The urodynamic effects of an alpha 1-adrenoceptor agonist on the bladder and urethra of female dogs]

It has been known that alpha 1-adrenoceptors play an important role in urethral contraction. The incompetence of the urethral contraction is a cause of stress incontinence. We studied the urodynamic effects of a selective alpha 1-adrenoceptor agonist (midodrine hydrochloride) on the bladder and urethra of female dogs. Under anesthesia with intravenous chloralose, four doses (0.03, 0.1, 0.3 and 1.0 mg/kg) of midodrine were administered intravenously and urodynamic studies including cystometry, urethral pressure profilometry and electromyography (EMG) of the external urethral sphincter were performed. The administration of midodrine induced a significant increase of the maximum closing pressure in the proximal portion of the urethra (p less than 0.05 at 0.03 mg/kg and p less than 0.01 at 0.1, 0.3, 1.0 mg/kg). There were no significant changes in the functional profile length, the closing pressure at the external sphincters, the maximum bladder pressure, bladder capacity and bladder compliance. The administration of 0.3 mg/kg or more of midodrine produced a significant increase in the mean arterial blood pressure. After midodrine administration, transient increases in the external sphincter EMG activities were recognized. The activities showed the synergistic pattern during the bladder contractions. In conclusion, lower dose administration of a selective alpha 1-adrenoceptor agonist (midodrine) specifically produced an increase of the closing pressure in the proximal portion of the urethra without affecting blood pressure. These results suggest that midodrine is useful for the treatment of stress incontinence in humans.     

Treatment of an infection from an intravenous cardiac stimulation lead with extracorporeal circulation]

The infection of a transvenous lead implanted for cardiac stimulation is a rare but serious complication, because it can lead to the development of septicemia, tricuspid endocarditis, recurrent pulmonary emboli or thrombus formation in right cardiac chambers. The most efficient treatment is the removal of the entire pacing system (generator and lead). We describe our experience with the removal of infected leads with the aid of cardiopulmonary bypass. Indications of this technique and its advantages and disadvantages over the percutaneous extraction methods are discussed. A review of the literature is also presented.     

Operative fiberoptic nephroureteroscope--removal of renal and upper ureteral stones

Two types of operative fiberoptic nephroureteroscopes were developed with the cooperation of the Olympus Optical Company mainly to remove the upper urinary tract calculi. Removal of the renal and upper ureteral stones was attempted in nine cases. The ureter was dilated with olive tip, balloon and Teflon dilators alone or in combination. The combination of balloon and Teflon dilators seemed the most promising. As a result of ureteral dilation, operative fiberoptic nephroureteroscopes, 4.5 mm and 3.5 mm in diameter, could be passed into the ureter in all the cases and the stones could be visualized clearly. Four of the 7 upper ureteral stones and 1 of the 2 pelvic stones could be removed. The success ratio was 56%. The method of stone removal still requires improvement. At present, application of the operative fiberoptic nephroureteroscope is indicated for upper ureteral and renal stones less than 1.0 cm in diameter. With the improved techniques of stone removal using this fiberscope, the indications of extracorporeal shock-wave lithotripsy or percutaneous nephrolithotripsy will probably be greatly reduced in the near future.     

Vesicoureteral reflux and renal scarring. Report of cooperative study of "Progressive renal disease" of Ministry of Health and Welfare

196 cases with vesicoureteral reflux (VUR) from multiple centers were analysed to examine the relationship between VUR and reflux nephropathy. The high correlation (p less than 0.01) was observed between reflux and renal scarring. Even in cases in whom VUR was not demonstrated at the time of testing, renal scarring of various degrees was recognized, suggesting either co-existed hypoplastic kidney or pre-existed infection. The renal scarring, but not VUR, had a significant correlation with proteinuria and hypertension. Retrospective analysis shows that the surgical treatment was closely related to the degree of renal scarring but not to the degree of reflux. Renal scarring progressed even when reflux did not become worse, which is probably accounted for by the presence of pyelonephritis. Although frequency of pyelonephritis decreased significantly (p less than 0.01) from 0.60 +/- 0.89 to 0.084 +/- 0.305 times/patient. year after anti-reflux surgery, renal scarring progressed in 13 kidneys (5.8%). Seven of the 13 kidneys became worse due to the surgical failure. The scar progression was recognized in the remaining six kidneys (three patients) including adult cases despite the successful surgical correction of reflux. Our study points to the urged need for a prospective clinical trial designed for the study of the pathological and clinical background of progressive renal failure in VUR.     

Localization of alpha 1-adrenoceptors in hypertrophic prostate]

In order to determine the localization of alpha 1-adrenoceptors in human hypertrophied prostates, in vitro autoradiography was performed on the frozen specimens from 13 enucleated hypertrophied prostates with [125I]-HEAT (iodo-2-[beta-(4-hydroxyphenyl)-ethylaminomethyl] tetralone) and [3H]-prazosin. In vitro autoradiograms showed macroscopically the specific binding site on the areas seemed to the nodular area for [125I]-HEAT, but not so clear specific binding sites for [3H]-prazosin. Microscopic autoradiograms seemed to show binding sites located mainly on the interstitial beneath the gland, and partly on the basement membrane and epithelium of the prostatic gland. Further studies are needed to show clearer specific binding sites of alpha 1-adrenoceptors.     

Significance of tumor markers in the treatment of urological malignancies

Clinical and laboratory studies have confirmed the efficacy of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCH) as tumor markers in the diagnosis, monitoring and assessment of prognosis in cases of testicular tumor. Serum AFP level is positive in 75% of yolk sac tumors, 70% of embryonal carcinomas and 62% of teratomas. All cases of choriocarcinoma show elevated serum hCG. In the treatment of prostatic cancer, prostatic acid phosphatase (PAP), prostatic-specific antigen (PA) and gamma-seminoprotein (gamma-Sm) are important serum markers, and the RIA method has improved their specificity and sensitivity. These markers are also correlated well with therapeutic efficacy. Especially, improvement of the serum PAP level in patients with stage C and D cancer indicates prolongation of survival time. Over 90% of the metastatic lesions of prostatic cancer are encountered in the skeletal system. Thus, serum alkaline phosphatase and urinary hydroxyproline are considered to be useful markers for indicating bone involvement. In other urological malignancies, there are no specific tumor markers. As non-specific markers for renal cell carcinoma, ESR, LDH, CEA, alpha 2-globulin, haptoglobin, fibrinogen and various hormones have been investigated. In the treatment of bladder cancer, it is important to distinguish the malignant potential of the tumor. From this viewpoint, various immunohistochemical investigations and flow cytometric analysis are now in progress. It is expected that some of the findings of the studies could prove to be of clinical use in the near future.     

Postoperative adjuvant chemotherapy in non-small cell lung cancer: prognostic value of DNA ploidy and post-recurrent survival.

Eighty-six patients with non-small cell lung cancer who underwent curative operations were postoperatively randomized to control and adjuvant chemotherapy groups. In the adjuvant chemotherapy group, patients received cisplatin-based combination chemotherapy 3 or 4 weeks after operation and the average cycle of chemotherapy was 2.3 (from 1 to 6 cycles). In this trial, no evidence of improved survival or delayed recurrence was seen in the treated patients. In multivariate analysis of prognostic variables, the most important factor was the pathological stage of the disease and, second, DNA ploidy of the primary tumor. Although histology (squamous vs. non-squamous cell carcinoma) had a trend to influence the survival, it was not a significant factor. A total of 33 patients had recurrences: 17 and 16 patients were in control and adjuvant chemotherapy groups, respectively. Postrecurrent survival in the adjuvant chemotherapy group was significantly shorter than that in the control group, as determined by the generalized Wilcoxon and log rank tests. Median survival time after recurrence in the control and adjuvant therapy groups was 18.5 and 7.5 months, respectively. These results suggest that DNA ploidy of primary tumors should be considered as a prognostic factor in future trials of adjuvant therapy. Furthermore, analysis of postrecurrent survival in the adjuvant chemotherapy trial, as well as that of overall and disease-free survivals should be done.     

Clinical usefulness of doxazosin in patients with type 2 diabetes complicated by hypertension: effects on glucose and lipid metabolism

This uncontrolled study investigated the effects of using the alpha 1-blocker doxazosin (2 mg or 4 mg daily for 3 months) to treat 21 hypertensive patients with type 2 diabetes, including eight obese individuals (body mass index [BMI] > or = 25.0 kg/m2). A significant reduction in systolic and diastolic blood pressure, beginning after 1 month of treatment, was seen. There was no significant change in BMI. Although there was no obvious improvement in glucose metabolism, doxazosin treatment noticeably reduced insulin resistance and significantly lowered triglyceride and free fatty acid levels. No significant changes were found in total cholesterol, high- or low-density lipoprotein-cholesterol, atherosclerotic index, or small or large subfractions of low-density lipoprotein-cholesterol. None of the patients showed any adverse effects. The beneficial effects of doxazosin on blood pressure and lipid and glucose metabolism shown in this study suggest that this drug is clinically useful as an anti-hypertensive agent for patients with diabetes.