The correct prediction of the viability of the isolated or preserved kidney is very important in cadaver transplantation. At present, while there are various methods for evaluating the viability of renal graft, none is complete. Furthermore, the assessment of its viability is frequently based on the duration of warm or cold ischemia in simple cold storage. Therefore, an accurate, rapid and complete method for the prediction of renal viability is desirable.
The author recently found that myo-inositol, a kind of cyclic polyol contained abundantly in the organ, is plentiful in the early effluent perfusate washed out from the preserved kidney. Based on these findings, attempts were made to develop for evaluating the viability of the preserved kidney by measuring the free myo-inositol (F. m-I) levels in the early effluent perfusate (EEP).
Herewith the satisfactory results of my experiments, in vitro and in auto-transplantation of the canine kidney, and clinical renal transplantation by the method are reported.
The canine kidney was kept in ischemic condition for various periods at 4°C or 37°C and it was washed out with 4°C lactated Ringer's solution (200ml). The first effluent perfusate of 25ml (EEP) was collected. As for the perfusate, F. m-I was trimethylsililated and measured by gas-chromatography using a 2m column of 5% ucon coated.
In vitro, the relationship between F. m-I levels (Y) and cold ischemic time (X, hrs) for kidney was Y=0.03X²-0.04X+17.72 (μg/ml), the coefficient of correlation (r) being 0.858. The relationship between F. m-I levels (Y) and warm ischemic time (X, hrs) came to Y=17.9X²-16.5X+15.6 (μg/ml), r=0.808, showing that F. m-I levels were correlated markedly with the ischemic time of the preserved kidney.
In auto-transplantation, the animals were classificated into the following three groups according to the graft function. I, the S - Cr is less than 5mg/dl. II, the S - Cr rises up to ca 10ml/dl but thereafter falls off gradually. III, the S - Cr rises transiently and animals die within a week. The mean F. m-I levels in EEP of those groups were I; 15.6±2.2 II; 32.2±3.5 and III; 67.1±14.5 μg/ml (mean±S. E), respectively. And the relationship between F. m-I in EEP and max. S-Cr levels of animals was Y=0.168X+1.70, r=0.815. In control kidneys, the mean F. m -I level in supernate of whole, cortex and medulla were 9.54±1.28, 2.85±0.38 and 21.20±2.32 μg/mg (mean±S. D). On the other hand, in a 3hr warm ischemic kidney, the mean F. m-I level in supernate of those were 5.90±1.07, 2.63±0.36 and 16.00±2.17μg/mg, respectively. F. m-I in renal tissue is contained mainly in its medulla. And F. m-I in renal medulla declines with long ischemia, although that of renal cortex dose not change.
In clinical renal transplantation, the mean F. m-I levels in total effluent perfusate of living and cadaver donor graft were 509.1±245.7 and 1138±130μg (mean±S. D). The mean F. m-I levels in total effluent perfusate per 1g of graft kidney were 3.08±1.35 and 7.57±1.40μg/g (mean±S. D). The mean F. m-I levels in total effluent perfusate of early postoperative good and bad function grafts were 483±231 and 1079±153μg.
The mean F. m-I levels in total effluent perfusate in per 1g of graft kidney were 2.95±1.28 and 6.95±1.62μg/g, respectively.
In summary, F. m-I levels in EEP were markedly correlated with the duration of cold and warm ischemia, with the renal graft function after auto - and clinical transplantation, suggesting that preserved kidney viability may be predicted by EEP - F. m-I determination.

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Two hundred and eighty-four patients with prostatic cancer were followed with survival and clinical data. The actual 5-year survival rate was 77% for stage A, 73% for B, 47% for C and 31% for D.
Two hundred and five patients had received endocrine therapy (stage A6, B9, C43, D147). In these cases, the actual 5-year survival rate was 50% for stage C and 39% for D. In the patients of stage D received hormonal therapy and castration (103), the actual 5-year survival rate was 52%.
Reduction of elevated serum acid phosphatase (SAP) and pathological classification also influenced prognosis. The actual 5-year survival rate of the patients whose elevated SAP returned normal was better than those whose SAP remained at pathological levels. Low grade adenocarcinoma also showed good prognosis.
In the patients who undergone TUR before any therapy, the actual 3-year survival rate was 40% for stage C and 67% for D. This result showed TUR influenced poor effect for stage C.
The cause of death of the patients of stage D with endocrine therapy were as follows. Prostatic cancer was the worst (75%) and cardiovascular accident was next (11%).

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Eight cases of hydronephrosis due to aberrant vessels experienced during the past 5 years (from 1975 to 1980) were studied, comparing them with 12 cases of hydronephrosis caused by congenital stenosis in the ureteropelvic junction (p-u stricture).
There were no remarkable differences in clinical pictures between the studied cases and those in the literature, including age and sex distribution, together with chief and side complaints. However, when compared with the congenital P-U stricture cases, the incidence of pain attack was higher and the duration of illness was shorter.
It was found that the renal damage of the studied cases was milder than in the others through preoperative IVP studies. This fact indicates that the sudden onset of sharp pain brought about by excerbation effect of aberrant vessels shortened the durationn of illness in the studied cases. This might propose the necessity of the sophisticated venography study in addition to the conventional angiography whenever hydronephrosis due to aberrant vessels are suspected.
Current general understanding is the dismembered pyeloplasty with conservation of the vessels is the best way to treat the hydronephrosis due to P-U stricture. Our results were also in accordence with it.

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To investigate the pathogenesis of chronic renal candidiasis, sublethal doses of Candida albicans were injected intravenously into female mice.
In the 6th week after injection, unilateral renal damage and contraction were found in most of the surviving mice. Histological examination in the damaged kidneys revealed pyelonephritic changes with perivascular lymph-follicule formation, but their contralateral kidneys were without remarkable changes.
Bacteriological studies revealed that C. albicans cells were obtained only from the contracted kidneys, and not from the contralateral unaffected kidneys. No C. albicans cells were found in either kidney, when the bilateral kidneys were apparently normal.
Asymmetry in size & weight of the kidneys in mice was observed at 3 weeks after injection, and became more marked thereafter.
By the time the contracted kidneys got atrophied, the contralateral kidneys was grossly hypertrophied, which was also proved by intravenous pyelography.
The count of C. albicans was decreased in the unaffected side, when the renal asymmetry was noted.
This experimental model may be useful in the study of hematogenous chronic pyelonephritis not only of fungal but of bacterial origin.

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Local administration of 6-Hydroxydopamine (6-OHDA) into the proximal urethra and bladder base was performed 18 patients suffering from neurogenic bladder dysfunction. The effects of chemical sympathectomy were studied for 43.4 months on the average. Ten cases maintained improved bladder function. Among them, 7 cases showed balanced bladder and remaining 3 cases required additional local injection of 6-OHDA. Two of these improved cases who had bladder deformity and hydropelviureter before the treatment showed improvement in cystometrogram and pyelography. Eight cases showed no improvement in bladder function. VUR was developed in two cases among them and caused deterioration of the upper urinary tracts.
The above results showed the effectiveness of local injection of 6-OHDA to certain cases of neurogenic bladder dysfunction.

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The human urinary bladder mucosa (6 cases) and bladder tumors (well-differentiated: 20 cases, poorly-differentiated: 3 cases) were observed under the scanning (SEM) and transmission electron microscopy (TEM).
SEM revealed that normal (non-tumor) bladder mucosa was covered penta-or hexagonal superficial cells. Reticular microridges and a small number of microvilli were found on the luminal surface of the superficial cells and their cell boundaries were defined with a few rows of short microvilli. Some superficial cells possessed numerous microvilli with relatively undeveloped microridges. TEM showed that normal bladder mucosa was covered with large flattened superficial cells. Their luminal surfaces appeared wavy by the presence of concave plaques and interposing ridges. Fusiform vesicles were found beneath the luminal membranes. Some superficial cells were elongated and tall in shape. These atypical superficial cells had concave plaques, relatively undeveloped microridges and many short microvilli on the luminal surface. In the cytoplasm, fusiform and small round vesicles were found beneath the luminal membrane. Membranes of the plaques and fusiform vesicles appeared as asymmetric in both typical and atypical superficial cells. It is suggested that atypical superficial cells are young maturing superficial cells from intermediate cells.
SEM revealed that pleomorphic microvilli were observed on the surfaces of the well-differentiated bladder tumors. There were 3 types in the shape of pleomorphic microvilli. The profiles of microvilli were similar not only in a given tumor cell but also in a given tumor. According to the shape of the microvilli, well-differentiated tumors were devided into 3 sub-types. Type A tumors (4 cases) showed branching microvilli of varying length and undeveloped microridges, type B (7 cases) short and long upright microvilli and type. C (9 cases) string-like elevations of variable length without branching.
TEM observations revealed that the outermost cells of well-differentiated tumors were either flattened or elongated, having many microvilli on their luminal surfaces. The microvilli were various in shape in type A, long and straight in type B and laying down on the cell surface in type C tumors. The luminal plasma membrane appeared symmetric in all tumors. Round vesicles were seen beneath the luminal membrane in type A tumor cells. Large secondary lysosomes were found in the outermost and intermediate cells of both type A and B tumors. The cells in intermediate and basal layers were small in size as compared with the outermost cells. The nuclei were pale in types A and B, while those in type C tumors appeared dark due to the abundant heterochromatins. Intermediate and basal cells of A and B tumors also contained secondary lysosomes and various shaped mitochondria. Nucleus was sometimes surrounded with cytoplasmic tonofibrils and/or lamellar rER in all 3 types of the tumors classified by SEM.
From the clinical aspect, all of type A tumors by SEM were transitional cell carcinoma grade 1 and were currently under control after a transurethral resection of bladder tumors (TUR-Bt) without recurrence. Type B tumors were mostly grade 2. More than two TUR-Bt and total cystectomy were necessary for the treatment. Type C tumors were also mostly grade 2. Total cystectomy was performed in 6 to 9 type C tumors.
The present study clearly demonstrated the difference of the surface structure between normal and neoplasmic human bladders. Furthermore, 3 subtypes could be classified in well-differentiated tumors according to the surface characteristics and were correlated to the difference of cytoplasmic organella. Among well-differentiated bladder tumors, type A tumors were highly differentiated and type C tumors were less differentiated. Thus, well-differentiated bladder tumors could be further classified into sub-types according to their surface characteristics.
In poorly-differentiated bladder tumors

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Nalidixic acid (NA) was administered to female patients with acute simple cystitis at a dose of 2g daily for 3 days to determine its efficacy. Recurrence rate and factors causing recurrence were also discussed based on the results of a follow-up survey.
Upon completion of a 3-day treatment with NA at a dose of 2g daily, efficacy of the drug was assessed according to the Criteria for Drug Evaluation by UTI Study Group. 430 out of 808 patients collected from 103 institutions were subjected to the evaluation. The remaining cases were excluded because of various reasons. 258 (60%) out of the 430 cases showed “Excellent” response to NA and “Good” in 110 patients (25.6%). The overall efficacy rate was 85.6%.
Then the follow-up treatment for 7 days was done in 368 patients of “Excellent” or “Good” and reexamined. Inter-group comparison was made, where Group A received NA 1g for 7 days and a low dose of antiinflammatory agent was given to Group B for a week following the initial treatment. No treatment was done in Group C following the initial treatment. The recurrence was less frequent in Group A, while higher incidence of recurrence was observed in Groups B and C. It was found that the recurrence rate in those patients showing “Good” response to the initial 3-day treatment with NA was higher than that of the “Excellent” Group. It is to note that relatively high incidence of recurrence was observed in those patients with persisting bacteria in urine, even if its bacterial count was less than 10⁴/ml.

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Menadiol sodium diphosphate (MSDP), which is employed clinically as a water-soluble vitamin K active drug, is used as a substrate for acid phosphatase determination. A method was developed with this new substrate, and its specificity in prostatic acid phosphatase determination was estimated through comparing the rate of hydrolysis of MSDP by human prostatic tissue with those of the kidney and liver tissues (P/K, P/L ratios). These ratios were also compared in animal experiments (dog and rat), between MSDP and other substrates (p-nitrophenyl phosphate and sodium thymolphthalein monophosphate) as well. The results suggest that this new substrate is comparatively specific for the prostatic acid phosphatase than the other commonly used substrates.
On the other hand, the prostatic tumor model experiments was devised for introduction into in vivo study of this agent. Experimental prostatic tumors were made in Wistar strain male rats by local administration of 20-methylcholanthrene (20-MC), and heterotransplantation of human prostatic tumors into nude mice. The acid phosphatase activities in tissues of these tumors were evaluated with MSDP as substrate and these values were compared with those of their proper organs (kidney and liver). In two rats (20%), 20-MC induced prostatic tumor was observed. Their histologic features were of fibrosarcoma. The acid phosphatase activity in these tumor was of slightly higher level than that of the prostatic tissues of normal rat. However, these values were fairly lower than those of their own liver and kidney. In nude mice, heterotransplantation of primary tissue fragments from human prostatic adenoma provided the best results. All tissues were taken (100%) and their histologic features were strikingly similar to the original tumors. The acid phosphatase activity in those tumor tissues was significantly higher than those of their own organs; prostate (approximately 43 times), liver (approx. 26 times), and kidney (approx. 23 times). Histochemical study by means of the azo-dye coupling technique demonstrated a great activity of acid phosphatase in the glandular epithelium of prostatic adenoma which was heterotransplanted into nude mice.

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Menadiol Sodium Diphosphate (2-methyl-1, 4-naphthohydroquinone diphosphoric acid ester tetrasodium salt;^® Synkavit) is a watersoluble preparation with physiological functions of natural fatsoluble vitamin K. This drug, however, was employed as antimitotic agent, radiosensitizer, and internal irradiation agent for neoplasms in experimental or clinical studies in the past. Furthermore, in the previous study, it was used as a substrate for acid phosphatase determination in in vitro studies, and its specificity for the prostatic acid phosphatase has been established. This paper deals with an in vivo study which investigated the distribution of tritiated menadiol sodium diphosphate (³H-MSDP) in nude mice bearing heterotransplanted human prostatic adenoma, by means of whole-body macroautoradiography and quantitative evaluation by a liquid scintillation spectrometer. Possibilities of its clinical use in the prostatic disorders are discussed. MSDP, labelled with tritium by RCC Amersham (TR 7 method), was purified through paper partition chromatography, and its purity was confirmed by autoradiochromatography.
Whole-body macroautoradiograms (ARG) were obtained at 5, 15, 30, and 60 minutes after an intravenous administration of ³H-MSDP, 34μCi/15.4μg of MSDP/50μl/10g body weight, into nude mice bearing heterotransplanted human prostatic adenoma. Accumulation of ³H-MSDP in the heterotransplanted tumor was defined by the ARG of 5, 15, 30, and 60min sections respectively. The optical concentration of radioactivity in the heterotransplanted tumor was comparatively constant throughout each ARG (at 5, 15, 30, and 60min). At five minutes after the administration, this tracer was distributed intensely in the kidney, liver, lung, and urinary bladder, the highest radioactivity being detected in the last. However, the radioactivity of these organs tended to decrease after 30min, while those of the urine and feces increased. At 60min after administration the optical concentration in the heterotransplanted tumor was nearly equal to that of the renal parenchyma, and was rather higher than those of the liver and other organs.
The distribution of ³H-MSDP in nude mice bearing heterotransplanted human prostatic adenoma was also investigated through measuring radioactivity in each organ by liquid scintillation spectrometer. Tissue samples were taken at 1, 2, 5, and 24 hour intervals after an intravenous administration of ³H-MSDP, 3.4μCi/1.54μg of MSDP/50μl/10g body weight. At one hour after the administration, the heterotransplanted tumor revealed an apparently higher radioactivity than circulating blood, liver, brain, spleen, muscle, testis, or seminal vesicle & prostate. On the other hand, the radioactivity of the kidney was three times higher than that of the heterotransplanted tumor. These findings paralleled to those of the ARG. Sequential analysis revealed that the radioactivity in the heterotransplanted tumor remained almost constant after a lag time, while in the kidney it tended to decrease with time. At 24 hours, Tumor/Blood ratio was almost comparable with Kiney/Blood ratio.
These findings suggest the potential usefulness of radiolabelled MSDP in the clinical diagnosis of prostatic disorders.

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