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 micromol/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 micromol/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.

Determining when a clinical activity should be classified as research requiring Institutional Review Board Review.

The boundary between therapy and research may at times be difficult to distinguish, and it is, therefore, important for health care professionals to recognize when a clinical activity should be properly classified as research. Research may be subject to federal regulations which require advance review and approval by an Institutional Review Board (IRB) in order to protect the rights and welfare of patients who serve as human subjects. This paper will discuss the criteria health care professionals can use to distinguish between therapy, innovative therapy, and therapeutic or clinical research.

Research involving fetal drug therapy: ethical, legal, and practical considerations.

Fetal drug therapies have emerged as a promising avenue for the prevention or correction of disease during fetal or immediate postnatal life. Despite slow progress, several medications have been developed for in utero therapy of disorders which relate to fetal and neonatal pulmonary, cardiac, neurologic, and growth disorders. However, ethical and regulatory constraints require protection of the mother and fetus while causing no more than necessary additional risk. Appreciating these constraints will lead to the identification of pragmatic questions which should be answered before evaluating the efficacy and safety of a particular treatment or research proposal.

Training teachers in the anatomical sciences.

A number of medical schools have initiated workshops to improve faculty teaching skills. Little effort, however, has been directed toward the pedagogical training of graduate students who are destined to become future medical science teachers. To help solve this problem, the faculty of the Department of Anatomy in the University of Nebraska College of Medicine recently developed a prototype teacher training program for graduate students in anatomy. Through formal course work and practical classroom experience, students are developing the skills requisite for effective teaching of the anatomical sciences. Student and faculty response to the training program has been enthusiastic, and the objectives and structure of the program can be applied to the production of competent and skilled teachers in other areas of the basic and clinical sciences.

Effects of hypophysectomy on DNCB-induced contact sensitivity in rats.

Cell-mediated immunity in hypophysectomized (HYX) and non-hypophysectomized (NHYX) rats was assessed by measuring lymph node weight and lymph node cellular proliferation responses to cutaneous application of the skin sensitizer dinitrochlorobenzene (DNCB). Differences were found in the lymph node weight assay, with the responses of the HYX rats being significantly lower than the responses of the NHYX rats. There were, however, no significant differences as measured by the lymph node cellular proliferation assay. An explanation for these contradictory results was sought by examining dose-responsiveness to DNCB. It was found that, over a range of doses of DNCB, HYX rats showed a linear dose-response relationship in terms of both lymph node weight and lymph node cellular proliferation. No dose-responsiveness was observed in NHYX rats. Since HYX rats required a greater degree of antigenic stimulation to achieve a response level equivalent to that of NHYX rats, it may be concluded that HYX rats are immunodeficient at lower antigen levels.

The impact of escalating regulatory requirements on the conduct of clinical research.

A discussion of the impact of escalating regulatory requirements is provided, from the point of view of the administration of the institutional review board of an academic institution, and from clinical investigators who conduct studies at that same institution. Current and anticipated future issues are discussed.

Stereoscopic anatomy: evaluation of a new teaching system in human gross anatomy.

Traditionally, human gross anatomy teaching has revolved around anatomical dissection. Unfortunately, during the last decade a number of medical schools have experienced a decrease in the number of hours allotted to gross anatomy instruction compounded by a shortage of anatomical donors. This, in turn, has served to increase the difficulties of providing students with truly effective anatomical instruction. To help overcome this problem, a stereoscopic slide-based auto-instructional program has been developed as a substitute for dissection. Evaluation data suggest that this program, while having minor limitations in terms of anatomical orientation, does provide a viable alternative to dissection.