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A commercial Pd catalyst based on Sibunit carbon support was treated with H6TeO6 in a reducing media to obtain a Te coating on the surface of Pd particles. The PdTe/C catalyst prepared in this way showed the ability to control the radical chain oxidation of 1,3-butadiene by promoting the selective formation of 2-butene-1,4-diol, 4-hydroxybut-2-enal and furan in DMA (total selectivity of 61% and yield of 7%). At the same time, the catalyst induced oxidation of 1,3-butadiene by a non-radical heterolytic mechanism involving the formation of two groups of primary products: (1) сrotonaldehyde and methyl vinyl ketone and (2) the products of oxygenation at the 1,4-positions. The compounds of the second group including 1,4-dimethoxy-2-butene and maleic acid dimethyl ester were formed on PdTe centers in MeOH. Increasing the Te concentration in the PdTe/C catalyst forced the conversion of 1,3-butadiene toward 1,4-oxygenation and simultaneously decreased the intensity of secondary oxidation, resulting in the selective formation of derivatives of the 1,4-oxygenation—1,4-dimethoxy-2-butene and allenic alcohol methyl ether (total selectivity of 84% and yield of 48%).

PURPOSE Screening with prostate specific antigen (PSA) only to detect prostate cancer was started in Tokushima City from 2001 as one of health check lists. We evaluated the first year result. MATERIALS AND METHODS Fifty-five years old or elder men living in Tokushima City who wants to measure serum PSA level to screen for prostate cancer were entered to screening program. The men whose PSA levels detected as over normal; range were recommended to visit to urologists for further examination to detect prostate cancer include prostate biopsy. The results of further examination were reported to Tokushima City and evaluated. RESULTS The population of fifty-five or elder men in Tokushima City was 25,416 and 9,019 (35.5%) men were measured serum PSA levels. In 801 (8.9%) men, PSA levels were over normal range, and recommended further examination to detect prostate cancer. 451 (56.3%) men visited to urologists for further examination, and prostate biopsy was performed in 231 (51.2%) men. Finally, 121 men were diagnosed as prostate cancer, 52.1% of 231 men performed prostate biopsy, 26.7% of 451 men visited to urologist for further examination, 1.34% of 9,019 men measured serum PSA levels. Patient number for each clinical stages were 49 in B0, 16 in B1, 16 in B2, 29 in C, one in D1, and 10 in D2. Patients number in each age range were 3 in 55-59, 11 in 60-64, 22 in 65-69, 37 in 70-74, 33 in 75-79, 15 in 80 or elder. Patient number of Stage B and 74 years old or younger was 48 (39.7%). CONCLUSION Prostate cancer was detected in 1.34% of 9,019 men who measured serum PSA levels, and early stage B was two thirds. PSA screening to detect prostate cancer as one of health check-lists in Tokushima City was useful to detect early prostate cancer.

This paper describes a fault diagnosis expert system installed at the Tohoku Electric Power Company. The main features of this system are careful selection of the inferencing input data, rapid inferencing, integration of the expert system with other systems in a practical structure, and the adoption of a domain shell. This system aims for improved practicability by using time-tagged data from circuit breakers, protective relays, and automatic reclosing relays in addition to the input data used in earlier systems. Furthermore, this system also uses data from fault detection systems that locate fault points within electric stations. This system uses an AI-specific back-end processor to perform inferencing rapidly. Additionally, this fault diagnosis expert system is interfaced and integrated with a restorative operations expert system, an intelligent alarm processing system, and a protective relay setting and management system. The authors developed and adopted a power system fault diagnosis domain shell to ease system development, and used the protective relay operation simulation function of a protective relay setting and management system for system verification. >

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.

Alkali therapy is widely accepted as a treatment for recurrent calcium stone patients with distal renal tubular acidosis (dRTA). Nine patients, five with complete and four with incomplete type of dRTA, were treated with alkali agents for more than three years; an average period of 10.8 years. In five patients, new stone formation and stone growth were completely prevented by this treatment. Among the four failed cases, three did not take enough alkali agents (in spite of our medication), and the other had recurrent urinary tract infection resulting in infectious stone formation. In conclusion, the long-term efficacy of alkali therapy for prevention of recurrent stone formation with dRTA is confirmed when the patient takes enough alkali agents and the urinary tract infection is well controlled.

Gelatinous transformation of the bone marrow is a rare disease characterised by a focal marrow hypoplasia, fat atrophy and accumulation of extracellular mucopolysaccharides abundant in hyaluronic acid, which is often associated with extreme malnutrition and weight loss. There are only two reports describing its association with systemic lupus erythematosus (SLE). One described underlying diseases in 155 cases of gelatinous transformation of the bone marrow and found one case with clinical diagnosis of SLE, but no clinical details were provided. The other described three SLE patients with gelatinous transformation of the bone marrow; however, two of these were cachectic and one was diagnosed with concomitant tuberculosis. We describe one active SLE patient without other comorbidities whose pancytopaenia was histologically confirmed as gelatinous transformation. The combination of high-dose steroid, intravenous immunoglobulin and mycophenolate mofetil improved the peripheral blood cytopaenia and reversed the bone marrow abnormalities.

Clinical results of ESWL for renal and ureteral stone with MPL-9000 were presented. We also reviewed correlation between stone burden and shock wave energy. We studied 210 cases (295 sessions) of renal stone and 109 cases (154 sessions) of ureteral stone that were treated from November 1988 till January 1989 and from November 1989 till May 1990. Of those sessions, 76 sessions of renal stone cases and 53 of ureteral stone cases were carried out ambulatorily. Successful disintegration (within 4 mm) rate was 86% of renal stones, 84% of ureteral stones, and stone free rate after 6 months was 72% of renal stones and 84% of ureteral stones. As for the complications, brain infarction occurred in one case, subcapsular hematoma of the kidney in one, and arythmia in 5. No other severe side effects were observed. Between shock wave energy (the number of shock wave shots x voltage) and stone burden (long axis x short axis of the stone), a significant correlation was found in renal stone cases, but not in ureteral stone cases. E/B (shock wave energy/stone burden) was 33,100 (kv.shots/cm2) for the renal stone and 56,000 (kv.shots/cm2) for the ureteral stone. These results suggest that there is still another unknown factor, which is not related with renal stone, for successful disintegration of ureteral stone. We also confirmed that more energy is necessary for destruction of ureteral stone than for that of renal stone.(ABSTRACT TRUNCATED AT 250 WORDS)

In 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.

This paper studies a multi-functional power conversion system (PCS) combined with the functions of energy storage and power quality. The multi-functional PCS controls active power and reactive power simultaneously, and it has nine functions. Furthermore, the functions of PCS are divided into normal mode and faulted mode to make use of the rated power of the PCS efficiently. Further, in order to achieve the multi-functions, the well-known coordinate transformations from static coordinate system to rotational one is used, and the control system is designed by classical control theory. Finally, the effectiveness of the multi functions is confirmed by several SCAT simulations and experiments.

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.

We previously reported that Takusya had the inhibitory effect on in vitro calcium oxalate crystallization and in vivo stone formation in an animal model and it could be a prophylactic agent against calcium oxalate stone formation. We studied the effect of Takusya on calcium oxalate crystallization in human urine. Takusya (500 mg/day and 1,000 mg/day) was administered to 16 healthy men for 3 days and then 24-hour urine samples were collected to measure the urinary excretion of calcium, phosphate, magnesium, uric acid, creatinine, citric acid and oxalic acid. The urine samples before the administration of Takusya was used as a control. The size and distribution of crystals, which were formed in the urine samples by adding calcium chloride and sodium oxalate, were measured using the Coulter counter technique. Urinary magnesium excretion was significantly reduced by 1,000 mg/day of Takusya compared with the control (p0.05). The growth of crystals was significantly inhibited by 500 mg/day of Takusya in the large crystal formers whose urine created crystals more than 3.5 microns before the administration of Takusya (p0.05). These findings suggested that Takusya inhibited the growth of crystals formed in human urine.

This study was undertaken to evaluate destructive spondylarthropathy (DSA) in patients long-term dialysis. The patients were investigated by plain X-ray examinations twice with a three-year interval, and the changes in severity of the illness in 66 patients undergoing dialysis for over 5 years were defined. Group A (9 patients) consisted of patients with progression in grades during the three years, while group B (57 patients) consisted of patients without deterioration. There was no differences in the two groups in age, duration and the modality of dialysis. However, in group A, the level of plasma beta 2-microglobulin (beta 2M) was 33.5 +/- 14.6 micrograms/ml at the first observation, and 33.1 +/- 15.1 micrograms/ml at the second (NS). In group B, the level of plasma beta 2M was 45.6 +/- 8.13 micrograms/ml at the first observation, and 39.7 +/- 9.18 micrograms/ml at the second (p0.05). No improvement in DSA was observed. The result of this study suggests that DSA will not improve once it has become overt, and the management for lowering the level of beta 2M may prevent the occurrence and progression of DSA.

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, alpha 1-acid glycoprotein, alpha 1-microglobulin, alpha 2-HS glycoprotein, retinol-binding protein, transferrin, and Tamm-Horsfall protein, but these proteins seemed to play no direct role in inhibitory activity.

Background Much emphasis has been placed on early diagnosis and treatment of rheumatoid arthritis (RA) 1 . In order to achieve the better outcome, the timing of referral and diagnosis of early arthritis should be optimized 2 . Objectives To examine the time to referral of patients with early arthritis, and diagnosis delay of RA in a rural community medical center in Japan. Methods A total of 296 who visited Kameda Medical Center from January 2009 to December 2010 with at least one swelling joint without any previous treatment were included. In the patients diagnosed as RA, the time intervals from the onset of symptom to primary care physician (PCP) (patient delay), from PCP referral to a rheumatologist (PCP delay), from the onset of symptoms to rheumatology visit (total delay) were determined. Results Ninety-four patients were diagnosed as having RA. The median patient, PCP, total delays [interquartile range [IQR]] were 8.8 weeks [3.4-30.1], 5 weeks [1.9-20.1], 26.9 weeks [10.9-69.4] respectively. The patient delay was significantly longer than PCP delay (p=0.046). Twenty-seven (29%) RA patients were assessed within 12 weeks from onset. At baseline, these patients had less bone erosion on radiograph, as compared with those assessed after≥12 weeks (7% vs 30%, p=0.03). Conclusions In a rural community medical center in Japan, the patient delay is longer than the PCP delay, which is comparable to earlier reports from Europe 3 . This study indicates the key delay in early arthritis diagnosis in Japan. References P, et al. Ann Rheum Dis 2002;61:290-7. Van der Linden MP, et al. Arthritis Rheum 2010;62:3537-46. K.Raza, et al. Ann Rheum Dis 2011;70:1822-1825 Disclosure of Interest None Declared

Objectives To assess real-life practice patterns of biologic discontinuation, including tocilizumab, for good response and factors associated with retreatment, we conducted a research on the Cohort of Arthritis, Biologic Users at Kameda Institute (CABUKI) registry [1]. Methods Proportions of patients who discontinued biologic agents for physician-perceived good response were calculated for each biologic agent. Baseline characteristics were compared to patients whose biologics were withdrawn for ineffectiveness or side effects. Disease and treatment characteristics at discontinuation for good response were compared to recommendations. Survival of biologic-free status and predictors of retreatment were analyzed. Results Among 265 eligible patients, 161 patients (ADA 3, ETN 58, IFX 77, TCZ 23) who discontinued their biologics during the study period were identified: 35 for good response (ADA1, ETN9, IFX22, TCZ3), 53 for side effects (ADA2, ETN21, IFX22, TCZ8), 39 for ineffectiveness (ETN11, IFX21, TCZ7), and 34 for other reasons [patient’s preference 24 (ETN11, IFX10, TCZ3), physician preference 9 (ETN5, IFX2, TCZ2), and unspecified 1 (ETN1)]. Age at initiation was lowest in the good response group and highest in the side effects group, and baseline prednisolone dose was highest in the ineffectiveness group. Patients in the good response group had been treated with biologics for 20 months on average, topping other groups. Prednisolone was used at the lowest dose in this group. Methotrexate doses were significantly lower in the side effects group. Among 35 patients in the good response group, 21 (60%) met DAS28-ESR criteria (5 patient lacked patient’s global assessment required for DAS28-ESR, thus were regarded as non-responders), and 27 (77%) met the DAS28-ESR low disease activity criteria ( 1 and patient global assessment >10 out of 100. First-line infliximab and adalimumab achieved the highest good response discontinuation rates at 22.5% and 25.0%, respectively, whereas first-line tocilizumab and etanercept achieved 10.5% and 7.6%, respectively. Among those who became biologic-free, 70.5% remained so at 6 months. Achievement of prednisolone-free status six or more months before biologic discontinuation was associated with longer biologic-free status (Table). Conclusions Biologic-free status is an achievable goal in routine practice. Stabilization of disease activity without prednisolone for more than six months is an important factor. References Yoshida K, et al. An observational study of tocilizumab and TNF-alpha inhibitor use in a Japanese community hospital: different remission rates, similar drug survival and safety. Rheumatology (Oxford). 2011;50:2093-2099. Disclosure of Interest None Declared

Background Clinical phenotype of ANCA-associated vasculitis (AAV) is different between Japan and European countries with microscopic polyangiitis (MPA) predominating in Japan.1 Objectives To investigate the diagnosis and prognosis of AAV in a community-based teaching hospital in Japan. Methods We performed a retrospective chart review of adult patients with AAV who admitted to Kameda Medical Center from January 2003 to July 2011. We evaluated the diagnoses by applying the European Medicines Agency (EMEA) algorithm2 and examined the remission rates. Remission is defined as symptom free, normal CRP/ESR and absence of renal disease activity. Results Forty-eight patients were included [33females; mean age at the time of diagnosis, 70.5 years (range, 23–92)]. The mean follow-up was 31.2 months (range, 0.5–92). The original diagnoses of 48 patients were Churg-Strauss syndrome (CSS) (n=7), granulomatosis with polyangitis (GPA) (n=9), MPA (n=32). After applying the EMEA algorithm, 4 of 32 patients with MPA were classified as GPA, and 4 as unclassified vasculitis. One patient with GPA was classified as MPA. ANCA tests were performed by enzyme-linked immunosorbent assay (for MPO-ANCA and PR3–ANCA) for all patients. Thirty-five (72.9%) and 5 (10.4%) patients were MPO-ANCA and PR3–ANCA positive respectively, and other one patient was both MPO-ANCA and PR3–ANCA positive. Among all, 34 patients received glucocorticoid (GC) alone (GC group), and 11 patients were treated with GC/cyclophosphamide (CYC) combination (CYC group). There were no difference in 6 months remission rates and GC dose at 12 months between two groups; however, remission rate at 12 months was numerically higher in CYC group (45.8% GC group vs. 87.5% CYC group). A total of 13 deaths were observed. These deaths were predominantly vasculitis-related, explaining 8/13 (62%) of them and comprised the following: acute renal failure for 3, interstitial lung disease for 2, alveolar hemorrhage for 1, cerebral infarction for 1, and cardiomyopathy for 1. Three of 13 (23%) deaths were attributed to infection: septic shock for 2 (1 with pyelonephritis and 1 with cholecystitis), and pneumonia for 1. The remaining 2 (15%) deaths were attributed to miscellaneous causes: congestive heart failure for 1 and sudden death for 1.Overall estimated 5 year survival rate was 63.2% by using Kaplan-Meier method, and it was 78.3% in patients with the Five-Factors Score (FFS)3 =0 (54.1% FFS ≥1, 54.5% FFS ≥2). Conclusions MPA accounted for the large part of AAV, as in previous studies. It is the same also after applying EMEA algorithm. At one year, more patients tend to be in remission in CYC group compared to GC group. 1. Ntatsaki E, Watts RA, Scott DG. Rheum Dis Clin North Am. 2010;36:447 2. Watts R, Lane S, Hanslik T, et al. Ann Rheum Dis. 2007;66:222 3. Guillevin L, Lhote F, Gayraud M, et al. Medicine (Baltimore). 1996;75:17 Disclosure of Interest None Declared

Coronary atherosclerosis and calcification score were assessed angiographically in 30 uremic patients receiving dialysis (8 patients with diabetes mellitus [DM dialysis group] and 22 patients without DM [non-DM dialysis group] who were suspected of having coronary artery disease because of their clinical symptoms and electrocardiographic findings. Thirty non-uremic subjects (11 with DM and 19 without DM) served as controls. Twelve dialysis patients (40%) did not have significant coronary artery disease, and the rate of significant coronary artery disease in dialysis patients overall was less than that in the control subjects. The calcification score of dialysis patients was significantly higher than that of the control patients (P0.0001), and also scores of the non-DM dialysis group and the DM dialysis group were higher than those of each group of control subjects. The scores were significantly correlated with the duration of dialysis in uremic patients as a group (r = 0.52; P0.01) and the non-DM dialysis group (r = 0.70; P0.01), but were not correlated with the duration of dialysis in the DM dialysis group. The scores were correlated with serum phosphate concentration, but not with serum calcium concentration, calcium phosphate product, alkaline phosphatase levels total cholesterol or age. Calcification scores were extremely high (21) in six uremic patients who had high serum c-terminal parathyroid hormone concentrations. These findings indicate that serum phosphate concentration, serum c-terminal parathyroid hormone concentration, and the duration of dialysis are closely associated with coronary calcification in long-term dialysis patients.

We examined the inhibitory effect of the two Kampo medicines, takusha and kagosou on the formation of calcium oxalate renal stones induced by ethylene glycol (EG) and 1 alpha(OH)D3 (1 alpha-D3) in rats. Wistar strain rats were divided into 4 groups (A: normal control, B: stone, C: kagosou, D: takusya). There was no significant difference in urinary calcium excretion or oxalate excretion between the stone group and kampo medicine groups. The calcium content of the kidneys was significantly lower in the takusha group than in the other two groups (Stone group and kagosou group). Takusha was effective in preventing oxalate stone formation in rats. Kagosou, which had strong inhibitory effect on calcium oxalate crystal growth and aggregation in vitro as well as takusha, was not effective against in vivo calcium oxalate stone formation in rats. These findings suggest that takusha prevents the formation of calcium oxalate stone by inhibiting calcium oxalate crystal growth and aggregation.

We investigated factors affecting net transperitoneal calcium balance (Ca-BL) and the level of parathyroid hormone in relation to stepwise changes in serum calcium, by short PET (peritoneal equibrium test during 240 min: using 2000 ml of 2.5% dextrose dialysate containing 1.75 mmol/L Ca) in uremic patients undergoing stable CAPD. We calculated Ca-BL (mg/effluent/PET) of 244 effluents obtained from 90 patients receiving calcium carbonate as a phosphate binder without vitamin D supplementation. Their serum calcium level corrected with albumin (cSCa), alkaline phosphatase activity (ALP) and intact-PTH level was 9.7 +/- 0.9 mg/dl, 236 +/- 83 mIU/ml and 153.0 +/- 172.4 pg/ml, respectively. We proposed two statistic significant regression lines between Ca-BL and total drainage effluent volume (Ca-BL = 133X - 0.056: r = 0.981, P0.001), cSCa (Ca-BL = -12.9X + 123.6: r = 0.941, P0.01). Total drainage volume (TDV) and cSCa were two major factors affecting Ca-BL. A TDV level of 2430 ml/240 min-PET or more was required for positive Ca-BL in cases with 9.5-10.0 mg/dl of cSCa, using this linear regression analysis. A cSCa level of 9.6 mg/dl or more was also required for positive Ca-BL in cases with 2400-2600 ml/240min-PET. We also proposed a significant linear regression line between the intact-PTH level and cSCa (i-PTH = -90.5X + 1015.8, r = 0.973, P0.01). This line suggest that 200 pg/ml of intact PTH was obtained by 9.0 mg/dl or less of cSCa level in 90 CAPD uremic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of parathyroidectomy on left ventricular muscle volume and mechanical performance were evaluated echocardiographically in 24 patients with secondary hyperparathyroidism due to chronic renal failure and in 7 with primary hyperparathyroidism. Intraventricular septum and posterior wall thickness, left ventricular end-diastolic diameters, shortening fraction, ejection fraction, and left ventricular mass index were measured by M mode recording by the parasternal short axis view prior to parathyroidectomy as baseline and repeated 12 months after parathyroidectomy. Serum basal carboxyterminal parathyroid hormone levels in patients with secondary hyperparathyroidism (34.4 +/- 13.7 ng/ml) were significantly higher than in those with primary hyperparathyroidism (3.4 +/- 5.1 ng/ml; p0.0001). At 12 months after parathyroidectomy, intraventricular septum and posterior wall thickness, left ventricular end-diastolic diameter and left ventricular mass index were reduced from 11.8 +/- 3.1 mm, 10.9 +/- 1.7 mm, 53.8 +/- 6.3 mm, 200.8 +/- 57.1 g/m2 to 10.0 +/- 2.1 mm (p0.05), 9.8 +/- 1.9 mm (p0.05), 50.7 +/- 7.2 mm (p0.05), 149.6 +/- 38.7 g/m2 (p0.0001), in patients with secondary hyperparathyroidism. In patients with primary hyperparathyroidism, all echocardiographic parameters remained in the normal range and did not show any significant changes before or after parathyroidectomy. From this study, parathyroid hormone at extremely high concentrations as seen in secondary hyperparathyroidism appears to be a cardiotoxic substance. Therefore, all patients with secondary hyperthyroidism should be examined by echocardiography and parathyroidectomy should be considered if myocardial hypertrophy is present.

The role of the organic stone matrix in stone formation is controversial. Some investigators have reported that the organic matrix is selectively incorporated into urinary calculi by promoting crystal growth and aggregation1, 2. Recently, Resnick et al reported that some particular proteins, which were adsorbed onto crystals, may promote calcium oxalate crystallization3, 4. Others, however, have suggested that matrix formation is the result of non-specific adsorption of urinary macromolecules onto urinary crystals and does not act as a promoter5-7. Moreover, still other researchers have shown that the soluble portion of stone matrix inhibits crystal growth and aggregation in vitro 8.

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.

Although several medicines are administered to prevent new stone formation or stone growth, we have not obtained a satisfactory result. The Kanpou medicines, whose safety has become well established during a long history of use, may be useful as new prophylactic agents if they exhibit strong inhibitory activity. In this study, we examined the inhibitory effect of Kanpou medicines on calcium oxalate crystallization in vitro.

The 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.

We investigated the influence of ionic strength on both the binding ability of macromolecules onto calcium oxalate crystals and the inhibitory activity of macromolecules related to calcium oxalate crystal growth and aggregation in vitro. The amount of heparin sodium salt adsorbed onto calcium oxalate crystals was studied in both a seed and a non-seed crystal system at various ionic strengths with the aid of radiolabelled heparin. In both adsorption models, adsorption of heparin was greater in the buffered solutions of lower ionic strength, and significantly so in the range of physiological ionic strength. The inhibitory activity of heparin in the non-seed crystal system, which was determined using a Coulter Multisizer, increased as the adsorbed dose increased. The naturally existing urinary macromolecules showed a similar change in their inhibitory activity on calcium oxalate crystal growth and/or aggregation in accordance with changes in ionic strength. These results indicate that macromolecular inhibitory activity seems to be enhanced in urine of lower ionic strength as a result of an increased adsorption of macromolecules on the surface of calcium oxalate crystals.

To evaluate the left ventricular early diastolic function after dipyridamole infusion or during exercise, the first pass radionuclide angiocardiography (FPRA) by a multicrystal gamma camera (SIM-400) was performed in 32 patients with coronary artery disease (CAD) and 14 normal subjects. Dipyridamole was administered intravenously (0.56 mg/kg in 4 min). The first third filling fraction (FF 1/3) and the first third mean filling rate (MFR 1/3) were calculated from the time-activity curve. FF 1/3 decreased and MFR 1/3 increased in both normal subjects and patients with CAD during exercise. After dipyridamole infusion, FF 1/3 and MFR 1/3 unchanged in normal subjects, in contrast, FF 1/3 and MFR 1/3 decreased in patients with CAD. Thus, dipyridamole infusion FPRA is more sensitive method to detect early diastolic dysfunction in patients with CAD than FPRA during exercise.

Summary— Between March 1981 and March 1990, 15 patients with locally advanced transitional cell carcinoma of the bladder were treated concurrently with cisplatin and radiotherapy. Treatment comprised a radiation dose of 40-50 Gy in 20-25 fractions over 4-5 weeks and intravenous infusion of cisplatin with hydration during days 1-5 and 22-26. The total scheduled dose of cisplatin was 200 mg. A complete response (CR) was seen in 3 patients (2 T2 tumours and 1 T3) and the other 12 were regarded as partial responders. Two of the 12 partial responders (1 T2 tumour and 1 T4) underwent cystectomy after treatment, but 9 patients (2 T2,6 T3 and 1 T4) underwent only transurethral resection. The remaining patient (with a T4 tumour) died from systemic disease, further treatment not being possible because of unrelated heart failure. In 3 CR patients and 9 with a partial response (PR), bladder function was preserved and they have survived for a mean of 18.3 months (range 5-47) after therapy. Although 4 patients in this group had recurrent bladder tumours and 1 died from cancer in another part of the body, 7 have survived with normal bladder function and no recurrence. It is concluded that concurrent cisplatin and radiation therapy is a safe and viable regimen and may be considered as a means of preserving the bladder in patients with locally advanced transitional cell carcinoma.

A plastic ankle foot orthosis (AFO) was developed, referred to as functional ankle foot orthosis Type 2 (FAFO (II)), which can deal with genu recurvatum and the severe spastic foot in walking. Clinical trials were successful for all varus and drop feet, and for most cases of genu recurvatum. Electromyogram studies showed that the FAFO (II) reduced the spasticity of gastrocnemius and hamstring muscles and activated the quadricep muscles. Gait analysis revealed a reduction of the knee angles in the stance phase on the affected side when using the FAFO (II). Mechanical stress tests showed excellent durability of the orthosis and demonstrated its effectiveness for controlling spasticity in comparison with other types of plastic AFOs.

A 72-year-old woman with bilateral non-Hodgkin's lymphoma of the adrenal glands causing adrenal insufficiency is reported. The left-side lymphoma (diffuse large B-cell lymphoma) was removed surgically but the right-side lymphoma could not be removed. Complete response was obtained with subsequent combined chemotherapy and was maintained for 6 months with repeated chemotherapies. However, the patient died of liver recurrence 1 year after admission. In cases of malignant lymphoma forming a bulky mass, surgery with subsequent chemotherapy appears to reduce the cancer volume and improve the therapeutic outcome.

Between 1959 and Oct. 1990, 307 cases of primary hyperparathyroidism (PHPT) were operated on in our hospital. Among them, 23 cases (7.5%) were asymptomatic chemical type of PHPT, and the incidence of this type has been increasing these days. Various symptoms or signs including urolithiasis, bone disease, cardiovascular disease, gastrointestinal disease, diabetes mellitus and others were associated with PHPT. Especially, as a lethal factor, malignant tumors developed in 14 cases (4.6%); 9 cases of non-medullary thyroid cancer and tumors of other organs. In consideration of these associated disorders, the chemical type of PHPT should be operated prophylactically. In order to reduce operative complications, unilateral exploration is available for the cases of single normally localized adenoma; 85.7% of our 307 cases. Moreover, the positive rate of preoperative localized test by CT and ultrasonography for such adenomas is 78% in the recent 5 years. The predictive values of successful operation by unilateral exploration are 89% in the cases of normally localized single adenoma and 76% in all PHPT.

Clinical results of ESWL for renal and ureteral stone with MPL-9000 were presented. We also reviewed correlation between stone burden and shock wave energy. We studied 210 cases (295 sessions) of renal stone and 109 cases (154 sessions) of ureteral stone that were treated from November 1988 till January 1989 and from November 1989 till May 1990. Of those sessions, 76 sessions of renal stone cases and 53 of ureteral stone cases were carried out ambulatorily. Successful disintegration (within 4 mm) rate was 86% of renal stones, 84% of ureteral stones, and stone free rate after 6 months was 72% of renal stones and 84% of ureteral stones. As for the complications, brain infarction occurred in one case, subcapsular hematoma of the kidney in one, and arythmia in 5. No other severe side effects were observed. Between shock wave energy (the number of shock wave shots x voltage) and stone burden (long axis x short axis of the stone), a significant correlation was found in renal stone cases, but not in ureteral stone cases. E/B (shock wave energy/stone burden) was 33,100 (kv.shots/cm2) for the renal stone and 56,000 (kv.shots/cm2) for the ureteral stone. These results suggest that there is still another unknown factor, which is not related with renal stone, for successful disintegration of ureteral stone. We also confirmed that more energy is necessary for destruction of ureteral stone than for that of renal stone.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of the compositional drugs of kanpou medicine on the growth and aggregation of calcium oxalate crystals were investigated in vitro. In the seeded crystal system, the inhibitory activities were calculated from the change of the number (Ia), total volume (Ig) and fractional volume (I) of crystals determined by a Coulter Multisizer. Among the tested drugs (Takusha, Akyou, Chorei, Bukuryou, Kasseki, Kinsensou, Kagosou), only Takusha and Kagosou had strong inhibitory activities on the growth and aggregation at the concentration of 5 micrograms/ml and 10 micrograms/ml (Ia greater than 80%, Ig, I greater than 90%). No significant correlation was observed between inhibitory activities and alcian blue precipitable polyanions (ABPP) of each drug. Thus some naturally existing substances composing the kanpou medicine may help prevent the stone formation in clinical use.

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.

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.

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.

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.

Carcinoma of the urachus is a rare disease with poor prognosis. This is probably due to the difficulty of preoperative diagnosis. Radiological modalities have been considered to be of little value, but in many cases, preoperative diagnosis can be established with the aid of CT scan. In patients with urachal carcinoma, CT scan visualize the primary tumor and its extension beyond the bladder wall into the space of Retzius. Although about 150 cases of urachal tumor have been reported in the English literature, computerized tomographic findings have not been established. We present two cases and emphasize the usefulness of CT scan in preoperative diagnosis.

Eighteen patients were identified in whom ultrasound (US) of the kidney demonstrated a hyperechoic medulla. Diagnoses in the patients included gout in seven; Sjogren syndrome in two; medullary sponge kidney in two; primary aldosteronism in two; and Lesch-Nyhan syndrome, hyperparathyroidism, glycogen storage disease type XI, Wilson disease, and pseudo-Bartter syndrome in one each. The pathogenesis of the echogenicity was evaluated by comparing the findings from computed tomography and conventional radiography. It appears that a hyperechoic medulla is caused by hyperuricemia, medullary nephrocalcinosis, or hypokalemia. US is considered to be useful in evaluating renal involvement in patients with these diseases.

Olfactory neuroblastoma is a malignant, slow growing, neurogenic tumor that originates in the olfactory mucosa of the upper nasal cavity. We report a case of olfactory neuroblastoma that presented with exuberant hyperostosis of the facial bone during the course. This unusual radiological finding has been discussed with literature review.

Twelve early-pubertal boys (12-3/12 to 14-11/12 years of age) who had received orchiopexy for bilateral cryptorchidism at 3-1/12 to 5-9/12 years of age were treated with long-term administration of hCG and hMG, 1000 IU and 150 IU, respectively, weekly during puberty. The restoration of spermatogenesis by the treatment was evaluated by measuring the mean sperm count in the seminal fluid ejaculated at late-pubertal age or after completion of puberty (16-6/12 to 18-1/12 years of age). Of the 12 patients treated with hCG and hMG, 5 showed moderate oligozoospermia (5-40 million sperm/ml), 2 showed severe oligozoospermia (less than 5 million sperm/ml), and 5 were azoospermic. Of another 11 such patients who were not treated with hCG and hMG during pubertal age, 9 patients were azoospermic and only 2 showed severe oligozoospermia. The rate of motile sperm assessed from all semen showed asthenozoospermia (20-61%). These findings suggest that gonadotropins administered during puberty may have some effects on restoration of spermatogenesis in patients who had orchiopexy for bilateral cryptorchidism in early childhood.