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Phillip Ruiz

Publications and source records attributed to Phillip Ruiz.

At least 37 records · Page 2Linked to original sources
PubMed2004

Treatment of established recurrent hepatitis C in liver-transplant recipients with pegylated interferon-alfa-2b and ribavirin therapy.

INTRODUCTION: The management issues of transplant patients with hepatitis C virus (HCV) are complex, and interferon therapy is often ineffective. We present data from a retrospective review in liver-transplant recipients suffering from HCV recurrence that were treated with pegylated alpha-2b interferon and ribavirin. METHODS: A retrospective review of transplant recipients that received combination pegylated alpha-2b interferon (1.5 mcg/kg/wk) and ribavirin (400-600 mg/day) therapy intended for at least 48 weeks. Complications were recorded and included neutropenia (<750 cells), anemia (hemoglobin <8 g) with and without treatment consisting of blood transfusions, erythropoietin, or dose reduction of ribavirin, and depression. The diagnosis of HCV recurrence was determined by an increase in liver chemistries, histopathologic findings with inflammation along with viral recurrence using the COBAS AMPLICOR HCV test. RESULTS: Fifty-seven liver-transplant recipients were included, 29 naive (group 1) to therapy and 28 nonresponders (group 2) to at least 6 months of interferon and ribavirin therapy. Eight (27.6%) patients in group 1 and six (21%) patients in group 2 were HCV nondetectable at the end of 48 weeks of therapy. Ribavirin therapy was decreased in 13 of 29 (45%) for group 1 and 11 of 28 (39%) in group 2. Therapeutic interventions were 4 of 57 (7%) blood transfusions, 23 of 57 (40%) erythropoietin, and 17 of 57 (30%) filgrastim. CONCLUSION: Combination pegylated interferon with ribavirin appears to effective therapy in HCV recurrence and in HCV nonresponsive to interferon and ribavirin. This data reveals the difficulty and caution that must be taken when treating HCV-R liver-transplant recipients with combination pegylated alpha-2b interferon and ribavirin therapy.

Adult↗
PubMed2004

Decreased expression of the Ets family transcription factor Fli-1 markedly prolongs survival and significantly reduces renal disease in MRL/lpr mice.

Increased Fli-1 mRNA is present in PBLs from systemic lupus erythematosus patients, and transgenic overexpression of Fli-1 in normal mice leads to a lupus-like disease. We report in this study that MRL/lpr mice, an animal model of systemic lupus erythematosus, have increased splenic expression of Fli-1 protein compared with BALB/c mice. Using mice with targeted gene disruption, we examined the effect of reduced Fli-1 expression on disease development in MRL/lpr mice. Complete knockout of Fli-1 is lethal in utero. Fli-1 protein expression in heterozygous MRL/lpr (Fli-1(+/-)) mice was reduced by 50% compared with wild-type MRL/lpr (Fli-1(+/+)) mice. Fli-1(+/-) MRL/lpr mice had significantly decreased serum levels of total IgG and anti-dsDNA Abs as disease progressed. Fli-1(+/-) MRL/lpr mice had significantly increased splenic CD8(+) and naive T cells compared with Fli-1(+/+) MRL/lpr mice. Both in vivo and in vitro production of MCP-1 were significantly decreased in Fli-1(+/-) MRL/lpr mice. The Fli-1(+/-) mice had markedly decreased proteinuria and significantly lower pathologic renal scores. At 48 wk of age, survival was significantly increased in the Fli-1(+/-) MRL/lpr mice, as 100% of Fli-1(+/-) MRL/lpr mice were alive, in contrast to only 27% of Fli-1(+/+) mice. These findings indicate that Fli-1 expression is important in lupus-like disease development, and that modulation of Fli-1 expression profoundly decreases renal disease and improves survival in MRL/lpr mice.

Animals↗
PubMed2004

Tenofovir therapy for lamivudine resistance following liver transplantation.

BACKGROUND: Resistant hepatitis B virus (HBV) strains develop in 30% of liver transplant recipients treated with lamivudine within 2 years from the time of transplantation. OBJECTIVE: To assess safety and outcomes of tenofovir salvage therapy for patients with lamivudine resistance in a retrospective cohort of liver-transplanted patients. METHODS: Medical records were retrospectively evaluated for patients who received tenofovir. Data collected included demographics, HBV serologic information prior to and during tenofovir therapy, drug-related complications, and creatinine clearance. Criteria for lamivudine resistance included elevation of liver chemistries along with reappearance of hepatitis B surface antigen, hepatitis Be antigen, and/or HBV DNA. RESULTS: Sixteen patients showed resistance to lamivudine at 10-85 months (median 26) following liver transplantation. Tenofovir 300 mg/day orally was added in 8 patients 1-66 months after the development of viral lamivudine resistance and continued for 14-26 months (median 19.3). All 8 patients experienced HBV DNA viral suppression, with 7 currently nondetectable. No adverse events were reported, and creatinine clearance was not impaired. CONCLUSIONS: Our results suggest that tenofovir safely and markedly decreases replication of lamivudine-resistant HBV variants after liver transplantation and is another potential option for the treatment of HBV lamivudine resistance.

Adenine↗
PubMed2004

Donor-specific B-cell tolerance after ABO-incompatible infant heart transplantation.

Although over 50 years have passed since its first laboratory description, intentional induction of immune tolerance to foreign antigens has remained an elusive clinical goal. We previously reported that the requirement for ABO compatibility in heart transplantation is not applicable to infants. Here, we show that ABO-incompatible heart transplantation during infancy results in development of B-cell tolerance to donor blood group A and B antigens. This mimics animal models of neonatal tolerance and indicates that the human infant is susceptible to intentional tolerance induction. Tolerance in this setting occurs by elimination of donor-reactive B lymphocytes and may be dependent upon persistence of some degree of antigen expression. These findings suggest that intentional exposure to nonself A and B antigens may prolong the window of opportunity for ABO-incompatible transplantation, and have profound implications for clinical research on tolerance induction to T-independent antigens relevant to xenotransplantation.

ABO Blood-Group System↗
PubMed2004

Modulation of renal disease in MRL/lpr mice by suberoylanilide hydroxamic acid.

Epigenetic regulation of gene expression is involved in the development of many diseases. Histone acetylation is a posttranslational modification of the nucleosomal histone tails that is regulated by the balance of histone deacetylases and histone acetyltransferases. Alterations in the balance of histone acetylation have been shown to cause aberrant expression of genes that are a hallmark of many diseases, including systemic lupus erythematosus. In this study, we determined whether suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor: 1) inhibits inflammatory mediator production in vitro and 2) modulates lupus progression in vivo. Mesangial cells isolated from 10-wk-old MRL/lpr mice were stimulated with LPS/IFN-gamma and incubated with SAHA. TNF-alpha, IL-6, NO, and inducible NO synthase expression were inhibited by SAHA. We then treated MRL/lpr mice with daily injections of SAHA from age 10 to 20 wk. The animals treated with SAHA had decreased spleen size and a concomitant decrease in CD4-CD8- (double-negative) T cells compared with controls. Serum autoantibody levels and glomerular IgG and C3 deposition in SAHA-treated mice were similar to controls. In contrast, proteinuria and pathologic renal disease were significantly inhibited in the mice receiving SAHA. These data indicate that SAHA blocks mesangial cell inflammatory mediator production in vitro and disease progression in vivo in MRL/lpr mice.

Adjuvants, Immunologic↗
PubMed2004

Sirolimus-associated hepatotoxicity in liver transplantation.

BACKGROUND: Sirolimus is an immunosuppressant that exerts anti-rejection activity by inhibiting T-cell activity and is used to treat chronic rejection and calcineurin-related nephrotoxicity. Unlike tacrolimus and cyclosporine, it has no effect on calcineurin activity in liver transplant recipients. OBJECTIVE: To report correlates of survival outcomes in a series of patients with putative sirolimus-related hepatotoxicity after liver transplant. METHODS: We retrospectively reviewed the medical records of patients who underwent a liver transplant for chronic hepatitis C virus (HCV) and who received sirolimus immunosuppressive therapy between November 2000 and November 2003. Extracted data included sirolimus serum concentrations, frequency of sirolimus-related adverse effects, drug-related clinical hepatitis, and survival outcomes. RESULTS: Ten patients were found to have been treated with sirolimus for either renal insufficiency (n = 6) or chronic rejection (n = 4). Six patients had liver biopsies, while the remaining 4 patients were clinically diagnosed with rejection. Two of the 6 patients demonstrated changes consistent with sinusoidal congestion and one with eosinophilia, consistent with an allergic drug reaction. HCV viral load increased slightly, from 600 000 to 700 000 IU/mL. Mean baseline transaminase levels were 45 IU/L for aspartate aminotransferase and 50 IU/L for alanine aminotransferase, with peak levels of 210 and 180 IU/L, respectively. The time to transaminase increase was a mean of 21 days when sirolimus was added, with resolution within 27 days (mean) after its discontinuation. No changes were evident in antiviral therapy. Combination sirolimus and tacrolimus concentrations were maintained at >10 ng/mL; average monotherapy with sirolimus was 12 ng/mL, and average time on therapy was 25 weeks. CONCLUSIONS: Sirolimus-related hepatotoxicity is an important complication after liver transplant. Immediate recognition is critical to avoid confusion with other causes of abnormal serum aminotransferases after liver transplant, and discontinuation of the drug may be required.

Alanine Transaminase↗
PubMed2004

The use of Campath-1H as induction therapy in renal transplantation: preliminary results.

BACKGROUND: In an attempt to reduce both initial and long-term (nephrotoxic) calcineurin inhibitor maintenance dosage and totally eliminate maintenance corticosteroids, alemtuzumab (Campath-1H) was used as induction therapy in first cadaver and non-HLA-identical living donor renal transplantation. METHODS: Forty-four de novo renal allograft recipients were treated with Campath-1H (0.3 mg/kg) on days 0 and 4 postoperatively, preceded by methylprednisolone boluses. Maintenance target 12-hr tacrolimus trough levels of 5 to 7 ng/mL were operational from the outset as well as (reduced) mycophenolate mofetil dosage of 500 mg twice daily. No corticosteroids were planned to be given after the first week postoperatively. RESULTS: With a median follow-up of 9 (range, 1-19) months, patient and graft survival rates are each at 100%. Biopsy-proven acute rejection was diagnosed in four patients. Infections requiring hospitalization developed in four patients. Thirty-eight recipients remain without the need for long-term corticosteroid therapy. CONCLUSIONS: In an early assessment, the combination of Campath-1H, low dosing of tacrolimus and mycophenolate mofetil, and avoidance of maintenance corticosteroid use seems to be safe and effective for kidney transplant recipients. Long-term outcomes will be reported in the future.

Alemtuzumab↗
PubMed2004

A retrospective review of liver transplant patients treated with sirolimus from a single center: an analysis of sirolimus-related complications.

BACKGROUND: Sirolimus (SRL) is a powerful immunosuppressant used primarily in calcineurin inhibitors (CNI)-related nephrotoxicity. However, reports of drug-related side effects are increasing. The aim of our report is to review the frequency and timing of these complications within our transplant patient population. METHODS: We retrospectively reviewed the medical records of liver-transplanted patients treated with sirolimus between November 1998 and April 2002. The data collected included SRL serum levels, frequency of reported and documented SRL-related side effects, and survival outcomes. Statistical evaluation included Pearson chi-square and the Fisher's exact tests. RESULTS: Overall, 205 patients were identified, with 30 patients removed from the analysis for different reasons. Of the remaining 175 patients, 91 (52%) patients developed a complication other than an increase in serum triglycerides and/or cholesterol. The most frequent complications were: bilateral lower extremity edema (57.1%), dermatitis (25.3%), oral ulcers (24.2%), joint pain (23.0%), pleural effusion (16.5%) and increase in abdominal girth (9.9%). Other complications included: generalized edema (5.5%), pericardial effusion (5.5%), facial edema (2.2%), and upper extremity edema (1.3%). In addition, we reported two cases of hepatic artery thrombosis, one case of wound dehiscence with evisceration that required surgical repair, and one case of skin cancer. Interestingly, we found that a previous history of myocardial ischemia correlates with the development of SRL side effects. CONCLUSIONS: SRL is a powerful immunosuppressant but not devoid of side effects. These results have elevated our level of suspicion when instituting SRL and may help with early recognition and prevention of drug related complications.

Edema↗
PubMed2004

Preliminary experience with alemtuzumab (Campath-1H) and low-dose tacrolimus immunosuppression in adult liver transplantation.

BACKGROUND: The administration of alemtuzumab (Campath-1H [C1H]; Berlex Laboratories, Montville, NJ) at transplantation prevents a vigorous immune response and is believed to allow a gradual engagement of the host immune system. We report our preliminary experience with C1H and tacrolimus (Tac) immunosuppression in adult liver transplantation. METHODS: We administered C1H and low-dose Tac to 40 adult recipients of cadaveric liver allografts between December 2001 and April 2003. A control group who met the same eligibility criteria consisted of 50 liver transplant recipients treated with our standard Tac and steroids protocol. RESULTS: Baseline characteristics and patient and graft survival were similar (P >0.15). The incidence of acute rejection was significantly lower during the first 2 months posttransplantation (P =0.002) and slightly lower overall in the study group versus the control group at 12 months (46% vs. 55%, P =0.12, log-rank test). Median time to rejection among those experiencing rejection was significantly longer in the study group versus control group (2.76 vs. 0.34 months, P =0.0007). The mean Tac dose, 12-hr trough level, and percentage of patients receiving maintenance steroids were significantly lower in the group receiving C1H and Tac (P <0.0001 during the first 3 months, P <0.05 thereafter), as were the mean creatinine levels (P <0.05) and incidence of nephrotoxicity (P =0.004, conversion from Tac to other agents). Finally, in the group receiving C1H/Tac, patients with an average Tac trough level less than 6.5 ng/mL during the first 2 months post-transplantation demonstrated a significantly higher rejection rate beyond that time (P =0.02). CONCLUSION: C1H and low-dose Tac seems to be at least as effective as our standard Tac and steroids regimen in preventing acute rejection in adult liver allotransplantation with less renal toxicity and less use of maintenance steroids.

Acute Disease↗
PubMed2004

A randomized long-term trial of tacrolimus and sirolimus versus tacrolimus and mycophenolate mofetil versus cyclosporine (NEORAL) and sirolimus in renal transplantation. I. Drug interactions and rejection at one year.

BACKGROUND: To reduce long-term nephrotoxic calcineurin inhibitor dosage, adjunctive sirolimus or mycophenolate mofetil (MMF) was used in a 150-patient, randomized, three-armed trial in cadaveric or human leukocyte antigen non-identical living-donor first renal transplant recipients (n=50/group). METHODS: Group A received tacrolimus and sirolimus. Target tacrolimus trough levels postoperatively were 10, 8, and 6 ng/mL at 1 month, 6 months, and 1 year, respectively. Group B received tacrolimus and MMF. Target tacrolimus trough levels were 10 and 8 ng/mL at 1 month and 1 year, with a targeted dose of MMF of 1 g twice daily. Group C received cyclosporine A (CsA) (Neoral, Novartis, Basel, Switzerland) and sirolimus with target CsA trough levels of 225 and 175 ng/mL at 1 month and 1 year. Maintenance sirolimus target trough levels were 8 ng/mL in groups A and C. Each group received daclizumab induction and methylprednisolone maintenance. This first of two companion 1-year reports details demographics, drug-dosing interactions, and rejection. RESULTS: There were no notable differences in group demographics, but a somewhat less favorable course occurred in group C, despite higher bioavailability of sirolimus in group C versus group A (P<0.001). Acute rejection rates were lower in groups A (4%) and B (4%) combined versus group C (14%) (P=0.03). Histopathologic findings were supported by comparing perioperative with 1-year postoperative protocol biopsies. CONCLUSIONS: This 1-year interim analysis indicates that a decreasing dosage of tacrolimus with either adjunctive sirolimus or MMF may optimize future graft survival versus a less favorable outcome using a similar algorithm with CsA and sirolimus.

Adult↗
PubMed2004

A randomized long-term trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus cyclosporine (NEORAL)/sirolimus in renal transplantation. II. Survival, function, and protocol compliance at 1 year.

BACKGROUND: In an attempt to reduce chronic calcineurin inhibitor induced allograft nephropathy in first cadaver and human leukocyte antigen non-identical living-donor renal transplantation, sirolimus (Siro) or mycophenolate mofetil (MMF) was tested as adjunctive therapy, with planned dose reductions of tacrolimus (Tacro) over the first year postoperatively. Adjunctive Siro therapy with a similar dose reduction algorithm for Neoral (Neo) was included for comparison. METHODS: The detailed dose reduction plan (Tacro and Siro, group A; Tacro and MMF, group B; Neo and Siro, group C) is described in our companion report in this issue of Transplantation. The present report documents function, patient and graft survival, protocol compliance, and adverse events. RESULTS: As mentioned (in companion report), group demographics were similar. The present study shows no significant differences in 1-year patient and graft survival but does show a trend that points to more difficulties in group C by way of a rising slope of serum creatinine concentration (P=0.02) and decreasing creatinine clearance (P=0.04). There were more patients who discontinued the protocol plan in group C. Thus far, no posttransplant lymphomas have appeared, and infectious complications have not differed among the groups. However, a greater percentage of patients in group C were placed on antihyperlipidemia therapy, with an (unexpected) trend toward a higher incidence of posttransplant diabetes mellitus in this group. Group A required fewer, and group B the fewest, antihyperlipidemia therapeutic interventions (P<0.00001). CONCLUSIONS: This 1-year interim analysis of a long-term, prospective, randomized renal-transplant study indicates that decreasing maintenance dosage of Tacro with adjunctive Siro or MMF appears to point to improved long-term function, with reasonably few adverse events.

Creatinine↗
PubMed2004

Prediction of sustained virological response in liver transplant recipients with recurrent hepatitis C virus following combination pegylated interferon alfa-2b and ribavirin therapy using tissue hepatitis C virus reverse transcriptase polymerase chain reaction testing.

The optimal duration of therapy for pegylated interferon combined with ribavirin in recurrent Hepatitis C virus (HCV) following liver transplantation is not known. We wanted to determine if testing for HCV in liver tissue by reverse transcriptase polymerase chain reaction (RT-PCR) was superior in predicting sustained virological response (SVR) in comparison to standard HCV ribonucleic acid (RNA) detection in the serum. All recipients received combination pegylated alpha-2b interferon (1.5 mcg/kg) and ribavirin (200-600 mg/d) therapy for at least 48 weeks of therapy and were found to have nondetectable HCV RNA by PCR serum testing at the end of therapy. Sustained virological response (SVR) was defined as nondetectable serum HCV RNA at 6 months post treatment withdrawal. Ten liver transplant recipients were included in the study; mean time from transplantation was 29.2 months. All had nondetectable serum HCV RNA by RT-PCR. In hepatic tissue 7/10 patients HCV RNA was found to be positive by RT-PCR while 3/10 had nondetectable HCV RNA in their liver by RT-PCR. SVR was attained in all 3/10 that were hepatic tissue HCV PCR negative after 12 months of combination therapy. In conclusion, direct detection of HCV RNA by RT-PCR of liver tissue appears to more effectively predict SVR following pegylated interferon and ribavirin therapy than the conventional use of serum.

Antiviral Agents↗
PubMed2004

Reliability of histopathologic assessment for the differentiation of recurrent hepatitis C from acute rejection after liver transplantation.

Histopathologic assessment is considered essential for the differentiation of recurrent hepatitis C (RHC) from acute cellular rejection (ACR) after liver transplantation (LT); however, there is limited information regarding its reliability. The aim of this study was to determine the interobserver and intraobserver agreement of the histopathologic diagnosis of RHC vs. ACR, and to determine the reliability of specific histopathologic features for the differentiation of RHC from ACR. Liver biopsy specimens from 105 consecutive patients transplanted for hepatitis C virus (HCV)-related liver disease were studied retrospectively. All the biopsies were performed for evaluation of abnormal liver enzymes within the 1st year after LT. The slides were blindly coded and assessed by 5 liver-transplant pathologists, practicing at 3 medical centers. The pathologists were asked to render a diagnosis, and determine the severity of the disease. Four of the pathologists were asked to determine the presence and severity of 36 histopathologic features. A total of 34 of the samples were then blindly resubmitted to each of the 4 pathologists to determine the intraobserver agreement. There was a slight agreement (kappa = .12) among the 5 pathologists on the histopathologic diagnosis. All 5 pathologists were in agreement on the diagnosis of RHC in only 5 patients (5%) and on the diagnosis of ACR in only 2 patients (2%). The best agreement among any 4 pathologists was fair (kappa = .20). Slight to moderate agreement occurred on the main histological features considered to be important in the diagnosis of ACR. Intraobserver agreement ranged from slight (kappa = .19) to moderate (kappa = .42) among 4 pathologists. In conclusion, the histopathologic differentiation of RHC from ACR after LT had relatively low interobserver and intraobserver agreement rates, and hence showed low reliability. Histopathologic assessment should be used cautiously for the differentiation of RHC from ACR post-LT.

Acute Disease↗
PubMed2004

Outcomes in liver transplant recipients with hepatitis B virus: resistance and recurrence patterns from a large transplant center over the last decade.

Hepatitis B virus (HBV) recurrence following liver transplantation (LTx) has been controllable primarily with the use of hepatitis B immune globulin (HBIg) and lamivudine (LAM). However, HBV resistance to LAM and/or HBIg has become an increasing problem prompting the use of newer antiviral agents. The purpose of our study was to investigate the association between therapy, HBV breakthrough, and allograft / patient survival in HBV-positive liver transplant recipients. We performed a retrospective review of the medical records of patients that were transplanted for HBV from June 1994 to May 2003. A total of 92 patients, positive for either hepatitis B surface antigen (HBsAg) or HBV deoxyribonucleic acid (DNA) pretransplant, received LAM monotherapy or HBIg (6 months) plus LAM therapy post-liver transplant. HBV breakthrough post-LTx was noted in 14 patients. All patients had detectable HBV DNA prior to liver transplantation; none of the patients that were HBV DNA negative prior to transplant had detectable HBV DNA posttransplant. Of these 14, 9 patients (64%) were switched from LAM to adefovir dipivoxil (ADF) and 5 patients (36%) to tenofovir disoproxil fumarate (TNV). In conclusion, pre-LTx HBV viremia should be considered in planning post-LTx prophylaxis. Trials to evaluate oral antiviral agents in combination with or without HBIg therapy are needed.

Adenine↗
PubMed2004

Factors that identify survival after liver retransplantation for allograft failure caused by recurrent hepatitis C infection.

Hepatitis C virus (HCV) is becoming the most common indication for liver retransplantation (ReLTx). This study was a retrospective review of the medical records of liver transplant patients at our institution to determine factors that would identify the best candidates for ReLTx resulting from allograft failure because of HCV recurrence. The patients were divided into 2 groups on the basis of indication for initial liver transplant. Group 1 included ReLTx patients whose initial indication for LTx was HCV. Group 2 included patients who received ReLTx who did not have a history of HCV. We defined chronic allograft dysfunction (AD) as patients with persistent jaundice (> 30 days) beginning 6 months after primary liver transplant in the absence of other reasons. HCV was the primary indication for initial orthotopic liver transplantation (OLT) in 491/1114 patients (44%) from July 1996 to February 2004. The number of patients with AD undergoing ReLTx in Groups 1 and 2 was 22 and 12, respectively. The overall patient and allograft survival at 1 year was 50% and 75% in Groups 1 and 2, respectively (P = .04). The rates of primary nonfunction and technical problems after ReLTx were not different between the groups. However, the incidence of recurrent AD was higher in Group 1 at 32% versus 17% in Group 2 (P = .04). Important factors that predicted a successful ReLTx included physical condition at the time of ReLTx (P = .002) and Child-Turcotte-Pugh score (P = .008). In conclusion, HCV is associated with an increased incidence of chronic graft destruction with a negative effect on long-term results after ReLTx. The optimum candidate for ReLTx is a patient who can maintain normal physical activity. As the allograft shortage continues, the optimal use of cadaveric livers continues to be of primary importance. The use of deceased donor livers in patients with allograft failure caused by HCV remains a highly controversial issue.

Adult↗
PubMed2004

Acute cellular rejection grading scheme for human gastric allografts.

The control of acute cellular rejection (ACR) in multivisceral transplantation improves long-term survival, but monitoring this process can be challenging because different allografts can display varying forms and degrees of rejection. Criteria for ACR of small bowel and liver have been established, but a systematic analysis for ACR in stomach is lacking. For this reason we have developed a comprehensive grading scheme for the evaluation of gastric allograft rejection. The grading scheme was designed to individually grade a variety of changes in the surface epithelium, lamina propria, and glandular structures. The individual values are cumulated, and the final score determines assignment of the rejection grade. The ACR grades range from no evidence of acute cellular rejection to severe rejection. We performed a retrospective study based on 70 gastric allograft biopsies from 20 patients who received multivisceral transplantation from 1995 to 2001. We found that the scoring system showed no significant interobserver variability and allowed for an accurate designation of the ACR grade to the gastric allografts. We found with this grading system that neither clinical symptoms nor gastric endoscopic findings could serve as specific indicators of gastric ACR. Our results also showed that there were differences in the occurrence and intensity of acute rejection between the stomach and other transplanted organs, suggesting that ACR can occur independently among different allografts of the same host. In conclusion, we find that this scheme for grading ACR in gastric transplants is objective and reproducible. This grading system will likely allow for improved correlation between gastric ACR grade and clinical symptoms, as well as improve interobserver uniformity within and between institutions.

Acute Disease↗
PubMed2004

Effects of ventricular unloading on apoptosis and atrophy of cardiac myocytes.

BACKGROUND: Ventricular unloading decreases cardiac ventricular mass. This loss of ventricular mass can be due to either atrophy (a reversible process) or apoptosis (an irreversible process) of the cardiac myocytes. We investigated the effect of ventricular unloading on atrophy and apoptosis of cardiac myocytes, using working and nonworking transplant heart models in rats. MATERIALS AND METHODS: ACI rats underwent heterotopic heart transplantation with two different techniques to create working and nonworking cardiac grafts. Cardiac grafts were harvested at different time points after transplantation. TUNEL, caspase-3 assay, and electron microscopy were used to assess the degree of apoptosis while cellular atrophy was estimated by calculation of the cytoplasmic index (CI = mean sectional cytoplasmic area/nucleus). RESULTS: Ventricular mass reduction was more pronounced in nonworking than in working hearts (P < 0.05). Apoptotic index and caspase-3 activities increased in both groups, peaking at 3 days after transplantation, but were not significantly different between the two models. The cytoplasmic index was significantly lower in nonworking than in working grafts (P < 0.05). CONCLUSIONS: These data suggest that cellular atrophy is the primary mechanism that accounts for myocardial weight reduction following ventricular unloading. The inference is that ventricular unloading by ventricular assist devices may not cause permanent loss of cardiac myocytes, thus allowing for functional recovery.

Animals↗