The effect of sildenafil on electrostimulation-induced erection in the rat model.

This study was conducted to show the effect of sildenafil on electrostimulation-induced erection in the rat model. Fifteen 12-week-old male Wistar Kyoto rats were used. The intracavernous pressure and arterial blood pressure were simultaneously monitored through electric cavernous nerve stimulation before and after the administration of sildenafil (2 mg/kg). Statistical analysis was performed on maximal intracavernous pressure (MIP), mean arterial blood pressure (MAP), the MIP/MAP and detumescence time. MAP decreased significantly by about 20 mmHg after sildenafil administration. The MIP/MAP increased significantly after sildenafil administration. The effect of sildenafil on the MIP/MAP was marked especially at lower (2-3 Hz) frequencies. The detumescence time significantly increased after sildenafil administration. We have shown that sildenafil is effective for enhancing erection at lower frequencies and prolonging penile erection in rats. After the administration of sildenafil, penile erection would be induced by weak stimuli that will not cause penile erection under normal conditions.

Phosphorylation of mitogen-activated protein kinase is inhibited by calcitonin in DU145 prostate cancer cells.

One of the causes of insensitivity to androgen ablation therapy in prostate cancer is thought to be attributable to elevated neuropeptides secreted by neuroendocrine cells in the tumor mass. Calcitonin (CT), one of these neuropeptides, is reported to be associated with the growth of prostate cancer. There is an increase in mitogen-activated protein (MAP) kinase activation as prostate cancer progresses to a more advanced and androgen-independent disease. We examined the effect of CT on signal transduction and the relation between CT and early-response genes in the human androgen-insensitive prostate cancer cell line, DU145. The basal phosphorylation level of extracellular signal-regulated kinase 1/2, which is a key kinase in the mediation of growth factor-induced mitogenesis in prostate cancer cells, was constitutively up-regulated. N-[2-(4-bromocinnamyl) aminoethyl]-5-isoquinoline-sulfonamide (H89), a specific inhibitor of protein kinase A, potentiated the effects of more increased phosphorylation of extracellular signal-regulated kinase 1/2. CT induced the inhibition of this MAP kinase phosphorylation, and this effect was completely abolished by pretreatment with H89. Our findings demonstrate that CT caused the inhibition of constitutive MAP kinase phosphorylation in a protein kinase A-dependent manner in DU145. The transient increase of c-fos expression was detected after CT treatment, whereas expression of c-jun RNA was down-regulated after CT treatment. These results suggest that CT may regulate early-response genes, c-fos and c-jun, via a MAP kinase cascade. In conclusion, these findings suggest that DU145 might be a useful model as a therapeutic approach of neuropeptides in androgen-independent prostatic carcinoma.

Prognostic significance of neuroendocrine differentiation, proliferation activity and androgen receptor expression in prostate cancer.

Androgen, acting via the androgen receptor (AR), is associated with the development and progression of prostate cancer. Anti-androgen therapy is widely used to manage prostate cancer. However, the conversion of the tumor from a hormone-sensitive to a hormone-insensitive status causes such therapy to fail. Several mechanisms have now been put forward for this conversion, including neuroendocrine (NE) differentiation of the tumor cells. In this study, we evaluated the prognostic significance of tumor-cell proliferation activity, NE differentiation and AR expression. Formalin-fixed, paraffin-embedded sections were prepared from 42 patients with adenocarcinoma of the prostate. Using antibodies to AR, the Ki-67 antigen (MIB-1), chromogranin A and synaptophysin, immunohistochemical expression of AR, tumor proliferation activity and NE differentiation were analyzed. Our study revealed that AR expression was significantly lower in adenocarcinoma (52.2 +/- 27.1%) than in non-tumorous prostate tissue (68.3 +/- 18.3%; P < 0.001). NE differentiation was found in 50% of the tumors, which was correlated with the Gleason score (P < 0.05). An univariate analysis revealed a significant correlation between progression-free survival with both AR expression (P < 0.01) and proliferation activity (P < 0.001). NE differentiation was not a prognostic factor in this study.

[Von Hippel-Lindau disease associated with renal cell carcinoma and bilateral cystadenoma of the epididymis: a case report].

We present a case report of von Hippel-Lindau disease associated with renal cell carcinoma and bilateral cystadenoma of the epididymis. A 26-year-old man appeared with painless tumors of the bilateral scrotal contents. Ultrasonography and other radiographic examinations including computed tomographic scan and dripinfusion pyelography showed multiocular tumors in the bilateral epididymis and a right renal tumor 3 cm in diameter. The tumors of the bilateral epididymis were surgically resected and of the right renal tumor enucleated. Histopathological examination revealed cystadenoma of the epididymis and renal cell carcinoma (clear cell carcinoma, G1, pT1a). He has not received adjuvant therapy, and is doing well with no evidence of metastatic disease 2 years after surgery.

Novel polymorphisms in prostate specific antigen gene and its association with prostate cancer.

Prostate-specific antigen (PSA) is now used widely for the diagnosis and monitoring of patients with prostate cancer. The PSA gene is a target of the androgen receptor (AR) which interacts with androgen response elements (AREs) in the PSA gene promoter. Recently, we identified two novel polymorphisms in the PSA promoter ARE2 region in breast cancer. We hypothesized that some genetic variations might also exist in the AREs of prostate cancer, and that feature might correlate with cancer development and/or progression. To test this hypothesis, three AREs of the PSA gene promoter were characterized for 47 prostate cancer cases and 105 controls from the Japanese population. We demonstrated the presence of two polymorphisms at positions -252 (G or A) and -205 (A or AA), which were the same as those we have found in breast cancer. Interestingly, the -252 A was linked with the presence of -205 AA, and the -252 G was always linked with the presence of -205 A. Therefore, only A-AA and G-A (-252--205) alleles were present in the Japanese population. The proportion of patients who were either heterozygotes or homozygotes for the A-AA allele was not significantly different from that observed among 105 individuals without cancer (p = 0.726). However, comparing with G-A allele homozygotes, prostate cancer patients carrying at least 1 A-AA alleles tended to exhibit high serum PSA levels (p = 0.0002), poor differentiation (p = 0.0149) and advanced clinical stage (p = 0.0077). These results suggest that the novel polymorphisms identified in the PSA gene promoter may affect transcriptional activity of the PSA gene, and an excess of PSA production may enhance rapid progression of prostate cancer.

Expandable metallic stent placement for nutcracker phenomenon.

A 40-year-old woman presented with asymptomatic gross hematuria caused by the nutcracker phenomenon. Despite treatment with hemostatic agents and injection of silver nitrate into the renal pelvis, the hematuria had continued, and severe anemia (hematocrit 17%) had developed. We performed expandable metallic stent (EMS) placement across the left renal vein. Although mild hematuria continued, the anemia resolved after this interventional radiotherapy. EMS placement is a minimally invasive therapy for the nutcracker phenomenon.

[Intravesical BCG therapy for superficial bladder cancer].

Intravesical instillation of Tokyo 172 strain bacillus Calmette-Guerin (BCG) after transurethral resection of bladder tumor (TUR-Bt) was applied to 35 patients with superficial bladder cancer. The patients received 80 mg of BCG in 40 ml saline infused into the bladder once a week for 6 weeks. Actuarial non-recurrence rates for all 35 patients were 81.7% and 58.4% at one and two years after the BCG therapy, respectively. The recurrence of the bladder cancer after the BCG therapy was observed in 12 patients 3-27 months later. Seven patients received an additional course of BCG instillation, and 6 (86%) showed no further recurrence. Thus, the overall success rate of 2 cycles of BCG instillation was 83% (29 of 35 patients). Moreover, in some cases intravesical BCG instillation was effective for recurrent superficial bladder cancer after intravesical instillation of anti-cancer agents and prolonged the period until recurrence. The progression rate was only 5% (2 of 35 patients). These results suggest that intravesical BCG therapy for superficial bladder cancer helps prevent disease progression.

[Epidermoid cyst of the scrotum: a case report].

A 52-year-old male visited our department for a painless swelling from the right side of the anus to the right scrotum that he first noticed 5 years earlier. Palpation revealed a small fist-sized elastic solid mass with a smooth surface from the central area to the inferior pole of the right scrotum. This mass was clearly demarcated from the contents of the scrotum and not adherent to the scrotal skin. A diagnosis of a tumorous lesion in the scrotum was made, and the tumor was resected. Histopathological examination demonstrated a scrotal epidermoid cyst. To our knowledge, this is the 17th case reported in Japan.

[Vesico-vaginal fistula with a giant vesico-vaginal stone: a case report].

The patient, a 73-year-old woman, had undergone hysterectomy and irradiation therapy 26 years ago. On September 4, 1997, the patient was referred to our hospital, and presented with low grade fever and lower abdominal dull pain of a one-month duration. Radiologic and vaginal examinations revealed bilateral hydronephrosis and a giant stone lying down between the bladder and vagina. Vaginal incontinence showed the presence of the vesico-vaginal fistula. She underwent bilateral ureterocutaneostomy and cystolithotomy. A giant vesico-vaginal stone was removed by using a hammer and chisel. It weighed 180 g. The stone was composed of calcium phosphate and magnesium ammonium phosphate. Persistent infection of the bladder and the vagina may have been a possible etiological factor of the vesico-vaginal stone formation. Three weeks after the operation, bilateral hydronephrosis was improved.

[Priapism treated by caverno-glandular shunt, caverno-saphenous shunt and caverno-spongiosum shunt: report of a case].

A 44-year-old man visited a local urologist complaining of continuous pain and tumescence at penis persisting for 3 days. He was diagnosed with priapism. A caverno-glandular and caverno-saphenous shunt was performed. He presented to our hospital 3 days later, because the symptoms especially tumescence continued. We confirmed the diagnosis of low-flow priapism from cavernosography and intracavenal blood-gasometry and performed caverno-spongiosum shunt. Detumescence was finally achieved after the operation.

[Idiopathic adrenal hemorrhage: a case report].

A 77-year-old man with a low grade fever persisting for 30 days consulted a local physician. A computed tomographic scan of the abdomen showed a mixed density mass on the left adrenal gland. He was referred to our hospital for further examination. Hormonal assay demonstrated a slightly high level of noradrenalin in the serum (18 pg/ml) and vanillyl mandelic acid in the urine (6.2 ng/ml). Magnetic resonance imaging revealed a heterogeneous mass lesion 3 cm in diameter with a high signal intensity on both T1 and T2 weighted images. Angiography showed a hypovascular mass in the supra-renal region suggesting an adrenal tumor or malignancy. Left adrenalectomy combined with en bloc nephrectomy was performed because of severe adhesion. Histologic evaluation showed hematoma without malignant cells due to idiopathic adrenal hemorrhage.

[Ureteral cancer producing carbohydrate antigen 19-9: report of a case].

A case of a CA19-9-producing ureteral cancer is reported. A 58-year-old man presented with gross hematuria. Retrograde pyelography showed an irregular filling defect in the right ureter. The serum CA19-9 level was 932 U/ml (normal < 37). Right total nephroureterectomy was performed. The histological diagnosis was grade 3 transitional cell carcinoma. Immunohistochemical analysis showed CA19-9 to be expressed not only in the cancer cells but also in the normal transitional cell epithelium of the renal pelvis.

[Congenital midureteral stricture with ectopic ureter: a case report].

A 7-year-old girl was hospitalized with urinary incontinence. Intravenous pyelography showed the dilatation of upper segment of the right kidney, in which slight radioisotopic accumulation was detected on renal scintigraphy with 99mTc-DMSA. On computerized tomographic (CT) scan, a cystic mass shadow occupied the retroperitoneal space. During surgery, the right kidney was found to be completely duplicated and the ectopic ureter opened in Vestibule vaginae accompanied with midureteral stricture. The ectopic ureter was incised above the strictural site and anastomosed with the ureter of the lower segment. Although approximately 700 cases of ectopic ureter have been reported in Japan, congenital midureteral stricture accompanying ectopic ureter is extremely rare.

The effect of pictorial context on sentence memory in Broca's and Wernicke's aphasia.

Eighteen aphasic patients (8 Broca's and 10 Wernicke's aphasics), 11 right hemisphere damaged patients and 12 normal subjects were tested to assess the effect of pictorial context on verbal memory with a sentence recognition task. The subjects were read aloud a stimulus sentence describing a simple event and simultaneously shown a picture congruent or incongruent with the sentence. Immediately following or after an interval of 30 sec, the subjects were read aloud a second sentence and asked to judge whether this sentence was the same or different from the stimulus sentence. The results indicated that verbal memory was better retained in supportive situations than in distracting situations, and that this contextual effect was greater in aphasic patients than in any of the other groups. Verbal memory declined rapidly after an interval in aphasic patients, but not in normal subjects. The Broca's and the Wernicke's aphasics demonstrated different performance patterns when semantic analysis of sentences was critical.

Sensitivity to functors in Japanese aphasics.

Forty-two aphasic patients (11 amnesic, 11 Wernicke's, and 20 Broca's) and 10 controls were tested for sensitivity to functors in affirmative declarative sentences with sentence- verification tasks. The stimuli were constructed according to the following factors: Reversibility of Subject and Object, Voice, Word Order and Truth. The task required the subject to decide if a sentence presented auditorily was true or false with respect to a picture. The results indicated that functors differed among themselves in their understandability depending on sentence types in which they were embedded, and that there were no qualitative differences in sensitivity to functors among different clinical types of aphasia.