Christine Weis

In-vivo studies on intraperitoneally administrated poly(vinyl alcohol)

The fate of poly(vinyl alcohol) (PVA, 195,000 g/mol) was studied in rabbits and nude mice after intraperitoneal (i.p.) administration. In-vivo fluorescence imaging using nude mice allowed for studies of tetramethylrhodamine labeled PVA distribution in the body and tracking the urinary excretion. The excreted PVA was studied in detail after collecting the urine of rabbits over a time period of 28 days. The PVA was separated from the urine by dialysis and analyzed by FTIR spectroscopy, (1)H-NMR spectroscopy, and size exclusion chromatography (SEC). Even after extensive dialysis, it was found that the excreted PVA showed a characteristic brownish color. The spectroscopic techniques revealed that this color was caused by the urine pigment (a metabolite of bilirubin) that could not be separated completely from the PVA. SEC showed unambiguously that the PVA with the very high molar mass had a glomerular permeability in the kidneys. Simultaneously, histological studies of the kidneys and the liver demonstrated that the tissues did not show any obvious damage.

Polyvinyl Alcohol Gel Prevents Adhesion Re-Formation After Adhesiolysis in a Rabbit Model

BACKGROUND Chronic pain, infertility, and bowel obstructions are possible consequences of abdominal adhesions, which can highly affect the patients quality of life. Patients in whom adhesiolysis has been performed are at high risk for recurrence of adhesions. For that reason, the present study focused on the re-formation of adhesions after adhesiolysis and on the possibility of avoiding it by using the adhesion barrier polyvinyl alcohol (PVA)-gel. MATERIALS AND METHODS A randomized controlled study was conducted to prove the effectiveness of PVA-gel in reducing postoperative adhesion re-formation after relaparotomy. Moreover, ultrasound was evaluated as a noninvasive technique to determine abdominal adhesion in a rabbit model. All animals underwent an initial laparotomy to cause adhesions and subsequent adhesiolysis in the relaparotomy. PVA-gel was placed onto a side wall defect in 12 animals. Another 12 rabbits served as a control group without PVA-gel being used. Ultrasound before final laparotomy was performed to predict the prevalence of adhesions. Macroscopic evaluation of adhesion formation and planimetry were used to determine the amount of adhesion. RESULTS PVA-gel was found to reduce significantly the amount of adhesion formation after relaparotomy (P = 0.0001) in comparison with the control group. Here severe adhesion formation was found to develop. The positive-predictive value (100%) for adhesion evaluation using ultrasound is highly satisfying in the rabbit model. CONCLUSIONS Adhesion re-formation after relaparotomy was found to decrease significantly through the use of PVA-gel. Ultrasound as a noninvasive technique of adhesion detection is a sufficient and reliable method for detecting adhesion formations.

A hydrogel for adhesion prevention: characterization and efficacy study in a rabbit uterus model

OBJECTIVE Postoperative peritoneal adhesions following gynaecological surgery remain a clinically relevant problem. One approach to prevent adhesion formation is to apply physical barriers such as hydrogels. STUDY DESIGN A physically crosslinked polyvinyl alcohol and carboxymethylcellulose (PVA/CMC) hydrogel (A-Part) was characterized in vitro. Three different traumatization methods were evaluated in a rabbit uterine study. To determine its anti-adhesion efficacy, the hydrogel was first tested in an in vivo pilot study and then in a larger trial to compare it with icodextrin 4% solution (Adept) and controls. RESULTS Rheological measurements showed an increased elasticity of the hydrogel after freezing. In vivo experiments revealed a clear reduction in incidence, extent and severity of adhesions compared to the icodextrin 4% solution and the untreated control group. CONCLUSIONS These results warrant further investigation of the PVA/CMC A-Part hydrogel in clinical trials focused on gynaecological procedures.

A prospective, randomised, controlled, double-blind phase I-II clinical trial on the safety of A-Part® Gel as adhesion prophylaxis after major abdominal surgery versus non-treated group

BackgroundPostoperative adhesions occur when fibrous strands of internal scar tissue bind anatomical structures to one another. The most common cause of intra-abdominal adhesions is previous intra-abdominal surgical intervention. Up to 74% of intestinal obstructions are caused by post surgical adhesions. Although a variety of methods and agents have been investigated to prevent post surgical adhesions, the problem of peritoneal adhesions remains largely unsolved. Materials serving as an adhesion barrier are much needed.Methods/DesignThis is a prospective, randomised, controlled, patient blinded and observer blinded, single centre phase I-II trial, which evaluates the safety of A-Part® Gel as an adhesion prophylaxis after major abdominal wall surgery, in comparison to an untreated control group. 60 patients undergoing an elective median laparotomy without prior abdominal surgery are randomly allocated into two groups of a 1:1- ratio. Safety parameter and primary endpoint of the study is the occurrence of wound healing impairment or peritonitis within 28 (+10) days after surgery. The frequency of anastomotic leakage within 28 days after operation, occurrence of adverse and serious adverse events during hospital stay up to 3 months and the rate of adhesions along the scar within 3 months are defined as secondary endpoints. After hospital discharge the investigator will examine the enrolled patients at 28 (+10) days and 3 months (±14 days) after surgery.DiscussionThis trial aims to assess, whether the intra-peritoneal application of A-Part® Gel is safe and efficacious in the prevention of post-surgical adhesions after median laparotomy, in comparison to untreated controls.Trial registrationNCT00646412