Hyperuricemia and Acute Renal Failure in Renal Transplant Recipients Treated With High-Dose Mizoribine.

BACKGROUND: Hyperuricemia is a common adverse event frequently found in renal transplant recipients with mizoribine (MZ). Hyperuricemia itself will be a cause of renal dysfunction, and renal dysfunction also will be a cause of hyperuricemia simultaneously. This study investigates frequency of hyperuricemia and renal failure in renal transplant recipients treated with high-dose MZ. PATIENTS AND METHODS: From December 2007 to October 2015, there was a total of 32 living related renal transplant recipients treated with high-dose MZ. Of the 32 patients, 28 were treated with urate-lowering medications. RESULTS: One patient received allopurinol (AP) and 13 patients received benzbromarone (BB). For 6 of them, their urate-lowering medications were converted to febuxostat (FX) form AP or BB. In the remaining 14 patients, FX was administered from the beginning. In 2 cases of ABO-incompatible living related renal transplant recipients who were maintained with high-dose MZ and BB, severe hyperuricemia and acute renal failure occurred. One patient was a 48-year-old man, and his creatinine (Cr) level increased to 8.14 mg/dL and his serum uric acid (UA) was 24.6 mg/dL. Another patient was a 57-year-old man, and his Cr level increased to 3.59 mg/dL and his UA was 13.2 mg/dL. In both cases Cr and UA were improved, and no finding of acute rejection and drug toxicity was observed in graft biopsy specimens. BB was switched to FX and discontinuance or reduction of MZ was done. CONCLUSION: Combination of MZ and BB has the risk of acute renal dysfunction after renal transplantation. Latent renal dysfunction should be watched for in renal transplant recipients receiving high-dose MZ.

How long should we follow the post-transplantation patient after graft loss? A case report of renal cancer in the grafted kidney that occurred 16 years after graft loss.

BACKGROUND: Renal cancers commonly occur in the native kidneys of renal transplant recipients, whereas renal cancer in the grafted kidney has been reported occasionally. Renal cancer in the grafted kidney occurred 16 years after graft loss in this case, which would be a more rare case. CASE REPORT: A 60-year-old man who had a kidney transplant from his mother at the age of 31 years and had hemodialysis again because of chronic rejection from the age of 44 years had right lower abdominal pain. Computerized tomography (CT) showed tumor involvement in the grafted kidney. Positron-emission tomography-CT also showed hot spots in the liver, cervical vertebra, and costal bone. Needle biopsy for grafted kidney and liver tumors were done, and pathologic findings revealed renal cancer of grafted kidney and metastatic liver tumor. Graftectomy was done, and renal cancer was diagnosed as spindle cell carcinoma. Irradiation for cervical bone metastasis was done after the surgery. He complained of abdominal pain and eating disturbance 2 months after the surgery. CT showed a huge recurrence tumor and multiple tumor dissemination. Small intestine was involved and obstructed by the main tumor. He died of recurrence of renal cancer 3 months after the surgery. CONCLUSIONS: It is reported that the rate of renal cell carcinoma in the grafted kidney was 0.19%-0.5% and it occurred at a mean of 12.6 years after renal transplantation. Herein, we report a rare case of renal cancer that occurred 29 years after renal transplantation. Long-term observation should be required for recipients who had rehemodialysis.

Acute renal failure caused by hyperuremic acidemia in ABO-incompatible kidney transplant maintained with cyclosporine and high-dose mizoribine: a case report.

INTRODUCTION: The shortage of cadaver organs has led to expansion of living donor kidney transplantations with, 30% increase among ABO-incompatible cases in Japan and the use of marginal extended donors. Herein we have reported the outcome after an ABO-incompatible kidney transplantation from an aged living-related donor who suffered from mild diabetes mellitus and hypertension. CASE REPORT: A 48-year-old man underwent ABO-incompatible kidney transplantation from his 76-year-old father, using anti-CD20 antibody induction, followed by cyclosporine (CsA), mycophenolate mofetil (MMF), and prednisolone. After the operation, MMF was switched to high-dose mizoribine (MZ). He was discharged from the hospital on postoperative day (POD) 28 with a serum creatinine (sCr) of 1.47 mg/dL. On POD 34 when the sCr was 8.14 mg/dL, his urine examination showed uric acid crystals with serum uric acid of 24.6 mg/dL. Biopsy findings showed no evidence of acute rejection but mild tubulointerstitial injury. Hemodialysis performed twice to reduce uric acid was accompanied by hydration. CsA/MZ was switched to tacrolims/MMF; benzbromarone, to febuxostat to treat hyperuric acidemia. On POD 58, sCr reduced to 1.75 mg/dL he was discharged. On POD 416, graft function was stable with sCr of 1.70 mg/dL. CONCLUSION: Common side effect of MZ is hyperuricemia which presumably caused acute renal failure of this aged marginal donor kidney.

Blinking and superficial punctate keratopathy in patients with diabetes mellitus.

AIM: To evaluate blinking patterns in patients with diabetes mellitus and whether blinking contributes to the formation of superficial punctate keratopathy in diabetic patients. METHODS: We examined 163 patients with type II diabetes mellitus and 76 without diabetes. Blinks were recorded, analysed using six parameters, and compared between patients with and without diabetes. Multivariate regression analysis was performed to assess the influence of other ocular factors, such as status of tear lipid layer, tear breakup time, corneal sensitivity, the result of cotton thread test, or blinking rate related to superficial punctate keratopathy. RESULTS: In patients with diabetes, the average mean and maximum interblinking times were longer, the average coefficient of variation of interblinking time was higher, and the average blinking rates were lower than those in patients without diabetes. Multivariate regression analysis revealed that the status of tear lipid layer and tear breakup time were significantly relevant to superficial punctate keratopathy (P < 0.01). CONCLUSION: Interblinking time was longer in diabetic patients, resulting in a decreased blinking rate. The prevalence of superficial punctate keratopathy cannot be predicted from blinking patterns in patients with diabetes.

Cimetidine modulates the antigen presenting capacity of dendritic cells from colorectal cancer patients.

Cimetidine, a H(2) receptor antagonist, has been reported to improve survival in gastrointestinal cancer patients. These effects have largely been attributed to the enhancing effects of cimetidine on the host's antitumour cell-mediated immune response, such as inhibition of suppressor T lymphocyte activity, stimulation of natural killer cell activity and increase of interleukin-2 production from helper T lymphocytes. We conducted an in vitro study on the effects of cimetidine on differentiation and antigen presenting capacity of monocyte-derived dendritic cells from advanced colorectal cancer patients and normal controls. As a result, an investigation of expression of surface molecules associated with dendritic cells by flow cytometric analyses showed that cimetidine had no enhancing effect on differentiation of dendritic cells from cancer patients and normal controls. An investigation of [(3)H]thymidine incorporation by allogeneic mixed lymphocyte reactions revealed that cimetidine increased the antigen presenting capacity of dendritic cells from both materials. Moreover, a higher antigen presenting capacity was observed in advanced cancer patients compared to normal controls. These effects might be mediated via specific action of cimetidine and not via H(2) receptors because famotidine did not show similar effects. Our results suggest that cimetidine may enhance the host's antitumour cell-mediated immunity by improving the suppressed dendritic cells function of advanced cancer patients.

Loss of motility-related protein 1 (MRP1/CD9) and integrin alpha3 expression in endometrial cancers.

BACKGROUND: MRP1/CD9 and integrin alpha3 have played crucial roles in cell adhesion, motility, and signaling events. The loss of MRP1/CD9 and integrin alpha3 has been involved in tumor growth and metastasis of cancer cells. The aim of the current study was to clarify the clinical significance of MRP1/CD9 and integrin alpha3 in endometrial cancer. METHODS: The expression of MRP1/CD9 and integrin alpha3 from the same tissue sample were examined immunohistochemically in 15 patients with normal endometrium and in 56 patients with uterine endometrioid adenocarcinoma. Disease-free survival curves were estimated using the Kaplan-Meier method and analyzed by the log-rank test between the positive and reduced expression statuses of both MRP1/CD9 and integrin alpha3. These expressions and clinicopathologic variables were analyzed univariately and multivariately. RESULTS: In normal endometrium, MRP/CD9 was expressed at the cell membrane of cell contact sites, and the expression of integrin alpha3 was detected also at the cell membrane of cell contact sites and at borders of stromal tissues. In patients with endometrioid adenocarcinoma, 17 cases showed reduced expression of MRP1/CD9, and 20 cases had reduced expression of integrin alpha3. Fourteen cases indicated a reduced expression of both MRP1/CD9 and integrin alpha3. Each reduced expression of MRP1/CD9 or integrin alpha3 was significantly correlated with histologic grade and metastasis. Multivariate analysis using the Cox regression model disclosed that age at surgery, metastasis, and expression status of MRP1/CD9 were significant prognostic factors for disease-free survival. CONCLUSIONS: These findings suggested that the analysis for the expression statuses of MRP1/CD9 and integrin alpha3 may provide important information on the clinical behavior of endometrial cancer.

Primary hepatic Burkitt's lymphoma with chronic hepatitis C.

The liver is an uncommon primary site for malignant lymphoma, and primary hepatic lymphoma has been found to make up 0.4% of all extranodal lymphomas. We report a rare case of a 75-year-old Japanese male with primary hepatic Burkitt's lymphoma, according to both the revised European-American Lymphoma classification and the new World Health Organization classification. As not only histological findings but also immunological features are deemed essential in the diagnosis of Burkitt's lymphoma, the previous 7 cases of primary hepatic Burkitt's lymphoma were not fully evaluated, using these criteria. As far as we know, this is the first case of primary hepatic Burkitt's lymphoma with typical features on histological, immunological and cytogenetical analysis. He had a history of chronic hepatitis C over several decades with subsequent liver cirrhosis. From our review of the literature and our case, the relationship between hepatitis C virus infection and the development of primary hepatic Burkitt's lymphoma remains obscure.

Relationship between age, histological type, and size of ovarian tumors.

OBJECTIVE: To clarify the relationship between age, histological type, and size of ovarian tumors. METHOD: A review was made of 1648 cases of histopathologically diagnosed ovarian tumors and tumor-like lesions, and information on the age of the patients and size of the tumor was obtained. Statistical analysis was performed using Kruskal-Wallis tests or Mann-Whitney U-tests. RESULTS: There were 840 (51%) cases of benign tumors, 73 (4%) cases of tumors of low malignant potential (LMP), 268 (16%) cases of malignant tumors and 467 (28%) cases of tumor-like lesions. The age of the patients was significantly different among tumor-like lesions (34.6+/-8.1 years), benign tumors (39.8+/-16.4 years), LMP tumors (45.2+/-18.3 years) and malignant tumors (51.9+/-13.0 years) (P<0.0001). The maximum diameter of the tumors was significantly different among tumor-like lesions (7.1+/-3.3 cm), benign tumors (10.9+/-5.6 cm), malignant tumors (13.6+/-6.5 cm) and LMP tumors (18.5+/-6.8 cm) (P<0.0001). CONCLUSION: The distribution of tumor histological type (tumor-like lesions, benign, LMP and malignant) was correlated against patient age and lesion diameter, with tumors in older patients or larger tumors more likely to be malignant.

[Locoregional adoptive immunotherapy using LAK cells and IL-2 against liver metastases from digestive tract cancer].

We investigated the clinical efficacy of locoregional and systemic adoptive immunotherapy (AIT) with or without interleukin-2 (IL-2) against solid metastatic lesions from digestive tract cancer. Eighteen patients, who were treated with more than 10(10) lymphokine-activated killer (LAK) cells, were enrolled in this study. Seven of the 18 patients received hepatic arterial infusion (HAI) of LAK cells with or without IL-2 against metastatic liver tumors (locoregional therapy group). The remaining 11 patients received systemic transfer of LAK cells with IL-2 against metastatic lesions located in organs other than the liver (systemic therapy group). Three of 7 locoregional therapy group patients showed clinically significant tumor regressions that were evaluated as being equivalent to partial response (PR). Two of the 11 systemic therapy group patients showed significant tumor regressions, but this response rate was much lower than that of the locoregional therapy group. The 2 effective cases in the systemic therapy group were esophageal cancer patients. Locoregional AIT with or without IL-2 against liver metastases from digestive tract cancer could be an effective therapeutic modality in some patients who are refractory to conventional therapies (e.g., chemotherapy and radiotherapy). It is necessary to find a new way to augment the anti-tumor effect of this therapy in combination with prior or concomitant chemotherapy.

Practical SEM system based on the montage technique applicable to ultralow-magnification observation, while maintaining original functions

A newly developed SEM system has been utilized for obtaining ultralow-magnification SEM images. It is a successful combination of the modern SEM equipped with a motor drive stage fully controlled with PC and digital image processing techniques for automatic montage. In order to accomplish a practical system, several problems peculiar to the field of SEM, i.e. raster rotation, peripheral distortion and charging effects, are discussed and solved. The function of ultralow-magnification (whole area) observation is important during a scanning electron microscopy session.

Intermittent intraperitoneal implantation of islets in rat islet transplantation.

Two critical issues need to be addressed regarding islet cell transplantation: obtaining sufficient supply of cells for implantation, and the maintenance of the viability of these cells. Our present study has two protocols. One is islet cell implantation under the renal capsule, and the other, repeated injection of islet cells into the peritoneal cavity. These two methods were compared in an isogeneic transplant model in the rat to determine the more clinically beneficial method. Transplantation of 2000-2500 islet under the capsule of the kidney resulted in normalized blood sugar levels for more than 100 days in four of five rats with hyperglycemia. However, normalization for the same duration by islet cell injection into the peritoneal cavity necessitated repetition of injections in two out of three tested rats. In view of the similarity of the results obtained with these two protocols, intraperitoneal implantation of a few cells is preferable, because the need for prolonged cell preservation is avoided.

Auxiliary heterotopic partial liver transplantation in pigs with acute liver failure.

Fulminant hepatic failure is usually fatal without liver transplantation; however, orthotopic liver transportation is often difficult to perform due to the high risk of coagulopathy and the development of multiple organ failure. Auxiliary heterotopic partial liver transplantation (APLT), However, has the potential to provide an effective hepatic support system considering that the host liver is left in situ and the surgical procedure is less invasive. In this report, we describe the beneficial effects of performing 60% APLT on the hepatic function and survival of pigs with acute hepatic failure induced by hepatic artery ligation. The pigs were divided into a control group of nine animals (group 1) that had portal vein and hepatic artery ligation with a side-to-side portacaval shunt, and an APLT group of seven animals (group 2) that had portal vein and hepatic artery ligation with APLT. The two left lateral lobes of the donor liver were resected, reducing the liver weight to about 60%, and the graft was placed in the right subhepatic space. No deaths occurred intraoperatively. In group 1, eight pigs died of massive liver necrosis within 48 h and one died between 48 and 72 h (median survival 23 h). In group 2, two pigs died within 72 h due to preservation or anesthetic problems, but five survived for more than 3 days (median survival 13.4 days), with a significant difference between the two groups (P < 0.05). One animal was killed 30 days after APLT and excellent graft function was demonstrated by the synthesis of clotting factors, ammonia detoxification, and glucohomeostasis. Moreover, evidence of hepatic regeneration was found in the transplanted livers.(ABSTRACT TRUNCATED AT 250 WORDS)

Accelerated recovery of antigen-presenting cell activity by the administration of interleukin 1 alpha in 5-fluorouracil-treated mice.

In this study, we investigated the effect of human recombinant interleukin-1 alpha (IL-1 alpha) on antigen-presenting cell (APC) activity of spleen cells in mice treated with 5-fluorouracil (5-FU). APC activity was determined by the antigen-specific proliferation of T cell clone D10.G4.1 cells. When mice were injected with 5-FU, APC activity of spleen cells was suppressed. The administration of IL-1 alpha accelerated the recovery from this suppression. The most accelerated recovery was observed when these mice were administered with IL-1 alpha both before and after the 5-FU treatment. The recovery was also accelerated when the mice were injected with IL-1 alpha after the 5-FU treatment, but not when injected before the 5-FU treatment. The injection of 5-FU also decreased the cell numbers of whole spleen cells, B cells, and non-T non-B cells (Ig- and Thy-1- cells). The administration of IL-1 alpha accelerated the recovery of the decreased cell numbers. Both B cells and non-T non-B cells possessed APC activity, but most APC activity of unseparated spleen cells was carried by non-T non-B cells. B cells possessed only 1/20 of the APC activity of non-T non-B cells. The injection of 5-FU decreased APC activity of both B cells and non-T non-B cells, but the administration of IL-1 alpha accelerated its recovery. Thus, the accelerated recovery of APC activity by IL-1 alpha was suggested to be due to the recovery in the numbers of APC activity-bearing cell subpopulations and also due to the recovery of the APC activity of each subpopulation. Possible mechanisms for the recovery were discussed.