The design of an industry-sponsored randomized controlled trial to compare synthetic mesh versus biologic mesh for inguinal hernia repair.

PURPOSE: Biologic prostheses are designed to support tissue regeneration rather than just result in a strong scar plate, as is the case with synthetic mesh. It is not known if these newer materials will result in earlier return to normal activities and/or less post-herniorrhaphy groin pain. METHOD/STUDY DESIGN: A prospective, randomized, controlled, third-party-blinded multicenter trial was designed to compare the use of a non-cross linked porcine dermis biologic graft [Strattice(TM) Reconstructive Tissue Matrix (RTM), LifeCell, Branchburg, NJ] versus light weight, large pore polypropylene mesh (UltraPro(TM), Ethicon, Somerville, NJ). The study design called for recruitment of 170 men. These men are being followed for a minimum of 2 years. The primary aim of this study is to compare the safety and effectiveness of the two materials in a Lichtenstein inguinal hernia repair as measured by resumption of activities of daily living. Secondary outcomes include chronic pain, postoperative complications and the incidence of re-herniation at 12 and 24 months. RESULTS: This paper discusses the study design, patient recruitment and the current status of the clinical trial. The study involves nine medical centers, all with extensive experience in hernia repair. After 24 months of enrollment, 172 men were randomized and recruitment was then closed. All patients underwent elective repair of primary unilateral inguinal hernias as an outpatient operation. Follow up data are being collected. Data analyses are scheduled at 3, 12, and 24 months postoperatively. CONCLUSION: We report the design of a multi-center, third-party blinded, randomized clinical trial comparing a new surgical device with existing technology in the repair of inguinal hernias. We believe this investigator-designed and conducted trial could serve as a model for similar trials examining surgical devices performed in collaboration with industry.

Lack of enhancing effect of human anti-human immunodeficiency virus type 1 (HIV-1) antibody on HIV-1 infection of human blood monocytes and peritoneal macrophages.

The influence of human anti-human immunodeficiency virus type 1 (HIV-1) antibody on HIV-1 infection of freshly isolated normal human peritoneal macrophages and blood monocytes was examined. Each of 14 HIV antibody-positive human serum samples was found to block the infection of four virus isolates (human T-cell lymphotropic virus type IIIBa-L [HTLV-IIIBa-L], HTLV-IIIB, D.U. 6587-7, and D.U. 7887-8) at serum dilutions ranging from 10(-1) to 10(-2). Three of these isolates (HTLV-IIIBa-L, D.U. 6587-7, and D.U. 7887-8) infected cultures of monocytes and macrophages rapidly and produced high levels of virus reverse transcriptase and p24 antigen. A fourth virus isolate (HTLV-IIIB) infected the monocytes and macrophages more slowly and produced low levels of viral protein. More dilute HIV antibody-positive sera had no significant effect on the overall level or rate of virus infection or expression. Complement did not appear to influence the course of infection by any combination of antisera or virus examined. Successful HIV-1 infection of the peritoneal macrophages and blood monocytes under the conditions tested showed strict dependence on CD4 since a recombinant CD4 polypeptide and an anti-CD4 monoclonal antibody effectively blocked the process.

Identification of sites within gp41 that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies.

In an effort to determine the functional activity of anti-HIV-1 human mAb and to define the epitopes against which they are directed, supernatants from 10 EBV-transformed lymphoblastoid cell lines producing mAb to HIV were tested. Five clones producing mAb to gp41 and five producing mAb to p24 were identified. The anti-HIV-1 human mAb were tested in neutralization and cell fusion assays in the form of cell culture supernatants at concentrations ranging from 1.7 to 22.0 micrograms/ml. None of the human mAb were found either to inhibit HIV-1-(IIIB or RF) associated cell fusion or to neutralize HIV-1 (IIIB) infection of AA5 cells. All human mAb were additionally tested in 6 h 51Cr release assays for their ability to direct HIV-1 specific antibody-dependent cellular cytotoxicity (ADCC). For ADCC assays, PBMC were isolated from healthy seronegative donors and used as effector cells. HIV-1 infected (IIIB, RF, and MN) CEM.NKR cells as well as CEM.NKR cells with purified gp120 adsorbed onto their surface served as targets. None of the anti-p24 mAb mediated ADCC. In contrast, three of the anti-gp41 mAb were able to direct a significant level of ADCC against each of the infected targets, but as expected, failed to lyse gp120 adsorbed cells. To define the specific epitopes against which the anti-gp41 mAb were directed, seven small peptides homologous to regions within the extracellular domain of gp41 were synthesized. Using RIA, two of the mAb could be mapped. The most effective ADCC-directing human mAb bound to a peptide comprising amino acids 644-663, whereas the least effective ADCC directing anti-gp41 human mAb bound to a region within the immunodominant portion of gp41 outlined by amino acids 579-604. Together, these results for the first time assign a functional activity to human mAb directed at specific regions within gp41 by demonstrating that areas within this molecule can serve as targets for ADCC.