16 alpha-Iodo-testosterone: chemical synthesis and evaluation as a potential radiopharmaceutical.

The chemical synthesis and characterization, including 1H NMR, of 16 alpha-iodo-androstenedione and 16 alpha-iodo-testosterone are described. Each has been synthesized with 125I and tested in rats in vivo for accumulation in androgen dependent tissues over a 24 hr time course. Neither compound was accumulated in prostate against the blood gradient of normal or 24 hr castrate animals. The metabolism, subcellular distribution and binding of 16 alpha-[125I]iodo-testosterone to protein in prostate has also been examined. By comparison with data obtained after the administration of [3H]testosterone we conclude that the failure of this iodinated androgen to accumulate in androgen dependent tissues arises because of its low binding affinity for receptor protein.

Anatomic limitations of prostatic urethra in using cylindrical stents.

The use of metal stents for the relief of prostate obstruction in the elderly has increased in popularity since 1980. The finding that fine metal wire stents become covered with prostatic epithelium led to the recent use of stents that can be left in place permanently. Because the prostatic urethra does not always conform to the cylindrical shape of these stents, and because the bladder neck/urethral angle is not a right angle and may not be circular in outline, problems may occur with positioning and subsequent inadequate epithelial covering. Three-dimensional imaging of the prostatic urethra using transrectal ultrasound scanning during voiding may give additional help in defining the variety of possible shapes of this area, but more work on the compliance of prostate tissue and the shape of the prostatic urethral lumen is essential in order to improve stent design and reduce the risks and complications of these useful devices.

A percutaneous perineal approach for cystoscopy in male dogs.

A percutaneous perineal approach is presented as a further technique for rigid cystoscopy in male dogs. The anatomy of the urethra in the male dog prevents rigid cystoscopy by non-surgical means but a fine flexible fibrescope may be used. Perineal urethrotomy and prepubic percutaneous puncture techniques using rigid endoscopes have been described; however, both have possible serious complications. This new procedure allows access for visual examination, biopsy and resection as necessary and appears to have few adverse sequelae.

Cystoscopic examination of male and female dogs.

The use of cystoscopy is advocated as an aid to the early differential diagnosis of disease of the canine bladder. Techniques are described for carrying out urethroscopy and cystoscopy in both male and female dogs using modern medical diagnostic instruments. Males were examined with flexible paediatric bronchofibrescopes, which permitted urethroscopy and cystoscopy, but to obtain extensive biopsies or undertake cauterisation of the bladder surface with rigid endoscopes, a simple perineal urethrostomy was necessary. The bladder of females, on the other hand, was examined by cystoscopy and biopsied using standard rigid cystoscopes and resectoscopes.

Bladder muscle biopsy and urethral sphincter EMG in patients with bladder dysfunction after pelvic surgery.

Eleven patients who suffered persistent bladder dysfunction after pelvic surgery have been investigated by needle urethral sphincter electromyography (EMG) and bladder muscle biopsy, and the results compared with those obtained in a series of controls. Individual motor units recorded from the urethral sphincter in patients who had undergone pelvic surgery were strikingly abnormal, suggesting the presence of reinnervation, and the density of detrusor innervation was significantly reduced. However, since reduction in the density of detrusor innervation may occur in circumstances other than peripheral nerve injury, we conclude that urethral sphincter EMG provides the most effective means of assessing damage to vesico-urethral innervation as a result of previous pelvic surgery.

Haemodynamic evidence for cardiac stress during transurethral prostatectomy.

OBJECTIVE: To compare haemodynamic performance during transurethral prostatectomy and non-endoscopic control procedures similar in duration and surgical trauma. DESIGN: Controlled comparative study. SETTING: London teaching hospital. PATIENTS: 33 men aged 50-85 years in American Society of Anesthesiologists risk groups I and II undergoing transurethral prostatectomy (20), herniorrhaphy (eight), or testicular exploration (five). MAIN OUTCOME MEASURES: Percentage change from baseline in mean arterial pressure, heart rate, Doppler indices of stroke volume and cardiac output, and index of systemic vascular resistance, and change from baseline in core temperature. RESULTS: In the control group mean arterial pressure fell to 11% (95% confidence interval -17% to -5%) below baseline at two minutes into surgery and remained below baseline; there were no other overall changes in haemodynamic variables and the core temperature was stable. During transurethral prostatectomy mean arterial pressure increased by 16% (5% to 27%) at the two minute recording and remained raised throughout. Bradycardia reached -7% (-14% to 1%) by the end of the procedure. Doppler indices of stroke volume fell progressively to 15% (-24% to -6%) below baseline at the end of the procedure, and the index of cardiac output fell to 21% (-32% to -10%) below baseline by the end of the procedure. The index of systemic vascular resistance was increased by 28% (17% to 38%) at two minutes, and by 46.8% (28% to 66%) at the end of the procedure. Core temperature fell by a mean of 0.8 (-1.0 to -0.6) degrees C. Significant differences existed between the two groups in summary measures of mean arterial pressure (p less than 0.05), Doppler indices of stroke volume (p less than 0.005) and cardiac output (p less than 0.005), index of systemic vascular resistance (p less than 0.0005), and core temperature (p less than 0.0001). CONCLUSIONS: Important haemodynamic disturbances were identified during routine apparently uneventful transurethral prostatectomy but not during control procedures. These responses may be related to the rapid central cooling observed during transurethral prostatectomy and require further study.

Reoperative parathyroid surgery.

The increasing recognition of hypercalcaemia caused by primary hyperparathyroidism has led to a rise in the number of failed parathyroid exploration. We report a series of 37 parathyroid re-explorations on 33 patients with persistent hypercalcaemia following the failure of their previous parathyroid surgery. Of these patients, 27 have been cured of their hypercalcaemia but 7 are permanently hypocalcaemic. The results of the parathyroid localization tests used in this series are described, and the difficulties of reoperative parathyroid surgery are discussed. The reasons for failure of the original operations are analysed. Many are avoidable. Based on our experience strategies are described for parathyroid localization and reoperative surgery.

Precautions and complications in the use of the urolume wallstent.

The Urolume Wallstent was first used to treat urethral strictures in 1987. Its place in the treatment of urethral strictures is now well established and we have used it successfully in over 100 patients. Recent interest in alternative methods of treating benign prostatic hyperplasia (BPH) has led to the use of this and other stents in patients with symptomatic BPH who are a poor surgical risk. Over 270 patients have been treated by us with the Urolume Wallstent with satisfactory results. More recently we have also used this stent as an alternative to transurethral resection of the prostate in fat patients. Although the Urolume Wallstent is easy to use and clinically effective, complications can arise if proper care is not taken during its insertion. As the stent has become more widely used more problems and difficulties have been experienced. We discuss these and describe the precautions which should be taken in the use of this device in order to achieve the best results.

Pain as the presenting symptom in renal tuberculosis.

Four cases of renal tuberculosis presented with severe renal pain. A search should be made for tuberculous bacilluria in patients with renal pain of no obvious aetiology.

The synthesis of 3H labelled steroid-nitrogen mustard derivatives and studies on their action in rat and human prostate.

Tissue receptor proteins are thought to be a key factor in selective retention and nuclear translocation of steroid hormones in their target tissues. Steroid-cytotoxic derivatives with high affinity for these receptor proteins may, therefore, be useful as site directed agents in the treatment of hormone dependent cancers. The prostatic retention and subcellular localisation of estramustine and a 17 beta nitrogen mustard derivative of 5 alpha-dihydrotestosterone have been compared since the latter compound has higher androgen receptor binding affinity than the former. The 5 alpha-dihydrotestosterone derivative was not retained more avidly than estramustine by either human or rat ventral prostatic tissue. Nuclear localisation could not be detected with either compound. The cytotoxic action of these compounds requires the liberation of the nitrogen mustard moiety. The cleavage rate of both compounds was low but similar in both benign and malignant prostatic tissues. We conclude that steroids are unlikely to be suitable agents for directing cytotoxic compounds to prostatic tissue particularly if the steroid-cytotoxic derivative requires metabolism for the expression of the cytotoxic activity.

Permanently implanted urethral stent for prostatic obstruction in the unfit patient. Preliminary report.

We describe the use of a new urethral stent implanted into 12 patients with prostatic outflow obstruction. All were in a high risk group for surgery and 11 were treated successfully, with a follow-up of 1 to 11 months (median 9). The majority of patients were satisfied with the procedure, which provided a quick, safe and effective alternative to conventional surgical treatment. The stent, woven from fine stainless steel in the form of a tubular mesh, was inserted via a delivery device using combined ultrasound and endoscopic control under local anaesthesia. The procedure was well tolerated, the stent becoming covered with epithelium by 6 to 8 months following insertion, yet allowing easy removal within the first 4 to 6 weeks should the need arise. This technique provides a useful alternative to conventional surgical treatment in the high risk patient.

A new treatment for urethral strictures: a permanently implanted urethral stent.

We describe a new urethral stent, originally developed for endovascular use, that we have implanted into 8 patients with urethral strictures. The stent is woven in the form of a tubular mesh from surgical grade stainless steel wire and is self-expanding when released from its small diameter delivery catheter. All patients have been treated successfully with a good caliber urethra visible on urethrography and direct endoscopy, and with improved urine flow rates. Mean followup of these patients is 8 months (range 6 months to 1 year). Urethroscopy had demonstrated complete epithelial covering of the implant at 4 to 6 months. Although the followup is short it seems that this simple technique may offer a lasting treatment for many urethral strictures.

A twelve-week placebo-controlled study of prazosin in the treatment of prostatic obstruction.

Fifty-eight normotensive patients with benign prostatic hyperplasia and maximum urinary flow rates of less than 15 ml/s were randomly assigned to receive a 12-week course of treatment with prazosin or placebo in a double-blind parallel group trial. Prazosin was administered orally in doses of 0.5 mg and then 1 mg twice daily for 4 days each and 2 mg twice daily for the remainder of the trial. Patients on treatment with prazosin had an increased urinary flow rate as compared to placebo with a significant reduction in maximum voiding detrusor pressure and maximum detrusor pressure at peak urinary flow. Although a significant effect on frequency was not demonstrated, standard parameters of detrusor instability were reduced. Investigators' double-blind overall assessment of efficacy significantly favoured the prazosin treatment. Twelve patients were excluded from the final analysis, 8 being withdrawn because of adverse effects, 5 on treatment with prazosin and 3 in the placebo group. Oral prazosin appears to be safe and effective in the long-term treatment of patients with benign prostatic hyperplasia.

Steroid 5 alpha-reductase deficiency and posterior urethral valves.

Posterior urethral valves were seen in a 2-year-old boy who also had steroid 5 alpha-reductase deficiency. This combination has not been reported before and has relevance for the physiology of sexual differentiation.