Clinicopathological study of vesicoureteral reflux (VUR)-associated pyelonephritis in renal transplantation

Abstract:  We retrospectively studied the occurrence of vesicoureteral reflux (VUR)-associated pyelonephritis using renal biopsies obtained from the transplanted kidneys, and correlated the histological changes with clinical parameters. Out of a total of 131 renal biopsies performed between 1990 and 2001 on renal transplant patients at the department of Urology of Nagasaki University Graduate School of Biomedical Sciences, 12 patients showed pyuria more than twice in a single year. Seven of these 12 patients were available for determining VUR by voiding cystourethrography (VCUG). Cystoureterography demonstrated VUR in three of seven studied patients with pyuria. A histopathological examination revealed dilatation of both proximal and distal tubules in renal biopsies of transplant patients with VUR, compared to renal biopsies of transplant patients without VUR, or non-transplanted patients with thin membrane disease. One of the patients with VUR showed advanced features of chronic pyelonephritis in four consecutive biopsies at different time points, suggesting a late stage of reflux nephropathy in the transplanted kidney. We conclude from our study that the occurrence of VUR-related pyelonephritis may be one of the important long-term complications in the survival of renal allografts.     

Disposition Characteristics of Macromolecules in Tumor-Bearing Mice

As part of the strategy for the design of macromolecular carriers for drug targeting, the disposition characteristics of macromolecules were studied in mice bearing tumors that served as target tissues. Eight kinds of macromolecules including four polysaccharides and four proteins with different molecular weights and electric charges were used; tissue distribution and tumor localization after intravenous injection were studied. Pharmacokinetic analysis revealed that the tissue radioactivity uptake rate index calculated in terms of clearance was different among the tested compounds; especially, the urinary radioactivity excretion clearances and the total hepatic radioactivity uptake clearances varied widely. Compounds with low molecular weights (approximately 10 kD) or positive charges showed lower tumor radioactivity accumulation; radioactivity was rapidly eliminated from the plasma via rapid urinary excretion or extensive hepatic uptake, respectively. On the other hand, large and negatively charged compounds, carboxymethyl dextran, bovine serum albumin, and mouse immunoglobulin G, showed higher radioactivity accumulation in the tumor (calculated total amounts were 15.6, 10.8, and 20.8% of the dose, respectively) and prolonged retention in the circulation. These results demonstrated that the total systemic exposure rather than the uptake rate index was correlated with total tumor uptake. Molecular weight and electric charge of the macromolecules significantly affected their disposition characteristics and, consequently, determined radioactivity accumulation in the tumor. It was concluded that a drug–carrier complex designed for systemic tumor targeting should be polyanionic in nature and larger than 70,000 in molecular weight.     

An aged case of hereditary xanthinuria with xanthine urinary calculi

A 74-year-old female with hereditary xanthinuria and xanthine stones is reported. She has a family history of consanguineous parents and a past history of right side nephrectomy due to a xanthine renal stone and vesicolithotomy of 3 bladder stones approximately 5 X 4 X 4 cm in size at the age of 58 and 71, respectively. Her young brother exhibited a slightly elevated urinary excretion of oxypurines. Laboratory examination showed a low serum level (0.3 mg/dl) and urinary excretion (1.56 mg/day) of uric acid, and high plasma and urine levels of oxypurines. No xanthine oxidase activity was detectably in duodenal mucosa by biopsy specimen obtained by duodenofiberscopy. Now she has another stone approximately 5 X 4 X 4 cm in her bladder. There have been are few elderly cases of hereditary xanthinuria with recurrent giant urolithiasis.     

Serum thymidine kinase,a possible marker for monitoring the effect of bone marrow transplant treatment in early recovery phase

We measured serum thymidine kinase (TK) activity with a radioenzyme assay system employing [I-125]-iododeoxyuridine as the tracer on serial specimens from five bone marrow transplant (BMT) patients before and after transplantation. The serum level of TK activity in the 4 patients with effective BMT treatment ranged from 3.0 to 16.9 U/L (mean, 7.80 U/L) before transplantation and from 27.3 to 236.1 U/L (mean, 82.95 U/L) after the BMT treatment. Mean serum TK activity increased 13.17-fold (range, 1.68 to 29.14-fold). In contrast, the activity in the patient with ineffective BMT treatment was not significantly different during, before, or after BMT treatment. In addition, serum TK activity in BMT patients was well correlated with the change in the number of leukocytes before and after BMT treatment [r = +0.709 (p less than 0.01), y = 0.012 x +0.87]. We conclude that the determination of serum TK activity in BMT patients is very useful in monitoring the course of bone marrow transplantation in the early recovery phase.     

Pharmacokinetics of carboplatin and etoposide in a haemodialysis patient with Merkel-cell carcinoma

We present a Merkel-cell carcinoma patient with chronic renal failure requiring haemodialysis and evaluate the pharmacokinetics of carboplatin and etoposide during haemodialysis. The area under the concentration-time curve of carboplatin was increased by prolonging the interval between administration and haemodialysis. However, that of etoposide was not changed. Carboplatin showed good membrane permeability in haemodialysis, while etoposide showed no permeability. In conclusion, the pharmacokinetics of carboplatin could be controlled by haemodialysis and the interval between chemotherapy and haemodialysis. However, the pharmacokinetics of etoposide were not affected.     

The value and limitation of resting 201Tl reinjection after stress-redistribution imaging for the assessment of myocardial viability: comparison with wall motion improvement by revascularization]

Clinical value and limitation of resting reinjection of small dose of thallium (37 MBq) for the assessment of myocardial viability were evaluated. The results were compared with the degree of wall motion improvement by revascularization to infarcted myocardium supplied by chronic total vessels in 12 patients with old myocardial infarction. Thallium uptake was visually scored and judged as normal, reversible defect (Group 1), new fill in after reinjection (Group 2A), and no fill in even after reinjection (Group 2B). Among 53 segments with initial perfusion abnormality, 21 segments reverted to almost normal, while 32 segments remained abnormal on redistribution images. New fill in after reinjection was observed in 11 segments of 32 segments showing persisting defect on stress and delayed image (37%). Wall motion score index of Group 2A improved significantly higher than Group 2B (p less than 0.01) and almost equal to Group 1, suggesting the utility of reinjection for the assessment of tissue viability which may be underestimated by conventional imaging. But significant wall motion improvement (greater than or equal to 0.6 mean SD/chords) was observed in 6 segments (29%) of 21 segments showing neither redistribution nor fill in after reinjection. These data indicate that small dose of thallium reinjection may enhance detection of viable but jeopardized myocardium, although some underestimation of viability remained to be resolved.