Clinical pharmacokinetic study of mizoribine in renal transplantation patients.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
H Toma
Publications and source records attributed to H Toma.
Current status of renal replacement therapy in Japan.
The study of the current status of renal replacement therapy in Japan is based on the analysis of data from the registry reports for regular dialysis therapy and kidney transplantation. The total number of patients receiving regular dialysis therapy was 123,926 at the end of 1992: 117,809 (95.1%) on hemodialysis and 6,117 (4.9%) on peritoneal dialysis. The primary diseases of newly accepted patients were chronic glomerulonephritis (42.2%), diabetic nephropathy (28.4%), nephrosclerosis (5.9%), polycystic kidney disease (2.7%), chronic pyelonephritis (1.6%), and others. The number of kidney transplant patients in Japan was 8,384 at the end of 1991: 6,154 (73.4%) received a living donor transplantation and 2,230 (26.9%) received a cadaver donor transplantation. Overall 5-year survival rates of dialysis patients were 60.4%: 69.7% for chronic glomerulonephritis, 41.7% for diabetic nephropathy, 39.6% for nephrosclerosis, 73.6% for diffuse polycystic kidney disease, and 66.6% for chronic pyelonephritis. The causes of death of dialysis patients were heart failure (31.1%), cerebrovascular accident (13.6%), infectious diseases (11.3%), malignancies (7.1%), cachexia/uremia (6.7%), myocardial infarction (5.8%), and others. The gross mortality rate of dialysis patients was increased in cases of less than 4 hours of the average length of each dialysis session, less than 4% and more than 9% of the average weight loss during each dialysis session, less than 1.0 of Kt/V, and less than 0.9 and more than 1.7 g/kg/d of protein catabolic rate. Overall 5-year patient and graft survival rates of kidney transplant patients since 1964 were 82.7% and 60.3%: 84.4% and 65.0% in living donor cases, and 77.4% and 46.2% in cadaver donor case, respectively. Those since 1983 were 90.1% and 68.2%: 91.3% and 72.6% in living donor cases, and 87.8% and 59.3%, respectively. Graft survival rates were superior in cases treated with combined steroid, cyclosporine and azathioprine or mizoribine, to those treated with other immuno-suppressive regimens, and they decreased as the number of HLA-A, -B and -DR increased.
Actuarial Analysis↗
ABO incompatible kidney transplantation in children.
We have performed 7 pediatric kidney transplantations from living related donors of ABO incompatibility. All patients preoperatively underwent plasmapheresis with or without immunoadsorption to reduce anti-A and/or anti-B antibodies. Immunosuppression initially consisted of methylprednisolone, cyclosporine, azathioprine, antilymphocyte globulin and deoxyspergualin. At transplantation splenectomy was simultaneously performed in all patients. Median followup is 44 months (range 31 to 58). Patient and graft survival rates are 100% to date. There were no uncontrollable vascular rejection episodes, and post-transplant anti-A and/or anti-B antibody titers were always less than 1:32. Transplantation across the ABO blood barrier remains challenging today. However, our small series clearly shows that the preoperative reduction of ABO antibody, simultaneous splenectomy and strict immunosuppressive therapy cause successful long-term results in children.
ABO Blood-Group System↗
Acute hemorrhagic cystitis caused by adenovirus after kidney transplantation.
We report on 10 kidney transplant patients with acute hemorrhagic cystitis caused by adenovirus, accompanied by the deterioration of kidney function. They developed macrohematuria with urgency, frequency and micturition pain for more than 7 days within 1 year after transplantation. Adenovirus type 11 was isolated from the urine of 6 patients, and complement-fixing antibody became positive in 9 patients. Hematuria and irritative voiding symptoms disappeared without any specific treatment; however, serum creatinine rapidly increased. The histological findings of the biopsy specimens indicated that renal impairment was attributed to acute rejection in some cases and virus-associated nephropathy in other cases. Acute hemorrhagic cystitis caused by adenovirus is an interesting complication after kidney transplantation, especially with regard to kidney impairment and treatment.
Adenoviridae Infections↗
Efficacy of stool examination for detection of Strongyloides infection.
To determine the efficacy of stool examination for detection of Strongyloides infection, 1,350 stool samples collected in Japan, Brazil, and Thailand were examined by four different methods (direct fecal smear, formalin-ether concentration. Harada-Mori filter paper culture, and agar plate culture). The newly developed agar plate culture method was highly effective; more than 96% of the positive cases were diagnosed by this method. The coprologic examination, however, was not sensitive enough for detecting chronic infections because more than 40% of the positive cases were overlooked even when persons with proven Strongyloides infection were re-examined several months later without intervening treatment. Therefore, it is essential to examine stool samples repeatedly to achieve a correct diagnosis, and even so, it is important to note that a negative result does not necessarily indicate the unequivocal absence of the infection.
Animals↗
[A case of urachal carcinoma associated with elevated levels of CA19-9].
A 53-year-old man was admitted with the chief complaint of gross hematuria. Cystoscopic examination revealed a non-papillary tumor at the dome of the bladder. The plasma level of CA19-9 was markedly elevated before treatment. Total cystectomy with en bloc removal of the tumor and radical lymphadenectomy were performed under the diagnosis of urachal carcinoma. The plasma CA19-9 level decreased to the normal level after operation and was well correlated with postoperative course. The monitoring of CA19-9 may be useful for follow up in patients showing a high elevation of CA19-9.
Adenocarcinoma↗
A case of massive adrenal malignant pheochromocytoma: management of a large pheochromocytoma.
A 69-year-old man was referred to our hospital for a left abdominal tumor measuring about 30 cm in diameter. Laboratory examination revealed an elevation of norepinephrine in plasma and of its metabolites in urine. CT scan disclosed a huge cystic tumor in the retroperitoneal space and an enlarged aortocaval lymph node, suggesting a diagnosis of malignant pheochromocytoma. The hemodynamic studies showed low blood volume and high vascular resistance, and therefore, he was treated with vasodilators and volume expansion. His hemodynamic status normalized and a complete excision was performed. Pathological examination revealed that the patient had a pheochromocytoma with metastasis to a lymph node. The total weight of the tumor was 5,930 g. Since pheochromocytomas can become a large with a risk of malignancy, they should be surgically excised as completely as possible with further treatment after making a definite diagnosis.
Adrenal Gland Neoplasms↗
[A clinico-pathological study of renal cell carcinoma with a diameter of less than 5 cm].
To examine the indication of nephron sparing operations, we searched 31 nephrectomized kidneys with renal cell carcinoma for small associated lesions in the normal-appearing portion of these kidneys. The diameter of the predominant tumors was between 15 and 50 mm. The kidneys were serially sectioned at 5-mm intervals, and all sections were examined microscopically. Two of the 31 kidneys had a small renal cell carcinoma, and four had a small adenoma in the normal-appearing portion. We recommend that the nephron-sparing operation should be is performed limitedly and that radical nephrectomy is yet a standard operation in the presence of a normal contralateral kidney.
Adenoma↗
A phase II study of prophylactic intravesical chemotherapy with epirubicin in the treatment of superficial bladder cancer. Tokyo Women's Medical College Bladder Cancer Collaborating Group.
Intravesical instillation of epirubicin was carried out to investigate the efficacy of this treatment in preventing postoperative recurrence of superficial bladder cancer. The subjects were 100 patients who had been treated with transurethral resection (TUR) for superficial transitional-cell carcinoma of the bladder (classified as primary or recurrent superficial bladder cancer of pathological stage Tis, Ta, or T1 and histological grade G1, G2, or G3) at Tokyo Women's Medical College Hospital and its affiliated hospitals during the 2-year period ranging from April of 1990 through March of 1992. A solution of epirubicin was prepared by dissolving 20 mg in 30 ml physiological saline, and this was instilled into the bladder a total of 17 times during 1 year: once immediately after TUR, once every 2 weeks for the next 4 months, and then once per month for the following 8 months. Thereafter, the course of each patient was followed by performing urinary cytodiagnosis once each month and cystoscopy once every 3 months. Of the 100 patients, 83 were evaluable. The mean duration of follow-up was 461 +/- 222 days, and the recurrence rate was 30.1% (25/83 cases). The recurrence rate determined for primary cases was 19.7%, whereas that recorded for recurrent cases was 61.9%. Adverse effects occurred in 9.3% (9/97) of the patients, but these side effects were mild in severity and the instillation regimen did not have to be discontinued in any of the patients. Analysis of the risk factors for recurrence revealed significantly higher recurrence in the recurrent-patient group and the multiple-tumor group. On the basis of these findings, the authors surmised that when given in an intravesical instillation regimen, epirubicin causes few adverse effects, and its efficacy in the prophylaxis of recurrence of superficial bladder cancer is equivalent to that thus for reported for other drugs. At present, the authors are carrying out a controlled clinical study on epirubicin that takes into account the risk factors for recurrence of superficial bladder cancer.
Administration, Intravesical↗
Application of enzyme immunoassay for postchemotherapy evaluation of human strongyloidiasis.
Posttherapy evaluation of strongyloidiasis is frequently difficult because coprologic examination is not sensitive enough for diagnosis of chronic infection. In the present study, anti-Strongyloides enzyme-linked immunosorbent assay antibodies were monitored before and after treatment with thiabendazole and pyrvinium pamoate in 199 patients with chronic strongyloidiasis in Okinawa, Japan. A significant decrease in antibody levels was observed in patients who became negative for fecal larvae after the treatment, whereas the antibody levels did not show a significant change after the treatment in patients who were still harboring the parasite. In the group coprologically negative in the follow-up examination, however, many individuals did not show a significant fall in antibody titers after treatment, which suggests that these cases were equivocal for complete cure. By the subsequent fecal reexamination performed on the equivocal cases, approximately 20% were additionally found to be still harboring the parasite. These results indicate that serologic testing is useful to check whether a real cure has been achieved among the patients in whose fecal samples the presence of larvae has not been demonstrated after treatment.
Adult↗
Basic fibroblast growth factor (FGF-2) in renal cell carcinoma, which is indistinguishable from that in normal kidney, is involved in renal cell carcinoma growth.
To investigate the role of basic fibroblast growth factor (FGF) in renal cell carcinoma growth, we have analyzed the expression of mRNA of basic FGF. In 7 of 15 cases, basic FGF mRNA level in renal cell carcinoma tissues was higher than that in corresponding normal tissues. However, the tumor-to-normal ratios of expression levels are chiefly less than 2.0 and, in 5 cases, are even less than 1.0. Furthermore, there was no correlation between the ratio and the clinical stage. In protein analysis, we could not find any difference between basic FGF extracted from renal cell carcinomas and that from normal kidney tissues in bioactivity, immunoreactivity, molecular weight and affinity to heparin. On the other hand, anti-basic FGF monoclonal antibody inhibited the growth of a renal cell carcinoma cell line, VMRC-RCW, and this inhibition was reversed by an extraphysiological amount of exogenous basic FGF (100 ng./ml.). These results suggest that basic FGF itself may have no pivotal role in renal cell carcinoma etiology but is involved in the growth of renal cell carcinomas in an autocrine manner.
Animals↗
Effect of deoxyspergualin on vascular rejection in canine kidney transplantation.
Deoxyspergualin (DSG), an analogue of spergualin produced by Bacillus laterosporus, has a strong immunosuppressive effect in various transplantation models. In this study, we investigated the effect of DSG on vascular rejection in canine kidney transplantation. To enhance vascular rejection, donor-specific blood transfusion (DST) was carried out on days 28, 21 and 14 preceding kidney transplantation. After DST, the donor kidney was transplanted to the recipient iliac fossa. The recipient animals were divided into five groups: namely, Group 1 (n = 7), no treatment; Group 2 (n = 6), DST only; Group 3 (n = 5), DSG only (treated with DSG intravenously at 1.2 mg./kg./day for the first 3 days after transplantation, 1.0 mg./kg./day for the following 3 days and 0.8 mg./kg./day for the following 8 days); Group 4 (n = 6), DST and DSG treatment (same protocol as Group 3); and Group 5 (n = 5), DST and cyclosporine (CsA) (treated with CsA orally at 10 mg./kg./day for 14 days after transplantation). In Group 2, DST treatment significantly reduced kidney graft survival time (8.6 +/- 2.2 days) compared with Group 1 (14.1 +/- 5.5 days). Despite DST, DSG treatment (Group 4) significantly prolonged graft survival time (29.5 +/- 2.6 days), whereas treatment with CsA (Group 5) did not prolong survival time (14.1 +/- 5.5 days) (Group 4 versus 5, p < 0.01). The onset of rejection was significantly delayed in Group 4 (22.1 +/- 2.7 days) compared with Groups 2 (5.7 +/- 2.4 days) and 5 (13.0 +/- 5.7 days) (p < 0.01). In contrast, the interval between rejection onset and animal death was significantly reduced in Groups 2 (3.0 +/- 0.6 days) and 5 (2.4 +/- 1.0 days) compared with Group 4 (7.3 +/- 1.7 days) (p < 0.01). These findings suggest that DSG successfully prevented humoral-type (accelerated acute-type) rejections. Histologically, nonDST groups (Groups 1 and 3) showed minimum vascular rejection. In contrast, all recipients in Group 2 showed severe vascular rejection, as did 80% of CsA treated-animals (Group 5). Despite DST, however, 84% of DSG treated-animals (Group 4) showed minimal or mild vascular rejection and only 17% had severe rejection (Group 4 versus 5, p < 0.04). These data suggest that both clinically and histologically, DSG has more potent immunosuppressive effects against humoral and vascular rejection than CsA.
Animals↗
[Flow cytometric DNA analysis on renal cell carcinoma--a study of 116 cases on fresh surgical specimens].
DNA ploidy was investigated using flow cytometry on fresh surgical specimens from 116 cases with renal cell carcinoma. DNA diploid tumor was observed in 39 cases (33.6%) and aneuploid in 77 cases (66.4%). DNA aneuploid group was further classified into 3 subgroups by DNA index (D.I.); near-diploid group (D.I.: 0.8-1.2, 21.6%), near-tetraploid group (D.I.: 1.8-2.2, 12.9%) and other aneuploid group (31.9%). DNA ploidy pattern correlated with clinical stages and histological grading, indicating significantly a higher incidence of DNA diploid in cases in stage I and grade 1. DNA clonal heterogeneity was observed in 48.1%, and homogeneously diploid was in 28.6% of 77 cases who were analyzed more than 2 specimens. Incidences of DNA heterogeneity and homogeneous diploid correlated with the number of analyzed specimens and our results showed that more than 4 specimens were necessary to diagnose the DNA ploidy patterns. The near-tetraploid group was shown to have an extremely poor prognosis compared with the diploid group and the other aneuploid group. There were no significant difference between the diploid group and the aneuploid group in terms of the early prognosis, however, the incidence of disease recurrence was significantly higher in the aneuploid group. Our results demonstrated that DNA ploidy was an useful prognostic factor in the evaluation of patients with renal cell carcinoma.
Adult↗
[Adenovirus-induced kidney graft pyelonephritis following renal transplantation].
A 16-year-old female received a kidney transplantation from her mother 13 months before she suddenly noticed gross hematuria and painful micturition, and developed high fever with chills. The serum creatinine (S-Cr) level rose from 1.5 to 2.6 mg/dl, but there was no clinical sign of acute rejection. Despite the treatment with antibiotics and gamma-globulin, the the high fever and hematuria did not improve. The adenovirus antibody titer elevated from x8 to x1,024, while adenovirus was not isolated from the urine. On the 15th day of the disease, hematuria disappeared spontaneously and on the 19th day she became afebrile. The S-Cr level also was normalized spontaneously. Histological examination of the graft biopsy on the 14th day, showed severe tubulointerstitial nephritis localized in the renal medulla and full type intranuclear inclusions were revealed in tubular epithelial cells. From these findings, we diagnosed this case as adenovirus-induced kidney graft pyelonephritis associated with acute hemorrhagic cystitis.
Adenovirus Infections, Human↗
[Present situation in self-injection therapy with interferon-alpha for patients with renal cell carcinoma].
Interferon-alpha (IFN alpha) is often used for the treatment of renal cell carcinomas. The injections are frequently self-administered at home. To assess how this therapy was accepted by the patient we sent out a questionnaire. For the past 2 years until March 1993, this therapy was performed in our department on 52 patients, of whom 45 were selected for the study. All patients were informed of their disease and consented to the necessity of this treatment. Thirty-eight patients answered this questionnaire. Almost all patients injected this agent mainly by themselves. These findings suggested that they regarded this therapy as a strategy to be executed by themselves for the treatment of carcinoma. The main toxic symptoms in this therapy were asthenia, fever and loss of appetite. Leukocytopenia occurred in about half of the patients, of whom 1 patient required medication because of a rapid decrease in the white blood cell count shortly after inception of this therapy. The treatment was discontinued in 50% of the patients because of these adverse effects. Systemic toxicity disappeared after cessation of IFN alpha administration. Additionally, over 80% of the patients expressed concern about effectiveness, the duration and high cost of this therapy. The patients had to be repeatedly instructed about the method of disposing used needles and syringes. This study revealed that self injection of IFN alpha, which required strict management particularly at the initiation, can be performed at home. However, countermeasures must be taken against the side actions and an optimum regimen of IFN alpha should be established as soon as possible.
Adult↗
Preventive equipment for urinary incontinence: a device employing lower abdominal impendance changes.
The object of this work was to develop a monitoring device for measuring the volume of urine in the bladder to signal, in advance, the need to urinate and thus help prevent urinary incontinence. A high-frequency electric current of 50 KHz transmitter was applied to a pair of terminals placed on the surface of a human body. The constant current was 2mA (p-p). A pair of voltage electrodes was placed in the path of the electric current to pick up high-frequency voltage signals. The best position for current electrodes was found to be on the surface of both femoral joints. Positioning the voltage electrode above the bladder on the lower abdomen was most efficient for detecting the volume of urine. New current electrodes sutured onto underpants were fitted on the surface above the femoral joints, which did not shift in the case of movement by the subjects. The reproducibility and stability were remarkably good with this electrode. The alarm level which foretold both maximum storage volume and maximum desire to void was examined. After that, when the alarm level was set within the range of impedance charge, 60% to 70%, the possibility of prediction of urination exists.
Clothing↗
ABO-incompatible renal transplantation.
From recent works, it can be concluded that renal transplantation across ABO incompatibility is acceptable if no other donor is available. Patient and graft survivals are nearly equal to those of ABO-compatible renal transplantation. Despite removal of ABO blood group antibodies before transplantation, hyperacute rejection may occur in some cases. Acute humoral rejection is the most frequent type of early rejection in an ABO-incompatible recipient, but most of these crises are controllable with the most effective antirejection therapy. Further immunopathologic studies are needed to clarify the rejection mechanism in the ABO-incompatible renal transplants. To obtain a successful outcome, immunologic preparation, including reduction of anti-A and anti-B antibody titers and splenectomy, is recommended, along with careful monitoring of antibodies, platelet counts, complement, and kidney function.
ABO Blood-Group System↗
Partial kidney transplantation: a successful kidney transplantation in a child with severe cardiac failure by surgical mass reduction of an adult donor kidney.
We report on a trial of partial kidney transplantation performed on a low body weight child with impaired cardiac function due to mitral valve stenosis and uremic cardiomyopathy. The weight of the donated kidney was successfully reduced by one-third using bench surgery in order to obtain sufficient graft perfusion and function. Our procedure is justified when a graft is too large to be adequately perfused in a recipient suffering from cardiac failure.
Adult↗