Cyclosporine therapy affects aminotransferase activity but not hepatitis C virus RNA levels in chronic hepatitis C

Interferon (IFN) therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and is often limited by side effects. Cyclosporine A (CsA) is a potent immunosuppressant widely used in organ transplantation. We conducted a pilot study to determine whether CsA therapy could affect aminotransferase activity and hepatitis C virus RNA levels in patients with chronic hepatitis C. Cyclosporine A was administered to 10 patients (mean age of 59 years; male: female = 9:1) who did not respond to IFN therapy previously and who had elevated serum alanine aminotransferase (ALT) values for at least 6 months. All patients were positive for HCV-RNA by RT-PCR with genotype 1b. Their mean duration of hepatitis was 15 years. Oral CsA was given for 3 months in a dose that was increased at 1 month intervals from 1.5–2.0 to 2.0–3.0 and 3.0–4.0 mg/kg per day. All patients completed the treatment schedule, although two patients developed mild non-symptomatic hypertension. Serum ALT levels gradually decreased in all but one patient. The mean percentage decrease was 59.5% at the end of therapy (from 153 ± 82 to 62 ± 48 IU/L; P < 0.02). The ALT levels fell to the normal range in five patients, although once therapy was discontinued the enzyme levels tended to return to pretreatment levels. Serum aspartate aminotransferase and g-glutamyl transpeptidase levels similarly decreased. The serum HCV-RNA titre, determined by competitive RT-PCR, did not change in any patient throughout the study period. There were no appreciable alterations in other laboratory tests, such as serum creatinine levels and lymphocyte subsets, except for an increase in serum alkaline phosphatase levels. These findings suggest that CsA, even in a relatively low dose, reduces serum aminotransferase levels without serious side effects in patients with chronic-hepatitis C, although an antiviral effect was not noted.     

Development of multiple calculi in the duplex system ureterocele

A 61-year-old man presented complaining of pollakisuria and nocturia. A plain radiograph of his kidney, ureter and bladder and intravenous urography revealed numerous calculi in the upper kidney of his left renal pelvis and ureterocele. A transurethral incision of ureterocele (TUI-ureterocele) and extracorporeal shock wave lithotripsy were performed. On TUI-ureterocele, the many calculi were found to be almost the same size and spherical in form. The postoperative clinical course was uneventful.     

Prostate-specific antigen doubling time among Japanese men in an annual health screening program

BACKGROUND: Prostate-specific antigen doubling time (PSA-DT) has been studied as a parameter reflecting the biological doubling rate of clinically localized prostate cancer treated expectantly. With the use of PSA-DT, we studied the natural history of PSA changes among Japanese men in a health screening program. METHODS: Between July 1994 and December 2002, a cohort of 1995 men aged 40-79 years underwent a total of 5700 PSA measurements in an annual multiphasic health screening program. Prostate-specific antigen doubling time was calculated using a log-linear regression model for 994 (49.8%) men who had three or more serial PSA measurements with a mean follow-up of 46.2 months. RESULTS: Of the 994 men, 192 (19.3%) had a PSA-DT of less than 10 years and 12 (1.2%) had a PSA-DT of less than 2 years. Median PSA-DT in 14 men with a subsequent diagnosis of prostate cancer was 41.6 months (range, 12.2 to stable). A log-linear model statistically fitted 65 of 180 non-cancer patients with a PSA-DT of less than 10 years. The percentages of statistically fit cases increased with higher baseline PSA (5.3%, 7.7% and 8.7% among men with <1.0, 1.0-1.99 and 2.0-3.99 ng/mL, respectively) and older baseline age (3.7%, 8.5% and 6.9% among ages 40-49, 50-59 and 60 or older, respectively). CONCLUSION: In a small but significant portion of men, PSA increases exponentially when it is still less than 4.0 ng/mL, with a PSA-DT of less than 10 years. The clinical significance of this finding should be evaluated by a prospective screening including biopsy.     

Novel technique for correcting penile curvature with severe hypospadias; Ventral lengthening with tunica vaginalis flap patching

The adequate correction of penile curvature is essential for successful hypospadias surgery. We describe a novel technique to correct severe penile curvature with a tunica vaginalis flap on the penile ventrum. We applied a tunica vaginalis flap to lengthen the ventral aspect of the tunica albuginea in two boys with significant curvature and proximal hypospadias. Tunica vaginalis flap patching to the ventral aspect of the penis is safe and technically feasible. If penile curvature is severe or the penis is small in hypospadiac patients, lengthening the ventral aspect using a tunica vaginalis flap is likely to expand instead of dorsal plication or ventral graft.     

Utility of immunohistochemical detection of prostate-specific Ets for the diagnosis of benign and malignant prostatic epithelial lesions

BACKGROUND: Human prostate-specific Ets (hPSE) belongs to the Ets family. It regulates the proliferation, differentiation, and development of prostate epithelial cells. A recent study showed that hPSE can be detected in normal glands but not in cell lines established from prostate cancer (PCA), suggesting a translational disorder of hPSE from mRNA to protein in PCA. Immunohistochemical detection of hPSE could therefore be another method of differential diagnosis of PCA from other proliferative conditions in the prostate. METHODS: An immunohistochemical detection of hPSE was carried out on the whole mounted prostatectomy specimen obtained from 19 cases with PCA. RESULTS: Basal and secretory luminar cells showed a diffuse cytoplasmic staining for hPSE in normal glands, hyperplastic glands, and prostate intraepithelial neoplasia lesions. Whereas approximately 30% of PCA lesions showed a negative staining for hPSE, the positive rate for hPSE between PCA and benign glands or prostate intraepithelial neoplasia (PIN), was statistically significant (P < 0.05). Staining intensities in normal glands, hyperplastic glands, and PIN lesions were similar, but generally stronger than those in PCA lesions. CONCLUSIONS: Negative immunoreactivity for hPSE strongly suggests malignancy in the prostate glands. Decreased immunoreactivities of glands for hPSE could suggest PCA.