thirty rats were divided randomly into 3 groups: Group I (control), untreated; Group II (Seprafilm); and Group III (linezolid). All rats were sacrificed on the 14th day after surgery. Macroscopic adhesion, inflammation, and fibrosis were evaluated.. The multiple comparisons between groups showed a statistically significant difference for adhesion. There were statistically significant differences between Group I and II and I and III, but no statistically significant difference between Group II and III. The multiple comparisons between the groups showed a statistically significant difference for inflammation and fibrosis. For inflammation and fibrosis, there was a statistically significant difference between Group I and II and I and III, but no statistically significant difference between Group II and III.. The efficiency of linezolid in reducing the formation of intraperitoneal adhesions was statistically significant compared with the control group.

Topics: Acetamides; Animals; Anti-Infective Agents; Biocompatible Materials; Carboxymethylcellulose Sodium; Cecum; Female; Hyaluronic Acid; Injections, Intraperitoneal; Linezolid; Oxazolidinones; Peritoneal Diseases; Postoperative Complications; Random Allocation; Rats; Rats, Wistar; Tissue Adhesions; Treatment Outcome

While bioresorbable solid barriers such as Seprafilm® prevent adhesions, their efficacy is limited to sites of application. The aim of this study was to assess the effectiveness of the sprayable adhesion barrier Sepraspray® in preventing adhesions to sites of direct application and to remote sites.. Intraabdominal adhesions were induced in 30 rats by creating three ischemic buttons on each side of a midline incision. To assess efficacy, Sepraspray (5 mg/button) or Seprafilm (1 cm(2)/button) was applied over three buttons on one side of the peritoneum. Operated control animals received no treatment. On day 7, adhesions were scored as percent of buttons with adhesions. To assess safety, 81 rats underwent a colonic transection repaired with an end-to-end anastomosis. Both barriers were applied circumferentially to anastomoses. Controls received no product. The integrity of healing anastomosed colonic wounds was assessed by burst pressure and tensile strength at days 3, 5, and 7 postoperatively.. The direct application of both Sepraspray and Seprafilm significantly (p < 0.001) reduced adhesion formation compared to controls. While Seprafilm had no remote effect on adhesion formation, Sepraspray significantly (p < 0.001) reduced adhesion formation to contralateral ischemic buttons. Neither barrier affected anastomotic integrity at any time point.. Sepraspray has widespread efficacy throughout the peritoneum in reducing adhesions without compromising intestinal healing. Furthermore, this sprayable alternative offers the potential for easier intraabdominal application.

Topics: Anastomosis, Surgical; Animals; Biocompatible Materials; Carboxymethylcellulose Sodium; Colon; Colonic Diseases; Drug Carriers; Hyaluronic Acid; Male; Membranes, Artificial; Peritoneal Diseases; Postoperative Complications; Powders; Rats; Rats, Wistar; Tissue Adhesions; Treatment Outcome; Wound Healing

Intraperitoneal adhesion is a serious surgical postoperative complication. Using a rat model, we compared the effectiveness of intraperitoneally administered zinc-modified sodium carboxymethyl cellulose (Zn(2+)-SCMC) and hyaluronic acid (HA) in preventing postoperative intraperitoneal adhesions.. Peritoneal adhesions were induced in 120 Wistar rats by scraping the cecal mucosa. The rats were randomized into a no treatment group (n = 40) or into a treatment group in which 3 ml of HA (n = 40) or Zn(2+)-SCMC (n = 40) was administered intraperitoneally before the abdominal wall was closed. Following sacrifice two weeks later, the intraperitoneal adhesions were scored and tissues were examined histologically using HE staining.. Eight animals died, five in the untreated group (mortality rate, 12.5%), two in the HA group (mortality rate, 5.0%) and one in the Zn(2+)-SCMC group (mortality rate, 2.5%). Relative to the untreated group, the incidence of intraperitoneal adhesions was 77.5% in the HA and 48.7% in the Zn(2+)-SCMC group, with the incidence significantly lower in the Zn(2+)-SCMC group (P < 0.001). Both agents prevented intraperitoneal adhesions by promoting the repair of the abdominal serosa.. Administration of Zn(2+)-SCMC was more effective in preventing intraperitoneal adhesions than HA.

Topics: Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Female; Hyaluronic Acid; Male; Peritoneal Diseases; Postoperative Complications; Rats; Rats, Wistar; Tissue Adhesions

This study compared Parietex composite mesh (PCM) with Sepramesh (SM) in terms of strength of tissue incorporation, adhesion formation, and mesh shrinkage, using an animal model.. A two-phase, prospective, randomized study using 44 New Zealand white rabbits. Each animal underwent creation of a standardized ventral hernia defect, followed by repair using either SM or PCM. Half of each group was sacrificed and examined at 1 month, and the remainder at 5 months. Outcomes measurements were strength of incorporation (SOI), type and area of adhesions (AA), and mesh shrinkage.. SOI for PCM was much greater than for SM, both at 1 month (60.8 N versus 42.6 N) and 5 months (70.9 N versus 31.5 N). The incidence of bowel adhesions was lower with PCM than SM, both at 1 month (1 versus 6) and at 5 months (0 versus 4). At 5 months, PCM demonstrated lower AA, both as a percentage of the mesh (5.6% versus 12.8%) and in terms of absolute area involved (321 mm(2) versus 840 mm(2)). PCM underwent considerably more shrinkage than SM, at both 1 month (38.2% versus 18.1%) and 5 months (17.4% versus 6.1%).. PCM demonstrated a substantially stronger SOI, which improved over time, and SOI of SM decreased. PCM was also superior in terms of adhesion prevention, but underwent considerably more shrinkage in this experimental model.

Topics: Abdominal Wall; Animals; Carboxymethylcellulose Sodium; Collagen; Disease Models, Animal; Equipment Design; Hernia, Ventral; Hyaluronic Acid; Hydrogel, Polyethylene Glycol Dimethacrylate; Intestinal Diseases; Omentum; Peritoneal Diseases; Polyesters; Polypropylenes; Prospective Studies; Rabbits; Random Allocation; Surface Properties; Surgical Mesh; Time Factors; Tissue Adhesions

The purpose of this study was to compare the effects of anti-adhesion materials in postoperative adhesions.. Rats were assigned to five groups: Group 1: Control. Group 2: chitin layers were used. Group 3: Na-hyaluronate / carboxymethylcellulose layers were used. Group 4: Na-hyaluronate gel was poured into the abdomen. Group 5: methylprednisolone was injected. The adhesion frequency and grade were scored according to Granat. Blood was taken for Hb, AST, BUN and albumin levels determination.. The adhesion frequencies (right and left) and grades were as follow in Groups; I: 82%, 91%, 2.63 +/- 1.22; II: 8.3%, 25%, 0.58 +/- 0.66; III: 17%, 33%, 1.08 +/- 1.08; IV: 50%, 58%, 1.41 +/- 1.44; V: 50%, 42%, 1.41 +/- 1.50. The adhesion phase in all study groups was found significantly low compared to control group, p < 0.05. No difference was observed among serologic and hematological parameters in all groups.. All the materials used significantly lowered the adhesion frequency and grade.

Topics: Abdominal Cavity; Animals; Anti-Inflammatory Agents; Biocompatible Materials; Carboxymethylcellulose Sodium; Chitin; Disease Models, Animal; Female; Hyaluronic Acid; Membranes, Artificial; Methylprednisolone; Peritoneal Diseases; Postoperative Complications; Rats; Rats, Wistar; Severity of Illness Index; Tissue Adhesions; Wound Healing

To investigate the effectiveness of melatonin in preventing post-operative adhesion formation and to compare it with the efficacy of hyaluronate/carboxymethylcellulose membrane in a rat model.. Following pilot studies, 35 rats were operated on in the full study. In 15 animals (group one), 10 standard lesions were inflicted in each uterine horn (total 30 horns) and melatonin was applied before closure of the abdomen. In the second group, 20 animals were operated on and one of the uterine horns (total 20 horns) with standard lesions was treated with hyaluronate/carboxymethylcellulose membrane and the other uterine horn served as a control. Second-look operations were performed 1 week later and adhesion scores were compared.. The adhesion scores of uterine horns treated with melatonin and of uterine horns treated with hyaluronate/carboxymethylcellulose membrane were significantly lower than the scores of the controls (P < 0.001). There was no statistically significant difference between the adhesion scores of uterine horns treated with melatonin and of uterine horns treated with hyaluronate/carboxymethylcellulose membrane (P > 0.05).. Both melatonin and hyaluronate/carboxymethylcellulose membrane were effective in prevention of adhesion formation in a rat uterine horn model.

Topics: Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Female; Free Radical Scavengers; Hyaluronic Acid; Melatonin; Membranes, Artificial; Peritoneal Diseases; Postoperative Complications; Rats; Rats, Wistar; Tissue Adhesions

There is a high incidence of adhesions after ventral hernia repair with polypropylene mesh. The purpose of the present study was to evaluate the efficacy of Seprafilm in the prevention of adhesion formation and effect on peritoneal fibrinolytic activity.. An incisional hernia model was created in rats. In the experimental group Seprafilm was placed between polypropylene mesh and abdominal organs. On the 14th day adhesions were evaluated and tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), plasminogen activator inhibitor (PAI) type 1 and 2 were measured in peritoneal biopsy specimens.. Adhesions were significantly reduced in the Seprafilm group (P = 0.002). Nevertheless, there were no difference between the two groups in levels of tPA, PAI-1 and PAI-2. However, the levels of uPA were significantly decreased in the Seprafilm group.. The adhesion preventive effect of Seprafilm is not directly related in peritoneal fibrinolytic activity. Instead, the physical properties (barrier, hydroflotation and sliconizing effect) of the membrane are primarily responsible for adhesion prevention.

Topics: Abdominal Wall; Animals; Carboxymethylcellulose Sodium; Female; Fibrinolysis; Hyaluronic Acid; Membranes, Artificial; Peritoneal Diseases; Peritoneum; Plasminogen Inactivators; Polypropylenes; Postoperative Complications; Rats; Rats, Wistar; Surgical Mesh; Tissue Adhesions; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

Intraperitoneal placement of prosthetic mesh causes adhesion formation after laparoscopic incisional hernia repair. A prosthesis that prevents or reduces adhesion formation is desirable. In this study, 21 pigs were randomized to receive laparoscopic placement of plain polypropylene mesh (PPM), expanded polytetrafluoroethylene (ePTFE), or polypropylene coated on one side with a bioresorbable adhesion barrier (PPM/HA/CMC). The animals were sacrificed after 28 days and evaluated for adhesion formation. Mean area of adhesion formation was 14% (SD+/-15) in the PPM/HA/CMC group, 40% (SD+/-17) in the PPM group, and 41% (SD+/-39) in the ePTFE group. The difference between PPM/HA/CMC and PPM was significant ( P=0.013). A new visceral layer of mesothelium was present in seven out of seven PPM/HA/CMC cases, six out of seven PPM cases, and two out of seven ePTFE cases. Thus, laparoscopic placement of PPM/HA/CMC reduces adhesion formation compared to other mesh types used for laparoscopic ventral hernia repairs.

Topics: Abdominal Wall; Animals; Biocompatible Materials; Carboxymethylcellulose Sodium; Coated Materials, Biocompatible; Female; Hernia, Ventral; Hyaluronic Acid; Intestines; Laparoscopy; Peritoneal Diseases; Polypropylenes; Polytetrafluoroethylene; Surgical Mesh; Swine; Tissue Adhesions

Treatments addressing variously theorised pathophysiological mechanisms of small intestinal adhesions have been reported. This study applied those classes of treatments to the most clinically relevant aetiology of post operative adhesions.. Treatments addressing the pathophysiology of ischaemia-reperfusion induced adhesions would accordingly reduce the incidence of adhesions from this model.. Four classes of treatments were administered for 72 h to 16 foals subjected to complete ischaemia followed by reperfusion to create peritoneal adhesions. These groups were: 1) FPG group--flunixin meglumine (1.1 mg/kg bwt i.v., divided q.i.d.), potassium penicillin G (22,000 iu/kg bwt i.v., q.i.d.) and gentamicin (2.2 mg/kg bwt i.v., t.i.d.); 2) HEP group--heparin (80 iu/kg bwt subcut., b.i.d.); 3) DMSO group--dimethylsulphoxide (DMSO) (20 mg/kg bwt [diluted in 500 ml normal saline] i.v., b.i.d.); and 4) SCMC group--sodium carboxymethylcellulose (500 ml 3% sterile solution intraperitoneally, administered only at the beginning of surgery).. Post operative intestinal obstruction did not occur in any foal. After 10 days, necropsy revealed bowel-to-bowel adhesions in none of the FPG or DMSO groups, in 2/4 of the SCMC group, in 3/4 of the HEP group and 5/6 foals subjected to the procedure without treatment (UIR group).. Inhibition of the inflammation associated with ischaemia and reperfusion in foals treated with FPG or DMSO decreased small intestinal adhesions in foals.. Although anti-inflammatory therapy was shown to eliminate bowel-bowel adhesions in this controlled study, it must be remembered that clinical cases are without control. These therapies are advised to improve the result but are unlikely to eliminate the problem.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Carboxymethylcellulose Sodium; Dimethyl Sulfoxide; Heparin; Horse Diseases; Horses; Intestinal Diseases; Intestine, Small; Ischemia; Peritoneal Diseases; Peritoneum; Postoperative Complications; Random Allocation; Reperfusion Injury; Tissue Adhesions

Intraperitoneal adhesions are a significant problem (increased morbidity, mortality, and cost) for patients undergoing abdominal procedures. Although a variety of approaches (e.g., fibrinolytic agents, anti-inflammatory drugs, or barrier/separation methods) have been used with some success in preventing adhesions, a comparison of these different modalities has yet to be performed in a model that objectively measures intraperitoneal adhesion formation. Our objectives were to establish an objective, reproducible model of intraperitoneal adhesion formation and to establish efficacy of different treatment modalities in decreasing the strength and extent of intraperitoneal adhesions. In this two-part study, a rat model establishing an objective measure of both the strength and extent of intraperitoneal adhesions was used to compare different treatment modalities. Fibrinolytic agents [recombinant tissue plasminogen activator (rtPA), streptokinase, and urokinase], anti-inflammatory drugs (dexamethasone and tolmetin sodium), and barrier methods [sodium carboxymethylcellulose (CMC), and sodium hyaluronate] and a control group were compared in the first phase. In the second phase, the two most successful agents (rtPA, CMC) were compared both alone and in combination against a commercially available barrier agent (Seprafilm) and a control group. In the first phase of the study, rtPA was the only agent that had a statistically significant effect in decreasing the strength of adhesions. CMC was the only agent that demonstrated a decrease in the extent of adhesions, and the difference tended toward significance. In the second phase, the combination of rtPA and CMC showed a significant decrease in both the strength and extent of adhesions when compared with those of the control group. This decrease was also observed in the group treated with Seprafilm, which showed no difference from the rtPA + CMC group. We conclude that, in this reproducible adhesion model, only the combination of rtPA + CMC and Seprafilm significantly reduced both the strength and the extent of intraperitoneal adhesions.

Topics: Animals; Anti-Inflammatory Agents; Biocompatible Materials; Carboxymethylcellulose Sodium; Disease Models, Animal; Fibrinolytic Agents; Hyaluronic Acid; Male; Membranes, Artificial; Peritoneal Diseases; Rats; Rats, Sprague-Dawley; Tissue Adhesions

Peritoneal adhesions continue to be a significant cause of postoperative complications. Elucidating the origin of these adhesions has been hampered by the lack of a reproducible animal model. The purpose of this study was to create a standardized model in which a single, specific adhesion could be objectively measured. With this model the kinetics of adhesion formation were then evaluated. A variety of potential antiadhesive agents were then tested and compared.. In this study a reproducible, quantitative rat model was developed that used uniform defects on the peritoneal wall and cecal surface. The resulting adhesions were subsequently scored, and their strength was measured with a tensiometer. An evaluation of the kinetics of peritoneal adhesion formation was obtained by using a timed removal of silicone elastomer sheeting held between the two injured surfaces. The following antiadhesive agents were evaluated: Ringer's lactate solution; dextran 70 (32%); modified carboxymethylcellulose (1.0% and 2.0%); an absorbable barrier of specially knitted material composed of oxidized regenerated cellulose; fibrin sealant; silicone elastomer film; and expanded polytetrafluoroethylene membrane.. Evaluation of the kinetics of peritoneal adhesion formation indicated that the susceptibility for adhesion formation was significantly decreased or eliminated after the first 36 hours. Evaluation of antiadhesion agents indicated that the magnitude of adhesion prevention was directly proportional to the agent's ability to remain at the site of injury during the critical period of adhesion formation. Permanent barriers (silicone elastomer film, expanded polytetrafluoroethylene membrane) provided the greatest antiadhesion effect but were not believed to be ideal agents because they remained at the site of injury well after the critical period of adhesion formation. The incidence of adhesion formation for the other agents was as follows: control (34 of 34), Ringer's lactate (12 of 12), absorbable barrier of knitted cellulose (10 of 10), 32% dextran 70 (8 of 12), 1% carboxymethylcellulose (6 of 12), fibrin sealant (4 of 9), and 2% carboxymethylcellulose (4 of 12).. The efficacy of antiadhesion agents appears to be related to the agent's viscosity, ability to coat the wound surface, and residence time at the site of injury. In this rat model an agent that remained on the injured surfaces for at least 36 hours after injury appeared to be more effective in reducing adhesion formation than an agent with a shorter residence time.

Topics: Animals; Biocompatible Materials; Carboxymethylcellulose Sodium; Cecal Diseases; Cellulose; Dextrans; Disease Models, Animal; Disease Susceptibility; Female; Fibrin Tissue Adhesive; Isotonic Solutions; Kinetics; Membranes, Artificial; Peritoneal Diseases; Polytetrafluoroethylene; Postoperative Complications; Rats; Rats, Sprague-Dawley; Ringer's Lactate; Silicone Elastomers; Stress, Mechanical; Time Factors; Tissue Adhesions

Although intraperitoneal administration of sodium carboxymethylcellulose (SCMC) prevents the formation of adhesions following laparotomy in rats, it remains unknown whether SCMC treatment prevents the recurrence of preformed peritoneal adhesions following surgical lysis. Additionally, the optimal amount of SCMC required for adhesion prevention, as well as the effects of SCMC upon the healing of bowel anastomoses, has yet to be determined. To study this, 114 male rats underwent laparotomy and adhesion induction via peeling of the cecal serosa with a gauze sponge. Two weeks later, all animals again underwent laparotomy, the adhesions were graded, and surgical lysis of adhesions was performed. Following this, 3 to 12 ml of either normal saline or 1% SCMC solution was instilled into the peritoneal cavity prior to closure. A segment of small bowel was transected and reanastomosed prior to administration of SCMC or saline in another group of 70 rats. After an additional 2 weeks, the animals were sacrificed, the adhesions graded, and all the abdominal contents removed for fixation. The results show that treatment with high volume (i.e., 12 ml) intraperitoneal SCMC prevents reformation of adhesions following surgical lysis. This effect is demonstrated by a proportionate and significant decrease in the incidence of intraabdominal adhesions associated with administration of increasing amounts of SCMC (P < 0.05). While high volume SCMC did prevent adhesion of peritoneal structures to newly formed small bowel anastomoses, SCMC did not impair anastomotic healing.

Topics: Animals; Carboxymethylcellulose Sodium; Intestine, Small; Laparotomy; Male; Peritoneal Diseases; Rats; Rats, Sprague-Dawley; Recurrence; Tissue Adhesions; Vitamin E

Various regimens to reduce postoperative intraperitoneal adhesion formation have been tested; however, none has been consistently successful. The purpose of this study was to compare the efficacy of three compounds instilled into the peritoneal cavity--32% dextran 70, 0.9% normal saline and sodium carboxymethylcellulose--to no therapy on their ability to prevent postoperative adhesion formation in the New Zealand white rabbit. Bilateral posterior uterine horn incisions and cecal and transverse colon abrasions were performed during a two-phased study on each of 25 rabbits that were randomly assigned in a blind fashion into one of four study groups. Two weeks postoperatively, each rabbit underwent an autopsy to assess the magnitude of intraperitoneal adhesion formation. Adhesion scores were determined by counting the number of adhesions and assigning one or two points for each thin, filmy or dense, broad adhesion. As compared to no therapy, all three substances tested significantly reduced adhesion formation. Although 32% dextran 70 and 0.9% normal saline showed similar results, the degree of adhesion formation was reduced most significantly with sodium carboxymethylcellulose (P < .002) Sodium carboxymethylcellulose is effective in preventing postoperative adhesion formation in the New Zealand white rabbit.

Topics: Animals; Carboxymethylcellulose Sodium; Dextrans; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Genital Diseases, Female; Instillation, Drug; Peritoneal Diseases; Postoperative Complications; Rabbits; Random Allocation; Severity of Illness Index; Single-Blind Method; Sodium Chloride; Tissue Adhesions

The deposition of fibrin in the peritoneal cavity leads to fibrous adhesion formation. Recombinant tissue plasminogen activator (rtPA), delivered locally, was investigated as a method of preventing adhesion formation. Six standardised areas of peritoneal ischaemia were formed in each of 36 male Wistar rats randomised to three intraperitoneal treatments: (A) no treatment control; (B) carboxymethylcellulose gel; (C) rtPA-carboxymethylcellulose gel combination. At 1 week all animals underwent relaparotomy and the number of ischaemic sites with an adhesion counted by an independent observer. rtPA-treated animals formed fewer adhesions compared with gel alone or controls (median number of adhesions 1.5 versus 2.5 versus 5, P < 0.001, ANOVA). Intraperitoneal rtPA in a slow-release formulation is able to reduce adhesion formation significantly in an animal model and may prove to have clinical benefit.

Topics: Administration, Topical; Animals; Carboxymethylcellulose Sodium; Drug Carriers; Gels; Laparotomy; Male; Peritoneal Diseases; Rats; Rats, Wistar; Recombinant Proteins; Tissue Adhesions; Tissue Plasminogen Activator

Previous studies have shown that dietary supplements of vitamin E or the intraperitoneal administration of sodium carboxymethyl cellulose (SCMC) solution reduces postoperative adhesions by approximately 50%. The aim of this study was to determine whether there is a synergistic beneficial effect of vitamin E and SCMC in reducing postoperative adhesions.. Sixty Sprague-Dawley rats were fed an identical diet containing 32 IU vitamin E/kg and were divided into four main groups: group A (control) and groups B, C, and D (experimental). Group D was further subdivided into three subgroups (D1, D2, and D3). Oral supplements of vitamin E in doses of 10 IU, 30 IU, and 30 IU/kg body weight were given to subgroups D1, D2, and D3 and group B, respectively, 5 days before operation and were continued until the fourteenth postoperative day when all animals were killed. Adhesions were created by scraping the cecum with mesh gauze followed by application of absolute alcohol and placement of silk suture in the parietal peritoneum. SCMC solution was administered intraperitoneally in groups C and D before closure. Adhesions were graded by two different investigators.. All control animals developed significant adhesions, compared with no adhesions in 30% of group B (vitamin E) (p < 0.04), 40% in group C (SCMC) (p = 0.0001), and an average of 90% in the D groups (SCMC+vitamin E) (p = 0.0001).. It appears that there is a synergistic beneficial effect of oral supplements of vitamin E and the intraperitoneal administration of SCMC solution in reducing the incidence and degree of intraperitoneal adhesions.

Topics: Administration, Oral; Animals; Carboxymethylcellulose Sodium; Female; Male; Peritoneal Diseases; Postoperative Complications; Rats; Rats, Sprague-Dawley; Tissue Adhesions; Vitamin E

Efficacy of a 1% solution of sodium carboxymethylcellulose (CMC) infused into the peritoneal cavity of ewes was evaluated for prevention of intraperitoneal adhesions resulting from surgery of the reproductive tract. Six ewes were assigned to each of 4 groups. Group-1 ewes were controls that underwent ventral midline celiotomy and exploration of the abdominal viscera. Group-2 ewes were treated similarly to group-1 ewes, except that a 1% solution of CMC (14 ml/kg of body weight) was infused into the peritoneal cavity. This group was studied to determine whether CMC would cause changes in the peritoneal cavity. Group-3 comprised ewes representing a uterine trauma model. Ewes underwent abdominal exploration, but in addition had a standard embryo collection technique performed on 1 uterine horn and hysterotomy performed on the opposite uterine horn. Group-4 ewes were treated like group-3 ewes, except that, similar to treatment of group-2 ewes, CMC was infused into the peritoneal cavity. All ewes were euthanatized and necropsied 12 to 14 days after surgery. Abdominal adhesions were evaluated, and an adhesion severity score was assigned to each ewe on the basis of number and severity of the adhesions. Ewes of all groups had abdominal adhesions. Significantly (P less than 0.05) lower adhesion score was observed in ewes given CMC (groups 2 and 4) than in the adhesion model (group 3). Significant difference was not observed in adhesion score when groups 1, 2, or 4 were compared. Though not statistically significant, fewer adhesions were observed in ewes of groups 2 and 4 than in group-1 ewes.

Topics: Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Female; Infusions, Parenteral; Omentum; Peritoneal Diseases; Sheep; Sheep Diseases; Tissue Adhesions; Uterus

Twelve ponies were used to evaluate the reliability of an abdominal adhesion model and the efficacy of intraperitoneal infusion of sodium carboxymethylcellulose in preventing abdominal adhesions. A celiotomy was performed on each of the 12 ponies and the serosa of the distal portion of the jejunum was abraded with a dry gauze sponge at 5 locations. In addition to the serosal damage, a single 2-0 chromic gut suture was placed through the seromuscular layer of the jejunum in the center of the abraded area. After closure of the celiotomy, a 1% solution of sodium carboxymethylcellulose (7 ml/kg of body weight) was infused into the peritoneal cavity of 6 ponies. The other ponies served as untreated controls. All ponies were euthanatized 14 days after surgery. All ponies in the control group had abdominal adhesions at the time of necropsy. Four of the 6 ponies in the treatment group were free of adhesions. There was a significant (P less than 0.0001) difference in the total number of adhesions between the 2 groups.

Topics: Animals; Carboxymethylcellulose Sodium; Drug Evaluation; Horse Diseases; Horses; Infusions, Parenteral; Peritoneal Diseases; Tissue Adhesions

With the use of a rabbit surgical model, the ability of 1%, 2%, and 3% solutions of sodium carboxymethylcellulose to reduce postoperative uterine adhesions was determined. At all concentrations sodium carboxymethylcellulose was more effective than either 32% dextran 70 or heparinized lactated Ringer's solution. Neither the dextran nor Ringer's solution had a significant (p less than or equal to 0.05) effect. The beneficial effects of sodium carboxymethylcellulose were closely dose-dependent (correlation coefficient 0.97). Sodium carboxymethylcellulose is highly effective in reducing postoperative adhesions in laboratory animals, and additional studies are warranted to further define its efficacy and safety.

Topics: Animals; Autopsy; Carboxymethylcellulose Sodium; Dextrans; Dose-Response Relationship, Drug; Female; Isotonic Solutions; Methylcellulose; Microsurgery; Peritoneal Diseases; Postoperative Complications; Rabbits; Ringer's Lactate; Solutions; Tissue Adhesions; Uterus