Masato Utsunomiya

Surgical repair of varicocele at puberty: preventive treatment for fertility improvement.

In 40 pubertal boys with a varicocele a comparative followup study was performed to evaluate the efficacy of surgical correction of the varicocele in this age group in regard to improvement of fertility after completion of sexual maturation. The varicocele was corrected surgically in 24 patients and it was left uncorrected in 16. Testicular atrophy was noted in all cases at the initial visit and after followup. Of the 24 corrected patients 16 had atrophy of at least 1 testis before surgical treatment, whereas only 7 demonstrated atrophy after followup. Of the 16 uncorrected patients testicular atrophy was noted in 8 at the initial visit but 12 had atrophy after followup. Semen examination of 23 patients who had completed sexual maturation demonstrated a higher quality of routine seminal parameters, for example sperm density, sperm motility and percentage of morphologically normal spermatozoa, in the corrected group than in the uncorrected group.

Heparan sulfate in the stone matrix and its inhibitory effect on calcium oxalate crystallization

SummaryThe nature of the soluble stone matrix and its possible role in urinary stone formation was studied. For this purpose we performed two-dimensional cellulose acetate membrane electrophoresis of the glycosaminoglycans (GAGs) which were contained in the soluble stone matrix, substances adsorbed onto calcium oxalate crystals in vitro (crystal surface binding substances, CSBS) and urinary macromolecules (UMMs). The main GAG in the soluble stone matrix and CSBS was found to be heparan sulfate, whereas the UMMs contained various GAGs usually seen in urine. An inhibition assay showed the soluble stone matrix to have the strongest inhibitory activity among these macromolecular substances when inhibitory activity was expressed in terms of uronic acid concentration. It is suggested that the main GAG in the soluble stone matrix consists of heparan sulfate, which has a strong inhibitory activity on calcium oxalate crystal growth and aggregation and constitutes part of the CSBS.

THE INHIBITORY EFFECT OF KAMPOU EXTRACTS ON IN VITRO CALCIUM OXALATE CRYSTALLIZATION AND IN VIVO STONE FORMATION IN AN ANIMAL MODEL

Kampou medicine is a traditional Japanese therapeutic system which originated in China and was used to treat various diseases for hundreds of years until it was superseded by Western medicine. In recent years, there has been a resurgence of interest in Kampou medicine among many physicians. Unfortunately, however, little evaluation has been performed using objective scientific methods until now, and the pharmacodynamics of Kampou medicine are still unclear. Generally speaking, Kampou medicine has been shown to have fewer side‐effects than Western medicine based on the experience gained from its long usage. We first selected 16 Kampou extracts for screening as possible calcium oxalate stone prophylactic agents in vitro. This resulted in the selection of two kinds of Kampou extracts, Takusya and Kagosou, as potential Kampou extracts for stone prophylaxis. Next, these two Kampou extracts were tested in vivo for their effects on stone formation in an animal model. Takusya showed significant stone prophylaxis, while Kagosou did not. Lastly, Chorei‐to, which contains Takusya and has been approved for prescription as a Kampou medicine for urolithiasis patients in Japan, was examined in vivo at two different concentrations. As a result, a low dose of Chorei‐to which corresponded to the human daily dose per unit of body weight exhibited apparent stone prophylaxis, despite the disadvantage of decreasing citrate excretion. In contrast, high doses of Chorei‐to did not exhibit stone prophylaxis in viva These results suggest that Chorei‐to has conflicting effects on stone prevention as a whole, but the Takusya extract in Chorei‐to seems to play a major role in stone prophylaxis and the remaining four Kampou extracts seemed to interfere with the prophylactic effect of Takusya on calcium oxalate stone formation.

Testicular Responsiveness to Long-Term Administration of hCG and hMG in Patients with Hypogonadotrophic Hypogonadism

Steroidogenic responsiveness and amelioration of sperm number and motility following long-term intramuscular hCG and hMG administration were evaluated in 18 males with hypogonadotrophic hypogonadism (HH). The patients consisted of 13 patients with isolated gonadotrophin deficiency (IGD) and 5 patients hypophysectomized at an early or middle pubertal period. Basal serum levels of testosterone and 17 beta-estradiol were within prepubertal range in all patients before the treatment. Serum testosterone levels reached the normal adult male levels within 12-24 months of the treatment in only 2 of 7 younger patients and 1 of 6 older patients with IGD, whereas in all hypophysectomized patients serum levels of both testosterone and 17 beta-estradiol increased to the levels found in normal adult males within 6 months of the treatment. The mean peak levels of serum testosterone and 17 beta-estradiol, respectively, during the treatment were 2.1 +/- 0.8 (SD) ng/ml and 10.8 +/- 4.9 (SD) pg/ml in younger patients with IGD, 1.4 +/- 0.9 ng/ml and 9.7 +/- 5.1 pg/ml in older patients with IGD and 6.0 +/- 1.2 ng/ml and 34.2 +/- 14.8 pg/ml in hypophysectomized patients. Quantitative improvement in both sperm density and sperm motility were found in 4 of 7 younger patients, 1 of 6 older patients with IGD and all hypophysectomized patients, but only 3 of hypophysectomized patients (3 of 18 patients) could become fertile.

Urinary crystal surface binding substances on calcium oxalate crystals

SummaryIn order to study the effect of urinary crystal surface binding substances (CSBS), we extracted the naturally existing CSBS from urine from healthy individuals by conducting homogeneous crystallization of calcium oxalate. CSBS proved not to be promoters but rather strong inhibitors of calcium oxalate crystal growth and aggregation. It is suggested that CSBS exhibited their inhibitory effect by masking the growing sites and aggregating sites on the crystal surface. As for the characteristics of CSBS, we found around 10 peaks of molecular weight, and all of them contained both peptides and saccharides. The findings suggest that CSBS are composed of various kinds of glycoproteins and proteoglycans.

Characterization of protein components of human urinary crystal surface binding substance

We previously extracted crystal surface binding substance (CSBS) from human urine and showed that it appeared to constitute a substantial proportion of urinary macromolecular inhibitors of calcium oxalate crystallization. CSBS was isolated from human urine and fractionated by three consecutive chromatography procedures in order to characterize protein inhibitors of calcium oxalate crystallization. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and NH2-terminal amino acid sequencing revealed that inhibitory fractions eluted from a final, hydroxyapatite column contained prothrombin and osteopontin. Hydroxyapatite column fractions also contained other, unidentified protein inhibitors of calcium oxalate crystallization. CSBS contained also human serum albumin, α1-acid glycoprotein, α2-microglobulin, α2-HS glycoprotein, retinol-binding protein, transferrin, and Tamm-Horsfall protein, but these proteins seemed to play no direct role in inhibitory activity.

Renal dysplasia with a single vaginal ectopic ureter: the role of computerized tomography

Renal dysplasia with a single vaginal ectopic ureter is relatively common in Japan. We report 2 cases in which delayed enhanced computerized tomography (1.5 hours later) contributed in detecting a dysplastic kidney that had been nonfunctioning on excretory urography. We believe that computerized tomography is a useful technique for the diagnosis of renal dysplasia with a single vaginal ectopic ureter.

A Strategy of Cystine Stone Management

Simple mechanical disintegration of cystine calculi by extracorporeal shock wave lithotripsy and/or percutaneous nephrolithotomy is being performed widely around the world. However, it cannot be denied that the cystine calculus is one of the most difficult stones for mechanical disintegration. We previously reported the oral medical chemolysis of cystine calculi in 1982 and a third of the patients became stone-free. In another third of the patients the cystine component was replaced by apatite during the medical treatment and apatite stones formed in this manner are easily disintegrated. In view of the complications of mechanical disintegration, oral medical treatment for chemolysis should be recommended before simple destruction of cystine calculi.

Xanthine Calculi in the Patient with the Lesch-Nyhan Syndrome Associated with Urinary Tract Infection

A Japanese boy with Lesch-Nyhan syndrome who passed xanthine calculi is reported. After pyelolithotomy for a left renal stone, made up of ammonium urate, associated with urinary tract infection, a high dose of allopurinol was given because of the persistence of pyuria. In the present case, the administration of a high dose of allopurinol, given for the prevention of ammonium urate stone formation in infected urine, induced xanthine calculi formation and we had difficulty in the management of this patient with Lesch-Nyhan syndrome associated with urinary tract infection. However, we believe it a basic necessity to cure our patient of his urinary tract infection and prevent recurrent ammonium urate stone formation because of the risk of renal deterioration.

A New Therapeutic Agent for Cystinuria

We have already demonstrated the effectiveness of tiopronin (α-mercaptopropionylglycine, Thiola®,) for cystine stone dissolution and for preventing stone formation in cystinuric patients1. Thiol compounds, such as D-penicillamine, tiopronin and captopril convert urinary cystine by a mixed disulfide exchange reaction, into a cysteine complex which is more soluble than cystine. Therefore, thiol compounds can dissolve cystine stones and effectively prevent cystine stone formation. Bucillamine (2-mercapto-2-methylpropanoyl-L-cysteine), which is a new therapeutic agent for rheumatoid arthritis, having been used for the last 5 years in Japan2, is a dithiol compound, while tiopronin and D-penicillamine are monothiol compounds (Fig. 1). Approximately 40% of bucillamine given per os is excreted into urine as various metabolites. Three major metabolites have been identified. About 10% of bucillamine appeared in urine as a non-metabolized free form and about 15% as a metabolized monothiol compound3. A small amount appeared as a metabolized non-thiol compound. Theoretically, bucillamine is a more effective medicine for cystinuria than tiopronin, because of its number of thiol groups. We studied the effect of bucillamine on urinary cystine both in vitro and in vivo clinical trials and compared the result with that of tiopronin in this study.