Symptoms Predictive for Efficacy of Naftopidil in Patients with Benign Prostate Hyperplasia

Objectives: To evaluate the lower urinary tract symptoms predicting the efficacy of the α1‐adrenoreceptor (AR) antagonist naftopidil in patients with benign prostate hyperplasia. Methods: The efficacy of naftopidil was examined on the basis of changes in the international prostate symptom score (IPSS). All patients received naftopidil (50 mg/day) for 12 weeks. We defined a “responder” as a patient whose total IPSS improved by five or more points and assessed the lower urinary tract symptoms predicting the efficacy of treatment by performing multivariate and probit analyses. Results: Among 132 patients whose data could be analyzed, the efficacy rate was 50.8%. All IPSS items except the urgency score were significantly higher in the responders than the non‐responders before treatment, and all IPSS items were lower in the responders after treatment. In the responder group, significant improvements were observed in the total IPSS score, quality of life (QOL) index, maximum flow rate (Q_max), residual urine volume, and all IPSS items after treatment. In contrast, in the non‐responder group, no parameter except the QOL index improved significantly. The probit analysis demonstrated that the score for weak stream (≥3) or nocturia (≥4) in the IPSS were factors predicting an effective response to naftopidil treatment. Conclusions: Weak stream and/or nocturia are the key symptoms that predict the efficacy of naftopidil treatment in patients with benign prostatic hyperplasia. Those with a score of ≥3 for weak stream or of ≥4 for nocturia are expected to achieve a good response in the subjective symptoms with administration of naftopidil.     

Monoclonal Gammopathy in Adult T-Cell Leukemia/ Lymphoma: A Report of Three Cases

Adult T-cell leukemia/lymphoma (ATL/L) is clustered in southwesternJapan, especially in the Nagasaki and Kagoshima areas. It wasshown that this clustering correlated with the presence of antibodiesto antigens of a new C-type RNA leukemia virus. Surface markeranalysis of neoplastic T-cells of ATL/L patients shows the helper/inducerphenotype (Leu-1⁺, Leu-2a^– and Leu-3a⁺). On the other hand, the association between T-cell malignancyincluding ATL/L and monoclonal gammopathy is very rare. Threeunique cases of ATL/L with monoclonal gammopathy are reported.Yet the meaning of an M-component in T-lymphocytic proliferationremains uncertain. The relationship between the leukemia virus,ATL/L-cells and monoclonal gammopathy is discussed.     

The Specificity of the Penetrating and the Superficial Spreading Types of Early Gastric Cancer—Classification of Early Gastric Cancer Using the Interactive Image Analysis System—

Abstract: Specific types of early gastric cancer were investigated in accordance with the cancer surface area and the degree of penetration by means of quantitative measurements of the surface area of early gastric cancer using the interactive image analysis system. The results indicated a significant correlation between the surface area and the penetration depth in ordinary early gastric cancer. However these correlations were not observed in both well and poorly differentiated adenocarcinoma cases of the so-called PEN and SUPER types, which showed a significant specificity when compared with ordinary early gastric cancer. The PEN and SUPER types of early gastric cancer also exhibited various clinicopathological characteristics, and it was suggested that the poorly differentiated PEN type might be the initial lesion of a linitis plastica type gastric cancer. Examination of the conditions of the mucosa surrounding the cancer revealed a difference between the PEN and the SUPER types, and this suggested that the environment at the site of a cancer growth influences the type of growth and the spread of early gastric cancer.     

Effects of the Pacing Site, Procainamide, and Lead Configuration on the Relationship Between the Upper Limit of Vulnerability and the Defibrillation Threshold

FAN, W., et.al .: Effects of the Pacing Site, Procainamide, and the Lead Configuration on the Relationship Between the Upper Limit of Vulnerability and the Defibrillation Threshold . In six open chest dogs, we determined the upper limit of vulnerability (ULV) and defibrillation threshold (DFT) by an up-down algorithm when the pacing site was at the right atrium, at the left ventricular apex, and at the left ventricular base. Monophasic shocks (6 ms) were given to epicardial patches at 20 and 40 ms before the peak of the T wave to bracket the mid-upslope. In an additional six closed-chest dogs, we determined the ULV and the DFT with transvenous leads with an 8-ms biphasic waveform. The S₁ pacing site was at the right ventricular apex and the right atrium, and the shocks were given at 20 ms and 40 ms before the peak of the T wave, and on the peak of T wave. The same test was repeated after intravenous procainamide infusion (20 mg/Kg loading, then 2 mg/min maintenance). In the first six dogs, the ULV determined when pacing was given to the left ventricular apex, the left ventricular base, and the right atrium was 4.2 ± 1.7 J, 4.4 ± 2.1 J, and 3.9 ± 1.5 J, respectively; values that were not significantly different from the DFT of 4.8 ± 1.9 J, 4.5 ± 1.9 J, and 4.2 ± 1.3 J, respectively. In the latter six dogs, the ULV versus the DFT was 13.5 ± 5.2 J versus 18.2 ± 6.2 J (right ventricular apex) and 12.8 ± 6.0 J versus 15.4 ± 6.0 J (right atrium) at baseline; 14.6 ± 4.6 J versus 19.5 ± 6.7 J (right ventricular apex) and 14.3 ± 5.5 J versus 18.7 ± 6.4 J (right atrium) during procainamide infusion (P = NS for all). We conclude that, when tested with 2–3 shocks on or before the peak of the T wave, the ULV can be used to estimate the DFT with both epicardial patch and transvenous lead configurations. Different S₁ pacing sites and procainamide did not change the relationship between the ULV and the DFT.     

Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo

PURPOSE: TAK-165 is a new potent inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase. Several reports suggest HER2 expression in bladder cancer, renal cell carcinoma (RCC) and androgen-independent prostate cancer. We therefore investigated the antitumor effect of TAK-165 on these urological cancer cells. MATERIALS AND METHODS: Western blot analysis was performed to confirm HER2 expression in cell lines. To study in vitro efficacy, cells were treated with TAK-165 at various concentrations for 72 h and then counted using a hemocytometer. Then the IC50 value was calculated. In the xenograft model, after the tumor reached 200-300 mm3 in volume, mice were orally administered TAK-165 10 mg/kg per day or 20 mg/kg per day or saline for 14 consecutive days (n=6-8). RESULTS: HER2 expression was observed in HT1376, UMUC3, T24 (bladder), ACHN (kidney), DU145, LNCaP, LN-REC4 (prostate), although the expression level in these cells was weak compared with BT474 (a breast cancer cell line which expresses HER2 strongly). IC50 was varied from 0.09 to greater than 25 micromol/L in the bladder cancer cell line. ACHN cells were less sensitive in vitro. The prostate cancer cell lines studied were all sensitive (IC50 0.053-4.62 micromol/L). In the xenograft model, treatment with TAK-165 significantly inhibited growth of UMUC-3, ACHN, and LN-REC4. The antitumor effect (T/C [%]=growth of TAK-165 treated tumor/average growth of control tumorx100) after 14 days treatment were 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively. CONCLUSIONS: TAK-165 may be a hopeful new agent for bladder, kidney and androgen-independent prostate cancer.     

The novel histamine H2 receptor antagonist FRG-8813 prevents delay of wound repair induced by hydrogen peroxide in a rabbit gastric epithelial cell system

Abstract The effects of a novel histamine H₂ receptor antagonist (FRG-8813) on the restoration process of gastric epithelial wounds were assessed using an in vitro wound healing model. FRG-8813 (1, 10 mol/L) was added to a complete confluent monolayer cell sheet after artificial wounding. The restoration process was analysed by a time-lapse video system and cell migration, proliferation and apoptosis were assessed. Hydrogen peroxide (1, 3 mmol/L) inhibited restoration after wounding by suppressing cell migration and proliferation and induced epithelial cell apoptosis around the wound. The addition of FRG-8813 abolished the hydrogen peroxide-induced retardation and prevented apoptosis, although FRG-8813 itself did not enhance wound healing. FRG-8813 may act as a radical scavenger as well as having an anti-secretory action and may have favourable effects on peptic ulcer healing.     

Clinical outcome of conservative therapy for stage T1, grade 3 transitional cell carcinoma of the bladder

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of transurethral resection of bladder tumor (TURBT) and intravesical instillation therapy for stage T1, grade 3 (T1G3) transitional cell carcinoma (TCC) of the urinary bladder. METHODS: Between January 1995 and December 1997, 97 patients with T1G3 TCC of the urinary bladder were treated by TURBT and adjuvant intravesical instillation with bacillus Calmette-Guérin (BCG) or other anticancer agents. The recurrence-free survival rates were evaluated according to several clinicopathological factors. The cases that progressed to muscle invasive disease were also analysed. RESULTS: In this series, the median follow-up period was 25 months (range, 5- 41) after the initial TURBT. Intravesical recurrence was noted in 44 patients (45%), and the 1, 2, and 3 year recurrence-free survival rates were 72%, 58%, and 42%, respectively. Multivariate analyses revealed that the risk of intravesical recurrence was significantly higher for patients who did not receive BCG therapy, irrespective of age, gender, tumor size, multiplicity, pathological stage, concomitant carcinoma in situ, and lymphovascular involvement. Moreover, after a median of 10 months, disease progression occurred in seven patients (7%), of which only one patient was treated by BCG therapy after initial TURBT. CONCLUSION: These findings suggest that intravesical instillation with BCG combined with TURBT is an effective conservative treatment for T1G3 TCC of the bladder. Patients with negative prognostic factors should be treated by BCG rather than other anticancer agents after TURBT.