A prospective, randomized, multicenter, controlled study of the safety of Seprafilm adhesion barrier in abdominopelvic surgery of the intestine.

Item does not contain fulltextINTRODUCTION: Seprafilm adhesion barrier (Seprafilm) has been proven to prevent adhesion formation after abdominal and pelvic surgery. This article reports safety results, including the postoperative incidence of abdominal and pelvic abscess and pulmonary embolism, from a large, multicenter trial designed to evaluate the safety and effectiveness of Seprafilm for reduction of adhesion-related postoperative bowel obstruction after abdominopelvic surgery. METHODS: A total of 1791 patients participated in this prospective, randomized, multicenter, multinational, single-blind, controlled study in patients undergoing abdominopelvic surgery, the majority of whom had inflammatory bowel disease. Just before closure of the abdomen, patients were randomized to a Seprafilm or no-treatment control group. Patients received an average of 4.4 and as many as 10 Seprafilm adhesion barriers applied to organs and tissue surfaces that sustained direct surgical trauma and to suspected adhesiogenic surfaces. Complications that occurred within the first month after surgery were evaluated. RESULTS: During the safety evaluation period, the difference between the Seprafilm and control groups for the incidence of abscess (4 vs. 3 percent, respectively) or pulmonary embolism ( 0.05). Foreign body reaction was not reported in either group. Fistula (2 vs. <1 percent) and peritonitis (2 vs. <1 percent) occurred more frequently (P <or= 0.05) in the Seprafilm group. In a subpopulation of patients in whom Seprafilm was wrapped around a fresh bowel anastomosis, leak-related events, which included anastomotic leak, fistula, peritonitis, abscess, and sepsis, occurred more frequently (P <or= 0.05). There were no other differences in the incidence, severity, or causative relationship of complications between study groups. CONCLUSIONS: This study confirmed the safety of Seprafilm adhesion barrier with respect to abdominal abscess, pelvic abscess, and pulmonary embolism when administered to patients undergoing abdominopelvic surgery. Foreign body reaction was not reported for any patient. However, wrapping the suture or staple line of a fresh bowel anastomosis with Seprafilm should be avoided, because the data suggest that this practice may increase the risk of sequelae associated with anastomotic leak

"Sero-switch" adenovirus-mediated in vivo gene transfer: circumvention of anti-adenovirus humoral immune defenses against repeat adenovirus vector administration by changing the adenovirus serotype

Recombinant, replication-deficient adenovirus (Ad) vectors have been successfully used to transfer and express the normal human cystic fibrosis transmembrane conductance regulator (CFTR) cDNA in vivo in the respiratory epithelium of experimental animals and humans with cystic fibrosis (CF). Since Ad-directed gene expression wanes over time, repeat administration is necessary to achieve an effective treatment for CF. A major hurdle to such a strategy is the possibility that anti-Ad humoral immunity may prevent gene expression in individuals with pre-existing anti-Ad immunity or following repeat administration. One strategy to circumvent such a problem would be alternating the use of Ad vectors belonging to different subgroups. Neutralizing antibodies developed with the administration of one Ad serotype do not cross-react with an Ad belonging to a second serotype in a manner that blocks infection and gene expression. To test this hypothesis, an immunizing dose of wild-type Ad5 (subgroup C), Ad4 (subgroup E), or Ad30 (subgroup D) was administered intratracheally to experimental animals, followed by an intratracheal administration of a replication-deficient subgroup C-derived vector coding for marker genes (chloramphenicol acetyl transferase or beta-galactosidase) or for the normal human CFTR cDNA. As expected, studies with vectors coding for marker genes or for CFTR cDNA demonstrated that airway administration of a vector does not yield efficient gene transfer, if there has been prior recent airway administration of the same Ad subgroup. In contrast, effective expression from the second administration can be achieved with an adenovirus vector belonging to a subgroup different from the first adenovirus administered. These data support the paradigm of alternating Ad vectors derived from different subgroups as strategy to circumvent anti-Ad humoral immunity, thus permitting the use of Ad vectors as a means to treat the respiratory manifestations of CF