Mads M. Christensen

29-Week Doxazosin Treatment in Patients with Symptomatic Benign Prostatic Hyperplasia: A Double-Blind Placebo-Controlled Study

In a placebo-controlled study, the safety and efficacy of the selective alpha 1-adrenoceptor-blocking agent doxazosin 4 mg once daily in the symptomatic treatment of benign prostatic hyperplasia (BPH) were evaluated. One hundred patients were primarily included in a 9-weeks study, and after this 75 patients accepted to continue in the present 20 weeks extension. Of the patients in the doxazosin-group (DG) 61% reported overall improvement against 53% in the placebo-group (PG)--(p = 0.56). In the DG, 49% of obstructive symptoms were improved compared to 27% in the PG (p < 0.01), and a reduction of 60% of irritative symptoms was found in the DG against 36% in the PG (p < 0.01). Daytime frequency was reduced by median 1.5 in the DG and remained unchanged in the PG (p < 0.01). Nocturia was reduced by median 1 and 0.5 respectively (p = 0.06). Maximum urinary flow rate (MFR) was improved by median 1.5 ml/s in the DG, while it deteriorated by median 0.5 ml/s in the PG (p < 0.05), Considering postvoid residual urine volume, cystometry variables (first sensation and bladder capacity), changes in sexual function and adverse events there was no difference between the two groups. In conclusion, doxazosin 4 mg once daily in long-term treatment of patients with BPH reduces both obstructive and irritative symptoms, daytime voiding frequency and although only slightly, significantly augments MFR without interference with sexual function and without other serious adverse effects.

Symptom Analysis and Uroflowmetry 7 Years After Transurethral Resection of the Prostate

The long-term result after transurethral resection of the prostate is not well documented. From 1981 to 1983, 84 consecutive consenting patients completed detailed symptom analysis and urodynamic examination before transurethral resection of the prostate. These studies were repeated 3 and 12 months postoperatively. Of the 84 patients 44 were interviewed at 86 months: 75% reported improvement compared to preoperative symptoms. In addition, 23 patients underwent uroflowmetry at 7 years. For this group the maximum urine flow rate remained virtually unchanged from 1 to 7 years postoperatively). When uroflowmetry results from all patients undergoing testing at the various followup intervals are considered, the maximum urine flow rate was 9.5 ml. per second preoperatively, 17.0 ml. per second at 3 months and 19.6 ml. per second at 1 year. Of the 44 patients 7 (16%) underwent repeat transurethral resection of the prostate.

A guinea pig model for study of bladder mast cell function : histamine release and smooth muscle contraction

To study the function of mast cells in bladder tissue, guinea pigs were sensitized with ovalbumin by intraperitoneal injections, bladder tissue strips were superfused, and tissue contractile force and histamine release were studied. Upon challenge with ovalbumin, bladder tissue contracted 64 +/- 4% (mean +/- S.E.M.) of the maximum carbachol contraction and released 14.1 +/- 1.6% of the total tissue histamine content. Incubation of sensitized bladder tissue with indomethacin led to an increased force and duration of the contraction while incubation with nordihydroguaiaretic acid combined with pyrilamine reduced histamine release and abolished the contraction. Tissue histamine content was significantly higher in the bladder neck than in the dome, and significantly elevated following sensitization. Histochemical studies of bladder tissue demonstrated mast cell degranulation in antigen challenge experiments. In addition, a group of guinea pigs were sensitized to ovalbumin through bladder instillations. With this model, study of the functional characteristics of bladder mast cells and the acute actions of mast cell products on the bladder microenvironment, should now be feasible.

In vitro effects of bladder mucosa and an enkephalinase inhibitor on tachykinin induced contractility of the dog bladder

Tachykinin-induced contractility of smooth muscle strips from dog bladders was studied in vitro, and the presence of substance P-like immunoreactivity and neurokinin A and neurokinin B-like immunoreactivity was examined in bladder sections. Nerve fibers with substance P-like immunoreactivity were present in the mucosa, submucosa and smooth muscle. Fibers were also found in nerves, intramural ganglia, and around blood vessels. Neurokinin A-like immunoreactivity had similar distribution, and no neurokinin B-like immunoreactivity was observed. Removal of the mucosa significantly enhanced the sensitivity and the maximum responses to the tachykinins. After removing the mucosa, the sensitivity to these tachykinins increased 0.4 to 0.5 log units (p less than 0.02). The responses to carbachol were not altered by mucosa removal. The leftward shifts of the concentration-response curves for neurokinin A were of similar magnitude after removal of the mucosa, and after pretreatment with phosphoramidon (10 microM), an enkephalinase inhibitor, in the presence of mucosa. However, phosphoramidon did not alter the sensitivity of the bladder strips to neurokinin B, and slightly changed the sensitivity to substance P (0.2 log units). Additional shifts of the substance P and neurokinin A curves to the left were observed in the presence of phosphoramidon when the mucosa was removed (0.6 and 0.5 log units, p less than 0.005). The order of potency for the tachykinins (neurokinin A greater than substance P) was not altered by mucosa removal, addition of phosphoramidon, or both. Neurokinin A was degraded by enkephalinase located in the bladder mucosa and addition of phosphoramidon or mucosa removal resulted in an inhibition or loss of enkephalinase activity. It is concluded that the responses to neurokinin A, which acts on NK-2 type of receptors, prevail on the dog bladder.

Urethral Strictures after Transurethral Bladder Tumor Resection

The charts on 241 patients, consecutively undergoing a total of 2043 transurethral resections of bladder tumors and subsequent controls, were reviewed to find the incidence and possible causes of postoperative urethral stricture. The incidence of urethral stricture was 15% in males and 4% in females, but less than one-third were symptomatic. The strictures were found distally in the urethra in 83% of the patients and were treated with optical urethrotomy. Cumulated duration of postoperative catheterization was significantly longer and size of resectoscope used larger in patients with stricture. Repeated transurethral instrumentations may increase the risk of stricture development.

Antimicrobial prophylaxis in transurethral resection of the prostate with special reference to preoperatively sterile urine

The literature on antimicrobial prophylaxis in connection with transurethral resection of the prostate (TURP) is reviewed, and it is concluded that there is no proof of clinically significant beneficial effect of prophylaxis when the urine is sterile preoperatively. Prophylaxis is indicated when bacteriuria or an indwelling urethral catheter is present at the time of operation. Other possible risk factors, such as diabetes mellitus, neurogenic bladder dysfunction, immunosuppression, earlier coronary bypass operation and the presence of prosthetic devices, need further investigation.

Radical Prostatectomy Versus Placebo in Early Prostatic Carcinoma: A Veterans Administration Cooperative Study

Carcinoma of the prostate is the second most common malignancy in American men and the third most common cause of death in men. Approximately 96000 new cases of prostate cancer were diagnosed in the United Stated in 1987, and 26000 deaths occurred due to cancer of the prostate. Despite intensive efforts, beginning with endocrine manipulations more than 40 years ago, there are still no data showing unequivocally the superiority of any particular therapy. Therefore, the proper treatment of prostate cancer remains controversial and the results of various treatments inconclusive. During the late 1960s and early 1970s, the Veterans Administration Cooperative Urological Research Group (VACURG) carried out several prospective randomized studies to investigate the effect of different primary treatments of adenocarcinoma of the prostate (Table 1) [1, 3].