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Effects of prostaglandin E1 on the progression of aristolochic acid nephropathy.

OBJECTIVE: To investigate the effects of prostaglandin E1 (PGE1) on the progression of aristolochic acid nephropathy (AAN). METHODS: Twenty-four patients diagnosed as AAN with serum creatinine (Scr) between 1.5 mg/dL and 4 mg/dL during September 2001 to August 2003 were randomly divided into 2 groups. All patients had ingested long dan xie gan wan containing aristolochic acid (0.219 mg/g) for at least 3 months. Twelve patients were injected with Alprostadil (10 microg/d for 10 days in one month, summing up to 6 months). Except for PGE1, the other therapy was same in both groups. Renal function was assessed using reciprocal serum creatinine levels (1/Scr). RESULTS: The level of Scr an d serum hemoglobin (Hgb) was similar in both groups prior to therapy. During follow-up, 1/Scr levels in PGE1 group were significantly higher than control group (P < 0.01), and Hgb levels in PGE1 group were significantly increased compared with control (P < 0.05). CONCLUSION: PGE1 can slow the progression of renal failure and increase Hgb level of AAN patient.

Adult↗

[Sexual and global health: the role of the general practitioner].

Erectile dysfunction, a global health problem, has to must be considered not only as a consequence of vascular and/or psychological and/or neurological but also as the cause of a psychobehavioural disorder. The general practitioner has to screen for erectile dysfunction, prescribe treatment and its follow-up (patient's compliance, check the efficacy and tolerance) and, when necessary, explain and show the patient how to self-administer the intracavernous injections of alprostadil alfadex, which are a safe and efficient alternative.

Alprostadil↗

Effect of heparin and dihydroergotamine on platelet adenosine-3',5'-cyclic monophosphate.

Human platelet adenosine-3',5'-cyclic monophosphate (cAMP) levels were determined in platelet rich plasma (PRP) and in washed platelets by a modification of the protein binding assay; the validation of the method is described. Dihydroergotamine (DHE) inhibited epinephrine induced platelet aggregation (ID50 = 2.5 X 10(-7) mol/l), and increased cAMP levels in platelets by an alpha-adrenergic receptor blocking effect, since phentolamine but not propranolol, behaved similarly. The DHE induced cAMP accumulation was correlated to the inhibitory effect on aggregation and showed a characteristic alpha-adrenergic receptor pattern in the presence of alprostadil (PGE1) and epinephrine but not collagen or adenosine diphosphate (ADP). Thrombin induced aggregation was similarly affected by DHE but with 100 times higher concentration. Heparin was found to increase slightly ADP and epinephrine induced aggregation and to decrease cAMP. Also, heparin was found to inhibit thrombin induced platelet aggregation. In washed platelets, the inhibitory effect of thrombin on PGE1 induced cAMP accumulation was counteracted by heparin. This indicates that the binding site of thrombin on platelets is important in the control of adenyl cyclase. Evidence is presented that some of the beneficial synergistic effect of DHE and heparin may consist in the ability of those compounds to produce opposite effects on cAMP system in platelets.

Alprostadil↗

Prostaglandin E1 treatment in ductus dependent congenital cardiac malformation. A review of the treatment of 34 neonates.

Thirty-four sick neonates with major duct dependent cardiac defects were given short term (1 h-408 h) intravenous infusions of prostaglandin E1 (alprostadil) in doses varying between 0.1 micrograms/kg/min (starting dose) and 0.01 micrograms/kg/min. The aim of the study was to establish an effective and safe regiment that could be initiated after clinical diagnosis of a severe duct dependent cardiac defect, whose clinical course would be adversely affected by ductus closure. After an initial dosage of 0.1 micrograms/kg/min, effective clinical improvement was achieved in 28 infants (82%). In all 28 responders, the effect was maintained at a reduced dosage of 0.05 micrograms/kg/min, and in 21 a low dosage of 0.01 micrograms/kg/min was effective. Side effects, which occurred in 21 infants (62%), were reversible and dose related, and no serious side effects were noted at a dosage of less than 0.05 micrograms/kg/min. A starting dose of 0.05 micrograms/kg/min with subsequent reduction is recommended, but in case of institution of treatment before transfer to a pediatric cardiac centre a lower starting dose of 0.01 micrograms/kg/min may be preferred.

Acidosis↗

[Use of series E prostaglandins in the treatment of essential hypertension].

Fifty-four hypertensive patients with the average BP level of 208 +/- 3.2/125 +/- 2.4 mm Hg were infused 2 doses of PGE. Forty patients received PGE2 in the form of protein (USA) and 14 patients were administered PGE1 in the form of alprostadil (USA). Each patient received on the average 3.5 mg of PGE2 or 0.7 mg of PGE1 during 48 hours. PGE infusion by the devised scheme induced no significant side-effects, was attended by an increase in the diuresis and natriuresis as well as a BP decrease (more pronounced with PGE1) not only in the period of the infusion but also during the 2-3 days following it. The hypotensive effect and BP fall in the orthostatic position were more marked following PGE2 infusion. PGE enhanced the sensitivity of the patients to obsidan, clophelin, hydrochlorothiazide and to a lesser degree to corinfar. Infusion of PGE2 to patients with essential hypertension resistant to hypotensive agents reduced the BP and made it possible to diminish the number of the drugs prescribed and their doses. The hypotensive effect of the drugs administered persisted for up to 5-7 months. It can be expected that repeated infusions of PGE2 every 6 months, will contribute to an alleviation of arterial hypertension, the patient's clinical improvement and the lowering of doses of hypotensive drugs.

Adult↗

The effect of prostaglandin E1 on liver adenine nucleotides and cytoplasmic enzymes in a porcine model of normothermic hepatic ischemia.

The liver has been judged relatively resistant to ischemia, but prolonged inflow occlusion at normothermic conditions can produce evidence of reversible or irreversible hepatocellular damage. Cytoprotective agents have been used both experimentally and clinically to afford extended viability of hepatocytes under reduced perfusion. One agent, prostaglandin E1, has been described clinically as effective in sustaining liver function under ischemic conditions. We have sought to verify this observation in an experimental model using prolonged normothermic inflow occlusion. Twenty miniature pigs were anesthetized and subjected to subtotal normothermic hepatic inflow occlusion (portal vein, hepatic artery, choledochal vessels) to allow for sufficient splanchnic decompression. Half of the animals received pretreatment with prostaglandin E1 (alprostadil) 500 micrograms intravenously. Inflow occlusion was maintained for 2 hours followed by reperfusion and killing 24 hours later. As a measure of functional preservation, the tissue adenine nucleotides adenosine monophosphate, diphosphate, and triphosphate (AMP, ADP, ATP) were measured in ischemic liver by freeze-clamping and high-performance liquid chromatography during occlusion and after reperfusion. Cytosolic enzyme determinations (aspartate transaminase, alanine transaminase, lactate dehydrogenase) were also made before occlusion and after reperfusion. As a possible indicator of cellular injury, blood ionized Ca++ was measured before inflow occlusion and after reperfusion. Although no difference was found in levels of AMP and ADP between prostaglandin E1 and control animals, ATP levels rose significantly higher during recovery in prostaglandin E1 animals at 60 minutes and 24 hours after reperfusion (13.97 +/- 1.29 and 13.60 +/- 0.91 mumoles/gm dry weight prostaglandin E1 vs. 9.25 +/- 0.97 and 9.80 +/- 0.85 mumoles/gm dry weight co control, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

Evaluation of real-time RigiScan monitoring in pharmacological erection.

PURPOSE: The clinical assessment of pharmacologically induced erectile response was compared to the real-time RigiScan* monitoring response. MATERIALS AND METHODS: Erection was induced by 521 intracavernous injections of a new alprostadil formulation. The clinical end point was "full rigidity" and the RigiScan criterion was radial rigidity of 70% or more for 10 consecutive minutes or longer. RESULTS: For 752 prostaglandin E1 injections the sensitivity and specificity of the RigiScan device compared to clinical evaluation were 53.8% (133 of 247 cases) and 92.9% (469 of 505), respectively. For rigidity of 60% or greater the sensitivity increased to 70.8% (175 of 247 cases) and specificity decreased to 85.0% (429 of 505). CONCLUSIONS: The RigiScan device is useful to document objectively a pharmacologically induced erection yet it appears to be more conservative than clinical evaluation.

Adult↗

[Nonspecific anaphylactoid reaction in low IgE patients].

We reported two cases of anaphylactoid reaction caused by ranitidine and alprostadil. We suggest that these anaphylactoid reactions are nonspecific reactions which are observed in low IgE patients, because plasma IgE was still low 6 weeks after allergic reaction and these drugs have not been given to them before and eosinophilic and basophilic cells showed no change at all. We have to consider that there is a high risk of allergic reaction during general anesthesia, because many drugs are injected intravenously during general anesthesia.

Adult↗

The rationale for prostaglandin E1 in erectile failure: a survey of worldwide experience.

PURPOSE: Prostaglandin E1 (PGE1, alprostadil) is used worldwide for self-injection therapy in erectile failure and was recently officially approved for this purpose in the United States and most European countries. Therefore a comprehensive overview on biochemistry, pharmacology and therapeutic results of PGE1 is provided. MATERIALS AND METHODS: The relevant literature on PGE1 was reviewed along with personal experience with 4,577 patients during a 7-year period. PGE1 was compared to other vasoactive drugs, such as papaverine, the mixture of papaverine and phentolamine or linsidomine alone. RESULTS: In Europe PGE1 was officially approved for the therapy of peripheral arterial occlusive disease of the lower limbs in 1984. The drug has direct relaxing effects on smooth muscle cells of vessels and cavernous bodies, shows inhibitory effects on platelet aggregation, on low-density lipoprotein entry into the vascular wall and on presynaptic noradrenaline release and, therefore, it prevents the progress of atherosclerosis. In erectile failure PGE1 shows a response rate of more than 70% and, compared to papaverine with phentolamine, a considerably lower risk of priapism (0.35% versus 6%, respectively) as well as of local fibrotic complications. Except for rare cases of blood pressure decrease, no systemic side effects were observed after intracavernous injection of PGE1. CONCLUSIONS: For self-injection therapy, PGE1 presently represents the most efficacious and safest drug. Ongoing trials with topical and especially intraurethral PGE1 are promising and may offer less invasive therapies in the near future.

Alprostadil↗

[Epidemiology and treatment of long-term male impotence].

Male impotence has assumed increasing clinical importance and the perfection of diagnostic and therapeutic methods has opened new horizons for medical treatment. The aim of this paper is to provide a review of the epidemiology of this disorder with the relative diagnostic and therapeutic correlations. The authors report a series of 161 patients who were treated for one year at most with prostaglandin E1 (Alprostadil alpha-cyclodextrin).

Adult↗

[Effectiveness of continuous intravenous prostaglandin E 1 against pulmonary hypertension].

Pulmonary hypertension is a progressive disease for which no effective therapy has been found. Short-team treatment with alprostadil alfadex (PGE 1) can improve hemodynamics but the effects of long-term treatment have not been reported. We administered intravenous PGE 1 to 16 patients with pulmonary hypertension for 4 weeks in addition to conventional therapy. Hemodynamic and symptomatic effects were evaluated. The infusion was interrupted in 7 patients (44%) because of fever and an increase in levels of C-reactive protein in serum. In the remaining 9 patients, the drug lowered pulmonary artery pressure and resistance, and imareased cardiac output significantly in 7 patients. PGE 1 can improve hemodynamics and relieve symptoms in patients with pulmonary hypertension, barring severe side effects.

Adult↗

Free fatty acid-induced platelet aggregation: studies with solubilized and nonsolubilized fatty acids.

The aggregation response of washed porcine platelets to the sodium salts of stearic, oleic, palmitic, and myristic acids was analyzed turbidometrically. The fatty acids were prepared as aqueous suspensions and as taurocholate- or albumin-solubilized systems. The final concentration of fatty acid in the platelet preparation varied between 70 and 600 microM. This range was within or below the normal physiological limits of 300-1200 microM. Platelet aggregation was observed with both the suspended and taurocholate-solubilized fatty acids. The extent of platelet aggregate formation increased with the fatty acid concentration and chain length. With the exception of stearate, the taurocholate-solubilized fatty acids were more active than the suspensions. Albumin-solubilized fatty acids were devoid of platelet aggregating activity. Particle-size analysis of the solubilized fatty acids indicated that fatty acid precipitation had occurred subsequent to the addition of taurocholate-solubilized fatty acids to the platelets. This precipitation did not occur with the albumin-solubilized systems, suggesting that the fatty acids must assume a particulate physical state to induce aggregation. Platelet aggregation induced by fatty acids was not inhibited by 80 nM epoprostenol, 75 microM alprostadil, or 150 microM indomethacin. This finding indicated that the fatty acid-induced platelet aggregation was independent of cyclic AMP-related calcium shift, cyclooxygenase-arachidonate, or granular nucleotide release mechanisms.

Adenosine Diphosphate↗

Intracavernous pharmacotherapy.

Intracavernous application of vasoactive substances not only has enhanced our understanding of penile hemodynamics, the physiology of penile erection, and the pathophysiology of erectile dysfunction but also has revolutionized the diagnosis and treatment of erectile dysfunction in the last 15 years. Virag was the first to report on the erectile effect of papaverine in humans, and Brindley later reported the effect of intracavernous application of alpha-receptor-blocking agents on cavernous tissue. These reports led to numerous basic and clinical investigations and ultimately established a new treatment alternative for patients with erectile dysfunction that is now considered to be the treatment of choice for most patients. Changes in penile hemodynamics include the relaxation of cavernous smooth musculature and arteries, which leads to an increase in arterial blood flow and a restriction of venous outflow through a compression of subtunical veins. These hemodynamic changes are the prerequisite for the induction and maintenance of penile erection. With the intracavernous application of vasoactive substances it was possible to influence penile hemodynamics at a local level and to induce an erection despite alterations in the nervous system, penile arterial blood flow, cavernous musculature, or neurotransmitter status. In addition, the local application of pharmacologically active substances directly to the end organ enabled the achievement of high local drug concentrations without severe systemic side effects. The commonly used substances are papaverine the combination of papaverine and phentolamine, and prostaglandin E1 (alprostadil). In addition to these established substances, several other regimens, such as linsidomine (SIN-1), calcitonin gene-related peptide (CGRP), moxisylyte, and various triple- or quadruple-drug mixtures have been described. In addition, several other compounds as well as different routes of administration are on the horizon and may prove to be effective in the future diagnosis and treatment of erectile dysfunction.

Animals↗

[Acute mediastinitis due to esophageal perforation--a case report].

A 55-year-old female consulted her family physician because of pharyngeal discomfort after eating a fish. She underwent rigid fiberscopy and was pointed out a fish bone. Family physician failed to extract the bone and the patient was referred to our hospital. However, there was no fish bone in the esophagus when she underwent second rigid fiberscopy. After eight days she complained of dyspnea and was referred to our hospital again. Chest X ray film showed marked enlargement of the mediastinum and she was diagnosed as acute mediastinitis. She underwent mediastinal drainage by thoracotomy. So tiny perforation was found in cervical esophagus by endoscopy that primary suture was not done. After two months' follow up with intravenous hyperalimentation, there was still esophageal perforation. She underwent the second operation of primary closure with reinforcement using sternocleidomastoid muscle. Two weeks after the second operation esophagogram still showed a fistula. So she received injections of alprostadil and factor XIII. One month after the injections esophagogram showed a diverticulum without leakage.

Acute Disease↗

[Quality assurance in the urologist's practice. Erectile dysfunction as an example of a multicenter approach to documenting treatment results].

Of 517 urologist practices approached, 93% participated in a pilot study on the quality of care in the treatment of erectile dysfunction (ED). Treatment modalities and satisfaction were documented for 10,750 ED patients in 2002-at a time when vardenafil and tadalafil had not yet been officially approved. Psychological factors (55%), BPH (42%), and hypertension (33%) were given as the most prevalent ED risk factors; 82% of the patients received sildenafil, 20% apomorphine, 12% yohimbine, and 10% intracavernous alprostadil. Of the patients, 81% were satisfied or very satisfied with one of the treatment options offered and 85% and more were satisfied or very satisfied with sildenafil's onset of action, duration of action, efficacy, and tolerability. Of the physicians, 97% rated the opportunity to compare their own treatment results with other urologists' results as important or very important.

Adult↗

Morphologic findings and blood flow parameters of penile vasculature in patients with erectile dysfunction.

The objective was to study the risk factors in patients with erectile dysfunction in correlation with ultrasound findings of penile vasculature. Patients with erectile dysfunction were classified in four groups according to their risk factors. Group A (37 pts) who were heavy smokers, group B (40 pts) who suffered from diabetes mellitus, group C (30 pts) who suffered from hyperlipidemia and group D (40 pts) with no risk factors. The peak systolic velocity (PSV) was measured after the intracavernous injection of 10 mg alprostadile. Normal values were PSV>35 cm/s and endiastolic venous velocity<4 cm/s. It was found that the mean PSV in group A was 22.2+/-2.25 cm/s without venous leakage, in group B the mean PSV was 24.6+/-1.29 cm/s but there was a significant venous leakage (mean end-diastolic velocity 6.2+/-1.37 cm/s). Patients with hyperlipidemia (group C) had a mean PSV of 26.2+/-1.74 cm/s and insignificant venous leakage and patients in group D had a normal vascular profile. Patients with erectile dysfunction who are heavy smokers are predisposed to have penile arterial insufficiency, while diabetics have both arterial insufficiency and venous leakage.

Adult↗

Gossypol attenuates selectively the blood pressure lowering effect of endothelium-dependent vasodilators in the rabbit in vivo.

The in vivo blood pressure lowering effect of three vasodilators whose in vitro effects are endothelium-dependent (acetylcholine, substance P and adenosine triphosphate) was reduced by 40-60% after systemic treatment of the animals with gossypol. In vitro, gossypol is an inhibitor of the production and/or release of endothelium-derived relaxing factor. Systemically administered gossypol had no effect on blood pressure decreases produced by the endothelium-independent agents prostaglandin E1 (alprostadil) and glyceryl trinitrate. These results suggest that endothelium-mediated vasodilator mechanisms could participate in blood pressure regulation.

Acetylcholine↗

Implantable left ventricular assist device for treatment of pulmonary hypertension in candidates for orthotopic heart transplantation-a preliminary study.

OBJECTIVES: Elevated pulmonary vascular resistance (PVR) unresponsive to pharmacological intervention is a major limitation in heart transplantation (HTX). The post-operative course of these patients is associated with an increased risk of life-threatening right heart failure. We evaluated the efficiency of an implantable left ventricular assist device (LVAD) to decrease PVR by unloading the left ventricle and to lower the risk of later orthotopic HTX. METHODS: Six patients with end-stage heart failure (NYHA class IV) and 'fixed' pulmonary hypertension (PVR 5.7+/-0.7, range 4.4-6.5 Wood units) were analyzed. Despite maximal pharmacological intervention at initial evaluation (oxygen inhalation, nitrates, alprostadil infusion) PVR could not be reduced to under 2.5 Wood units. Four patients received a TCI Heartmate, one patient a Novacor, and one patient a Jarvik 2000. RESULTS: All patients survived the LVAD implantation, four patients could be discharged from hospital. Cardiac index and pulmonary artery pressure values returned to normal during the early post-operative phase. After a mean support time of 191+/-86 days PVR had fallen to 2.0+/-1.2 (range 0.8-3.6) Wood units. All patients could be bridged to transplantation, one patient died 3 months after transplant, five patients are still alive after a mean follow-up of 16.2+/-10.5 months. CONCLUSIONS: Mechanical support using an implantable LVAD is a very efficient approach with an acceptable risk to treat severe pulmonary hypertension in end-stage heart failure patients before HTX. Adequate reduction of PVR can be expected within 3-6 months. Subsequent HTX is associated with a good outcome.

Adolescent↗