Infection of the urinary tract is one of the most important diseases in the urological field. In recent years, the frequency of clinical isolates of Pseudomonas aeruginosa from urine obtained from patients with urinary tract infection has declined considerably, most likely due to the development of antipseudomonal antibiotics. However, the treatment of the urinary tract infection with P. aeruginosa remains to be difficult.
For the purpose of clarification of the mechanism of the antibacterial activity of β-lactam antibiotics against P. aerguinosa, their morphological responses (cell growth, division and lysis) and binding affinities to penicillin-binding proteins (PBPs) were studied.
The agents CBPC, SBPC, TIPC and CTX inhibited cell growth and caused cell lysis at a low concentration, but PIPC, MZPC, APPC, CPZ and CFS arrested cell division and turned the shape of P. aeruginosa into filamentous cells. No cell lysis was caused at a high concentration. P. aeruginosa has six major PBPs, which are designated as PBP 1a, 1b, 2, 3, 4 and 5. All β-lactams exhibited high affinity to PBP 3 and CBPC, SBPC, TIPC and CTX bound to both PBP 1a, and 1b at a low concentration. In this study it was assumed that β-lactams which had high affinity to both PBP 1a and 1b caused cell lysis easily as in the cases of CBPC, SBPC, TIPC and CTX.
The effects of β-lactams on macrophage phagocytic and killing activity of P. aeruginosa are summarized as in the following. On antibioticfree control culture, the count of viable cells in macrophages increased. Cells pretreated with CBPC, CTX, CAZ or CA, however, caused a greater degree of decline of viable cells than the untreated control cells.
Morphological changes were observed with a scanning electron microscope. Elongated cells pretreated with antibiotics were subject to phagocytosis and were digested by the macrophages, but the untreated control cells showed an increase in the macrophages and caused their lysis.

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At the Department of Urology, Tokyo Jikeikai University, School of Medicine, since 1960 in treating T₃ and T₄ adavanced cancers of the bladder, in order to preserve bladder function, we have been combining transurethral resection (TUR) of bladder tumor with irradiation therapy. The results are as follows:
1. Subjects
During the 21 year period from the beginning of 1960 through 1980 we personally observed 183 patients with advanced cancers of the bladder but only 87 of these patients were treated with a combination of TUR and irradiation (66 cases with T₃ and 21 cases with T₄). These patients ranged in age from 41 to 83 years old with a mean age of 63. There were 70 males and 17 females.
2. Methods
During TUR, the tumorous focus was completely excised from within the bladder (except in cases of biopsy). External irradiation alone was applied starting from the 10th-14th day after TUR using either ⁶⁰Co or Linac irradiation. The total dose to the bladder region ranged from 5000 to 7500 rads (6-8W).
3. Results
1) The therapeutic results of this combined treatment showed a 5 year survival rate of 46.9% for T₃ cancer patients and 0% for T₄ cancer patients so that the overall 5 year survival rate for both groups was 33.3%. This survival rate was significantly improved in comparison with the group of patients who was treated only with TUR. This combined method was only effective in stage T₃ patients with relatively small sized tumors.
2) Side-effects due to the combined use of irradiation treatments
Acute responses were observed in almost all of the patients but they disappeared within 3 to 4 weeks after the completion of irradiation treatments. Late damage included contracted bladder, radiocystitis, radiation proctitis which were observed in 18.3% of these patients of which only 11.7% required surgical intervention.
3) Using this method of combined therapy, it was possible to preserve bladder function for 5 years in 66.7% of the cases.

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Strips of the prostatic hyperplastic nodules were studied by observing the mechanical response to application of certain drugs. Phenylephrine in doses over 5×10^-7g/ml produced contraction which was abolished following treatment with phentolamine or prazosin. Adiministration of PGF_2α(>5×10^-7g/ml) also produced contraction, however, neither phentolamine nor atropine inhibited the PGF_2α-induced contraction. Low concentrations (10^-8-10^-7g/ml) of PGE₂ inhibited the spontaneously generated contraction while high concentrations (10^-6g/ml) produced a slight contraction. Administration of acetylcholine or isoproterenol to the muscle bath produced no response.
The small hyperplastic nodules showed a higher sensitivity to phenylephrine. Sensitivity to the PGs, however, was independent from the size of nodules.
The sensitivity to KCl, phenylephrine and PGs was about double that seen in case of the normal prostate tissues. Neural elements distributed in the hyperplastic nodules were fewer than in the normal prostate. Furthermore, in smooth muscle, the main component of hyperplastic nodules was estimated from the mechanical response and also from histological observations. The dense distribution of α-adrenergic receptor on the smooth muscle cell membrane of hyperplastic nodules was also evident.
In patients with benign prostatic hypertrophy, the urethral pressure profile in cases of acute urinary retention could be estimated from the high prostatic pressure and reduced length of the prostatic adenoma. Administration of prazosin produced a remarkable decrease in the prostatic pressure observed from the urethral pressure profile, and the clinical effects were excellent. Therefore, acute urinary retention in patients with benign prostatic hypertrophy probably is related to the contraction of smooth muscle cells in the hyperplastic nodule following activation of the α-adrenergic receptors.

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Twenty-four cases of primary hyperparathyroidism proved surgically between January 1974 to December 1982 at Tokushima University Hospital and affinity hospitals were studied. The diagnosis was made in 22 cases during the screening tests for urolithiasis and 2 cases were referred by other departments.
1) The patients aged from 19 to 69 years with a mean of 42.6 years. Females outnumbered males by 13 to 11.
2) When classified by the type of the disease, 2 cases belonged to the bone type, 19 the urolithiasis type and 2 the mixed type. The remaining one case had a familial hypocalciuric hypercalcemia. Patients with the mixed type disease mainly have symptoms related to urolithiasis, while on X-rays bone lesions are evident.
3) Associated malignancy was noted in 2 cases, one of which had a papillary thyroid carcinoma and the other a cancer of the gall bladder. Also, 2 cases were associated with a nodular goiter.
4) Histopathological findings were adenomas in 22 and hyperplasia in 2 cases. Surgery was successful in 22 cases with ademoma, however failed in the 2 with hyperplasia. Of the latter two, one had multiple endocrine neoplasia type I and the other hypocalciuric hypercalcemia.
5) Various preoperative methods were used to localize parathyroid lesions, however, none was definitive. We feel that computerized tomography has a superior value.
6) Seventeen cases with ademoma were followed-up postoperatively for an average of 40 months. None had evidence suggesting recurrent hyperparathyroidism, while 2 cases suffered from recurrent urinary stones and 3 had continuous hypercalciuria.
7) At surgery, identification of all 4 parathyroid glands is mandatory especially in cases of hyperplasia. However, in cases of ademoma, resection of adenomatous lesion seems to be sufficient when otherwise normal glands are found.

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Effect of reduced glutathione (GSH) on N-butyl-N-(4-hydroxybutly) nitrosamine (BHBN)-induced urinary bladder cancer in rats was studied. F344 male rats at the age of 6 weeks old were used. BHBN was dissolved in the drinking water at a concentration of 0.05%. GSH was mixed with poweder diet at a concentration of 0.5%. Rats were treated with or without BHBN for 6 weeks from the 4th experimental day, and were also treated with or without GSH from the start of experiments to the 3d day after the end of BHBN treatment. All the animals were killed 40 weeks after the start of BHBN treatment.
The incidences of papilloma and carcinoma were 60% (6/10) and 20% (2/10) respectively in the group treated with BHBN and GSH, and 47% (7/15) and 7% (1/15) in the group treated with BHBN alone. There was no statistically significant difference between these two groups.
In this experment, GSH failed to inhibit BHBN-induced bladder carcinogenesis in rats. Application of GSH at higher doses or during promotion step of BHBN-carcinogenesis appears important.

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To shed further light on the function of external urethral spincter its activity was electromyographically investigated in spinal subjects.
1) Study was done in 8 paraplegics during acute spinal shock. All paraplegics (number 6) with complete lesion demonstrated persistent electromyographic activity in the external urethral sphincter while none in the external anal sphincter, suggesting the presence of functional dissociation between the two sphincters from the onset of injury. Two patients with incomplete lesion showed intact sphincter activities.
With passage of time there was a tendency of increasing activities in both sphincters.
The genesis of dissociated activity was discussed by referring to recent experimental works of the different innervation pattern and cellular architecture between the urethral and anal sphincters.
2) Only the external urethral sphincter of chronic paraplegics demonstrated increased activity after alpha-adrenergic stimulation. Alpha-adrenergic activity seems to become unmasked in the chronically denervated external urethral sphincters.
3) Increased activity of external urethral sphincter to alpha-adrenergic stimulation continued to be seen even after pretreatment with competitive muscle relaxant (pancronium bromide). This suggests that the mechanism of alpha-adrenergic activity on the denervated external urethral sphincter is direct postsynaptic rather than indirect through the mechanism involved in neuromuscular transmission.

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A conformation radiotherapy system with collimators, whose openings can be controlled symmetrically by computerized techniques during rotational irradiation by a linear accelerator, has been developed for routine use in our hospital. Forty-four patients underwent radiation therapy, including this particular modality of radiotherapy, for prostatic cancer during the period of July 1976 through December 1981. Eight patients were classified as stage A, 10 stage B, 10 stage C, and 16 as stage D. Twenty-nine patients underwent conformation radiotherapy, two rotation radiotherapy, eight 2-port opposing technique radiotherapy, one 4-field radiotherapy, and four underwent a combination of 2-port opposing technique and conformation radiotherapy. Transient mild side effects such as diarrhea occurred in seven cases, while severe side effects such as rectal stricture or contracted bladder occurred in three cases. The latter occurred only in one case among 29 of conformation radiotherapy and in two among eight of 2-port opposing technique radiotherapy.
The results of the treatment of short intervals in stage B, C, and D are as follows: prostatic size was reduced in 26 cases among 36, serum acid phosphatase level was reduced in 15 among 18 who had showed high acid phosphatase levels before treatment, although almost all cases underwent simultaneous hormonal therapy. The effects of radiotherapy alone were verified in two cases of stage B in which radiotherapy preceded hormonal therapy. Prostatic size and serum acid phosphatase level were reduced by radiotherapy alone.

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Histopathological features, especially the cell type, histological organization, histological gradings and clinical stagings with prognosis were studied. The subjects consisted of 162 cases treated from January 1957 to December 1980.
The type of tumor cells were classified into four types according to the appearance of cytoplasmic content as follows: 1) clear cell, 2) granular cell, 3) mixed cell, 4) spindle cell types. Looking into the prognosis as related to these cell types, no significant difference in survival curves was seen between the clear cell type and the granular. The survival ratio for mixed cell type tended to be inferior to those for the former 2 cell types, althought the difference was not significant. The survival ratio for the spindle cell type was the lowest with significant difference from the survivals for the others.
To examine the relation with histologic organization, we first classified the histologic organization largely into three patterns; 1) single histologic pattern, 2) multiple histologic pattern, 3) anaplastic pattern. Since the organization classified as the single hitologic pattern consists of the same histologic organization, it was further classified into alveolar, papillary, tubular, cystic and trabecular patterns. When the incidence for each of these patterns was examined, the alveolar pattern had the highest incidence among the single histologic pattern and it accounted for 86 cases (92%). In studying the relation between the histologic organization and the prognosis, there was no significant deference in the survival curves between the single and the multiple histologic patterns. Compared to these two patterns, the survival ratio calculated for the anaplastic pattern was significantly lower.
In studying the relation of prognosis with histologic gradings, we classified histologic grades into four from grade I to grade IV based on the nuclear atypism with consideration on structual atypsim. When these grades were inspected in relation to the survival curves, no significant difference was seen between grade I and II or between grade III and grade IV. However, a significant difference was seen between grade II and grade III. The survival ratio differed significantly between the low grade group; (grade I and grade II) and high grade group; (grade III and grade IV).
The clinical staging from stage 1 to stage 4 according to the plan by Robson was employed. The prognosis became poor with elevation in the staging, with significant difference between any of the two stages excepting between stage 2 and stage 3.
When the stage and the grade were inspected in relation to the survival ratio, among grade I cases higher survival was recorded for stage 3 cases as compared to stage 1 and stage 2 cases according to the five-year survival ratio and significant correlation with stages was seen in the survival ratio for all stages but stage 3. Similarly the relation with the survival ratio was examined for grade II. There was a definite significant survival correlation between any of the two stages excepting between stage 2 and stage 3. However, among high graded cases such as grade III or grade IV cases the prognosis was poor in general with no significant difference in the survivals between stages. A significant difference in the survival ratio was noted between the low grade group; (grade I and grade II) and high grade group (grade III and grade IV) for stage 1. Similarly, significant difference from stage 1 or other stages was seen in the survival for stage 3. However, for stage 2 no significant difference in the survival ratio was seen because of the scarcity of cases. The survival ratio caluculated for stage 4 was poor in general with no signidicant difference for any of the grades.

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Changes of fasting serum levels of total cholesterole (TC) triglycerides (TG) and lipidperoxide (LPO) were studied after estrogen therapy for prostatic cancer. Furthermore, therapeutic and preventive effects of riboflavin tetrabutyrate (vitamine B₂) for hyperlipidemia after and during estrogen therapy were estimated.
The results were as follow:
1) Serum levels of TG and LPO were increased markedly after estrogen therapy and these changes were statistically significant. No remarkable change of TC levels Was observed.
2) The elevated TG levels were significantly decreased after the administration of riboflavin tetrabutyrate and elevated LPO levels showed a tendency to decrease.
3) When estrogen therapy was started with simultaneous administration of riboflavin tetrabutyrate in 7 patients, evident elevation of TG levels was not observed in 6 patients except for one who was diagnosed as hyperlipidemia of type II-B according to the classification of WHO before estrogen therapy, but LPO levels were slightly increased.
From these results, we consider that it is neccessary to take care of cardiovascular complication in estrogen treatment of prostatic carcinoma, because a significant elevation of LPO levels as well as TG is present: simultaneous treatment with anti-hyperlipidemic drugs, such as liboflavin tetrabutyrate is suggested.

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The incidence of lower urinary tract and prostate infections caused by indwelling urethral catheters has been investigated in 212 patients with underlying urinary tract disease, and the usefulness of the antibody-coated bacteria (ACB) test as a means of localizing the site of urinary tract infections (UTI) has been studied in 165 patients with lower UTI. The urinary leukocyte and bacterial counts in the 165 patients were at least 5 cells/hpf and 10⁴/ml, respectively. The accuracy of the ACB test in lower UTI was confirmed by using the direct immunofluorescence method of the bladder wall, urine-recoated ACB technique, single radial immunodiffusion method for serum and urinary immunoglobulin levels and bacterial hemagglutination test for serum antibody titers.
The following results were obtained:
1) Lower UTI was observed in 141 of 161 catheterized patients (87.6%) and 24 of 51 patients without catheters (47.1%). Prostatitis was noted in 67 of 124 catheterized patients (54.0%) and 13 of 46 patients without catheters (28.3%). The incidences of lower UTI and prostatitis were significantly higher in catheterized patients than in those without.
2) ACB were detected in urine of 46 of 165 patients with lower UTI (27.9%).
3) In male patients with lower UTI, ACB were observed in urine of 30 of 64 patients with prostatitis (46.9%) and 9 of 64 patients without prostatitis (9.4%). The detection rate of ACB was significantly higher in patients with prostatitis than in those without prostatitis.
4) Fluorescent cells, possibly plasma cells, were found in the bladder wall in 4 of 10 ACB-positive patients, but not in 11 ACB-negative patients nor in 8 patients without UTI.
5) Urinary immunoglobulin levels were significantly higher in ACB-positive patients than in ACB-negative patients. Urine-recoated ACB were detected in 1 of 18 ACB-positive patients, but in none of 7 ACB-negative patients. The patient with positive urine-recoated ACB had very high urinary IgG and IgA levels.
These findings indicate that an antibody which can coat bacteria may be produced in the bladder wall, and that bacteria may be coated by the antibody contained in bladder urine. In male patients with lower UIT, particularly those with catheters, some of the ACB detected in bladder urine may be from the infected prostate.

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We carried out an operation to insert a double rod silicone penile prosthesis (semi-rigid type) into the penis in 15 individuals suffering from erectile impotence. The prosthesis was newly developed for Japanese by Shirai recently. It is an intermediate between Small-Carrion prosthesis and Finney prosthesis types.
An incision was made between the root of the penis and the lap and a silicone prosthesis was inserted into the corpus cavernosum penis. Erection had been incomplete due to spinal injury in 6, rectal amputation in 3, total cystectomy in 2, subtotal prostatectomy in 1, diabetes in 1, pelvic fructure in 1, and psychogenic impotence in 1 of the operated cases.
Twelve of the 15 cases have pursued nearly satisfactory sex life, but the prosthesis was taken off in the remaining 3. The reason for this was postoperative wound infection in one, long-lasting pain in the penis due to unfitness of the prosthesis in one and disapproval by his wife in one. The other two wives were cooperative for the insertion of prosthesis. It is important to make a subject understand well that the treatment is only a temporary one for organic impotence and its application should be done with caution.

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We report a case of left renal cell carcinoma with contralateral adrenal metastasis. Such a renal cell carcinoma is rare. In our case, careful preoperative computed tomographic evaluation detected the presence of contralateral adrenal metastasis, and simultaneous left radical nephrectomy and right adrenalectomy were performed. No case of renal cell carcinoma metastatic to the contralateral adrenal gland, which was diagnosed preoperatively and treated surgically, is found in the Japanese literature.

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A case of mixed gonadal dysgenesis with gonadoblastoma. The patient, who is sixteen years old and was reared as male, came to our University Hospital for his short stature. The physical examination showed Turner's stigmata and male type in his external genitalia. The pathologic histology after exploratory laparotomy showed gonadoblastoma in the testicular tissue and a hypoplastic uterus with Fallopian tube in the peritoneal cavity, and a streak gonad in the left scrotum. Chromosomal analysis revealed 46XY. The hormonal study showed no significant impairment of pituitary-adrenal axis for his age.
Only 32 cases of mixed gonadal dysgenesis have been reported and 2 cases of them with gonadoblastoma have been reported in Japanese literature including our case. Our case is the second one in Japan.

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A 61-year-old female was admitted because of urinary retention. A soft, fluctuated mass was palpated on the anterior wall of the vagina by pelvic examination. IVP revealed a mass protruding upward toward the bladder neck, which was similar to BPH in male patients. The mucosa of the bladder and urethra was normal cystourethroscopically. Ultrasonography by the transrectal radial scanning and CT revealed a mass consisting of fluid and solid components around the urethra. Bloody fluid obtained through the transvaginal puncture from the paraurethral mass was malignant cytologically.
The anterior pelvic exenteration and urinary diversion were carried out subsequently. The cystic tumor was located between the urethra and the vagina, and the urethra was surrounded by the tumor circumferentially. With careful inspection of the resected specimen, the papillary component was seen arising from the cystic wall. Histologically the epithelium of the cystic wall had one layer of cuboidal cells and the papillary tumor had tubular structures consisting of cancer cells with large nucleoli and clear cytoplasm. The mucosa of the urethra and the vagina was intact. The histological diagnosis was mesonephric adenocarcinoma arising from the Gartner's duct cyst. She had unevenful postoperative course and was discharged after irradiation of 4400 rad to the pelvic cavity.
The mesonephric adenocarcinoma was reported first by Schiller as “mesonephroma ovarii” in 1939. Although the origin of the mesonephroma was thought to be mesonephric remnants at that time, the persuasive theory on the histogenesis is not yet concluded so far. Herein we reviewed the reported theories regarding the origin of the mesonephric adenocarcinoma through the perusal of Japanese and English literature. Our case was the 11th reported in the urological field.

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A partial deletion of the long arm of the normal Y chromosome was found in an 11 year-old boy with hypospadia and incomplete penoscrotal transposition. The terminal two third of the long arm of the Y chromosome was missing. The chromosome studies of his normal father and younger brother showed the presence of the same deleted Y chromosome. The deleted Y chromosome has descended from the father of the propositus, so we conclude that the terminal large part of the long arm of the Y chromosome has no effect on fertility. It seems likely that the genital abnormalities of this patient did not result from the deleted Y chronosome but some prenatal disturbance.
The plastic operations for the genital abnormalities were performed in two stages, the course after operations was good.
This is the first report in Japan that the deleted Y chromosome is sometimes hereditary.

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Three cases of sarcomatoid renal adenocarcinoma are presented.
Case 1: A 54-year-old male complained of pain and a mass of infant-head-size at the right flank. The mass originating from the right kidney, invading the liver and ascending colon, was removed en bloc except for the invaded portion of the liver. Histologically the majority of the mass was made up of hemangioendothelioma-like structure that was transformed partly into spindle cell sarcoma or clear cell adenocarcinoma. He died of renal failure on the 83rd postoperative day.
Case 2: A 33-year-old male complained of gross hematuria and left flank colicly pain. The left kidney of infant-head-size, invading the pancreatic tail and descending colon, was excized en bloc. Histology revealed mostly spindle cell sarcoma-like structure and partly clear cell adenocarcinoma. He died of recurrence 7 months after the operation.
Case 3: A 49-year-old male complained of gross hematuria and was diagnosed as having a right kidney mass of fist-size. At operation a small metastasis to the liver was found. The right kidney and adrenal were removed. Massive metastases to the renal hilar nodes adhering to the vena cava were left in place. Histology showed spindle cell sarcoma-like structure that was transformed in part into tubular adenocarcinoma. He died of widespread metastases on the 175th postoperative day.
Histological examination of the 3 cases demonstrated gradual transition from sarcoma-like structure to clear cell adenocarcinoma. This fact indicates that the neoplasm of the 3 cases is a sarcomatous variant of renal adenocarcinoma. Sarcomatous renal adenocarcinoma is rare and its prognosis is extremely poor.

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