Scandiatransplant acceptable mismatch program (STAMP) a bridge to transplanting highly immunized patients.

BACKGROUND: Highly immunized patients are a challenge for organ transplantation programs. One way of increasing the likelihood of transplantation in this group of patients is to expand the possible donations by defining acceptable HLA mismatches. In the Scandiatransplant Acceptable Mismatch Program (STAMP), a de-centralized approach has been implemented in 2009. AIMS: The program has been improved during the years from utilizing HLA-A, -B, -DR matching only to include typing of all deceased donors for HLA-A, -B, -C, -DRB1 and -DQB1. The calculation of a transplantability score (TS) has been introduced in order to take both HLA and AB0 into consideration resulting in a more realistic picture of the transplantability chance. MATERIALS AND METHODS: Patients were selected for eligibility and results of immunisation status were prepared in each of the 9 tissue typing laboratories, while access to the program is finally governed by a common steering group of immunologists and clinicians. RESULTS: In the period from March 2009 until February 2015, 96 patients were transplanted within this program. The mean recipient age was 49 years and 57% were females, 30% of the patients were first transplants and of these 93% were females. The majority of the patients had 2-5 HLA-A, -B. -DR mismatches. The allograft survival at 60 months was 79.1%. Applying the TS to the cohort confirmed that patients with a low TS score had longer waiting times. CONCLUSION: The program has matured during the years and now proves to be a valid approach for transplanting highly immunized patients.

The Use of Blood Products in Adult Patients with Burns.

INTRODUCTION: Burn anemia represents a common complication following a burn injury. Burn anemia etiology carries distinct features occurring at each stage of the post-injury and treatment periods resulting from different causes. We aimed to analyze the use of blood components in Finnish burn victims and to identify patient- and injury-related factors influencing their use. METHODS: To study the use of blood products in burn patients, we used data collected from the Optimal Use of Blood registry, developed through co-operation between 10 major hospital districts and the Finnish Red Cross Blood Service. Burn patients ⩾18 years treated at the Helsinki University Hospital between 2005 and 2011 with an in-hospital stay ⩾1 day who received at least one transfusion during their hospital stay were included in this study. RESULTS: Among all 558 burn patients, 192 (34%) received blood products during their hospital stay. The transfused cohort comprised 192 burn patients. The study cohort received a total of 6087 units of blood components, 2422 units of leukoreduced red blood cells, 1728 units of leukoreduced platelets, and 420 units of single-donor fresh frozen plasma or, after 2007, 1517 units of Octaplas(®) frozen plasma. All three types of blood components were administered to 29% of patients, whereas 45% received only red blood cells and 6% received only Octaplas. Transfused patients were significantly older (p < 0.001), experienced fire-/flame-related accidents and burns to multiple locations (p < 0.001), and their in-hospital mortality exceeded that for non-transfused burn patients fivefold (p < 0.05). DISCUSSION: We show that Finnish adult burn patients received ample transfusions. The number of blood components transfused varied according to the anatomical location of the injury and patient survival. Whether the additional mortality is related directly to transfusions or is merely a manifestation of the more severe burn injury remains unknown.

Conflicting HLA assignment by three different typing methods due to the apparent loss of heterozygosity in the MHC region.

Loss of heterozygosity (LOH) has been reported to cause false human leukocyte antigen (HLA) homozygous typing results in pre-transplant patients suffering from haematological malignancies, who in fact are HLA heterozygous. This poses a challenge for histocompatibility testing, as a stem cell graft from a genuinely HLA homozygous donor to a mistyped patient may lead to acute life-threatening graft-vs-host disease. LOH in the HLA region on chromosome 6 is known to be quite common in solid tumours, helping malignant cells to escape T-cell surveillance, but the incidence in haematological malignancies is less well known and the estimates vary. Here we report LOH in the HLA region of five patients with haematological malignancy. We found considerable differences in sensitivity between the three different HLA typing methods used in our laboratory: SSP was clearly the most sensitive method for detecting the lost haplotype, followed by rSSO, while SBT was the least sensitive technique. A subsequent, retrospective genotyping of 65 HLA homozygous haematological patients by SSP method showed no mistyped LOH cases in our laboratory in the past 10 years. The frequency of HLA homozygosity was found to be similar between haematological patients and control groups. It is important for an HLA laboratory to be aware of the differences in various HLA typing techniques' sensitivity for detecting an under-represented haplotype between HLA typing techniques when genotyping patients with haematological diseases. It is advisable for HLA laboratories to have at least two different methods with different sensitivities in their repertoire to be able to retype samples when a false homozygous result is suspected.

HLA antigen, allele and haplotype frequencies and their use in virtual panel reactive antigen calculations in the Finnish population.

The human leukocyte antigen (HLA) antigen, allele and haplotype frequencies of the Finnish population are quite unique because of a rather restricted and homogeneous gene pool. This has a strong influence on finding suitable donors for transplant patients; hence knowledge about the HLA frequencies of the patient population is essential. Here we report the HLA antigen frequencies for a large population sample and show high resolution HLA allele frequencies for 11 loci, including the rarely typed DPA1 and DQA1 loci. Furthermore, the most common Finnish high resolution haplotypes are presented for five HLA loci. The study shows that there are fewer HLA haplotypes in the Finnish population compared with mixed populations, and the common Finnish HLA haplotypes are more frequent. Using HLA antibody identification and panel reactive antibody calculations we show that a virtual population-specific panel, combined with single antigen testing, gives a more accurate and reliable estimate of the reactivity of the recipient serum against potential solid organ donors within the Finnish population. The results can be directly used to improve donor search for patients waiting for stem cell transplantation and to allocate highly immunised patients accurately to acceptable mismatch programs.

Cholesterol metabolism altered and FGF21 levels high after pediatric liver transplantation despite normal serum lipids.

Liver transplantation (LT) predisposes to metabolic derangements and increases the risk for cardiovascular disease. We conducted a national cross-sectional study of all pediatric recipients who underwent LT between 1987 and 2007. We measured serum levels of noncholesterol sterols (surrogate markers of cholesterol synthesis and intestinal absorption) and fibroblast growth factor 21 (FGF21) in 49 patients (74% of survivors) at a median of 10 years posttransplant and in 93 controls matched for age and gender. Although serum cholesterol levels were similar in patients and controls, patients displayed increased whole-body synthesis and decreased intestinal absorption of cholesterol compared with controls (lathosterol to cholesterol ratio 129 ± 55 vs. 96 ± 41, respectively, p < 0.001; campesterol to cholesterol ratio 233 ± 91 vs. 316 ± 107, respectively; p < 0.001). Azathioprine (r =-0.383, p = 0.007) and low-dose methylpredisolone (r =-0.492, p < 0.001) were negatively associated with lathosterol/sitosterol ratio reflecting a favorable effect on cholesterol metabolism. FGF21 levels were higher in patients than in controls (248 pg/mL vs. 77 pg/mL, p < 0.001). In healthy controls, FGF21 was associated with cholesterol metabolism, an association missing in LT recipients. Normal serum lipids are achievable in long-term survivors of pediatric LT, but changes in cholesterol metabolism and increased FGF21 levels may explicate later cardiovascular risk.

General health, health-related quality of life and sexual health after pediatric liver transplantation: a nationwide study.

The long-term impact of pediatric liver transplantation (LT) and its complications on general health, health-related quality of life (HRQoL) and sexual health were assessed. We conducted a national cross-sectional study of all pediatric recipients who underwent LT between 1987 and 2007. Of 66 survivors, 57 participants (86%) were compared to randomly chosen healthy controls (n = 141) at 10.7 ± 6.6 years posttransplant. PedsQL4.0, SF-36, DISF-SR and AUDIT questionnaires for appropriate age groups were used. Patients and controls <7 years had similar HRQoL and 54% of patients aged over 7 scored within the controls' normal range on all HRQoL domains. In adult survivors, physical functioning and general health were decreased (p < 0.05). Biliary complications, reoperations and obesity were independently associated with reduced HRQoL (p < 0.05 for all). Still 64% of adult survivors considered their health excellent. Sexual health was similar to controls but LT recipients may experience problems with their orgasm strength (p = 0.050) and condom-based contraception was more common after LT than among controls (58% and 12%, p < 0.001). In conclusion, normal HRQoL and sexual health are achievable post-LT.

Ischemic intestinal injury during cardiopulmonary bypass does not show an association with neutrophil activation: a porcine study.

BACKGROUND: Neutrophil activation and tissue sequestration are crucial events in intestinal ischemia-reperfusion injury, but their role in the gut wall after clinical cardiopulmonary bypass (CPB) remains unclear. We tested whether local post-CPB inflammatory response in the gut wall would be associated with intestinal mucosal perfusion. METHODS: Twenty pigs underwent 60 min of aortic clamping and 75 min of normothermic perfusion. Intestinal biopsies were taken after 120 min of reperfusion. Based on ileal myeloperoxidase activity (MPO), the animals were divided into 2 groups, CPB-induced increase in MPO (MPO+) versus no such increase (MPO-), for comparison of the parameters that measure gut mucosal perfusion. Ileal p(CO)((2)) and intramucosal pH were determined, and arterial gases were analyzed. Additionally, several hemodynamic parameters and blood thrombin-antithrombin complexes (TAT) were measured. RESULTS: Myocyte degeneration, endothelial activation and vasculitis were more pronounced in the MPO+ group (p < 0.05), while the MPO- group showed significantly increased pi(CO)((2)) and lower mucosal pH values during reperfusion. Hemodynamics and TAT levels did not differ between the groups. CONCLUSION: Tissue sequestration of neutrophils was poorly associated with perturbed mucosal perfusion after CPB. Mechanisms of gut wall injury after a low-flow/reperfusion setting can differ from those in reperfusion injury after total ischemia.

Antithrombin reduces pulmonary hypertension during reperfusion after cardiopulmonary bypass in a pig.

BACKGROUND: Antithrombin (AT) may alleviate many cardiopulmonary bypass (CPB) and ischemia-reperfusion (I/R)-related adverse effects. Using a porcine model of clinical cardiac surgery on CPB, we tested the effects of supplementary AT on myocardial and lung I/R injury. METHODS: Twenty pigs undergoing 60-min aortic clamping and 75-min normothermic perfusion were randomized in a blinded setting to receive an intravenous (i.v.) bolus of AT (250 IU/kg) (AT group, n = 10) or placebo (n = 10) 15 min before aortic declamping. An additional group of five animals received 500 IU/kg AT in an open-label setting (AT+). Thrombin-antithrombin complexes (TAT), activated clotting times (ACT), AT and myeloperoxidase (MPO) activities, troponin T, and several hemodynamic parameters were measured before CPB and after weaning from CPB up to 120 min after aortic declamping. After 120 min of reperfusion, myocardial and lung biopsies were taken for histological examination. RESULTS: AT effectively inhibited coagulation as assessed by ACT. In the AT and AT+ groups only, cardiac output (CO) and stroke volume (SV) showed a trend of post-ischemic recovery during the first 15 min after CPB. AT-attenuated reperfusion induced an increase in pulmonary arterial diastolic pressure (PAPD) but did not have significant effects on systemic or pulmonary vascular resistance. The effects of AT on SV, CO, and PAPD were fortified in the AT+ group. AT did not show effects on inflammatory changes in either myocardial or pulmonary tissue specimens. AT did not reduce post-ischemic troponin T release. CONCLUSION: Supplementary AT, in doses with significant anticoagulant effect, did not alleviate myocardial I/R injury in terms of histological inflammatory changes or post-ischemic troponin T release. Instead, however, AT-attenuated reperfusion induced an increase in pulmonary pressure after CPB. Mechanisms and clinical implications of these effects remain to be explored.

Effects of extrinsic denervation with or without ischemia-reperfusion injury on constitutional mucosal characteristics in porcine jejunoileum.

We investigated the effects of jejunoileal denervation with or without ischemia-reperfusion on mucosal characteristics and small intestinal structure. Growing pigs underwent sham laparotomy, jejunal transection, or extrinsic jejunoileal denervation with or without in situ ischemia-reperfusion. Small intestinal morphology, crypt cell proliferation, enterocyte ultrastructure, and disaccharidase activities were analyzed from jejunum and ileum after eight weeks. Immunohistological analysis of the ileum showed no staining of catecholaminergic neurons after extrinsic denervation. Neural isolation of the jejunoileum with or without ischemia-reperfusion injury reduced weight gain and villous enterocyte density in the ileum, abolished the proximodistal gradient of sucrase activity, and increased mucosal thickness, villus height, and villus surface area in the ileum. However, gross jejunoileal morphology, crypt cell proliferation, and enterocyte ultrastructure remained unchanged. In conclusion, jejunoileal denervation in growing pigs selectively modulates constitutional mucosal characteristics in the ileum, presumably due to altered enterocyte turnover, without a decrease in small intestinal absorptive surface area. These changes are independent of short ischemia and subsequent reperfusion.

Autotransplantation modulates ileal enteroendocrine cell expression in the pig.

BACKGROUND: Enteroendocrine cell-derived peptides modulate postresectional small bowel adaptation, which may be attenuated by transplantation. We investigated whether autotransplantation modulates the number and distribution of ileal enteroendocrine cells in pigs with proximal small bowel resection. MATERIALS AND METHODS: Fifteen pigs were assigned into either small intestinal transection or 75% proximal small intestinal resection with or without autotransplantation of the remaining ileum. After 14 weeks the number and subtype distribution of enteroendocrine cells, crypt cell proliferation, and mucosal histology were analyzed from the proximal and distal ends of the remaining ileum. RESULTS: When compared to resected controls, autotransplantation of the ileum decreased the absolute (P < 0.05 in proximal ileum) and proportional (P < 0.05 in distal ileum) crypt enteroendocrine cell number. In addition, autotransplantation reduced somatostatin and glicentin expressing cell counts and abolished the proximodistal gradient of the enteroendocrine cell number. When compared to transected controls, villus height, crypt depth, number of proliferating crypt cells, and crypt cell proliferation index increased after the proximal resection (P < 0.05 in all except in crypt depth and proliferation index of the distal ileum) but remained virtually unchanged after autotransplantation of the ileal remnant. CONCLUSIONS: Autotransplantation decreases the crypt enteroendocrine cell number and alters their proximodistal and subtype distribution in the remaining ileum in pigs with proximal small bowel resection. These alterations are associated with attenuated adaptive response of the autotransplanted ileum.

Does increased crypt cell proliferation impair cholesterol absorption after proximal gut resection?

BACKGROUND: The effects of proximal small-bowel resection on absorption and synthesis of cholesterol are unclear. METHODS: To study cholesterol absorption and synthesis after proximal gut resections of variable length, plasma plant sterols, cholestanol, and cholesterol precursors were measured 1 and 2 months after 50% and 75% proximal small-bowel resection or transection. To examine the effect of increased crypt cell proliferation and brush border development on cholesterol absorption, the results were related to the mucosal morphology, crypt cell proliferation, and disaccharidase activities of the remaining small bowel. RESULTS: Campesterol levels in proportion to cholesterol decreased markedly more, and those of cholestanol markedly less, than would be expected simply due to the amount of proximal small intestine removed, whereas sitosterol proportions decreased in proportion to the length of gut resection. Campesterol proportions markedly (P = 0.06) increased between 1 and 2 months after 50% resection but remained unchanged after 75% resection. Crypt cell proliferation was only increased in the 75% resection group (P < 0.05). The longer the proximal gut resection, the lower was the mucosal enzyme activity. Both resection groups showed increased plasma cholesterol precursor proportions and crypt depth (P < 0.05), whereas villus height remained unchanged. After massive proximal resection campesterol and sitosterol proportions were inversely related to crypt cell proliferation (r = -0.86-0.83, P < 0.01). CONCLUSIONS: Increased crypt cell proliferation activated by massive proximal gut resection may act as a previously unrecognized factor in aggravating cholesterol malabsorption and retarding its recovery during the early postoperative period. These findings warrant further investigation.

Synchronous ileal autotransplantation impairs adaptation of remaining gut in pigs with proximal small bowel resection.

This study investigates the effects of ileal autotransplantation on morphology, crypt cell proliferation, and brush border disaccharidases of the remaining jejunoileum and colon in growing pigs with 75% proximal small bowel resection. Resection was performed on 30 pigs, of which 15 underwent an autotransplantation of the remaining ileum. The autotransplanted pigs showed reduced weight gain and remnant ileal length when compared to the resected controls. In the autotransplanted pigs, small bowel diameter and weight, mucosal weight and protein content, villus height and surface area, crypt depth, and the number of proliferating crypt cells were reduced similarly both in the intact jejunum and in the autotransplanted ileal remnant. Autotransplantation also decreased the number of proliferative crypt cells of the colon. Specific activities of maltase and sucrase tended to increase in the autotransplanted ileal remnant, whereas the total enzyme activities decreased. These results suggest that ileal autotransplantation disturbs postresectional adaptation of the remaining gut.

Nerve terminals containing neuropeptides decrease in number after massive proximal small bowel resection in the piglet.

The aim of this study was to evaluate possible changes in the neuropeptide innervation pattern of the remaining porcine ileum following 75% proximal resection of the small intestine. Three-month-old piglets were operated on and two months postoperatively full-thickness specimens of the proximal part of the distal ileum wall were taken. Age-matched 3- and 5-month-old unoperated piglets were used as controls. The number and intensity of VIP-, galanin-, enkephalin-, substance P-, and somatostatin-containing nerve fibers were estimated in sections processed for immunofluorescence microscopy and subjected to quantitative scoring. The VIP-, galanin-, and enkephalin-immunoreactive fibers of the circular muscle layer and villi were also quantitated by computer-assisted morphometry. The number and intensity of VIP-immunoreactive fibers in the mucosa and circular muscle layer markedly decreased after resection as compared to 3-month-old and 5-month-old controls (P < 0.05). The galanin immunoreactivity index decreased significantly after resection in the circular muscle layer as compared to both control groups (P < 0.05). The increase in the number of enkephalin-immunoreactive nerve fibers that normally occurred from 3 to 5 months of age was inhibited by the resection. We were not able to see any differences in somatostatin or substance P immunoreactivity between the groups. The results suggest that massive resection induces significant changes in the neuropeptide-containing innervation of the remaining small intestine. These findings are compatible with altered motor activity and mucosa function in the remain intestine.

Absorption, excretion, and distribution of plant sterols after proximal gut resection and autotransplantation of porcine ileum.

Contribution of different gut segments to plant sterol absorption, adaptation of plant sterol absorption after partial small bowel resection, and effects of gut transplantation (necessitates extrinsic autonomic denervation and lymphatic disruption) on plant sterol biodynamics are unclear. We studied the consequences of massive proximal small bowel resection and autotransplantation of the remaining ileum on the adaptive absorption and biodynamics of plant sterols. Dietary, fecal, biliary, hepatic and plasma plant sterols, fecal elimination and absorption of cholesterol, small bowel morphology, and intestinal transit were determined before (n = 5) and at 4, 8, and 14 wk after resection of the proximal 75% of the jejunoileum (n = 15) and autotransplantation of the remaining ileum (n = 15) or transection (n = 5). Proximal gut resection significantly reduced cholesterol absorption efficiency; percentage absorption and biliary secretion of plant sterols; plasma, biliary and hepatic campesterol-to-cholesterol proportions; and sitosterol proportions in plasma and bile. Autotransplantation of the remaining ileum further significantly decreased cholesterol absorption efficiency; percentage absorption and biliary secretion of campesterol; campesterol proportions in plasma, bile and liver; and plasma proportions of sitosterol while increasing fecal excretion of neutral and acidic steroids. Plasma proportions of the two plant sterols, but absorption of just campesterol, were gradually improved with increasing cholesterol absorption and villus height after proximal gut resection; the same result was observed to a lesser degree after ileal autotransplantation. In addition, significant positive correlations were found between percentage cholesterol and campesterol absorption and the plasma plant sterol proportions in both proximal resection groups, between campesterol absorption and ileal villus height in the resection group, and between campesterol absorption and intestinal transit time in the autotransplantation group. In conclusion, plasma campesterol and sitosterol closely reflect absorption of cholesterol and plant sterols from intact and autotransplanted ileum during adaptation to proximal gut resection. A loss of proximal gut absorptive surface impairs cholesterol and campesterol absorption more than sitosterol absorption, the latter being apparently less dependent on available jejunal villus surface area.

Intestinal adaptation after massive proximal small-bowel resection in the pig.

BACKGROUND: Small-intestinal adaptation to resection has been extensively studied in rats. The present study investigates morphology, crypt cell proliferation, and disaccharidase activities of the remaining small intestine and colon after 75% proximal resection of porcine small intestine. METHODS: Specimens were obtained from the proximal jejunum, middle and distal ileum, and proximal colon preoperatively (n = 5) and 14 weeks after small-bowel transection (n = 5) or resection (n = 5). Proliferation was analyzed immunohistochemically with the Ki-67 antigen MIB-1. Disaccharidase activities were determined in accordance with the method of Dahlqvist. RESULTS: In addition to macroscopic enlargement, resection markedly increased the villi and crypts of the remaining small bowel. Crypt cell proliferation decreased with advancing age after transection but remained at the preoperative level after resection. Specific, but not total, activities of maltase and sucrase in the mid-ileum decreased after resection. CONCLUSION: Small-intestinal adaptation in the pig involves macroscopic enlargement and a prompt increase in villus size, which is associated with high crypt cell proliferation.

How to diagnose chronic rejection. A study in porcine intestinal allografts.

Porcine small bowel allografts were followed for 18 weeks during immunosuppression with cyclosporine-A (CyA), azatioprine and prednisone. The mucosal alterations noted at the 12th week were epithelial vacuolation and loss of Goblet cells. Moderate infiltration of inflammatory cells, mainly lymphocytes, was found in the lamina propria. In addition, a few grafts exhibited oedema and fibrosis. Vessels already showed endothelial swelling and intimal proliferation at the 12th week. In the submucosa, the infiltration of inflammatory cells was not present till the 18th week. Further changes in the mucosa at the 18th week were the blunting of villi, cuboidal epithelium, crypt abscesses and epithelial atrophy. The histological alterations of mucosa and lamina propria existing in the full thickness biopsies were mostly also detectable in mucosal biopsies, provided that multiple biopsies were taken. Thus these parameters analyzed from mucosal biopsy material are suitable for the diagnosis and monitoring of chronic small bowel rejection. In autopsy, the most prominent features were in the mesenterial arteries: intimal proliferation, vasculitis, proliferation of media and endothelial alterations. The activity of the mucosal disaccharidases maltase and sucrase remained near the initial level till the 12th week and had decreased markedly by the 18th week.

Adaptive lipid metabolism after ileal autotransplantation in pigs with proximal gut resection.

BACKGROUND: Transplantation of the small intestine impairs intestinal absorptive function, but the adaptive response of a segmental graft is unknown. The aim of this study was to investigate the effects of ileal autotransplantation on the adaptive absorption and metabolism of lipids in pigs that had undergone proximal gut resection. METHODS: Serum lipids, plasma vitamins A and E, absorption and excretion of cholesterol, bile acids and fat, plasma cholesterol precursor and plant sterol proportions to cholesterol (respective markers of cholesterol synthesis and absorption), enteric structure, and transit were determined 4, 8, and 14 weeks after 75% proximal resection with (n = 15) or without (n = 15) autotransplantation of the remaining ileum. RESULTS: As compared with pigs that underwent proximal gut resection, the additional autotransplantation reduced the adaptive increase in total serum and high-density lipoprotein cholesterol, plasma plant sterol proportions and vitamin E concentrations, cholesterol and fat absorption efficiency, and villus height (p < 0.05 for all) during the 14 postoperative weeks and resulted in increases of up to 4.6, 2.7, 1.3, and 2.1 times the plasma cholesterol precursors (p < 0.005), fecal excretion of bile acids (p < 0.0005), neutral steroids (p < 0.005), and net elimination of cholesterol (p < 0.0005), respectively. Cholesterol and fat absorption and plasma plant sterols were significantly enhanced between 8 and 14 weeks after autotransplantation (p < 0.05, p < 0.005, and p < 0.05, respectively), whereas fecal elimination of cholesterol remained increased until the end of the follow-up. CONCLUSIONS: Autotransplantation of the ileum in pigs that have undergone proximal small bowel resection disturbs the adaptive absorption of cholesterol, bile acids, fat, and fat-soluble vitamins, resulting, through increased fecal elimination of cholesterol, in decreased serum cholesterol despite a marked compensatory increase in cholesterol synthesis.

Brush cytology in the course of acute small bowel allograft rejection.

OBJECTIVE: To examine the changes in brush cytology during acute small bowel allograft rejection and to evaluate the usefulness of cytology in detecting acute rejection. STUDY DESIGN: Heterotopic porcine small bowel allografts were followed by brush cytology and full-thickness biopsies during unmodified rejection. RESULTS: The most prominent changes in cell differential counts were an increase in the proportion of granulocytes and decrease in the proportion of epithelial cells. In brushed epithelial fragments, infiltration of granulocytes and acidophilia increased, and cell cohesion was gradually lost with the degeneration of nuclei and necrosis of epithelium. The cell differential count was compared to the histologic acute rejection index, which was created on the basis of five semiquantitatively evaluated histologic parameters. The sensitivity of cell differentiation in detecting histologically moderate or severe rejection was 87% (13 of 15 cases) and the specificity 76% (5 false positives in 21 negative cases). CONCLUSION: Suspicion of acute rejection can be assessed with reasonable reliability by cytology, but it cannot be detected earlier than by histology. Brush cytology complements mucosal biopsies in the evaluation of rejection and, as a rapid and cost-effective method, may even partly replace them. It may also prove valuable in detecting opportunistic bowel infections in immunosuppressed patients.