Subtherapeutic ganciclovir (GCV) levels and GCV-resistant cytomegalovirus in lung transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) infection results in significant morbidity and mortality in lung transplant recipients. Ganciclovir (GCV) has dramatically reduced complications caused by CMV infections. Unfortunately, GCV resistance is identified in 5-10% of CMV-infected patients. Mismatched CMV status and ongoing replication due to immunosuppression are risk factors for drug resistance. Whether subtherapeutic GCV levels contribute to resistance remains unknown. METHODS: A retrospective review was conducted in all 51 patients who underwent lung transplantation between March 2007 and June 2008 at Loyola University Medical Center. GCV resistance and outcome data of CMV-infected patients were analyzed to identify variables that may contribute to suboptimal response to CMV infection. RESULTS: During the 16-month period, CMV infection was identified in 21 of 51 lung transplant recipients. Ten of 21 patients (47.6%) had CMV infection with early response to GCV, and 11 patients (52.4%) had CMV infection with suboptimal response to GCV. GCV levels were obtained in the 11 CMV-infected patients with suboptimal response. In 6 patients, GCV levels were therapeutic; all 6 had delayed response to GCV. In 5 patients, GCV levels were subtherapeutic; each had persistent suboptimal response to GCV. Genotyping documented GCV-resistant (GCV-R) CMV in all 5 patients. Cystic fibrosis as the diagnosis requiring lung transplantation was associated with GCV-R CMV infection (P = 0.01). CONCLUSION: In our lung transplant recipient cohort, GCV levels were subtherapeutic in all patients with persistent suboptimal response to GCV, each of whom had GCV-R CMV infection. In contrast, GCV levels were therapeutic in CMV-infected patients with delayed GCV response.

Successful emergent lung transplantation after remote ex vivo perfusion optimization and transportation of donor lungs.

A recent clinical trial provided evidence that ex vivo lung perfusion (EVLP) results in optimized human donor lungs for transplantation. Excellent recipient outcomes were documented after 4 h of normothermic perfusion. We report a clinical case utilizing remote EVLP to assess and improve function of initially otherwise unacceptable injured donor lungs followed by transportation and subsequent bilateral lung transplantation in a patient with virally induced refractory respiratory failure supported with extracorporeal membrane oxygenation. This is the first lung transplantation with the application of remote EVLP, wherein the donor lungs were transported from the donor hospital to a center for EVLP and then transported to another hospital for transplantation. It is also the first case of lung transplantation in the United States utilizing EVLP for functional optimization leading to successful transplantation. Organ procurement data, EVLP assessment, and the pre- and postoperative course of the recipient are presented. The available evidence supporting EVLP, the humanitarian and cooperative utilization of lungs otherwise discarded, are discussed.

A review of the potential applications and controversies of non-invasive testing for biomarkers of aspiration in the lung transplant population.

Despite improvements in one-yr survival following lung transplantation, five-yr survival lags significantly behind the transplantation of other solid organs. The contrast in survival persists despite advancements in anti-rejection regimens, suggesting a non-alloimmune mechanism to chronic lung transplant failure. Notably, markers of aspiration have been demonstrated in bronchoalveolar lavage (BAL) fluid concurrent with bronchiolitis obliterans syndrome (BOS). This recent evidence has underscored gastroesophageal reflux (GER) and its associated aspiration risk as a non-alloimmune mechanism of chronic lung transplant failure. Given the suggested safety and efficacy of laparoscopic anti-reflux procedures in the lung transplant population, identifying those at risk for aspiration is of prime importance, especially concerning the potential for long-term improvements in morbidity and mortality. Conventional diagnostic methods for GER and aspiration, such as pH monitoring and detecting pepsin and bile salts in BAL fluid, have gaps in their effectiveness. Therefore, we review the applications and controversies of a non-invasive method of defining reflux injury in the lung transplant population: the detection of biomarkers of aspiration in the exhaled breath condensate. Only by means of assay standardization and directed collaboration may such a non-invasive method be a realization in lung transplantation.

Lung transplantation for cystic fibrosis: current concepts and one center's experience.

BACKGROUND: Although new approaches to the treatment of patients with cystic fibrosis (CF) are significantly prolonging their lives, most patients will eventually develop respiratory failure due to progressive bronchiectasis caused by chronic lung infection and inflammation and die from to respiratory failure. We examined our center's (University of Wisconsin Hospital and Clinics) experience with lung transplantation for patients with CF and reviewed the literature to examine current and evolving approaches to transplantation for this indication. METHODS: We reviewed all published literature pertaining to lung transplantation for CF through 2006, and we reviewed all aspects of transplantation for patients with CF at our institution from 1994 to 2005. RESULTS: Major complications following lung transplantation include acute rejection, bacterial infection, and bronchiolitis obliterans. Five-year survival at UWHC (Kaplan-Meier) is 67%, and survival was not adversely affected by transplanting patients receiving mechanical ventilation. The major cause of death for transplant recipients was bronchiolitis obliterans syndrome (BOS). CONCLUSIONS: Lung transplantation for CF is associated with acceptable survival rates and can improve quality of life. Lung transplant should be offered to all patients with advanced CF lung disease if they meet currently accepted inclusion and exclusion criteria.

Impact of donor and recipient factors on allograft survival in lung transplantation: A single-center analysis.

BACKGROUND: It remains unclear which donor and recipient factors influence long-term allograft function in lung transplantation (LTx). METHODS: From October 1988 to February 2005, a total of 280 recipients underwent LTx at our center. Donor data and cause of death (CoD) were analyzed. The CoD was categorized according to rate of increase in intracranial pressure at the time of death. Each donor and recipient factor was correlated with long-term graft function. Recipient details, type of transplant, indication for transplant, and time on waiting list were analyzed. Recipients were stratified based on allograft ischemia time (AIT): 0 to 6, 6 to 8, 8 to 10, and >10 hours. RESULTS: Mean donor age was 30.9 years (36.7% male); 49.8% were cytomegalovirus (CMV) positive. Donor CoD was characterized by a slow rise in intracranial pressure (ICP) in 34.4%, rapid ICP in 18.7%, an intermediate ICP in 44.3%, and with no rise in 2.6%. A graft survival benefit was seen with female donors (P = .048); 34.4% of recipients ultimately developed graft failure at long term follow-up. Mean recipient age was 48 years; 63% were male and mean body-mass index (BMI) was 23.6; 60.2% had single lung transplantation, and mean wait list time was 323 days. Mean AIT totaled 421 minutes. Graft survival was longer with AIT of 8 to 10 hours compared to 6 to 8 hours (P = .03). CONCLUSIONS: Donor factor analysis implied only female donor status conferred a long-term graft survival advantage. Intracranial pressure rise differences appear clinically unimportant. Prolonged cold ischemic time (>10 hours) or low recipient BMI did not adversely affect allograft function in our review.

Effects of University of Wisconsin and Euro-Collins solutions on interstitial pulmonary edema in isolated rat lungs.

Macromolecules are present in lung preservation solutions to limit liquid filtration out of the pulmonary circulation and minimize pulmonary edema. We tested the effectiveness of these molecules by measuring interstitial edema in rat lungs perfused with macromolecular solutions (University of Wisconsin [UW] solution and Euro-Collins solution supplemented with modified pentastarch [pentafraction, PEN]) or with solutions that lacked macromolecules (UW solution with PEN and Euro-Collins solution.) The lungs were inflated with air and perfused with one of the test solutions, then rapidly frozen and prepared for histological analysis. From tissue sections, we measured cross-sectional areas of pulmonary arteries and veins, and also measured cross-sectional areas of the interstitial spaces surrounding arteries and veins. We then calculated the interstitium-to-vessel cross-sectional area ratio. In lungs perfused with macromolecular solutions these ratios were 0.09+/-0.15 and 0.53+/-0.56 (mean +/- SD) for UW solution and Euro-Collins solutions solution with PEN, respectively (P

Successful extrarenal transplantation from non-heart-beating donors.

The current organ shortage has made utilization of organs from less-than-ideal donors more common. Although several transplant centers use kidneys from non-heart-beating donors (NHBDs), there has been reluctance to extend the use of these donors to extrarenal organs. Of the 130 donors referred to our organ procurement organization between January 1993 and May 1994, 16 (12.3%) were NHBDs. Organ retrieval from 10 of these resulted in extrarenal donation, 5 resulted in renal donation only, and 1 resulted in no retrieval as a result of prolonged warm ischemia (> 2 hr). A total of 39 organs were transplanted from these NHBDs. A rapid en bloc retrieval technique was used for extrarenal NHBDs. The mean warm ischemic time was 15.4 min; preservation times were similar for both NHBDs and heart-beating donors. After liver transplantation (n = 5), one episode of primary nonfunction that was technical in origin required retransplantation. Following simultaneous pancreas-kidney transplantation (n = 6), all patients were insulin independent and free of graft pancreatitis; one patient required hemodialysis (16.7%). After isolated renal transplantation (n = 21), 3 patients (14.3%) required hemodialysis. Three of 4 liver recipients are alive after a mean follow-up period of 12.7 months; all simultaneous pancreas-kidney and renal transplant recipients are alive after a mean follow-up period of 8.4 and 8.3 months, respectively. Three liver allografts, 5 pancreas and kidney allografts, and 19 renal allografts are functioning. The lung allograft was lost to rejection 81 days after transplantation; however, the recipient is alive 3 months after retransplantation. Our results demonstrate that in controlled situations, extrarenal organs can be utilized from NHBDs and can be expected to function similarly to organs retrieved from heart-beating donors. We increased the number of transplanted organs by 8.6% using NHBDs for both renal and extrarenal donation. Continued application of these techniques will likely further increase the number of organs retrieved for transplantation.

Human fetal pancreas--a potential source for transplantation.

Human fetal pancreas (HFP) represents an ideal tissue source for transplantation into diabetic patients. Transplantation of HFP lacks many of the technical problems associated with whole organ transplantation and HFP is readily available. In order to proceed with clinical HFP transplantation it must be demonstrated that HFP can reverse experimentally induced diabetes, that HFP can respond to glucose challenge in a manner similar to adult tissue, and that the immunogenicity of HFP can be reduced. We transplanted HFP (13-17 weeks gestational age) beneath the kidney capsule of streptozotocin-induced diabetic BALB/c nu/nu mice. Within 6 to 8 weeks following transplantation, 6 out of 7 (88%) animals became normoglycemic. Oral glucose tolerance tests were performed to determine in vivo graft function. Results in cured animals were identical to those of normal BALB/c nu/nu mice. In vitro insulin response to glucose challenge demonstrated that grafted HFP was capable of insulin secretion in the presence of high glucose while fresh fetal tissue was not. Human passenger leukocytes, identified immunohistologically at various times after transplantation with monoclonal antibodies to HLA-DR and Leu 10, were greatly reduced by 32 weeks posttransplant. Our data demonstrate that HFP will differentiate and mature in the diabetic nude mouse and that human passenger leukocyte content can be reduced. These findings suggest that HFP is functionally suitable for transplantation into diabetic patients.

Stable lung allograft outcome correlates with the presence of intragraft donor-derived leukocytes.

BACKGROUND: The role of bone marrow-derived "passenger" leukocytes in the outcome of solid organ transplantation remains controversial. This study tested the relationship between high levels of donor-derived leukocytes within the transplanted organ and clinical outcome after lung transplantation. METHODS: Sequential bronchoalveolar lavage samples were obtained from human lung allograft recipients. Leukocytes of donor origin in the bronchoalveolar lavage fluid were detected using two-color immunofluorescence, and the results were correlated with multiple clinical parameters. RESULTS: Mean donor leukocyte levels for the first 200 days after transplantation were higher in patients with a good transplantation outcome compared with those patients who lost their grafts due to acute rejection (AR) or developed bronchiolitis obliterans syndrome. The presence of low numbers of donor-derived leukocytes for the first 200 days after transplantation was found to be a significant risk factor for graft loss due to either acute or chronic rejection (P=0.032). Nearly all patients (85%) experienced AR episodes. However, the time to onset of severe AR episodes was significantly longer (P=0.049), and the incidence of these episodes reduced, in patients who maintained high numbers of donor-derived leukocytes for the first 200 days after transplantation. CONCLUSIONS: The presence of high numbers of donor-derived leukocytes, particularly macrophages, in the transplanted lung in the first 200 days after transplantation was associated with stable graft function. Donor-derived leukocytes were reduced or absent in patients with a poor transplantation outcome. These findings rule out a negative influence of persisting donor leukocytes and are consistent with the emerging two-way models of transplant tolerance.

Safety, tolerance, and efficacy of adenosine as an additive to blood cardioplegia in humans during coronary artery bypass surgery.

Myocardial stunning after heart surgery is associated with increased morbidity and mortality in patients with severe multivessel disease and reduced myocardial function. The purpose of this study was to evaluate the safety, tolerance, and efficacy of adenosine as a cardioprotective agent when added to blood cardioplegia in patients undergoing coronary artery bypass surgery. Sixty-one patients were randomized to standard cold-blood cardioplegia, or cold-blood cardioplegia containing 1 of 5 adenosine doses (100 microM, 500 microM, 1 mM, 2 mM, and 2 mM with a preischemic infusion of 140 microg/kg/min of adenosine). Invasive and noninvasive measurements of ventricular performance and rhythm were obtained preoperatively, prebypass, and then at 1, 2, 4, 8, 16, and 24 hours postbypass. Use of inotropic agents and vasoactive drugs pastoperatively was recorded; blood samples were collected for measurement of nucleoside levels. High-dose adenosine treatment was associated with a 249-fold increase in the plasma adenosine concentration and a 69-fold increase in the combined levels of adenosine, inosine, and hypoxanthine (p <0.05). Increasing doses of the adenosine additive were also associated with lower requirements of dopamine (p = 0.003) and nitroglycerine (p = 0.001). The 24-hour average doses for dopamine and nitroglycerine in the placebo group were 28-fold and 2.6-fold greater than their respective high-dose adenosine treatment cohorts. Finally, the placebo- and 100 microM-adenosine group was associated with a lower ejection fraction when compared to patients receiving the intermediate dose or high-dose treatment. These findings are consistent with the hypothesis that adenosine is effective in attenuating myocardial stunning in humans.

Soluble HLA class I in epithelial lining fluid of lung transplants: associations with graft outcome.

We hypothesized that the small amounts of donor HLA-A and HLA-B proteins detected in the serum during organ allograft rejection are indicative of higher local releases within the graft itself. We determined the concentrations of total HLA class I (HLA-I) and, in selected cases, specific donor and host HLA-A and HLA-B proteins, in the epithelial lining fluid (ELF) sampled by bronchoalveolar lavage (BAL) of lung transplant recipients (n = 37) and of normal controls (n = 25). We found that 1) HLA-I proteins were enriched in the lung ELF relative to other proteins; 2) the concentration of HLA-I in the ELF of well-functioning transplants was similar to that in normal lungs; 3) HLA-I proteins and total proteins were elevated in the ELF of patients who developed chronic rejection or refractory acute rejection; 4) the concentration of HLA-I was correlated with the percentage of neutrophils but not with the percentage of lymphocytes in the ELF of transplanted lungs; and 5) only the percentage of lymphocytes was elevated in the ELF of transplant patients with active CMV infections. Total HLA-I from the ELF was found to contain a mixture of both donor- and recipient-type HLA-A and HLA-B proteins and the donor-type HLA-A2 was found to be highly enriched in the ELF relative to serum.

Soluble donor HLA class I and beta 2m-free heavy chain in serum of lung transplant recipients: steady-state levels and increases in patients with recurrent CMV infection, acute rejection episodes, and poor outcome.

We determined the concentration of donor sHLA/beta(2)m and total beta(2)m-free heavy chain (HC) in the serum of lung transplant recipients with ELISA assays. While we were unable to detect specific donor beta(2)m-free HCs due to a lack of available antibodies, we could determine if events that led to an increase in the release of beta(2)m-free HC also led to an increase in the release of donor sHLA/beta(2)m, particularly the 36 kDa, proteolytically cleaved form. We found that lung transplants constituitively release donor sHLA/beta(2)m at ng/ml levels. The levels (both of donor sHLA/beta(2)m and total beta(2)m-free HC) were significantly increased in CMV-sero-negative recipients (but not in CMV-sero-positive recipients) at the onset of post-transplant CMV disease. Acute rejection episodes were also associated with an increased release of donor sHLA/beta(2)m, but not of beta(2)m-free HC. However, in patients with particularly poor outcome (i.e., graft loss within 1 year) there was a significant release of beta(2)m-free HC. Analysis of one such patient showed a predominance of 36 kDa forms of donor-sHLA/beta(2)m. Our data are consistent with the hypothesis that the metalloproteinase that cleaves beta(2)m-free HC is active during uncontrolled CMV infection and acute rejection. However, recall responses to CMV and controlled immune responses to donor may result in little or no activation of sHLA class I release.

The therapeutic potential of nitric oxide in lung transplantation.

Endogenously produced oxides of nitrogen appear to play important roles in tissue and organ homeostasis. Endogenous production of nitric oxide, which can be altered in response to various stimuli, can modulate vascular tone, oxyradical cascades, cell adhesion, and other aspects of inflammation. Because exogenously administered (inhaled) nitric oxide can mediate pulmonary vasodilatation and improve pulmonary function in some patients with lung injury, treatment of lung allograft recipients with inhaled nitric oxide may ameliorate ischemia-reperfusion injury, thereby improving perioperative pulmonary function and diminishing ventilatory support requirements. This review examines the biology of nitric oxide and present data that support its potential therapeutic effects for lung transplant recipients.

Vascular endothelial growth factor in human lung transplantation.

STUDY OBJECTIVES: To determine levels of the vascular endothelial growth factor (VEGF) isoform consisting of 165 amino acids (VEGF(165)) in BAL fluid (BALF) from lung transplant recipients (LTXs). DESIGN: Bronchoscopy with BAL was performed on LTXs and normal volunteers (NVs). SETTING: University hospital. PARTICIPANTS: LTXs (n = 57) and NVs (n = 15). MEASUREMENTS AND RESULT: VEGF(165) concentrations in BALF were higher (mean +/- SEM, 240 +/- 32 pg/mL) for NVs (n = 15) vs 133 +/- 14 pg/mL for LTXs (n = 37) who were stable without evidence of significant rejection or infection at 6 months after transplantation (p < 0.0001). BALF VEGF concentrations sampled at 24 to 48 h, 2 weeks, 4 weeks, and 6 months after transplantation for 11 LTXs who lacked rejection or infection at any time point were 71 +/- 8 pg/mL, 80 +/- 20 pg/mL, 82 +/- 13 pg/mL, and 167 +/- 31 pg/mL, respectively. VEGF concentrations in BALF for LTXs with cytomegalovirus (CMV) pneumonia were 55 +/- 12 pg/mL (n = 10), 117 +/- 33 pg/mL for grade A3 acute rejection (n = 9), and 82 +/- 17 pg/mL (n = 14) for active bronchiolitis obliterans syndrome (BOS). Concentrations of VEGF in BALF at 6 months for the 32 stable recipients with bilateral lung transplantation were significantly higher for those with higher values for FEV(1), and BALF VEGF concentrations were significantly lower in BALF at 6 months for those recipients who subsequently went on to develop BOS (86 +/- 19 pg/mL) vs those who did not (158 +/- 18 pg/mL; p = 0.03). Serum concentrations of VEGF did not correlate with VEGF concentrations in BALF, but serum VEGF was 291 +/- 62 pg/mL at 10 to 14 days after transplantation vs 130 +/- 20 pg/mL at 4 weeks for nine LTXs with paired samples (p < 0.02). Serum VEGF concentrations for NVs (n = 15) were 102 +/- 15 pg/mL vs 94 +/- 17 for stable LTXs (n = 12) at 24 weeks after transplantation and 123 +/- 33 pg/mL for LTXs with active BOS (n = 10). CONCLUSIONS: BALF VEGF concentrations are particularly depressed at early time points following lung transplantation, gradually improve in the absence of significant rejection or infection, and are lower with active rejection or CMV pneumonia.

Does University of Wisconsin solution harm the transplanted heart?

BACKGROUND: University of Wisconsin solution (UW) has been shown to be an effective preservative for the cardiac allograft. Recently, the high potassium content of UW has been implicated in causing coronary endothelial damage, allegedly contributing to development of cardiac allograft vasculopathy (CAV) and eventually to poorer survival. METHODS: We examined our experience using UW for preservation of cardiac allografts between 1990 and 1994 (n = 94), and compared these to hearts preserved with the lower potassium-containing Stanford solution used at our center between 1986 and 1990 (n = 65). Indices of graft function, ischemic injury, CAV incidence, CAV severity, and survival were evaluated. RESULTS: The 2 groups were similar in age, gender, diagnosis, donor inotropic support, donor-recipient weight ratio, incidence of acute graft failure, and cytomegalovirus seroconversion. UW-preserved hearts came from older donors (30.5 vs 24.1 years, p < .001), and were transplanted into more status 1 recipients (56% vs 22%, p < .001), consistent with current trends. Mean ischemic time of UW-preserved hearts was significantly longer (184 vs 155 minutes, p < .005) although time required to wean from bypass was less (45.5 vs 73.8 minutes, p < .001) and there was a trend towards less inotropic requirement. CPK-MB release was less with UW preservation (63 vs 87 microg/ dL, p = .001). Three years after transplantation, both groups were similar in the incidence of CAV (UW, 27.3%; STNF, 37.5%; p = 0.27), and also the severity of CAV (p = 0.78). Deaths attributed to CAV were equal in each group (UW, 11.4% vs STNF, 10.7%; p = 0.79). Kaplan-Meier survival analysis revealed equivalent survival curves (p = 0.26). CONCLUSIONS: We conclude that UW is a safe and effective myocardial preservative, allowing longer ischemic times with equivalent graft function. Our data suggest that when UW is used for cardiac allograft preservation, both CAV and survival are comparable to the experience with other preservatives containing lower concentrations of potassium.

Efficacy of tacrolimus in the treatment of refractory rejection in heart and lung transplant recipients.

BACKGROUND: Refractory acute cellular rejection may occur despite triple-drug immunosuppression (cyclosporine A, steroids, azathioprine/mycophenolate mofetil). The purpose of this study was to determine the efficacy of tacrolimus rescue therapy in patients maintained on cyclosporine-based immunosuppression (CBI). METHODS: Between December 1993 and October 1996, 208 patients underwent thoracic organ transplantation at the Hospital of the University of Wisconsin at Madison. One hundred forty-nine patients underwent heart replacement; 59 underwent lung transplantation. One hundred thirty-nine of the heart transplant cohort received CBI preceded by induction therapy with OKT3. Forty-six of the lung transplant cohort received CBI without induction cytolytic therapy. Refractory rejection was defined as failure to respond to high-dose steroids (500 mg to 1 g IV methylprednisolone for 3 days) and/or monoclonal antibody therapy (OKT3, 5 to 10 mg IV/day for 7 to 14 days). In patients with refractory rejection, cyclosporine was replaced with tacrolimus. RESULTS: Overall, 16% (30/185) of patients receiving CBI experienced refractory rejection. Thirty-one episodes of grade IIIa or greater rejection occurred in 11% (15/139) of heart transplant recipients. Twenty episodes of grade II to IV rejection occurred in 33% (15/46) of lung transplant recipients. After tacrolimus rescue therapy, 93% (14/15) of patients in the heart transplant group converted to grade II or less rejection. Refractory rejection was reversed in 73% (11/15) of the lung transplant group. Reversal was documented at biopsy in all (8/8) lung recipients in whom it had been histologically identified. FEV1 values of 3 additional patients stabilized. CONCLUSIONS: The incidence of refractory rejection in thoracic organ transplant recipients on CBI is significant. Reversal of refractory rejection follows rescue immunotherapy with tacrolimus.

Donor-derived human leukocyte antigen class I proteins in the serum of heart transplant recipients.

BACKGROUND: Human leukocyte antigen class I proteins are expressed on most cell types in all organ allografts but are constitutively secreted only by certain organs, for example, the liver. We hypothesized that detectable levels of donor-derived human leukocyte antigen proteins would be released from transplanted cardiac allografts only when the allograft was immunologically stimulated, that is, during rejection and perhaps during viral infection. If so, then the release of donor human leukocyte antigen might be a noninvasive monitor of these events. METHODS: We used an enzyme-linked immunosorbent assay to detect donor-derived human leukocyte antigen-A2 in the serum of 21 human leukocyte antigen-A2 negative recipients of human leukocyte antigen-A2-positive heart transplants. The level of donor human leukocyte antigen-A2 during the first 100 days after transplantation was correlated with the clinical status of the patient. RESULTS: We found little or no donor human leukocyte antigen in the serum of heart transplant recipients whose postoperative clinical course was unremarkable for infection or rejection. We did find donor-derived human leukocyte antigen in the serum of heart transplant recipients transiently in the week immediately after transplantation, continuously from patients in whom chronic rejection was developing, during cytomegalovirus infection, and during some, but not all, acute rejection episodes as determined by endomyocardial biopsy. CONCLUSIONS: These findings are consistent with the hypothesis that the donor human leukocyte antigen serum level reflects vascular diseases, rather than myocardial disease in the transplanted heart. Therefore, the serum level of donor human leukocyte antigen cannot be used as a monitor of cellular infiltration and myocyte damage as currently assessed by endomyocardial biopsy but may be an early indicator of the development of vascular disease such as chronic rejection.

Fatal gastric artery dissection and rupture occurring as a paraesophageal mass: a case report and literature review.

Gastric artery aneurysms are rare, and the majority occur as life-threatening hemorrhage with few premonitory signs or symptoms. We report an unusual hemorrhagic manifestation of a ruptured gastric artery aneurysm, occurring as a pleural effusion and an apparent paraesophageal mass. Acute intraperitoneal and mediastinal bleeding from the extravisceral portion of the left gastric artery resulted in hemorrhagic shock, prompting an emergency laparotomy. Extensive medial degeneration in the gastric artery probably contributed to dissection and rupture.

Acute colonic ileus (pseudo-obstruction) in renal transplant recipients.

Colon complications are a potential source of serious morbidity to the immunosuppressed patient. Because of multiple predisposing factors, renal transplant patients are a high-risk group for the development of acute colonic pseudo-obstruction. During a recent 18-month period, 290 renal transplants (79 living, 211 cadaveric donors) were performed and prospectively analyzed for colonic dysmotility. A total of 34 episodes of acute colonic ileus (30 primary, 4 recurrent) occurred in 30 (10.3%) renal transplant recipients. Acute colonic ileus was more frequent after living-donor transplantation (19.0% vs. 7.1%, p = 0.006). Analysis of multiple variables revealed that the incidence of acute colonic ileus was directly related to mean cumulative prednisone dosage (p less than 0.05). Medical therapy (rapid steroid reduction, bowel rest) resulted in a 76.7% response, whereas 8 patients underwent colonoscopy because of progression to acute pseudo-obstruction. The success rate for colonoscopic decompression was 87.5%; in 1 patient cecal perforation developed after unsuccessful decompression. Overall, 33 of 34 (97.1%) episodes of acute colonic ileus were successfully treated. Steroid-induced ileus (pseudo-obstruction) is a potentially malignant early form of colonic dysmotility infrequently reported in transplant recipients. Successful management requires early clinical recognition, reduction in steroid dosage, bowel rest, and urgent colonoscopic decompression in select cases.