Oral Prostaglandin E2 Research Articles

BRIDGING GAPS: ADDRESSING TREATMENT CHALLENGES WITH ORAL PGE2 IN DUCTUS-DEPENDENT CONGENITAL HEART DEFECTS

circulation. During fetal development, it diverts approximately 90% of the right ventricular output from the high-resistance pulmonary circulation to the umbilical-placental circulation for gas exchange with maternal blood. After birth, the ductus arteriosus usually shuts within 72 hours to help with lung circulation. Failure to close leads to a persistent left-to-right shunt known as patent ductus arteriosus (PDA). PDA affects up to 80% of premature infants and constitutes 5–10% of all congenital cardiac abnormalities in term infants. Hemodynamically significant PDA is associated with various morbidities, including neurodevelopmental impairment and respiratory distress syndrome (Slaughter et al., 2019). Conversely, in ductus-dependent heart lesions, which account for 20–25% of all congenital heart defects, it is crucial to maintain patency of the neonatal DA to uphold life-saving pulmonary or systemic circulation before corrective surgery (Subramaniam and Solomon, 2013). Treatment for closing patent ductus arteriosus (PDA) mostly involves nonsteroidal anti-inflammatory medicines (NSAIDs) such as indomethacin and ibuprofen, which block cyclooxygenase enzymes necessary for prostaglandin production. Although effective, NSAIDs carry dangers such as renal impairment and intestinal problems. Acetaminophen is considered a safer option, although its effectiveness in premature infants is unclear because it may not fully inhibit prostaglandin synthesis. However, few medications exist for preserving ductus arteriosus (DA) patency, with prostaglandin E1 (PGE1) being the sole pharmacological option despite its associated side effects, such as peripheral vasodilation, apnea, fever, and physiological disturbances (Sear, 2019). Furthermore, the shortage of PGE1 in certain countries like Pakistan highlights the urgent need for alternate solutions. In such situations, adopting other available choices like PGE2, which is accessible in Pakistan as an oral drug, becomes crucial for the efficient management of ductus-dependent congenital heart anomalies. Prostaglandin E2 (PGE2) has been successfully utilized orally in newborns with ductus-dependent cyanotic congenital heart disease. In research by Silove et al., PGE2 was supplied orally in doses ranging from 12 to 65 micrograms/kg at 1 to 4 hours intervals. This treatment regimen resulted in consistent increases in oxygen saturation (SaO2) and plasma PGE2 concentrations within 15-30 minutes after administration, equivalent to those achieved with intravenous infusions. Treatment lasted for durations ranging from 5 days to 4 months, during which the ductus remained open for extended periods, allowing for delayed surgical intervention to support the growth of the infants and their pulmonary arteries. While adverse effects during oral medication were similar to those found with intravenous administration, they were generally less severe in this series, underlining the effectiveness and simplicity of oral PGE2 administration for long-term treatment (Nabavi et al., 2019). Furthermore, a 1987 study by B.D. Thanopoulos et al. supported the effectiveness of oral PGE2 in the treatment of neonates with cyanotic congenital heart disease, which primarily depends on the ductus. The data from this investigation revealed that oral PGE2 treatment, while less productive than intravenous infusions, nonetheless proved useful for long-term therapy, affording more convenience and lower morbidity (Fernández-Francos et al., 2021). It is crucial to highlight that side effects such as apnea and hypotension may occur in newborns following PGE2 therapy and require close monitoring during treatment. In conclusion, oral PGE2 offers a viable alternative for addressing congenital heart defects in resource-limited countries like Pakistan. Its effectiveness and convenience make it a viable choice, especially if access to injectable drugs is limited. This underlines the necessity to investigate alternative treatments for appropriate care in such circumstances.

Induction of Labor in Twins—Double Trouble?

To determine and compare the safety and efficacy of different methods of induction of labor in twin gestations and their effect on maternal and neonatal outcomes. A retrospective observational cohort study was conducted at a single university-affiliated medical center. Patients with a twin gestation undergoing induction of labor at >32 + 0 weeks comprised the study group. Outcomes were compared to patients with a twin gestation at >32 + 0 weeks who went into labor spontaneously. The primary outcome was cesarean delivery. Secondary outcomes included operative vaginal delivery, postpartum hemorrhage, uterine rupture, 5 min APGAR < 7, and umbilical artery pH < 7.1. A subgroup analysis comparing outcomes for the induction of labor with oral prostaglandin E1 (PGE1), IV Oxytocin ± artificial rupture of membranes (AROM), and extra-amniotic balloon (EAB)+ IV Oxytocin was performed. Data were analyzed using Fisher's exact test, ANOVA, and chi-square tests. 268 patients who underwent induction of labor with a twin gestation comprised the study group. 450 patients with a twin gestation who went into labor spontaneously comprised the control group. There were no clinically significant differences between the groups for maternal age, gestational age, neonatal birthweight, birthweight discordancy, and non-vertex second twin. There were significantly more nulliparas in the study group compared to the control group (23.9% vs. 13.8% p < 0.001). The study group was significantly more likely to undergo a cesarean delivery of at least one twin (12.3% vs. 7.5% OR, 1.7 95% CI 1.04-2.85 p = 0.03). However, there was no significant difference in the rate of operative vaginal delivery (15.3% vs. 19.6% OR, 0.74, 95% CI 0.5-1.1 p = 0.16), PPH (5.2% vs. 6.9% OR, 0.75 95% CI 0.39-1.42 p = 0.37), 5-min APGAR scores < 7 (0% vs. 0.2% OR, 0.99 95%CI 0.99-1.00 p = 0.27), umbilical artery pH < 7.1 (1.5% vs. 1.3% OR, 1.12 95% CI 0.3-4.0), or combined adverse outcome (7.8% vs. 8.7% OR, 0.93 95% CI 0.6-1.4 p = 0.85). Furthermore, there were no significant differences in the rates of cesarean delivery or combined adverse outcomes in patients undergoing induction with oral PGE1 compared to IV Oxytocin ± AROM (13.3% vs. 12.5% OR, 1.1 95% CI 0.4-2.0 p = 1.0) (7% vs. 9.3% OR, 0.77 95% CI 0.5-3.5 p = 0.63 ) or EAB+ IV Oxytocin (13.3% vs. 6.9% OR, 2.1 95% CI 0.1-2.1 p = 0.53) (7% vs. 6.9% OR, 1.4 95% CI 0.15-3.5 p = 0.5) or between patients undergoing induction of labor with IV Oxytocin ± AROM and EAB+ IV Oxytocin (12.5% vs. 6.9% OR, 2.1 95% CI 0.1-2.4 p = 0.52) (9.3% vs. 6.9% OR, 0.98 95% CI 0.2-4.7 p = 0.54). There were no cases of uterine rupture in our study. Induction of labor in twin gestations is associated with a two-fold increased risk of cesarean delivery, although this is not associated with adverse maternal or neonatal outcomes. Furthermore, the method of induction of labor used does not affect the chances of success nor the rate of adverse maternal or neonatal outcomes.

Oral Misoprostol Versus Vaginal Prostaglandin E2 Labor Induction Efficiency, Safety, and Labor Outcomes

BACKGROUNDProstaglandin E1 (oral misoprostol) and the other Prostaglandin E2 (Dinoprostone gel) are promising agents for cervical ripening and induction of labor.AIMS OF STUDYTo compare the efficiency and safety on maternal-fetal outcomes using 25 micrograms oral misoprostol PGE1 with 50 micrograms of intra-vaginal PGE2 for induction of labor.METHODSThis was a retrospective study design reviewing medical records of induced labor at Al Shifa hospital in Gaza Strip.RESULTSIn general, the results showed that women who used oral misoprostol with an age less than 30 years and parity less than 3 was effective for delivery and safe outcomes with an odds ratio (OR) of 15.8 (CI 6.9–39.8) and OR 29.2 (CI 10.7–80.3) respectively. The most common indication for labor induction in both methods was reputure of the membrane (ROM) more than 24 hours, postdates, and a medical disorder. However, the total interval hours for both methods was 8.4 hours. The mode of delivery was similar in both groups as vaginal delivery outcome was 73.6% for oral misoprostol E1 and 75% for prostaglandin E2 cases. However, PGE2 induction showed a higher cesarean delivery 25% rate versus 18.4%. Clinically the use of oral misoprostol showed a higher percentage of birth canal injury, failed induction, uterine rupture by 9.3%, 8%, 1.3% respectively. Fetal distress was found as the most common fetal complication and the most common cause for cesarean section.CONCLUSIONThe study recommended more research is needed as present evidence does not support use of oral misoprostol versus Prostaglandin E2.

Outcomes of 'one-day trial of vaginal delivery of twins' at 36-37 weeks' gestation in Japan.

ObjectiveThe lack of obstetricians in Japan has prevented the implementation of a 24–hour delivery monitoring system for high-risk deliveries such as twin vaginal delivery at many obstetric facilities. To examine the outcomes of a 1-day trial of the vaginal delivery of twins at 36–37 weeks' gestation.MethodsWe induced the vaginal delivery of twins at 36–37 weeks' gestation of 256 women who provided consent between January 2007 and December 2016 using the following protocol: 1) administration of 0.5 mg oral prostaglandin E2 every 1 hour (maximum: 1.5 mg) in the morning; 2) intravenous administration of oxytocin and amniotomy in the afternoon; and 3) selection of caesarean delivery when vaginal delivery was not expected by evening. We examined their perinatal outcomes in a chart review.ResultsThe completion rates of vaginal delivery in total, nulliparous, and multiparous women were 79%, 72%, and 84%, respectively. There were no cases of neonatal asphyxia. The total incidence of neonatal respiratory disorders was 2.1%, but there were no cases of persistent pulmonary hypertension. The total incidence of postpartum hemorrhage requiring transfusion was 2.7%.ConclusionThe 1-day planned vaginal delivery of twins at 36–37 weeks' gestation appears valid and safe, and our findings suggest that it can be an option for the delivery of twins.

Establishment of a Charge Reversal Derivatization Strategy to Improve the Ionization Efficiency of Limaprost and Investigation of the Fragmentation Patterns of Limaprost Derivatives Via Exclusive Neutral Loss and Survival Yield Method.

Sensitivity is generally an issue in bioassays of prostaglandins and their synthetic analogs due to their extremely low concentration in vivo. To improve the ionization efficiency of limaprost, an oral prostaglandin E1 (PGE1) synthetic analog, we investigated a charge reversal derivatization strategy in electrospray ionization mass spectrometry (ESI-MS). We established that the cholamine derivative exhibits much greater signal intensity in the positive-ion mode compared with limaprost in the negative ion mode. Collision-induced dissociation (CID) involved exclusive neutral mass loss and positive charge migration to form stable cationic product ions with the positive charge on the limaprost residue rather than on the modifying group. This has the effect of maintaining the efficiency and specificity of multiple reaction monitoring (MRM) and avoiding cross talk. CID fragmentation patterns of other limaprost derivatives allowed us to relate the dissociation tendency of different neutral leaving groups to an internal energy distribution scale based on the survival yield method. Knowledge of the energy involved in the production of stabilized positive ions will potentially assist the selection of suitable derivatization reagents for the analysis of a wide variety of lipid acids. Graphical Abstract ᅟ.

Effect of misoprostol on patients with aspirin-exacerbated respiratory disease undergoing aspirin challenge and desensitization

BackgroundProstaglandin E2 (PGE2) is an anti-inflammatory compound that inhibits 5-lipoxygenase activity. Diminished PGE2 regulation in aspirin-exacerbated respiratory disease (AERD) leads to respiratory reactions on cyclooxygenase 1 inhibition. In vitro studies have found that exogenous PGE2 stabilizes inflammatory mediator release. ObjectiveTo examine whether misoprostol (oral prostaglandin E1 analogue) use during aspirin challenge and desensitization might decrease the severity of aspirin-induced symptoms and make desensitization safer for patients with AERD. MethodsForty-five patients undergoing aspirin challenge and/or desensitization were randomized to misoprostol (n = 30) or placebo (n = 15) and compared with a group of historical controls (n = 31). Misoprostol (200 μg) was administered at 30 minutes, 90 minutes, and 4 hours after the first dose of nasal ketorolac. Measured end points included change in forced expiratory volume in 1 second (FEV1), peak nasal inspiratory flow rate (PNIF), number of treatments received for induced reactions, and adverse gastrointestinal effects. ResultsA difference in FEV1 and PNIF reduction was detected between misoprostol and placebo (P = .03) and misoprostol and historical controls (P = .01), respectively, during nasal ketorolac challenge. No difference was detected among aspirin reactors. Among all reactors, no difference in magnitude was found for FEV1 (P = .13) or PNIF (P = .07) reduction across all 3 groups. Total treatment requirement was similar (P = .14). Patients receiving misoprostol were more likely to report adverse gastrointestinal effects (P = .02). ConclusionThe addition of misoprostol to current aspirin challenge and/or desensitization protocols reveals no protective effect in reducing the intensity of nonsteroidal anti-inflammatory drug–induced symptoms and is not recommended based on the findings in this study.

LA HISTERECTOMIA VAGINAL COMO TRATAMIENTO DEL PROLAPSO GENITAL

Se ha estudiado 60 casos de pacientes portadores de distopias del perfil vaginal en diversos grados, cuyas edades fluctuaban entre 40 y 70 años, es decir en la premenopausia o post-menopausia y con ciertas características socio-económicas y nutricionales, factor es que se tuvo en cuenta para la elección del tratamiento operatorio. Se realizó en todas ellas la Histerectomía Vaginal por la técnica de Campbell modificada, todas se acompañaron de Colporrafía anterior y posterior, la transfusión sanguínea fue indicada en el 100% de los casos variando entre 500 cc y 1500 cc, la anestesia más empleada fue la general, no habiéndose presentado ninguna complicación anestésica. Las complicaciones post-operatorias más frecuentes fueron la infección urinaria (20%), seguida del hematoma de la cúpula vaginal (10%), resaltando que el 64% de nuestra casuística evolucionó sin complicaciones, habiendo necesitado el 13% de los casos, tratamiento quirúrgico post-operatorio. El promedio de estancia hospitalaria fue de 10.8 días. El seguimiento de las pacientes fue mínimo.

Inducción de Trabajo de Parto con Prostaglandina E2 Oral

La inducción del trabajo de parto con prostaglandina E2 oral (PGE2) en 110 pacientes, tuvo éxito en 100 partos vaginales; hubo 9 fallas de inducción y una cesárea, con un porcentaje de efectividad de 90.9%. Se hace el análisis de los resultdos de las 100 gestantes con parto vaginal: 53 fueron electivas y 47 indicadas; por post madurez (18 pacientes), trabajo de parto disfuncional (13), ruptura prematura de membranas (9), toxemia (5), diabetes (2). El 86% tuvieron el parto con una sola sesión de inducción sin haber diferencia entre las electivas e indicadas. La PGE2 fue administrada en dosis progresiva horaria de 0,5 - 2 mg. Las pacientes tuvieron monitoría clínica anotando los incidentes en relación a la estimulación, parto, alumbramiento y recién nacidos. El puntaje pélvico de Bishop fue tomado como indicador pronóstico de éxito de la inducción. El 24,5% de las inducciones electivas y el 47% de las indicadas tuvieron puntajes superiores a 7, considerado como muy favorable. Este indicador, guarda relación indirecta con la dosis total de PGE2 necesaria para conseguir el parto vaginal y el tiempo total de inducción; pero no guarda relación con la edad, el índice ponderal de la madre ni con la condición electiva de la inducción. En los 95 recién nacidos se presentó hipoxia severa (Apgar 1); esta se relacionó con las alteraciones de contracción uterina, secundarias a la administración de PGE2. Los efectos secundarios maternos, febrícula, naúseas y diarreas, fueron leves.

PG E2 gel supplemented with oral PG E2 for induction of labour in high risk pregnancy

INTRODUCTION: The risks to the fetus-infant increase substantively in high risk pregnancies. The efforts are always to ensure a vaginal rather than a caesarian delivery. The present study aims to assess the safety and efficacy of Prostaglandin E2( PGE2) intracervical gel and oral PGE2 in inducing and augmenting labour in such patients. METHODS: PGE2 intracervical gel was used for induction oflabour in 100 high risk pregnancies. PGE2 gel was supplemented by oral PGE2 afterARM. RESULTS: PGE2 successfully induced labour in 60% of women while it improved the Bishop's score in the rest of the cases. L.S.C.S. was needed in only 7% of women. CONCLUSION: Intracervical PGE2 gel application is a safe and efficacious method of inducing labour, which can be augmented with oral PGE2 when needed. DOI: http://dx.doi.org/10.3126/jucms.v1i4.9568 Journal of Universal College of Medical Sciences (2013) Vol.1 No.04: 22-25

Systemic Prostaglandin E1 to Treat Acute Central Retinal Artery Occlusion

To report the efficacy of systemic prostaglandin E1 (PGE1) monotherapy for treating acute central retinal artery occlusion (CRAO). The best-corrected visual acuity (BCVA) and side effects were evaluated retrospectively in 10 consecutive eyes (nine patients; mean age, 61.3 years) with acute CRAO treated with PGE1 monotherapy. The protocol included intravenous injection of 40 μg PGE1 twice daily (80 μg per day) for 5 days then oral PGE1 three times daily (30 μg per day) for at least 1 month. In four eyes, the retinal vessel diameters were assessed on serial fundus photographs. The mean time to treatment was 7.1 hours (range, 1-18 hours). The mean ± SD logarithm of the minimum angle of resolution (logMAR) BCVAs at baseline and 1 month after initiation of therapy were 2.67 ± 0.54 (range, 3.00-1.70) and 0.52 ± 0.62 (range, 2.00 to -0.18), respectively (P = 0.005); the BCVA improved by 1.0 or more logMAR unit at 1 month in all eyes. The BCVA improvement was correlated negatively with the time to treatment (ρ = -0.655, P = 0.0492), but was not correlated with age (ρ = -0.473, P = 0.156) and did not differ between sexes (P = 0.0871). Compared with baseline, the mean changes in the vessel diameters in four cases were 151.1% (range, 115.1%-188.0%) in the arteries and 191.0% (range, 127.2%-246.4%) in the veins 1 day after initiation of therapy. Angialgia during injection was the only side effect. Systemic administration of PGE1 for acute CRAO rapidly restores retinal blood flow by its vasodilatory effects, improves VA, is well tolerated with few side effects, and requires no special training.

The effect of a prostaglandin E1 derivative on the symptoms and quality of life of patients with lumbar spinal stenosis

BackgroundQuality of life (QOL) is a concern for patients with lumbar spinal stenosis (LSS). In this study, QOL was examined using the 5-item EuroQol (EQ-5D). MethodsQOL and activities of daily living (ADL) were surveyed for 91 patients who visited 18 medical institutions in our prefecture and were diagnosed with LSS-associated intermittent claudication. A second survey was performed after ≥6weeks for 79 of the subjects to evaluate therapy with limaprost (an oral prostaglandin E1 derivative) or etodolac (an NSAID). Symptoms, maximum walking time, QOL, ADL items, and relationships among these variables were investigated for all 91 patients. Leg pain, leg numbness, and low back pain while walking were surveyed by use of VAS scores (0–100). ResultsLeg pain, leg numbness, and low back pain while walking (VAS ≥25) were present in 83.5, 62.6, and 54.9% of the patients in the first survey, and approximately half of the patients had a maximum walking time <15min. The mean EQ-5D utility value for QOL was 0.59±0.12. This value was significantly associated with maximum walking time (p=0.030) based on classification of patients into groups with walking times <7.5, 7.5–15, 15–30, and >30min, showing that maximum walking time affected health-related QOL. Of the 79 patients who completed the second survey, 56 had taken limaprost and 23 (control group) had received etodolac. Limaprost improved possible walking time, reduced ADL interference, and significantly increased the EQ-5D utility score, whereas no significant changes occurred in the control group. Maximum walking time was prolonged by ≥10min and the EQ-5D utility value was improved by ≥0.1 points in significantly more patients in the limaprost group than in the control group. ConclusionAccording to the findings of this survey, at an average of 8weeks after administration limaprost improved symptoms, QOL, and ADL in LSS patients whereas treatment with an NSAID reduced pain but did not have any other effects.

1128 Evaluation of Oral Prostaglandin E1 in Management of Ductus Dependent Congenital Heart Disease

IntroductionIntravenous prostaglandin E1 (PGE1) infusion is a treatment which effect is proven in ductus dependent congenital heart disease. However, PGE1 is very expensive, needed continuous infusion and its supply is...

Duktus Bağımlı Konjenital Kalp Hastalıklarında Oral Prostaglandin E1 Tedavisinin Değerlendirilmesi

Purpose: Intravenous prostaglandin E1 (PGE1) infusion is a treatment which has been proven to be effective in ductus dependent congenital heart disease. However, PGE1 is very expensive, needed continuous infusion and its supply is difficult by every center. When its long term use is necessary, these problems become more important. The aim of this study was to show whether oral PGE1could keep the ductus open or not till the supply of intravenous PGE1. Method: Ten patients, who were admitted to newborn intensive care unit with the diagnosis of ductus dependent congenital heart disease and received oral PGE1 till the supply of intravenous PGE1, were evaluated. The PO2 with the arterial blood gas analysis and SO2 levels with pulse oxymeter at skin were recorded before and after the administration of oral and intravenous PGE1. Results: The mean oral PGE1 initiation age was 5.5 hours (0.5-25), and mean administration period was 28 hours (18-46). It was observed that the PO2 and SO2 levels of patients measured 2 hours after the initiation of oral PGE1 were significantly increased compared to the levels before initiation of PGE1. The improvement in PO2 and SO2 levels continued till the initiation of intravenous PGE1. It was also observed that the PO2 and SO2 levels of patients measured 2 hours after the initiation of intravenous PGE1 were slightly increased compared to levels before initiation of intravenous PGE1. Conclusion: Although intravenous PGE1 is more effective than oral PGE1 in short term usage, oral PGE1 is also sufficiently effective in keeping the dustus open. For this reason until the intravenous PGE1 is supplied oral PGE1 may be used as an alternative treatment choice. We think that in long term use oral PGE1, which is cheaper and easy to use, could be used instead of intravenous PGE1 without need of admission to hospital and opening intravenous line. However for this further studies are needed to confirm this assumption.

Oral Prostaglandin E1 in Combination with Sodium Bicarbonate and Normal Saline in the Prevention of Contrast-Induced Nephropathy: A Pilot Study

The purpose of this study was to evaluate the use of prostaglandin E1 (PGE1) as a renal protective medication for patients exposed to contrast agents, as well as to demonstrate the safety, efficacy, and low side-effect profile of PGE1. A prospective, randomized, double-blind study was designed to compare combination of intravenous sodium bicarbonate, normal saline, and oral PGE1 200 μg versus the combination and placebo for renal protection from contrast agents. All patients receiving nonionic contrast during their interventional procedure were eligible for enrollment. Creatinine levels were recorded before and after the administration of contrast and renal protective medications. Contrast-induced nephrotoxicity (CIN) was defined as an increase of 0.5 mg/dL or greater in creatinine level, or an increase of 25% or more above baseline. Age, gender, total amount of contrast used, and incidence of renal failure requiring dialysis were recorded. We conducted the study on 41 patients. Of these, 20 patients received PGE1 and 21 received the placebo. The study group comprised 29 males and 12 females. Diabetes mellitus occurred in 41.5% of the cases (including 40% of PGE1 and 43% of placebo patients). Average contrast use was 77.2 mL (range, 15 to 200 mL). Mean age of the groups was 67.2 years. Average baseline creatinine level was 1.17. The differences between the groups were not statistically significant. CIN by definition occurred in one patient, who received the placebo. Incidence of new onset renal failure requiring dialysis was zero. Postcontrast change in creatinine level for the study was 0.11. There was a change in the creatinine level of 0.161 in the PGE1 group and 0.061 in the placebo group; an improvement of 0.10. PGE1 was not effective in significantly altering postcreatinine levels (p = 0.176). None of the patients enrolled in the study suffered any side effects from taking the PGE1 tablet. Although preliminary, this study shows that the addition of PGE1 for the prevention of CIN is well-tolerated by patients and is a safe modality. Additional studies are required to evaluate efficacy.

Induction of Labour with Oral Prostaglandin E2 (PGE2sb&gt;)

A randomly selected trial between oral prostaglandin E2 (PGE2) and intravenous Syntocinon (sandoz) revealed that both the drugs were equally effective in inducing labour. The action of PGE2 works better when the membranes were ruptured than when the membranes were left intact. When the failure rates of induction were assessed, there was no appreciable difference in the two drugs; but oral PGE2 has the advantage of convenience of administration.

The Efficacy of Prostaglandin E1 Derivative in Patients With Lumbar Spinal Stenosis

Randomized controlled trial. To examine the effect of limaprost, an oral prostaglandin (PG) E1 derivative, on health-related quality of life (HRQOL) in patients with symptomatic lumbar spinal stenosis (LSS), compared to etodolac, a NSAID. Limaprost, an oral PGE1 derivative, was developed in Japan to treat numerous ischemic symptoms of thromboangiitis obliterans (TAO) and LSS. Previous studies have demonstrated the effectiveness of limaprost in the symptoms in patients with LSS. However, the evidence for effect on patient-reported outcomes, such as patient's HRQOL or satisfaction, is limited. This study was conducted at 4 study sites in Japan. Briefly, inclusion criteria were: age between 50 and 85 years; presence of both neurogenic intermittent claudication (NIC) and cauda equina symptoms (at least presence of bilateral numbness in the lower limbs); and MRI-confirmed central stenosis with acquired degenerative LSS. Limaprost (15 microg/d) or etodolac (400 mg/d) was administered for 8 weeks. The primary outcome was Short Form (SF)-36, and the secondary outcomes were the verbal rating scale of low back pain and leg numbness, walking distance, subjective improvement, and satisfaction. A total of 79 participants were randomized (limaprost:etodolac = 39:40). Thirteen participants withdrew from the study (limaprost:etodolac = 5:8) and 66 completed the study (limaprost:etodolac = 34:32). Comparisons showed that limaprost resulted in significantly greater improvements in the SF-36 subscales of physical functioning, role physical, bodily pain, vitality, and mental health. Limaprost was also significantly better than etodolac for leg numbness, NIC distance, and subjective improvement and satisfaction. In the subgroup analysis stratified by symptom severity, limaprost seemed more effective for milder symptoms. No serious adverse effects were reported in either treatment group. In this study, limaprost was found to be efficacious on most outcome measures, such as HRQOL, symptoms and subjective satisfaction, in LSS patents with cauda equina symptoms.

Effects of treatment with oral prostaglandin E1on lumbar spinal canal stenosis

Background: We studied the clinical effects of oral treatment with prostaglandin E1, which improves the microcirculation, on lumbar spinal canal stenosis associated mainly with symptoms such as neurological intermittent claudication and lower extremity pain. Methods: Oral prostaglandin E1 was given for 6 weeks to 30 patients with lumbar spinal canal stenosis who did not respond to physical therapy or nerve block. Results: The mean continuous walking distance significantly increased from 132 ± 45 to 698 ± 254 m. The mean severity score of lower extremity pain, evaluated on a 11-point (0–10) verbal rating scale (VRS), significantly decreased from 7.3 ± 1.3 to 4.6 ± 2.4. Thermography revealed a significant elevation of lower extremity peripheral temperature. Conclusions: These results suggested that oral prostaglandin E1 is useful for the treatment of lumbar spinal canal stenosis.

Massive Epistaxis and Subconjunctival Hemorrhage Due to Combination of Paroxetine and Limaprost Alfadex

Sir: A patient presented to us having experienced a few days of massive epistaxis and hyposphagma (severe hemorrhage into the conjunctiva) while taking paroxetine. Pharmaceutical use was also notable for the peripheral vasodilator limaprost alfadex. To our knowledge, no such case has been reported in the literature. We believe the combination of paroxetine and limaprost alfadex led to the bleed. Case report. Ms. A, a 66-year-old woman with blood counts and blood coagulation tests within normal limits, presented in June 2005 to the orthopedic surgery department with complaints of coldness of limbs, continuing lower-extremity pain, insomnia, and loss of appetite. She underwent a nerve-root block for lumbar spinal canal stenosis and started limaprost alfadex 15 µg/day. Limaprost alfadex, an oral prostaglandin E1 derivative, is frequently used in Japan for the treatment of peripheral circulatory disturbances. Because the symptoms overall did not improve, she was referred to the psychiatry service (July 2005). She had lost 10 kg in 2 months and complained strongly of anxiety and frustration due to inability to do housework and to memory loss. She was admitted in September 2005. The patient was diagnosed with DSM-IV major depressive disorder with psychotic features based on hypochondriacal and persecutory delusions and aggression. When she refused food and medication due to delusions of being poisoned, electroconvulsive therapy (ECT) was introduced (October–November 2005, total of 11 treatments). ECT was effective, and she began to take medication again after the sixth ECT treatment. She was restarted on limaprost alfadex treatment (15µg/day). When ECT was completed in early November, paroxetine 20 mg/day was started, increasing to 40 mg/day after 2 days and to 50 mg/day after 4 days. The patient's mood remained normal. On the 29th and 30th days after starting paroxetine, she experienced massive epistaxis (more than 500 mL per episode). On the 30th day of treatment, paroxetine was decreased to 40 mg/day, but similar epistaxis recurred the next day. An otolaryngologist determined that hemorrhage was from the right Kiesselbach plexus; however, no other abnormality was observed. Complete blood count and blood coagulation findings were within normal limits. On the 36th day of paroxetine treatment, limaprost alfadex was reduced from 15 µg/day to 10 µg/day. No further epistaxis episodes occurred. Upper (day 45 of paroxetine treatment) and lower (day 50 of paroxetine treatment) gastrointestinal endoscopy were performed, and no hemorrhage was observed. Because of intermittent complaints of lower extremity coldness and pain, the dosage of limaprost alfadex was returned to 15 µg/day. Since January 2006, prescriptions for paroxetine 40 mg/day and limaprost alfadex 15 µg/day have continued, and the patient has been followed at the outpatient clinic. There has been no recurrent epistaxis as of September 2006. However, right eye hyposphagma was recently observed at a psychiatry clinic appointment. If this continues, we will consider decreasing paroxetine to 30 mg/day. Mild epistaxis during selective serotonin reuptake inhibitor (SSRI) treatment is a well-known rare adverse effect, but our patient's epistaxis was severe. Hyposphagma with paroxetine might be very rare.1 Since only a few case reports2 have suggested SSRI use alone can trigger even mild bleeding, including ecchymoses, purpura, and epistaxis, we cannot make a strong conclusion. After carefully examining the drugs in concurrent use for our patient, it is quite possible that limaprost alfadex, in combination with paroxetine, contributed to severe epistaxis and hyposphagma. When patients present with severe symptoms, including psychotic features, many clinicians use relatively high doses of antidepressants for continuation and maintenance treatment.3 Because vasodilating prostaglandins such as limaprost alfadex are used frequently in fields such as orthopedic surgery, it is important that clinicians know there may be a tendency for hemorrhage when an SSRI is also used; physicians should consider decreasing the SSRI maintenance dose in such instances.

Interrupción del embarazo. Estudio comparativo entre diferentes pautas de inducción médica

Objective To compare the effectiveness of distinct medical induction regimens used for second trimester abortions. Materials and methods We performed a retrospective review of 145 pregnancies between 13 and 22 weeks that underwent an induced abortion using four different methods: 1) intraamniotic prostaglandin F2α and endocervical E2; 2) endocervical prostaglandin E2; 3) intravaginal and oral prostaglandin E1; and 4) intravaginal prostaglandin E1. All these methods were followed by oxytocin infusion. Results The mean induction to abortion interval was 20.2 ± 7.6 h; 17.5 ± 8.2 h; 16.8 ± 8.7 h, and 12.6 ± 4.2 h, respectively. The differences were statistically significant when the mean interval was analyzed globally (p = 0.02, ANOVA) and in nonprimigravidas (p = 0.02, ANOVA). The rate of successful abortions within 12 hours was 5.5%, 31%, 32.5% and 50%, respectively (p = 0.002 χ 2 test). Surgical abortion and serious side effects (one case of disseminated intravascular coagulation) occurred only with prostaglandin E2. Conclusions Vaginal administration of prostaglandin E1 resulted in a shorter mean induction to abortion interval and a higher rate of successful abortions within 12 hours.

THE EFFECT OF ASPIRIN AND PROSTAGLANDINE1ON THE PATENCY OF MICROVASCULAR ANASTOMOSIS IN THE RATS

The purpose of this study was to evaluate the effect of oral prostaglandin E(1)(PGE(1)) on the patency of the microvascular anastomosis of the carotid artery in rat. A total of 48 rats were used, and divided into three groups. The first group (A) was used as a control with no medical agent being used after anastomosis, the second group (B) was medicated with aspirin, and the third group (C) was medicated with oral PGE(1). In each group, four rats were sacrificed serially on every post-operative 3, 5, 10 and 15 days after arterial anastomosis. Patency and histologic evaluations at the anastomotic site were observed. The results revealed that the PGE(1) therapied group showed highest patency rate (100%), lesser formation of mural thrombosis, and also minimal changes in the intimal hyperplasia and medial fibrosis. From these findings, we could conclude that PGE(1) has superior effect on maintaining the patency after microvascular surgery.