Pathology of human intestinal transplantation

BACKGROUND & AIMS: Intestinal transplantation is a developing therapeutic option for patients with irreversible intestinal failure or short bowel syndrome. The aim of this study was to delineate the histopathology of human intestinal allografts and to define the features of intestinal rejection. METHODS: The histological features of 3015 endoscopic biopsy specimens and 23 allograft specimens from 62 intestinal recipients were analyzed retrospectively and correlated with clinical findings. RESULTS: Acute allograft rejection was characterized by a varying combination of crypt injury, mucosal infiltration primarily by mononuclear cells (including blastic lymphocytes), and increased crypt cell apoptosis (more than 2 per 10 crypts). It represented a patchy, often ileal-centered process that could progress to mucosal ulceration; later episodes (more than 100 days posttransplant) tended to show lesser cellular infiltration and greater apoptosis than earlier episodes. Correlation with clinical rejection was good (false-positive rate of 9%; false-negative rate of 26%). Two resected specimens showed obliterative arteriopathy indicative of chronic rejection. In other specimens, preservation injury, cytomegalovirus infection, post-transplant lymphoproliferative disorder, and nonspecific features of active or past mucosal injury could be recognized. CONCLUSIONS: Mucosal biopsy specimens are a useful means of monitoring intestinal allografts. Based on features validated by clinical correlation, acute rejection can be identified reliably and can be differentiated from the other pathological processes affecting the intestinal allograft. (Gastroenterology 1996 Jun;110(6):1820-34)     

Modulation of in vitro and in vivo T-cell responses by transferrin- gallium and gallium nitrate

Gallium is a group IIIa metal that has efficacy in the therapy of malignant disorders such as lymphoma and urothelial tract tumors. Preclinical studies also indicate a role for gallium in autoimmune disorders, suggesting that gallium is able to modulate T-cell immune reactivity. The purpose of this study was to examine the in vitro and in vivo immunomodulatory action of gallium on T-cell function. Since gallium binds to transferrin in vivo, in vitro studies evaluated the effect of transferrin-gallium (Tf-Ga) on human T cells. Tf-Ga inhibited the mitogen-induced proliferative response of peripheral blood mononuclear cells (PBMC) in a dose-dependent fashion. Alloantigen- induced proliferation was also potently suppressed when evaluated in a mixed lymphocyte culture assay. Tf-Ga affected a significant reduction in the density of IL-2 receptors on activated T cells and a slight reduction in the number of CD3+/CD25+ T cells in PHA-stimulated cultures. Neither secretion of interleukin-2 (IL-2) nor the induction of IL-2-stimulated lymphokine-activated killer activity, however, was inhibited by Tf-Ga. Tf-Ga produced significant upregulation of the transferrin receptor (CD71) in T cells as determined by flow cytometric analysis and northern blot assay, but did not affect the percentage of CD3+/ CD71+ T cells after mitogen stimulation. To assess the in vivo effects of gallium on alloreactive T cells, we evaluated the immunosuppressive effect of gallium in a murine model of graft-versus- host disease (GVHD). Administration of gallium significantly prolonged survival in mice undergoing severe GVHD, suggesting that gallium can ameliorate GVH reactivity. Collectively, these data demonstrate that, at clinically achievable concentrations, Tf-Ga potently inhibits T-cell activation and that this immunosuppressive property of gallium may be of adjunctive therapeutic value in the management of disorders characterized by the presence of autoreactive or alloreactive T-cell populations.     

Surface shield: device to reduce personnel radiation exposure

A simple device is described that can reduce personnel exposure from scatter radiation by up to 75%. The device consists of an oblong piece of shielding (0.75-mm lead equivalent) that is taped to the side of the patient during percutaneous renal stone removal and other interventional procedures. Contrary to other shields and barriers, this does not interfere with access to the patient. Scatter exposure data from phantom studies are presented and the rationale for surface shielding discussed.     

Fibrosing alveolitis: CT-pathologic correlation

Computed tomography (CT) was performed within 10 days of open lung biopsy in nine patients with fibrosing alveolitis. One-centimeter collimation contiguous scans through the chest were obtained in all patients. Additional 1.5-mm collimation scans were obtained in the area in which lung biopsy was later performed in six patients. In seven patients, CT demonstrated patchy involvement of the lung parenchyma, areas with a reticular pattern being intermingled with areas of normal lung. The reticular pattern was associated with cystic spaces 2-4 mm in diameter and was more severe in the lung periphery. Histologically, the reticular pattern corresponded to areas of irregular fibrosis. One patient had diffuse honeycombing (2-20-mm cysts), and one had honeycombing only in the lung periphery. In all patients, CT clearly defined the architectural changes seen on open lung biopsy. These changes were much better seen on the 1.5-mm than on the 10-mm collimation scans. CT may be helpful in determining the pattern and distribution of lung involvement in patients with fibrosing alveolitis and in guiding the surgeon to the most appropriate area(s) for biopsy.     

Urine-compatible polymer for long-term ureteral stenting

Internal double-J ureteral stents were designed from a urine-compatible polymer (C-Flex), and 35 stents were placed in patients. The overall patency rate for the stents was 80%, with most stent failures occurring before 2 months; the follow-up period ranged from 2 to 16 months, with a mean follow-up for all stents of 5.0 months. Stents were considered patent at last follow-up only if they had been in place for at least 2 months. No migration or fracture of the stents occurred. Physical properties of urine-exposed stents were compared with those of virgin tubing and tubing exposed for 1 year to shelf conditions. Stent patency was optimized by increasing urine flow by increasing the patient's voluntary oral intake, administering prophylactic oral antibiotics, and avoiding placement of stents into grossly bloody or infected collecting systems.     

Work in progress: the application of temporal filtering techniques to hybrid subtraction in digital subtraction angiography

Temporal filtering methods were applied to iodine signal-to-noise ratio (SNR) restoration in intravenous hybrid subtraction digital subtraction angiography (DSA). For equal detected exposure rates hybrid subtraction had approximately 35% of the SNR of temporal subtraction. When matched filtering was applied to a DSA run, the filtered result had approximately two times higher SNR than the peak contrast image in the run. Thus, when matched filtering techniques were applied to the hybrid image sequence, the resultant SNR increased to about 70% of that of temporal subtraction. With an additional factor-of-two increase in exposure rate for the hybrid run, SNR parity with temporal subtraction could be achieved. This compared with a factor-of-nine increase in exposure that would be required if no filtering were performed. Experimental hybrid matched filter results, generated with intravenous canine DSA studies, supported the predictions in SNR performance.