In a review of 1057 consecutive prostatectomies of which 95% were performed transurethrally, carcinoma was present in 11.8%. There were 10 deaths within a month of operation (0.9%), 9 of these patients having been exceptionally old and unfit. The rate of complications and the end results appear to justify using transurethral resection as the method of choice for prostatectomy whenever it is feasible.

Objective To investigate the effect of superoxide dismutase (SOD, the enzyme that accelerates the breakdown of the superoxide anion, O 2 ± to H 2 O) on nitric oxide (NO)-mediated and electrical ®eld stimulated (EFS) relaxation in diabetic rabbit cavernosal smooth muscle. Materials and methods Diabetes was induced with alloxan (65 mg/kg) in six adult New Zealand White rabbits. After 6 months, cavernosal smooth muscle strips from age-matched controls and diabetic animals were mounted in organ baths. After precontraction with phenylephrine (10 mmol/L) in the presence of atropine (1 mmol/L), guanethidine (5 mmol/L) and indomethacin (10 mmol/L), relaxation responses to EFS (1±20 Hz), carbachol (10 x8 x10 x4 mol/L) and sodium nitroprusside (SNP, 10 x9 x10 x4 mol/L) were assessed in the presence and absence of SOD (100 IU/ mL). Results SNP-and carbachol-mediated (endotheliumindependent and -dependent, respectively) relaxations were impaired in the diabetic cavernosal smooth muscle strips compared with controls (concentration required for 50% inhibition, 1.4 mmol/L for diabetic and 0.75 mmol/L for control with SNP, and 44 mmol/L for diabetic and 0.4 mmol/L for control with carbachol). SOD signi®cantly enhanced both SNP-and carbachol-mediated diabetic cavernosal smooth muscle relaxations (both P<0.05). EFS-mediated relaxations were also signi®cantly (P<0.05) impaired in the diabetic cavernosal smooth muscle strips; these relaxations were also signi®cantly (P<0.05) enhanced by SOD. Conclusion NO-and EFS-mediated cavernosal smooth muscle relaxation is impaired in a rabbit model of diabetes but SOD signi®cantly reversed the impaired relaxation. Therefore, in diabetes, the generation of reactive oxygen species may play an important role in the development of erectile dysfunction.

Previous reports have shown that Her-2/neu oncogene expression in human breast cancer and ovarian cancer may be associated with poorer prognosis. We report the expression of Her-2/neu on fresh samples of known prostatic adenocarcinoma but not on those of benign prostatic hypertrophy. Using a monoclonal antibody (TA1) directed against human Her-2/neu oncogene product and an immunohistochemical staining method, no Her-2/neu expression was noted with benign prostatic hypertrophy (15 samples). With prostatic adenocarcinoma samples, a subset (9 of 25) showed overexpression of Her-2/neu. Such overexpression is correlated with higher histological grade, higher stage of disease, and high S phase and aneuploidy on flow cytometric analysis. These findings suggest that Her-2/neu may be a prognostic marker in prostate cancer as well.

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NO is neither pre-stored nor packed in vesicles but is produced on demand. It then diffuses randomly from its site of production, being highly membrane-permeable. Endogenous NO is formed by the hydroxylation of Larginine to citrulline [14], a reaction catalysed by one of the three isoforms of NO synthase (NOS) [15]. Because NO has a short half-life (0.1±6 s) and is very reactive, NO physiology has largely been investigated indirectly by techniques that identify the distribution and activity of the NOS isoforms (Table 1). These distinct isoforms of NOS have been named after the cells in which they were ®rst isolated, puri®ed and cloned [15]. Each NOS isoform, i.e. endothelial (eNOS), neuronal (nNOS) and macrophage inducible (iNOS), varies considerably in subcellular location, structure, kinetics, regulation and function [15]. Each of the enzymes is a product of a unique gene, located on human chromosomes 7 (eNOS), 12 (nNOS) and 17 (iNOS) [15]. Both nNOS and eNOS are normal constituents of cells and are termed constitutive. The activity of both eNOS and nNOS is transient (minutes) and is triggered by Ca 2+ -elevating agonists [16]. In contrast, iNOS is not present in resting

SUMMARY The effects of cytotoxic therapy on the structure and function of the proximal jejunum were studied in six patients receiving intravenous cyclophosphamide (300 mg/M2), methotrexate (40 mg/M2), and 5-fluorouracil (600 mg/M2) as adjuvant therapy for breast cancer. Using a steady state, triple lumen tube perfusion system the absorption of water and electrolytes was measured before and 48 h after administration of the cytotoxic agents. Jejunal biopsies were obtained at each perfusion. Median (range) water absorption fell from 126 (40-142) to 84 (46-142) ml/h/30 cm, with parallel changes for electrolytes; none of the changes was significant. Brush border disaccharidases did not change at 48 h after chemotherapy, while mature enterocytes appeared normal by both light and electron microscopy. Crypt cells and immature enterocytes, however, showed focal vacuolation by light microscopy, corresponding to the occurrence of large residual bodies (secondary lysosomes) containing partially degraded fragments of damaged crypt cells. The confinement of ultrastructural changes to the immature cell population may explain the failure of this study to show a consistent change in the absorptive function of the jejunum 48 h after chemotherapy.Cytotoxic therapy can cause structural and functional changes in the human proximal intestine. '-3 This effect may be important in the development of gastrointestinal symptoms such as diarrhoea and may lead to malabsorption of orally administered drugs, including cytotoxic agents.4 5 Smith et a!6 could find no change in xylose absorption and faecal fat estimation in patients with biopsy proved depression of crypt cell mitosis, but most previous studies of cytotoxic damage have examined changes of gastrointestinal function and structure independently.The technique of small intestinal perfusion is a sensitive method for detecting changes in the transport of water and electrolytes across the jejunal mucosa and might therefore show relatively minor abnormalities of enterocyte function more readily than conventional intestinal absorption tests.7 We have used small intestinal perfusion to investigate IPresent address:

Bladder outlet obstruction (BOO) is a common disorder that is associated with urinary tract symptoms. Nitric oxide (NO), synthesized by NO synthase (NOS) is a potent vasodilator that is present throughout the urinary tract and the corpus cavernosum. Endothelin-1 (ET-1) conversely is a potent vasoconstrictor peptide that is similarly distributed throughout the urinary tract. ET-1 and NO as well as possessing opposing actions regulate each other's synthesis. The disruption of the balance between ET-1 and NO is associated with various vascular pathologies. However, their potential roles in the pathogenesis of urinary tract disorders, secondary to BOO, is not well established. New Zealand White rabbits with BOO are considered to be a suitable model of the human condition. Hence, using this model, we systematically investigated the potential roles of ET-1 and NO in the pathogenesis of the various urological disorders associated with BOO. In this review we discuss the results of our studies, which support the concept that an imbalance between ET-1 and NO may be associated with the pathogenesis of urinary tract disorders secondary to BOO. We also discuss the potential clinical implications of this association. This review is based on the Bard Silver Medal Lecture given (by MAK) at the 2002 British Association of Urological Surgeons (BAUS) annual meeting.