The urinary sediments of 75 patients with urinary tract infections (30 patients with acute pyelonephritis, 25 patients with chronic pyelonephritis, 10 patients with acute cystitis and 10 patients with chronic cystitis) were studied with a direct immunofluorescence technique in order to detect the presence of antibody-coated bacteria (ACB). The serum immunoglobulin levels were measured in 44 of 75 patients, the urinary immunoglobulin levels in 8 of 75 patients and the serum antibody titers in 17 of 75 patients.
The results obtained were as follows:
1) ACB were present in the urine from a) 27 of 30 patients (90.0 per cent) with acute pyelonephritis and b) 19 of 25 patients (76.0 per cent) with chronic pyelonephritis. ACB were not observed in the urine from 20 patients with acute or chronic cystitis.
2) Thirty-seven of 46 immunofluorescence positive urine specimens were examined using fluorescein-conjugated monospecific antisera. Coated bacteria with IgG were found in all of 37 specimens, with IgM in 13 of 37 specimens (35.1 per cent) and with IgA in 11 of 37 specimens (29.7 per cent).
3) The detection of ACB was not influenced by the bacterial species.
4) There was no significant difference in the serum immunoglobulin levels between the patients with ACB in urine (ACB positive patients) and the patients without ACB in urine (ACB negative patients).
5) There was no significant difference in the urinary immunoglobulin levels between the ACB positive patients and the ACB negative patients, but there was significant increase of serum antibody titer noted in the ACB positive patients compared with the ACB negative patients.
It is suggested that the ACB test may be a useful method for localization of the site of urinary tract infections.

View full abstract

Clinical application of the oral administration of phenoxybenzamine has been investigated in 41 patients with benign prostatic hypertrophy and 5 patients with bladder neck contracture. Residual amount of urine was reduced in 46% of cases after the treatment. The change in length of continence zone and the value of maximum urethral pressure, which were measured with urethral pressure profile, was not statistically significant comparing to the values prior to the treatment. The improvement of uroflowmetrogram and subjective symptom was observed in 76% and 91% of cases, respectively. The effective maintenance dose was found 7.5 to 15mg per day. Adverse effects were noted in 26% of cases. 39 cases were successfully treated with phenoxybenzamine, while 3 were not. The remaining 4 had to be changed to other medication due to the adverse effects.
Phenoxybenzamine does not shrink the prostatic adenoma per se, but functionally reduces the urethral resistance and alleviates the obstructive symptoms present in the lower urinary tract. Phenoxybenzamine was found quite of promise to achieve a satisfactory voiding in patients suffering from benign prostatic hypertrophy and bladder neck contracture also.

View full abstract

Fibrin/fibrinogen degradation products (FDP) and plasminogen activator activity were measured by means of latex agglutination test and standard fibrin plate method respectively on urine specimens from 60 patients with bladder carcinoma, and the following results were obtained.
1) Urinary FDP was positive in 25 of 28 pretreated cases (89.3%), but it was not detected in 10 of 14 cases (71.4%) treated by neocarzinostatin and in all of 8 cases trated by transurethral resection and intravesical infusion of mitomycin C. It was positive in 9 of 10 cases performed total cystectomy with urinary diversion.
2) Urinary plasminogen activator activity showed no definite tendency in pretreated cases but tended to be normalized or decreased after treatment.
3) Urinary FDP had a close relation to grade and stage of carcinoma, but urinary plasminogen activator activity had no relation with urinary FDP and grade or stage of carcinoma.
4) Recarcification time, Quick's prothrombin time and Duke's bleeding time were in normal range in most cases and thrombosis or hemorrhagic tendency was not observed in all cases.
The results demonstrated that urinary FDP originating in tumor was detected in most patients with bladder carcinoma, however, urinary plasminogen activator originating mostly in the kidney had no definit relationship with bladder carcinoma. The results also suggests the urinary FDP may be useful to diagnose the grade and stage of tumor, to estimate the effect of reatment and to forsee the recurrence of bladder carcinoma.

View full abstract

Existence of uric acid and urate stone was reported before Christ and also reported as a complication of gout. Complications of uric acid and urate stone with hyperuricemia are said to be 5 to 33% and hyperuricemia has been recently studied extensively. It has become possible to produce hyperuricemia experimentally since Johnson et al., in 1969, succeeded in making an experimental animal hyperuricemia with oxonic acid potassium salt as uricase inhibitor.
In this study, male rats of Wister line weighing about 150g were used and a control group and was fed on JAPAN-CLEA-CE-2 alone and an experimental group was fed on calculus meals of 2% of uric acid, 5% of oxonic acid potassium salt and 93% of JAPAN-CLEA-CE-2 to induced hyperuricemia and urate renal stone and time-course measurement was done on blood urea nitrogen, serum creati nine, serum uric acid and body weight. The following results were obtained after light microscopic observation of the kidney for the generation mechanism of urate stone.
1) In comparison with the control group, blood urea nitrogen, serum creatinine and serum uric acid increased as time elapsed and body weihgt decreased remarkably in an experimental group.
2) Rat kidney of the experimental group was somewhat atrophic and hard, its surface was uneven, a fan-shaped deposition of yellowish white granullar substances were seen corresponding with renal pyramid at the section and many cysts were observed at the cortico-marrow junction. Many small crashable stones were observed in the renal pelvis and the ureter.
3) During light microscopic observation of experimental rats, no marked change was seen in the glomerulus and the vascular system, and in renal tubules, edema-like swellings and degenerations of epithelial cells were observed and the epithelial cells was PAS positive. Inside of the tubule cavity, there observed PAS positive muddy substances, PAS positive protein-like substances, PAS positive casts, decidual cells and inflammatory cells.
4) Collecting tubules showed degreneration of epithelial cells and PAS positive protein-like substances, amorphous substances, cellular casts and hyaline casts were seen in the tubule cavity and the amorphous substances were present either inside of cellular casts or surrounded by inflammatory cells and exfoliated cells.
5) Intra-tubular amorphous substances showed positive by De Galantha's stain and urate crystals were observed like radiating pins in the center of them. Deposition of urates, however, was not recognized in the epithelial cells and on the basal membrane of the collecting tubule.
6) Although strong fibrication, proliferation of connective tissue and infiltration of lymphocytes were recognized in stroma, no depositiion of urate was recognized.

View full abstract

Complications of uric acid or urate stones with hyperuricemic kidney are well known.
For the purpose of studying the developing mechanisms of urate kidney stone, the author used male rats of Wister line of about 150g body wieght and fed them on urate stone meals including oxonic acid potassium salt and uric acid and induced hyperuricemic kidney and urate kidney stone and observed electron microscopically the generation mechanisms of urate stone.
The following results were obtained:
1) High dense body (electron opaque material) with processes of 300mμ-7μ of mainly round, circuloid or columnar or sometimes club-like in shape were observed in glomerular epithelial cells and epithelial cells of proximal tubule and they were considered morphologically as perioxisome (microbody) which includes urate oxidase.
2) Inside the cavity of proximal tubule were observed amorphous or irregular substances of various electron densities, cytoplasmic materials by herniation, decidual cells including high dense body or intracellurlar micro-organs and exfoliating cell bodies by necrosis of epithelial cell.
3) Flowing substances such as homogeneous substances, degenerating substances, decidual cells and others were observed in the canal cavity of Henle's loop.
4) Inside the cavity of the distal tubule, there were observed many leucocytes besides of flowers-down substances from upper renal tubules, and in leucocyte cells were observed crystallike structures which were supposed to be phagocytized, but urate crystals were not observed.
5) Hyaline casts and cellular casts were observed in the cavity of collecting tubule and urate crystals were observed scattering as rhombic, columnar or round spaces of 50mμ-2μ in hyaline casts and urate crystals as rhombic, columnar or pin-shaped spaces of 50mμ-5μ were observed in cellular cast and glycoprotein was observed at the margen of cystals.
6) Urate crystals were observed neither in epithelial cells of glomerulus, renal tubules, collecting tubules nor stroma. They were observed only in the lumen of the collecting tubule.

View full abstract

The purpose of this study was to elucidate the relationship between the duration of renal vascular occlusion and restoration of renal function after the occlusion was removed. Eighteen white rabbits, weighing 2.5 to 4kg, were used for this study. Under anesthesia with Nembutal i, v., the animal's uniltaeral renal vessels (arteries and veins) were exposed extraperitoneally and clamped for varying periods of time. The animals were allocated to four groups according to the duration of clamping; group I, 30min; group II, 60min, group III, 90min and group IV, 120min. After the predetermined clamping time had elapsed, a dose, 1μc/Kg of body weight, of ¹³¹I hippuran was injected intravenously and renograms were obtained immediately (usually within 60min), 1, 7 and 28 days after the clamp had been removed in groups I and II.
In groups III and IV, renograms were obtained immediately, 7, 14 and 21 days after the clamp had been removed.
In normal rabbits, like in man, three main segments of the curve could be readily distinguished; the initial sharp rise to a peak point A (segment A), the more gradual secondary rise to point B (segment B) and a rapid precipitous fall in radiocativity reaching a plateau (segment C). In the segment C, a point which reached the level of point A was designated as point A'. A point which reached a half level of point B was designated as point B'. The height of each point on the renogram was estimated. The means with standard deviations were as follows:
C_A, a relative measure of the blood volume of the kidney, 42.5±8.0 (1 S. D.) cps C_B, the rate of tubular cell uptake and secretion into the kidney tubules and pelvis, 75.7±15.0 cps T_A, time to reach level A, 28.1±7.8 sec T_B, time to rash level B, 155±44.6 sec T_H, time reach level B' from level B, 261.4±9.7 sec T_A', time to reach level A' from level A, 314±120 sec K=C_B-C_A, /T_B-T_A a gradient of segment B, representing the relative volume of tubular uptake and secretion into tubules and pelvis per unit of time, 0.285±0.115, The values obtained for these indices after vascular occulsion was removed were expressed as percent of normal values. The results are summarized as follows:
1. In groups I and II, both C_A and C_B were slightly lower than those before the occlusion but remained within normal limit one day after the clamp was removed. T_B was prolonged and K value decreased markedly, but they returned to normal by day 7.
2. In group III, C_A was normal, but C_B was low immediately after the clamp was removed, while in group IV, both C_A and C_B were decreased markedly immediately after the clamp was removed. In group III, both C_A and C_B were returned to normal by day, 7 whereas in group IV only C_B returned to normal. By day 14, no difference was found between the two groups and all indices showed normal values.
3. In groups I to III, C_A was restored to normal by day 7, while in group IV it took 14 days to recover.
4. In groups I and II, C_B was normal immediately after the clamp was removed, while in groups III and IV it was lower than normal. In group IV, C_B was low at day 7, while ther ewas no difference in C_B among the other three groups. By day 14, C_B was restored to normal in all groups.
5. K value was significantly lower in groups III and IV than in groups I and II until day 7 but after day 14 it was returned to normal.
These results suggest that restoration of the kidney function can be expected to cocur in situations where the duration of unilateral renal vascular occulsion does not exceed 120 minutes.

View full abstract

Twenty-two totally extirpated urinary bladders with tumor were examined microangiographically and histologically and the following facts were revealed. Bladder tumors are divided into three groups according to the pattern of the vascular supply, i. e., tumors which are mainly supplied from the submucosal arteries (submucosal artery type), those mainly supplied from the arteries of the bladder adventitia (adventitial artery type) and those supplied from both of them (mixed type).
The tumor of the submucosal artery type is benign and has a tendency to make a stalk because of loose fixation to the bladder wall. On the other hand the tumor of the adventitial artery type is malignant and devoid of a stalk because the arteries are connected to the tumor from outside of the bladder. The tumor of the mixed type had intermediate properties of the above two.
Capillary loops are formed in the periphery in papillomatous tumors but not in non-papillomatous tumors. This property is noticed even in the bottom of an ulcerative papillomatous tumor.

View full abstract

The authors have been studying the significance of free amino acids in urine on the formation of calculi in the upper urinary tract. Since the epidemiological research on urinary calculi revealed that the formation of calculi depended on sex and age, in this study the excreted amounts of free amino acids in urine were determined and compared as to sex and age on 47 normal adults (30 males and 17 females), and also the factors contributing to the difference of the excreted amounts of free amino acids in urine were discussed.
The results are as reported below.
From female subjects, urine was collected in the non-pregnant period and at the almsot midst between the menstruations.
1. Difference in the 24-hour excretion as to sex and age
(1) In general, the excretion was more in the female, and particularly the excreted amounts of asparagine, glutamine and glycine were significantly larger in the female than in the male.
(2) Concerning the change of the excreted amount of the total amino acid depending on age, it was at the peak in the 30's of age in both the male and the female, and rapidly decreased after the 50's in the male, while it did not tend to decrease so rapidly in the female as in the male. The respective amino acids tended to decrease remarkedly in the males older than 50 years of age, and particularly, the excreted amounts of taurine, aspartic acid, serine, glutamic acid, glutamine, glycine, alanine, cystine, valine, leucine, tyrosine, phenylalanine, ethanolamine, and histidine decreased greatly.
2. Factors determining the personal difference in excreted amounts of amino acids (1) The excreted amount of the total amino acid was positively correlated to the excreted amounts of creatinine and urea nitrogen and the 24-hour endogenous creatinine clearance value, and particularly the individual difference of the total amino acid seemed to depend greatly on the renal clearance value.
(2) Considering the factors for the personal difference, the excreted amount of each amino acid was divided by the 24-hour endogenous creatinine clearance value and the obtained quotients were compared with each other; they were seldom different with respect to age in both the male and female, but when comparing them between the male and female, asparagine and glycine were significantly more in the female than in the male.
According to the above-described results, the excretion of free amino acids in mine appeared to be obviously different with respect to sex in the adult, and particularly the difference of the glycine excretion with respect to sex was very interesting in the aspect of the formation of urinary calculus, since glycine is considered to be related to the metabolism of oxalic acid.

View full abstract

In vitro sensitivity of an established cell line from human urinary bladder cancer to various chemotherapeutic agents was determined by ¹⁴C-leucine incorporation into the target cells. Of 12 drugs tested, Carboquone, Neocarzinostatin, Actinomycin D, Adriamycin, Mitomycin C and Chromomycin A₃ produced intensive cytotoxic effects, while Thio-Tepa, Bleomycin, 5-Fluorouracil and Vincristine were less cytotoxic. Intravesical instillation of Carboquone, one of the most toxic agents in vitro, resulted in a complete or partial tumor remission in 6 of 9 patients with bladder cancer. Prophylactic effects of periodic intravesical Carboquone were also indicated in 7 of 8 patients with recurring superficial bladder tumors.

View full abstract

High ligation of the left internal spermatic vein was performed for seventeen cases of varicocele with disturbance of spermatogenesis. Following varicocelectomy, six became pregnant and eleven remained infertile. In the infertile cases, six represented improvement in count of sperm and five represent no improvement. Each case was studies preoperatively on grade of varicocele, on volume of both testes, on count of sperm, on histology of both testis on Johnsen's score count, on plasma testosterone on HCG (10, 000 i. u/M²) and on plasma LH and FSH on LH-RH (100μg/M²). Four cases were studied postoperatively on plasma testosterone on HCG (10, 000 i. u/M²) and on plasma LH and FSH on LH-RH (100μg/M²). Cases with moderate grade, normal volume in right testis, high score count, not elevated plasma LH and FSH fared better prognosis in fertility than those with high grade, decreased volume in both testes, low score count, elevated plasma LH and FSH. For plasma testosterone on HCG, no correlation was found in prognosis of fertility. In plasma testosterone on HCG and LH and FSH on LH-RH studied postoperatively, no remarkable changes were found, in comparison with those studied preoperatively.

View full abstract

The term of detrusor-sphincter dyssynergia, which has appeared in many literatures on neurogenic bladder dysfunction, means the dysfunction of cooperative working of the detrusor and external urethral sphincter. This dyssyneriga contains the following conditions.
1. The external sphincter stays flaccid during the filling phase of the urinary bladder.
2. The external sphincter can not relax when the detrusor begins to contract.
3. When it is impossible to produce a detrusor contraction due to pelvic nerve lesion, voiding action in straining or Credé maneuver leads to contraction of the external sphincter.
The first condition causes urinary incontinence and the latter two conditions lead to the difficulty of micturition.
Clinically, persistent difficulty of micturition causes urinary infection and/or dilatation of the upper urinary tract.
In this paper we described the detrusor-sphincter dyssynergia with difficulty of micturition.
The most common causes of this dyssynergia are the upper spinal cord lesions (upper motor neurone lesions). When these patients have severe spastic paralysis of lower extremities, spasm of the external sphincter leads to acute urinary retention. When the pelvic nerve was injured by intrapelvic surgery and the pudendal nerve was intact, the dyssynergia occurs in consequence of the disturbance of the so-called vesico-urethral reflex arch.
The other common causes are Parkinsonism, disc hernia and myelodysplasia. Inflammatory changes of the bladder and urethra also cause the temporary dyssynergic condition. In some cases of distal urethral stenosis, the dyssynergia is found by precise urodynamic examinations.
As mentioned above, the detrusor-sphincter dyssynergia is not a restricted rare pathological condition, but can be found relatively often, if precise urodynamic examinations are carried out.
A sign of sphincter spasm on voiding cysto-urethrogram suggests the dyssynergia, but for definitive diagnosis electromyographic examination of the external urethral sphincter or perineal muscles is indispensable. To find out the dyssynergic condition, we routinely carried out electromyographic examination of perineal muscles with simultaneous cystometry during micturition.
When the condition is caused by inflammation or distal urethral stenosis therapies to original disease may cure the dyssynergia. But, if the dyssynergia are caused by neurological disorders, it is not so easy to cure the dyssynergia.
Today, many therapeutic procedures are carried out, that is, pudendal neurotomy, sphincterotomy, alcohol block of cauda equina and so on. But these procedures need admission and particulary alcohol block may predispose to complications, paralysis of the lower estxremities.
We have made a new simple pudendal nerve block under the guide of direct nerve stimulation using 5 or 10% phenolglycerin to dissolve the detrusor-sphincter dyssynergia and have been getting good results.
We presented here two typical cases, 34 year-old man with dyssynergia due to vertebral and sacral dysgenesis, and 27 year-old man with spinal cord lesion. After simple phenol block of the pudendal nerve, remarkable improvement of urination has been observed in these two cases.
The technique of this nerve block was described here in detail.
The only problem of this procedure is that the effect of this phenol block disappears within one to three months. But this problem is settled by repeated nerve block which causes degeneration of the pudendal nerve.

View full abstract

Using a plasma recalcification time test and fibrin plate assay system, saline and 2M KSCN extracts from in vitro cultivated KK-47 cells (130 passages) possessed minimal thromboplastic and fibrinolytic (tissue plasminogen activator) activities, respectively. The saline extracts exhibited a slight urokinase inhibitory activity (0.4 CTA units/ml) as well.
Fibrinolysis autography showed areas with less lysis of fibrin related to the cells on plasinogenrich fibrinogen.
No thromboplastic and fibrinolytic activities were observed in any of culture supernates of KK-47 cells (76, and 130 passages) using serum-free medium (Ham F 12+2% gelatin), for up to 36 hours.
Possible relationships between the tumor growth and the activities are discussed.

View full abstract

1) A simple and reliable method was developed for assay of calcium oxalate crystal growth. A metastable solution of CaCl₂ (1mM) and sodium oxalate (0.2mM) in 0.05M barbiturateacetate buffer, pH 5.7, NaCl 0.15M was seeded with calcium oxalate monohydrate cystals (0.06mg/ml). Tubes (12ml) were stirred and, at 40 min., aliquots were removed and filtered through Millipore filters (0.22μm). The ¹⁴C radioactivity was determined in the filtrate, and the ratio of the count to control, preseeding, was used to estimate the fraction of oxalate that had been lost from the liquid phase and had entered the solid phase by combining during growth of the seed crystals. The validity of this method was confirmed by many experiments.
2) Non-dialysable, high molecular weight inhibitor (s) in human urine contribute about half or more than half of the calcium oxalate crystal growth inhibitory activity of whole urine.
3) Although magnesium is weaker than inorganic pyrophosphate and citrate at the concentrations usually present in urine, its potency increases greatly when its concentration increases.

View full abstract

A calcium oxalate crystal growth inhibitory substance was obtained by 3M MgCl₂ extraction and ethanol precipitation. The density of this substance was found to be very high by applying the material to CsCI buoyant density gradient centrifugation.
The rat liver was homogenized in water and heated at 80°C for 30min. This active substance was applied to a DEAE-cellulose column and eluted from EADE by increasing the concentration of NaCl in the buffer. Each fraction was assayed for inhibitory activity, protein, RNA, DNA, and uronic acid.
The active fraction from DEAE was further purified by preparative disc gel electrophoresis using 3% polyacrylamide 0.5% agarose composite gel. The substance was electrophoresed faster than bromophenol blue. It became clear since this substance is very acidic.
These two characteristics along with the elution pattern from DEAF-cellulose column suggested that this material is RNA. This hypothesis was confirmed by the ultraviolet absorption spectra and the digestion experiment with RNases.

View full abstract

It was reported in the previous report that RNA was a principal calcium oxalate crystal growth inhibitor in rat liver. From the comparison of inhibitory activity of RNA with DNA or 4 kinds of homopoly nucleotides, the OH group in 2' position of ribose was found to be important for the activity. That the inhibitory properties of RNA were dependent on the intactness of the chain became clear from the following two experiments. 1) Alkali hydrolysis of RNA diminishes or destroys the activity according to the degree of hydrolysis. 2) Sephadex G-50 column chromatography of partially digested RNA by RNases showed that the fragment eluted in the salt volume was inactive. Because poly-L-aspartic acid and poly-L-glutamic acid have these two properties, they were tested for their activity and found to be very strong inhibitors. Polymer of aspartic acid was especially active. To be high molecular weight substances and to have free OH or -COOH groups are apparently the general requirements for inhibitors. The number of monomeric unit to make a polymer or oligomer active is not known and the study is now under way.

View full abstract

Pepsinogen has relatively strong inhibitory activity as anticipated from its high content of aspartic acid and glutamic acid. Urinary pepsinogen level in human was not so high as reported by Gottlieb, so that the percent of the contribution of pepsinogen to the activity of dialysed urine was only 0.8-3.4. The hypothesis that mucopolysaccharide is the main urinary high molecular weight inhibitor cannot be accepted because its activity is weak compared to dialysed urine.
It is concluded from these results that the urinary high moleular weight inhibitor is an absolutely unknown material.

View full abstract

In this paper, we report 250 enucleations for benign prostatic hyperplasia during 10 years from 1967 to 1976. Retropubic and suprapubic methods were performed. In this series of 250 prostatectomies, 100 cases were operated on under general anesthesia (GOF-method), 100 cases under spinal anesthesia and 50 cases under epidural anesthesia. Cases operated under spinal or epidural anesthesia presented a considerably remarkable reduction of the blood loss level as compared with those under general anesthesia.
1) The average blood loss levels were as follows; 303.8g in the spinal group, 310.6g in the epidural and 568.1g in the general. When the two-way classification analysis of variance was used, a significant reduction of the blood loss level was observed between the spinal and the general group (p<0.05) and also between the epidural and the general group (p<0.05). No significant reduction was observed between the spinal and the epidural groups.
2) As to the blood transfusion level in each group during and after the operation, results similar to those of the blood loss level were obtained. Namely the reduction of the blood transfusion level was observed in both the spinal and epidural groups.
3) No significant differences were observed between the two operation methods as to the blood loss and the transfused blood volume.
4) Regarding the behaviors of the lowest systolic blood pressure during the course of the operation under spinal or epidural anesthesia, significant reduction was observed as compared with those under general anesthesia (p<0.05). Accordingly it is considered that the reduction of the blood loss level was contributed by the reduction of the lowest blood pressure.
5) Operating time under spinal or epidural anesthesia was significantly shorter than that under general anesthesia (p<0.05).
6) Correlation was observed among the following factors regardless of anesthesia methods adopted: the blood loss level and the weight of the enucleated prostate gland; the blood loss level and the operating time.
7) The following matters had no influence on hemorrhage in cases prostatectomized under spinal or epidural anesthesia; preoperative blood pressure, preoperative hemoglobin, bleeding time, coagulation time and count of platelet. On the other hand, a significant correlation was observed between the blood loss level and the bleeding time in cases of general antsthesia.
8) Hospital stay and catheter days did not correlate with blood loss level regardless of the adopted anesthetic method.
9) No operative mortality was observed when prostatic enucleation was performed under spinal or epidural anesthesia, but two operative mortalities were observed under general anesthesia.
In this study, both spinal and epidural anesthesia seem to have advantages for prostatic surgery.

View full abstract