Use of intravenous alprostadil in patients with severe critical ischemia of the lower limbs.

OBJECTIVES: To determine the indications for the use, potential benefits, and adverse reactions of alprostadil in a group of Colombian patients. METHODS: A retrospective cross-sectional study was conducted in patients diagnosed with critical limb ischemia who received alprostadil in five hospitals in Colombia between September 2011 and July 2017. We reviewed the clinical records of each patient to obtain the sociodemographic and pharmacological variables, clinical stages, complications, comorbidities, reported effectiveness and adverse reactions. RESULTS: Sixty-one patients treated with alprostadil were evaluated; 50.8% of patients were men, and the average age of 72.5 ± 10.7 years. A total of 86.9% of patients were hypertensive, and 65.6% were diabetic. A total of 77.0% presented ulceration, and this condition was considered as a diabetic foot in 57.4% of patients. A total of 81.9% of patients were classified as Fontaine stage 4; 60.7% received therapy as initially indicated, with an average of 19 days of alprostadil use. Regarding the therapy results, 58.0% of the patients with ulcers or trophic lesions showed improvement, 86.2% showed improvement of pain, and the limb was saved in 72.1% of patients. CONCLUSIONS: Critical limb ischemia was presented by patients with advanced age and high cardiovascular risk who were treated during severe and advanced stages where therapeutic options are limited. Treatment with alprostadil achieved satisfactory results with improvement in ulcers, pain, and limb salvage rates in this series of patients.

Morphological Findings in Trophozoites during Amoebic Abscess Development in Misoprostol-Treated BALB/c Mice.

During amoebic liver abscess (ALA) formation in susceptible animals, immune response is regulated by prostaglandin E2 (PGE2) dependent mechanisms. The aim of this study was to analyze the effect of misoprostol (MPL), a PGE1 analogue, on ALA formation in BALB/c mice. Male mice from BALB/c strain were intrahepatically infected with 7.5 × 10(5) trophozoites of E. histolytica strain HM1:IMSS and treated with 10(-4) M of MPL daily until sacrifice at 2, 4, and 7 days postinfection (p.i.). ALA formation was evaluated at 2, 4, and 7 days postinfection; trophozoite morphology was analyzed using immunohistochemistry and image analysis. Results showed an increase in frequency of ALA formation in infected and MPL-treated mice only at 2 days p.i. (P = 0.03). A significant diminution in the size of trophozoites was detected in abscesses from mice independently of MPL treatment (from 5.8 ± 1.1 µm at 2 days p.i. to 2.7 ± 1.9 µm at 7 days p.i.) compared with trophozoites dimensions observed in susceptible hamsters (9.6 ± 2.7 µm) (P < 0.01). These results suggest that MPL treatment may modify the adequate control of inflammatory process to allow the persistence of trophozoites in the liver; however, natural resistance mechanisms cannot be discarded.

Percutaneous radiofrequency ablation of renal parenchyma: experimental study on the optimal temperature and the impact of vasoactive drugs.

BACKGROUND AND PURPOSE: Radiofrequency (RF) is an efficient, inexpensive, safe, and friendly option for the management of small renal tumors. The objective was to evaluate the ideal temperature for renal cell destruction in dogs by RF and to verify whether the injection of vasoactive drugs, such as prostaglandin E1 and adrenaline, can help to improve the results, compared with "dry" RF ablation. MATERIALS AND METHODS: The study was divided into three phases: Initially, 16 dogs of comparable weight underwent RF ablation of the renal parenchyma at temperatures of 80°C, 90°C, and 100°C. After that, seven other dogs received adrenaline (vasoconstrictor) and seven received prostaglandin E1 (vasodilator). Finally, the results from 14 animals were compared with those of the 16 (dry RF) dogs at the optimum temperature found. After 14 days, the animals underwent nephrectomy to evaluate the size of the lesions (width and depth), histology examination, and were then sacrificed. RESULTS: There were no clinical or surgical complications in any of the dogs, and none died before the 14th day after the procedure. The optimum temperature was found to be 90°C. Prostaglandin E1 resulted in significantly larger lesions (in depth and width) than adrenaline, with lower impedance. Prostaglandin did not increase the lesions compared with dry RF. All the kidneys presented total coagulation necrosis, with no viable cells in the histologic analysis of the treated tissue. CONCLUSION: In the ablation of renal cells by RF, prostaglandin produced larger lesions (in depth and width) than the same procedure using adrenaline, and its performance was similar to that of RF without injection of drugs.

[Neonatal cortical hyperostosis. A side effect of prolonged prostaglandin E1 infusion]. / Hiperostosis cortical neonatal. Un efecto colateral de la administración prolongada de prostaglandinas E1.

Prostaglandin E1 (PGE1) infusion is usually administered for short periods to maintain patency of ductus arteriosus in infants with cyanotic heart disease. Prolonged therapy may be necessary while patients are awaiting surgical treatment. Several side effects occur at the onset of the treatment, most of them reversible once the treatment is discontinued. Cortical hyperostosis is a frequent complication of prolonged PGE1 infusion. Objective is to determine the incidence and severity of cortical hyperostosis in newborn requiring prolonged prostaglandin E1 infusion. 61 newborn babies were admitted in the Neonatal Intensive Care Unit at Bazterrica Clinic, Buenos Aires City, from January 2006 to May 2010. Five newborn received prolonged PGE1 therapy defined as a longer-than-one-week treatment. Four of them had radiologic evidence of cortical hyperostosis and elevated serum alkaline phosphatase. Accurate and rapid diagnosis of this condition is critical to reduce unnecessary laboratory tests and to avoid cardiac surgery cancelling.

Enteral feeding in prostaglandin-dependent neonates: is it a safe practice?

In many centers presurgical term neonates with prostaglandin-dependent cardiac lesions experience nutritional deficiency because of postponed enteral feeds. We recently adopted early enteral feeding in these infants. This retrospective study demonstrates feeding tolerance in 33 of 34 neonates fed enterally while receiving prostaglandin, suggesting the safety of this practice.

Effects of prostaglandin E(1) in the genesis of blood capillaries in the ischemic skeletal muscle of rats: ultrastructural analysis.

Our aim was to study the ultrastructural aspects in the genesis of blood capillaries in the lower limb skeletal muscle of rats submitted to ischemia under the action of intramuscular or endovenous prostaglandin E(1) (PGE(1)). Twelve Wistar-UEM rats were used, randomly distributed into three groups of four animals each, equally redistributed into two subgroups, observed at 7 and 14 days as follows: group only with ischemia was considered as control (I), group with ischemia and intramuscular injection of PGE(1) (IM), and group with ischemia and endovenous injection of PGE(1) (EV). Results were analyzed by transmission electronic microscopy (TEM). TEM analysis revealed evidence of new capillary formation. TEM permitted us to identify morphological structures and phenomena in vascular neoformation that might have occurred through angiogenesis and/or vasculogenesis.

Estrous cycle-dependent differences in responsiveness to prostaglandins and contractile agents in sheep (Ovis aries) cervical smooth muscle.

We investigated the influence of the phase of the estrous cycle on mechanical responses elicited in sheep cervix by potassium chloride (KCl), acetylcholine chloride (ACh), prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E1 (PGE1). The cervix of adult ewes (n = 48) were classified according to the presence or absence of corpora lutea (luteal or follicular phase, respectively). Muscle strips of the circular and longitudinal layers were prepared in an organ bath and coupled to an isometric force transducer. Concentration-response curves were obtained noncumulatively. KCl and ACh produced concentration-dependent contractions in all preparations in both phases of the estrous cycle. However, maximum effect, EC50 and slope values of KCl and ACh were not significantly different between muscle layers, as well as between the phases of the estrous cycle. The prostanoid, PGF2 alpha, produced a significant reduction in the amplitude of spontaneous contractions for all preparations. The depressant effect of PGF2 alpha on spontaneous contractions of circular smooth muscle was significantly greater during the follicular than the luteal phase, whilst the depressant effect of PGF2 alpha on the longitudinal layer did not differ between phases of the estrous cycle. PGE1 significantly reduced the amplitude of spontaneous contractions on circular but not on longitudinal preparations. In conclusion, we have characterized with in vitro preparations of circular and longitudinal muscle layers of ewes during the follicular and luteal phases of the estrous cycle, the parameters of the K- and ACh-induced contractions on cervix and the efficacy of PGF2 alpha and PGE1 on inhibition spontaneous contractile activity.

Topical alprostadil cream for the treatment of erectile dysfunction.

Erectile dysfunction (ED) has serious negative consequences on both sexual experience and emotional well being and affects a broad range of age groups. The prevalence of ED is associated with increasing age and has been reported to be as high as 70%. Although the disorder is common and underdiagnosed, its treatment can significantly improve patients' quality of life. Systemic treatment with oral phosphodiesterase type-5 (PDE-5) inhibitors is the current standard of care for patients with ED. Some patients, however, have absolute contraindications for PDE-5 inhibitors. In addition, these agents can be associated with adverse effects. Furthermore, because PDE-5 inhibitors are not as effective in patients who have undergone radical prostatectomy or who have severe vascular disease, a substantial unmet medical need exists among patients who have ED as a result of these conditions. Consequently, PDE-5 inhibitor therapy is associated with a high rate of discontinuation, as are intracavernosal or transurethral therapies, which are inconvenient and invasive. Several studies, including four double-blind, placebo-controlled, Phase II trials, show that alprostadil topical cream is efficacious and well-tolerated in ED in patients with mild-to-severe symptoms, in those undergoing treatment for cardiovascular diseases and diabetes and in otherwise healthy ED patients. Thus, alprostadil topical cream is a potential first-choice alternative for ED in patients who do not respond or who cannot tolerate or do not accept PDE-5 inhibitor therapy.

Anxiety and high plasma catecholamines do not impair pharmaco-induced erection of psychogenic erectile dysfunctional patients.

The aim of this study was to assess the influence of anxiety and plasma catecholamines on the pharmaco-induced erection of psychogenic erectile dysfunction (ED) patients. A total of 23 patients with psychogenic ED aged from 19 to 43 y were submitted to: (1) anxiety evaluation by the Spielberger's State and Trait Anxiety Inventory-STAI; (2) intracavernous injection of PGE1 10 microg+phentolamine 1 mg with the response monitored by Rigiscan; (3) blood sampling from cavernous bodies and cubital vein for adrenaline and noradrenaline levels determination by high performance liquid chromatography. The whole procedure was done in a single clinical setting at the same day. We found no significant correlation between the erection rigidity and the cavernous or peripheral catecholamines or between erection rigidity and anxiety scores. Some patients showed rigid erections despite high anxiety scores or penile catecholamine levels while others, with incomplete erections, had much smaller levels. These results are suggestive of a more complex mechanism controlling the penile sympathetic responsiveness in psychogenic ED patients.

Duplex Doppler ultrasound assessment of clitoral hemodynamics after topical administration of alprostadil in women with arousal and orgasmic disorders.

There are limited hemodynamic data in women with arousal or orgasmic disorders and even fewer normative control hemodynamic data in women without sexual dysfunction. In addition, there is limited experience with topical vasoactive agents (used to maximize genital smooth muscle relaxation) applied to the external genitalia during hemodynamic evaluations. The aim of this study was to report duplex Doppler ultrasound clitoral cavernosal arterial changes before and after topical PGE-1 (Alprostadil) administration in control women and in patients with arousal and orgasmic sexual disorders. We found that women with sexual arousal and orgasmic disorders had significantly (p < 0.05) diminished clitoral peak systolic and end diastolic velocity responses compared to controls. Further research is needed to establish the diagnostic role of topical vasoactive agents in the hemodynamic evaluation of women with sexual dysfunction.

Cervical ripening with prostaglandin E1: how an ambulatory method decreases the hospital stay in abortus with intrauterine fetal demise.

OBJECTIVE: This study was designed to determine whether use of prostaglandin E(1 )(PGE(1)) is justified to improve the known clinical outcome of prostaglandin E(2) (PGE(2)) gel, because PGE(2) gel preparations are more costly than PGE(1) tablets in most countries, and data to support the use of the gel in clinical practice is not conclusive. The aim was to compare the safety and efficacy of PGE(1) gel when applied in both an in-hospital or ambulatory setting to oxytocin infusion in those women with unfavorable cervical conditions prior to surgical abortion for either medical or obstetrical indications with intrauterine fetal demise. Surgical dilatation of the unripe cervix may result in cervical injury of uterine perforation which could prolong the hospital stay. METHODS: We used PGE(1) gel prepared from tablets and administered in the ambulatory form (group 1), the same PGE(1) gel administered in the labor room (group 2) and intravenously administered oxytocin in the labor room (group 3) for the induction of abortus in women complicated with intrauterine fetus death and missed abortion. Patients requesting abortion were eligible for inclusion, with >8 and <13 weeks of gestation. Eighty-nine women with unfavorable cervices (Bishop score

Clitoral hemodynamic changes after a topical application of alprostadil.

We performed duplex ultrasonography of the clitoris to assess the local hemodynamic changes after a topical application of alprostadil. Color duplex ultrasonography was used to evaluate 18 women before and after the application of 1 g of 0.2% alprostadil gel. The peak systolic velocity and end diastolic velocity showed a statistically significant difference after the application. All women showed labial and clitoral engorgement, 72% reported a pleasant sensation of warmth, and no systemic side effects were found. These findings are similar to the values reported after sexual stimulation, indicating that topical vasoactive drugs might help in the differential diagnosis of the vascular component of female sexual dysfunction.

Intracavernous injection in the treatment of erectile dysfunction after radical prostatectomy: an observational study.

CONTEXT: Despite the recent improvements in performing radical retropubic prostatectomy that have led to a considerable decrease in the complication rate, erectile dysfunction still represents a major problem. Moreover, less invasive treatment options that are emerging for erectile dysfunction have not shown satisfactory results in managing these patients. OBJECTIVE: To study the efficacy and side effects of self-injection therapy in the treatment of men who had become impotent after undergoing radical prostatectomy due to prostate cancer, over a study period of 96 months. DESIGN: Observational study. SETTING: University Referral Center. PARTICIPANTS: 168 patients with erectile dysfunction, aged 43 to 78 years old, who underwent radical retropubic prostatectomy due to localized prostate cancer. PROCEDURES: The patients were treated with self-injection therapy using papaverine, phentolamine and prostaglandin E1, at home. RESULTS: This study showed an acceptable 94.6% success rate, with no life-threatening complications. In addition to this, our series presented a 13.1% cure rate with this therapy. CONCLUSION: Self-injection therapy with papaverine, phentolamine and prostaglandin E1 is effective and safe in the treatment of erectile dysfunction after radical prostatectomy.

Embarazo a término: inducción del trabajo de parto con análogos de prostanglandina E1 y E2 / Term pregnancy: induction of the labor with prostanglandins analog E1 y E2

Lograr la inducción del trabajo de parto en embarazo a término, mediante el uso de análogo sintético de prostanglandina E1 intravaginal y E2 intracervical, comparando la eficacia, seguridad y costos de ambos. Estudio prospectivo, descriptivo, comparativo en 60 pacientes distribuidas al azar en dos grupos, uno de 29 y otro de 31 pacientes para recibir 50 µg de misoprostol intravaginal cada tres horas por seis dosis y 0,5 mg de dinoprostona intracervical cada 6 horas por tres dosis, respectivamente, desde abril de 1996 hasta octubre del mismo año. Hospital Universitario de Caracas, Venezuela. El grupo que recibió misoprostol requirió menor número de dósis, utilizados con mayor frecuencia una sola dosis (73 por ciento vs 43 por ciento), no requirió uso adicional de oxitocina y los costos fueron menores en comparación con el grupo que recibió dinoprostona, estas diferencias fueron estadísticamente significativas (p<0,10). El microprostol intravaginal es más efectivo, económico e igualmente seguro que la dinoprostona intracervical

Alprostadil transuretral no tratamento da disfunçäo erétil / Transuretral alprostadil in the treatment of erectile dysfunction

Foram estudados 31 pacientes com disfunçäo erétil de várias etiologias, com idade entre 21 e 72 anos (mediana de 57 anos) que receberam três aplicadores contendo placêbo e três contendo 500 mcg de alprostadil, para administraçäo transuretral. Num seguimento de seis meses, apenas nove pacientes (29,03 porcento) relataram ereçöes rígidas ou suficientes para penetraçäo vaginal. Dentre esses nove pacientes que responderam bem ao tratamento, seis (66,66 porcento) apresentaram ereçöes adequadas para manter relaçöes sexuais também com o placebo; sete (77,77 porcento) apresentavam disfunçäo erétil de etiologia psicogênica e seis (66,66 porcento) tinham idade igual ou inferior a 45 anos. O alprostadil transuretral apresentou resultados muito ruins entre os pacientes com disfunçäo erétil orgânica e näo apresentou nenhuma resposta naqueles pacientes com disfunçäo erétil pós prostatectomia radical. Por outro lado, as complicaçöes foram discretas, representadas por 12,90 porcento de dor peniana; 3,22 porcento de uretrorragia e 3,22 porcento de lesäo do meato uretral. O alprostadil transuretral apresentou resultados insatisfatórios no tratamento da disfunçäo erétil, näo se constituindo até o momento numa opçäo terapêutica adequada para os pacientes com disfunçäo erétil orgânica por nós estudados

Drop-out reasons and complications in self-injection therapy with a triple vasoactive drug mixture in sexual erectile dysfunction.

The usefulness, complications and reasons for discontinuing the self-injection program with a combination of papaverine, phentolamine and prostaglandin E1 were evaluated in 189 patients (mean age 57.2 y), who were included from April 1993 to September 1995 (mean follow-up 10.25 months). Patients were split into two groups: Active, those who continued with the program (48%); and Inactive, those who discontinued treatment or failed to attend consultation after five months from the last visit (52%). Only 30% of the inactive group reported failure to achieve response with the self-injected doses. Fibrosis in 5.3% and prolonged erection in 3.7% were the most severe complications. Patients lacking organic pathology showed a clear tendency to reduce the drug dose during treatment, recover spontaneous erections and discontinue the program for reasons unrelated to drug efficacy. The triple drug mixture provides an effective alternative in the treatment of impotence, with a low rate of complications.

Tratamiento de la impotencia post traumática con alprostadil intracavernoso / Treatment of the post-traumatic impotence with intracavernous alprostadil

Con el fin de tratar la impotencia sexual post-traumática se inició en 1995, el tratamiento con alprostadil intracavernoso. Se realizó diagnóstico con doppler de arteria cavernosa, potenciales evocados del nervio cavernoso y test de tumescencia peneana nocturna. Aquellos pacientes con impotencia orgánica se realizó una titulación progresiva; una vez conocida la dósis óptima se instruyó al paciente para la autoinyección. Un total de 15 pacientes entraron a este protocolo, con un seguimiento promedio de 12 meses. Después del análisis de los resultados, podemos concluir, que el tratamiento con alprostadil en este tipo de pacientes resulta ser eficiente; seguro y con gran satisfacción para los enfermos

The value of a second injection on the pharmaco-induced erection test.

In order to test the capability of a reinjection to improve an incomplete pharmaco-induced erection, we submitted 30 impotent patients, with incomplete erectile responses to 10 micrograms PGE1 + 1 mg phentolamine, to a second injection of 15 micrograms PGE1 + 1.5 mg phentolamine + 30 mg papaverine, fifteen minutes after the first injection. Twenty-one patients improved their erection including nine who achieved complete rigidity. We conclude that incomplete pharmaco-induced erections can frequently be improved by reinjection.

Comparative study of papaverine plus phentolamine versus prostaglandin E1 in erectile dysfunction.

PURPOSE: We compared the efficacy and short-term adverse effects of 1 ml. 30 mg./ml. papaverine plus 0.5 mg./ml. phentolamine versus 1 ml. 30 micrograms./ml. prostaglandin E1 in patients undergoing pharmacological erection testing. MATERIALS AND METHODS: A total of 60 patients (mean age 58 years) with a history of sexual erectile dysfunction longer than 6 months was randomly classified into 6 groups to be tested 1 week apart with the 2 solutions and with placebo to evaluate erection response and short-term adverse effects. RESULTS: Of the patients tested with papaverine plus phentolamine 54% responded with erections adequate for penetration, compared to 50% of those tested with prostaglandin E1 (p > 0.05). Prolonged erection occurred in 18% of patients tested with papaverine plus phentolamine and 15% of those tested with prostaglandin E1 (p > 0.05). Pain was reported by 15 and 35% of patients, respectively (p < 0.05). CONCLUSIONS: One ml. 30 mg./ml. papaverine plus 0.5 mg./ml. phentolamine has the same efficacy and equal prolonged erection rate as 1 ml. 30 micrograms./ml. prostaglandin E1 but the latter agent induces significantly more pain.