Ernest D. Prentice

Extracorporeal liver perfusion using human and pig livers for acute liver failure.

Background. Patients with fulminant hepatic failure (FHF) often die awaiting liver transplantation.Extracorporeal liver perfusion (ECLP) has been proposed as a method of “bridging” such patients to transplantation. We report the largest experience to date of ECLP using human and porcine livers in patients with acute liver failure. Methods. Patients with FHF unlikely to survive without liver transplantation were identified. ECLP was performed with human or porcine livers. Patients underwent continuous perfusion until liver transplantation or withdrawal of support. Two perfusion circuits were used: direct perfusion of patient blood through the extracorporeal liver and indirect perfusion with a plasma filter between the patient and the liver. Findings. Fourteen patients were treated with 16 livers in 18 perfusion circuits. Nine patients were successfully “bridged” to transplantation. ECLP stabilized intracranial pressure (ICP) and cerebral perfusion pressure (CPP). Arterial ammonia levels fell from a median of 146 to 83 &mgr;mol/liter within 12 hr and this reduction was maintained at least 48 hr. Pig and human ECLP lowered ammonia levels equally. Serum bilirubin levels also fell from a median of 385 to 198 &mgr;mol/liter over the first 12 hr but the response was not sustained as well with porcine livers. There was no immunological benefit to using the the filtered perfusion circuit. Interpretation. These data demonstrate that ECLP is safe and can provide metabolic support for comatose patients with fulminant hepatic failure for up to 5 days. While labor and resource intensive, this technology is available to centers caring for patients with acute liver failure and deserves wider evaluation and application.

Patients Beware: Commercialized Stem Cell Treatments on the Web

A report by the International Society for Stem Cell Research (ISSCR)s Task Force on Unproven Stem Cell Treatments outlines development of resources for patients, their families, and physicians seeking information on stem cell treatments.

An update on the PEG-SOD study involving incompetent subjects: FDA permits an exception to informed consent requirements.

project commonly referred to as the PEG-SOD study. This study raised the question of whether the FDA and HHS requirements for informed consent are unnecessarily restrictive when applied to ER research. In a recent article published in this journal, we reported on the review and approval of the PEG-SOD study by the institutional review board (IRB) of the University of Nebraska Medical Center (UNMC).1 The protocol as described in our article is a multi-

Protection of human subjects in the United States: a short history.

The purpose of this article is to describe a few pivotal events that led to the development of federal regulations that now govern human subjects research in the United States.

Women in early phase trials: an IRB's deliberations

he University of Nebraska Medical Center institutional review board (UNMC IRB) recently gave considerable attention to issues concerning respect for persons, justice, and beneficence. Our deliberations were occasioned by review of a protocol of a new biological agent for treatment of Type II diabetes, specifically the protocols inclusion criteria regarding women of childbearing potential. The study was a randomized Phase I/II study of the safety and efficacy of three doses of a specific agent, compared to placebo, given in combination with other agents over a three-month period in patients with a particular condition. Among the inclusion criteria was a requirement that while on study women of childbearing potential (i.e., premenopausal females capable of becoming pregnant) use either oral contraceptives or an IUD as the only acceptable method of contraception. Prior to the start of study medication, women of childbearing potential must have had a negative urine pregnancy test. Animal teratogenicity studies of the agent had not been completed at the time of the IRB review.

Conflict between research design and minimization of risks in pediatric research.

The University of Nebraska Medical Center (UNMC) Institutional Review Board (IRB) reviewed a protocol for the treatment of short bowel syndrome (SBS) in children. The SBS protocol proved to be quite problematic in terms of whether was approvable under 45 CFR 46 subpart D, which specifies additional protections for children who are subjects of research. The protocol was designed as a multicenter study, but was not federally funded. The IRBs review required extensive interaction with the institutional