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OBJECTIVE To evaluate the efficacy and safety of onabotulinumtoxinA (botulinum toxin type A) 100 U in patients with overactive bladder and urinary incontinence. METHODS This was a phase III, randomized, double-blind, placebo-controlled trial in Japanese patients who were inadequately managed with overactive bladder medications (anticholinergics and/or β3 -adrenergic receptor agonists). Eligible patients were randomized 1:1 to receive a single dose of either onabotulinumtoxinA or placebo into the detrusor muscle (n = 124 each). The primary end-point was the change in the number of daily urinary incontinence episodes at week 12 from baseline. Secondary end-points included volume voided per micturition, other symptomatic measures (urinary urgency incontinence, micturition, urgency and nocturia) and patient-reported outcomes. RESULTS In the onabotulinumtoxinA group, there was a significantly greater decrease from baseline in the mean number of daily urinary incontinence episodes compared with the placebo group (2.16; P

Introduction Two percent of testicular germ cell tumors occur in family clusters. Here, we report metachronous testicular germ cell tumors in two brothers. Case presentation An elder brother was diagnosed at the age of 30 years old and the pathological diagnosis was mixed testicular germ cell tumor. A tumor in the younger brother was suspected during testicular self-examination. It was confirmed by ultrasound examination at the age of 30 years old, 3 years and 6 months after the diagnosis of the testicular tumor in elder brother. The pathological diagnosis was pure seminoma. Both brothers had stage 1 testicular germ cell tumors and no recurrence was observed during the follow-up period of 4 years and 4 months and 10 months, respectively. Conclusion Various histological types of tumor can occur in members of one family. Besides genetic predisposition, shared diet, environmental exposure and other factors can contribute to the familial testicular cancer. Testicular self-examination is recommended for family members of a person with testicular germ cell tumor.

Unilateral or bilateral cryptorchidism is found in 80-100% of male patients with Prader-Willi syndrome (PWS). Recently, the relationship between Yq deletions and cryptorchidism has been assessed. However, the relationship between Yq deletions and PWS patients with cryptorchidism remains unclear. Polymerase chain reaction (PCR) amplification of 51 DNA loci encompassing all of the regions for azoospermia factor (AZF) of the Y chromosome, including the deleted in azoospermia (DAZ) and ribonucleic acid-binding motif (RBM) genes, were examined for microdeletions in 10 PWS males with cryptorchidism and 20 healthy control male subjects. No microdeletions of 51 loci were found in any of the PWS males. The present study therefore suggests that microdeletions in the AZF regions of the Y chromosome do not relate to the occurrence of cryptorchidism in PWS patients.

We report an 11-year-old boy with undermasculinized genitalia and an abnormally expanded CAG repeat length at exon 1 of the androgen receptor (AR) gene. He had microphallus and scrotal hypospadias with chordee, and underwent urethroplasty at 4 years of age. At 11 years of age, a gonadotropin releasing hormone (GnRH) test yielded a relatively high leutinizing hormone (LH) response (0.7-->20.4 IU/l) and a relatively low follicle-stimulating hormone (FSH) response (1.7-->4.8 IU/l), and an human chorionic gonadotropin (hCG) test showed sufficient responses of testosterone (0.7-->23.0 nmol/l) and dihydrotestosterone (0.38-->2.95 nmol/l). The CAG repeat length was 44 for the boy and ranged from 12 to 32 for 100 control males. The DNA sequences of the AR gene were normal for the exons 1-8 and for the splice donor, splice acceptor and branch sites. The markedly expanded CAG repeat length appears to be relevant to the undermasculinized genitalia of this boy, because such an expandsion, which has previously been reported only in spinal and bulbar muscular atrophy, is known to reduce AR function.

Peroxiredoxins are novel peroxidases that exhibit divergent biological functions. The fourth member, Prx4, is synthesized with a signal sequence and, after processing, secreted as a 27-kDa form in most tissues. A 31-kDa Prx4 which corresponds to the unprocessed, membrane-bound form is found only in testis. This study was undertaken in order to investigate the role of the membrane-bound Prx4 during spermiogenesis in rats. The Prx4 transcript was observed in testes at 14 days of age, the age before puberty, and its level increased only slightly during aging. Only the secretable form of Prx4 was present before 30 days of age, but the membrane-bound Prx4 became detectable in adult testes, although sum of the two forms appeared to be the same after 21 days old. While weak immunoreactivity to the Prx4 antibody was detected in spermatogenic cells for all ages, a strong immunoreactivity was observed in the elongating spermatid and residual body of adult testis. Prx4 was present in the lumen of the endoplasmic reticulum, Golgi bodies, and the perinuclear space in young rat testes. However, the localization of Prx4 was restricted to membranes of the acrosomal vesicle of the elongated spermatid and was not detected in spermatozoon. Once spermiogenesis is accomplished, vesicles containing the membrane-bound Prx4 were released into the residual body, along with residual membranous components. Thus the conversion of the soluble form to the membrane-bound form may have a role in the acrosome formation during vesicular reorganization during spermiogenesis.

Objective To determine the expression of CD34 (to evaluate vascularity) and Ki-67 (as a proliferative index) in a variety of phaeochromocytomas and thus assess the utility of these markers as possible predictors of malignancy. Patients and methods Deparaffinized tissue sections from 21 patients with benign and four with malignant phaeochromocytoma were assessed immunohistochemically to evaluate microvascular counts (using CD34 antigen) and the proliferative index (Ki-67 antigen, monoclonal antibody MIB-1). Results There was no statistical association between high microvascular counts and malignancy, but there was between the MIB-1 score and malignancy (P

BACKGROUND Although malignant pheochromocytoma is a life-threatening illness, there is no excretory profile that is predictive of malignancy. Reliable prediction of malignant behavior on the basis of histopathology is also notoriously difficult. Although DNA ploidy can be a helpful indicator, aneuploidy per se is not considered to be a specific marker of malignancy. Mutations in p53 have been reported to occur frequently in cases of benign pheochromocytoma. Thus, molecular analysis of this protein is not a useful diagnostic tool. The authors analyzed telomerase activity in benign and malignant pheochromocytomas and assessed its utility as a prognostic marker. METHODS Telomerase activity was estimated in 16 benign pheochromocytomas, 3 malignant pheochromocytomas, and 16 normal adrenal medullae by the fluorescence-based telomeric repeat amplification protocol. The telomerase activities of each group of samples were compared. RESULTS No telomerase activity was detected in any of the normal adrenal medullae or the benign pheochromocytomas. By contrast, all of the three malignant pheochromocytomas had elevated telomerase activity. The telomerase activity in each tumor was determined to be 87.6 units, 71.2 units, and 180.3 units, respectively. CONCLUSIONS The expression of telomerase activity in pheochromocytoma clearly suggests the malignant behavior of the component cells. Analysis of telomerase activity appears to be a powerful tool for the diagnosis of malignant pheochromocytoma. Cancer 1998;82:176-9. © 1998 American Cancer Society.

There have only been a few studies of chemo-endocrine therapy compared with endocrine therapy alone in newly diagnosed prostate cancer patients. We assessed the effects of these two therapies by comparing long-term survival rates. One hundred and twenty-nine patients were entered in this study between November 1977 and March 1992. Seventy-seven patients were treated with endocrine therapy alone. Other 52 patients received chemo-endocrine therapy, which included orchiectomy and/or diethylstilbestrol diphosphate (DES-DP) plus Cisplatin, with or without other cytotoxic agents. All patients had bone metastasis at the beginning of the study. There was a significant difference in survival between patients who received endocrine therapy and chemo-endocrine therapy (P = 0.0078). That is, survival rate was superior for the chemoendocrine therapy patients throughout the entire follow-up period. These data suggest that early chemo-endocrine therapy containing Cisplatin, with or without maintenance chemotherapy, is a potentially effective treatment for newly diagnosed metastatic prostate cancer and is worth further investigation via a randomized trial.

Summary Circulating levels of pituitary and adrenal hormones were measured in patients with benign prostatic hyperplasia before and after transurethral resection of the prostate (TURP).TURP caused a significant increase in plasma LH levels 2 weeks and 3 weeks after surgery. The plasma prolactin level decreased significantly 3 weeks after prostatectomy but plasma concentrations of FSH and ACTH were unchanged. TURP did not alter circulating levels of aldosterone, Cortisol, DHEA-S and testosterone. These data suggest that the human prostate has a role in regulating the pituitary secretion of LH and prolactin.

Objective To assess the significance of immunosuppressive acidic protein (IAP) for detection of renal cell carcinoma in patients undergoing haemodialysis. Patients and methods The serum concentration of both IAP and creatinine was measured in 74 patients undergoing haemodialysis, 10 of whom had renal cell carcinoma and 64 of whom had no renal cell carcinoma. Control data was obtained from 13 healthy blood donors. Results The serum IAP level of patients undergoing haemodialysis was significantly elevated compared with that of the controls. The serum level of IAP inpatients with renal cell carcinoma who were undergoing haemodialysis was also considerably higher than that of patients with no renal cell carcinoma. The serum creatinine levels were not significantly different between patients with and without renal cell carcinoma but were significantly elevated when compared with the controls. Conclusion The measurement of serum IAP concentration is of value in the detection of renal cell carcinoma in patients undergoing haemodialysis.