Modeling of relationships between pharmacokinetics and blockade of agonist-induced elevation of intraurethral pressure and mean arterial pressure in conscious dogs treated with alpha(1)-adrenoceptor antagonists.

Fiduxosin is a new alpha(1)-adrenoceptor antagonist targeted for the treatment of symptomatic benign prostatic hyperplasia. The purpose of this study was to determine and compare the potencies of the alpha(1)-adrenoceptor antagonists terazosin, doxazosin, tamsulosin, and fiduxosin, based on relationships between plasma drug concentrations and blockade of phenylephrine (PE)-induced intraurethral (IUP) and mean arterial pressure (MAP) responses after single oral dosing in conscious male beagle dogs. Magnitude of blockade and plasma concentrations were evaluated at selected time points over 24 h. All drugs produced dose-dependent antagonism of PE-induced IUP and MAP responses. When IUP and MAP blockade effects were plotted against drug plasma concentrations, direct relationships were observed that were well described by the sigmoidal maximal effect model. IUP IC(50) values for terazosin, doxazosin, tamsulosin, and fiduxosin were 48.6, 48.7, 0.42, and 261 ng/ml, respectively. MAP IC(50) values were 12.2, 13.8, 1.07, and 1904 ng/ml, respectively. Uroselectivity index values, defined as MAP IC(50)/IUP IC(50), were 0.25, 0.28, 2.6, and 7.3, respectively. These results extend previous observations with terazosin in this model, showing that doxazosin exhibits a uroselectivity index comparable to terazosin, consistent with the lack of alpha(1)-adrenoceptor subtype selectivity or uroselectivity of these drugs. Tamsulosin, an alpha(1a)-/alpha(1d)-subtype selective agent, had an index value approximately 10-fold greater than the nonselective drugs. Based on its pharmacokinetic profile and a relative uroselectivity 29-fold greater than the nonselective drugs, fiduxosin is expected to exhibit greater selectivity for urethral compared with vascular alpha(1)-adrenoceptors in human and should be a novel, long-acting, uroselective alpha(1)-adrenoceptor antagonist.     

Asymmetric and Axisymmetric Constant Curvature Liquid-Gas Interfaces in Pulmonary Airways

Airway closure and gas trapping can occur during lung deflation and inflation when fluid menisci form across the lumina of respiratory passageways. Previous analyses of the behavior of liquid in airways have assumed that the airway is completely wetted or that the contact angle of the liquid-gas interface with the airway wall is 0, and thus that the airway fluid forms an axisymmetric surface. However, some investigators have suggested that liquid in the airways is discontinuous and that contact angles can be as high as 67. In this study we consider the characteristics of constant curvature surfaces that could form a stable liquid-gas interface in a cylindrical airway. Our analysis suggests that, for small liquid volumes, asymmetric droplets are more likely to form than axisymmetric toroids. In addition, if the fluid contact angle is greater than 13, asymmetric droplets can sustain larger liquid volumes than axisymmetric toroids before collapsing to form menisci. These results suggest that (1) fluid formations other than axisymmetric toroids could occur in the airways; and (2) the analysis of the behavior of fluids and the development of liquid menisci within the lungs should include the potential role of asymmetric droplets.     

Transnational health resources, practices, and perspectives: Brazilian immigrant women's narratives

This paper examines the representations of transnational health resources, practices, and perspectives in the narratives of Brazilian immigrant women. The results of this qualitative narrative research indicated that in taking care of their health, these Brazilian immigrants often relied on a combination of personal and collective transnational resources. They engaged in a variety of premigration and transnational health practices and demonstrated a high degree of personal responsibility for their health, although they frequently delayed or postponed seeking formal health care. In responding to health and illness concerns, these immigrant women moved back and forth across informal and formal health care systems, crossing multiple national, cultural, and health care system borders. Their stories illustrated the transnational nature of personal, cultural, and political perspectives on health and health care and highlighted the layered complexities of immigrant women's health practices and resources.     

Levetiracetam for the treatment of hot flashes: a phase II study

Goals of work The objectives of this pilot trial were to assess the potential efficacy and safety of levetiracetam for the treatment of hot flashes, a major cause of morbidity among breast cancer survivors. Patients and methods Women, aged 18 years or more, with a history of breast cancer or those who wished to avoid estrogen because of a perceived increased risk of breast cancer, who were experiencing bothersome hot flashes (more than or equal to 14 times per week, for more than or equal to 1 month before study entry), were included. During the baseline week, general demographic characteristics, hot flash information, and quality of life data were obtained. At the beginning of week 2, patients were started on levetiracetam for a total of 4 weeks. Information about hot flashes, quality of life, and toxicity were collected during these 4 weeks and compared with the baseline week. Main results After treatment with levetiracetam for 4 weeks (N = 19), mean hot flash scores (frequency times mean severity) were reduced by 57%, and mean hot flash frequencies were reduced by 53%, compared to the baseline week; both these reductions were greater than what would be expected with a placebo (20–25% reduction). There were significant improvements in abnormal sweating (p = 0.004), hot flash distress (p = 0.0002), and satisfaction of hot flash control (p = 0.0001), when comparing data from the fourth week of treatment to the baseline week. Twenty-nine percent of the subjects did not complete the study because of treatment-related adverse events, with the most frequently reported side effects being somnolence, fatigue, and dizziness, usually with mild to moderate intensity. Conclusion The results of this pilot trial suggest that levetiracetam might be an effective therapy for the treatment of hot flashes. Further data are needed to test this hypothesis, evaluating the efficacy and toxicity of this agent. Financial Disclosure: None     

Pharmacokinetics of Sustained-Release and Transdermal Buprenorphine in G?ttingen Minipigs (Sus scrofa domestica)

The opioid buprenorphine has been shown to provide adequate postoperative analgesia in both companion and laboratory animals. However, its use is still hindered by the need for multiple parenteral injections to achieve continuous analgesia. The purpose of the current study was to conduct a pharmacokinetic analysis of 2 new long-acting formulations of buprenorphine—an injectable sustained-release buprenorphine (SRB) and a transdermal buprenorphine (TDB) patch—in healthy Göttingen minipigs by using liquid chromatography–electrospray ionization–tandem mass spectrometry. Administration of 0.18 mg/kg SC SRB and 30 μg/h TDB achieved AUC_0-Tlast of 221.6 ± 26.8 and 25.2 ± 3.9 ng × h/mL, respectively, compared with 9.7 ± 1.4 ng*h/mL for 0.02 mg/kg IV buprenorphine. By using a hypothesized therapeutic plasma buprenorphine concentration threshold of 0.1 ng/mL, therapeutic concentrations were achieved at the first study time point (5 to 30 min) and lasted an average of 8.0 ± 1.3 h for intravenous buprenorphine and 264.0 ± 32.2 h for SRB. TDB achieved therapeutic concentrations in 12 to 24 h after patch application, which lasted until the patch was removed at 72 h. The results of this study suggest that SRB and TDB are long-acting alternatives for pain management, and their use could decrease animal handling and stress, thereby simplifying pain management and improving welfare in laboratory swine.Abbreviation: AUC_0-Tlast, AUC to last quantifiable plasma concentration; C_max, peak plasma concentration; SRB, sustained-release buprenorphine; TDB, transdermal buprenorphine; T_max, time of peak plasma concentration; VAP, vascular access portBuprenorphine is a semisynthetic, partial µ-opioid receptor agonist used for analgesia in many companion and laboratory animal species.^7,29 Its popularity is due to a lower risk of respiratory depression and prolonged analgesia in comparison to pure µ-opioid agonists, such as fentanyl and hydromorphone.^7,29 Buprenorphine is often the analgesic of choice in swine because a single 0.01- to 0.1-mg/kg dose can provide analgesia for as long as 8 to 12 h with minimal adverse effects.^7,33Swine are valuable animal models for cardiovascular, digestive, urinary, and integumentary research.^32,33 As a result, laboratory swine often undergo major surgeries resulting in considerable postoperative pain. To provide analgesia of adequate efficacy and duration throughout the postoperative period, multiple injections of buprenorphine are necessary. Repeated injections and the associated handling and momentary pain can become increasingly stressful to swine with each subsequent injection. In addition, the recurrent peak and trough plasma concentrations associated with multiple parenteral injections potentially result in periods of inadequate pain relief at trough levels. A buprenorphine formulation that can be administered less frequently or in a noninjectable formulation but that can deliver a controlled and constant amount of drug over time potentially would eliminate the disadvantages of repeated dosing.Recently 2 new formulations of buprenorphine have become available: an injectable sustained-release buprenorphine (SRB) and a transdermal buprenorphine (TDB) patch. Both formulations are designed to provide a consistent, controlled release of buprenorphine over the course of several days after a single administration. Recent studies in mice,⁴ rats,⁸ cats,⁵ and dogs²⁴ support the ability of SRB to provide an extended duration of analgesia compared with that of the standard buprenorphine formulation. In addition, therapeutic plasma concentrations have been shown to last as long as 72 h in rats⁸ and 5 d in both macaques²³ and dogs.²⁴ Although SRB has been studied in several animal species, it has yet to be evaluated in swine.TDB has been extensively used in human medicine however, unlike SRB, there are relatively few studies evaluating the efficacy of TDB in animals. High-dose (35, 52.5, and 70 µg/h) and low-dose (5, 7.5, 10, 15, and 20 µg/h) TDB patches, lasting 3 and 7 d, respectively, have been used effectively in humans to treat moderate to severe, chronic pain such as lower back pain and that due to osteoarthritis or cancer.^{6,9,14,20,26,30,31,35} Currently, TDB studies in animals have only been performed by using high-dose patches and have been limited to dogs^1,21,25 and cats.²² In dogs, detectable plasma buprenorphine concentrations have been shown to last 72 h after the application of a single 52.5-µg/h TDB patch²⁵ and 108 h with a 70-µg/h patch.¹ In addition, a 70-µg/h TDB patch has been reported to provide equal postoperative analgesia in dogs that underwent an ovariohysterectomy when compared with 0.2 mg/kg of the standard formulation of buprenorphine administered subcutaneously every 6 h during the postoperative period. ²¹ To date, TDB has not been evaluated in swine.Because of the success seen with both SRB and TDB in other species, further investigation into the pharmacokinetics and clinical efficacy of SRB and TDB in swine is warranted. These buprenorphine formulations have the potential for extended drug delivery with a single administration and thus the potential to positively affect animal welfare by minimizing animal stress. The purpose of this study was to evaluate the pharmacokinetics of these 2 new formulations of buprenorphine compared with a standard dose of intravenous buprenorphine in Göttingen minipigs. We hypothesized that both SRB and TDB would achieve quantifiable plasma buprenorphine concentrations above an estimated therapeutic threshold of 0.1 ng/mL for a longer duration than that of a standard dose of intravenous buprenorphine, thus supporting the use of these new formulations as long-acting analgesics for pain management in swine.     

Continuous SvO2 monitoring. A research review.

Nurses have access to continuous SvO2 monitoring as one parameter for evaluating the hemodynamic status in critically ill patients. The research studies on SvO2 monitoring have demonstrated inconsistent results regarding the utility of SvO2 as an assessment tool. Hence, it is necessary to carefully review these research findings for their impact on nursing practice. Nurses must be aware of the possibility of overreliance on continuous SvO2 monitoring and of the limitations of the SvO2 measurement itself.     

Living in Limbo: Latinas' Assessment of Lower Rio Grande Valley Colonias Communities

Community asset mapping (CAM) is the collective process of identifying local assets and strategizing processes to address public health issues and concerns and improve quality of life. Prior to implementing a community‐based physical activity intervention with Latinas in the Texas Lower Rio Grande Valley, promotoras [community health workers] conducted 16 interactive sessions in 8 colonias. The analysis of the transcribed CAM recordings and on‐site observational data resulted in the construction of Living in Limbo as the thematic representation of these Latinas' social isolation and marginalization associated with pervasive poverty, undocumented immigration status or lack of citizenship, their fears emanating from threats to physical and emotional safety, and the barriers created by lack of availability and access to resources.