The effect of pelvic floor muscle training on sexual function in men with lower urinary tract symptoms after stroke.

BACKGROUND: Erectile dysfunction and lower urinary tract symptoms (LUTS) are common sequelae in men after stroke. OBJECTIVE: The objective of this study was to evaluate the effect of pelvic floor muscle training (PFMT) on measured erectile function as an indicator of sexuality in men with LUTS after stroke. METHOD: A sample of 516 men with stroke was invited to participate in this single-blinded, randomized controlled trial according to in- and exclusion criteria. This resulted in 31 participants who were randomized to either a Treatment Group (n = 16) or a Control Group (n = 15). The intervention included 12♣weeks of PFMT. The effect was measured on the International Index of Erectile Function (IIEF-5) questionnaire. RESULTS: Thirty participants (median age: 68 years; interquartile range: 60-74 years) completed the study, 15 in each group. The results of the IIEF-5 sum score showed a significant improvement (P < 0.04) from pre-test to post-test in the Treatment Group, but not in the Control Group. Within pre-test and 6-month follow-up, the median sum score decreased in both groups, worsened in the Control Group [Treatment Group, 3 (17%) versus Control Group, 5 (31%)]. There were differences between the groups at post-test and at follow-up, but they were not statistically significant. CONCLUSION: The results showed that, as measured by erectile function in men with LUTS after stroke, PFMT may have short-term and long-term effect, although no statistically significant effect was demonstrated between the groups.

Conservative treatment for urinary incontinence in Men After Prostate Surgery (MAPS): two parallel randomised controlled trials.

OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of active conservative treatment, compared with standard management, in regaining urinary continence at 12 months in men with urinary incontinence at 6 weeks after a radical prostatectomy or a transurethral resection of the prostate (TURP). BACKGROUND: Urinary incontinence after radical prostate surgery is common immediately after surgery, although the chance of incontinence is less after TURP than following radical prostatectomy. DESIGN: Two multicentre, UK, parallel randomised controlled trials (RCTs) comparing active conservative treatment [pelvic floor muscle training (PFMT) delivered by a specialist continence physiotherapist or a specialist continence nurse] with standard management in men after radial prostatectomy and TURP. SETTING: Men having prostate surgery were identified in 34 centres across the UK. If they had urinary incontinence, they were invited to enroll in the RCT. PARTICIPANTS: Men with urinary incontinence at 6 weeks after prostate surgery were eligible to be randomised if they consented and were able to comply with the intervention. INTERVENTIONS: Eligible men were randomised to attend four sessions with a therapist over a 3-month period. The therapists provided standardised PFMT and bladder training for male urinary incontinence and erectile dysfunction. The control group continued with standard management. MAIN OUTCOME MEASURES: The primary outcome of clinical effectiveness was urinary incontinence at 12 months after randomisation, and the primary measure of cost-effectiveness was incremental cost per quality-adjusted life-year (QALY). Outcome data were collected by postal questionnaires at 3, 6, 9 and 12 months. RESULTS: Within the radical group (n = 411), 92% of the men in the intervention group attended at least one therapy visit and were more likely than those in the control group to be carrying out any PFMT at 12 months {adjusted risk ratio (RR) 1.30 [95% confidence interval (CI) 1.09 to 1.53]}. The absolute risk difference in urinary incontinence rates at 12 months between the intervention (75.5%) and control (77.4%) groups was -1.9% (95% CI -10% to 6%). NHS costs were higher in the intervention group [£ 181.02 (95% CI £ 107 to £ 255)] but there was no evidence of a difference in societal costs, and QALYs were virtually identical for both groups. Within the TURP group (n = 442), over 85% of men in the intervention group attended at least one therapy visit and were more likely to be carrying out any PFMT at 12 months after randomisation [adjusted RR 3.20 (95% CI 2.37 to 4.32)]. The absolute risk difference in urinary incontinence rates at 12 months between the intervention (64.9%) and control (61.5%) groups for the unadjusted intention-to-treat analysis was 3.4% (95% CI -6% to 13%). NHS costs [£ 209 (95% CI £ 147 to £ 271)] and societal costs [£ 420 (95% CI £ 54 to £ 785)] were statistically significantly higher in the intervention group but QALYs were virtually identical. CONCLUSIONS: The provision of one-to-one conservative physical therapy for men with urinary incontinence after prostate surgery is unlikely to be effective or cost-effective compared with standard care that includes the provision of information about conducting PFMT. Future work should include research into the value of different surgical options in controlling urinary incontinence.

Anxiolytic properties of the selective, non-peptidergic CRF(1) antagonists, CP154,526 and DMP695: a comparison to other classes of anxiolytic agent.

The selective, non-peptidergic corticotropin-releasing factor (CRF)(1) receptor antagonists, CP154,526 and DMP695, dose-dependently increased punished responses of rats in a Vogel conflict test and enhanced social interaction (SI) of rats in an unfamiliar environment. They were, however, inactive in a plus-maze procedure and failed to reduce ultrasonic vocalizations (USV) associated with an aversive environment. In contrast, the benzodiazepine, chlordiazepoxide, was effective in all these procedures. Further, the serotonin (5-HT)(1A) agonist, flesinoxan, was active in each paradigm (except the plus-maze) while the 5-HT(2C) antagonist, SB242,084, was effective in the SI and Vogel but not the plus-maze and USV procedures. In contrast to chlordiazepoxide, flesinoxan and SB242,084, CP154,526 did not modify dialysate levels of 5-HT, norepinephrine (NE) and dopamine (DA) in the frontal cortex (FCX) of freely moving rats. In conclusion, CP154,526 and DMP695 possess a common and distinctive profile of anxiolytic action expressed in the absence of an intrinsic influence upon monoamine release.

Protective effect of the antioxidant 6-ethoxy-2,2-pentamethylen-1,2-dihydroquinoline (S 33113) in models of cerebral neurodegeneration.

In a previous study Dorey et al. [Bio. Org. Chem. Lett., 10 (2000) 935] a series of novel dihydroquinoline compounds were developed, based on the potent antioxidant 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline (ethoxyquin), and permitted the selection of the analogue 6-ethoxy-2,2-pentamethylen-1,2-dihydroquinoline (S 33113) lacking the hypothermic effects associated with ethoxyquin at equivalent doses. Herein, an extensive investigation of the neuroprotective capacity of S 33113 in different in vitro and in vivo paradigms of oxidative stress-mediated cellular degeneration was undertaken. In vitro S 33113 was a potent inhibitor (IC(50) = 0.29 microM) of Fenton-reaction-induced lipid peroxidation in mouse cortical membranes. Administration of S 33113 either intraperitoneally (< or =150 mg/kg i.p.) or orally (< or =600 mg/kg p.o.) did not significantly modify body temperature in NMRI mice. Furthermore, S 33113 (150 mg/kg i.p. or 600 mg/kg p.o.) markedly reduced the lethality induced by an intracerebroventricular injection of t-butylhydroperoxide in NMRI (naval medical research institute) mice for up to 5 h. Oral administration of S 33113, significantly attenuated alloxan-mediated hyperglycaemia in NMRI mice at 400 and 600 mg/kg (60%; P < 0.001). Administration of S 33113 (150 mg/kg i.p.) 30 min before transient global ischaemia significantly prevented delayed neuronal cell death in the CA1 region of the rat hippocampal formation, 7 days post-ischaemia (33% cell loss vs. 88% in ischaemia controls; P < 0.001). Similarly, a single pre-administration of S 33113 (150 mg/kg i.p.) prevented kainic acid-induced cell death in the CA3 hippocampal region at 7 days post-exposure (17% cell loss vs. 52% in kainate-treated controls; P < 0.01). Furthermore, D-methamphetamine-mediated dopamine depletion in the striatum of C57BL/6 mice (39-46%) was significantly prevented with S 33113 administered at either (2 x 150mg/kg i.p.) (11%; P < 0.01) or (2x150 mg/kg p.o.) (17%; P < 0.001). In conclusion, S 33113 represents a novel dihydroquinoline compound with potential for the treatment of cerebral pathologies implicating chronic neurodegeneration.

Partners' perspective of erectile dysfunction: literature review.

Erectile dysfunction is a problem which men may or may not share with their partners for a variety of reasons. This literature review of 26 articles revealed the partners' perspective of men with erectile dysfunction. Partners fell into four groups: supportive partner/acceptable to patient (the optimum category); supportive partner/unacceptable to patient; non-supportive partner/acceptable to patient; and non-supportive partner/unacceptable to patient. With comprehensive education and counselling by urology nurses, the couples could move into the optimal category. There is increasing recognition that the partner should be involved in the assessment, diagnosis, patient education, counselling and choice of treatment for long-term treatment to be successful, unless the informed patient is unwilling.

Is smoking a cause of erectile dysfunction? A literature review.

Erectile dysfunction is common, and its prevalence increases with age owing to age-related diseases of vascular, hormonal, neurogenic and psychogenic factors. A literature review was undertaken to explore the impact of smoking on erectile dysfunction. The literature review of 18 studies revealed the detrimental effect of smoking on erectile function. Smokers were 1.5 times more likely to suffer erectile dysfunction than non-smokers. Men may be unaware of the effect of tobacco on erectile function. This literature review presents strong reasons for stopping smoking, and highlights the need for education within a comprehensive smoking cessation programme. All men should be offered smoking cessation treatment which includes nicotine replacement therapy and continued support. Randomized controlled trials are needed to explore the effect of smoking and smoking cessation on erectile dysfunction.

New quinolinic derivatives as centrally active antioxidants.

A series of new 1,2-dihydro and 1,2,3,4-tetrahydroquinolines, synthesized from the corresponding propargylaniline intermediates, have been developed as antioxidants for the potential treatment of pathologies implicating central oxidative stress.

Male patients with lower urinary tract symptoms. 2: Treatment.

The first part of this article (Dorey, 2000) described the subjective and objective assessment of men with lower urinary tract symptoms (LUTS). This article will examine treatment protocols for stress incontinence, urge incontinence, post-prostatectomy incontinence, post-micturition dribble, overflow incontinence, reflex incontinence and functional incontinence. Pelvic floor muscle exercises, biofeedback, electrical stimulation, urge suppression techniques, and fluid intake are discussed. It is concluded that men with LUTS can benefit from conservative treatment.

Male patients with lower urinary tract symptoms. 1: Assessment.

Male lower urinary tract symptoms include frequency, nocturia, urgency, urge incontinence, stress incontinence, post-micturition dribble and post-prostatectomy incontinence. All of these symptoms can be treated conservatively. In this article, the first of two parts, a detailed subjective and objective assessment is provided based on a Delphi study undertaken by the author. The objective assessment includes a digital rectal examination to assess the pelvic floor muscle strength in order to provide a patient-specific exercise programme. The diagnosis of stress incontinence, urge incontinence, post-prostatectomy incontinence, post-micturition dribble and functional incontinence is made from the assessment. Men with lower urinary tract symptoms need a detailed subjective and objective assessment before a diagnosis is made and individual treatment is planned.

Conservative treatment of erectile dysfunction. 1: Anatomy/physiology.

This is the first of a three-part article addressing whether physiotherapy involving pelvic floor muscle exercises is efficacious as a first-line treatment for erectile dysfunction (ED). In this, the first part of the article, the prevalence of ED and associated risk factors are considered after which the anatomy of the penis and the physiology of erection are outlined. This provides background for the second and third parts of the article which review the outcomes of published clinical trials investigating the treatment and prevention of ED, and assess the evidence for pelvic floor exercises relieving ED.

Conservative treatment of erectile dysfunction. 2: Clinical trials.

This is the second of a three-part paper addressing whether physiotherapy involving pelvic floor muscle exercises (PFMEs) is efficacious as a first-line treatment for erectile dysfunction (ED). The first part (Vol 9(11): 691-4) highlighted the prevalence of ED, associated risk factors, the anatomy of the penis and the physiology of erection. This part concentrates on the computer-aided and manual search for published clinical trials investigating the treatment and prevention of ED. The methodological quality of the trials was assessed using criteria based on generally accepted principles of interventional research. The literature search revealed 14 trials which met the broad inclusion criteria. Of these, eight trials used PFMEs with or without biofeedback or electrical stimulation.

Conservative treatment of erectile dysfunction. 3: Literature review.

This is the third of a three-part article addressing whether physiotherapy involving pelvic floor muscle exercises (PFMEs) is efficacious as a first-line treatment for erectile dysfunction (ED). The first part (Vol 9(11): 691-4) highlighted the prevalence of ED, associated risk factors, the anatomy of the penis and the physiology of erection. The second part (Vol 9(12): 755-62) concentrated on the published clinical trials investigating the treatment and prevention of ED. This part will critically analyse the literature. PFMEs using ischiocavernosus muscles (ICMs) and bulbocavernosus muscles (BCMs) seem to have merit as a treatment for ED due to mild or moderate venous leakage. Men suffering from ED due to other causes may also benefit. There is no strong evidence that electrical stimulation or electroacupuncture is effective or ineffective. No studies demonstrating preventive conservative treatments were found. There is evidence that the ICMs and BCMs increase penile rigidity in the tumescent penis, that pelvic floor muscle efficiency is higher in potent men than impotent men and that perineal muscle efficiency reduces with age in impotent men. There is limited evidence that pelvic floor exercises relieve ED due to venous leakage and are a realistic alternative to surgery. Randomized controlled trials are needed to explore the use of PFMEs as a first-line treatment for men with ED.

2-2'-Pyridylisatogen, a selective allosteric modulator of P2 receptors, is a spin trapping agent.

2-2'-Pyridylisatogen (PIT) has been reported to be a relatively selective irreversible antagonist of responses to adenosine 5'-triphosphate (ATP) in some smooth muscle preparations and to be an allosteric modulator of responses to ATP at recombinant P2Y receptors from chick brain. PIT is also a potent inhibitor of mitochondrial oxidative phosphorylation. However, the compound has a unique nitrone structure, so PIT was compared with dimethyl-pyrroline-N-oxide (DMPO) as a spin trapping agent for superoxide and hydroxyl radicals using electron spin resonance (ESR). PIT was found to be a potent spin trapper of both hydroxyl and superoxide radicals. PIT was more potent than DMPO to trap the hydroxyl radical forming an adduct which was more stable than the DMPO adduct in aqueous media. PIT was an effective spin trap of hydroxyl radical in aqueous buffer at pH 7.4. PIT more slowly trapped the superoxide anion but at concentrations where DMPO trapped none.

Synthetic routes to 4-amino-3-carboxy-beta-carboline derivatives: incidental formation of novel furo[3,4-c]-beta-carbolin-2-ones displaying high affinities for the benzodiazepine receptor.

The synthesis of the first 4-amino-3-carboxy-beta-carboline derivative (35) is described. This synthesis is based on ozonolysis of the 4-vinyl-beta-carboline-3-carboxamide 17 to give the 4-aldehyde 20 and potassium permanganate oxidation of the latter to the 4-carboxylic acid 34 followed by a DPPA-promoted Curtius rearrangement. During the course of these transformations, a number of furo[3,4-c]-beta-carbolin-2-ones, differing in substituents at the C-10 position, were formed. While these beta-carboline lactones (15,25,26,33) generally displayed good affinities for the central type benzodiazepine receptor in vitro (IC50's in the 10-50 nM range), one compound, 29, demonstrated an exceptionally high binding affinity (IC50 = 0.2 nM). Compound 29 was shown in electrophysiological and behavioral studies to act as a benzodiazepine receptor antagonist. The unusually high binding affinity of compound 29 corroborates the hypothesis that the benzodiazepine receptor preferentially recognizes the C-3 carbonyl function of 3-carboxy-beta-carbolines in an s-cis conformation (i.e., the carbonyl oxygen on the same side as the pyridinyl nitrogen).

Synthesis and benzodiazepine receptor affinities of rigid analogues of 3-carboxy-beta-carbolines: demonstration that the benzodiazepine receptor recognizes preferentially the s-cis conformation of the 3-carboxy group.

1H-Indolo[3',2':4,5]pyrido[3,2-b]-2-penten-5-olide (6) and 1H,5H-indolo[3',2'-c]-6,7-dihydro-2-pyridone (7), rigid analogues of methyl 4-ethyl-beta-carboline-3-carboxylate (8) and N-methyl-4-ethyl-beta-carboline-3-carboxamide (9), respectively, were synthesized and their in vitro binding affinities to the central type benzodiazepine receptors were compared. The IC50 values of 6 and 8 were approximately equivalent (42 and 27 nM, respectively). The amide derivative 9, for which theoretical energy calculations indicate that the s-trans carbonyl conformation is the preferred one, displayed very low affinity (IC50 greater than 10(4) nM). However, when the carbonyl group of 9 was forced to adopt the s-cis conformation as in lactam 7, binding to the benzodiazepine receptor was largely restored (IC50 = 150 nM), indicating that the s-cis carboxy conformation at C-3 of beta-carbolines is preferentially recognized by this receptor. In vivo, compound 6 showed neither convulsant, proconvulsant, nor anticonvulsant activity in mice. Moreover, 6 did not antagonize methyl beta-carboline-3-carboxylate induced convulsions in mice. This lack of activity of 6 was attributed to its inability to cross the blood-brain barrier since no significant displacement of [3H]Ro 15-1788 from mouse brain benzodiazepine receptors by 6 could be observed in vivo.

The influence of androgens on enzymes (chymotrypsin-and trypsin-like proteases, renin, kallikrein and amylase) and on cellular structure of the mouse submaxillary gland.

1. The effect of age and androgen level on enzyme activity and cellular structure has been determined in the mouse submaxillary gland.2. A new protease which resembles chymotrypsin in its substrate specificity has been characterized in the gland.3. Activity of the chymotrypsin- and trypsin-like proteases and renin increased considerably in male mice concomitantly with proliferation of granules in the secretory tubules of the gland.4. The androgen dependence of the chymotrypsin- and trypsin-like enzymes, renin and the organelles within the secretory tubules was confirmed in castrated male mice. The activity of these enzymes increased and correlated with the appearance of intracellular granules in the secretory tubules when the castrated male mice and in addition female mice were treated with testosterone preparations.5. Kallikrein, a closely related protease, and amylase increased in activity with age but showed no sex-linked differences.6. The results suggest that kallikrein is sequestered in acinar cells whereas the androgen-dependent enzymes (chymotrypsin, trypsin and renin) are located in the secretory tubules.