The current status of hepatic transplantation at the University of Pittsburgh.

Tacrolimus is a more potent and satisfactory immunosuppressant than CyA for combination therapy with prednisone. In randomized trials comparing the 2 drugs, the ability of tacrolimus to rescue intractably rejecting grafts on the competing CyA arm allowed equalization of patient and graft survival on both arms when the intent-to-treat analytic methodology was applied. The ability of tacrolimus to systematically rescue the treatment failures of CyA suggested, as a matter of common sense, that it is the preferred baseline drug for hepatic transplantation. This conclusion was supported by analysis of secondary end points, including the ability to prevent rejection. Hepatic-intestinal, multivisceral and isolated intestinal transplantation became feasible on a practical basis only after the advent of tacrolimus. Nevertheless, better management strategies must be devised before intestinal transplantation, alone or with other abdominal viscera, will meet its potential. One such strategy is based on the discovery of the presence of previously unsuspected, low-level donor leukocyte chimerism in long-surviving allograft recipients. We believe that this chimerism is the essential explanation for the feasibility of organ transplantation and a link to the acquired neonatal tolerance demonstrated by Billingham, Brent and Medawar (32). The hematolymphopoietic chimerism in organ recipients explains why weaning to a drug-free state in selected long-term survivors is frequently feasible and particularly if the allograft is a liver. Weaning should never be attempted without a stepwise protocol and careful monitoring of graft function. Recognition of the natural chimerism that develops after whole organ transplantation has led to efforts to augment it with perioperative donor BM infusion. This procedure has been shown to be free of significant complications (including GVHD) in all kinds of whole organ recipients, including those given intestine. The prospects of clinical xenotransplantation must be evaluated in the same context of chimerism as that delineated for allotransplantation with the discovery of spontaneous chimerism. Before addressing chimerism-related questions in xenotransplantation, the additional barrier of the complement activation syndromes that cause hyperacute rejection will have to be surmounted. Although measures to effectively transplant xenografts have so far eluded us, the availability of the more potent drug, tacrolimus, and recognition of the seminal basis of allograft (or xenograft) acceptance via chimerism has inserted an element of reality into the largely wishful thinking that has been evident in discussions about the future of xenotransplantation

Polarimetric Multispectral Imaging Technology

The Jet Propulsion Laboratory is developing a remote sensing technology on which a new generation of compact, lightweight, high-resolution, low-power, reliable, versatile, programmable scientific polarimetric multispectral imaging instruments can be built to meet the challenge of future planetary exploration missions. The instrument is based on the fast programmable acousto-optic tunable filter (AOTF) of tellurium dioxide (TeO2) that operates in the wavelength range of 0.4-5 microns. Basically, the AOTF multispectral imaging instrument measures incoming light intensity as a function of spatial coordinates, wavelength, and polarization. Its operation can be in either sequential, random access, or multiwavelength mode as required. This provides observation flexibility, allowing real-time alternation among desired observations, collecting needed data only, minimizing data transmission, and permitting implementation of new experiments. These will result in optimization of the mission performance with minimal resources. Recently we completed a polarimetric multispectral imaging prototype instrument and performed outdoor field experiments for evaluating application potentials of the technology. We also investigated potential improvements on AOTF performance to strengthen technology readiness for applications. This paper will give a status report on the technology and a prospect toward future planetary exploration

Quantum critical dynamics of a S = 1/2 antiferromagnetic Heisenberg chain studied by 13C-NMR spectroscopy

We present a 13C-NMR study of the magnetic field driven transition to complete polarization of the S=1/2 antiferromagnetic Heisenberg chain system copper pyrazine dinitrate Cu(C_4H_4N_2)(NO_3)_2 (CuPzN). The static local magnetization as well as the low-frequency spin dynamics, probed via the nuclear spin-lattice relaxation rate 1/T_1, were explored from the low to the high field limit and at temperatures from the quantum regime (k_B T << J) up to the classical regime (k_B T >> J). The experimental data show very good agreement with quantum Monte Carlo calculations over the complete range of parameters investigated. Close to the critical field, as derived from static experiments, a pronounced maximum in 1/T_1 is found which we interpret as the finite-temperature manifestation of a diverging density of zero-energy magnetic excitations at the field-driven quantum critical point.Comment: 5 pages, 4 figure

Abdominal multivisceral transplantation

Under FK506-based immunosuppression, 13 abdominal multivisceral transplantations were performed in 6 children and 7 adults. Of the 13 recipients, 7 (53.8%) are alive and well with functioning grafts after 9 to 31 months. Six recipients died: Three from PTLD, one from rejection, one from sepsis, and one from respiratory failure. In addition to rejection, postoperative complications occurring in more than isolated cases included PTLD (n=6), abdominal abscess formation (n=5), pancreatitis (n=3), and ampullary dysfunction (n=2). In addition, infection by enteric microorganisms was common during the early postoperative period. Currently, all 7 survivors are on an oral diet and have normal liver function. Two recipients (one insulin-dependent) require antidiabetes treatment, in one case following distal pancreatectomy and in the other after two episodes of pancreatic rejection. Thus, abdominal multivisceral transplantation is a difficult but feasible operation that demands complex and prolonged posttransplantation management. It is not yet ready for application and awaits a better strategy of immune modulation. © 1995 by Williams & Wilkins

Outcome analysis of 71 clinical intestinal transplantations

Objective: The aim of the study was to determine risk factors associated with graft failure and mortality after transplantation of the intestine alone or as pad of an organ complex. Summary Background Data: Even with modern immunosuppressive therapies, clinical intestinal transplantation remains a difficult and unreliable procedure. Causes for this and solutions are needed. Methods: Between May 1990 and February 1995, 71 intestinal transplantations were performed in 66 patients using tacrolimus and low-dose steroids. The first 63 patients, all but one treated 1 to 5 years ago, received either isolated grafts (n = 22), liver and intestinal grafts (n = 30), or multivisceral grafts (n = 11). Three mere recipients of allografts who recently underwent surgery and one undergoing retransplantation were given unaltered donor bone marrow cells perioperatively as a biologic adjuvant. Results: Of the first 63 recipients, 32 are alive: 28 have functioning primary grafts and 4 have resumed total parenteral nutrition after graft enterectomy. Thirty-five primary grafts were lost to technical and management errors (n = 10), rejection (n = 6), and infection (n = 19). Regression analysis revealed that duration of surgery, positive donor cytomegalovirus (CMV) serology, inclusion of graft colon, OKT3 use, steroid recycle, and high tacrolimus blood levels contributed to graft loss. All four intestine and bone marrow recipients are alive for 2-3 months without evidence of graft- versus-host disease. Conclusion: To improve outcome after intestinal transplantation with previous management protocols, it will be necessary to avoid predictably difficult patients, CMV seropositive donors, and inclusion of the graft colon. Bone marrow transplantation may further improve outcome by ameliorating the biologic barriers of rejection and infection and allowing less restrictive selection criteria

Rejection of human intestinal allografts: Alone or in combination with the liver

The current results of the present series demonstrate that intestinal allografts are more vulnerable to rejection and continue to be at a significantly higher risk long after transplantation compared with isolated liver allograft recipients. Unexpectedly, a combined liver allograft does not protect small bowel from rejection. The necessarily continuous heavy immunosuppression for these unique recipients is potentially self-defeating. This is clearly demonstrated by their high susceptibility to early and late infectious complications after transplantation as reported in this issue. With the minimal graft-versus-host disease threat in this clinical trial, our revised protocol for future intestinal transplantation is to maximize the passenger leukocyte traffic with supplementary bone marrow from the same intestinal donor in an attempt to augment the development of systemic chimerism and the gradual induction of donor-specific nonreactivity