Kimio Takai

Microbial contamination of dialysate and its prevention in haemodialysis units.

At the haemodialysis centres of nine hospitals in Japan, microbial contamination of treated water (reverse osmosis method), acid and bicarbonate concentrates, and dialysate was investigated. Among these fluids used in haemodialysis, the dialysate was most frequently contaminated and had the highest concentration of bacteria. Of 40 dialysate samples analysed, 42.5% showed a bacterial count of more than 2000cfu/mL, which was above the Association for the Advancement of Medical Instrumentation (AAMI) standard. However, among the 40 samples from 20 dialysis machines, all six dialysate samples from three dialysis machines that used an ultrafiltration membrane in the circuit before the entrance of the dialysate into the dialyser, showed a bacterial count of < or =10 cfu/mL. In addition, when an ultrafiltration membrane was used in the circuit before the entrance of the dialysate into the dialyser for four dialysis machines showing dialysate samples contaminated with 10(4)-10(5)cfu/mL the bacterial count in dialysate samples from these machines became zero. Because dialysis machines are susceptible to microbial contamination, it is necessary to take measures such as placing an ultrafiltration membrane into the circuit before the entrance of dialysate into the dialyser.

Urinary tract infections following renal transplantation.

The incidence of urinary tract infections (UTIs) in 363 adult renal transplant recipients transplanted during the period 1990-96 has been analysed. UTI occurred in 96 patients (26%), most frequently during the first year after transplantation. Female recipients had significantly more UTI than male recipients (49% vs. 14%, p < 0.0001). There was no difference in the incidence of UTI between recipients receiving pig-tail catheters as ureteral stents or not, the figures being 21% vs. 28%, respectively. Age had no influence on the incidence of UTI. In 341 patients treated with cyclosporine the incidence of UTI was 28%, while in 15 patients treated with FK-506 only 1 patient (7%) had a UTI (ns). The majority of organisms cultured were gram-negative (76%), with approximately 1/3 being Escherichia coli and 1/5 being Enterococcus and Klebsiella/Enterobacter. The bacterial spectrum was not influenced by the recipients age. UTI had no effect on the number of rejections, or on graft and patient survival in living donor transplant recipients. No significant difference was found in graft and patient survival rates at 3 yr between patients who had UTI or no UTI.

Effects of FK506 on rat thymus: time-course analysis by immunoperoxidase technique and flow cytofluorometry.

The effect of administration of FK506 at 1 mg/kg body weight for 14 days on rat lymphoid tissues, especially the thymus, and recovery after discontinuation of treatment, were investigated by the immunoperoxidase technique and flow cytofluorometry using monoclonal antibodies OX6, OX7, OX8, OX18 and W3/25, reactive with rat lymphocytes. Marked reduction of the thymic medulla upon treatment was clearly demonstrated by staining with OX18 and OX6. Changes produced by FK506 were also observed in the cortical area of the thymus, and were especially marked in the subcapsular area and around blood vessels. Eventually, the thymic cortex appeared patchy, this change being maximal 14 days after the start of administration. Obvious restitution of the thymic medulla was evident about 14 days after withdrawal of FK506. Flow cylometric analysis of the thymus showed that the percentages of cells labelled positively with OX7, OX8 and W3/25 were increased with FK506 treatment, and recovered to the normal levels soon after withdrawal. Furthermore, the peak of fluorescence intensity of OX7+, OX8+ and W3/25+ cells showed a temporary shift to the right during FK506 treatment; however, the peak of fluorescence intensity of OX18+ cells showed a temporary shift to the left. Treatment with FK506 also produced a significant change in 3H‐thymidine uptake by thymocyte. These results suggest that FK506 may inhibit the proliferation, maturation and differentiation of thymocytes. However, thymocytes prepared from FK506‐treated rats and labelled with FITC behaved similarly to rat thymocytes in normal recipient rats. This suggests that during FK506 treatment thymocytes may retain their potential for peripheral mobilization.

Risk group stratification to predict recurrence after transurethral resection in Japanese patients with stage Ta and T1 bladder tumours: validation study on the European Association of Urology guidelines

Study Type – Therapy (case series) 
Level of Evidence 4

A Case of Primary Adrenal Lymphoma Diagnosed from Percutaneous Needle Biopsy

A case of bilateral lymphoma of the adrenal glands is reported. A 72-year-old woman was admitted to our hospital for evaluation of bilateral adrenal masses. A 20-gauge core needle biopsy of the left adrenal tumor was performed under ultrasonographic guidance. The pathological specimen revealed a malignant lymphoma. The diagnostic procedure for adrenal lymphoma is discussed.

22-Oxacalcitriol Upregulates p21WAF1/Cip1 in Human Parathyroid Glands

In the era of 22-oxacalcitriol (OCT), newly synthesized 1α,25-dihydroxyvitamin D3 analogue, against secondary hyperparathyroidism, the indications of parathyroidectomy (PTx) has been restricted. Recent investigations on animal models have revealed the inhibitory effects on PTH secretion after OCT treatment, whereas there has been no evidence about human parathyroid glands. A 38-year-old man with a 19-year history of hemodialysis was performed PTx after the failure of OCT treatment. Expressions of proliferative nuclear cell antigen (PCNA), calcium-sensing receptor (CaSR), vitamin D receptor (VDR), p53 and p21WAF1/Cip1 were analyzed by Western blotting and immunohistochemistry on resected parathroid glands. We confirmed up-regulations of CaSR and VDR, which contribute the reduction of serum PTH, by OCT treatment. Concomitant up-regulation of p21WAF1/Cip1 but not p53, especially in nodular hyperplasia, can be considered to induce cell cycle arrest of the parathyroid cells, but not cytocidal effect of OCT.

FTY720 mediates cytochrome c release from mitochondria during rat thymocyte apoptosis

FTY720 is known to not only accelerate lymphocyte homing to secondary lymphoid organs but also induce apoptosis in lymphocytes. To investigate the effect of FTY720 in rat thymocytes, rats were intramuscularly injected with 10 mg/kg/day of FTY720. Light microscopy revealed obvious reductions in the size of the cortical region of thymuses treated with FTY720. FTY720 significantly reduced the total number of thymocytes, particularly affecting the CD4(+)8(+)TCRalphabeta(negative/low) population. TUNEL analysis showed that thymocyte apoptosis was induced in the cortical region and western blotting revealed activated caspase-3 and -6. Furthermore, caspase-9 was activated and the level of cytochrome c was increased. In contrast, the protein level of Bax did not increase following FTY720 treatment, suggesting that FTY720 may have perturbed mitochondrial function. Therefore, FTY720-induced apoptosis is initiated by the release of cytochrome c from mitochondria, resulting in the activation of caspases in rat thymocytes.

Idiopathic Clitoral Hypertrophy

We report a case of clitoral hypertrophy of unknown origin. A 3-year-old girl showed clitoral hypertrophy at birth. Biochemical analysis of peripheral blood and endocrinological examinations were normal. Other virilizing symptoms were not recognized. Clitoroplasty was carried out, and the clitoris has not enlarged 20 months after the operation. Her mother was administered cefotiam and terbutaline (β-stimulant) during pregnancy because of threatened abortion. No virilizing agents such as progesterone were used during pregnancy.

Impact of a Genetic Polymorphism of the Interleukin-1 Receptor Antagonist on Technique Survival in Peritoneal Dialysis Patients

Background/Aims: There is a clear association between one allele of the interleukin-1 receptor-antagonist gene (IL-1RN) and inflammatory diseases in which IL-1 is implicated. We evaluated patient survival and technique survival of peritoneal dialysis (PD) patients, while analyzing independent risk factors, in a PD program. We also tested the association between IL-1RN polymorphism, patient survival and technique survival. Methods: We retrospectively evaluated 129 Japanese CAPD patients undergoing initial treatment in eight centers in Japan. Using PCR, IL-1RN genotype and allele frequencies were determined, and clinical and biochemical variables were recorded at the start of PD. The relation of patient survival or technique survival with IL-1RN polymorphism and those variables was analyzed with a multivariate Cox’s proportional-hazard model. Results: The frequencies of IL-1RN*1/IL-1RN*1 and IL-1RN*1/IL-1RN*2 genotypes were 84.5 and 15.5%, respectively. Median patient survival was 37.0 months, and overall patient survival was 92.8 and 87.9% at 2 and 5 years, respectively. Age, cardiovascular disease and serum albumin were found to be independent predictors of patient survival. Median technique survival was 32 months. PD failure occurred in 37 patients, with technique survival rates of 92.0 and 72.7% at 2 and 5 years, respectively. Serum albumin, peritonitis and the presence of the IL-1RN*2 genotype were found to be independent predictors of technique survival. Conclusion: Serum albumin was the strongest predictive factor for mortality and technique failure in PD. Technique failure was also affected by IL-1RN polymorphism in this patient population.

Effects of FK506 on rat thymic microenvironment in thymocyte maturation, proliferation, and mobilization

THYMOCYTES are divided into four major populations: CD4CD8, CD4CD8, CD4CD8, and CD4CD8 thymocytes. Immature thymocytes develop into mature thymocytes through the expression of T cell receptors (TCR). These developmental sequences in phenotypic and TCR expression are considered important for the production of mature thymocytes. FK506 or Tacrolimus, which is a macrolide antibiotic produced by Streptomyces tsukubaensis, is a strong immunosuppressant drug that has been widely used for renal and other organ transplantations. In several studies it has been observed that FK506 also affects the thymus in rodent models. We have analyzed and reported the effects of FK506 on rat thymocytes using immunohistochemical stainingand 3–color flow cytofluorometry. In this study we also investigated and presented the effects of FK506 on rat thymic tissues analyzing the vascular structures in the thymus.