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Biomedical subjects

Laurent Alexandre

Publications and source records attributed to Laurent Alexandre.

17 recordsLinked to original sources

The melanocortin agonist, melanotan II, enhances proceptive sexual behaviors in the female rat.

Melanocortins have been reported to play a role in the control of both male and female sexual behavior. The present study examined the effects of melanotan-II (MT-II), a cyclic peptide analogue of alpha-melanocyte stimulating hormone on appetitive and consummatory aspects of female sexual behavior, including aspects of sexual proceptivity (solicitations, hops and darts, ear wiggling, pacing) and receptivity (lordosis). One group of ovariectomized Long-Evans rats (n=7) was primed subcutaneously with estradiol benzoate (EB) and progesterone (P) (10 microg and 500 microg respectively) and another group (n=7) with EB (10 microg) and oil (EB alone). Paced mating tests were performed with sexually experienced males in unilevel chambers, which were bisected by a Plexiglas divider containing three holes, through which only the female could pass. MT-II (1 and 3 mg/kg) or saline was injected intravenously 10 min before each 30-min paced mating test. Each female received the 3 treatments. In females primed with EB+P both doses of MT-II increased the number of hops and darts and ear wiggling significantly, but did not alter pacing or lordosis. With EB alone, no effect of MT-II was observed on any of the parameters measured. These results suggest that P can interact with MT-II to increase proceptive behaviors. Because hops and darts are essentially solicitations, made in close proximity to the male, that indicate a desire on the part of females to receive mounts and intromissions, these data suggest that activation of melanocortin receptors may represent a promising mode of action for the treatment of women with hypoactive sexual desire.

Animals↗

Relaxation of phasic contractile activity of human detrusor strips by cyclic nucleotide phosphodiesterase type 4 inhibition.

OBJECTIVES: Detrusor smooth muscle relaxation is mainly mediated by the cyclic adenosine monophosphate (cAMP) pathway. Elevation of cAMP levels by phosphodiesterase type 4 (PDE4) inhibition relaxes smooth muscles of various origins. We aimed to determine the effect of a PDE4 inhibitor, rolipram, on human detrusor contractions. METHODS: Human bladder strips (from 20 different donors) with no known overactive bladder (OAB) were studied in organ baths. Detrusor samples with or without urothelium were incubated with carbachol 10(-6)mol/l (in presence or absence of forskolin, 3.10(-7)mol/l) or with KCl 10mmol/l to enhance phasic contractile activity. Concentration response curves for rolipram or vehicle were then performed. RESULTS: Rolipram (10(-9) to 3.10(-5)mol/l) induced a moderate relaxing effect on carbachol-induced contractions. This effect was enhanced when cAMP levels were increased by forskolin (the maximal effect was 53.0+/-5.1 vs. 83.1+/-5.7%, p<0.01) or in strips with urothelium. In contrast, rolipram (10(-9) to 10(-4)mol/l) drastically inhibited phasic contractile activity: The developed tension, the area under the curve, and the amplitude of phasic activity were reduced to 64.8+/-3.6, 91.2+/-5.3, and 82.3+/-7.3%, respectively, versus 23.6+/-9.5, 34.7+/-18.8, and 18.0+/-16.2% for vehicle, respectively (p<0.05). Frequency of phasic activity was 0.96+/-0.45 contractions per minute versus 2.6+/-0.18 for vehicle (p<0.001). In strips with urothelium, the inhibitory effect of rolipram on phasic contractile activity was similar. CONCLUSIONS: PDE4 isoenzymes are strongly involved in the regulation of phasic myogenic activity of human bladder strips. Because an increase of this phasic activity may play a role in the pathophysiology of detrusor overactivity, PDE4 inhibitors might represent an attractive strategy for the treatment of OAB.

3',5'-Cyclic-AMP Phosphodiesterases↗

Supraspinal site of action for the inhibition of ejaculatory reflex by dapoxetine.

OBJECTIVES: The aim of the study was to determine whether dapoxetine, a short-acting selective serotonin reuptake inhibitor, acts at the spinal or supraspinal level to inhibit the ejaculatory reflex. METHODS: The pudendal motoneuron reflex discharges (PMRDs) model was used as an experimental paradigm of the ejaculatory expulsion reflex in anaesthetised male rats. A spinal site of action was evaluated by testing the effect of intrathecal delivery of dapoxetine on PMRDs elicited by electric stimulation of the dorsal nerves of the penis (DNP). A supraspinal site of action was evaluated by testing the effect of intravenous administration of dapoxetine on DNP-induced PMRDs in rats with chemical bilateral lesion of the lateral paragigantocellular nucleus (LPGi). RESULTS: Compared with control (NaCl 0.9%, intrathecally), intrathecal injection of dapoxetine (1 and 80 microg) significantly increased amplitude of DNP-elicited PMRDs in a similar fashion than serotonin (5-HT; 10 and 100 microg, intrathecally). In rats having received bilaterally NaCl 0.9% into LPGi, intravenous treatment with dapoxetine (3mg/kg) induced significant delay in PMRD latency and decrease in PMRD amplitude compared with pretreatment values. These effects were abolished in rats having received bilaterally kainic acid into LPGi 1 d before testing. CONCLUSIONS: The present study showed that dapoxetine inhibits ejaculatory expulsion reflex by acting at a supraspinal level with LPGi as a necessary brain structure for this effect.

Animals↗

Comparison between tamsulosin and alfuzosin on the expulsion phase of ejaculation in rats.

OBJECTIVE: To investigate the effects of acute intravenous (i.v.) delivery of tamsulosin and alfuzosin on the contractions of bulbospongiosus muscles (BS) induced by central delivery of a serotonin agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), in anaesthetized rats, as an experimental model of the expulsion phase of ejaculation. MATERIALS AND METHODS: Under urethane anaesthesia, adult male rats were implanted with a cannula into the lateral cerebral ventricle for intracerebroventricular (i.c.v.) injection, and with recording electrodes in the BS for electromyogram (EMG) monitoring. Tamsulosin (1 microg/kg) and alfusozin (10 microg/kg) were injected i.v. and 15 min later 8-OH-DPAT (20 microg) was delivered i.c.v. BS-EMG recording was continued for 30 min after i.c.v. 8-OH-DPAT. The area under the curve (AUC) of the BS cluster of contractions was determined as reflecting the energy of BS contractions. RESULTS: After i.c.v. delivery of 8-OH-DPAT, there were rhythmic BS contractions in the form of clusters of bursts in vehicle-, tamsulosin- and alfuzosin-treated rats. The number of BS clusters was not altered by the alpha1-blockers as compared with vehicle, but the AUC was significantly less in tamsulosin-treated rats than in vehicle- or alfuzosin-treated (both P < 0.05) rats. CONCLUSION: Systemic injection of tamsulosin impaired BS contractile capacity whereas alfuzosin did not. This might explain anejaculation in men treated with tamsulosin.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Role of peripheral innervation in p-chloroamphetamine-induced ejaculation in anesthetized rats.

The occurrence of ejaculation, which consists of 2 distinct phases (emission and expulsion), requires a tight coordination of peripheral autonomic and somatic nerves. However, some aspects of the mechanism of ejaculation are not clearly defined. To clarify this issue, we used the p-chloroamphetamine (PCA)-induced ejaculation model in anesthetized rats and investigated the effects of selective peripheral nerves lesions on seminal vesicle and bulbospongiosus (BS) muscle activities as representing physiological markers of emission and expulsion phases, respectively. In intact rats, ejaculation induced with PCA (intraperitoneal 5 mg/kg) correlated with coordinated increases in seminal vesicle pressure (SVP) and BS electromyographic activity. PCA-induced ejaculation was still observed in rats with bilateral lesion of hypogastric nerves (HNx), lumbar paravertebral sympathetic chain (LSCx), or dorsal nerves of the penis (DNPx). Conversely, bilateral section of pelvic nerves (PNx) or L6-S1 dorsal roots (DRx) abolished PCA-induced ejaculation. The amplitude of SVP increases induced by PCA was reduced in PNx, HNx, and LSCx rats, whereas it was unchanged in DRx and DNPx rats. The time interval between SVP increases and BS muscle contractions induced by PCA was comparable in the different neural lesion groups. In conclusion, PCA initiates both emission and expulsion independently from each other. In this model, afferents conveyed by the pelvic nerves appear to be unnecessary for occurrence of BS muscle contractions but are essential for a complete ejaculatory response.

Animals↗

Effects of potassium channel modulators on human detrusor smooth muscle myogenic phasic contractile activity: potential therapeutic targets for overactive bladder.

OBJECTIVES: Increased urinary bladder detrusor smooth muscle phasic contractility has been suggested to be associated with idiopathic bladder overactivity (OAB). We examined the role of voltage-dependent L-type calcium channels, adenosine triphosphate-sensitive potassium (K(ATP)) channels, and calcium-activated potassium (BK(Ca) and SK(Ca)) channels in the regulation of human detrusor phasic contractile activity. METHODS: Isolated human bladder strip phasic contractions were measured and quantified as the mean area under the force-time curve, amplitude, and frequency of phasic contractions in 22 bladder samples. RESULTS: Human detrusor strips displayed myogenic phasic contractions in the presence of atropine (10(-6) M), phentolamine (10(-6) M), propranolol (10(-6) M), suramin (10(-5) M), and tetrodotoxin (10(-6) M). The L-type calcium channel inhibitor nifedipine (300 nM) abolished the contractile activity. Blockade of K(ATP) channels by glibenclamide (1 and 10 microM) did not alter myogenic contractions. In contrast, the K(ATP) channel opener pinacidil (10 microM) markedly inhibited phasic contractility. Iberiotoxin (100 nM) and apamin (100 nM), potent and selective inhibitors of BK(Ca) and SK(Ca) channels, respectively, significantly increased the area under the force-time curve and the amplitude of contractions. CONCLUSIONS: Phasic contractions of human detrusor are dependent on calcium entry through L-type calcium channels. BK(Ca) and SK(Ca) channels play a key role in the modulation of human detrusor smooth muscle phasic contractility. Furthermore, these observations support the concept that increasing conductance through K(ATP), BK(Ca), and SK(Ca) channels may represent attractive pharmacologic targets for decreasing phasic contractions of detrusor smooth muscle in OAB.

Calcium Channels, L-Type↗

L6-S1 spinal nerve stimulation reduces micturition frequency in anaesthetized rats with cyclophosphamide-induced cystitis.

OBJECTIVE: To further investigate the rationale for using spinal nerve stimulation (SNS) for treating bladder overactivity associated with cystitis in a rat model of cyclophosphamide-induced cystitis, as several studies suggested that symptoms associated with chronic cystitis could be treated using stimulation of sacral spinal nerves, but the mechanisms by which it works are unknown. MATERIALS AND METHODS: Cystitis was induced by i.p. injection of cyclophosphamide 48 h before the experiments in anaesthetized male rats. Neurograms were taken by placing a recording electrode onto the pelvic nerve and a stimulating electrode on either the L6 or S1 ipsilateral spinal nerves. Two selected intensities were then evaluated for SNS in control and cyclophosphamide-treated rats during cystometry. RESULTS: Cyclophosphamide resulted in significant bladder overactivity. There was no apparent difference in the neurograms generated in response to SNS of the S1 and L6 spinal nerves, and between cyclophosphamide and control rats. Intensities of 200 microA (Adelta-fibre-specific) and 2 mA (Adelta+ C-fibres) were chosen for SNS. Continuous SNS at 200 microA significantly reduced the frequency of voiding and non-voiding contractions in cyclophosphamide-treated rats. SNS at 2 mA resulted in the abolition of voiding contractions, accompanied by continuous leakage of urine. CONCLUSION: SNS recruiting only Adelta-fibre produced fewer voiding contractions in cyclophosphamide-treated rats, to a level similar to that from the control rats. These results support the ability of SNS to decrease bladder overactivity in a pathophysiological model of chemical irritation of the bladder.

Animals↗

Effect of the 5-HT receptor agonist DOI on female rat sexual behavior.

INTRODUCTION: Female rats display a repertoire of behaviors during a sexual encounter with a male, including sexually receptive (the lordosis response) and proceptive (darts and hops, and ear wigglings) behaviors. AIM: We investigated the effects of subcutaneous injection of the 5-HT(2A/2C) receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride (DOI) on sexual behaviors of ovariectomized female rat hormonally supplemented with estradiol benzoate (10 microg) and progesterone (250 microg). METHODS: Both female and male sexual behaviors were observed for 10 minutes (pretest). Then females were injected with the treatment and after a 10-minute delay replaced with the same male for a 30-minute mating test (posttreatment period). RESULTS: DOI (0.5 and 1 mg/kg) significantly increased the number of darts and hops/mounts. In contrast, no significant differences in ear wigglings/mounts were observed. In addition, DOI failed to modify sexual receptivity. CONCLUSION: These data suggest that 5-HT(2A/2C) receptors are important in the regulation of female proceptivity.

Amphetamines↗

Erectile dysfunction in hypercholesterolemic atherosclerotic apolipoprotein E knockout mice.

INTRODUCTION: Erectile dysfunction (ED) and cardiovascular diseases share the same risk factors. Although the use of hypercholesterolemic rabbit models has proven to be useful to illustrate the link between ED and hypercholesterolemia, the cost of daily maintenance of the animals and necessity for important amounts of drug have limited their use. AIM: We aimed to develop a new model of atherosclerosis-associated ED in a well-known experimental model of atherosclerosis, the apolipoprotein E knockout (ApoE KO) mouse. METHODS: Erectile function was evaluated by recording frequency-dependent increases in intracavernous pressure following electrical stimulation of the cavernous nerve in 26-, 32-, and 38-week-old ApoE KO mice fed a Western-type diet and age-matched C57BL6/J anesthetized mice. Atherosclerotic lesions were evaluated by planimetry in oil red O-stained aortas. RESULTS: We found that in contrast to C57BL6/J mice, ApoE mice displayed atherosclerotic lesions covering 22% of the aortic luminal surface at 26 weeks of age and increasing to 27% and 35% at 32 weeks and 38 weeks of age, respectively. The amplitude of erectile responses to electrical stimulation of the cavernous nerve was markedly impaired in 26-week-old ApoE KO mice as compared with age-matched C57BL6/J mice. Impairment in erectile function persisted in ApoE KO mice 32 and 38 weeks of age. CONCLUSIONS: The ApoE KO mouse, a well-characterized model to study disorders associated with hypercholesterolemia and atherosclerosis in cardiovascular research, could therefore be suitable for investigation of disease-modifying effects of new therapeutic strategies aiming to target both atherosclerosis and ED.

Animals↗

D2-like receptors mediate the expulsion phase of ejaculation elicited by 8-hydroxy-2-(di-N-propylamino)tetralin in rats.

The mechanism of action by which 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) facilitates ejaculation in conscious rats is not clearly established. The serotonin (5-HT) 1A agonist 8-OH-DPAT may actually act on cerebral dopaminergic receptors to exert its proejaculatory effect. The present work was undertaken to clarify this issue by testing various compounds i.c.v. delivered in an experimental model of the expulsion phase of ejaculation in anesthetized Wistar rats. Intracerebroventricular delivery of 8-OH-DPAT dose-dependently (ED(50) = 17 microg) induced rhythmic contractions of bulbospongiosus (BS) muscles, which are of paramount importance for the expulsion of semen, occurring in the form of cluster of bursts evidenced by the recording of BS muscle electrical activity. The 5-HT1A antagonist WAY100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide) (20 microg) i.c.v. coadministered with 8-OH-DPAT (20 microg) was unable to inhibit the effect of 8-OH-DPAT on BS muscle contractile activity. Conversely, raclopride (40 microg) and spiperone (10 microg), both dopamine D2-like receptor antagonists, i.c.v. coinjected with 8-OH-DPAT (20 microg), abolished BS muscle contractions. The involvement of D2-like receptors was further supported by the fact that the D2-like agonist quinelorane (20 microg i.c.v.) also induced BS muscle rhythmic contractions. Our data demonstrate that D2-like receptors mediate the induction by 8-OH-DPAT of rhythmic BS muscle contractions and suggest that i.c.v. delivery of D2-like receptor agonists to anesthetized rats represents a relevant experimental model to study the expulsion phase of ejaculation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Chronic sildenafil improves erectile function and endothelium-dependent cavernosal relaxations in rats: lack of tachyphylaxis.

OBJECTIVES: Sildenafil is a widely-prescribed effective on-demand treatment of erectile dysfunction (ED). Chronic treatment with sildenafil could help patients with ED. METHODS: The effects of an 8-week long treatment with sildenafil (60 mg/kg/d sc) in male Sprague Dawley rats were evaluated on electrically-elicited erectile responses in vivo before and after an acute injection of sildenafil (0.3mg/kg iv). In addition, endothelium-dependent and -independent relaxations of strips of corpus cavernosum in vitro were examined. All experiments were performed 36 hours after the last injection of sildenafil. RESULTS: Endothelium-dependent relaxations of cavernosal strips to acetylcholine were enhanced after chronic treatment with sildenafil while relaxations to A23187 or sodium nitroprusside were unchanged. Frequency-dependent erectile responses elicited by cavernous nerve stimulation were significantly improved. Moreover, the erectile responses to acute sildenafil were greater in chronically-treated rats with sildenafil. CONCLUSIONS: This is the first report providing experimental support for chronic dosing with sildenafil which could be of use for patients that are poor responders to on-demand treatment. Chronic sildenafil may regulate the transduction pathway leading to the activation of eNOS but has no effect on NO bioavailability or on the cGMP pathway, thereby eliminating a possible concern for tachyphylaxis.

Animals↗

Erectile dysfunction: an early marker for hypertension? A longitudinal study in spontaneously hypertensive rats.

Erectile dysfunction (ED) is another manifestation of vascular disease. We evaluated the natural history of ED in the spontaneously hypertensive rat (SHR) and the respective participation of associated pathophysiological modifications, i.e., endothelial dysfunction and tissue remodeling. SHR and their normotensive counterparts [Wistar-Kyoto rats (WKY)] of 6, 12, and 24 wk of age (n = 12) were used to evaluate erectile function, erectile and aortic tissue reactivity, and remodeling. Erectile responses in SHR are reduced at all ages (P < 0.001). In both aortic and erectile tissues of SHR and WKY, relaxations to ACh are altered progressively with age, although more markedly in SHR. They are decreased at 12 wk of age in erectile tissue of SHR compared with WKY (maximal relaxation: -19.2 +/- 2.8% vs. -28.3 +/- 3.9%, P < 0.001) but only at 24 wk of age in aortas (-47.9 +/- 6.4% vs. -90.5 +/- 2.9%, P < 0.001). Relaxations to sodium nitroprusside are unaltered in aortic rings of both strains but enhanced in erectile tissue of SHR at 12 wk of age. Major modifications in the distribution of collagen I, III, and V in SHR occur in both types of tissue and are detectable sooner in erectile tissue compared with aortic tissue. The onset of ED is detectable before the onset of hypertension in the SHR. Structural and functional alterations, while similar, occur earlier in erectile compared with vascular tissue. If confirmed in humans, ED could be an early warning sign for hypertension, and common therapeutic strategies targeting both ED and hypertension could be investigated.

Acetylcholine↗

Patient followup after radical prostatectomy by Internet medical file.

PURPOSE: The development of the Internet and the need for regular followup of patients often living a long way from the hospital led us to develop a followup dossier for those with localized prostate cancer treated with laparoscopic radical prostatectomy. MATERIALS AND METHODS: This feasibility study was based on 140 patients who agreed to test this system. The website was opened on a server specifically devoted to this project with all required computer security. The website is composed of pages comprising the hospital discharge summary, and operative and histology reports. A quality of life questionnaire based on the assessment of urinary continence and sex life, and a prostate specific antigen (PSA) assay form are also included. RESULTS: The patient is able to enter his PSA data and complete the questionnaire at home. Results are then sent to the treating physician. A contact page allows the patient and physician to exchange information by text. Of these 100 patients 92 connected regularly to the site with a mean connection rate of 8 per patient (range 1 to 22). Of the patients 98% were satisfied with the various sections of the site, 95% were satisfied with the medical file, 11% noticed connection problems and 14% reported technical problems essentially attributable to incorrect PSA data entry or incorrect functioning of videos due to the absence of appropriate software. CONCLUSIONS: This type of Internet medical service for patients who have undergone surgery requiring regular followup appears to be a useful approach for the future by allowing the maintenance of close contact between the patient and physicians, while avoiding problems related to hospital visits regardless of the patient place of residence. It also provides general practitioners with access to the patient file with patient permission.

Feasibility Studies↗

Erectile dysfunction in spontaneously hypertensive rats: pathophysiological mechanisms.

Hypertensive men have a higher prevalence of erectile dysfunction (ED) than the general population. Experimental evidence of ED in hypertensive animals is scarce. This study evaluates the erectile function of spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) in vivo by the increase in intracavernosal pressure after electrical stimulation of the cavernous nerve (CN) and by isometric tension studies on corporal strips. Frequency-dependent erectile responses to CN stimulations were reduced in SHR. Phenylephrine induced lower corporal contractions in SHR although pD2 values were similar to WKY. Endothelium-dependent relaxations to ACh were impaired significantly in SHR, and indomethacin improved these relaxations in both WKY and SHR, the latter thus reaching values similar to WKY. Corporal relaxations to sodium nitroprusside were enhanced in SHR. Thus a dysfunctional alpha-adrenergic contraction of the corporal smooth muscle, an increased cyclooxygenase-dependent constrictor tone, and/or a defect in endothelium-dependent reactivity are associated with the altered erectile mechanisms in SHR. Drugs targeting endothelial dysfunction may delay the occurrence of ED as a complication of hypertension.

Acetylcholine↗

Distinct mechanisms implicated in atherosclerosis-induced erectile dysfunction in rabbits.

Ageing and atherosclerosis (ATH) are well-known risk factors for erectile dysfunction (ED). To identify the mechanisms implicated in ATH-induced ED, independently of its ageing-associated component, we studied (i) erectile responses in vivo, and, (ii) endothelium-dependent and independent relaxations of corporal strips from young adult (YAD, n=6), adult (AD, n=6), and cholesterol-fed (ATH, n=8) New-Zealand white rabbits. Measurement of Intima/Media (I/M) ratio on iliac arteries from ATH rabbits determined those with moderate (Mod ATH, 0.5+/-0.3) or severe (Sev ATH, 1.5+/-0.4, P<0.05 Mann-Whitney) atherosclerotic lesions. Erectile responses were reduced in AD compared with YAD rabbits (at 6 V to 10 Hz: 51.6+/-4.6% vs. 57.5+/-1.4%); they were similar in AD and mod ATH rabbits (48.1+/-4.6%) but drastically impaired in Sev ATH rabbits (34.8+/-5.4%, P<0.05, two-way analysis of variance (ANOVA)). Corporal endothelium-dependent and -independent relaxations were comparable in YAD and AD rabbits (maximal relaxation to acetylcholine: 51.3+/-9.5 vs. 56.1+/-9.3%) but decreased in ATH rabbits (37.1+/-1.6%, P<0.001, two-way ANOVA). These results suggest that the mechanisms implicated in ATH-induced ED are distinct from the ageing-related process in rabbits. Thus, future therapeutic targets to treat or prevent ATH-induced ED may include the reduction of the atherosclerotic plaque size or progression, as well as an improvement of the smooth muscle and endothelial reactivity of the corpus cavernosum.

Animals↗

Pro-erectile effect of systemic apomorphine: existence of a spinal site of action.

PURPOSE: Apomorphine exerts pro-erectile effects by acting on neurons in the paraventricular nucleus of the hypothalamus. In spinal cord injured rats we assessed whether apomorphine also directly activates the spinal autonomic and somatic neurons controlling penile erection MATERIALS AND METHODS: Intracavernous and blood pressure was monitored in groups of 10 anesthetized rats to quantify intracavernous pressure increases elicited after intravenous apomorphine. We determined the number and duration of increases, percent of maximum intracavernous pressure/mean diastolic blood pressure using the formula, maximum intracavernous pressure/diastolic blood pressure x 100, area under the intracavernous pressure curve/diastolic blood pressure and sum of the area under the curve/diastolic blood pressure. RESULTS: Of 2, 10, 50 and 250 microg./kg. intravenous apomorphine 50 microg./kg. induced significant pro-erectile effects and was subsequently used. In spinal cord injured rats 50 microg./kg. intravenous apomorphine significantly increased median maximum intracavernous pressure/diastolic blood pressure x 100 compared with vehicle injection (56 versus 27 seconds, p <0.001), area under the curve/diastolic blood pressure (21 versus 12 seconds, p = 0.07) and the sum of area under the curve/diastolic blood pressure (132 versus 32 seconds, p = 0.01). These pro-erectile effects of apomorphine were prevented by 50 mg./kg. hexamethonium intravenously or bilateral transection of the pelvic nerves. They were not affected by 3 mg./kg. of the peripheral D1/D2 antagonist domperidone intraperitoneally. In spinal cord injured rats subcutaneous pretreatment with 0.2 mg./kg. of the D1 antagonist SCH23390 significantly enhanced apomorphine induced erections, as indicated by an area under the curve/diastolic blood pressure of 23 to 30 seconds (p = 0.003), whereas they were not changed by 25 mg./kg. of the D2 antagonist sulpiride intraperitoneally. Under the same conditions 1 mg./kg. of the central D1/D2 antagonist haloperidol intraperitoneally only reduced the number of responding rats to 5 versus 10 of 10. CONCLUSIONS: In spinal cord injured rats systemic apomorphine elicits erection by acting at the spinal cord level. This finding suggests that systemic apomorphine elicits penile erections via spinal and supraspinal targets.

Animals↗

[Follow-up, with Internet medical file, of patients who have undergone radical prostatectomy].

The development of Internet and the need for regular follow-up of patients often living a long way from hospital have led us to develop a follow-up dossier for patients with localized prostate cancer treated by laparoscopic radical prostatectomy. This feasibility study is based on 100 patients who agreed to test this system. After approval by the Commission Nationale d'Informatique et de Liberté (CNIL) (French Computers and Privacy Commission) ensuring medical secrecy and confidentiality of data, the website was opened on a server specifically devoted to this project and presenting all of the required computer securities. The website is composed of pages comprising the hospital discharge summary, and the operative and histology reports. A quality of life questionnaire based on assessment of urinary continence and sex life and a PSA assay form are also included. The patient is therefore able to enter his PSA level and complete the questionnaire at home and the results are then sent to the doctor who treated him. A contact page allows the patient and the doctor to exchange information by text. 92 of these 100 patients connected regularly to the site with a mean connection rate of 8 per patient (range: 1 to 22). 98% of patients were satisfied with the various sections of the site and 95% were satisfied with their medical file. 11% of patients encountered connection problems and 14% reported technical problems essentially attributed to incorrect PSA data entry or incorrect functioning of videos due to the absence of appropriate software. This type of Internet medical service for patients who have undergone a surgical operation requiring regular follow-up appears to be a useful approach for the future by allowing: maintenance of close contact between the patient and his doctors while avoiding the problems related to hospital visits, regardless of the patient's place of residence. It also provides general practitioners with access to the patient's file, with the patient's permission.

Feasibility Studies↗