Epidemiology and treatment of priapism in sickle cell disease.

Ischemic priapism is a common but underrecognized morbidity affecting about 33% of adult men with sickle cell disease (SCD). The onset of priapism occurs in the prepubertal period and tends to be recurrent with increasing age. Significantly, priapism is associated with an unrecognized high burden of mental duress and sexual dysfunctions. The diagnosis of priapism is clinical. Many episodes of priapism will resolve spontaneously, but when an episode lasts longer than 4 hours, the episode is considered a urologic emergency requiring quick intervention with either corporal aspiration or shunt surgery. Only 3 randomized clinical trials (stilbesterol, ephedrine or etilefrine, and sildenafil) have been conducted for secondary priapism prevention in SCD. All 3 trials were limited with small sample sizes, selection biases, and inconclusive results after completion. The current molecular understanding of the pathobiology of priapism suggests a relative nitric oxide (NO) deficiency secondary to chronic hemolysis in SCD and associated phosphodiesterase type 5 dysregulation. We posit an increase in NO levels will restore the normal homeostatic relationship between voluntary erection and detumescence. Currently, 2 randomized phase 2 trials (1 double-blind, placebo-controlled trial and 1 open-label, single-arm intervention) are being conducted for secondary priapism prevention in men at high risk for recurrent priapism (NCT03938454 and NCT05142254). We review the epidemiology and pathobiology of priapism, along with mechanistic therapeutic approaches for secondary prevention of priapism in SCD.

Effects of adding hypertonic saline solutions and/or etilefrine to standard diuretics therapy in cirrhotic patients with ascites.

OBJECTIVE: The renin-angiotensin-aldosterone system (RAAS) activation is the milestone in ascites formation. Hypertonic saline solution (HSS) has attracted considerable interest over the last years in ascites control. Other therapeutic models and concepts have been introduced to overcome diuretic resistance and control ascites. We aimed to evaluate the effects of adding HSS infusion and/or etilefrine to oral diuretics therapy on inflammatory and metabolic pathways, renal and systemic hemodynamics, and clinical outcomes by estimating the changes in selected biochemical and biological markers in cirrhotic patients with ascites. PATIENTS AND METHODS: Ninety cirrhotic patients with ascites were studied after administration of HSS infusion (n=25) or etilefrine tablets (n=25), or both (n=25) plus standard diuretics therapy (SDT), or SDT alone (n=15). Serum levels of interleukin-6 (IL-6), aldosterone, leptin, and C-reactive protein (CRP). Hepatic and renal functions were measured at baseline, after eight days, then after 38 days. RESULTS: A significant reduction in serum IL-6, serum aldosterone, Child-Pugh score, MELD-Na score, and increase in serum leptin, and mean arterial pressure (p<0.05) were noted after 38 days in HSS and combination groups. A significant improvement in diuresis, in all groups, urinary sodium excretion, and creatinine clearance (p<0.05) were increased after 38 days in all groups except the SDT group. CONCLUSIONS: The results suggest that HSS, etilefrine, and their combination plus SDT are superior to SDT alone for ascites control and can exert some benefits on clinical, systemic, inflammatory, renal, and metabolic pathways without renal or hepatic dysfunction.

Development and application of a membrane assisted solvent extraction-molecularly imprinted polymer based passive sampler for monitoring of selected pharmaceuticals in surface water.

In this work, we demonstrate the development, evaluation and pre-liminary application of a novel passive sampler for monitoring of selected pharmaceuticals in environmental waters. The samplers were calibrated in laboratory-based experiments to obtain sampling rates (Rs) for carbamazepine, methocarbamol, etilefrine, venlafaxine and nevirapine. Passive sampling was based on the diffusion of the target pharmaceuticals from surface water through a membrane bag which housed an ionic liquid as a green receiving solvent and a molecularly imprinted polymer. Effects of biofouling, deployment time and solvent type for the receiver phase were optimized for selective uptake of analytes in surface water. Notably, there was a decrease in the uptake of selected pharmaceuticals and consequently a decrease in their sampling rates in the presence of biofouling. The optimum matrix-matched sampling rates ranged from 0.0007 - 0.0018 L d-1 whilst the method detection and quantification limits ranged from 2.45 - 3.26 ng L-1 and 8.06 - 10.81 ng L-1, respectively. The optimized passive sampler was deployed in a dam situated in the heart of a typical highly populated township in the Gauteng Province of South Africa. Only etilefrine and methocarbamol were detected and quantified at maximum time weighted average concentrations of 12.88 and 72.29 ng L-1, respectively.

Preparation and evaluation of fast-dissolving films of etilefrine hydrochloride for practical buccal dosing.

Etilefrine hydrochloride (ET) is an important drug in the treatment of hypotension, and parenteral injections and oral tablets are the conventional dosage forms. However, parenteral injections may cause abnormally high plasma levels as well as pain and necrosis, and oral tablets undergo first-pass metabolism. Although fast-dissolving buccal tablets were previously reported, the initial absorption rate was a little slow and the plasma levels were varied extensively. Recently, many films have been developed as novel dosage forms. Therefore, in the present study, film dosage forms containing ET were produced using water-soluble polymers and glycerin (GLY) as excipients to obtain a practical buccal dosage form. Films composed of ET, GLY, and sodium alginate (AL) exhibited good physical characteristics and rapid release in vitro (more than 70% at 2 min). The compacted AL film containing 2 mg ET (1 × 1 cm) exhibited rapid absorption (>19 ng/mL at 0.5 h), maintained an effective plasma level (>7 ng/mL) for a long time period (0.5-4 h), and had an adequate plasma concentration-time profile with a smaller standard error (<15.3 ng/mL). These results suggest that the present compacted buccal film is a superior dosage form of ET for practical use.

Refractory lymphorrhoea of the neck treated with etilefrine.

BACKGROUND: Intraoperative injury of the thoracic duct is an uncommon complication of head and neck surgery, which is difficult to manage and associated with serious consequences. We report a case of lymphorrhoea of the neck refractory to all the usual treatments that resolved in response to a treatment strategy described in thoracic and visceral surgery: use of a sympathomimetic drug, etilefrine. To our knowledge and after review of the literature, this is the first reported case of lymphorrhoea of the neck treated by etilefrine. CASE REPORT: Our patient presented massive lymphatic fluid leakage following left neck dissection as part of the management of oropharyngeal cancer with lymph node metastases. The treatments usually proposed, such as intraoperative repair and appropriate dietary and drug management, were not effective, resulting in multiple, severe complications. After evaluation of the benefit-risk balance, treatment with etilefrine was introduced at the dosages proposed in the literature for the management of chylothorax. This treatment allowed complete resolution of the lymphatic fluid leak after one week. DISCUSSION: Etilefrine can therefore be added to the treatment options for the management of lymphatic fluid leaks refractory to the usual treatments.

Dexmedetomidina en anestesia espinal para cesárea / Dexmedetomidine in spinal anesthesia with cesarean

Dexmedetomidina un α- agonista, de amplio uso y popular nivel mundial, que poco conocimiento se tiene sobre su uso de forma intratecal en la población boliviana, de manera especial en pacientes obstétricas. OBJETIVOS: evaluar el efecto de dexmedetomidina intratecal en anestesia obstétrica y observar los efectos secundarios del medicamento. MÉTODOS: ensayo clínico aleatorizado y simple ciego. La muestra fue de 123 pacientes, cada grupo de 41 pacientes cumpliendo ambos criterios. Grupo B (bupivacaina + fentanil); grupo D2 (bupivacaina + fentanil+ dexmedetomidina 2 µg) y grupo B3 (bupivacaina + fentanil+ dexmedetomidina 3 µg). Análisis estadístico: se utilizó el software SPSS® 25 y Excel® 2016. Con un nivel de confianza del 95 % y error muestral del 13 %. RESULTADOS: duración del bloqueo motor fue de 106,5 ± 16 minutos en el grupo B; 142,3 ± 28,2 minutos en el grupo D2 y 145,6 ± 16,7 minutos en el grupo D3. Siendo significativo entre los grupos de estudio (valor p < 0,000). PAM con significancia estadística antes y después del nacimiento. Frecuencia cardiaca significativo a los 15, 30 y 45 minutos (valor p < 0,000; 0,001; 0,004; 0,000 y 0,002). Etilefrina en el grupo B fue de 3,44 ± 1,8 ml; para el grupo D3 fue de 1,8 ± 2,7 ml y grupo D2 fue de 0,85 ± 1,6 ml. CONCLUSIONES: mejor estabilidad hemodinámica con 2 µg dexmedetomidina, menor incidencia de hipotensión, uso de vasopresores, las complicaciones escasas y un excelente estado de sedación materna

Dexmedetomidine an α-agonist, widely used and popular worldwide, with little knowledge about its use intrathecally in the Bolivian population, especially in obstetric patients. OBJECTIVES: evaluate the effect of spinal dexmedetomidine in obstetric anesthesia and observe the side effects of the medication. METHODS: randomized and simple blind clinical trial. The sample consisted of 123 patients, each group of 41 patients meeting both criteria. Group B (bupivacaine + fentanyl); group D2 (bupivacaine + fentanyl + 2 µg dexmedetomidine) and group B3 (bupivacaine + fentanyl + 3 µg dexmedetomidine). Statistical analysis: it was carried out in SPSS® 25 and Microsoft Excel® 2016. With a confidence level of 95% and sampling error of 13%. RESULTS: duration of the motor block was 106,5 ± 16 minutes in group B; 142,3 ± 28,2 minutes in group D2 and 145,6 ± 16,7 minutes in group D3. Being significant among the study groups (p value <0,000). MAP with statistical significance before and after birth. Significant heart rate at 15, 30 and 45 minutes (p value <0,000; 0,001; 0,004; 0.000 and 0,002). Ethylephrine in group B was 3,44 ± 1,8 ml; for group D3 it was 1,8 ± 2,7 ml and group D2 was 0,85 ± 1,6 ml CONCLUSIONS: better hemodynamic stability with 2 µg dexmedetomidine, lower incidence of hypotension, use of vasopressors, limited complications and an excellent state of maternal sedation.

Preparation of orally fast-dissolving tablets of etilefrine hydrochloride to achieve efficient absorption.

Etilefrine hydrochloride (ET) is commonly used in the treatment of hypotension in dosage forms of oral tablets and parenteral injections. However, oral tablets only temporarily achieve high plasma levels and have low bioavailability (BA), while intravenous injections may cause pain and necrosis around administration sites. In an attempt to overcome these limitations, the buccal delivery of ET using oral droplets has been investigated. In this study, a buccal tablet as an alternative dosage form was developed for practical use. Buccal tablets were prepared by the direct compression method with sodium alginate (AL) and mannitol (MA) as excipients. Their disintegration and in vitro drug release were rapid (more than 50% being released after 3 min). Furthermore, effective plasma levels (> 5-7 ng/mL) were reached within 0.5 h of buccal administration in rats. The systemic absorption of these tablets was similar to that of buccal droplets. Therefore, the ET buccal tablets developed herein have potential as an alternative dosage form for hypotension therapy.

Treatments for priapism in boys and men with sickle cell disease.

BACKGROUND: Sickle cell disease comprises a group of genetic haemoglobin disorders. The predominant symptom associated with sickle cell disease is pain resulting from the occlusion of small blood vessels by abnormally 'sickle-shaped' red blood cells. There are other complications, including chronic organ damage and prolonged painful erection of the penis, known as priapism. Severity of sickle cell disease is variable, and treatment is usually symptomatic. Priapism affects up to half of all men with sickle cell disease, however, there is no consistency in treatment. We therefore need to know the best way of treating this complication in order to offer an effective interventional approach to all affected individuals. This is an update of a previously published review. OBJECTIVES: To assess the benefits and risks of different treatments for stuttering (repeated short episodes) and fulminant (lasting for six hours or more) priapism in sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries. Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 09 September 2019. Date of most recent search of trial registries and of Embase: 01 October 2019. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing non-surgical or surgical treatment with placebo or no treatment, or with another intervention for stuttering or fulminant priapism. DATA COLLECTION AND ANALYSIS: The authors independently extracted data and assessed the risk of bias of the trials. MAIN RESULTS: Three trials with 102 participants were identified and met the criteria for inclusion in this review. These trials compared stilboestrol to placebo, sildenafil to placebo and a four-arm trial which compared ephedrine or etilefrine to placebo and ranged in duration from two weeks to six months. All of the trials were conducted in an outpatient setting in Jamaica, Nigeria and the UK. None of the trials measured our first primary outcome, detumescence. However, all three trials reported on the reduction in frequency of stuttering priapism, our second primary outcome; and from the evidence included in this review, we are uncertain whether stilboestrol, etilefrine or ephedrine reduce the frequency of stuttering priapism as the certainty of the evidence has been assessed as very low. Additionally, we conclude that sildenafil may make little or no difference (low-certainty evidence). Two trials reported on immediate side effects and we are uncertain whether etilefrine or ephedrine reduce the occurrence of these (very low-certainty of evidence) and also conclude that sildenafil may make little or no difference in side effects (low-quality evidence). Given that all of the trials were at risk of bias and all had low participant numbers, we considered the certainty of the evidence to be low to very low. AUTHORS' CONCLUSIONS: There is a lack of evidence for the benefits or risks of the different treatments for both stuttering and fulminant priapism in sickle cell disease. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions for priapism in sickle cell disease.

Preparation of phenylephrine 3-O-sulfate as the major in vivo metabolite of phenylephrine to facilitate its pharmacokinetic and metabolism studies.

INTRODUCTION: The in vivo disposition and metabolism of phenylephrine have not been establishedby previous analytical methods and there is a lack of available standards for quantitating the metabolites. METHODS: We pursued and compared the preparation of sulfation metabolites of phenylephrine and its ethyl analog etilefrine via chemical and bio-synthesis. RESULTS: Both sulfates were obtained in higher yield and purity through chemical syntheses compared to biosynthesis. DISCUSSION: A facile method for the production of phenylephrine 3-O-sulfate and etilefrine 3-O-sulfate was established. These compounds will be useful in the development of analytical assays for studying the pharmacokinetics of phenylephrine and its main route of metabolism in the presence of formulation changes and pharmacogenetic variation.

Bolus administration of ephedrine and etilefrine induces transient vasodilation just after injection in combined epidural and general anesthesia patients: A randomized clinical study.

Hypotension commonly accompanies combined epidural and general anesthesia, and intravenous bolus ephedrine and etilefrine are widely used to correct hypotension. We have noticed that systemic vascular resistance (SVR) transiently decreases just after intravenous bolus administration of these drugs. The goal of the present study was to investigate whether bolus administration of these drugs decrease SVR just after intravenous administration in combined epidural and general anesthesia patients. We investigated 40 patients who were scheduled for elective abdominal surgery. Patients were chosen as subjects if their systolic arterial pressure decreased by 20% or to <100 mmHg at 30 min after the induction of general anesthesia. Baseline hemodynamic values were recorded, and after ephedrine 10 mg injection or etilefrine 2 mg injection (equipotent), the parameters were recorded again at 0.5 min and once each min for the next 5 min thereafter. The 40 patients were enrolled into the ephedrine (n = 20) or etilefrine (n = 20) treatment groups. Patient characteristics were comparable in both groups. After ephedrine injection, SVR decreased significantly at the 1-min time point, whereas after etilefrine injection, SVR decreased significantly at the 0.5- to 2-min time points compared with baseline values. SVR at the 0.5- to 1-min time points was lower in the etilefrine versus the ephedrine group. Both drugs transiently decreased SVR after intravenous injection, but etilefrine decreased SVR much more than ephedrine, indicating that more vasodilation occurred after the injection of etilefrine than after ephedrine. It is thus important to recognize the different characteristics of these drugs.

Absorption behavior of etilefrine after buccal administration in rats.

Etilefrine hydrochloride (ET-HCl) is used in the treatment of hypotension. Dosage forms of orally administered tablets and parenteral injections are clinically available, but exhibit unfavorable characteristics, including cardiac toxicity, headaches, and damage at the injection site for the parenteral dosage form, and initially high plasma levels, fast elimination, and first-pass effects for its oral administration. Therefore, the buccal application of ET-HCl was herein investigated as an alternative to conventional administration routes. I.v., intragastric, and buccal administration were performed using rats, and absorption features were compared. Buccal application at open conditions for 1 h exhibited absolute bioavailability of more than 20%, while the intragastric administration gave much lower bioavailability (<10%). The drug residue and drug distribution in the oral mucosa were investigated in order to clarify drug transfer behaviors. In the application of ET-HCl solution using a cotton ball, higher plasma concentrations and their maintenance at higher levels were achieved at 10 mg/kg than at 2.5 mg/kg. In addition, absorption was greater with a longer application (4 h) than with a shorter application (1 h). Etilefrine (ET) was rapidly absorbed using aqueous buffer of pH 9.5 as the solvent. Open application was appropriate for achieving and maintaining higher plasma levels. Thus, in the buccal application of ET-HCl aqueous droplets, a wide distribution throughout the mucosal surface is important for achieving rapid absorption and the maintenance of plasma levels. These findings suggested that the buccal application should be feasible administration of ET-HCl.

[A Case of Successful Management of Postoperative Chylous Ascites by Combination Therapy with Octreotide and Etilefrine].

We have report a case of an 81-year-old woman who underwent distal pancreatectomy for pancreatic body cancer. Chy- lous ascites with high triglyceride(TG)level, 201mg/dL, occurred on postoperative day 2. Continuous drainage and conservative management, such as low fat diet, fasting, total parental nutrition, and octreotide monotherapy, could not resolve the problem. Successful treatment was achieved using subcutaneous octreotide injection and intravenous etilefrine infusion without any adverse side-effect. These medications were able to cause smooth muscle contraction in the thoracic duct, and also to reduce chyle flow. The amount of drainage decreased and the TG level was restored to 66mg/dL. The drainage tube was removed on postoperative day 22, 5 days after the start of both octreotide and etilefrine. This combination therapy with octreotide and etilefrine would be one of effective and safety treatment for management of postoperative intractable chylous ascites.

Successful Management of Chylothorax With Etilefrine: Case Report in 2 Pediatric Patients.

Chylothorax is defined as the accumulation of chyle within the pleural space. Originally described in 1917 by Pisek, it is the most common cause of pleural effusion in the neonatal period. The leading cause of chylothorax is laceration of the thoracic duct during surgery, which occurs in 0.85% to 6.6% of children undergoing cardiothoracic surgery. Few authors of reports in the literature have looked at etilefrine, a relatively unknown sympathomimetic, as an option for the medical treatment of chylothorax. In this case report, we review the clinical course of 2 infants with type III esophageal atresia who developed chylothorax after thoracic surgery and were successfully treated with intravenous etilefrine after failing initial dietary and pharmacological management.

Anesthesia for intrauterine myelomeningocele correction: first successful experience in Peru. Case report / Anesthesia for intrauterine myelomeningocele correction: first successful experience in Peru. Case report

Abstract Introduction: In pregnancies with a diagnosis of fetal myelomeningocele (MMC), studies have shown that prenatal correction, as compared with postnatal correction, results in better outcomes in infancy, requiring less ventriculoperitoneal shunts, and resulting in improved motor function of the lower limbs. However, maternal morbidity, the risk of uterine repair dehiscence, uterine rupture secondary to hysterotomy, and the need for cesarean section are all increased. This case report is the first successful experience of intrauterine repair of a MMC in Peru. Case presentation: We describe the case of a primigravida at 25 weeks of gestation with a diagnosis of fetal malformation (MMC and Arnold Chiari II syndrome) taken to intrauterine correction of the neural tube defect under general anesthesia plus epidural analgesia. Conclusion: The use of total intravenous anesthesia associated with nitroglycerine infusion for uterine relaxation, ethylephrine infusion to maintain maternal hemodynamic stability, and adequate postoperative pain management with epidural analgesia was successful in this case.

Resumen Introducción: En los embarazos con diagnóstico de Mielomeningocele fetal, los estudios han demostrado que la corrección prenatal conlleva a mejores resultados en la infancia que la corrección postnatal, requiriendo menos derivaciones ventrículo peritoneales y mejor función motora de miembros inferiores. Sin embargo se incrementa la morbilidad materna, el riesgo de dehiscencia de histerorrafia, ruptura uterina secundaria a la histerotomía y la necesidad de parto por cesárea. El presente reporte de caso es la primera experiencia exitosa de reparación intrautero de MMC en Peru. Presentación del caso: Describimos el caso de una primigesta de 25 semanas de gestación, con diagnóstico de malformación fetal (Mielomeningocele y Síndrome de Arnold Chiari II) en quien se realizó una corrección intrautero del defecto neural y cuya técnica anestésica fue anestesia general más analgesia epidural. Conclusiones: El uso de anestesia total intravenosa asociado a la infusión de nitroglicerina para la relajación uterina, la infusión de etilefrina para mantener la estabilidad hemodinámica materna y el adecuado manejo del dolor postoperatorio vía epidural fue exitoso en este caso.

Spectrofluorimetric determination of certain adrenergic agonist drugs in their pure forms and pharmaceutical formulations: Content uniformity test application.

A new, simple, sensitive and rapid spectrofluorimetric method has been developed for determination of certain adrenergic agonists such as isoxsuprine hydrochloride, ritodrine hydrochloride and etilefrine hydrochloride in their pure forms and pharmaceutical dosage forms. The method depends on micellar enhancement of the native fluorescence of investigated drugs by using 2% w/v sodium dodecyl sulfate (SDS) as an anionic surfactant. The enhanced fluorescence intensity of investigated drugs was measured at 305 nm after excitation at 278 nm. The interaction of studied drugs with SDS was studied, and the enhanced fluorescence intensity was exploited to develop an assay method for the determination of investigated drugs. The relative fluorescence intensity-concentration plots were rectilinear over the range 0.15-3.00 µg ml-1 , with low quantification limits of 0.132, 0.123 and 0.118 µg mL-1 for isoxsuprine, ritodrine and etilefrine, respectively. The proposed method was successfully applied for determination of studied drugs in their pharmaceutical formulations. Moreover, the high sensitivity of the proposed method allows performing the content uniformity testing of the studied drugs in their tablets by using the official United States Pharmacopeia (USP) guidelines. Statistical comparisons of the results with those of the reported methods revealed excellent agreement and indicated no significant difference in accuracy and precision.

New Combined Medical Treatment With Etilefrine and Octreotide for Chylothorax After Esophagectomy: A Case Report and Review of the Literature.

Postoperative chylothorax is a rare but well-known complication of general thoracic surgery. Medical treatment of chylothorax was reported in the past, but there is still considerable controversy on the appropriate management strategies.Two patients with esophageal cancer underwent esophagectomy, 2-field lymph node dissection, and resection of thoracic duct together with ileocolic reconstruction via the retrosternal route at our hospital. Chylothorax developed on the 32nd postoperative day (POD) in 1 patient and the 12th POD in the other, manifesting as a change in the character of thoracic drainage to turbid white. Both were immediately started on octreotide (300 µg/ day) and etilefrine (120 mg/day). When the amount of pleural effusion decreased to <50 mL/day, we performed pleurodesis with Picibanil (OK432). Thereafter, the patients gradually made satisfactory progress and resumed oral food intake, and the thoracotomy tubes were eventually removed. They have remained recurrence-free at the time of writing.In this report, we demonstrated the clinical efficacy of etilefrine for the management of postesophagectomy chylothorax. New medical treatment options for this condition are now broad and the usefulness of combined therapy consisting of a sclerosing agent, etilefrine, and octreotide is underscored, regardless of the status of the thoracic duct.

Drugs for hypotension: disproportionate harms with etilefrine and heptaminol. .

The French Health Products Agency concluded that etilefrine and heptaminol have an unfavourable harm-benefit balance, and also placed restrictions on the use of midodrine.

Evaluation of cardiovascular changes in dogs administered three positive controls using jacketed external telemetry-blood pressure (JET-BP).

INTRODUCTION: Nonclinical safety studies are increasingly incorporating cardiac safety endpoints to discover potential cardiovascular liabilities. This trend for more thorough cardiovascular nonclinical safety evaluation is prudent given the high attrition rate of potential therapeutics due to unexpected cardiovascular liabilities discovered in late-stage clinical trials or post-market approval. In particular, the causal relationship of blood pressure changes that lead to risk of major adverse cardiac events suggests hemodynamic changes should be critically evaluated in preclinical studies of novel therapeutics. METHODS: Jacketed external telemetry with an implanted miniature blood pressure transmitter (JET-BP) was used to characterize the tolerability, functionality, and sensitivity of this study design in dogs. Thirty-six male or female beagles (n=6 dogs/sex/group) were administered vehicle control (reverse osmosis water) or etilefrine (1, 10mg/kg), sotalol (3, 30mg/kg), and hydralazine (1, 10mg/kg) on separate days. Telemetry data were evaluated for positive control article-related changes and retrospective power analysis was also completed. Animals were evaluated for instrumentation-related changes in clinical and anatomic pathology endpoints. RESULTS: All three positive controls elicited the expected pharmacologic responses that were statistically different at high and low doses. Retrospective power analysis confirmed this study design was able to statistically differentiate minor (approximately 5 to 15%) changes in electrocardiography and blood pressure values. This study also demonstrated the potential advantages of combining cardiovascular data across sex when the test article exposure and pharmacodynamics were consistent. Data collection using miniature telemetry blood pressure transmitters did not result in anatomic or clinical pathology findings that would prevent their use in general toxicology studies. DISCUSSION: This characterization study indicates that JET-BP in dogs offers a scientifically-robust method to evaluate novel therapeutics for potential cardiovascular liabilities.

Practical application of color Doppler ultrasonography in patients with ejaculatory dysfunction.

We describe two cases in which dynamic analysis of ejaculation using color Doppler ultrasonography was useful in diagnosis of ejaculatory dysfunction and planning of therapy. The first patient was a 32-year-old man with a diagnosis of retrograde ejaculation. A bladder neck collagen injection was carried out, as the main cause was thought to be the bladder neck remaining open during ejaculation. The patient had antegrade ejaculation 1 week later. The second patient was a 48-year-old man with a diagnosis of anorgasmia accompanied by decreased seminal emission and insufficient function of the rhythmic pelvic striated muscles. The patient was prescribed etilefrine hydrochloride 15 mg/day. The symptom improved 2 weeks after starting this drug. These cases suggest that the use of color Doppler ultrasonography during ejaculation can improve the understanding of ejaculatory dysfunction and therapy for this condition.