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Summary In 130 consecutive patients treated by renal transplantation in the years 1961 to 1972 there were 9 patients who developed a vesical fistula, 4 developed a ureteric fistula and 3 a calyceal fistula (1 patient had both a ureteric and calyceal fistula). Continuous bladder drainage by an indwelling urethral catheter is recommended for the treatment of a vesical fistula. The treatment of a ureteric fistula may be difficult and a temporary uretero-ileostomy may be of value. Provided that distal obstruction is excluded, omentopexy is valuable for treating a calyceal fistula. Immunosuppressive drug therapy may have to be withdrawn but this is not always followed by rejection of the transplanted kidney.

SUMMARY Experimental studies of renal blood flow have been made with radio-Hippuran I125using isolated perfused canine kidneys. These studies were made in two groups. First, the renogram curve was analysed by applying theoretical equations and it was shown that quantitative values could be obtained for the effective renal blood flow. In the second group of experiments the analysis of the rate of disappearance of the isotope from the blood showed a definite relationship with directly measured renal blood flow, but this could not be resolved into a quantitative value. The authors' thanks are due to Professor Ralph Shackman for his encouragement and guidance in this work, to Mr E. Gains and his technical staff for their help, to the Department of Photography and Medical Illustration of the Post-graduate School for their assistance in drawing of the charts, and to Mr Ole Kalnaes, Radiofysisk laboratorium, Arhus Kommunehospital, for his help with mathematical equations. The expenses incurred in these experiments were defrayed by a grant to one of us (A. E. K.) from the Medical Research Council.

SUMMARY AND CONCLUSIONS A retrospective study of 61 adult patients with primary reflux is reported. The presentation, clinical findings, investigations, treatment and follow up are discussed and the following conclusions have been made. 1 Primary reflux probably occurs more often in adult life than has been previously suggested. 2 Primary reflux in adults occurs more often in women than in men. 3 The diagnosis is made mainly in the third and fourth decades. 4 The onset of symptoms is commonly 10 to 20 years before the diagnosis. 5 A urinary infection or a history of infection is almost always present. 6 The pathology of reflux in adults is similar to the pathology in children. 7 The occurrence of this condition in adult life may be explained either as a recurrence of reflux or that a normal or only marginally competent valve becomes incompetent due to infection. 8 At the time of diagnosis more than one third of the kidneys showed no function on i.v.p. Ureteronephrectomy was the usual treatment in these cases. If nephrectomy only is done reflux into the ureteric stump will persist and may be associated with recurrent infection. 9 Most of the patients were treated successfully by conservative methods; the results from treating a small group by antireflux procedures was inconclusive. 10 Reflux will be diagnosed more often only if micturating cystography is performed more frequently. Patients with pyelonephritis, small or contracted kidneys, malformations, and recurrent urinary infections and bladder symptoms are recommended for this investigation.

The outcome of conservative management in a consecutive series of 107 localized prostate cancers (mean age 73.5 years) has been analyzed. Follow-up ranged from 1 to 12 years. Following regular surveillance and no initial treatment, 3 died from prostate cancer with a median survival of 6.3 years compared to 34 who died from intercurrent disease with a median survival of only 2.6 years. The observed survival for the whole group was similar to the expected survival for an age-matched population in Scotland. This was despite the fact that the nodal status and the capsular invasion were unknown.

Controversy regarding the relative efficacy of treatments for the relief of the symptoms of benign prostatic hyperplasia (BPH).This was a 6-month double-blind randomized equivalence study that compared the effects of a plant extract (320 mg Permixon) with those of a 5 alpha-reductase inhibitor (5 mg finasteride) in 1,098 men with moderate BPH using the International Prostate Symptom Score (IPSS) as the primary end-point.Both Permixon and finasteride decreased the IPSS (-37% and -39%, respectively), improved quality of life (by 38 and 41%), and increased peak urinary flow rate (+25% and +30%, P = 0.035), with no statistical difference in the percent of responders with a 3 ml/sec improvement. Finasteride markedly decreased prostate volume (-18%) and serum PSA levels (-41%); Permixon improved symptoms with little effect on volume (-6%) and no change in PSA levels. Permixon fared better than finasteride in a sexual function questionnaire and gave rise to less complaints of decreased libido and impotence.Both treatments relieve the symptoms of BPH in about two-thirds of patients but, unlike finasteride, Permixon has little effect on so-called androgen-dependent parameters. This suggests that other pathways might also be involved in the symptomatology of BPH.

To determine whether BCG therapy could upregulate interleukin-6 (IL-6) production in human transitional cell carcinomas (TCC).Immunohistochemistry of tumor biopsies and urinary cytospins and ELISA studies of urine from bladder cancer patients and TCC cell-line supernatants, before and after exposure to BCG, were performed.Constitutive staining for IL-6 was found in the majority of bladder tumors. Interleukin-6 was detected in the urine of all 13 patients with carcinoma in situ and increased 5-fold during BCG therapy. Levels were variable but were greater in nonresponders (p0.01). During therapy both detached bladder urothelial cells and polymorphonuclear leukocytes stained for IL-6. Production of IL-6 increased in only 3 cell lines after exposure to BCG, but all 7 cell lines showed increases after exposure to interferon-gamma (p = 0.015). Grade 3 cell lines showed much greater upregulation than grade 1 and 2 cell lines.The increase in IL-6 during BCG therapy may be caused by urothelial cells as well as leukocytes. The higher levels seen in nonresponders may be due to either higher grade or persisting tumor.

The prostate gland has attracted a remarkable increase in interest in the past few years. The two most common diseases of this gland, benign prostatic hyperplasia and carcinoma of the prostate, have been brought into greater prominence by new diagnostic methods, public interest, and a wider choice of surgical and non-surgical treatments. Uncertainty about the significance of these changes has occurred because of the rapidity of change, the profusion of statements, opinions and promotions, and the relatively little guidance available from the profession. Ten urologists and two general practitioners have reviewed the relevant evidence about these two prostate diseases and the newer diagnostic methods; their conclusions are summarised here. Management options and guidance on clinical practice are also discussed. Because of a number of unresolved diagnostic and management issues, detailed requirements for practice guidelines have not been specified.

The emergence of alternatives in the surgical treatment of benign prostatic hyperplasia (BPH) over time may be examined during five periods. The rapidity of these developments has been exponential.

The TNM working group acknowledges the multinational agreement reached in the 1992 TNM classification, but nevertheless gives some suggestions for modifications. The main interest of the group has been to evaluate parameters suitable for further ramification of the system. The group found that parameters such as DNA ploidy, PSA, nuclear roundness factor, are not yet ready for this purpose. Grade is an established parameter and should be incorporated into the TNM-categories of localized disease. In metastatic disease a number of parameters are available to subdivide this category according to prognosis, and these will be more uniformly and extensively studied in the several large trials that are now in progress.

The prognosis of bladder cancer is worsened by delay in its management. To reduce such delay we have organised a clinic where intravenous urography and cystoscopy, using a flexible cystoscope, are carried out at the patient's first visit. In a two-year period 321 patients attended this clinic. The results of investigation in 305 patients are reported. A total of 6% of patients with microscopic haematuria (n = 52) and 15% of patients with macroscopic haematuria (n = 253) had transitional cell carcinomata. This difference was not significant (P = 0.08, chi-squared). The delay between referral and trans-urethral resection of tumour for patients with bladder tumours was reduced from a mean of 60 days to a mean of 33 days by the institution of the clinic (P0.01, Mann-Whitney). We recommend that all patients referred to a urological service with haematuria, whether macroscopic or microscopic, should be investigated. The integration of that investigation in a single day decreases delays in diagnosis and management.

Die Verabreichung des Impfstoffs Bacille-Calmette-Guerin (BCG) fuhrt zu einer Stimulation des Immunsystems (Davies 1982); doch stellt sich die Frage, ob die vorteilhafte antitumorale Wirkung der intravesikalen BCG-Behandlung immunologischer Art ist und welche Immunmechanismen an dieser Reaktion beteiligt sind. Dies kann zur Losung praktischer Probleme wie der Wahl des optimalen Behandlungsverlaufs und Indikation zur Fortfuhrung der Therapie beitragen.

The management of invasive bladder cancer in Edinburgh, as in many other centres in the UK, has been by radical radiotherapy, with cystectomy reserved for local treatment failure or relapse. A review of the results of this policy in 1987 highlighted what was felt to be an unacceptably severe morbidity rate of 15%. The dose of radiation was therefore reduced from 55 Gy in 20 daily fractions to 52.5 Gy. Forty of 80 patients (50%) treated in this way have achieved a complete response at 6 months which is a similar response rate to that in previous reports. In addition, ten of 23 frail or elderly patients (43%) achieved a complete response with a lower dose of 50 Gy given as a split course over 7 weeks. Eighteen patients have had a salvage cystectomy, and 12 of 18 (67%) are alive and disease-free. Although follow-up is short, to date toxicity has been reduced, and our results support our decision to reduce the radiation dose.

One hundred and thirteen patients with genuine stress incontinence were treated by a modified Burch Colposuspension after having failed an adequate trial with medical management. Three-quarters of patients were evaluated with pre-operative video-cystometry (video-C.M.G.) while a third underwent post-operative video-cystometry. Flow rates were generally lower after surgery with 3 of the 113 patients developing post-surgery bladder instability. Previous incontinence surgery and higher parity produced statistically a greater number of failures. The overall subjective success of the operation was 80% with another 12% improved at 2 years. A 5 year long-term questionnaire follow-up did not demonstrate marked changes in these figures. The operation itself carries a 16% incidence of significant early complications, while late complications totalled 23%, the latter being primarily minor conditions. Patients left hospital after an average of 10 days.

Techniques of prostatic lymphoscintigraphy using 99mTc phytate (TP) and 99mTc antimony sulphide colloid (ASC) have been evaluated in 30 patients. The most successful technique was a superficial perianal injection of ASC. In general, definition of the regional lymph nodes lacked the precision and clarity that would be required for the technique to be used in staging of prostatic or other pelvic tumours; further development of the technique is recommended.

Phaeochromocytomas of the bladder are rare, only about 100 cases having been reported previously. Four adults with these lesions have been managed at Hammersmith Hospital in the past 10 years. Three patients had hypertension, together with syncopal attacks and/or headaches, induced by micturition. The fourth patient presented with haematuria. After control of blood pressure and localization of the tumours by various combinations of cystoscopy, intravenous urography, venous sampling, ultrasound, angiography and computerized coaxial tomography (CT scanning), 3 patients underwent partial cystectomy, and the fourth pelvic exenteration. Two patients were apparently cured of the disease, but 2 were not. One developed nodal metastases and recurrence of hypertension after 18 months and one rapidly developed metastases in the lungs and elsewhere. Effective therapy probably requires a high index of suspicion in diagnosing the condition and possibly an aggressive surgical and radiotherapeutic policy.

Fifty-four patients on haemodialysis for chronic renal failure underwent renal transplantation. Basal and maximum acid output and the incidence of peptic ulcer before transplantation were not significantly different from those of controls. But after renal transplantation the incidence of symptoms of peptic ulcer was high (22%) and four out of six patients who developed gastrointestinal bleeding died from this complication. In men peak acid output was significantly increased after renal transplantation and was associated with a 30% incidence of symptoms of peptic ulcer compared with 10% in women, who showed no significant change in mean basal or peak acid output. Peptic ulceration after transplantation was not associated with steroid dosage, hyperparathyroidism, or the height of blood urea concentrations. Given criteria of a history of dyspepsia, abnormal barium meal findings, or gastric hypersecretion, it was not possible to identify patients at risk from peptic ulceration or life-threatening complications after renal transplantation. Thus the routine screening of these patients for peptic ulcer has no practical value, and the incidence of fatal complications is not high enough to justify routine prophylactic anti-ulcer surgery aimed at reducing acid secretion before renal transplantation.

In a series of 120 patients with renal stones 60% were found to have a treatable metabolic abnormality. Idiopathic hypercalciuria and the incomplete form of renal tubular acidosis were the two most common abnormalities. Both conditions in the untreated form were associated with an unacceptably high stone recurrence rate and incidence of change. In view of this, follow-up is considered essential and if medical treatment is to be offered this should be in the form of a controlled clinical trial.

Serum 5α-dihydrotestosterone (DHT) and testosterone (T) were measured in 98 normal adult men aged between 20–80 years, separating T and DHT by thin layer chromatography and using a sensitive and reliable radioimmunoassay. In three age groups between 20–40, 40–60 and 60–80, the means ± sem for serum DHT were 84 ± 4, 79 ± 3 and 67 ± 3 (ng/100 ml) respectively. The corresponding values for testosterone were 559 ± 25, 491 ± 25 and 475 ± 28 (ng/100 ml). A significant decrease was observed in the DHT level of the 60–80 years age group compared to either the 20–40 (P < 0.01) or the 40–60 (P < 0.02) age groups. There was a moderate decline in the testosterone level of the 60–80 years age group compared to 20–40 years (P < 0.05) but there were no significant changes in the testosterone levels between other groups.

The uptake of 125I-labelled human prolactin by subcellular fractions obtained from the human hyperplastic prostate was investigated and the specific binding sites were characterized. The binding was both time- and temperature-dependent with maximum specific uptake achieved after incubation for 20 h at 4°C (dissociation constant = 2·4 × 10−10 mol/l). The present studies also indicate that the bulk of the specific prolactin binding was confined to the 105 000 and 15 000g membrane fractions whilst the cytosol and nuclear pellet exhibited a lower capacity for the peptide hormone. Attempts to optimize the binding revealed that pretreatment of the subcellular fractions with 4 mol MgCl2/l quadrupled the binding sites; a similar effect was produced after pretreatment with dextran-coated charcoal, but the changes were less pronounced. Furthermore, our studies suggest that the binding was specific for the human prolactin, with other hormones such as ovine prolactin, human LH, human FSH and human GH showing little or no competition. The addition of magnesium and copper ions to the incubation medium also markedly increased the specific binding, whereas calcium, manganese and EDTA inhibited the prolactin uptake. Freezing and storage of tissue at −70 °C did not greatly affect the binding sites. The results suggest that we are clearly dealing with a specific prolactin-binding protein.

The criteria for the diagnosis of progression of prostatic cancer after primary treatment by androgen suppression (oestrogen escape) were studied in 30 patients. Objective criteria are essential for this diagnosis and in this study the bone scan was the most useful criterion. Twenty-one of these patients had a secondary orchiectomy: one patient showed a partial objective response and 3 had a subjective response. It is concluded that an orchiectomy following failed primary oestrogen therapy is an ineffective procedure and therefore unjustifiable and that alternative treatments must continue to be evaluated.

The prostate of the rhesus monkey (Mucacca mulatta) consists of a cranial and a caudal lobe. The uptake of [3H] testosterone by these 2 lobes has been measured and compared with control tissues. A significantly higher uptake of radioactivity was found in the caudal lobe when compared to cranial as well as other control tissues. The uptake of radioactivity by the caudal and cranial lobes was suppressed when unlabelled testosterone was introduced into the incubation media. The relationship between these 2 lobes of the monkey prostate and the central and peripheral zones of the human prostate is described.

A double antibody, semi-automated radioimmunoassay for serum prostatic acid phosphatase (PAP) is described, which uses the 125I-labelled N-succinimidyl-3-(4-hydroxyphenyl) propionate ester of PAP. This type of label has substantially higher immunoreactivity than that prepared using the chloramine-T method of radioiodination. Chromatographic purification of either label on Ultrogel ACA44 further improved immunoreactivity. The lowest detection limit (0·35 μg/l) was achieved with the chromatographically purified ester label.

The interaction between prolactin and zinc was examined in vitro in the human prostate gland. The results indicated that prolactin did not modulate the acute uptake of zinc into benign prostatic hypertrophy tissue whereas zinc, in contrast, increased the uptake of prolactin into the prostate gland. Our study further showed that the augmented uptake of prolactin by zinc was partly due to an increase in the non-specific binding properties of the peptide hormone. We were also able to demonstrate that the specific binding of 125I-labelled human prolactin to the receptor was reduced in the presence of zinc by a competitive mechanism. J. Endocr. (1984) 102, 73–76

We have compared the staging of renal carcinomas in 36 patients as judged preoperatively by angiography (T stage) and postoperatively by histopathology (P stage). Using the standard abdominal aortogram and selective renal arteriogram we found a considerable error rate in T staging (40%). The commonest error was preoperative overstaging, and this is probably determined by the behaviour of renal carcinoma, rather than by inadequate angiography. We conclude that whilst renal arteriography remains a useful diagnostic aid, it cannot answer questions on tumour extent with any accuracy. Staging by histopathology is essential for proper assessment and management of these patients.

Established urodynamic and electrophysiological techniques have been applied to assess the frequency and extent of autonomic and peripheral neuropathy in 60 subjects with diabetes mellitus; 38 were diabetics with suggestive symptoms and the others were representative newly diagnosed (11) or treated (11) diabetics. Objective evidence of neuropathic bladder dysfunction was detected in 43 of them (71.7%). The commonest abnormality was a hypotonic, insensitive large capacity bladder, which condition was usually asymptomatic. Less frequently (15%) this was complicated by bladder decompensation and sphincter involvement, resulting in excessive residual urine and infection; some of these had bladder paralysis with chronic painless retention of urine (7%). Electrophysiological studies found a sensory defect in the lower limbs in all tested patients (100%), and in 41 patients (69%) an associated motor conduction abnormality, which was more frequent and marked in the lower than the upper limb. These functional abnormalities appeared to be related to the severity of diabetes, but less to its duration. Indeed of 11 newly diagnosed diabetics tested 7 had a peripheral neuropathy and 4 urodynamic abnormalities. The high incidence of bladder dysfunction and peripheral neuropathy in this series indicates the frequency of subclinical diabetic neuropathy and a factor needing more emphasis in diabetic uropathy.

30 patients with oestrogen-escaped carcinoma of the prostate have been treated with estramustine phosphate (Estracyt). 27% showed a partial objective response and 33% had a subjective response. The terms used for defining a response are challenged and it is recommended that comparative controlled trials are necessary to judge the place of this drug in the management of advanced prostatic cancer.

Summary The incidence of urinary infection before and after operation for benign prostatic hypertrophy has been reviewed in 140 patients. Repeated screening for bacteriuria was used throughout the hospital admission. Infection was present in 24% before operation and there was a significant correlation between the incidence of infection and the duration of preoperative catheterisation. Postoperative infection developed in 31 % and there was no relation between this incidence and the type of prostatectomy; specific antibacterial therapy was significantly more effective in eradicating urinary infection acquired after operation than before. At the time of discharge from the ward, 10% had infected urine, but only 3% of patients had persistent infection at follow-up 6 weeks after operation.

Summary The female of the species Praomys (Mastomys) Natalensis has a ventral prostate similar both in position and in histological appearance to the ventral lobe of the male prostate. The hormonal uptake of this female prostate has been investigated using [3H] testosterone and [3H] oestradiol. The results showed that the uptake of these steroid hormones by the prostate was identical to our findings in the male prostate. The potential value of a female prostate in prostatic research is discussed.

The effects of 4 antiandrogens and stilboestrol on the cytosol receptor of the rat ventral prostate have been compared. Equimolar doses of cyproterone acetate, chlormadinone acetate, SC 9022 and flutamide inhibited the binding of dihydrotestosterone to the receptor complex in vivo by 44 to 50% whereas stilboestrol had no effect. In the in vitro studies an equimolar concentration produced similar effects to those observed in vivo with the exception of flutamide which had no effect. This technique provides a method for assessing and comparing the effectiveness of antiandrogens on the androgen receptor complex of the prostate.

The reduced and oxidized metabolites of testosterone and dihydrotestosterone were measured in the stromal and epithelial components of 23 human hyperplastic prostates. Our studies indicate differences in the hormonal metabolic patterns of the stroma and epithelium of the resected specimens when compared with tissues obtained retropubically. Testosterone 5 alpha-reductase was evenly distributed between the two components of the specimens obtained retropubically whereas the 3 alpha (beta)-hydroxysteroid dehydrogenase was predominantly located in the stroma. The measurements on the resected specimens suggest, on the other hand, that the bulk of the 5 alpha reductase and 3 alpha (beta)-hydroxysteroid dehydrogenase activities were confined to the stroma although these activities were considerably lower than those measured in the corresponding components of the retropublically obtained specimens. The conversion of testosterone to androstenedione was negligible in all the samples analysed. We therefore conclude that the stroma is the main site for the transformation of dihydrotestosterone to the androstanediol epimers and that the asymmetric distribution of the 3 alpha (beta)-hydroxysteroid dehydrogenase may be instrumental in the development of hyperplasia in the prostate gland. Furthermore, the results of this study indicate that electroresection impairs the enzymatic activities of the tissue.

Serum dihydrotestosterone (DHT) and testosterone were measured by radioimmunoassay in 24 normal men aged 60 to 80 years and in 25 patients with benign prostatic hypertrophy in the same age range. There was a significant increase in the level of dihydrotestosterone in patients with prostatic hypertrophy but no significant difference was found between the testosterone levels of the 2 groups. The scatter of the individual values for DHT indicated that this measurement has little practical clinical application in the diagnosis of prostatic hypertrophy. It is suggested that the increase in DHT may be due, at least in part, to a prostatic contribution to the circulating level and the relevance of this observation in relation to the aetiology of benign prostatic hypertrophy is discussed.

The inhibitory effects of stilboestrol and representatives from three main classes of antiandrogens on the dihydrotestosterone receptor complex isolated from the nuclei of rat ventral prostate were compared. After labelling of the tissue in vivo or in vitro with [ 3 H]testosterone in the presence or absence of test drugs, the nuclear extracts were prepared and the inhibitory effect on the steroid-receptor complex was evaluated. Equimolar doses (1 μmol/100 g body weight) of cyproterone acetate, chlormadinone acetate, SC 9022 and flutamide inhibited the binding of dihydrotestosterone to the receptor complex by 48–54%, whereas in the in vitro studies an equimolar concentration (0.1 μM) inhibited the binding by 45–58% with the exception of flutamide which had no effect. Under these experimental conditions stilboestrol had no effect on the binding of dihydrotestosterone to the nuclear receptor.

The distribution of two aminoglycosides and three penicillins was studied in dogs. Serial samples of interstitial tissue fluid were obtained from subcutaneous silicone rubber capsules and compared with simultaneous serum samples. The results showed the reproducibility of the method both between animals and between experiments. Tobramycin showed a trend to higher serum and tissue fluid concentrations compared to gentamicin but these differences were not statistically significant. The striking differences between the tissue fluid concentrations of ampicillin and cloxacillin were related to the high protein binding of the latter. It is concluded that an adequate tissue fluid concentration requires an adequately maintained serum concentration; drugs that are rapidly excreted and especially those that are highly protein bound, should be given in doses sufficient to produce such a serum concentration.