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PubMed1998

[Exploration of the deep dorsal vein of the penis using pulsed Doppler ultrasonography. Preliminary study].

OBJECTIVES AND METHODS: This was an open preliminary study of 36 unselected men suffering from erectile dysfunction (DE) for the evaluation of the deep dorsal vein of the penis (VDP) by duplex scan (EDP). All men had an intravenous injection (IIC) with a vaso active agent: alprostadil (Edex) (n = 24), a mixture of papaverine ifenprodyl tartrate (Vadilex) (n = 4) or papaverine, ifenprodyl tartrate and alprostadil (n = 7). The deep dorsal vein was evaluated, with a 13 mHz mechanical probe 5 and 10 minutes after the injection, during visual sexual stimulation (SSV) carried on for 10 mn, and 3 mn after having stopped SSV. The influence of deep breathing and contraction of the ischio and bulbo-cavernous muscles was recorded at each of the periods. RESULTS: The deep dorsal vein was identified in all cases. After pharmacological stimulation flow was present in 61% of the cases, with a statistically significant difference between alprostadil (80%) and both mixtures (20%). The addition of sexual stimulation caused flow to disappear in 64% of the cases (91% for the mixture and 44% for alprostadil). There was a range of variation under breathing and muscular contraction which deserves further evaluation. CONCLUSIONS: 1) The deep dorsal vein is easily studied under duplex scan and should be part of the routine examination of the vascular component of erection during erectile dysfunction. 2) The vein is subjected to modification of flow after intracavernous injection and sexual stimulation which varies with the agent injected and the clinical condition of the patients. 3) Absent flow early after injection seems to be predictive of the possibility of a prolonged erection.

Adult↗
PubMed1999

Comparative tolerability and efficacy of treatments for impotence.

Modern pharmacological treatment of impotence is determined by the presenting symptoms. Since this involves symptomatology with a heterogenous aetiology, many different drugs are involved in the treatment of impotence. Drugs used for libido and arousal problems include testosterone, yohimbine, trazodone and apomorphine. Since patient self-assessment is the only parameter that can be used to measure the result of treatment and positive results are seldom affirmed, no positive benefit of these agents can be assumed at present. Oral medications for erectile dysfunction include yohimbine, trazodone, apomorphine, phentolamine, arginine and sildenafil. Of these drugs, sildenafil has been the most systematically studied for effectiveness, but long term safety data await the results of post-marketing surveillance. Of the ejaculation disorder therapies, treatments for premature ejaculation are the best studied. Favourable results have been obtained with clomipramine, paroxetine and fluoxetine. The safety of these medications has been assessed through their long term use in psychiatry. Intracavernous self-injections for erectile disorders are performed using a variety of drugs and drug mixtures. Only alprostadil and the combination of papaverine with phentolamine are widely used. Alprostadil is very well tolerated; however, penile pain is a serious problem in a significant proportion of patients. Papaverine in combination with phentolamine is effective, but penile fibrosis and priapism occur more often than with the use of alprostadil. Several new developments in this area are currently under way. Alternative routes for medication for erectile dysfunction include ointments and patches to the penile skin and the glans. Only transurethral alprostadil, 'MUSE' (medicated urethral system for erection) has been shown to be effective in large trials. Long term safety still has to be demonstrated, but the 1-year safety profile is encouraging. In general, the end points of impotence treatment studies are very diverse so efficacy data can only be assessed in comparative studies. However, long term comparison studies have not been performed. Safety demands must be set very high for this type of treatment since the disorders being treated present no threat to the patient's health.

Aphrodisiacs↗
PubMed1983

Transport of prostaglandins through normal and diabetic rat hepatocytes.

Transport of alprostadil (prostaglandin E1) and dinoprost (prostaglandin F2 alpha) was studied in enzymatically dispersed normal and streptozocin-treated rat hepatocytes prepared by collagenase perfusion. Cell suspensions incubated at 37 degrees were sampled at time intervals for a period of 5 min and the supernatant analyzed for prostaglandins after centrifugation. The data analysis employed a theory and a model for solute transfer at the cell membrane-water interphase. Biophysical parameters such as the effective partition and the apparent permeability constants were used to define the transport mechanism. The apparent permeability coefficient of alprostadil and dinoprost transfer through normal hepatocytes was calculated to be 5 X 10(-3) and 3 X 10(-3) cm/sec with a mean partition coefficient of 1345 and 764 for both solutes, respectively. The permeability coefficient of alprostadil and dinoprost transfer through diabetic hepatocytes were 3 X 10(-3) and 2 X 10(-3) cm/sec with partition coefficient of 572 and 206, respectively. The results showed differences in prostaglandin transport between normal and diabetic hepatocytes, resulting from morphological and lipid alteration in the cytoplasmic membrane.

Alprostadil↗
PubMed1998

Genital plus audiovisual sexual stimulation following intracavernous vasoactive injection versus re-dosing for erectile dysfunction--results of a prospective study.

PURPOSE: We assessed whether re-dosing of a vasoactive agent or the combination of a vasoactive injection and genital plus audiovisual sexual stimulation caused the greatest erectile effect to determine which of the 2 procedures would be better for dynamic penile color Doppler sonography in patients with erectile dysfunction. MATERIALS AND METHODS: A total of 20 consecutive patients with erectile dysfunction underwent 2 sessions under real-time RigiScan* recording of penile erection. Session 1 consisted of adaptation in 10 minutes, intracavernous injection of 10 micrograms. alprostadil in 10 minutes and re-dosing of 10 micrograms. alprostadil in 10 minutes. Session 2 consisted of adaptation in 10 minutes, injection of 10 micrograms. alprostadil in 10 minutes and genital plus audiovisual sexual stimulation in 10 minutes. The total duration of each session was 30 minutes. The order of the 2 sessions was randomly assigned with a week interval between each session. RESULTS: Re-dosing and genital plus audiovisual sexual stimulation caused a significant increase in erectile response compared to the result seen after the first injection (re-dosing p < 0.05, injection plus stimulation p < 0.01). However, erectile response after the genital stimulation session was significantly greater than that after re-dosing (p < 0.01). An erection comparable to the greatest spontaneous erection reported by the patient was much more frequently achieved after genital stimulation than after the re-dosing session (p < 0.01). CONCLUSIONS: The combination of injection and stimulation caused a significantly greater erectile response than re-dosing. We suggest that the former should always be used during color Doppler sonography to optimize the accuracy of the test. Re-dosing is suggested when an incomplete erectile response occurs after the injection plus stimulation phase.

Adult↗
PubMed2001

Short-term histopathologic effects of different intracavernosal agents on corpus cavernosum and antifibrotic activity of intracavernosal verapamil: an experimental study.

OBJECTIVES: To evaluate the short-term effects of different intracavernosal agents and to investigate the antifibrotic effect of verapamil combined with these intracavernosal agents. METHODS: Forty-five Sprague-Dawley rats weighing 400 to 500 g each (mean weight 435.27 +/- 13.65 g) were equally divided into nine groups (n = 5). Papaverine (group 1), alprostadil (group 2), sodium nitroprusside (group 3), and verapamil (group 4) were injected alone intracavernously in 0.2-mL doses. Verapamil combined with papaverine, alprostadil, and sodium nitroprusside in 0.2-mL doses (0.1 mL verapamil and 0.1 mL vasoactive agent) were injected in groups 5 through 7. Group 8 was kept as a control group without injection, and isotonic saline alone was injected in group 9 during the same period. The intracavernous injection was done twice weekly with a 4-day interval. At the end of the study, total penectomy and multiple liver biopsies were performed to evaluate the histopathologic effects of the vasoactive agents and to test the liver function. RESULTS: In all groups, the structure of the corpora cavernosa was well preserved generally and appeared similar to the control tissue. However, localized edema, fibrosis, macrophage infiltration, and polymorphonuclear leukocytes were found only at the injection site. Although these findings were not different from the findings in the saline and alprostadil groups, they were slightly more extensive in the papaverine and sodium nitroprusside alone groups and also in the vasoactive agent plus verapamil groups. Although mononuclear lymphocyte infiltration was found in the portal areas, advancing into the liver parenchyma, the liver function tests were within normal limits. CONCLUSIONS: We observed that intracavernous injection, except with nitroprusside, caused focal intracavernosal fibrosis and edema. We believe these effects might not be caused by just the drug, but also by needle trauma, since general fibrosis was not observed in the short term. However, nitroprusside has a severe fibrotic effect on cavernosal tissue in the short term. Moreover, intracavernous verapamil injection could not prevent the fibrosis in the short term.

Alprostadil↗
PubMed2001

[Intracavernous injections in the treatment of erectile dysfunction in spinal cord injured patients: experience with 36 patients].

OBJECTIVES: To confirm the efficiency of intracavernous injections in the treatment of erectile dysfunction in spinal cord injured (SCI) patients and to determine the mean necessary dose to obtain functional erection. MATERIALS: This prospective study concerns 36 spinal cord injured men. None of them had erectile dysfunction before the neurologic impairement. Sixty four intracavernous injections were performed. METHOD: The first injection was done with the usually recommended starting dose. The injections were then repeated with increasing dosage to archive a rigid erection. The erection was evaluated with Schramek grading. A grade 4 or 5 erection was considered as functional. RESULTS: Nine tetraplegics and 27 paraplegics were included. Twenty two were grade A in ASIA classification. The mean age was 31 years. Twenty for patients had a level above T10, 11 between T11 and L2, one below L2. Twenty seven patients obtained an erection of grade 4 or 5. Alprostadil was used 51 times, moxisylite nine times and papaverine four times. The average dose necessary to obtain a grade 4 or 5 functional erection adequate for coitus was 12.3 +/- 4.8 microgram with alprostadil and 14 +/- 5.4 mg with moxisylite. No side effects were noted. The nine left patients did not archive satisfying erection during this study. No clinical differences were noted in this population, compared with the 27 other patients. CONCLUSION: The findings confirm the efficiency of intracavernous injections in the management of erectile dysfunction in SCI. The average doses required to obtain a functional erection was 12.3 (+/- 4.8) microgram with alprostadil and 14 (+/- 5.4) mg with moxisylyte.

Adult↗
PubMed2001

The influence of intraarterial prostaglandin E(1) on vascular hydraulic impedance and infrainguinal graft patency.

OBJECTIVES: To evaluate the influence of intraoperative arterial prostaglandin E(1)(alprostadil) infusion on hydraulic impedance in relation to graft patency. METHODS: Hydraulic impedance was measured in 115 infrainguinal bypasses by means of the extracorporeal-bypass-flow method (EBF). Fifty-eight femoro-popliteal and 57 femoro-crural polytetrafluoroethylene (PTFE) grafts were included. 10 microg of alprostadil were administered into a temporary bypass and the haemodynamic changes were recorded. The reactions of input (Z(x)) and characteristic (Z(0)) impedances as well as phase relations were derived and related to graft outcome after three years. RESULTS: Significant changes after administration of prostaglandin were observed for overall pressure (74 vs. 84 mmHg, p<0.01), flow rate (194 vs 160 ml/min, p<0.01), input impedance (0.55 vs. 0.75 PRU, p<0.01) and the phase angle of the first harmonic (-18 degrees vs -26 degrees, p<0.01). An increase of at least one degree of the first harmonic phase angle following alprostadil injection in the crural bypass group was associated with a significant better graft prognosis of crural (p<0.01) but not popliteal grafts. Primary and secondary patency rates after three years for crural grafts with an increase of at least one degree were 62% and 63% (n=45) and for non-responders 18% and 0% (n=12, p(prim)<0.01, p(sec)<0.001). All crural bypasses with poor prostaglandin reaction occluded within 9 months (n=12) after the operation. CONCLUSIONS: The EBF method allows a combined assessment of peripheral resistance and impedance parameters. The response of the first harmonic phase angle provides important predictive information regarding femoro-crural grafts.

Adult↗
PubMed1999

Prostanoids for chronic critical leg ischemia. A randomized, controlled, open-label trial with prostaglandin E1. The ICAI Study Group. Ischemia Cronica degli Arti Inferiori.

BACKGROUND: No effective pharmacologic intervention is available for critical leg ischemia, a severe clinical condition associated with high morbidity and mortality. OBJECTIVE: To assess the safety and efficacy of prostaglandin E1 in improving the prognosis and quality of life in patients with critical leg ischemia. DESIGN: Multicenter, centrally randomized, controlled, open-label trial. SETTING: 56 vascular surgery and angiology departments of the Italian National Health Service. PATIENTS: 1560 patients with chronic critical leg ischemia. INTERVENTIONS: In addition to routine treatments practiced in each center, patients were randomly assigned to receive either a daily intravenous infusion of 60 microg of prostaglandin E1 in the form of alprostadil-alpha-cyclodextrine (n = 771) or no prostaglandin E1 (n = 789) during their hospital stay. The treatment period lasted for up to 28 days. MEASUREMENTS: A combined end point consisting of death and peripheral and cardiocerebrovascular illness (major amputation or persistence of critical leg ischemia, acute myocardial infarction, or stroke) evaluated at hospital discharge and during 6 months of follow-up. RESULTS: The incidence of the combined outcome measure was lower in the alprostadil group than in controls at hospital discharge (493 [63.9%] patients compared with 581 [73.6%] patients; relative risk, 0.87 [95% CI, 0.81 to 0.93]; P < 0.001) but differed only modestly at 6 months (348 of 661 [52.6%] patients compared with 387 of 673 [57.5%] patients; relative risk, 0.92 [CI, 0.83 to 1.01]; P = 0.074). Most of the observed benefit was due to recovery from critical leg ischemia. CONCLUSIONS: Short-term treatment with alprostadil-alpha-cyclodextrine provides patients with critical leg ischemia clinical benefit that is apparent in the short term but decreases over time.

Aged↗
PubMedDate not supplied

Intraurethral and topical agents.

In early 1997, the FDA approved a transurethral delivery system for a urethral suppository containing alprostadil (PGE(1)), manufactured by Vivus and called the MUSE system. Pharmacokinetic studies showed rapid absorption from the urethra (80%) in the first 10 minutes after an intraurethral dose. 873 patients tried home use of alprostadil or blinded placebos. 64.9% of the patients on alprostadil reported intercourse compared to only 18.6% of the placebo group. Successful use of MUSE at home seemed to be equal in all categories of impotence. The consistency of response increased slightly over a period of 3 months. Penile pain occurred in 32.1% of patients receiving the active ingredient (10.8% of all applications). With the MUSE system, there was minor urethral trauma in 5.1% of the patients. A small subset of patients who used MUSE reported that previous intracavernosal injection therapy was not effective. Of these, 58% reported erections sufficient for intercourse after MUSE introduction. Recently, further efficacy studies were performed in a FDA trial of the combination of the MUSE system with the veno-occlusive band (Actis). Topical medications have been anecdotally reported and do not produce spectacular results. These include organic nitrates and nitrites, minoxidil, papaverine and PGE(1) or PGE2.

Journal Article↗
PubMed2000

Economic cost of male erectile dysfunction using a decision analytic model: for a hypothetical managed-care plan of 100,000 members.

OBJECTIVE: This paper examined the economic cost of male erectile dysfunction (ED) for a hypothetical managed-care (MC) model. DESIGN AND SETTING: A prevalence-based cost-of-illness approach was used to estimate the direct medical cost for ED treatment. A treatment plan algorithm was developed from a MC perspective to model the initial treatment selection of various patient groups [vacuum erection device, intracavernosal injection (ICI) therapy, transurethral alprostadil suppository, sildenafil, testosterone replacement therapy, penile prosthesis] and their therapy outcomes during a 3-year period. Overall cost was based on 1998 US dollars. Total direct medical cost of ED considered in this model included the cost of initial physician consultation and evaluation, the cost incurred by patients from various treatment groups (pharmacological and surgical options), as well as the cost related to patients' follow-up for treatment within the 3-year period. Consideration for therapy switches made by patients who failed initial therapy was included as part of the clinical assumptions for this model. Treatment response and expected outcomes (dropouts) were considered for the various treatment options. PARTICIPANTS: A total of 100,000 enrolled members were included in the study. MAIN OUTCOME MEASURES AND RESULTS: The total cost of ED was $US3,204,792 for the 3-year period in the hypothetical MC plan. The treatment portion accounted for approximately 80% of the total cost while the cost of medical services and diagnostic tests were minimal in comparison. The 3 year total cost of nonsurgical treatment was $US2,473,045. Costs associated with each treatment alternative were $US81,866 (testosterone transdermal patch), $US51,930 (vacuum erection device), $US384,624 (ICI therapy), $US226,483 (transurethral alprostadil suppository) and $US1,728,142 (sildenafil citrate). Results from the model showed a noticeable trend of decreasing cost patterns over time and reflected the attrition observed for many of the standard medical therapies for ED. CONCLUSIONS: Sildenafil and the vacuum erection device should be considered as first-line management strategies for ED whereas ICI therapy, transurethral alprostadil suppository and penile prosthesis implant should be reserved for second- or third-line therapy. Because costs associated with switches related to successive treatment failures can be high, treatment considerations should, therefore, focus on achieving long term patient satisfaction. The patient's preferred treatment choice, using goal-directed therapy during the initial consultation and evaluation visit, should be used.

Adult↗
PubMed1998

Combination therapy using oral alpha-blockers and intracavernosal injection in men with erectile dysfunction.

OBJECTIVES: Intracavernosal injection with a combination of agents (ie, phentolamine plus papaverine or alprostadil) has been used in an effort to increase efficacy and reduce side effects compared with single agents. The purpose of this pilot study was to determine the potential role of oral alpha-blockers in combination with intracavernosal therapy in men with erectile dysfunction, for whom intracavernosal therapy alone failed. METHODS: Thirty-eight consecutive men with moderate to severe erectile dysfunction on the basis of history and examination and with minimal or no therapeutic response to intracavernosal alprostadil injection therapy were evaluated. All patients received daily doxazosin titrated to 4 mg over 3 weeks in combination with intracavernosal therapy as needed for 12 weeks. Efficacy was assessed at 4, 8, and 12 weeks after doxazosin titration using the 1 5-item, self-administered International Index of Erectile Function (IIEF) and a global efficacy question (GEQ: Did treatment improve your erections?). RESULTS: For the group, the mean baseline IIEF score before therapy was 29.7+/-9.8. After intracavernosal therapy (mean dose 34.7+/-7.3 microg), IIEF improved to 36.1+/-1 1.4 (17.7%). After addition of doxazosin, IIEF improved to 48.6+/-13.4, 46.4+/-10.9, and 51.5+/-14.3 at 4, 8, and 12 weeks, respectively (P < 0.01). The GEQ response improved from 25.7% at baseline to 81.4% at 12 weeks. Overall 22 (57.9%) of 38 patients with the combined regimen had a significant (more than 60% improvement in IIEF) therapeutic response. CONCLUSIONS: The addition of an oral alpha-blocker may have a beneficial effect in patients with erectile dysfunction for whom intracavernosal therapy alone fails. The synergistic effects of vascular dilation and blockade of sympathetic inhibition may explain this response. The potential role of alpha-blockade in synergy with other agents designed to treat erectile dysfunction remains to be determined.

Administration, Oral↗
PubMed2003

Hemostatic and fibrinolytic effects of systemic prostaglandin E1 therapy in patients with peripheral arterial disease.

BACKGROUND: The study was designed to evaluate if there is any evidence of a hyperfibrinolytic bleeding-risk under systemic treatment with prostaglandin E1 (PGE1) of patients with peripheral arterial disease (PAD). PATIENTS AND METHODS: The in vivo effect of PGE1 on the fibrinolytic and hemostatic process was tested on 15 patients before and after treatment with Alprostadil for 21 days using D-dimers (DD), fibrinogen, prothrombin time (PT), partial thromboplastin time (PTT), antithrombin (AT), ProC-Global, plasminogen, plasminogen activator inhibitor activity (PAI), alpha 2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity (fib. cap.). RESULTS: There was no significant difference in DD, fibrinogen, PT, PTT, AT, ProC-Global, plasminogen, PAI, alpha 2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity observed after the treatment. CONCLUSION: Summarizing this study there is no hyperfibrinolytic bleeding-risk after the systemic therapy with Alprostadil to be expected.

Aged↗
PubMed2005

Use of combined intracorporal injection and a phosphodiesterase-5 inhibitor therapy for men with a suboptimal response to sildenafil and/or vardenafil monotherapy after radical retropubic prostatectomy.

OBJECTIVE: To report experience with combined therapy using intracorporal injection (ICI) of alprostadil and oral phosphodiesterase 5 (PDE-5) inhibitors for the minimally invasive treatment of erectile dysfunction (ED) after radical prostatectomy (RP), as PDE-5 inhibitors are effective but a few patients may have a suboptimal response. PATIENTS AND METHODS: In a retrospective study, 34 men (aged 46-66 years) had a nerve-sparing retropubic RP and subsequent ED. Patients were titrated on sildenafil citrate or vardenafil to maximum doses. All had a suboptimal response after a maximum of eight doses of oral therapy and were then treated with ICI therapy using 15 or 20 microg alprostadil. Erectile function was assessed with the Sexual Health Inventory for Men (SHIM). RESULTS: Of the 32 patients who continued combined therapy, 22 (68%) had an improvement in erectile function after ICI therapy, as assessed by the SHIM score. On follow-up, 36% of these patients used ICI therapy only intermittently, instead of regularly, as they felt that this was adequate enough for good results. CONCLUSIONS: PDE-5 oral pharmacotherapy is the most commonly used effective therapy for ED but may not be as effective in patients who have radical surgery; the addition of testosterone patches may have side-effects or be considered a risk in patients with a history of prostate cancer. The use of ICI therapy as an adjunct or maintenance therapy to their oral medication may be another alternative in these patients.

Administration, Oral↗
PubMed2001

Inhibition of salivary secretion by lipopolysaccharide: possible role of prostaglandins.

Inducible (calcium-independent) nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important in the regulation of the function of different organs during infection. A single dose of lipopolysaccharide (LPS; 5 mg/kg ip) within 6 h increased NOS activity (20%) and prostaglandin E (PGE) content (100%) in submandibular glands (SMG) and blocked stimulated salivary secretion in adult male rats. The administration of an iNOS synthesis inhibitor, aminoguanidine (AG), with LPS decreased NOS activity and PGE content. Furthermore, the administration of meloxicam (MLX), an inhibitor of COX-2, blocked the increase in PGE and the production of NO. The incubation of slices of SMG in the presence of 3-morpholinosydnonimine, a donor of NO, increased the release of PGE highly significantly. The incubation of SMG in the presence of a PGE(1) analog (alprostadil) increased the production of NO. These results indicate that LPS activates NOS, leading to NO release, which activates COX, generating PGEs that act back to further activate NOS, causing further generation of PGEs by activation of COX. Because the alprostadil administration inhibited stimulated salivation, LPS-induced inhibition of salivation appears to be caused by increased PGE production. Diminished salivary secretion produces poor oral health; thus the use of COX-2 inhibitors to counteract the effects of inhibited salivation should be considered.

Alprostadil↗
PubMed2004

Pharmacologic treatments for acute respiratory distress syndrome and acute lung injury: systematic review and meta-analysis.

BACKGROUND: Multiple pharmacologic treatments have been studied for patients with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Our objective was to systematically evaluate this literature to determine the effects of these interventions on important clinical outcomes. METHODS: We searched OVID versions of CENTRAL (The Cochrane Library Issue 3, 2003), MEDLINE (1966-week 2, January 2004), EMBASE (1980-week 4, 2004), CINAHL (1982-week 2, January 2004), and HEALTHSTAR (1995-December 2003); proceedings from four conferences (1994-2003); and bibliographies of review articles and included studies. We included randomized controlled trials (RCTs) of pharmacologic treatments compared with no therapy or placebo for established ARDS and ALI in adults admitted to an intensive care unit, with measurement of early mortality, late mortality, duration of ventilation, ventilator-free days, non-pulmonary organ dysfunction, or adverse events. We excluded trials in other populations incorporating subgroup analyses of patients with ARDS and ALI and studies of nitric oxide, partial liquid ventilation, and fluid and nutritional interventions. Two reviewers independently screened studies and abstracted data from studies included in the analysis. Data were pooled using random effects models where appropriate. RESULTS: We retrieved 75 potentially relevant articles and abstracts, of which 33 trials randomizing 3272 patients met our selection criteria. Meta-analysis showed no effect on early mortality for alprostadil ([prostaglandin E(1)] seven studies; 693 patients; relative risk [RR] 0.95; 95% confidence interval [CI], 0.77, 1.17), acetylcysteine (five studies; 235 patients; RR 0.89; 95% CI, 0.65, 1.21), early high-dose corticosteroids (two studies; 180 patients; RR 1.12; 95% CI, 0.72, 1.74), or surfactant therapy (nine studies; 1418 patients; RR 0.93; 95% CI, 0.77, 1.12). Most trials of alprostadil, early high-dose corticosteroids, and surfactant therapy showed more adverse events in the active therapy arm. Single small RCTs demonstrated lower hospital mortality (24 patients, RR 0.20; 95% CI, 0.05, 0.81) with corticosteroids for late phase ARDS and lower 1-month mortality (30 patients, RR 0.67; 95% CI, 0.47, 0.95) with pentoxifylline for patients with metastatic cancer and ARDS. Individual trials of nine additional interventions failed to show beneficial effects on prespecified outcomes. CONCLUSIONS: Effective pharmacotherapy for ARDS is extremely limited. Corticosteroids for late phase ARDS and pentoxifylline for patients with metastatic cancer and ARDS reduced mortality in single small studies. However, further research is required to investigate their potential benefit in the treatment of ALI/ARDS.

Acetylcysteine↗
PubMedDate not supplied

[Place of intra-urethral prostaglandin E1 for the treatment of erectile dysfunction].

Transurethral alprostadil (MUSE) is an effective and safe treatment of erectile dysfunction. Never the less, the result after its exit on the US market two years ago were not as good as the investigational studies which claimed around 60% of success rate. In the literature success rate were between 35% and 40% all together. The MUSE had a better acceptance than the intra-cavernous injection despite a lower success rate (40% vs 75%). Since sildenafil came on the market, it seems that the place of MUSE is reduced because comparative studies give better results for sildenafil than MUSE (70% vs 40%) and of course with a better acceptance. Never the less there are absolute and relative counter-indications to the sildenafil which could benefit to the treatment by MUSE. All the comparative studies, IIC, vs MUSE and sildenafil vs MUSE will be studied in this article. In conclusion MUSE should be used as an alternative and should remain an effective tool that must be available to all physicians dealing with erectile dysfunction, perhaps using new formula with a combination of alprostadil with an alpha-blocker.

Alprostadil↗
PubMedDate not supplied

Prospects of prostanoid therapy. Preliminary results.

BACKGROUND: To evaluate the efficacy of treatment with prostaglandins (Iloprost and Alprostadil) in patients with peripheral arterial disease in whom a surgical act or a redo operation is not proposable and to set the role of these drugs in the therapy of arterial diseases. METHODS: We analyzed the results of 96 treatments in patients with peripheral arterial diseases of different etiology, treated in the Day Hospital in the Division of Vascular Surgery from the 1/1/1993 to the 30/6/1998. The efficacy of the treatment has been evaluated on the basis of the clinical picture (healing or reduction of ulcers, reduction of rest-pain, improvement of the ability to walk). RESULTS: We had positive results in 60% of the patients who completed the treatment, a good outcome for patients with particularly severe arterial disease. Interruptions induced by the occurrence of uncontrolled side-effects are a few (6.25%). Better results have been found in a special category of disease (arterial diseases not associated with diabetes, not very advanced clinical picture, female gender). Iloprost proved to be superior to Alprostadil. CONCLUSIONS: Prostaglandins today represent an effective therapeutic solution to be considered. Further studies need to be done to find a category of patients who can have the best benefit from this kind of drug.

Adult↗
PubMed2002

[Retrospective study on the incidence and cause of drop-out during intracavernous pharmaco-prosthesis therapy].

OBJECTIVE: We report a retrospective analysis of 394 patients affected by erectile dysfunction and enrolled in a self-injection program after a positive injection test with alprostadil or vasoactive mixture, evaluating the rate and the causes of drop-out. We analyzed these data in two different groups of patients, classified on the basis of the training received before home therapy. METHODS: 286 patients, included in group I, were trained in a single visit, in which the technique of injection was demonstrated on a rubber model. 108 patients, included in group II, were trained in a first office visit, consisting in demonstration and guided self-injection, and a home training trial of 3 self-injections, each followed by an office visit in which any questions or problems encountered during home therapy were discussed with the physician. All the patients enrolled in the self-injection program were contacted, after a follow-up of 2-8 years, and invited to an office visit or a phone interview, in order to answer to a questionnaire. RESULTS: 62% of the patients of group I had discontinued therapy. Among these inactive patients, 79% had ceased therapy during the initial four self-injections. The most commonly cited reason for attrition was ineffectiveness (61%), followed by recovery of spontaneous erectile activity (17%). Satisfaction rate with therapy in active patients was high, with 89% of patients reporting a score of 3 (satisfied) or 4 (very satisfied). Among the 99 patients of group II, only 4 had discontinued therapy. Two of them had dropped out because of a recovery of potency. A high rate of patients satisfied with therapy was observed also in this group (78%). CONCLUSIONS: Data provided by the patients enrolled in a self-injection protocol confirm alprostadil as a very effective and well tolerated therapeutic option for erectile dysfunction. The high drop-out rate registered during the initial period of therapy, and ineffectiveness as the most cited reason, underline the importance of a closer monitoring of patients in the early therapy in order to improve acceptance.

Adult↗