Addition of deoxyspergualin to standard triple immunosuppressive regimen in kidney transplantation.
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Biomedical subjects
Publications and source records attributed to M Togashi.
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Three patients with lung metastases of renal cell carcinoma (RCC) were treated with a combination of interferon-alpha, leucovorin and 5-fluorouracil. All patients were male between 60 and 66 years and had been treated by nephrectomy prior to the combination therapy. Interferon-alpha was administered at the dose of 9 x 10(6) IU intramuscularly 3 times/week, leucovorin at 30 mg/m2 per day intravenously (day 1 to 5) and 5-fluorouracil at 500 mg/m2 daily by continuous infusion intravenously (day 1 to 5) followed by weekly bolus therapy. One patient achieved complete response for 17 months and the other two achieved stable disease for 6 and 16 months. Side effects related to this therapy were diarrhea, stomatitis, alopecia, leucocytopenia and thrombocytopenia. Grade 3 stomatitis occurred after the continuous administration of 5-fluorouracil in one patient; he recovered by discontinuation of 5-fluorouracil. Combination therapy with interferon-alpha, leucovolin and 5-fluorouracil might be effective for the treatment of lung metastases of RCC.
A prospective randomized study on the administration of recombinant granulocyte colony stimulating factor (rG-CSF) was conducted on 15 patients with testicular germ cell tumors. The clinical stagings of all patients except one were minimal to moderate extent according to the Indiana University staging system. Combination chemotherapy using bleomycin, etoposide and cisplatinum (BEP) was performed as the initial treatment on the eligible patients. rG-CSF was administered by two different methods; 1) routine administration on the 6th day after BEP chemotherapy (group A), and 2) the same method, but after granulocytopenia of 1,500/mm3 had developed (group B). The administration of rG-CSF in group A significantly reduced the severity of leucocytopenia and also the incidence of stomatitis compared with group B. Although rG-CSF produced no significant side effects, the thrombocytopenia was prominent in the group A patients (not significant). BEP chemotherapy itself is an easily-tolerable and well established method for treating young adult patients. The method used in group B seems to be suitable in situations where thrombocytopenia and cost effectiveness.
Ifenprodil, a cerebral vasodilator and non-competitive glutamate antagonist, is also an anti-ischaemic agent; it has been shown to inhibit both forms of MAO in rat brain and lung (with slightly greater potency towards MAO-A), but it does not inhibit SSAO. The effects of ifenprodil on rat brain regional levels of monoamines and their principal metabolites following transient global ischaemia have been investigated 1 h after reperfusion. Among the three most ischaemically vulnerable brain regions (striatum, hippocampus and cortex), striatal DA, DOPAC, HVA, 5-HT and 5-HIAA levels were the most markedly increased. Simultaneous treatment with ifenprodil during reperfusion reversed the increases in the striatum, except for HVA, to the level similar to those of sham-operated controls. In contrast to the striatum, ifenprodil failed to reverse the increases seen in the cortex and hippocampus.
Zona-free embryos at the 4-cell stage were classified into four types according to the total points of contact between the 4 blastomeres. Types A, B, C, and D had 3, 4, 5, and 6 points of contact, respectively. Embryos of these types were cultured individually in 20 microliters of Whitten's medium. Blastocysts derived from types A and D embryos at the 4-cell stage were transferred and observed on Day 17 of gestation. The number of live fetuses was significantly lower for type A than for type D embryos (p < 0.05). In spite of the removal of the zone pellucida, both types A and D blastocysts had cell numbers similar to those in zona-intact control embryos at 96 h after insemination. However, type A embryos had fewer (p < 0.05) inner cell mass (ICM) cells than did either the zona-intact control or type D embryos. Type D embryos did not have significantly fewer ICM than did the zona-intact control. Our data show that the cell association of zona-free embryos at the 4-cell stage influences differentiation of cells within the ICM and thus affects subsequent embryonic development. We suggest that one role of the zona pellucida after fertilization, in addition to protecting the preimplantation embryo, is to maintain the cell arrangement of 4-cell stage embryos to ensure subsequent successful cell lineage.
Prostate specific antigen (PSA) and gamma-seminoprotein (gamma-Sm) have been revealed to be the same protein and used as tumor markers for prostate cancer (CaP). However, it seems impossible to detect prostate cancer in the cases with PSA levels of 10.0 ng/ml or less. We now report on PSA/gamma-Sm ratio in the cases with PSA levels of 10.0 ng/ml or less, and on the relation between PSA and gamma-Sm in those cases. Serum samples were obtained from the patients with no cancer (NC) (n = 118) and CaP (n = 39). In the cases with PSA ranging from 4.1 to 10.0 ng/ml, gamma-Sm levels in the patient with CaP were significantly lower than in those with NC (3.744 +/- 2.481 (mean +/- SD, n = 27) VS. 7.573 +/- 4.182 (n = 41), p < 0.0001) though PSA levels in both groups were not significantly different, and consequently, PSA/gamma-Sm ratio in the patients with CaP were significantly higher than in those with NC (2.181 +/- 0.802 VS. 1.095 +/- 0.804, p < 0.0001). In the cases with PSA levels of 4.0 ng/ml or less, gamma-Sm levels in the patient with CaP were significantly lower than in those with NC (1.600 +/- 0.705 (n = 12) VS. 3.243 +/- 2.456 (n = 77), p = 0.0064), while PSA levels in the patients with CaP were not significantly different from those in the patients with NC, and consequently, PSA/gamma-Sm ratio in the patients with CaP were significantly higher than in those with NC (1.762 +/- 0.544 VS. 0.808 +/- 0.330, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
PURPOSE: We evaluated the technical feasibility and followup outcomes of a nephron sparing operation for localized renal cell carcinoma and von Hippel-Lindau disease. MATERIALS AND METHODS: Our 5 patients underwent initial nephron sparing surgery followed by serial computerized tomography. RESULTS: All but 1 renal lesion was resected in 9 initial nephron sparing operations. Postoperative computerized tomography revealed 35 lesions of which 8 had enlarged. Four patients underwent secondary renal surgery and adequate renal function was preserved. CONCLUSIONS: Even with the high risk of local recurrence nephron sparing surgery is an appropriate approach for these patients.
A multicentric randomized trial was conducted to evaluate the efficacy of intravesical chemoprophylaxis for primary superficial bladder cancer. The 299 eligible patients with primary superficial bladder cancer were randomized into four groups (A, B, C, and D) after pathological confirmation. Intravesical instillation of drugs, which were dissolved in 20 ml physiological saline (PS; group A, 20 mg Adriamycin; group B, 20 mg epirubicin; group C, 20 mg pirarubicin; group D (control), PS alone], was performed once a week for 2 weeks after trasurethral resection and then once every 2 weeks for 14 weeks, once monthly for 8 months, and once every 3 months for 1 year. No significant difference in the patients' characteristics was found among the four groups. The follow-up period ranged from 3 to 31 months (mean, 14 months). The nonrecurrence rates were estimated by the method of Kaplan and Meier. The relative effects of five variables (the tumor status, size, grade, and stage and the treatment) on the efficacy of the chemoprophylaxis regimens were evaluated using a multiple regression model. Although the nonrecurrence rates determined for groups A and B were significantly higher than that found for group D (P < 0.05), no significant difference in the nonrecurrence rate was detected among groups A, B, and C. The multiple regression model indicated that the most important factors in preventing tumor recurrence at 12 or 24 months were the intravesical instillation of an anthracycline and the tumor status (solitary). These results demonstrate that intravesical instillation of the tested anthracyclines is effective for at least 2 years as prophylactic chemotherapy for primary superficial bladder cancer.
To investigate the possible involvement of endogenous endothelin (ET) in cyclosporin A (CsA) nephrotoxicity, we examined the renal effects of the selective [125I]ET-1 binding to porcine aortic membrane (ETA) receptor antagonist, BQ-123 (BQ), on CsA-treated rats. An osmotic minipump filled with BQ or its vehicle (saline), was subcutaneously implanted and animals were treated with CsA (50 mg/kg/d, i.p.) for 4 d. In both BQ- and its vehicle-treated rats, the 24-hour urine volume, urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion, urinary Ca/creatinine (Cr) and urinary NAG/Cr ratios were significantly increased compared with those before administration of CsA. In contrast, after administration of CsA, urinary Cr excretion was significantly decreased in both rat groups. Although urinary NAG excretion and the NAG/Cr ratio in the rats treated with BQ were significantly increased compared with those treated with saline, the serum Cr levels in BQ-treated rats were significantly lower than those in saline-treated rats. Urinary immunoreactive ET-1 (irET-1) excretion in all animals was significantly increased after administration of CsA. There were no significant differences in urinary irET-1 excretion in both BQ-treated and saline-treated rats with and without CsA. Expression of irET-1 was seen in the cytoplasm of renal tubules, but the degree of expression was similar in the BQ-treated and saline-treated rats on CsA. In the BQ-treated rats, small round areas with high grain densities over the glomeruli in the cortex and vesa recta bundles in the outer medulla were masked by the antagonist action of BQ.(ABSTRACT TRUNCATED AT 250 WORDS)
An 80-year-old man, who had been treated for colon cancer 25 years ago, presented with gross hematuria. Rectal examination revealed a soft nodule in the right lobe. The serum prostatic specific antigen (PSA) was elevated to 5.2 ng/ml, while prostatic acid phosphate (PAP) was normal. Transrectal ultrasound revealed a hypoechoic mass in peripheral zone of the prostate and dilated seminal vesicle. A needle biopsy of the prostate showed mucinous adenocarcinoma. Under the diagnosis of prostatic tumor with seminal vesicle involvement, radical prostatectomy was performed. Histological findings showed organ confined cancer, of which most was composed of extracellular mucin lakes. Immunohistochemical study revealed the tumor cells positive for PSA and PAP. Mucinous adenocarcinoma of the prostate has been known to be clinically different from non-mucinous adenocarcinoma, in that the former is insensitive to hormonal therapy, is rarely associated with elevated PAP and rarely metastasize to the bone. But our analysis of the literatures is Japan showed no significant difference clinically between mucinous and non mucinous prostatic adenocarcinoma. However mucinous adenocarcinoma with signet ring cell rarely responds to hormonal therapy, which should not be classified to true mucinous adenocarcinoma in the current criteria. True mucinous adenocarcinoma could be a variant of prostatic adenocarcinoma, which is peripheral origin and should be treated like non-mucinous adenocarcinoma.
Prostate specific antigen (PSA) and gamma-seminoprotein (gamma-Sm) are revealed to be the same protein. However, the serum concentrations of PSA and gamma-Sm in the same samples are frequently different. We previously measured a ratio of serum PSA concentration and gamma-Sm concentration (P/S ratio), and evaluated its usefulness for diagnosis of prostate cancers. In this paper, we tried to determine the cutoff value which brings better efficiency and diagnose prostate cancer by means of P/S Ratio. Between April 1988 and September 1992, 221 men underwent prostatic biopsy and/or TUR-P, and were diagnosed pathologically. Of 221 patients, 130 were diagnosed as BPH, prostatis or normal prostate (no cancer; NC) and 91 were diagnosed as prostate cancer (CaP). 1) The mean +/- SD of P/S ratio in 130 patients with NC was 0.919 +/- 0.563. While, the mean +/- SDs of P/S ratio were 12.447 +/- 44.353 in 91 patients with CaP and 2.052 +/- 0.751 in 39 Cap patients with serum PSA level of < or = 10 ng/ml. The mean P/S Ratios in CaP patients with serum PSA of < or = 10 ng/ml as well as in all CaP patients were significantly higher than those in NC patients (p < 0.0001). 2) When the cutoff value of P/S Ratio was determined to be 1.45, the highest efficiency (= sensitivity x specificity divided by 100), 83.4, was obtained. The sensitivity and specificity were 91.2% and 91.5%, respectively as a cutoff value of 1.45.(ABSTRACT TRUNCATED AT 250 WORDS)
We report 4 patients, 1 female and 3 males aged 26-74 years, who underwent surgical treatment for renal malignant tumors with supradiaphragmatic extension into the vena cava. All of their tumor thrombi extended to the right atrium as confirmed by magnetic resonance imaging. The distinctive symptom was liver dysfunction caused by disturbance of the hepatic vein drainage in two patients. However, there was no common symptom in these 4 patients. Preoperative metastasis was found only in the female, whose metastasis was solitary in the lung and seemed to be able to be removed easily after radical nephrectomy. All of these 4 patients had radical nephrectomy and removal of the tumor thrombi with the use of cardiopulmonary bypass and temporary exsanguination. In 3 of these patients, the liver was mobilized to expose the retrohepatic vena cava by incision of the falciform, triangular and coronary ligaments. Two patients with vena caval wall invasion had vena cavectomy and an artificial vascular graft was then sutured to replace the caval wall in one of them. Preoperative liver dysfunction was gradually improved after operation and completely recovered about 1 week later. A postoperative complication, wound infection, occurred in only one patient. Pathological examination revealed renal cell carcinoma in 3 patients and nephroblastoma in the remaining one. In renal cell carcinoma, both patients without distant metastasis were alive about 15 months postoperatively. However, the one with lung metastasis died with newly appeared multiple metastases 9 months postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)
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To compare the effects of MMC + UFT (A) with MMC + 5-FU (B) therapy on the response rate, survival time and changes with time in quality of life (QOL) in unresectable or recurrent gastric cancer, we carried out a study by a multicenter, randomized controlled trial from June 1990 to August 1992. 39 patients were randomly divided into A group and B group, including 6 incompletely evaluated cases and 3 in eligible cases. Responses were recognized in 3 out of 13 evaluable cases (23.1%) treated with regimen A and in one out of 15 evaluable cases (6.7%) treated with regimen B. Mean survival time was 150 days (A) and 116 days (B), respectively. These results suggested that MMC + UFT therapy is one of the effective regimens for advanced gastric cancer and as useful as MMC + 5-FU therapy. Moreover, it showed that regimen A was superior to B on QOL.
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Monolayer cultures of renal tubular (hKEC) cells were established. These cells formed empty spheroids after 2-3 weeks of culture in a collagen gel matrix. A subcellular polarity from the apex to basement was induced in these "spheroidal" hKEC cells. The weak expression of laminin at the outer surface was evident on spheroidal but not on monolayered hKEC cells. The regulation of HLA-ABC, DR, and intercellular adhesion molecule-1 (ICAM-1) antigens on hKEC cells in the gel matrix was investigated utilizing digestion of gel matrix by collagenase. Enzymatic digestion of the collagen gel did not significantly affect the surface expression of HLA-ABC and ICAM-1, but reduced HLA-DR expression as shown by flow cytometry. The MHC and ICAM-1 molecules on both spheroid-forming and monolayered hKEC cells were upregulated by adding a supernatant of mixed lymphocyte reaction (MLR) and recombinant human interferon (IFN)-gamma. HLA-DR antigen expression was inconsistently induced on the hKEC cells cultured in collagen gel without MLR supernatant or IFN-gamma. In contrast, no HLA-DR expression was found on monolayered hKEC cells in the absence of MLR supernatant or IFN-gamma. Spheroid-forming hKEC cells, when dispersed by enzymatic digestion, were more susceptible to cytolysis by lymphokine-activated killer (LAK) cells than were the enzymatically dispersed, monolayered cells in the 51Cr-release assay. The LAK cells were seen to migrate into the collagen gel and kill the hKEC cells. Thus, LAK cells may function to favor the acceleration of graft rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
We reviewed 14 male and 9 female patients with adrenal tumor discovered incidentally by imaging studies in an attempt to assess adrenal function, mainly cortical function. Pathological diagnosis consisted of cortical adenoma in 12 patients, cortical nodular hyperplasia in 2, medullary hyperplasia in 1, cavernous hemangioma in 1, metastatic tumor in 4 and cyst in 2. Another adrenal cyst was diagnosed by percutaneous puncture. In all patients peripheral levels of plasma cortisol and aldosterone were normal. Plasma catecholamine levels were also normal except for 1 patient with medullary hyperplasia who had equivocal elevation. Among the patients with cortical adenoma and hyperplasia, however, 5 of 10 (50%) had excessive excretion of 24-hour urinary 17-hydroxycorticosteroids, 4 of 13 (31%) had a loss of plasma cortisol circadian rhythm and 7 of 14 (50%) had insufficient suppression on the dexamethasone test. Furthermore all patients had an increased ipsilateral uptake that was not suppressed after dexamethasone on 131iodine-adosterol scintigraphy, while a diminished contralateral uptake was noted in 5 of 15 (33%). Postoperatively, hypertension decreased to normal in 2 of 3 patients and impaired glucose tolerance was improved in 1 of 2. Two patients with cortical adenoma who exhibited a loss of plasma cortisol circadian rhythm experienced postoperative adrenal insufficiency. These data indicate that a considerable number of incidentally discovered adrenal tumors are not nonfunctioning particularly in reference to glucocorticoid secretion, and adrenalectomy seems to be beneficial in some of those patients with hypertension or impaired glucose tolerance.