[Influence of cyclosporin on steroid-induced cataract].

PURPOSE: To study the effect of cyclosporin on steroid-induced cataract in patients after renal transplantation. SUBJECTS AND METHODS: 140 patients who received renal transplantation and ophthalmological examinations before and over 12 months after surgery at Kanazawa Medical University were investigated retrospectively. The subjects were divided into the following two groups: the conventional therapy group(Group C) who were administered azathioprin and methylprednisolone and the triple therapy group(Group T) who were administered azathioprin, methylprednisolone and cyclosporin. There were 73 subjects in group C and 67 in group T. Judgement of steroid cataract followed Crew's classification and steroid cataract was diagnosed when vacuoles or opacity were seen in the posterior subcapsular region. Subjects that had any lens opacity before renal transplantation were excluded. RESULTS: The total dose of systemic steroid during the first year and in the final observation period in group T was significantly higher than in group C. The prevalence of steroid cataract was 55% and 63% for the 1st year, 72% and 89% for the 2nd year, 74% and 92% for the 3rd year and 83% and 96% for the 5th year in groups C and T, respectively. By the third year, the rate of subjects whose corrected visual acuity was less than 0.8 or who received cataract surgery was significantly higher in group T than in group C. There was no significant difference in the total dose between the subjects with cataract over grade I and those of grade 0 and I in both groups C and T. In group C, the total dose of steroid pulse therapy was significantly higher in the subjects with steroid cataract over grade I than in those with grade 0 and I. CONCLUSIONS: Using cyclosporin, although the total dose of systemic steroid was decreased, the rate of steroid cataract increased. Cyclosporin may accelerate the development of steroid cataract. Steroid pulse therapy is considered to be a risk factor for developing steroid cataract.

[Prophylaxis of recurrence in superficial bladder carcinoma by intravesical chemotherapy--comparative study between instillation of combined double anticancer agents and single anticancer agent].

We performed a study to compare the usefulness of double or single anticancer agents in the prophylactic treatment after the transurethral resection (TUR) of superficial bladder cancer. We experienced 127 superficial bladder cancer cases. Of these cases, 42 were treated with intravesical adriamycin (ADR) and peplomycin (PEP), 56 with ADR, PEP, epirubicin (epi-ADR) or pirarubicin (THP) only, and the remaining 29 with TUR only. Nonrecurrence rates were significantly higher in the intravesical treated cases than in the cases with TUR only, and also significantly higher in the cases treated with ADR and PEP than the other treated cases. We concluded that intravesical chemotherapy with combined agents was more effective than with a single agent.

Hypertension due to coexisting pheochromocytoma and aldosterone-producing adrenal cortical adenoma.

A 49-year-old male was diagnosed as having primary aldosteronism at age 39, and he was treated with antihypertensive drugs. In 1995, a computed tomogram revealed a mass in the right adrenal gland. Radiological examinations and endocrinological data revealed the presence of a pheochromocytoma in the right and an adrenocortical tumor in the left adrenal gland. Right adrenalectomy and left partial adrenalectomy were performed. Histologically, the right adrenal mass was compatible with pheochromocytoma, and the left adrenal mass was an adrenocortical adenoma. Endocrinological data as well as blood pressure returned to normal after operation.

[Indication for the steroid therapy for acute rejection].

Between January 1, 1986 and March 31, 1997, 103 kidney transplantations were performed at our institution. Seventy-nine grafts were from living related donors; one was from a living unrelated donor; 23 were from cadaveric donors. Basic immunosuppression consisted of cyclosporin (CYA), azathioprine (AZ) and methylprednisolone (MP). Twenty of these grafts (14.9%) developed steroid resistant rejection (SRR). The 5-year graft survival rate of patients with SRR (57.9%) was lower than that with no rejection (92.9%) and steroid responded rejection ( 85.6%). (p = 0.002) Treatment methods of SRR were methylprednisolone pulse (n = 5), plasma exchange (n = 7) and others (n = 8) such as, OKT 3, 15-deoxyspergualin, anti-thymocyte globulin, Tacrolimus rescue and cyclosporin rescue. No significant differences could be seen on the 5-year graft survival between the 3 groups. We reviewed 9 episodes of acute rejection, and compared the Banff classification with the degree of reversibility of rejection. Of the 9 biopsies examined, 5 were classified as borderline change, 2 had mild rejection (grade I), 2 had moderate rejection (grade II), 1 had severe rejection (grade III). Complete reversal of rejection by steroids was observed in only 3 patients; 2 were borderline and one was grade II.

[The relationship between the production of interleukin-6 and the proliferating cell nuclear antigen (PCNA) expression in renal cell carcinoma].

The relationship between the proliferating cell nuclear antigen (PCNA) expression in renal cell carcinoma (RCC) determined by immunohistochemical staining using the PC10 clone, and the preoperative serum interleukin-6 (IL-6) value determined by ELISA was examined. The secretion of IL-6 in RCC was also examined immunohistochemically using an anti-IL-6 antibody. The PCNA labeling rate was significantly higher in grade 3 tumors than in grade 1 tumors (p < 0.05), but there were no significant differences between the other grades or TNM stages. No significant correlation was obtained between the serum level of IL-6 or the positive cell rate of IL-6 and the pathological grade of the RCC. A correlation was observed between the PCNA labeling rate and positive cell rate, and between the serum IL-6 value and CRP or ESR. In conclusion, the secretion of IL-6 was detected in RCC tissue, and was suggested to be a tumor factor responsible for the growth and spread of RCC. The serum IL-6 value is considered to reflect the total secretion of IL-6 produced by the RCC and accessory cells, i.e., monocyte-macrophage lineage cells, endothelial cells and fibroblasts.

Family study of 2,8-dihydroxyadenine stone formation: report of two cases of a compound heterozygote for adenine phosphoribosyltransferase deficiency (APRT*J/APRT*Q0).

The family members of 2 formers of 2,8-dihydroxyadenine stones were examined for history, adenine phosphoribosyltransferase (APRT) activity, genotype, urinary sediment, and urinary constituents. The patients' father showed a genotype of APRT*1/APRT*Q0, and their mother showed APRT*1/APRT*J. Patients 1 and 2 were compound heterozygotes for adenine phosphoribosyltransferase deficiency (APRT*J/APRT*Q0), and APRT activities were 4.5% and 4.0% of normal, respectively. 2,8-Dihydroxyadenine crystals could be seen in the urinary sediment. Treatment with allopurinol completely stopped new stone formation for 5 years in patient 1.

Damage attributable to extracorporeal shockwave lithotripsy and deposition of calcium oxalate crystals on ureteral stents.

Ureteral stents have been widely used during and after SWL depending on the size of the stones and the condition of the urinary tracts. The use of stents can help to reduce complications and contributes to stone passage. However, some reports note complications that were attributed to indwelling ureteral stents. We attended to the role of obstruction of ureteral stents in those complications. The aim of this study was to analyze factors that influence ureteral stent obstruction and damage caused by SWL. Crystal deposition and the damage by SWL were examined in all ureteral stents by the use of continuous flow system and were evaluated by scanning electron microscopy. The degree of crystal deposition and damage differed depending on the individual stent. The material properties of the stent surface are the major factor influencing crystal deposition and the degree of damage by SWL. The indications for ureteral stenting must be considered in each case, because the routine use of ureteral stents has a possibility to increase complications.

[A case of chronic scrotal hematocele].

We report a case of chronic scrotal hematocele. A 94-year-old man complained of urine retention and a painless mass in the right scrotum. He had no history of trauma at the perinium. Tumor markers such as human chorionic gonadotropin, alpha fetoprotein and carcinoembryonic antigen were within normal limits. A transillumination test was negative. A right high orchiectomy was carried out after admission with the diagnosis of suspicion testicular cancer. The extracted mass measured 85 x 60 x 75 mm and contained old brownish black blood. The right testis was located separately from the mass and had a normal appearance. Microscopic examination revealed depositions of cholesterin crystals characteristic of chronic hematocele.

Hypertension and unilateral renal ischemia (Page kidney) due to compression of a retroperitoneal paraganglioma.

We describe a 17-year-old hypertensive man with a left abdominal mass on the computed tomographic scan. Radiologic studies revealed a large tumor near the left renal hilus, resulting in renal compression and displacement toward the posterolateral abdominal cavity. Aortography excluded stenosis of the renal arterial vessels. Plasma and urinary catecholamines were normal and plasma renin activity (PRA) was high. The left renal vein renin was 2.1-fold higher than the right one. After resecting the tumor including the left kidney and adrenal, high blood pressure and elevated PRA returned to normal. Histologically, the tumor was a paraganglioma, and the affected kidney showed hyperplasia of the juxtaglomerular apparatus. Thus, the hypertension in our patient was probably due to renal ischemia extrinsically compressed by a non-functioning retroperitoneal paraganglioma (Page kidney).

Inhibitory potency of crystal matrix protein on the crystallization of calcium oxalate.

The presence of macromolecular substances is among the multiple factors that may influence the complex process of urinary stone formation. The aim of this study was to evaluate the inhibitory potency of crystal matrix protein (CMP). Purification of CMP consisted of calcium oxalate crystal formation, dissolution of crystals, electrodialysis and high-performance liquid chromatography (HPLC). The inhibitory potency of crystal aggregation was examined by the seed crystal method, the undiluted urine method, and the use of scanning electron microscopy (SEM). CMP showed the protein band of 31 kDa in SDS-PAGE. Anti-CMP polyclonal antibody and antihuman prothrombin antibody cross-reacted well with human prothrombin and CMP in Western blotting. CMP and human prothrombin had high inhibitory potency by the seed crystal method and undiluted urine method. Using SEM, we were able to observe the high inhibitory potency of human prothrombin and undiluted CMP on the aggregation of calcium oxalate crystals.

[Symposium (2). Diagnosis and treatment of renal parenchymal mass. Chairmen's comments].

Although renal cell carcinoma occupies clinically the majority of renal parenchymal mass lesions, indeterminate renal masses among renal cystic lesions and benign renal tumors have been frequently found with recent advances in renal imaging modalities. Renal mass lesions to be differentiated from renal cell carcinoma were focused on in the symposium and the points discussed were divided into four categories. 1. Indeterminate renal cystic masses, especially focused on multilocular cystic lesions and renal malignant lesions associated with acquired cystic disease of the kidney (ACDK) and von Hippel Lindau disease. 2. Angiomyolipoma and oncocytoma, as representative ones among a variety of benign renal tumorous lesions. 3. How to treat small renal masses serendipitously detected by abdominal CT and/or ultrasound, radical nephrectomy or renal parenchyma-preserving operation? 4. Feasibility of percutaneous ultrasound-guided fine needle biopsy for suspicious renal mass lesions. In this symposium, the diagnosis and treatment of various renal mass lesions other than renal cell carcinoma were mainly discussed and the important points to diagnose and treat patients with renal cell carcinoma have been clarified.

[Renal cell carcinoma and acquired cystic disease of the kidneys in patients on long-term hemodialysis].

Since the first report in 1977 by Dunnill et al., a substantial number of articles have been written concerning the complications of acquired cystic disease of the kidneys (ACDK) and renal cell carcinoma developing in the native kidneys of patients undergoing long-term hemodialysis. The incidence has been reported to be 35% to 95% of ACDK in patients undergoing long-term hemodialysis. In addition, renal cell carcinoma has been described in 4% to 7% of the ACDK. The etiology of ACDK and renal cell carcinoma in the native kidneys of patients undergoing long-term hemodialysis remains unresolved. Because ACDK and renal cell carcinoma are usually asymptomatic, several reports described the use of imaging studies in the native kidneys of patients undergoing long-term hemodialysis and suggest a variety of management schemes to screen or monitor the status of the native kidneys. Ultrasonography is the most common screening study, but CT scan is more sensitive. Both studies are necessary to diagnose ACDK and renal cell carcinoma in the native kidneys of patients. We review our 10 cases and the Japanese literature with particular attention to the diagnosis and treatment of patients with ACDK and renal cell carcinoma. Our findings were similar to those reported by others. Patients receiving dialysis treatment for more than three years should have a baseline radiologic examination of the kidneys so that subsequent problems can be more easily identified and evaluated. The best surgical treatment for patients with ACDK and renal cell carcinoma is simple nephrectomy by flank incision in order to prevent surgical side effects, for example postoperative bleeding.

Backscattered electron imaging of crystal matrix protein on the surface of calcium oxalate crystals using colloidal gold.

In order to clarify the presence and localization of crystal matrix protein (CMP) upon calcium oxalate crystals, scanning electron microscopy (SEM) and backscattered electron imaging (BEI) techniques were used. This protein exhibits a remarkable affinity with calcium oxalate crystals and may be important in stone pathogenesis. In this paper, rabbit anti-human CMP polyclonal antibody was used as first antibody, and for the second antibody, goat anti-rabbit IgG conjugated with 20 nm immunogold was used. Freshly prepared crystals from male urine were fixed in SEM fixative, then blocked and washed with phosphate-buffered saline and bovine serum albumin (PBS/BSA). First and second antibodies were reacted in PBS/BSA. Crystals were then dehydrated and finally coated for SEM study. The SEM technique showed bipyramidal shaped dihydrate calcium oxalate crystals in every sample and even at high magnification, colloidal gold could barely be seen. BEI clearly demonstrated the presence and localization of the gold on the surface of the crystals as well as on the macromolecules eluted from the crystals by dissolving them in ethylenediamminetetraacetic acid solution.

Analysis of glycosaminoglycans induced in newly formed calcium oxalate crystals using an undiluted urine system.

The aim of this study was to examine the effect of sodium pentosan polysulfate (SPP) in an undiluted urine system and to study its relative affinity to calcium oxalate (CaOx) crystals in the presence or absence of heparan sulfate (HS). CaOx crystals were induced with an overload of oxalate above the metastable limit in spun and filtered urine (SF) and ultrafiltered urine (UF). Then, the crystals were dissolved with EDTA (ethylenediaminetetraacetic acid), electrodialysed and lyophilized. The polyanions, HS or SPP were added to the UF prior to the addition of oxalate. Polyanions in crystal matrices were examined by cellulose acetate electrophoresis. Crystal volume and size were suppressed according to the increase of the concentration of SPP when compared with those of the UF. Scanning electron microscopy (SEM) showed marked aggregation of the crystals in the UF and no aggregation in the presence of SPP. HS was the only polyanion found in CaOx crystals formed after overload of oxalate in SF. Crystals formed in UF did not contain any polyanions. When SPP was added to UF, SPP appeared in the crystal matrix in accordance with its concentration. Once HS in physiological concentration was added to the UF containing SPP, HS and SPP obtained from crystals were strongly stained with Alcian blue in electrophoretic study, where SPP is stained stronger than HS. These results suggest that SPP strongly binds to CaOx crystals as well as HS and that HS and SPP competitively bind to the crystal, then, as a result, they are incorporated into the crystals. The fact that SPP suppressed the aggregation of CaOx crystals in undiluted urine showed the possibility that SPP might be one of the useful drugs for preventing CaOx urolithiasis.

[Studies on the modified dimethylmethylene-blue (DMB) method for determining glycosaminoglycans (GAG) in urine].

The measurement of glycosaminoglycans (GAG) in urine is very important because GAG is an essential constituent of urinary diseases. Since previously reported methods of determination of GAG are quite complicated, dangerous or not stable, we developed a very simple and rapid method to estimate the content of GAG in urine using a microplate and microplate reader. An aliquot of diluted urine is mixed with a 1,9, dimethylmethylene blue (DMB) dye. The assay is based on the metachromatic shift in absorption maximum which occurs when sulfated glycosaminoglycans are added to the dye. The recovery of GAG is good. Other urinary compounds such as sugar, protein and blood did not influence the measurement of GAG. A good correlation was obtained between the modified DMB method and Blumenkrantz and Asboe-Hansen's method (r = 0.737, p < 0.001). The accuracy of this method makes it useful for screening urinary diseases.

Influence of RF capacitive heating on the alpha 1-adrenergic receptors of rat prostates.

The aim of this study was to find out the influence of radiofrequency (RF) capacitive heating on the alpha 1-adrenergic receptor of rat prostates. The prostates of 30-week-old Wistar rats were submitted to a 1-hour single session of RF capacitive heating at 45 degrees C. The ventral prostates that were submitted to heating were compared to those of other rats that were not submitted to heating. In order to determine the density of alpha 1-adrenergic receptors in rat ventral prostates, binding assays for alpha 1-adrenergic receptor were performed with [3H]prazosin in membrane preparations. The receptor density in the control group was 27.07 +/- 3.75 fmol/mg protein. The alpha 1-adrenergic receptor density (Bmax) in the thermotherapy group was 17.91 +/- 5.15 fmol/mg protein. A remarkable decrease in the density of alpha 1-adrenergic receptors was observed in the rat prostates of the thermotherapy group. In conclusion, the present results demonstrate that heating the rat prostate by RF capacitive heating damages the alpha 1-adrenergic receptors.

Isolation and partial characterization of crystal matrix protein as a potent inhibitor of calcium oxalate crystal aggregation: evidence of activation peptide of human prothrombin.

In order to clarify the characteristics of crystal matrix protein (CMP), which exhibits a remarkable affinity for calcium oxalate crystals and may be important in stone pathogenesis, we have isolated CMP from macromolecular matrix substances of newly-formed calcium oxalate crystals. Purification of CMP consisted of calcium oxalate crystal formation, dissolution of crystals, electrodialysis, anion exchange chromatography and high-performance liquid chromatography. CMP showed the protein band of 31 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of CMP was identical to that of human prothrombin. Both anti-CMP polyclonal antibody and anti-human prothrombin antibody cross-reacted well with human prothrombin and CMP in Western blotting. Its amino acid composition and its molecular weight of 31 kDa strongly suggest that CMP is the activation peptide of human prothrombin.

[Treatment of staghorn calculi: combined therapy and stone recurrence].

Between April 1986 and September 1992, 29 extensive staghorn calculi were treated in 24 patients. Treatment was with extracorporeal shock-wave lithotripsy (ESWL) monotherapy in 11, initial ESWL followed by percutaneous nephrolithotomy (PNL) in 7 and initial PNL followed by ESWL in 11. A comparison based on treatment demonstrated that initial PNL followed by ESWL resulted in a lower rate and shorter duration of the "stone street" while stone-free rate at 1 year after the last treatment, recurrence rate, residual stone-growth rate and other complication rates were similar. Initial PNL followed by ESWL should be considered the efficacious treatment option, especially for patients with extensive traghorn calculi.

[The inhibitory effects of Takusha on the formation, growth and aggregation of calcium oxalate crystals in vitro].

The inhibitory effects of Takusha on the formation, growth and aggregation of calcium oxalate crystals were estimated by the microplate method and the use of Coulter counter TAII in the diluted urine system and undiluted urine system. In the diluted urine system, the inhibitory effect on aggregation and growth was calculated from the changes in the number and volume of crystals by the seed crystal method. Takusha had a strong inhibitory effect on the aggregation and growth when the concentration was above 10 micrograms/ml. In measuring the metastable limit by the microplate method, Takusha had a mild inhibitory effect on the formation of crystals above the concentration of 1 mg/ml. In the undiluted urine system, after determining the metastable limit, the formation and growth of calcium oxalate crystals which precipitated in response to a load of sodium oxalate were measured. Takusha had a strong inhibitory effect on the formation and growth at the concentration of 0.1-1 mg/ml. Takusha had no glycosaminoglicans in the dimethylmethylene blue assay and had an inhibitory effect on aggregation and growth when its molecular weight was over 10,000. Therefore, Takusha might be useful for preventing stones in recurrent stone formers.