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We describe a new method of drug dosage adjustment. The method simultaneously considers glomerular and tubular functions as parameters, because nonparallel decreases in both functions limit the use of the conventional endogenous creatinine clearance (CLCR) method for dosage adjustment. In the new method, CLCR and the 15-minute phenolsulfonphthalein (PSP15') test were used and applied to patients with renal insufficiency with cephalexin (CEX) as a model drug for renal tubular secretion. The results clearly demonstrate good control of plasma CEX concentrations by the CLCR-PSP15' method, whereas there were marked changes in plasma CEX levels with the CLCR method alone. Our method appears to be more useful for patients with renal impairment than the conventional CLCR method for CEX, which is mainly excreted in urine by renal tubular secretion. A nomogram for the CEX dosing interval is proposed for application to clinical practice.

Among 65 patients who underwent simple suprapubic prostatectomy, three consecutive quantitative estimations of clean voided midstream urine were carried out, i.e. before operation, on discharge from hostpital and six months or later after operations (late review), respectively, and some factors that will affect persistent significant bacteriuria were discussed. The results thus obtained were as follows. 1. Incidence of persistent significant bacteriuria at late review was 30.8% in patients with significant bacteriuria preoperatively and this figure was higher than 17.7% in patients without significant bacteriuria preoperatively. 2. Duration of postoperative indwelling urethral catheterization plays a less significant role than the presence of preoperative bacteriuria in the persistent significant bacteriuria on discharge and at late review. 3. Size of the enucleated prostate also showed no significant relationship to the persistent significant bacteriuria at late review.

The immunological properties of human serum testosterone-estradiol binding globulin (TeBG) which was purified by affinity chromatography and hydroxyapatite column chromatography were investigated and a specific radioimmunoassay (RIA) for human TeBG was established. The purified TeBG here obtained was 86,000 in molecular weight and the antibody prepared against this TeBG slightly cross-reacted with human immunoglobulin G (IgG). The human TeBG labeled with 125I had a high binding activity to the antihuman TeBG antibody, and the sensitivity of the RIA thus obtained was enough to detect the TeBG in 2 μl of the serum.

Bovine serum TeBG was purified by 17 alpha -carboxyethynyl-17-hydroxy-4-androsten-3-one sepharose 4B affinity chromatography (T-sepharose) and hydroxylapatite column chromatography. The chemical and immunological properties of the purified TeBG were surveyed and the following results were obtained. 1) The procedures yielded 400 microgram of protein from 1 L of bovine serum with an overall purification of about 7,560 fold. 2) The purified TeBG was homogenous and was about 80,000 in molecular weight based on sucrose density gradient ultracentrifugation and polyacrylamide gel electrophoresis. 3) The antibody prepared against the purified bovine TeBG did not cross-react with dog and human sera, suggesting the species specificity of TeBG. 4) 125I-bovine TeBG, labelled by the lactoperoxidase method, had a high binding capacity to the anti-bovine TeGB antibody. These results indicate the applicability of purified TeBG and the antiserum for TeBG RIA.

Diuretic effects of furosemide (FM) alone or combined with dopamine (DA) were inves-tigated in subjects with normal renal function and in patients with renal impairment. The renal excretion rate constant and the urinary recovery of FM were significantly decreased in the patients. However, there was no correlation between pharmacokinetic parameters and diuretic responses to FM in the patients. In contrast, linear regression line for urine flow rate vs.(Na++K+) excretion rate (UVNa+K), and that for Cl- excretion rate vs. UVNa+K showed high correlations, regardless of DA infusion, although diuretic responses and creatinine clearance in the patients were increased with DA. To clarify the variations of the sensitivity to FM, a urinary excretion-response curve, which was expressed by UVNa+K vs. urinary excretion rate of FM, was analyzed. Increased apparent sensitivity to FM diuresis was observed in patients with renal failure, although the max imal and total diuretic responses were decreased. Therefore, highdose FM may not always be effective for patients with severe renal impairment. The sustained administration of FM or the co-administration of low-dose DA, by which the hemodynamics in the kidney are improved, may be a more effective treatment.

To study the participation of cAMP in the action of gonadotropin on testicular steroidogenesis in the human testis in vivo, we have measured the concentrations of cAMP, testosterone, 5 alpha-dihydrotestosterone, estrone, 17 beta-estradiol, and hCG in the spermatic venous blood of the patients with prostatic cancer after hCG injections into the testis. Five minutes after hCG administration, spermatic cAMP increased to 5 times the pretreated level, and after 30 min, it increased to 20 times the pretreated level. Testosterone increased gradually after hCG injection, and the 2-fold increase was demonstrated at 50 min. Although the pattern of the changes in spermatic 5 alpha-dihydrotestosterone was similar to that of testosterone, a statistically significant increase was not observed after hCG administration. Estrogen production was also stimulated by hCG. These results are consistent with the view that cAMP may participate in the action of hCG upon steroidogenesis in the testis of human beings in vivo, as has previously been observed with rat and human testes in vitro.

The interrelationship of the liver function tests and the 5-year survival rates were studied in 62 patients with prostatic carcinoma who were treated with antiandrogens. Abnormally high bilirubin, and glutamic oxaloacetic and pyruvic transaminase serum levels were a significant index with regard to the 5-year survival rates.

On eight volunteers with reduced kidney function, 1 g of carbenicillin indanyl sodium was administered orally for the single dose studies and was given orally in a dose of 1 g every 6 h for 7 days for the multiple dose studies. The patients were divided into two groups according to their kidney functions: group I moderately impaired and group II severely impaired. In the single dose studies, the mean peak level was 12.6 microgram/ml for group I and 26.9 microgram/ml for group II. In the multiple dose studies, the drug tended to accumulate in group II, but the level obtained in group II did not exceed more than 300 microgram/ml. In the single dose studies, the mean peak level in the urine was 1,478.5 microgram/ml for group I and 350.0 microgram/ml for group II. In the multiple dose studies, despite the multiple dose regimen, the level obtained from group II patients only transiently exceeded more than that which will effectively inhibit the growth of Pseudomonas, Klebsiella and Enterobacter. In the single dose studies, the mean cumulative amount excreted in the urine within 24 h was 314.2 mg for group I and 120.1 mg for group II and the difference between both groups was significant (p less than 0.05). For the multiple dose studies, the amount was 278.0 mg for group I and 127.2 mg for group II, respectively. The total amount excreted in the urine within 24 h and the serum level obtained 6 h after ingestion of 1 g of carbenicillin indanyl sodium was correlated to the creatinine clearance and the rate of PSP excreted in the urine within the first 15 min of the test.

Immunoperoxidase methods were used to study ABO(H) blood group antigens and carcinoembryonic antigens in patients with transitional cell carcinoma of the bladder. In our study absence of blood group antigens in cancer tissues was not found to be correlated with histologic grade, stage and survival rate in patients with bladder carcinoma, while it was correlated with subsequent intravesical recurrences. In contrast, the presence of carcinoembryonic antigens in cancer tissues was correlated well with histologic grade, stage and survival rate. Our results suggest that immunoperoxidase detection of blood group antigens could not predict poor survival. In contrast, immunoperoxidase detection of carcinoembryonic antigens is of prognostic value in patients with transitional cell carcinoma of the bladder.

Testosterone-estradiol binding globulin (TeBG) is known to change in various endocrinological environments such as estrogen administration, pregnancy and aging. Several methods, including dextran coated charcoal, equilibrium dialysis and ammonium sulfate precipitation, were used to measure the binding capacity of TeBG, but these were not simple and accurate. We therefore measured TeBG levels in human serum by means of a steady state polyacrylamide gel electrophoresis and found that this method was simple and accurate for the determination of the binding capacity of TeBG. The value of TeBG in normal adults (27 approximately 32 years old) was 3.88 +/- 0.45 x 10(-8) Mol and in patients with benign prostatic hypertrophy the value was high (5.49 +/- 1.35 x 10(-8) Mol compared to that of normal adults.

A newly synthesized 18-membered hexaamine carrying an acetate moiety on each nitrogen, L2, has been demonstrated to be a more efficient dissolving agent that ethylenediaminetetraacetic acid for human urinary calculi whose major components are calcium phosphate and magnesium phosphate. L2 is a good chelating agent for Ca2+ and Mg2+, and this chelating action is presumably responsible for the dissolution of inorganic calculi.

The status of Thomsen-Friedenreich antigen (T antigen), in histological sections of human hyperplasia (30 cases) and adenocarcinoma (45 cases) of the prostate, was investigated by the immunohistochemi

Adrenal biopsy was carried out at the time of operations for renal diseases and the histological findings in 62 cases were studied with systemic biochemical laboratory examinations. Adrenalitis prevalent in infected renal diseases as a probable sequence of contiguous involvement had apparently no direct relation to the level of urinary 17-OHCS. Hyperplasia of the adult glomerulosa was high in incidence in cases with hypertension and/or low levels of serum potassium. Outward transformation of fasciculata cells was prevalent in cases with high levels of NPN, hypertension and/or abnormal levels of serum potassium. Inward transformation of fasciculata cells was closely related with elevated levels of urinary 17-OHCS and 17-KS. This lesion as well as hyperplasia of the reticularis was frequently associated with low A/G ratios.

We report a case of 2,8-dihydroxyadenine urinary lithiasis with complete deficiency of adenine phosphoribosyl transferase. Adenine phosphoribosyl transferase activities in the erythrocytes, lymphocytes and granulocytes of the patient’s family also were determined. The propositus and her younger brother were homozygotes for adenine phosphoribosyl transferase deficiency and her parents were heterozygotes. This is the third family with this disease to be reported.

The 23rd case of metastatic breast carcinoma of prostatic origin was reported. In the breast mass of this case, a high concentration of the R1881 receptor was detected.

The localization of the testosterone-estradiol-binding globulin (TeBG) in prostate, liver and metastatic lymph node cells of a patient with hormone-independent prostatic carcinoma was studied by the t

A rare case of metastatic renal tumor originating in a cervical carcinoma in a 59-year-old Japanese woman is presented and the clinical and autopsy features discussed.

This study was conducted to examine if an aminoglycoside (dibekacin sulfate, DKB) incorporated into a coating layer on outer and inner surface of indwelling catheters would be released into urine both in vitro and in clinical cases on a sustained basis and if the released DKB would have any efficacy on delaying lower urinary tract infections. Released amounts of DKB from the catheter silicone rubber (SR) catheter were periodically measured both in vitro and in clinical applications. During the clinical applications, the catheters were indwelled in 14 patients. Organism counts in the patients' urine were determined and organisms were isolated from bacteriuria (defined as greater than or equal to 10(4) CFU/mL) and MICs to DKB were measured. Observations on several combined symptoms frequently associated with indwelling catheterization were performed. Results showed that sustained release of DKB continued for more than 25 days and 13 days in vitro and in clinical cases, respectively. Clinical studies suggested that 8 days of sterile urine after catheterization might be expected in patients without systemic administration of antibiotics and more than 2 weeks if combined with it. No particular problems in its use and associated symptoms were recognized.

Mechanically isolated epithelium and stroma from benign hypertrophic prostates were highly pure on the basis of histochemical and biochemical criteria. By electrophoretic analyses, whole cellular and nuclear proteins were compared among whole tissues, epithelium, and stroma. The characteristic protein profiles of benign hypertrophic prostates were reflected in the electrophoretic patterns of the stroma. Two-dimensional gel electrophoretic patterns of the epithelium were different from those of the stroma with exception of about 18 major spots that were common to both fractions. Of the protein species separated, 35K/6.7 (molecular weight/pI) and 36K, which was composed of two species with pI of 4.4 and 4.6, were abundant in the epithelium and stroma, respectively. Nuclei prepared from whole tissues of benign hypertrophic prostates contained three kinds of nonhistone proteins (NHP) closely associated with benign prostatic hypertrophy (BPH); 42 K-NHP, 55 K-NHP and 190 K-NHP. Electrophoretic analysis of the nuclear proteins revealed that all the BPH-associated nonhistone proteins were abundantly distributed in the nuclei of the stroma.

A 6-year-old boy was seen for post-traumatic priapism which had been present for 4 days. Intracavernous injection of metaraminol was performed to reduce the arterial blood inflow of the penis. Within 30 min after the injection, the penis became flaccid, and the prognosis was good. Recently it was reported that there are two different types of priapism. Type 1 priapism is due to blood stasis. This type is well known and characterized by extremely hard corpora and painful penis. Type 2 is caused by increased arterial blood flow of penis. It differs clinically from type 1 by a more elastic consistency of the penis and the absence of pain. Generally the prognosis of type 2 priapism is favorable. In our case, the penis was relatively elastic and not painful. It was considered to be type 2 priapism.

Since 1968, 152 patients with unexplained renal hematuria have been treated at our clinic. Renal angiography in 46 patients who did not respond to conservative therapy revealed 21 abnormalities of the vascular system. Of these 21 patients 10 had or were suspected to have renal pelvic and ureteral varices, and 8 had congenital anomalies of either the inferior vean cava or the renal vein. Therefore, it was confirmed that vascular abnormalities were associated with the unexplained renal hematuria in these cases. Since these congenital anomalies might easily induce congestion in the renal venous system they might be the predisposing condition of the renal hematuria. Epinephrine-assisted renal phlebography has been a useful technique to detect anomalies of the venous system.

The levels of plasma testosterone, testosterone-oestradiol binding globulin (TeBG) and total serum acid phosphatase (TSAP) following antiandrogenic hormone therapy were investigated in 17 patients with prostatic carcinoma. The low levels of plasma total and free testosterone induced by castration decreased further after diethylsitlboestrol diphosphate (DES-D) administration. Plasma TeBG binding capacity after castration was 118.9% of the pre-treatment level and increased to 193.9%, 204.0% and 212.7% at 1, 2 and 3 weeks after DES-D dosing. The in vitro binding of 3H-testosterone to TeBG was not influenced in the presence of DES-D or stilboestrol. Clinical response following the DES-D therapy was associated with a decrease in the levels of TSAP. A significantly inversed correlation was found between the decrease in TSAP and increase in TeBG at completion of DES-D therapy. These results suggest that the high binding capacity of TeBG lowers the biologically active fraction of testosterone and thus may produce clinical effects.

The measurement of androgen receptor and 5α-dihydrotestosterone (DHT) levels in prostatic carcinoma may be of value in predicting responsiveness to anti-androgenic therapy. A sufficient amount of prostatic carcinoma tissue must be removed for measuring androgen receptor and DHT levels. We have studied the usefulness of Kaplan cold punch-resection compared with electroresection for obtaining tissue in 29 cases of enucleated benign prostatic hyperplasia. DHT level in electroresected specimens was similar to controls. However, following low, moderate, and high-power electroresection an average of total R1881 binding sites (Bmax) of electroresected specimens was reduced to 82.2, 71.9, and 52.1 per cent of corresponding controls, respectively. In contrast, the per cent decrease of Bmax of Kaplan cold punch-resected specimens was only 10 per cent of the control. From our data, Kaplan cold punch-resection of the prostate appears to be a useful tool for obtaining tissue suitable for measuring androgen receptor levels.

The effects of transcatheter embolization on lymphocyte proliferation in patients with renal cancer were investigated. Prognosis was good in 12 patients who underwent preoperative transcatheter embolization and 2 of 5 patients with distant metastases survived for 2 years or more. The remaining 9 patients underwent transcatheter embolization as a conservative procedure and 4 of 7 with distant metastases survived more than 1 year. Lymphocyte response to phytohemagglutinin before treatment in the presence of autologous or homologous serum was significantly lower in all patients than in healthy persons (p less than 0.01 and less than 0.05, respectively). The response after transcatheter embolization decreased slightly only in the presence of autologous serum for a short interval but recovered to the pre-treatment level 1 month after embolization. However, only in the presence of autologous serum was the response significantly higher at 2 months after nephrectomy than before treatment in patients who underwent preoperative transcatheter embolization (p less than 0.05). The serum inhibitory factor levels changed in inverse proportion to the post-treatment lymphocyte response. In patients who underwent preoperative transcatheter embolization the serum inhibitory factors essentially disappeared 2 months after nephrectomy.

In cases with untreated bladder carcinoma, mean levels of SLDH and SLDH-V were significantly higher than that of the control, but frequency of abnormally elevated cases were observed in only 19 and 41