Sample records for breakthrough pain pharmacokinetics

  1. Breakthrough cancer pain

    DEFF Research Database (Denmark)

    Davies, Andrew; Buchanan, Alison; Zeppetella, Giovambattista


    Breakthrough pain is common in patients with cancer and is a significant cause of morbidity in this group of patients.......Breakthrough pain is common in patients with cancer and is a significant cause of morbidity in this group of patients....

  2. Breakthrough cancer pain – still a challenge (United States)

    Margarit, Cesar; Juliá, Joaquim; López, Rafael; Anton, Antonio; Escobar, Yolanda; Casas, Ana; Cruz, Juan Jesús; Galvez, Rafael; Mañas, Ana; Zaragozá, Francisco


    Breakthrough cancer pain is defined as transient pain exacerbation in patients with stable and controlled basal pain. Although variable, the prevalence of breakthrough cancer pain is high (33%–95%). According to the American Pain Foundation, breakthrough pain is observed in 50%–90% of all hospitalized cancer patients, in 89% of all patients admitted to homes for the elderly and terminal-patient care centers, and in 35% of all ambulatory care cancer patients. The management of breakthrough cancer pain should involve an interdisciplinary and multimodal approach. The introduction of new fentanyl formulations has represented a great advance and has notably improved treatment. Among these, the pectin-based intranasal formulation adjusts very well to the profile of breakthrough pain attacks, is effective, has a good toxicity profile, and allows for convenient dosing – affording rapid and effective analgesia with the added advantage of being easily administered by caregivers when patients are unable to collaborate. PMID:23204865

  3. Breakthrough cancer pain – still a challenge

    Directory of Open Access Journals (Sweden)

    Mañas A


    Full Text Available Cesar Margarit,1 Joaquim Juliá,2 Rafael López,3 Antonio Anton,4 Yolanda Escobar,5 Ana Casas,6 Juan Jesús Cruz,7 Rafael Galvez,8 Ana Mañas,9 Francisco Zaragozá101Pain Unit, Alicante University General Hospital, Alicante, Spain; 2Department of Integral Support-Palliative Care, Catalan Institute of Oncology (ICO, Germans Trias i Pujol University Hospital, Badalona, Spain; 3Department of Clinical Oncology, University Hospital Complex, Santiago de Compostela, Spain; 4Department of Clinical Oncology, Miguel Servet Hospital, Zaragoza, Spain; 5Department of Clinical Oncology, Gregorio Marañón Hospital, Madrid, Spain; 6Department of Oncology, Virgen Macarena Hospital, Seville, Spain; 7Department of Clinical Oncology, Salamanca Hospital, Salamanca, Spain; 8Pain and Palliative Care Unit, Virgen de las Nieves Hospital, Granada, Spain; 9Department of Oncology–Radiotherapy, La Paz Hospital, Madrid, Spain; 10Department of Pharmacology, University of Alcalá de Henares, SpainAbstract: Breakthrough cancer pain is defined as transient pain exacerbation in patients with stable and controlled basal pain. Although variable, the prevalence of breakthrough cancer pain is high (33%–95%. According to the American Pain Foundation, breakthrough pain is observed in 50%–90% of all hospitalized cancer patients, in 89% of all patients admitted to homes for the elderly and terminal-patient care centers, and in 35% of all ambulatory care cancer patients. The management of breakthrough cancer pain should involve an interdisciplinary and multimodal approach. The introduction of new fentanyl formulations has represented a great advance and has notably improved treatment. Among these, the pectin-based intranasal formulation adjusts very well to the profile of breakthrough pain attacks, is effective, has a good toxicity profile, and allows for convenient dosing – affording rapid and effective analgesia with the added advantage of being easily administered by

  4. Single-dose fentanyl sublingual spray for breakthrough cancer pain

    Directory of Open Access Journals (Sweden)

    Taylor DR


    Full Text Available Donald R Taylor Comprehensive Pain Care PC, Marietta, GA, USA Abstract: Breakthrough cancer pain (BTCP is defined as a transient exacerbation of pain that arises in patients with otherwise controlled persistent pain. BTCP typically has a rapid onset and relatively short duration, but it causes a significant amount of physical and psychological distress for patients. Several rapid-onset fentanyl formulations have been introduced in the USA to replace traditional oral opioids for the treatment of BTCP: a transmucosal lozenge, a sublingual orally disintegrating tablet, a buccal tablet, a buccal soluble film, a pectin nasal spray and, the newest formulation to enter the market, a sublingual spray. This article reviews the six rapid-onset formulations of fentanyl approved in the USA for the management of BTCP with emphasis on describing the published literature on fentanyl sublingual spray. The different fentanyl formulations vary in pharmacokinetic properties and ease of use, but all have a rapid onset and a relatively short duration of analgesia. Fentanyl sublingual spray has demonstrated absorption within 5 minutes of administration, with fentanyl plasma concentrations increasing over the first 30 minutes and remaining elevated for 60–90 minutes in pharmacokinetic studies in healthy subjects. Fentanyl sublingual spray shows linear dose proportionality, and changes in the temperature or acidity of the oral cavity do not alter its pharmacokinetic properties. In patients with BTCP, statistically significant pain relief is measurable at 5 minutes after administration of fentanyl sublingual spray, when compared with placebo, with significant pain relief lasting at least 60 minutes after administration. Adverse events are typical of opioid treatment and are considered mild to moderate in intensity. In summary, fentanyl sublingual spray provides rapid onset of analgesia and is a tolerable and effective treatment for BTCP. Keywords: breakthrough pain

  5. The management of breakthrough pain during labour. (United States)

    Akerman, Nicholas; Dresner, Martin


    There is a long history of attempts to alleviate the pain of childbirth, particularly in Asian and Middle Eastern civilisations. In the UK, it was the administration of chloroform to Queen Victoria by John Snow in 1853 that is widely credited with popularizing the idea that labour pain should and could be treated. Medical analgesia is now well established around the globe with a wealth of research evidence describing methods, efficacy and complications. In this article, we define 'primary breakthrough pain' as the moment when a woman first requests analgesia during labour. The management of this can include simple emotional support, inhaled analgesics, parenteral opioids and epidural analgesia. 'Secondary breakthrough pain' can be defined as the moment when previously used analgesia becomes ineffective. We concentrate our discussion of this phenomenon on the situation when epidural analgesia begins to fail. Only epidural analgesia offers the potential for complete analgesia, so when this effect is lost the recipient can experience significant distress and dissatisfaction. The best strategy to avert this problem is prevention by using the best techniques for epidural catheterisation and the most effective drug combinations. Even then, epidurals can lose their efficacy for a variety of reasons, and management is hampered by the fact that each rescue manoeuvre takes about 30 minutes to be effective. If the rescue protocol is too cautious, analgesia may not be successfully restored before delivery, leading to patient dissatisfaction. We therefore propose an aggressive response to epidural breakthrough pain using appropriate drug supplementation and, if necessary, the placement of a new epidural catheter. Combined spinal epidural techniques offer several advantages in this situation. The goal is to re-establish analgesia within 1 hour. The primary aim of pain management during labour and delivery is to provide the level of comfort determined as acceptable to each

  6. Management of breakthrough pain in patients with cancer. (United States)

    William, Leeroy; Macleod, Rod


    Breakthrough pain (BTP) in patients with cancer lacks a consensus definition and is subsequently inadequately diagnosed and assessed, therefore making it more challenging to manage. Cancer pain is generally moderate to severe in intensity and persistent in nature. Despite the problematic definition of BTP, it is generally described as having similar intensity, but may also be transitory and variable in predictability. Most breakthrough analgesia fails to be effective in the time required for BTP. No useful analgesia is therefore provided but drug adverse effects escalate. Cancer pain management relies on the WHO analgesic ladder. The frequency of BTP and its inadequate management means that it has significant adverse effects on patients, their families and those involved in their care. This article outlines a systematic, clinical and evidence-based approach to managing BTP in patients with cancer that emphasizes a holistic approach and an understanding of multidimensional 'total pain'. Guidelines for managing BTP are presented and areas of developing research are identified.

  7. Back to the future, current trends in breakthrough pain treatments

    Directory of Open Access Journals (Sweden)

    Max Watson


    Full Text Available The importance of effectively managing breakthrough pain for patients on long term background analgesia has recently lead to the development of a range of new products aimed at filling this need. This review article looks at the reasons behind these developments and their implications for clinical practice in resource limited situations.

  8. Breakthrough cancer pain – still a challenge


    Mañas A; Galvez R; Cruz JJ; Casas A; Escobar Y; Anton A; López R; Juliá J; Margarit C; Zaragozá F


    Cesar Margarit,1 Joaquim Juliá,2 Rafael López,3 Antonio Anton,4 Yolanda Escobar,5 Ana Casas,6 Juan Jesús Cruz,7 Rafael Galvez,8 Ana Mañas,9 Francisco Zaragozá101Pain Unit, Alicante University General Hospital, Alicante, Spain; 2Department of Integral Support-Palliative Care, Catalan Institute of Oncology (ICO), Germans Trias i Pujol University Hospital, Badalona, Spain; 3Department of Clinical Oncology, University Hospital Complex, Santia...

  9. Breakthrough Pain Associated with a Reduction in Serum Buprenorphine Concentration during Dialysis. (United States)

    Salili, Ali Reza; Müller, Daniel; Skendaj, Roswitha; Jehle, Andreas W; Taegtmeyer, Anne B


    To describe a case of breakthrough pain associated with a reduction in serum buprenorphine concentration during dialysis. Pharmacokinetic sampling of total and free buprenorphine and norbuprenorphine in an 80 year old male undergoing haemodialysis three times per week who received 5760 µg oral and transdermal buprenorphine daily was performed. The patient's serum albumin concentration was 23g/l (reference range: 35-52 g/l). Pharmacokinetic sampling revealed a free buprenorphine fraction of 32% (consistent with the hypoalbuminaemia), which was markedly reduced at the end of dialysis (free buprenorphine concentration 2.4 µg/l before vs. buprenorphine doses during dialysis to prevent significant falls in the concentration of active drug. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  10. Breakthrough cancer pain: twenty-five years of study. (United States)

    Mercadante, Sebastiano; Portenoy, Russell K


    Breakthrough cancer pain (BTcP) is an episode of severe pain that "breaks through" a period of persistent pain at least partly controlled by a stable opioid regimen. Although mentioned in the literature decades ago, it has been only 25 years since the first effort to define and measure it. Controversy about the definition of BTcP continues despite an international effort to achieve consensus. Nevertheless, common approaches to measurement of BTcP have led to a robust literature, including many surveys that have described prevalence, characteristics, and association with adverse outcomes. Measurement also has been important for clinical trials of new drug formulations specifically designed for BTcP. Several approaches have been reported in the literature, although most of them have never been substantiated with appropriate studies. Administration of an opioid as needed is the most common treatment. Twenty-five years of research has produced a more refined understanding of the safety and efficacy of oral opioids in this context, and provided the clinical trials data necessary to attain regulatory approval of multiple new formulations specifically developed for BTcP. Transmucosal formulations of fentanyl may provide meaningful analgesia within 5 to 15 minutes. Given the difference in cost, transmucosal formulations should be considered in a subset of patients with BTcP, including those with pain that are not adequately controlled with an oral drug and those with distress associated with the rapid pain onset. The long-term use of opioids for BTcP remains to be clarified. Future studies should assess the potential of personalized treatment of BTcP.

  11. A European survey of oncology nurse breakthrough cancer pain practices. (United States)

    Rustøen, Tone; Geerling, Jenske I; Pappa, Theodora; Rundström, Carina; Weisse, Isolde; Williams, Sian C; Zavratnik, Bostjan; Kongsgaard, Ulf E; Wengström, Yvonne


    Breakthrough cancer pain (BTCP) is a prevalent type of pain in which the nurse can play an important role in improving patients' pain symptoms and overall well-being. Nurses' experience with BTCP (number of patients, and estimates of severity and frequency), the treatment of BTCP (pharmacological and nonpharmacological treatments normally used), ratings of the importance of treatment factors, and reasons given for not advising patients to take strong painkillers are presented in the present paper. Nurses from 12 European countries, who cared for patients with cancer, took part in a survey. In total 1618 nurses were recruited and 1241 completed the survey questionnaire. Almost 90% of the nurses were female, and 50.4% had >9 years of experience in oncology nursing. The majority of the nurses (47%) said that a patient typically suffered from BTCP 2-3 times a day, and the severity of the pain for the patients was described as severe by 75.5%. In all, 38.4% of the nurses were unaware that medications specifically intended for treatment of BTCP exist, and 57% reported that oral opioids were normally prescribed for BTCP at their workplace. While 38% said they did not use nonpharmacological treatments for BTCP, the most common treatment approach was positional change (used by 76.6%). The treatment varied between the European countries. Patients do not receive the appropriate medical treatment for their BTCP. Nurses need better training about BTCP in general, and BTCP assessment and management specifically. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. The management of breakthrough cancer pain--educational needs a European nursing survey. (United States)

    Wengström, Y; Rundström, C; Geerling, J; Pappa, T; Weisse, I; Williams, S C; Zavratnik, B; Rustøen, T


    Poorly managed cancer pain is well known to profoundly impact the patient's daily life and interfere with quality of life. Nurses who cared for patients with cancer from 12 European countries participated in a survey of breakthrough cancer pain practice. The purpose was to investigate how nurses assess breakthrough cancer pain, use of standardised tools, confidence in supporting patients and awareness of medications. Responses from 1241 participants showed country variations. The majority of the sample was female, Germany had the highest proportion of male nurses (21.0%), followed by Greece (15.8%). A significantly larger proportion of nurses with longer experience and more education (78.8%) used a comprehensive definition of breakthrough cancer pain. Significant variations in training were found; 71% of Finnish nurses had received training compared with 6% of Greek nurses. Training and using a standardised assessment tool was associated with a significant increase in the nurses' perceived ability to distinguish between breakthrough and background pain. Nurses in countries with the highest proportion of training were most confident in supporting patients. In conclusion, there still exists problems with effective management of patients' breakthrough cancer pain, continuing inability to define the difference between background and breakthrough cancer pain leads to poor treatment. © 2013 John Wiley & Sons Ltd.

  13. Breakthrough pain in opioid-treated chronic non-malignant pain patients referred to a multidisciplinary pain centre: a preliminary study

    DEFF Research Database (Denmark)

    Højsted, J; Nielsen, P R; Eriksen, Jacob Gram


    Breakthrough pain (BTP) has not formerly been discussed as such in chronic non-malignant pain patients referred to pain centres and clinics. The purpose of the study was to investigate the prevalence, characteristics and mechanisms of BTP in opioid-treated chronic non-malignant pain patients...... referred to a pain centre and to assess the short-term effects of pain treatment....

  14. Multi-centre European study of breakthrough cancer pain: pain characteristics and patient perceptions of current and potential management strategies

    DEFF Research Database (Denmark)

    Davies, Andrew; Zeppetella, Giovambattista; Andersen, Steen


    This study involved 320 cancer patients from four Northern European countries. Patients with breakthrough pain were questioned about the characteristics of their pain, the current management of their pain, and the acceptability/utility of alternative routes of administration. The median number of...

  15. Central Hyperexcitability in Chronic Musculoskeletal Pain: A Conceptual Breakthrough with Multiple Clinical Implications

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    Jan Lidbeck


    Full Text Available Recent investigations of dysfunctional pain processing in the central nervous system have contributed much knowledge about the development of chronic musculoskeletal pain. Many common chronic musculoskeletal pain syndromes - including regional myofascial pain syndromes, whiplash pain syndromes, refractory work-related neck-shoulder pain, certain types of chronic low back pain, fibromyalgia and others - may essentially be explained by abnormalities in central pain modulation. The growing awareness of dysfunctional central pain modulation may be a conceptual breakthrough leading to a better understanding of common chronic pain disorders. A new paradigm will have multiple clinical implications, including re-evaluation of clinical practice routines and rehabilitation methods, and will focus on controversial issues of medicolegal concern. The concept of dysfunctional central pain processing will also necessitate a mechanism-based classification of pain for the selection of individual treatment and rehabilitation programs for subgroups of patients with chronic musculoskeletal pain due to different pathophysiological mechanisms.

  16. How do nurses in specialist palliative care assess and manage breakthrough cancer pain? A multicentre study. (United States)

    Soden, Katie; Ali, Simone; Alloway, Lara; Barclay, David; Barker, Stephanie; Bird, Lydia; Hall, Lesley; Perkins, Paul


    To gain a better understanding of how registered nurses working in specialist palliative care assess and manage breakthrough cancer pain. A mixed-methodology study was undertaken in two stages-this paper reports findings from stage two. Anonymous postal questionnaires, designed based on themes identified in interviews undertaken during stage one, were sent to trained nurses working in ten specialist palliative care services in England. A total of 104 questionnaires were returned. Respondents were experienced nurses mainly working in inpatient settings. Some 82% of the nurses wanted more training on the assessment of breakthrough cancer pain. Although there were inconsistencies around the use of terminology, pain management appeared to be good. The use of terminology in the field of breakthrough cancer pain remains variable. However, this does not appear to have a negative impact on patient management, which was broadly in line with recently published consensus recommendations. There is a desire for more education within this area of practice.

  17. A new transmucosal drug delivery system for patients with breakthrough cancer pain: the fentanyl effervescent buccal tablet


    Freye, Enno


    Enno FreyeCenter of Ambulatory Pain Medicine, Neuss-Uedesheim, GermanyAbstract: Breakthrough pain, a transitory severe pain with the background of otherwise controlled persistent pain has a prevalence between 52% and 67% in outpatients with cancer. Medications for such sudden-onset pain require non-invasive delivery of a potent and short-acting opioid for rapid pain relief. Although oral transmucosal delivery of fentanyl citrate (OTFC) has been shown to provide better pain relief than a typic...

  18. Accuracy of a Diagnostic Algorithm to Diagnose Breakthrough Cancer Pain as Compared With Clinical Assessment. (United States)

    Webber, Katherine; Davies, Andrew N; Cowie, Martin R


    Breakthrough cancer pain (BTCP) is a heterogeneous condition, and there are no internationally agreed standardized criteria to diagnose it. There are published algorithms to assist with diagnosis, but these differ in content. There are no comparative data to support use. To compare the diagnostic ability of a simple algorithm against a comprehensive clinical assessment to diagnose BTCP and to assess if verbal rating descriptors can adequately discriminate controlled background pain. Patients with cancer pain completed a three-step algorithm with a researcher to determine if they had controlled background pain and BTCP. This was followed by a detailed pain consultation with a clinical specialist who was blinded to the algorithm results and determined an independent pain diagnosis. The sensitivity, specificity, and positive and negative predictive values were calculated for the condition of BTCP. Further analysis determined which verbal pain severity descriptors corresponded with the condition of controlled background pain. The algorithm had a sensitivity of 0.54 and a specificity of 0.76 in the identification of BTCP. The positive predictive value was 0.7, and the negative predictive value was 0.62. The sensitivity of a background pain severity rating of mild or less to accurately categorize controlled background pain was 0.69 compared with 0.97 for severity of moderate or less; however, this was balanced by a higher specificity rating for mild or less, 0.78 compared with 0.2. The diagnostic breakthrough pain algorithm had a good positive predictive value but limited sensitivity using a cutoff score of "mild" to define controlled background pain. When the cutoff level was changed to moderate, the sensitivity increased, but specificity reduced. A comprehensive clinical assessment remains the preferred method to diagnose BTCP. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  19. Relationship between onset of pain relief and patient satisfaction with fentanyl pectin nasal spray for breakthrough pain in cancer. (United States)

    Torres, Luis M; Revnic, Julia; Knight, Alastair D; Perelman, Michael


    Satisfaction with pain relief in patients with breakthrough pain in cancer (BTPc) has typically been assessed by overall efficacy without consideration of the rapidity of that response. To determine the relationship between speed of onset of pain relief and patient satisfaction for treated BTPc episodes overall and for individual treatments. Pooled data from two randomized, double-blinded crossover studies. Patients having 1-4 BTPc episodes per day on ≥60 mg/day oral morphine or equivalent. Episodes treated with fentanyl pectin nasal spray (FPNS; 100-800 μg), immediate-release morphine sulfate (IRMS), or placebo. Pain intensity was measured on an 11-point scale (5-60 minutes posttreatment); satisfaction was measured on a 4-point scale (30 and 60 minutes). The primary analysis assessed the overall relationship of time to onset of pain relief (pain intensity difference [PID]≥1) or time to clinically meaningfully reduction in pain (PID≥2) versus patient satisfaction and overall pain intensity (summed pain intensity difference at 30 [SPID30] and 60 minutes [SPID60]) assessed by analysis of variance (ANOVA). A secondary analysis assessed whether satisfaction was different between treatments using a within-patient comparison. Eight hundred thirty-one FPNS-treated, 368 IRMS-treated, and 200 placebo-treated episodes were analyzed. Overall, within the pool there was a statistically significant relationship between time to onset of pain relief (PID≥1 and PID≥2) and patient satisfaction (both speed of relief and overall) at 30 and 60 minutes (ppain intensity reduction. When treatment groups were compared using within-patient data, FPNS provided earlier onset of pain relief than IRMS or placebo (ppain relief resulted in greater patient satisfaction and overall relief of pain; between-treatment comparisons showed that FPNS provided earlier pain relief and greater satisfaction than IRMS or placebo.

  20. Nurse-based monitoring and management of breakthrough pain in an acute pain relief and palliative care unit. (United States)

    Mercadante, Sebastiano; Prestia, Giovanna; Casuccio, Alessandra


    To assess the nurses' performance in assessing, treating, and documenting breakthrough pain (BTP) in a palliative care unit where traditionally there is continuous training. The study was performed in an acute palliative care unit. Once a week, a research nurse examined the documentation regarding all the episodes of BTP registered in a specific pain chart, designed by the institutional nurse board, as part of the routine nurse activity. The charts of 50 consecutive eligible patients (32 M/18 F), were analysed. The mean number of episodes/patient was 3.3 (SD 1.61; range 1-7). 166 episodes occurred. The main BTP pain intensity was 7.06 (SD 0.82). In 7 episodes, pain intensity was not evaluated at T0. The pain intensity after 15 minutes after BTP medication was 3.01 (SD1.19). In 28 episodes, pain intensity was not evaluated at T15. The change in pain intensity was highly significant (P nurse diary. Training in a research environment allows a good nurse capability in evaluating and treating BTP, and above all, providing documentation for each BTP episode. The theoretical work and recommendations around BTP need to be translated into day-to-day clinical practice.

  1. Fentanyl sublingual spray for breakthrough cancer pain in patients receiving transdermal fentanyl. (United States)

    Alberts, David S; Smith, Christina Cognata; Parikh, Neha; Rauck, Richard L


    To investigate the relationship between effective fentanyl sublingual spray (FSS) doses for breakthrough cancer pain (BTCP) and around-the-clock (ATC) transdermal fentanyl patch (TFP). Adults tolerating ATC opioids received open-label FSS for 26 days, followed by a 26-day double-blind phase for patients achieving an effective dose (100-1600 µg). Out of 50 patients on ATC TFP at baseline, 32 (64%) achieved an effective dose. FSS effective dose moderately correlated with mean TFP dose (r = 0.4; p = 0.03). Patient satisfaction increased during the study. Common adverse event included nausea (9%) and peripheral edema (9%). FSS can be safely titrated to an effective dose for BTCP in patients receiving ATC TFP as chronic cancer pain medication. identifier: NCT00538850.

  2. Efficacy, safety, and tolerability of fentanyl pectin nasal spray in patients with breakthrough cancer pain

    Directory of Open Access Journals (Sweden)

    Ueberall MA


    Full Text Available Michael A Ueberall,1 Stefan Lorenzl,2 Eberhard A Lux,3,4 Raymond Voltz,5 Michael Perelman6 1Institute of Neurological Sciences, Nuremberg, Germany; 2Institute of Nursing Science and Practice, Paracelsus Private Medical University of Salzburg, Salzburg, Austria; 3Faculty of Medicine, Witten/Herdecke University, Witten, Germany; 4Clinic for Pain and Palliative Care Medicine, St.- Marien-Hospital, Luenen, Germany; 5Department of Palliative Medicine, University Hospital Cologne, Cologne, Germany; 6Archimedes Development Ltd., Nottingham, United Kingdom Objective: Assessment of analgesic effectiveness, safety, and tolerability of fentanyl pectin nasal spray (FPNS in the treatment of breakthrough cancer pain (BTcP in routine clinical practice.Methods: A prospective, open-label, noninterventional study (4-week observation period, 3 month follow-up of opioid-tolerant adults with BTcP in 41 pain and palliative care centers in Germany. Standardized BTcP questionnaires and patient diaries were used. Evaluation was made of patient-reported outcomes with respect to “time to first effect”, “time to maximum effect”, BTcP relief, as well as changes in BTcP-related impairment of daily life activities, ­quality-of-life restrictions, and health care resource utilization.Results: A total of 235 patients were recruited of whom 220 completed all questionnaires and reported on 1,569 BTcP episodes. Patients reported a significant reduction of maximum BTcP intensity (11-stage numerical rating scale [0= no pain, 10= worst pain conceivable] with FPNS (mean ± standard deviation = 2.8±2.3 compared with either that reported at baseline (8.5±1.5, experienced immediately before FPNS application (7.4±1.7, or that achieved with previous BTcP medication (6.0±2.0; P<0.001 for each comparison. In 12.3% of BTcP episodes, onset of pain relief occurred ≤2 minutes and in 48.4% ≤5 minutes; maximum effects were reported within 10 minutes for 37.9% and within 15 minutes

  3. Cost-effectiveness analysis of oral fentanyl formulations for breakthrough cancer pain treatment. (United States)

    Cortesi, Paolo Angelo; D'Angiolella, Lucia Sara; Vellucci, Renato; Allegri, Massimo; Casale, Giuseppe; Favaretti, Carlo; Kheiraoui, Flavia; Cesana, Giancarlo; Mantovani, Lorenzo Giovanni


    Breakthrough cancer Pain (BTcP) has a high prevalence in cancer population. Patients with BTcP reported relevant health care costs and poor quality of life. The study assessed the cost-effectiveness of the available Oral Fentanyl Formulations (OFFs) for BTcP in Italy. A decision-analytical model was developed to estimate costs and benefits associated with treatments, from the Italian NHS perspective. Expected reductions in pain intensity per BTcP episodes were translated into, percentage of BTcP reduction, resource use and Quality-Adjusted-Life-Years (QALYs). Relative efficacy, resources used and unit costs data were derived from the literature and validated by clinical experts. Probabilistic and deterministic sensitivity analyses were performed. At base-case analysis, Sublingual Fentanyl Citrate (FCSL) compared to other oral formulations reported a lower patient's cost (€1,960.8) and a higher efficacy (18.7% of BTcP avoided and 0.0507 QALYs gained). The sensitivity analyses confirmed the main results in all tested scenarios, with the highest impact reported by BTcP duration and health care resources consumption parameters. Between OFFs, FCSL is the cost-effective option due to faster reduction of pain intensity. However, new research is needed to better understand the economic and epidemiologic impact of BTcP, and to collect more robust data on economic and quality of life impact of the different fentanyl formulations. Different fentanyl formulations are available to manage BTcP in cancer population. The study is the first that assesses the different impact in terms of cost and effectiveness of OFFs, providing new information to better allocate the resources available to treat BTcP and highlighting the need of better data.

  4. Correlations between plasma endothelin-1 levels and breakthrough pain in patients with cancer

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    Yan XB


    Full Text Available Xue-bin Yan, Tuo-chao Peng, Dong Huang Department of Anesthesiologist, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, People’s Republic of China Abstract: Endothelin-1 (ET-1 may be involved in driving pain in patients with advanced cancer. However, a few studies focus on the role of ET-1 in breakthrough pain (BP. The aim of this pivotal study was to explore the correlation between the plasma (ET-1 level and BP intensity. A total of 40 patients were enrolled in the study, and they were divided into two groups: BP group and non-BP group. Moreover, 20 healthy adults were used as the normal control group. Pain intensity was measured using visual analog scale (VAS scores of 1–10. Plasma ET-1 levels were detected by an ET radioimmunoassay kit. Subsequently, the correlation of ET-1 level with the VAS score and cancer types was analyzed by Pearson’s correlation coefficient. The plasma ET-1 level in the BP group (35.31±8.02 pg/mL was higher than that in the non-BP group (29.51±6.78 pg/mL and the normal control group (24.77±10.10 pg/mL, P<0.05. In addition, the VAS score in the BP group (7.45±0.82 was higher than that in the non-BP group (2.80±1.23, P<0.05. The plasma ET-1 level was positively correlated with the VAS score of the BP group (Pearson’s r=0.42. There was no significant correlation between the plasma ET-1 level and VAS score of the non-BP group (Pearson’s r=–0.22 or/and cancer types (P>0.05. The elevated plasma ET-1 levels were positively related to BP, and targeting ET-1 may provide a novel pain-reducing therapeutic treatment in BP. Keywords: visual analog scale, correlation, cancer types, background pain

  5. Development, validation and psychometric properties of a diagnostic/prognostic tool for breakthrough pain in mixed chronic-pain patients. (United States)

    Samolsky Dekel, Boaz Gedaliahu; Remondini, Francesca; Gori, Alberto; Vasarri, Alessio; Di Nino, GianFranco; Melotti, Rita Maria


    Breakthrough pain (BTP) shows variable prevalence in different clinical contexts of cancer and non-cancer patients. BTP diagnostic tools with demonstrated reliability, validation and prognostic capability are lacking. We report the development, psychometric and validation properties of a diagnostic/prognostic tool, the IQ-BTP, for BTP recognition, its likelihood and clinical features among chronic-pain (CP) patients. n=120 consecutive mixed cancer/non-cancer CP in/outpatients. Development, psychometric analyses and formal validation included: Face/Content validity (by 'experts' opinion and assessing the relationship between the IQ-BTP classes and criteria derived from BTP operational-case-definition); Construct validity, by Principle Component Analysis (PCA); and the strength of Spearman correlation between IQ-BTP classes and the Brief Pain Inventory (BPI) items; Reliability, by Cronbach's alpha statistics. Associations with clinical/demographic moderators were assessed applying χ(2) analysis. Potential-BTP was found in 36.7% of patients (38.4% of non-cancer and 32.4% of cancer patients). Among these the likelihood for BTP diagnosis was 'high' in 25%, 'intermediate' in 41% and, 'low' 34% of patients. Analyses showed significant differences between IQ-BTP classes and between the latter BPI pain-item scores. Correlation between IQ-BTP classes and BPI items was moderate. PCA and scree test identified 3 components accounting for 62.3% of the variance. Cronbach's alpha was 0.71. The IQ-BTP showed satisfactory psychometric and validation properties. With adequate feasibility it enabled the allocating of cancer/non-cancer CP patients in three prognostic classes. Results are sufficient to warrant a subsequent impact study of the IQ-BTP as prognostic model and screening tool for BTP in both CP populations. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. A novel once daily microparticulate dosage form comprising lansoprazole to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease: preparation, pharmacokinetic and pharmacodynamic evaluation. (United States)

    Alai, Milind; Lin, Wen Jen


    The objective of this study was to formulate and evaluate the lansoprazole (LPZ)-loaded microparticles to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease (GERD). The microparticulate delivery system was prepared by solvent evaporation method using Eudragit RS100 as a matrix polymer followed by enteric coated with Eudragit S100 and hydroxypropyl methylcellulose phthalate HP55 using spray drying method. The enteric coated microparticles were stable in gastric pH condition. In vivo pharmacokinetic and pharmacodynamic studies in male Wistar rats demonstrated that enteric coated microparticles sustained release of LPZ and promoted ulcer healing activity. In other words, the microparticulate dosage form provided effective drug concentration for a longer period as compared to conventional extended release dosage form, and showed sufficient anti-acid secretion activity to treat acid related disorders including the enrichment of nocturnal acid breakthrough event based on a once daily administration.

  7. Budget impact analysis of the fentanyl buccal tablet for treatment of breakthrough cancer pain

    Directory of Open Access Journals (Sweden)

    Darbà J


    Full Text Available Josep Darbà,1 Lisette Kaskens,2 Rainel Sánchez-de la Rosa31University of Barcelona, Barcelona, 2BCN Health Economics and Outcomes Research SL, Barcelona, 3Medical and HEOR Department, TEVA Pharmaceutical Industries Ltd, Madrid, SpainBackground: The purpose of this study was to assess the economic impact of the fentanyl buccal tablet for the management of breakthrough cancer pain (BTcP in Spain.Methods: A 4-year budget impact model was developed for the period 2012–2015 for patients with BTcP from the perspective of the Spanish National Health System. BTcP products included in this model were rapid-onset opioids containing fentanyl (buccal, sublingual, or nasal transmucosal. Prevalence data on cancer, BTcP, opioid use, and number of BTcP episodes were obtained from the literature. Input data on health care resources associated with opioid use and opioid-induced side effects were obtained by consulting experts in oncology from different Spanish hospitals. Resources used included drugs, medical and emergency visits, other nonpharmacologic treatments, and treatment of opioid-induced side effects. Unit costs were obtained from the literature, and a 3% discount rate was applied to costs. Based on the unit costs for drugs and health care resources, the annual BTcP treatment costs per patient associated with each fentanyl product were determined to estimate the overall budget impact based on the total treatment population and the percentage of drug utilization associated with each product. One-way sensitivity analyses were conducted to test the robustness of the model.Results: Patients treated with oral opioids for BTcP were estimated at 23,291 in 2012, with an increase up to 23,413 in 2015. The average annual budget savings, with an increase of fentanyl buccal tablets, fentanyl sublingual tablets, and intranasal fentanyl spray, and a decrease in oral transmucosal fentanyl citrate, was estimated at €2.6 million, which represents a 0.5% decrease in

  8. Stereoselective pharmacokinetics of methadone in chronic pain patients

    DEFF Research Database (Denmark)

    Kristensen, K; Blemmer, T; Angelo, H R


    Ten patients with chronic pain were randomized to an open, balanced, crossover study. Each patients received two different preparations of racemic methadone, i.e., tablets and intravenous infusion. The pharmacokinetic parameters of the R- and S-enantiomers of the racemate are reported. The analge......Ten patients with chronic pain were randomized to an open, balanced, crossover study. Each patients received two different preparations of racemic methadone, i.e., tablets and intravenous infusion. The pharmacokinetic parameters of the R- and S-enantiomers of the racemate are reported....... The analgesically active R-methadone has a significantly longer mean elimination half-life than the optical antipode S-methadone (t1/2 = 37.5 and 28.6 h, respectively). The mean total volume of distribution is 496.6 L for R-methadone and 289.1 L for S-methadone. Significant differences in the mean clearance between...... R- and S-methadone are seen (0.158 and 0.129 L/min, respectively). However, the lagtime after oral administration and the bioavailability did not show differences between the isomers. The data suggest that both enantiomers of methadone should be measured if correlations between pharmacodynamics...

  9. Safety and Efficacy of Oral Transmucosal Fentanyl Citrate Compared to Morphine Sulphate Immediate Release Tablet in Management of Breakthrough Cancer Pain (United States)

    Bhatnagar, Sushma; Devi, Saraswathi; Vinod, NK; Jain, PN; Durgaprasad, G; Maroo, Sanjaykumar H; Patel, Ketan R


    Aim: To compare the efficacy and safety of oral transmucosal fentanyl citrate (OTFC) and oral morphine in Indian patients with breakthrough episodes of cancer pain. Materials and Methods: In this randomized, open label, active controlled, clinical study, total 186 patients who regularly experienced 1-4 episodes of breakthrough cancer pain (BTCP) daily, over the persistent pain controlled by taking oral morphine 60 mg/day or its equivalent were randomized to receive either OTFC 200 mcg or oral morphine 10 mg for the treatment of BTCP for 3 days. Improvement in pain as determined by numerical rating scale (NRS) at 5, 15, 30, and 60 minutes of drug administration and percentage of BTCP episodes showing reduction in pain intensity by >33% at 15 minutes were primary efficacy endpoints. Secondary efficacy endpoints were requirement for rescue analgesia and global assessment by physician and patient. Data of both treatment groups were analysed by appropriate statistical test using software, STATISTICA, version 11. Results: Patients treated with OTFC experienced significantly greater improvement in pain intensity of breakthrough episodes compared to those treated with oral morphine at all assessment time points (P breakthrough pain episodes treated with OTFC showed a greater than 33% reduction in pain intensity from baseline at 15 minutes compared to 39% episodes treated with oral morphine (P 0.05). Both study drugs were well tolerated. Conclusions: OTFC was found to provide faster onset of analgesic effect than immediate release oral morphine in management of breakthrough cancer pain. PMID:25191003

  10. The Alberta Breakthrough Pain Assessment Tool for cancer patients: a validation study using a delphi process and patient think-aloud interviews. (United States)

    Hagen, Neil A; Stiles, Carla; Nekolaichuk, Cheryl; Biondo, Patricia; Carlson, Linda E; Fisher, Kim; Fainsinger, Robin


    Breakthrough pain is a prevalent cancer pain syndrome, and research is needed to identify more effective interventions to manage it. A validated tool to assess breakthrough pain in a standard and reliable manner is urgently needed to support the conduct of clinical trials in breakthrough pain. To address this need, we developed a breakthrough pain assessment tool for research purposes. The current study was undertaken to gather validity evidence for this breakthrough pain assessment tool, using a Delphi process involving an expert panel review, followed by a think-aloud process involving patients with cancer-related breakthrough pain. Two expert panels were formed: a national panel (within Canada; n=16) and an international panel (including experts from North America, UK, Europe, the Middle East, Australia, and New Zealand; n=22). Each panel participated in one anonymous survey round. Response rates were 56% (national panel) and 73% (international panel). The Delphi process revealed substantial consensus on the content of the tool, which increased between rounds of review. The overall level of agreement with the tool, averaged over the four evaluated aspects of all items, was 80% among national panelists and 88% among international panelists. Nine patients completed the think-aloud study. They were able to understand and complete the tool and provided specific direction on its improvement. The validity evidence gathered in this study suggests the Alberta Breakthrough Pain Assessment Tool is conceptually grounded and is understandable by patients and clinicians. Further validation of this tool as an assessment measure within clinical trials research is warranted.

  11. Population pharmacokinetics of oral diclofenac for acute pain in children. (United States)

    Standing, Joseph F; Howard, Richard F; Johnson, Atholl; Savage, Imogen; Wong, Ian C K


    To develop a population pharmacokinetic model for a new diclofenac suspension (50 mg 5 ml(-1)) in adult volunteers and paediatric patients, and recommend a dose for acute pain in children. Blood samples were drawn at the start and end of surgery, and on removal of the venous cannula from 70 children (aged 1 to 12 years, weight 9 to 37 kg) who received a preoperative oral 1 mg kg(-1) dose; these were pooled with rich (14 post-dose samples) data from 30 adult volunteers. Population pharmacokinetic modelling was undertaken with NONMEM. The optimum adult dose of diclofenac for acute pain is 50 mg. Simulation from the final model was performed to predict a paediatric dose to achieve a similar AUC to 50 mg in adults. A total of 558 serum diclofenac concentrations from 100 subjects was used in the pooled analysis. A single disposition compartment model with first order elimination and dual absorption compartments was used. The estimates of CL/F and V(D)/F were 53.98 l h(-1) 70 kg(-1) and 4.84 l 70 kg(-1) respectively. Allometric size models appeared to predict adequately changes in CL and V(D) with age. Of the simulated doses investigated, 1 mg kg(-1) gave paediatric AUC((0,12 h)) to adult 50 mg AUC((0,12 h)) ratios of 1.00, 1.08 and 1.18 for ages 1-3, 4-6 and 7-12 years respectively. This study has shown 1 mg kg(-1) diclofenac to produce similar exposure in children aged 1 to 12 years as 50 mg in adults, and is acceptable for clinical practice; patients are unlikely to obtain further benefit from higher doses.

  12. An evaluation of total disintegration time for three different doses of sublingual fentanyl tablets in patients with breakthrough pain. (United States)

    Nalamachu, Srinivas


    Breakthrough pain is common among patients with cancer and presents challenges to effective pain management. Breakthrough pain is characterized by rapid onset, severe intensity, and duration typically lasting disintegration time of three different doses of sublingual fentanyl tablets in opioid-tolerant patients. This was a single-center, non-randomized, open-label study. Opioid-tolerant adult patients (N = 30) with chronic pain were assigned to one of three dose groups and self-administered a single 100, 200, or 300 μg sublingual fentanyl tablet (Abstral(®), Galena Biopharma, Portland, OR, USA). Time to complete disintegration was measured by each patient with a stopwatch and independently verified by study personnel. Disintegration time (mean ± SD) for sublingual fentanyl tablets (all doses) was 88.2 ± 55.1 s. Mean disintegration times tended to be slightly longer for the 200 μg (96.7 ± 57.9 s) and 300 μg doses (98.6 ± 64.8 s) compared to the 100 μg dose (69.5 ± 40.5 s). Differences were not statistically significant. Disintegration time was not significantly different between men and women and was not affected by age. Sublingual fentanyl tablets dissolved rapidly (average time <2 min) in all patients, with the higher doses taking slightly more time to dissolve.

  13. How nurses assess breakthrough cancer pain, and the impact of this pain on patients' daily lives--results of a European survey. (United States)

    Rustøen, Tone; Geerling, Jenske I; Pappa, Theodora; Rundström, Carina; Weisse, Isolde; Williams, Sian C; Zavratnik, Bostjan; Wengström, Yvonne


    To increase our knowledge of how nurses assess breakthrough cancer pain (BTCP); and whether they find it difficult to distinguish BTCP from background pain; how they estimate the impact of BTCP on patients' daily lives, and the factors that nurses consider to induce BTCP. Variations in their use of assessment tools and their ability to distinguish between different types of pain were also examined in terms of the number of years of oncology nursing experience and the practice in different countries. In total, 1241 nurses (90% female) who care for patients with cancer, from 12 European countries, completed a survey questionnaire. Half the sample had >9 years of experience in oncology nursing. Although 39% had no pain assessment tool to help them distinguish between types of pain, 95% of those who used a tool found it useful. Furthermore, 37% reported that they had problems distinguishing background pain from BTCP. Movement was identified as the factor that most commonly exacerbated BTCP across all countries. The nurses reported that BTCP greatly interfered with patients' everyday activities, and they rated the patients' enjoyment of life as most strongly affected. The use of tools and the ability to distinguish between different pains varied between European countries and with years of experience in oncology nursing. The nurses reported that BTCP greatly interfered with patients' lives, and many nurses had problems distinguishing between background pain and BTCP. Nurses require more knowledge about BTCP management, and guidelines should be developed for clinical use. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Nitrous oxide/oxygen mixture for analgesia in adult cancer patients with breakthrough pain: A randomized, double-blind controlled trial. (United States)

    Liu, Q; Gao, L-L; Dai, Y-L; Li, Y-X; Wang, Y; Bai, C-F; Mu, G-X; Chai, X-M; Han, W-J; Zhou, L-J; Zhang, Y-J; Tang, L; Liu, J; Yu, J-Q


    The aim of this study was to assess the efficacy of a fixed nitrous oxide/oxygen mixture for the management of breakthrough cancer pain. A double-blind, placebo-controlled, randomized clinical trial was undertaken in the Medical ward of Tumor Hospital of General Hospital of Ningxia Medical University. 240 cancer patients with breakthrough pain were recruited and randomly received a standard pain treatment (morphine sulphate immediate release) plus a pre-prepared nitrous oxide/oxygen mixture, or the standard pain treatment plus oxygen. The primary endpoint measure was the numerical rating scale (NRS) score measured at baseline, 5 and 15 min after the beginning of treatment, and at 5 min post treatment. In all, analysis of pain score (NRS) at 5 min after the beginning of treatment shown a significant decrease in nitrous oxide/oxygen mixture treated patients with 2.8 ± 1.3 versus 5.5 ± 1.2 in controls (p nitrous oxide/oxygen was 2.0 ± 1.1 compared with 5.6 ± 1.3 for oxygen (p nitrous oxide/oxygen mixture was effective in reducing moderate to severe breakthrough pain among patients with cancer. The management of breakthrough cancer pain is always a challenge due to its temporal characteristics of rapid onset, moderate to severe in intensity, short duration (median 30-60 min). Our study find that self-administered nitrous oxide/oxygen mixture was effective in reducing moderate to severe breakthrough cancer pain. © 2017 European Pain Federation - EFIC®.

  15. Impact of opioid rescue medication for breakthrough pain on the efficacy and tolerability of long-acting opioids in patients with chronic non-malignant pain (United States)

    Devulder, J.; Jacobs, A.; Richarz, U.; Wiggett, H.


    Background There is little evidence that short-acting opioids as rescue medication for breakthrough pain is an optimal long-term treatment strategy in chronic non-malignant pain. We compared clinical studies of long-acting opioids that allowed short-acting opioid rescue medication with those that did not, to determine the impact of opioid rescue medication use on the analgesic efficacy and tolerability of chronic opioid therapy in patients with chronic non-malignant pain. Methods We searched MEDLINE (1950 to July 2006) and EMBASE (1974 to July 2006) using terms for chronic non-malignant pain and long-acting opioids. Independent review of the search results identified 48 studies that met the study selection criteria. The effect of opioid rescue medication on analgesic efficacy and the incidence of common opioid-related side-effects were analysed using meta-regression. Results After adjusting for potentially confounding variables (study design and type of opioid), the difference in analgesic efficacy between the ‘rescue’ and the ‘no rescue’ studies was not significant, with regression coefficients close to 0 and 95% confidence intervals that excluded an effect of more than 18 points on a 0–100 scale in each case. There was also no significant difference between the ‘rescue’ and the ‘no rescue’ studies for the incidence of nausea, constipation, or somnolence in both the unadjusted and the adjusted analyses. Conclusions We found no evidence that rescue medication with short-acting opioids for breakthrough pain affects analgesic efficacy of long-acting opioids or the incidence of common opioid-related side-effects among chronic non-malignant pain patients. PMID:19736216

  16. Efficacy and Safety of Sublingual Fentanyl Tablets in Breakthrough Cancer Pain Management According to Cancer Stage and Background Opioid Medication. (United States)

    Guitart, Jordi; Vargas, María Isabel; De Sanctis, Vicente; Folch, Jordi; Salazar, Rafael; Fuentes, José; Coma, Joan; Ferreras, Julia; Moya, Jordi; Tomás, Albert; Estivill, Pere; Rodelas, Francisco; Jiménez, Antonio Javier; Sanz, Almudena


    Our objective was to assess the effect of sublingual fentanyl tablets (SFTs) on pain relief, quality of life, and adverse effects in patients with cancer pain, according to cancer stage and background opioid regimen. Subgroup analyses from a recently completed study were performed according to cancer stage (locally advanced cancer [LAC] vs. metastatic cancer) and most frequent background opioid medication (fentanyl vs. oxycodone/naloxone). The efficacy and safety of SFTs were evaluated, recording pain intensity (PI), onset of pain relief, and adverse events (AEs). Health status was assessed with the Short Form 12, version 2 (SF-12v2) questionnaire and the Hospital Anxiety and Depression Scale (anxiety subscale [HADS-A] and depression subscale [HADS-D]). In total, 54 (67.5%) patients had LAC and 26 (32.5%) had metastatic cancer. The oxycodone/naloxone group included 39 patients (48.1%) and the fentanyl group 29 (35.8%). In all subgroups, pain relief was achieved within 5 min in an increasing number of individuals over time; at the end of the study, PI values decreased (PI-end: 44.4% for LAC vs. 57.9% for metastatic cancer; 44.4% for fentanyl vs. 38.6% for oxycodone/naloxone). HADS and mental component summary (MCS) SF-12v2 scores significantly improved in the LAC group (HADS-A 9.44-8.04; HADS-D 10.46-8.15; MCS 44.69-45.94) and in the fentanyl group (HADS-A 10.05-8.33; HADS-D 11.95-8.76; MCS 44.38-47.19). AEs were reported in few patients and were mostly mild. Exploratory subgroup analyses show the efficacy and safety of SFTs for the treatment of breakthrough pain in patients with cancer, regardless of their cancer stage and background opioid medication.

  17. A Canadian online survey of oncology nurses' perspectives on the management of breakthrough pain in cancer (BTPc). (United States)

    Fitch, Margaret I; McAndrew, Alison; Burlein-Hall, Stephanie


    This paper explores Canadian oncology nurses' perception of management of breakthrough pain in cancer (BTPc). An online questionnaire was distributed to 668 oncology nurses across Canada, and 201 participated. More nurses reported that patients used hydromorphone (99.5%), morphine (97.0%), codeine (88.1%), or oxycodone (88.1%) for BTPc, than fentanyl preparations (64.7%). Problems with opioid administration reported by nurses included failure to work quickly enough (35.7%), difficulty swallowing (16.6%), need for caregiver assistance (13.2%), mouth sores (12.6%) and dry mouth (11.5%). Although most nurses discussed BTPc management with their patients, the vast majority (72.2%) were not very satisfied with current treatment modalities. Effective dialogue with patients and access to educational resources/tools may help optimize therapy and enhance concordance with BTPc medications.

  18. A Comparison of Change in the 0–10 Numeric Rating Scale to a Pain Relief Scale and Global Medication Performance Scale in a Short-term Clinical Trial of Breakthrough Pain Intensity (United States)

    Farrar, John T.; Polomano, Rosemary C.; Berlin, Jesse A.; Strom, Brian L.


    Background Pain intensity is commonly reported using a 0–10 numeric rating scale in breakthrough pain clinical trials. Analysis of the change on the Pain Intensity Numerical Rating Scale as a proportion as most consistently correlated with clinically important differences reported on the Patient Global Impression of Change. The analysis of data using a different global outcome measures and the pain relief scale will extend our understanding of these measures. Use of the pain relief scale is also explored in this study Methods Data came from the open titration phase of a multiple crossover, randomized, double-blind clinical trial comparing oral transmucosal fentanyl citrate to immediate-release oral morphine sulfate for treatment of cancer-related breakthrough pain. Raw and percent changes in the pain intensity scores on 1,307 from 134 oral transmucosal fentanyl citrate-naive patients were compared to the clinically relevant secondary outcomes of the pain relief verbal response scale and the global medication performance. The changes in raw and percent change were assessed over time and compared to the ordinal pain relief verbal response scale and global medication performance scales. Results The p-value of the interaction between the raw pain intensity difference was significant but not for the percent pain intensity difference score over 4 15 minute time periods (p = 0.034 and p = 0.26 respectively), in comparison with the ordinal pain relief verbal response scale (p = 0.0048 and p = 0.36 respectively), and global medication performance categories (p = 0.048 and p = 0.45 respectively). Conclusion The change in pain intensity in breakthrough pain was more consistent over time and when compared to both the pain relief verbal response scale and global medication performance scale when the percent change is used rather than raw pain intensity difference. PMID:20463579

  19. Fentanyl Buccal Tablet: A New Breakthrough Pain Medication in Early Management of Severe Vaso-Occlusive Crisis in Sickle Cell Disease. (United States)

    De Franceschi, Lucia; Mura, Paolo; Schweiger, Vittorio; Vencato, Elisa; Quaglia, Francesca Maria; Delmonte, Letizia; Evangelista, Maurizio; Polati, Enrico; Olivieri, Oliviero; Finco, Gabriele


    Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder. The principal clinical manifestations of SCD are the chronic hemolytic anemia and the acute vaso-occlusive crisis (VOCs), which are mainly characterized by ischemic/reperfusion tissue injury. Pain is the main symptom of VOCs, and its management is still a challenge for hematologists, requiring a multidisciplinary approach. We carried out a crossover study on adult SCD patients, who received two different types of multimodal analgesia during two separate severe VOCs with time interval between VOCs of at least 6 months. The first VOC episode was treated with ketorolac (0.86 mg/kg/day) and tramadol (7.2 mg/kg/day) (TK treatment). In the second VOC episode, fentanyl buccal tablet (FBT; 100 μg) was introduced in a single dose after three hours from the beginning of TK analgesia (TKF treatment). We focused on the first 24 hours of acute pain management. The primary efficacy measure was the time-weighted-sum of pain intensity differences (SPID24). The secondary efficacy measures included the pain intensity difference (PID), the total pain relief (TOTPAR), and the time-wighted sum of anxiety (SAID24). SPID24 was significantly higher in TKF than in TK treatment. All the secondary measures were significantly ameliorated in TKF compared to TK treatment, without major opioid side effects. Patients satisfaction was higher with TKF treatment than with TK one. We propose that VOCs might require breakthrough pain drug strategy as vaso-occlusive phenomena and enhanced vasoconstriction promoting acute ischemic pain component exacerbate the continuous pain of VOCs. FBT might be a powerful and feasible tool in early management of acute pain during VOCs in emergency departments. © 2015 World Institute of Pain.

  20. Procedural Pain in Palliative Care: Is It Breakthrough Pain? A Multicenter National Prospective Study to Assess Prevalence, Intensity, and Treatment of Procedure-related Pain in Patients With Advanced Disease. (United States)

    Magnani, Caterina; Giannarelli, Diana; Casale, Giuseppe


    To assess the prevalence of breakthrough pain (BTP) provoked by 6 common procedures in patients with advanced disease. A prospective, cross-sectional, multicenter, national study was performed in 23 palliative care units in Italy. Patients were recruited if they were undergoing one of the following procedures as part of normal care: turning, personal hygiene care, transfer from bed to chair, bladder catheterization, pressure ulcer care, and subcutaneous drug administration. The Numerical Rating Scale was used to measure pain intensity before, during, and after the procedure. One thousand seventy-nine eligible patients were enrolled: 49.7% were male and their mean age was 78.0±11.2 years. Of all patients, 20.9% had experienced a BTP episode within the 24 hours before recruitment. The overall prevalence of procedure-induced BTP was 11.8%, and the mean intensity score (Numeric Rating Scale) was 4.72±1.81. Notably, patients experienced a significant increase in pain intensity during all procedures (Ppatients (12.7%) received analgesics before undergoing any of the procedures, and almost none (1.7%) received analgesics during the procedures to alleviate acute pain. Our findings highlight that simple daily care procedures can lead to BTP among patients with advanced disease. Because such procedures are performed very often during palliative care, more individualized attention to procedural pain control is necessary. Additional research on procedural pain in patients with advanced disease should be encouraged to provide further evidence-based guidance on the use of the available medication for predictable pain flares.

  1. The Influence of Low Salivary Flow Rates on the Absorption of a Sublingual Fentanyl Citrate Formulation for Breakthrough Cancer Pain. (United States)

    Davies, Andrew; Mundin, Gill; Vriens, Joanna; Webber, Kath; Buchanan, Alison; Waghorn, Melanie


    Salivary gland hypofunction may affect the absorption of drugs through the oral mucosa, which in turn may affect their clinical efficacy (e.g., onset of action). The aim of this study was to assess the pharmacokinetics of a sublingual fentanyl orally disintegrating tablet (Abstral, Prostrakan Inc.) in a group of cancer patients with salivary gland hypofunction. Nine cancer patients with salivary gland hypofunction underwent a series of three pharmacokinetic studies with the sublingual fentanyl orally disintegrating tablet. In the first phase, the patients received no pretreatment; in the second phase, the patients were allowed to moisten the oral cavity before dosing; in the third phase, the patients were given pilocarpine hydrochloride (saliva stimulant) before dosing. Fentanyl concentrations were measured using a method of high-performance liquid chromatography with validated tandem mass spectrometric detection. The Tmax was longer, the Cmax was lower, the AUC0-30 lower, and the AUClast lower in the phase involving no pretreatment; the Tmax/Cmax/AUC0-30/AUClast were similar in the phase involving moistening of the oral cavity and the phase involving giving pilocarpine hydrochloride. The pharmacokinetics of the sublingual fentanyl orally disintegrating tablet appear to be negatively affected by the presence of salivary gland hypofunction, although the moistening of the oral cavity before dosing results in a pharmacokinetic profile similar to that seen with the giving of pilocarpine hydrochloride. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  2. Clinical efficacy, safety and pharmacokinetics of a newly developed controlled release morphine sulphate suppository in patients with cancer pain

    NARCIS (Netherlands)

    Moolenaar, F.; Meijler, W.J.; Frijlink, H.W.; Visser, Jan; Proost, J.H.

    Objective: To compare the efficacy, safety and pharmacokinetics of a newly developed controlled-release suppository (MSR) with MS Contin tablets (MSC) in cancer patients with pain. Methods: In a double-blind, randomised, two-way crossover trial, 25 patients with cancer pain were selected with a

  3. A randomized, placebo-controlled study of a new sublingual formulation of fentanyl citrate (fentanyl ethypharm) for breakthrough pain in opioid-treated patients with cancer. (United States)

    Novotna, Stanislava; Valentova, Klara; Fricova, Jitka; Richterova, Eva; Harabisova, Sarka; Bullier, Françoise; Trinquet, Françoise


    Oromucosal fentanyl is currently used for the treatment of breakthrough pain (BTP) in opioid-treated cancer patients. Ethypharm developed a sublingual formulation of fentanyl suprabioavailable to oral transmucosal fentanyl citrate with a higher early systemic exposure and a shorter Tmax. This study evaluated the efficacy and safety profile of fentanyl Ethypharm (FE) in relieving BTP in opioid-treated cancer patients. Opioid-treated adult cancer patients, experiencing 1 to 4 episodes of BTP per day, were included in the study. After an open-label titration period to identify an optimal dose that would provide adequate pain relief for 2 consecutive episodes of BTP with an acceptable level of adverse events, patients were randomly assigned to a double-blind, placebo-controlled, crossover period with 1 of 13 prespecified sequences of 9 tablets (6 tablets of FE of the dose identified during the open-label titration and 3 placebo). Pain intensity and pain relief were recorded at 3, 6, 10, 15, 30, and 60 minutes after study drug administration. Adverse events were recorded. The primary end point was the sum of pain intensity differences (SPID) at 30 minutes. The distribution of optimal dosages of FE was as follows: 133 µg, 35.9%; 267 µg, 30.8%; 400 µg, 14.1%; 533 µg, 12.8%; and 800 μg, 6.4%. In the modified intention-to-treat population (n = 73), FE significantly improved mean (SE) SPID compared with placebo at 30 minutes (75.0 [49.8] vs 52.5 [52.8]; P pain intensity difference, and pain relief compared with placebo from 6 to 60 minutes' postadministration. Patients with BTP who received placebo required the use of rescue medication more often than those treated with FE (38.4% vs 17.5%; P pain scores (>33% and >50% reductions) was also reported for BTP treated with FE. Pain scores for patients with BTP with a neuropathic component (13 patients) were lower with FE than for those receiving placebo, but the difference was not significant. AEs were of mild or moderate

  4. A review of morphine and morphine-6-glucuronide's pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain

    DEFF Research Database (Denmark)

    Sverrisdóttir, Eva; Lund, Trine Meldgaard; Olesen, Anne Estrup


    Morphine is a widely used opioid for treatment of moderate to severe pain, but large interindividual variability in patient response and no clear guidance on how to optimise morphine dosage regimen complicates treatment strategy for clinicians. Population pharmacokinetic-pharmacodynamic models can...

  5. Treatment of pain in fibromyalgia patients with testosterone gel: Pharmacokinetics and clinical response. (United States)

    White, Hillary D; Brown, Lin A J; Gyurik, Robert J; Manganiello, Paul D; Robinson, Thomas D; Hallock, Linda S; Lewis, Lionel D; Yeo, Kiang-Teck J


    To test our hypothesis that testosterone deficiency plays an important role in chronic pain, a Phase I/II pilot study was initiated with 12 fibromyalgia patients to verify that a daily dose for 28days with transdermal testosterone gel would 1) significantly and safely increase mean serum testosterone concentrations from low baseline levels to mid/high-normal levels, and 2) effectively treat the pain and fatigue symptoms of fibromyalgia. Pharmacokinetic data confirmed that serum free testosterone concentrations were raised significantly above baseline levels, by assessment of maximum hormone concentration (Cmax) and area under the curve (AUC) parameters: free testosterone Cmax was significantly raised from a mean of 2.64pg/mL to 3.91pg/mL (pfibromyalgia by patient questionnaire and tender point exam demonstrated significant change in: decreased muscle pain, stiffness, and fatigue, and increased libido during study treatment. These results are consistent with the hypothesized ability of testosterone to relieve the symptoms of fibromyalgia. Symptoms not tightly related to fibromyalgia were not improved. Copyright © 2015. Published by Elsevier B.V.

  6. Effect of electro-acupuncture stimulation of Ximen (PC4) and Neiguan (PC6) on remifentanil-induced breakthrough pain following thoracal esophagectomy. (United States)

    Xie, Yan-hu; Chai, Xiao-qing; Wang, Yue-lan; Gao, Yan-chun; Ma, Jun


    The clinical analgesic effect of electro-acupuncture (EA) stimulation (EAS) on breakthrough pain induced by remifentanil in patients undergoing radical thoracic esophagectomy, and the mechanisms were assessed. Sixty patients (ASAIII) scheduled for elective radical esophagectomy were randomized into three groups: group A (control) receiving a general anesthesia only; group B (sham) given EA needles at PC4 (Ximen) and PC6 (Neiguan) but no stimulation; and group C (EAS) electrically given EAS of the ipsilateral PC4 and PC6 throughout the surgery. The EAS consisting of a disperse-dense wave with a low frequency of 2 Hz and a high frequency of 20 Hz, was performed 30 min prior to induction of general anesthesia and continued through the surgery. At the emergence, sufentanil infusion was given for postoperative analgesia with loading dose of 7.5 μg, followed by a continuous infusion of 2.25 μg/h. The patient self-administration of sufentanil was 0.75 μg with a lockout of 15 min as needed. Additional breakthrough pain was treated with dezocine (5 mg) intravenously at the patient's request. Blood samples were collected before (T1), 2 h (T2), 24 h (T3), and 48 h (T4) after operation to measure the plasma β-EP, PGE2, and 5-HT. The operative time, the total dose of sufentanil and the dose of self-administration, and the rescue doses of dezocine were recorded. Visual Analogue Scale (VAS) scores at 2, 12, 24 and 48 h postoperatively and the incidence of apnea and severe hypotension were recorded. The results showed that the gender, age, weight, operative time and remifentanil consumption were comparable among 3 groups. Patients in EAS group had the lowest VAS scores postoperatively among the three groups (P217.74±76.45 ng/mL) groups. For intra-group comparison, plasma 5-HT and PGE2 levels in control and sham groups at T2 and T3, and β-EP in EAS group at T3 and T4 were significantly higher than those at T1 (P0.05). No apnea or severe hypotension was observed in any group

  7. Population Pharmacokinetic Modeling of Tapentadol Extended Release (ER) in Healthy Subjects and Patients with Moderate or Severe Chronic Pain. (United States)

    Huntjens, Dymphy R; Liefaard, Lia C; Nandy, Partha; Drenth, Henk-Jan; Vermeulen, An


    Tapentadol is a centrally acting analgesic with two mechanisms of action, µ-opioid receptor agonism and noradrenaline reuptake inhibition. The objectives were to describe the pharmacokinetic behavior of tapentadol after oral administration of an extended-release (ER) formulation in healthy subjects and patients with chronic pain and to evaluate covariate effects. Data were obtained from 2276 subjects enrolled in five phase I and nine phase II and III studies. Nonlinear mixed-effects modeling was conducted using NONMEM. The population estimates of apparent oral clearance and apparent central volume of distribution were 257 L/h and 1870 L, respectively. The complex absorption was described with a transit compartment for the first input. The second input function embraces saturable "binding" in the "absorption compartment", and a time-varying rate constant. Covariate evaluation demonstrated that age, aspartate aminotransferase, and health (painful diabetic neuropathy or not) had a statistically significant effect on apparent clearance, and bioavailability appeared to be dependent on body weight. The pcVPC indicted that the model provided a robust and unbiased fit to the data. A one-compartment disposition model with two input functions and first-order elimination adequately described the pharmacokinetics of tapentadol ER. The dose-dependency in the pharmacokinetics of tapentadol ER is adequately described by the absorption model. None of the covariates were considered as clinically relevant factors that warrant dose adjustments.

  8. Pharmacological and pharmacokinetic studies with agaricoglycerides, extracted from Grifola frondosa, in animal models of pain and inflammation. (United States)

    Han, Chuncho; Cui, Bo


    The objective of the present study was to demonstrate the anti-inflammatory and antinociceptive properties of agaricoglycerides of the fermented mushroom of Grifola frondosa (AGF). The effects of AGF on interleukin-1β (IL-1β) levels, tumor necrosis factor-α (TNF-α) levels, nuclear factor kappa B (NF-κB) levels, intercellular adhesion molecule-1 (ICAM-1) levels, cyclooxygenase-2 (COX-2) levels, and inducible nitric oxide synthase (iNOS) levels were determined by ELISA. The antinociceptive effects of AGF were also analyzed in acetic acid-induced pain model and formalin-induced inflammatory pain model, respectively. At the same time, the pharmacokinetic assay of AGF was also made. AGF at the dose level of 500 mg/kg significantly inhibited LPS-induced upregulation of NF-κB activation and the production of IL-1β, TNF-α, iNOS, ICAM-1, and COX-2. Moreover, AGF at the dose level of 500 mg/kg suppressed the acetic acid-induced abdominal constrictions (p inflammation and in some models of pain and thus may be used as an alternative medicine for inflammatory pain.

  9. Diclofenac pharmacokinetic meta-analysis and dose recommendations for surgical pain in children aged 1-12 years. (United States)

    Standing, Joseph F; Tibboel, Dick; Korpela, Reijo; Olkkola, Klaus T


    Diclofenac is an effective, opiate-sparing analgesic for acute pain in children, which is commonly used in pediatric surgical units. Recently, a Cochrane review concluded the major knowledge gap in diclofenac use is dosing information. A pharmacokinetic meta-analysis has been undertaken with the aim of recommending a dose for children aged 1-12 years. Studies containing diclofenac pharmacokinetic data were identified during a Cochrane systematic review, and authors were asked to provide raw data. A pooled population analysis was undertaken in NONMEM to define the pharmacokinetics of intravenous, oral, and rectal diclofenac in children. Simulations were performed to recommend a dose yielding an equivalent area under diclofenac concentration-time curve (AUC) to a 50-mg dispersible tablet in adults. Data from 111 children aged 1-14 years consisting of 375 samples following intravenous, oral suspension, and suppositories were used. Adult dispersible tablet and suspension data were added to provide a reference AUC and support the absorption modeling, respectively. A three-compartment model described disposition, a dual-absorption compartment model was used for suspension and dispersible tablet data, and single-absorption compartment model for suppositories. The estimate of clearance was 16.5 l·h(-1) ·70 kg(-1) and bioavailabilities were 0.36, 0.63, and 0.35 for suspension, suppository, and dispersible tablets, respectively. Single doses of 0.3 mg·kg(-1) for intravenous, 0.5 mg·kg(-1) for suppositories, and 1 mg·kg(-1) for oral diclofenac in children aged 1-12 years are recommended as they yield a similar AUC to 50 mg in adults. © 2011 Blackwell Publishing Ltd.

  10. Pharmacokinetics of hydrocodone/acetaminophen combination product in children ages 6-17 with moderate to moderately severe postoperative pain. (United States)

    Liu, Wei; Dutta, Sandeep; Kearns, Greg; Awni, Walid; Neville, Kathleen A


    Lortab® Elixir, a proprietary combination product containing hydrocodone and acetaminophen, is approved in the US for the treatment of moderate to moderately severe pain in children. Despite this approval, pediatric pharmacokinetic data using this product have not been previously published. Using a single-dose open-label study approach, we evaluated the pharmacokinetics, tolerability, and safety of this product in 17 healthy children 6-17 years of age. Results showed that the body weight-normalized oral clearance (L/h/kg) of hydrocodone and acetaminophen were 42% and 27% higher, respectively when compared to data from healthy adults. This suggests that a higher mg/kg dose would be required in children to achieve exposures similar to adults. We found adjustment of hydrocodone and acetaminophen dose by body surface area to be more optimal than body weight-based dose adjustments for achieving similar systemic exposure in children and adults. However, body weight-based hydrocodone and acetaminophen dosing regimens provided close approximation of adult exposures in pediatric patients with approximately 22% to 24% lower hydrocodone and acetaminophen dose/BW-normalized AUC in pediatric patients compared to adults. Finally, the adverse event profile in our pediatric cohort was consistent with that expected of opioid-naive subjects receiving opioid-combination therapy. © 2014, The American College of Clinical Pharmacology.

  11. A pharmacokinetic-pharmacodynamic model of morphine exposure and subsequent morphine consumption in postoperative pain

    DEFF Research Database (Denmark)

    Juul, Rasmus Vestergaard; Nyberg, Joakim; Lund, Trine Meldgaard


    Purpose To characterize the pharmacokinetic-pharmacodynamic (PK-PD) relationship between exposure of morphine and subsequent morphine consumption and to develop simulation tools for model validation. Methods Dose, formulation and time of morphine administration was available from a published study...... in 63 patients receiving intravenous, oral immediate release or oral controlled release morphine on request after hip surgery. The PK-PD relationship between predicted exposure of morphine and morphine consumption was modeled using repeated time to event (RTTE) modeling in NONMEM. To validate the RTTE...... model, a visual predictive check method was developed with simulated morphine consumption given the exposure of preceding morphine administration. Results The probability of requesting morphine was found to be significantly related to the exposure of morphine as well as night/day. Oral controlled...

  12. The efficacy and pharmacokinetics of sodium salicylate in post-operative dental pain.


    Seymour, R A; Rawlins, M D; Clothier, A


    Sodium salicylate, 537 mg and 1074 mg were compared in a double-blind cross-over study in 24 patients with post-operative pain following removal of impacted lower third molars. No significant analgesic effect was observed after either dose of sodium salicylate, either overall or at any time point during the 5 h investigation period. Peak plasma concentrations of salicylate after 537 mg were observed at 30 min after dosage, whereas peak plasma salicylate concentrations after 1074 mg sodium sal...

  13. Breakthroughs in statistics

    CERN Document Server

    Johnson, Norman

    This is author-approved bcc: This is the third volume of a collection of seminal papers in the statistical sciences written during the past 110 years. These papers have each had an outstanding influence on the development of statistical theory and practice over the last century. Each paper is preceded by an introduction written by an authority in the field providing background information and assessing its influence. Volume III concerntrates on articles from the 1980's while including some earlier articles not included in Volume I and II. Samuel Kotz is Professor of Statistics in the College of Business and Management at the University of Maryland. Norman L. Johnson is Professor Emeritus of Statistics at the University of North Carolina. Also available: Breakthroughs in Statistics Volume I: Foundations and Basic Theory Samuel Kotz and Norman L. Johnson, Editors 1993. 631 pp. Softcover. ISBN 0-387-94037-5 Breakthroughs in Statistics Volume II: Methodology and Distribution Samuel Kotz and Norman L. Johnson, Edi...

  14. Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of 177Lu-EDTMP, a potential bone pain palliation agent

    International Nuclear Information System (INIS)

    Mathe, Domokos; Balogh, Lajos; Polyak, Andras; Kiraly, Reka; Marian, Terez; Pawlak, Dariusz; Zaknun, John J.; Pillai, Maroor R.A.; Janoki, Gyozo A.


    Introduction: Radionuclide therapy (RNT) is an effective method for bone pain palliation in patients suffering from bone metastasis. Due to the long half-life, easy production and relatively low β- energy, 177 Lu [T 1/2 =6.73 days, E βmax =497 keV, E γ =113 keV (6.4%), 208 keV (11%)]-based radiopharmaceuticals offer logistical advantage for wider use. This paper reports the results of a multispecies biodistribution and toxicity studies of 177 Lu-EDTMP to collect preclinical data for starting human clinical trials. Methods: 177 Lu-EDTMP with radiochemical purity greater than 99% was formulated by using a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH). Biodistribution studies were conducted in mice and rabbits. Small animal imaging was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels of activity (9.25 through 37 MBq/kg body weight) of 177 Lu-EDTMP were injected in four groups of three dogs each to study the toxicological effects. Results: 177 Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41% of the injected activity in bone with terminal elimination half-life of 2130 and 1870 h in mice and rabbits, respectively) with a peak uptake during 1-3 h. Excretion of the radiopharmaceutical was through the urinary system. Imaging studies showed that all species (mouse, rat, rabbit and dog) take up the compound in regions of remodeling bone, while kidney retention is not visible after 1 day postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight) led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi with no toxicity. Conclusion: The protracted effective half-life of 177 Lu-EDTMP in bone supports that modifying the EDTMP molecule by introducing 177 Lu does not alter its biological behaviour as a specific bone-seeking tracer. Species-specific pharmacokinetic behavior

  15. Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of {sup 177}Lu-EDTMP, a potential bone pain palliation agent

    Energy Technology Data Exchange (ETDEWEB)

    Mathe, Domokos [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary)], E-mail:; Balogh, Lajos; Polyak, Andras; Kiraly, Reka [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary); Marian, Terez [Institute of Nuclear Medicine, Debrecen University, Debrecen (Hungary); Pawlak, Dariusz [Institute of Atomic Energy, Radioisotope Centre POLATOM, Swierk-Otwock (Poland); Zaknun, John J.; Pillai, Maroor R.A. [International Atomic Energy Agency (IAEA), Vienna (Austria); Janoki, Gyozo A. [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary)


    Introduction: Radionuclide therapy (RNT) is an effective method for bone pain palliation in patients suffering from bone metastasis. Due to the long half-life, easy production and relatively low {beta}- energy, {sup 177}Lu [T{sub 1/2}=6.73 days, E{sub {beta}}{sub max}=497 keV, E{sub {gamma}}=113 keV (6.4%), 208 keV (11%)]-based radiopharmaceuticals offer logistical advantage for wider use. This paper reports the results of a multispecies biodistribution and toxicity studies of {sup 177}Lu-EDTMP to collect preclinical data for starting human clinical trials. Methods: {sup 177}Lu-EDTMP with radiochemical purity greater than 99% was formulated by using a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH). Biodistribution studies were conducted in mice and rabbits. Small animal imaging was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels of activity (9.25 through 37 MBq/kg body weight) of {sup 177}Lu-EDTMP were injected in four groups of three dogs each to study the toxicological effects. Results: {sup 177}Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41% of the injected activity in bone with terminal elimination half-life of 2130 and 1870 h in mice and rabbits, respectively) with a peak uptake during 1-3 h. Excretion of the radiopharmaceutical was through the urinary system. Imaging studies showed that all species (mouse, rat, rabbit and dog) take up the compound in regions of remodeling bone, while kidney retention is not visible after 1 day postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight) led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi with no toxicity. Conclusion: The protracted effective half-life of {sup 177}Lu-EDTMP in bone supports that modifying the EDTMP molecule by introducing {sup 177}Lu does not alter its biological behaviour as a specific bone

  16. From "breakthrough" to "episodic" Cancer Pain?

    DEFF Research Database (Denmark)

    Løhre, Erik Torbjørn; Klepstad, Pål; Bennett, Michael I


    of consensus on BTCP classification were refined into 20 statements. The participants rated their degree of agreement with the statements on a numeric rating scale (0-10). Consensus was defined as a median numeric rating scale score of ≥7 and an interquartile range of ≤3. Results Fifty-two authors had...

  17. Fentanyl Formulations in the Management of Pain: An Update. (United States)

    Schug, Stephan A; Ting, Sonya


    Fentanyl is a synthetic, highly selective opioid with many desirable physicochemical properties, including a high lipophilicity and predictable pharmacokinetics. These properties have an established record in the management of pain in a variety of settings, particularly acute pain and breakthrough cancer pain. Fentanyl was initially developed for parenteral use; however, this is invasive and impractical in the outpatient setting. Unfortunately, the high first-pass metabolism of fentanyl makes oral formulations unfeasible. However, its high lipophilicity allows fentanyl to be absorbed via a number of other routes. Thus new formulations were designed to allow non-invasive methods of administration. Transmucosal and transdermal fentanyl formulations are well established, and have proven useful in the settings of breakthrough cancer pain, emergencies and in the paediatric population. The iontophoretic transdermal system was developed to provide a needle-free system of delivering bolus doses of fentanyl on demand, a novel way of delivering patient-controlled opioid analgesia. Transpulmonary administration of fentanyl remains experimental. The aim of this review is to provide an update on current non-parenteral fentanyl formulations, with attention to their particular pharmacokinetics and features relevant to clinical use in pain management.

  18. Breakthrough Propulsion Physics Research Program (United States)

    Millis, Marc G.


    In 1996, a team of government, university and industry researchers proposed a program to seek the ultimate breakthroughs in space transportation: propulsion that requires no propellant mass, propulsion that can approach and, if possible, circumvent light speed, and breakthrough methods of energy production to power such devices. This Breakthrough Propulsion Physics program, managed by Lewis Research Center, is one part of a comprehensive, long range Advanced Space Transportation Plan managed by Marshall Space Flight Center. Because the breakthrough goals are beyond existing science, a main emphasis of this program is to establish metrics and ground rules to produce near-term credible progress toward these incredible possibilities. An introduction to the emerging scientific possibilities from which such solutions can be sought is also presented.

  19. NASA Breakthrough Propulsion Physics Program (United States)

    Millis, Marc G.


    In 1996, NASA established the Breakthrough Propulsion Physics program to seek the ultimate breakthroughs in space transportation: propulsion that requires no propellant mass, propulsion that attains the maximum transit speeds physically possible, and breakthrough methods of energy production to power such devices. Topics of interest include experiments and theories regarding the coupling of gravity and electromagnetism, vacuum fluctuation energy, warp drives and worm-holes, and superluminal quantum effects. Because these propulsion goals are presumably far from fruition, a special emphasis is to identify affordable, near-term, and credible research that could make measurable progress toward these propulsion goals. The methods of the program and the results of the 1997 workshop are presented. This Breakthrough Propulsion Physics program, managed by Lewis Research Center, is one part of a comprehensive, long range Advanced Space Transportation Plan managed by Marshall Space Flight Center.

  20. Effect of Co-Administration of Lidocaine on the Pain and Pharmacokinetics of Intramuscular Amikacin in Children with Multidrug-Resistant Tuberculosis: A Randomized Crossover Trial. (United States)

    Garcia-Prats, Anthony J; Rose, Penelope C; Draper, Heather R; Seddon, James A; Norman, Jennifer; McIlleron, Helen M; Hesseling, Anneke C; Schaaf, H Simon


    Currently recommended treatment for multidrug-resistant (MDR) tuberculosis (TB) includes 4-8 months of an injectable medication, which is poorly tolerated. We evaluated the impact of co-administering lidocaine on pain and pharmacokinetics of intramuscular injections of amikacin in children with MDR-TB. Children 8-18 years of age, receiving amikacin for MDR-TB treatment in Cape Town, South Africa, were eligible for this randomized crossover trial. Participants received a 15 mg/kg dose of intramuscular amikacin with and without additional lidocaine (0.2-0.4 mg/kg) on different days, and were randomized to the order of the treatments (the sequence). Participants and staff completing evaluations were blinded to sequence. Samples were drawn pre-dose, and at 1, 2, 4, 6 and 8 hours post-dose for measurement of plasma amikacin concentrations. Pain was assessed by participants using the Wong Baker FACES pain scale (0 to 5) pre-dose, immediately after the injection and then at 30 and 60 minutes. Pharmacokinetic measures were calculated using noncompartmental analysis. Twelve children were included, median age 11.5 years (IQR 9.9-13.4y). Participant-reported pain scores immediately after the amikacin injection were lower when lidocaine was co-administered: 1.0 (IQR 0.5-2.0) with lidocaine vs. 2.5 (1.0-4.0) without lidocaine (p=0.004). The median area under the concentration time curve (AUC)0-8 and median maximum plasma concentration (Cmax) of amikacin were 109.0 μg*h/mL (IQR 84.7-121.3) and 36.7 μg/mL (IQR 34.1-40.5) with lidocaine compared to 103.3 μg*h/mL (IQR 81.7-135.0; p=0.814) and 34.1 μg/mL (IQR 35.6-46.4; p=0.638) without lidocaine, respectively. The co-administration of lidocaine resulted in reduced pain immediately after the injection and did not alter amikacin AUC or Cmax.

  1. Breakthrough Drugs and Turtle Soup


    Chabner, Bruce A.


    The U.S. Food and Drug Administration (FDA) category of Breakthrough Therapy drugs was established in 2012, fostered by collaboration between legislators, researchers, industry representatives, and cancer research advocates. This category allows the FDA to designate certain lifesaving drugs for expedited review, and it has been successful in speeding the approval of several new drugs.

  2. Recurring Utterances - Targeting a Breakthrough

    Directory of Open Access Journals (Sweden)

    Jacqueline Stark


    The most interesting phenomenon is KB’s production of words from former sessions indicating that they are still ‘active’ and the production of completely novel incorrect words. The observable features indicate that immediate auditory processing is possible in the form of repeating target words. However, as soon as KB must retrieve information from the (semantic lexicon, even after being able to correctly ‘repeat’ the target word several times, he responds with a RU, perseveration, or paraphasia. Several of his productions can be characterized as aphasic confabulations which stem from a memory gap. Thus, although KB’s language impairment is severe, his responses across time indicate that step-by-step a breakthrough is being made.

  3. The Breakthrough Behind the Chevy Volt Battery (United States)

    Lerner, Louise


    A revolutionary breakthrough cathode for lithium-ion batteries—the kind in your cell phone, laptop and new hybrid cars—makes them last longer, run more safely and perform better than batteries currently on the market.

  4. Researchers Realize Major Breakthrough in Understanding Endometriosis (United States)

    ... 16, 2014 Researchers Realize Major Breakthrough in Understanding Endometriosis For a disease that affects an estimated 6 ... 10% of women, surprisingly little is known about endometriosis — a disorder that causes uterine tissue to grow ...

  5. Breakthrough Listen: Searching for Signatures of Technology (United States)

    Isaacson, H. T.; Siemion, A. P. V.


    Breakthrough Listen is searching for signals of extra-terrestrial technologies using radio and optical telescopes. Very nearby stars of all types. Stars across the HR diagram and galaxies are all of interest in the search for techno-signatures.

  6. Innovation Impact: Breakthrough Research Results (Brochure)

    Energy Technology Data Exchange (ETDEWEB)


    The Innovation Impact brochure captures key breakthrough results across NREL's primary areas of renewable energy and energy efficiency research: solar, wind, bioenergy, transportation, buildings, analysis, and manufacturing technologies.

  7. Pain


    H.W. Snyman


    The medical profession has always been under pressure to supply public explanations of the diseases with which it deals. On the other hand, it is an old characteristic of the profession to devise comprehensive and unifying theories on all sorts of medical problems. Both these statements apply to pain - one of the most important and clinically striking phenomena and expressions of man since his origin in the mists of time.

  8. Pain

    Directory of Open Access Journals (Sweden)

    H.W. Snyman


    Full Text Available The medical profession has always been under pressure to supply public explanations of the diseases with which it deals. On the other hand, it is an old characteristic of the profession to devise comprehensive and unifying theories on all sorts of medical problems. Both these statements apply to pain - one of the most important and clinically striking phenomena and expressions of man since his origin in the mists of time.

  9. NASA Breakthrough Propulsion Physics Workshop Proceedings (United States)

    Millis, Marc G. (Editor); Williamson, Gary Scott (Editor)


    In August 1997, NASA sponsored a 3-day workshop to assess the prospects emerging from physics that may eventually lead to creating propulsion breakthroughs -the kind of breakthroughs that could revolutionize space flight and enable human voyages to other star systems. Experiments and theories were discussed regarding the coupling of gravity and electromagnetism, vacuum fluctuation energy, warp drives and wormholes, and superluminal quantum tunneling. Because the propulsion goals are presumably far from fruition, a special emphasis was to identify affordable, near-term, and credible research tasks that could make measurable progress toward these grand ambitions. This workshop was one of the first steps for the new NASA Breakthrough Propulsion Physics program led by the NASA Lewis Research Center.

  10. Breakthrough Propulsion Physics Workshop Preliminary Results (United States)

    Millis, Marc G.


    In August, 1997, a NASA workshop was held to assess the prospects emerging from physics that might lead to creating the ultimate breakthroughs in space transportation: propulsion that requires no propellant mass, attaining the maximum transit speeds physically possible, and breakthrough methods of energy production to power such devices. Because these propulsion goals are presumably far from fruition, a special emphasis was to identify affordable, near-term, and credible research that could make measurable progress toward these propulsion goals. Experiments and theories were discussed regarding the coupling of gravity and electromagnetism, vacuum fluctuation energy, warp drives and wormholes, and superluminal quantum tunneling. Preliminary results of this workshop are presented, along with the status of the Breakthrough Propulsion Physics program that conducted this workshop.

  11. Cancer Pain Management Education Rectifies Patients' Misconceptions of Cancer Pain, Reduces Pain, and Improves Quality of Life. (United States)

    Koh, Su-Jin; Keam, Bhumsuk; Hyun, Min Kyung; Ju Seo, Jeong; Uk Park, Keon; Oh, Sung Yong; Ahn, Jinseok; Lee, Ja Youn; Kim, JinShil


    More than half of the patients have reported improper management of breakthrough cancer pain. Empirical evidence is lacking concerning the effectiveness of cancer pain education on breakthrough pain control. This study aimed to examine the effects of individual pain education on pain control, use of short-acting analgesics for breakthrough pain, quality of life outcomes, and rectification of patients' misconceptions regarding cancer pain. A quasi-experimental design was used. In total, 176 (102 inpatients and 74 outpatients) and 163 (93 inpatients and 70 outpatients) cancer patients completed questionnaires on pain intensity, quality of life, use of short-acting medication for breakthrough pain, and misconceptions about cancer pain and opioid use before and immediately and/or seven days after individual pain education. The mean age of the participants was 60.9 years (±11.2), and 56.3% were male. The most common cancers were lung cancer (17.0%), colon cancer (15.9%), and breast cancer (12.5%). The subjects' reasons for attrition were conditional deterioration, death, or voluntary withdrawal (N = 13, 7.4%). Following the education, there was a significant reduction in overall pain intensity over 24 hours (P misconceptions regarding cancer pain management. The present educational intervention was effective in encouraging short-acting analgesic use for breakthrough pain, improving quality of life outcomes, and rectifying patients' misconceptions about analgesic use.

  12. Successful pregnancy outcome in paroxysmal nocturnal hemoglobinuria (PNH following escalated eculizumab dosing to control breakthrough hemolysis

    Directory of Open Access Journals (Sweden)

    Ruby Sharma


    Full Text Available Pregnancy in women with paroxysmal nocturnal hemoglobinuria (PNH is associated with increased maternal and fetal morbidity and mortality. There is limited published experience regarding therapy of PNH during pregnancy. We describe a case of a 30 year old female with hypoplastic myelodysplastic syndrome and PNH. After two years of treatment with eculizumab, she became pregnant. She developed breakthrough hemolysis at 20 weeks gestation. Pharmacokinetic and pharmacodynamic studies demonstrated a subtherapeutic eculizumab level with absence of complement blockade. Escalation of her eculizumab dose successfully controlled hemolysis and restored therapeutic eculizumab level and activity. She delivered a healthy baby at 36 weeks.

  13. The Breakthrough Listen Search for Intelligent Life (United States)

    Croft, Steve; Siemion, Andrew; De Boer, David; Enriquez, J. Emilio; Foster, Griffin; Gajjar, Vishal; Hellbourg, Greg; Hickish, Jack; Isaacson, Howard; Lebofsky, Matt; MacMahon, David; Price, Daniel; Werthimer, Dan


    The $100M, 10-year philanthropic "Breakthrough Listen" project is driving an unprecedented expansion of the search for intelligent life beyond Earth. Modern instruments allow ever larger regions of parameter space (luminosity function, duty cycle, beaming fraction, frequency coverage) to be explored, which is enabling us to place meaningful physical limits on the prevalence of transmitting civilizations. Data volumes are huge, and preclude long-term storage of the raw data products, so real-time and machine learning processing techniques must be employed to identify candidate signals as well as simultaneously classifying interfering sources. However, the Galaxy is now known to be a target-rich environment, teeming with habitable planets.Data from Breakthrough Listen can also be used by researchers in other areas of astronomy to study pulsars, fast radio bursts, and a range of other science targets. Breakthrough Listen is already underway in the optical and radio bands, and is also engaging with facilities across the world, including Square Kilometer Array precursors and pathfinders. I will give an overview of the technology, science goals, data products, and roadmap of Breakthrough Listen, as we attempt to answer one of humanity's oldest questions: Are we alone?

  14. Breakthroughs in Action Research through Poetry (United States)

    Barrett, Terry


    This paper discusses how major breakthroughs in generating, analysing and disseminating action research about problem-based learning were made through the medium of poetry. I used poetry in three ways: as data, as an interpretive device and as a reflective medium. Poetry helped me to disseminate my research in provocative, memorable and…

  15. Information and Announcements The Breakthrough Prize

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 10. Breakthrough Prize. B Sury Rajaram Nityananda Dipshikha Chakravortty. Information and Announcements Volume 19 Issue 10 October 2014 pp 966-969. Fulltext. Click here to view fulltext PDF. Permanent link:

  16. Exploring the Market for Breakthrough Technologies

    NARCIS (Netherlands)

    Ortt, J. Roland; Langley, David J.; Pals, Nico


    In this article, the gap between futures research (long term) and market research (short term) is closed in two ways. Firstly, by describing methods of market exploration that can be used earlier on in the process of development and diffusion of breakthrough technologies, so market research can be

  17. Pharmacokinetics of mitragynine in man. (United States)

    Trakulsrichai, Satariya; Sathirakul, Korbtham; Auparakkitanon, Saranya; Krongvorakul, Jatupon; Sueajai, Jetjamnong; Noumjad, Nantida; Sukasem, Chonlaphat; Wananukul, Winai


    Kratom, known botanically as Mitragyna speciosa (Korth.), is an indigenous tree in Southeast Asia. Kratom is currently easily available worldwide via special shops and the Internet to use as a drug of abuse, opioid alternative, or pain killer. So far, the pharmacokinetics of this plant has been studied only in animals, and there is no such study in humans. The major abundant active alkaloid in Kratom, mitragynine, is one of the promising new chemical substances to be developed as a new drug. The aim of this study was to examine the pharmacokinetics of mitragynine and assess the linearity in pharmacokinetics in chronic users. Since Kratom is illegal in Thailand, studies in healthy subjects would be unethical. We therefore conducted a prospective study by enrolling ten chronic, regular, healthy users. We adjusted the steady state in each subject by giving a known amount of Kratom tea for 7 days before commencement of the experiment. We admitted and gave different oral doses to subjects to confirm linearity in pharmacokinetics. The mitragynine blood concentrations at 17 times points and the urine concentrations during the 24-hour period were collected and measured by liquid chromatography-tandem mass spectrometry method. Ten male subjects completed the study without adverse reactions. The median duration of abuse was 1.75 years. We analyzed one subject separately due to the abnormal behavior of blood concentration. From data of nine subjects, the pharmacokinetic parameters established were time to reach the maximum plasma concentration (0.83±0.35 hour), terminal half-life (23.24±16.07 hours), and the apparent volume of distribution (38.04±24.32 L/kg). The urine excretion of unchanged form was 0.14%. The pharmacokinetics were observed to be oral two-compartment model. This was the first pharmacokinetic study in humans, which demonstrated linearity and was consistent with the oral two-compartment model with a terminal half-life of about 1 day. The pharmacokinetic

  18. Usefulness of competitive inhibitors of protein binding for improving the pharmacokinetics of {sup 186}Re-MAG3-conjugated bisphosphonate ({sup 186}Re-MAG3-HBP), an agent for treatment of painful bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuma [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan)]|[Kanazawa University, Advanced Science Research Center, Kanazawa (Japan); Mukai, Takahiro [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan)]|[Kyushu University, Graduate School of Pharmaceutical Sciences, Fukuoka (Japan); Kawai, Keiichi [Kanazawa University, Graduate School of Medical Sciences, Kanazawa (Japan)]|[University of Fukui, Biomedical Imaging Research Center, Yoshida, Fukui (Japan); Takamura, Norito [Kyushu University of Health and Welfare, School of Pharmaceutical Sciences, Nobeoka (Japan); Hanaoka, Hirofumi; Saji, Hideo [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Hashimoto, Kazuyuki [Japan Atomic Energy Agency, Tokai-mura, Ibaraki (Japan); Shiba, Kazuhiro; Mori, Hirofumi [Kanazawa University, Advanced Science Research Center, Kanazawa (Japan)


    We have developed a {sup 186}Re-mercaptoacetylglycylglycylglycine complex-conjugated bisphosphonate ({sup 186}Re-MAG3-HBP) for the treatment of painful bone metastases. We assumed competitive inhibitors of protein binding to be useful for procuring a favorable biodistribution of {sup 186}Re-MAG3-HBP for the palliation of bone pain because it has been reported that the concurrent administration of {sup 99m}Tc-MAG3 and drugs with high affinity for serum protein produced competitive displacement at specific binding sites and enhanced total clearance and tissue distribution. The displacement effects of several protein-binding inhibitors on the protein binding of {sup 186}Re-MAG3-HBP were investigated. Biodistribution experiments were performed by intravenously administering {sup 186}Re-MAG3-HBP into rats with ceftriaxone as a competitive protein-binding inhibitor or saline. The protein binding of {sup 186}Re-MAG3-HBP in rat serum, human serum, and a human serum albumin solution was significantly decreased by the addition of ceftriaxone, which has high affinity for binding site I on serum albumin. In the biodistribution experiments, pretreatment with ceftriaxone enhanced the clearance of the radioactivity of {sup 186}Re-MAG3-HBP in blood and nontarget tissues but had no effect on accumulation in bone. The findings suggested that the use of protein-binding competitive inhibitors would be effective in improving the pharmacokinetics of radiopharmaceuticals with high affinity for serum protein. (orig.)

  19. Prospects for Breakthrough Propulsion From Physics (United States)

    Millis, Marc G.


    "Space drives", "Warp drives", and "Wormholes:" these concepts may sound like science fiction, but they are being written about in reputable journals. To assess the implications of these emerging prospects for future spaceflight, NASA supported the Breakthrough Propulsion Physics Project from 1996 through 2002. This Project has three grand challenges: (1) Discover propulsion that eliminates the need for propellant; (2) Discover methods to achieve hyper-fast travel; and (3) Discover breakthrough methods to power spacecraft. Because these challenges are presumably far from fruition, and perhaps even impossible, a special emphasis is placed on selecting incremental and affordable research that addresses the critical issues behind these challenges. Of 16 incremental research tasks completed by the project and from other sponsors, about a third were found not to be viable, a quarter have clear opportunities for sequels, and the rest remain unresolved.

  20. How to use analogies for breakthrough innovations


    Schild, Katharina; Herstatt, Cornelius; Lüthje, Christian


    Analogies can trigger breakthrough ideas in new product development. Numerous examples demonstrate that substantial innovations often result from transferring problem solutions from one industry or domain to another. For instance, the designers of the new running shoe generation of Nike, “Nike SHOX”, use the same suspension concept like the technologies applied for Formula 1 racing cars, or the biological Lotus-effect led to the development of various self-cleaning surfaces. Academic resea...

  1. Breakthrough Propulsion Physics Project: Project Management Methods (United States)

    Millis, Marc G.


    To leap past the limitations of existing propulsion, the NASA Breakthrough Propulsion Physics (BPP) Project seeks further advancements in physics from which new propulsion methods can eventually be derived. Three visionary breakthroughs are sought: (1) propulsion that requires no propellant, (2) propulsion that circumvents existing speed limits, and (3) breakthrough methods of energy production to power such devices. Because these propulsion goals are presumably far from fruition, a special emphasis is to identify credible research that will make measurable progress toward these goals in the near-term. The management techniques to address this challenge are presented, with a special emphasis on the process used to review, prioritize, and select research tasks. This selection process includes these key features: (a) research tasks are constrained to only address the immediate unknowns, curious effects or critical issues, (b) reliability of assertions is more important than the implications of the assertions, which includes the practice where the reviewers judge credibility rather than feasibility, and (c) total scores are obtained by multiplying the criteria scores rather than by adding. Lessons learned and revisions planned are discussed.

  2. Breakthrough at NIF 'unlikely' in 2010 (United States)

    Harris, Margaret


    Hopes of reaching a milestone in fusion research by the end of 2010 have dimmed following a US government report that plays down the chances of an early breakthrough and sharply criticizes management of the 4bn National Ignition Facility (NIF). In the report, officials from the Government Accountability Office (GAO) state that ignition - fusion's "break-even" point - is "unlikely" to occur at the laser-fusion lab this year and that "significant scientific and technical challenges" could delay or even prevent the facility from achieving ignition by 2012.

  3. Creating breakthrough products from hidden needs


    Goffin, Keith


    Many managers want their organizations to develop breakthrough products and ask their R&D departments to come up with the equivalent of the iPod or iPhone. Unfortunately, the reality is very different-most organizations struggle to come up with novel product concepts, and of the thousands of new products introduced worldwide each year, product failure is more common than success. What are the reasons for product failure and what steps can companies take to avoid it? In this ...

  4. Breakthrough curve moments scaling in hyporheic exchange (United States)

    Bellin, A.; Tonina, D.; Marzadri, A.


    The interaction between stream flow and bed forms creates an uneven distribution of near-bed energy heads, which is the driving force of hyporheic exchange. Owing to the large disparity of advection characteristic times in the stream and within the hyporheic zone, solute mass exchange is often modeled by considering the latter as an immobile region. In a recent contribution Gónzalez-Pinzón et al. (2013) showed that existing models employing this hypothesis are structurally inconsistent with the scaling revealed by the analysis of 384 breakthrough curves collected in 44 streams across five continents. Motivated by this result, we analyze the scaling characteristics of a model that we recently developed by combining the analytical solution of the advective flow within the hyporheic zone with a Lagrangian solute transport model. Results show that similarly to the experimental data our model predicts breakthrough curves with a constant skewness, irrespective of the stream size, and that the scaling of the first three moments observed by Gónzalez-Pinzón et al. (2013) is also respected. Moreover, we propose regression curves that relate the first three moments of the residence time distribution with the alternate bar dimensionless depth (YBM*), a quantity that is easily measurable in the field. The connection between BTC moments and YBM* opens new possibilities for modeling transport processes at the catchment scale.

  5. Pharmacokinetics of mitragynine in man

    Directory of Open Access Journals (Sweden)

    Trakulsrichai S


    Full Text Available Satariya Trakulsrichai,1,2 Korbtham Sathirakul,3,4 Saranya Auparakkitanon,5 Jatupon Krongvorakul,5 Jetjamnong Sueajai,5 Nantida Noumjad,5 Chonlaphat Sukasem,5 Winai Wananukul2,6 1Department of Emergency Medicine, Faculty of Medicine Ramathibodi Hospital, 2Ramathibodi Poison Center, Faculty of Medicine Ramathibodi Hospital, 3Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; 4Center for Drug Research Discovery and Development, Thammasat Univerisity, Prathumthani, Thailand; 5Department of Pathology, Faculty of Medicine Ramathibodi Hospital, 6Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Background: Kratom, known botanically as Mitragyna speciosa (Korth., is an indigenous tree in Southeast Asia. Kratom is currently easily available worldwide via special shops and the Internet to use as a drug of abuse, opioid alternative, or pain killer. So far, the pharmacokinetics of this plant has been studied only in animals, and there is no such study in humans. The major abundant active alkaloid in Kratom, mitragynine, is one of the promising new chemical substances to be developed as a new drug. The aim of this study was to examine the pharmacokinetics of mitragynine and assess the linearity in pharmacokinetics in chronic users.Methods: Since Kratom is illegal in Thailand, studies in healthy subjects would be unethical. We therefore conducted a prospective study by enrolling ten chronic, regular, healthy users. We adjusted the steady state in each subject by giving a known amount of Kratom tea for 7 days before commencement of the experiment. We admitted and gave different oral doses to subjects to confirm linearity in pharmacokinetics. The mitragynine blood concentrations at 17 times points and the urine concentrations during the 24-hour period were collected and measured by liquid chromatography-tandem mass spectrometry method. Results: Ten male subjects completed

  6. Controlled Nucleosynthesis Breakthroughs in Experiment and Theory

    CERN Document Server

    Adamenko, Stanislav; Merwe, Alwyn


    This book ushers in a new era of experimental and theoretical investigations into collective processes, structure formation, and self-organization of nuclear matter. It reports the results of experiments wherein for the first time the nuclei constituting our world (those displayed in Mendeleev's table as well as the super-heavy ones) have been artificially created. Pioneering breakthroughs are described, achieved at the "Proton-21" Laboratory, Kiev, Ukraine, in a variety of new physical and technological directions. A detailed description of the main experiments, their analyses, and the interpretation of copious experimental data are given, along with the methodology governing key measurements and the processing algorithms of the data that empirically confirm the occurrence of macroscopic self-organizing processes leading to the nuclear transformations of various materials. The basic concepts underlying the initiation of self-sustaining collective processes that result in the formation of nuclear structures a...

  7. Breakthrough seizures after starting vilazodone for depression. (United States)

    McKean, James; Watts, Hannah; Mokszycki, Robert


    Vilazodone is a new selective serotonin reuptake inhibitor (SSRI) and serotonin 5-HT1a partial agonist that is approved by the United States Food and Drug Administration to treat major depression. SSRI-induced seizures are rare and are more likely to be associated with larger doses and severe symptoms such as those present in serotonin syndrome. Several case reports have implicated SSRIs, buspirone, or the combination of these agents as the cause of seizures, but these reports were confounded with either coingestions or doses that exceeded FDA recommendations. We describe a 22-year-old woman with a history of seizure disorder who had been seizure free for the previous 8 years and experienced two breakthrough seizures shortly after starting vilazodone. Her dose of vilazodone had recently been titrated to 40 mg/day when she experienced the first seizure. She was instructed to taper vilazodone over the next several days, then discontinue the drug, and then follow up with her neurologist. Based on the patient's history, physical examination, and recent dose increase, it was plausible that vilazodone was the cause of the seizures. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship (score of 4) between her development of seizures and vilazodone therapy. The pharmacodynamics of this particular class of SSRI has both proconvulsive and anticonvulsive mechanisms. This is of particular concern in patients with a history of seizure disorder who are starting antidepressive therapy. In persons with epilepsy who are taking vilazodone and experience breakthrough seizures, practitioners should consider this drug as a potential cause of these seizures. Thus, until future research and experience with vilazodone can provide a definitive answer, clinicians should be cautious when prescribing this medication to treat depression in patients with a history of seizure disorder. © 2015 Pharmacotherapy Publications, Inc.

  8. Pharmacokinetics and physiologic effects of intramuscularly administered xylazine hydrochloride-ketamine hydrochloride-butorphanol tartrate alone or in combination with orally administered sodium salicylate on biomarkers of pain in Holstein calves following castration and dehorning. (United States)

    Baldridge, Sarah L; Coetzee, Johann F; Dritz, Steve S; Reinbold, James B; Gehring, Ronette; Havel, James; Kukanich, Butch


    To determine the pharmacokinetic parameters of xylazine, ketamine, and butorphanol (XKB) administered IM and sodium salicylate (SAL) administered PO to calves and to compare drug effects on biomarkers of pain and distress following sham and actual castration and dehorning. 40 Holstein bull calves from 3 farms. Calves weighing 108 to 235 kg (n = 10 calves/group) received one of the following treatments prior to sham (period 1) and actual (period 2) castration and dehorning: saline (0.9% NaCl) solution IM (placebo); SAL administered PO through drinking water at concentrations from 2.5 to 5 mg/mL from 24 hours prior to period 1 to 48 hours after period 2; butorphanol (0.025 mg/kg), xylazine (0.05 mg/kg), and ketamine (0.1 mg/kg) coadministered IM immediately prior to both periods; and a combination of SAL and XKB (SAL+XKB). Plasma drug concentrations, average daily gain (ADG), chute exit velocity, serum cortisol concentrations, and electrodermal activity were evaluated. ADG (days 0 to 13) was significantly greater in the SAL and SAL+XKB groups than in the other 2 groups. Calves receiving XKB had reduced chute exit velocity in both periods. Serum cortisol concentrations increased in all groups from period 1 to period 2. However, XKB attenuated the cortisol response for the first hour after castration and dehorning and oral SAL administration reduced the response from 1 to 6 hours. Administration of XKB decreased electrodermal activity scores in both periods. SAL administered PO through drinking water decreased cortisol concentrations and reduced the decrease in ADG associated with castration and dehorning in calves.

  9. Neonatal pain (United States)

    Walker, Suellen M


    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback. PMID:24330444

  10. Developing Standards for Breakthrough Therapy Designation in Oncology (United States)

    Horning, Sandra J.; Haber, Daniel A.; Selig, Wendy K.D.; Ivy, S. Percy; Roberts, Samantha A.; Allen, Jeff D.; Sigal, Ellen V.; Sawyers, Charles L.


    In July 2012, Congress passed the Food and Drug Administration Safety and Innovation Act (FDASIA). The Advancing Breakthrough Therapies for Patients Act was incorporated into a Title of FDASIA to expedite clinical development of new, potential “breakthrough” drugs or treatments that show dramatic responses in early phase studies. Using this regulatory pathway, once a promising new drug candidate is designated as a “Breakthrough Therapy”, the FDA and sponsor would collaborate to determine the best path forward to abbreviate the traditional three-phase approach to drug development. The breakthrough legislation requires that an FDA Guidance be drafted that details specific requirements of the bill to aid FDA in implementing requirements of the Act. In this article, we have proposed criteria to define a product as a Breakthrough Therapy, and discussed critical components of the development process that would require flexibility in order to enable expedited development of a Breakthrough Therapy. PMID:23719260

  11. Breakthrough Listen - A New Search for Life in the Universe (United States)

    Worden, Pete

    On July 20, 2015 Yuri Milner and Stephen Hawking announced a new set of scientific initiatives - a SETI search called Breakthrough Listen and a contest to devise potential messages in response to a detection entitled Breakthrough Message. These are the first of several privately-funded Breakthrough Initiatives, designed to answer the fundamental science questions surrounding the origin, extent and nature of life in the universe. The initiatives are managed by the Breakthrough Prize Foundation. With Breakthrough Listen, Radio SETI observations have begun at the Green Bank Radio Telescope (GBT) and optical SETI at the Lick Observatory Automated Planet Finder (APF). Observations will soon commence at the CSIRO Parkes Radio Telescope. Other SETI instruments and observations are under consideration. In addition, several other initiatives are under development including an expanded search for life in the universe.

  12. Inertial frames and breakthrough propulsion physics (United States)

    Millis, Marc G.


    The term ;Breakthrough Propulsion Physics; comes from the NASA project by that name which examined non-rocket space drives, gravity control, and faster-than-light travel. The focus here is on space drives and the related unsolved physics of inertial frames. A ;space drive; is a generic term encompassing any concept for using as-yet undiscovered physics to move a spacecraft instead of existing rockets, sails, or tethers. The collective state of the art spans mostly steps 1-3 of the scientific method: defining the problem, collecting data, and forming hypotheses. The key issues include (1) conservation of momentum, (2) absence of obvious reaction mass, and (3) the net-external thrusting requirement. Relevant open problems in physics include: (1) the sources and mechanisms of inertial frames, (2) coupling of gravitation to the other fundamental forces, and (3) the nature of the quantum vacuum. Rather than following the assumption that inertial frames are an immutable, intrinsic property of space, this paper revisits Mach's Principle, where it is posited that inertia is relative to the distant surrounding matter. This perspective allows conjectures that a space drive could impart reaction forces to that matter, via some as-yet undiscovered interaction with the inertial frame properties of space. Thought experiments are offered to begin a process to derive new hypotheses. It is unknown if this line of inquiry will be fruitful, but it is hoped that, by revisiting unsolved physics from a propulsion point of view, new insights will be gained.

  13. The pharmacokinetics and safety of an intraoperative bupivacaine-collagen implant (XaraColl® for postoperative analgesia in women following total abdominal hysterectomy

    Directory of Open Access Journals (Sweden)

    Cusack SL


    Full Text Available Susan L Cusack,1 Philip Reginald,2 Lisa Hemsen,3 Emmanuel Umerah21Cusack Pharmaceutical Consulting, Burlington, NJ, USA; 2Departments of Gynaecology and Anaesthetics, Wexham Park Hospital, Slough, SL2 4HL, UK; 3Innocoll Technologies, Athlone, IrelandBackground: XaraColl®, a collagen-based intraoperative implant that delivers bupivacaine to the site of surgical trauma, is under development for postoperative analgesia. We examined the pharmacokinetics, safety and efficacy of XaraColl following implantation in women undergoing total abdominal hysterectomy.Methods: Three XaraColl implants, each containing 50 mg bupivacaine hydrochloride, were implanted in 12 women undergoing total abdominal hysterectomy for a benign condition. Serum samples were obtained through 96 hours for pharmacokinetic analysis. Patients received acetaminophen 1000 mg every 6 hours, diclofenac 50 mg every 8 hours, and were given access to intravenous morphine for breakthrough pain via patient-controlled analgesia during the first 24 hours. Pain intensity was assessed at regular intervals using a 100 mm visual analog scale. Safety was assessed through 30 days.Results: The pharmacokinetic profile displayed a double peak in bupivacaine concentration with the second peak occurring up to 24 hours after the first and at a generally higher concentration. The time to maximum concentration (tmax varied from 0.5 to 24 hours (median 12 hours according to which peak predominated. The mean maximum concentration (Cmax was 0.22 µg/mL and the maximum individual Cmax was 0.44 µg/mL, which are well below the established systemic toxicity threshold. Morphine use was generally low (mean 16.8 mg; median 6.5 mg and compared favorably with institutional experience. At 6 hours post-surgery, 11 patients recorded pain scores ≤ 20 mm, 6 recorded ≤ 10 mm, and 2 reported no pain. Scores continued to decline throughout the study. The product was considered safe and well tolerated.Conclusion: Xara

  14. Perioperative Pharmacokinetics of Methadone in Adolescents (United States)

    Sharma, Anshuman; Tallchief, Danielle; Blood, Jane; Kim, Thomas; London, Amy; Kharasch, Evan D.


    Background Methadone is frequently used in adult anesthesia and pain treatment. Methadone pharmacokinetics in adults are well characterized, including the perioperative period. Methadone is also used in children. There is, however, no information on methadone pharmacokinetics in children of any age. The purpose of this investigation was to determine the pharmacokinetics of intravenous methadone in children undergoing surgery. Perioperative opioid-sparing effects were also assessed. Methods Eligible subjects were children 5–18 yr undergoing general anesthesia and surgery, with an anticipated postoperative inpatient stay exceeding 3d. Three groups of 10–11 patients each received intravenous methadone HCl after anesthetic induction in ascending dose groups of 0.1, 0.2, and 0.3 mg/kg (up to 20 mg). Anesthetic care was not otherwise changed. Venous blood was obtained for 4d, for stereoselective determination of methadone and metabolites. Pain assessments were made each morning. Daily and total opioid consumption was determined. Perioperative opioid consumption and pain was determined in a second cohort, which was matched to age, sex, race, ethnicity, surgical procedure, and length of stay, but not receiving methadone. Results The final methadone study cohort was 31 adolescents (14 ± 2 yr, range 10–18) undergoing major spine surgery for a diagnosis of scoliosis. Methadone pharmacokinetics were linear over the dose range 0.1–0.3 mg/kg. Disposition was stereoselective. Methadone administration did not dose-dependently affect postoperative pain scores, and did not dose-dependently decrease daily or total postoperative opioid consumption in spinal fusion patients. Conclusions Methadone enantiomers disposition in adolescents undergoing surgery was similar to that in healthy adults. PMID:22037641

  15. Clinical characterization of breakthrough bacteraemia: a survey of 392 episodes. (United States)

    López Dupla, M; Martinez, J A; Vidal, F; Almela, M; López, J; Marco, F; Soriano, A; Richart, C; Mensa, J


    Few data are available on the clinical features of patients who develop breakthrough bacteraemia, understood as positive blood cultures despite appropriate antibiotic therapy. To determine the clinical significance and outcome of a large series of breakthrough bacteraemia. Retrospective analysis of a prospectively collected database. Two university-affiliated hospitals in Catalonia, Spain. A total of 392 individuals who suffered an episode of breakthrough bacteraemia recorded between 1997 and 2002. Demographic characteristics, underlying diseases, origin of infection, sources of infection, microorganisms isolated, McCabe and Jackson prognostic criteria, and mortality were analysed. Breakthrough bacteraemia was detected in 392 of 6324 (6.1%) episodes of bacteraemia. Eighty per cent of episodes were nosocomial. The most frequent source of infection in breakthrough bacteraemia was endovascular (70%). Coagulase-negative staphylococci, Staphylococcus aureus, and Pseudomonas aeruginosa were the most significant microorganisms involved. Nosocomial acquisition together with selected sources (central venous catheter, endocarditis and other endovascular foci), underlying conditions (neutropenia, polytraumatism, allogenic bone marrow and kidney transplantation), and particular microbial aetiologies (S. aureus, P. aeruginosa and polymicrobial) were independently associated with increased risk for developing breakthrough bacteraemia. Crude mortality rate was greater in patients with breakthrough bacteraemia (16% vs. 12.3%; P<0.05), and this condition was an independent predictor of death (OR 1.4, 95% CI, 1-1.9; P=0.04). In view of a case of breakthrough bacteraemia it is mandatory to search for an endovascular focus. Empiric treatment should be directed to cover S. aureus, coagulase-negative staphylococci and nonfermentative Gram-negative bacilli. Breakthrough bacteraemia is an independent predictor of death.

  16. Pharmacokinetics of fexofenadine

    DEFF Research Database (Denmark)

    Lappin, Graham; Shishikura, Yoko; Jochemsen, Roeline


    A human pharmacokinetic study was performed to assess the ability of a microdose to predict the pharmacokinetics of a therapeutic dose of fexofenadine and to determine its absolute oral bioavailability. Fexofenadine was chosen to represent an unmetabolized transporter substrate (P-gP and OATP). F...

  17. [Methodologic problems of pharmacokinetics]. (United States)

    Gor'kov, V A; Krylov, Iu F


    The subject of pharmacokinetics, method of research, aims and tasks of fundamental and applied aspects, place and importance for pharmacology are discussed. Discrepancy between a high scientific potential of pharmacokinetics and a low practical realization are analyzed, priority trends of future research are formulated.

  18. Methadone for Cancer Pain

    Directory of Open Access Journals (Sweden)

    Eric E. Prommer


    Full Text Available Pain is one of the most common and incapacitating symptoms experienced by patients with advanced cancer. Methadone is a potent opioid with strong affinity for the µ opioid receptor. In addition to being a potent µ opioid receptor ligand, methadone blocks the N-methyl-D-aspartic acid receptor and modulates neurotransmitters involved in descending pain modulation. These 3 properties enhance analgesic activity. Methadone’s lack of active metabolites makes it an attractive option when opioid responsiveness declines and renal insufficiency complicates opioid therapy. A lipophilic opioid, methadone can be given by multiple routes. Clinical trial data show equivalence with morphine as an analgesic in moderate to severe cancer pain. Further investigations are needed to define the role of methadone in the management of breakthrough pain and neuropathic pain and to determine whether it is truly superior to morphine, the gold standard of cancer analgesia.

  19. Back Pain and Modic

    DEFF Research Database (Denmark)

    Manniche, Claus; Jordan, Alan; Mikkelsen, Connie

    a significant step forward with the advent of the new back pain diagnosis, ”Modic changes”. During the coming years, thousands of back pain patients will now be given a precise diagnosis as well as a useful treatment in cases where we previously we unable to provide either a diagnosis or a useful treatment......Long awaited breakthrough Approximately 25 years ago a few researchers managed to publish an article in the renowned medical journal, The Lancet. The article demonstrated that intensive exercise was most useful for patients with chronic back pain. Many of our colleagues found this difficult...... to accept, nonetheless, intensive exercise has for chronic back pain has spread across the world and has become – in different forms – the most commonly prescribed treatment for back pain patients. Since that time, there has not been much research based progress in back science, however, we have taken...

  20. The development of new analgesics over the past 50 years: a lack of real breakthrough drugs. (United States)

    Kissin, Igor


    Fifty-nine drugs identified as analgesics were introduced from 1960 to 2009 and remain in use. Seven can be regarded as having novel molecular targets; however, only one, sumatriptan, was sufficiently effective to motivate the introduction of many similar drugs acting at the same target (triptans). Publication productivity in the area of pain grew exponentially during this period. Pain-related publications on morphine were dominant among other analgesics. Very intensive research efforts directed at diverse molecular targets related to pain mechanisms produced thousands of publications, but those efforts have not yet yielded new analgesics with sufficient effectiveness to change the share of publications on opioids or nonsteroidal antiinflammatory drugs. Morphine and aspirin, introduced for the treatment of pain more than a century ago, continue to dominate biomedical publications despite their limited effectiveness in many areas (e.g., neuropathic pain) and multiple serious adverse effects. The present assessment reveals the lack of real breakthroughs in analgesic drug development despite intense research efforts. Possible factors contributing to the apparent drought of novel analgesics are discussed.

  1. Pharmacokinetics: curiosity or cure

    International Nuclear Information System (INIS)

    Notari, R.E.


    What is the fate of a drug from the time of its introduction into the body to the end of its duration. Pharmacokinetic studies are often designed to provide an answer to this question. But this question may be asked of any drug and research that is limited to answering it will remain empirical. Pharmacokinetic studies can provide answers to many other drug-related questions. In doing so pharmacokinetic research has the potential of improving drug therapy as well as the design and evaluation of drugs. While significant contributions can be cited, the future of pharmacokinetics depends upon its increased impact on clinical practice and drug design. How can a molecule be tailored for site specificity. Can chemical modification selectively alter absorption, distribution, metabolism, binding or excretion. In what new ways can pharmacokinetic information increase the predictability of drug therapy. Such questions, to which pharmacokinetics should provide answers, are numerous and easily identified. But the definitive studies are difficult both to create and conduct. Whether or not pharmacokinetics can achieve its full potential will depend upon the extent to which it can provide answers to these currently unanswered questions

  2. Organophosphorus Insecticide Pharmacokinetics

    Energy Technology Data Exchange (ETDEWEB)

    Timchalk, Charles


    This chapter highlights a number of current and future applications of pharmacokinetics to assess organophosphate (OP) insecticide dosimetry, biological response and risk in humans exposed to these agents. Organophosphates represent a large family of pesticides where insecticidal as well as toxicological mode of action is associated with their ability to target and inhibit acetylcholinesterase (AChE). Pharmacokinetics entails the quantitative integration of physiological and metabolic processes associated with the absorption, distribution, metabolism and excretion (ADME) of drugs and xenobiotics. Pharmacokinetic studies provide important data on the amount of toxicant delivered to a target site as well as species-, age-, gender-specific and dose-dependent differences in biological response. These studies have been conducted with organophosphorus insecticides in multiple species, at various dose levels, and across different routes of exposure to understand their in vivo pharmacokinetics and how they contribute to the observed toxicological response. To access human exposure to organophosphorus insecticides, human pharmacokinetic studies have been conducted and used to develop biological monitoring strategies based on the quantitation of key metabolites in biological fluids. Pharmacokinetic studies with these insecticides are also useful to facilitate extrapolation of dosimetry and biological response from animals to humans and for the assessment of human health risk. In this regard, physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models are being utilized to assess risk and understand the toxicological implications of known or suspected exposures to various insecticides. In this chapter a number of examples are presented that illustrate the utility and limitation of pharmacokinetic studies to address human health concerns associated with organophosphorus insecticides.

  3. Pharmacokinetics of Snake Venom


    Suchaya Sanhajariya; Stephen B. Duffull; Geoffrey K. Isbister


    Understanding snake venom pharmacokinetics is essential for developing risk assessment strategies and determining the optimal dose and timing of antivenom required to bind all venom in snakebite patients. This review aims to explore the current knowledge of snake venom pharmacokinetics in animals and humans. Literature searches were conducted using EMBASE (1974–present) and Medline (1946–present). For animals, 12 out of 520 initially identified studies met the inclusion criteria. In general, ...

  4. Aldosterone breakthrough during aliskiren, valsartan, and combination (aliskiren + valsartan) therapy. (United States)

    Bomback, Andrew S; Rekhtman, Yelena; Klemmer, Philip J; Canetta, Pietro A; Radhakrishnan, Jai; Appel, Gerald B


    Aldosterone levels increase in 30%-40% of patients on angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers over the long term. This "aldosterone breakthrough" may carry important clinical consequences given aldosterone's nonepithelial, pro-fibrotic actions. The renin inhibitor, aliskiren, by suppressing the renin-angiotensin-aldosterone system (RAAS) proximally, may limit breakthrough compared to conventional RAAS blockade. This open-label study (NCT01129557) randomized subjects to aliskiren 300 mg daily (A), valsartan 320 mg daily (V), or aliskiren 150 mg + valsartan 160 mg daily (A+V) for 9 months. Eligible subjects had proteinuria >300 mg/day, estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m(2), and systolic blood pressure (BP) >130 or diastolic BP >80 mm Hg. Serum and 24-hour urine aldosterone (indexed to 24-hour urine Na) were checked before initiation of therapy and at 3, 6, and 9 months. Aldosterone breakthrough was defined as a sustained increase from baseline aldosterone by study end. The study was intended to enroll 120 subjects but was terminated early by the sponsor. We present here the results of 33 subjects who completed the protocol, of which 12 were randomized to A, 11 were randomized to V, and 10 were randomized to A+V. Mean baseline eGFR was 75.5 (±23.3) mL/min/1.73 m(2); baseline proteinuria was 3104 (±2943) mg/day; and baseline BP was 134.7 (±10.5)/84.8 (±8.4) mm Hg. Three (27%) subjects on V, three (25%) subjects on A, and three (30%) subjects on A+V had aldosterone breakthrough. Mean proteinuria reduction was 31% from baseline in all subjects: 30% in subjects with breakthrough vs. 32% in subjects without breakthrough. Mean BP reduction was 11.0/8.8 mm Hg in all subjects: 8.4/6.1 mm Hg in subjects with breakthrough vs. 12.0/9.8 mm Hg in subjects without breakthrough. Aliskiren, alone or in combination with valsartan, did not reduce the incidence of aldosterone breakthrough in subjects with hypertension

  5. Voriconazole pharmacokinetics following HSCT: results from the BMT CTN 0101 trial. (United States)

    Hope, William W; Walsh, Thomas J; Goodwin, Joanne; Peloquin, Charles A; Howard, Alan; Kurtzberg, Joanne; Mendizabal, Alan; Confer, Dennis L; Bulitta, Jürgen; Baden, Lindsey R; Neely, Michael N; Wingard, John R


    Voriconazole is a first-line agent for the prevention and treatment of a number of invasive fungal diseases. Relatively little is known about the relationship between drug exposure and the prevention of invasive fungal infections. A pharmacokinetic-pharmacodynamic substudy was performed as part of the BMT CTN 0101 trial, which was a randomized clinical trial comparing voriconazole with fluconazole for the prevention of invasive fungal infections in HSCT recipients. A previously described population pharmacokinetic model was used to calculate the maximum a posteriori Bayesian estimates for 187 patients. Drug exposure in each patient was quantified in terms of the average AUC and average trough concentrations. The relationship between drug exposure and the probability of breakthrough infection was investigated using logistic regression. AUC and trough concentrations in patients with and without breakthrough infection were compared. Pharmacokinetic data from each patient were readily described using the maximum a posteriori Bayesian estimates. There were only five patients that had a breakthrough infection while receiving voriconazole in the first 100 days post-HSCT. For these patients, there was no statistically significant relationship between the average AUC or average trough concentration and the probability of breakthrough infection [OR (95% CI) 1.026 (0.956-1.102) and 1.108 (0.475-2.581), respectively]. P value for these estimates was 0.474 and 0.813, respectively. Given the very small number of proven/probable infections, it was difficult to identify any differences in drug exposure in HSCT recipients with and without breakthrough fungal infections. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail:

  6. Pharmacogenetic evaluation to assess breakthrough psychosis with aripiprazole long-acting injection: a case report. (United States)

    Eum, Seenae; Schneiderhan, Mark E; Brown, Jacob T; Lee, Adam M; Bishop, Jeffrey R


    Given the complex nature of symptom presentation and medication regimens, psychiatric clinics may benefit from additional tools to personalize treatments. Utilizing pharmacogenetic information may be helpful in assessing unique responses to therapy. We report herein a case of wearing-off phenomena during treatment with aripiprazole long-acting injectable (LAI) and a proof of concept strategy of how pharmacogenetic information may be used to assess possible genetic factors and also hypothesize potential mechanisms for further study. A 51-year-old African American male with schizoaffective disorder was referred to a psychiatric clinic for medication management. After unsuccessful trials of multiple antipsychotics, oral aripiprazole was initiated (up to 30 mg/day) and transitioned to aripiprazole LAI with symptom improvement. At a high dose of aripiprazole LAI (400 mg Q3wks), the patient experienced breakthrough symptoms approximately 3 days prior to his next injection. Various considerations were examined to explain his atypical dose requirements, including but not limited to pharmacogenetic influences. Pharmacogenetic testing ruled out genetic influences on drug metabolism but noted a -141C Del variant in the dopamine-D2 receptor (DRD2) gene associated in prior studies of poor-response to antipsychotics. At this time, a new formulation, aripiprazole lauroxil, was explored due to its availability in higher dose options. Transition to the new formulation (882 mg Q4wks) greatly improved and stabilized the patient's symptoms with no breakthrough psychosis. Comparable daily dose equivalents were achieved with two different formulations due to the Q3wks vs Q4wks dosing strategies, although the two agents have some differences in pharmacokinetic profiles. We report a case of a patient experiencing wearing-off symptoms with aripiprazole LAI who benefited from switching to aripiprazole lauroxil. Pharmacogenetic testing revealed normal activity for relevant metabolism

  7. Characteristics and prognostic factors for pain management in 152 patients with lung cancer

    Directory of Open Access Journals (Sweden)

    Shi L


    Full Text Available Lei Shi,1,* Yumei Liu,2,* Hua He,1 Cong Wang,1 Hongwei Li,1 Nanya Wang1 1Cancer Center, The First Hospital of Jilin University, Changchun, 2Department of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China *These authors contributed equally to this work Objective: The objective of this study was to analyze the pain characteristics and factors influencing the outcome of pain control in patients with lung cancer having pain. Methods: Pain characteristics, the effectiveness, and prognostic factors for pain control were analyzed in 152 patients with lung cancer having moderate or severe chronic pain admitted to Cancer Center of The First Hospital of Jilin University, People’s Republic of China, between January 2012 and May 2013. Information about sex, age, pathological type, TNM stage, presence/absence of bone metastases, characteristics of pain, methods, and effectiveness of pain management was recorded. Results: Patients with non-small-cell lung cancer and small-cell carcinoma accounted for 132/152 (86.8% and 20/152 (13.2% cases, respectively. Among them, moderate (72.4% or severe pain (27.6% was reported in 73.7% of the cases at stage IV, chest or back pain was reported in 76.3% of the cases, and pain in other locations in the rest of the cases. Bone metastases were apparent in 44.1% of the patients. Neuropathic pain was noted in 46.7% of the patients, and frequent breakthrough pain was noted in 25.7% of the patients. High pain intensity was associated with frequent breakthrough pain. Pain was adequately controlled in 81.6% of the patients prescribed 3 days of analgesics. More patients reported a KPS higher than or equal to 80 after 3 days of analgesic treatment (P<0.001. Severe pain, frequent breakthrough pain, and presence of bone metastases were independent risk factors for poor pain control. Severe pain, frequent breakthrough pain, or neuropathic pain in the patients using opioids required higher

  8. Foreknowledge of breakthroughs science and technology foresight, and the early identification of areas of breakthrough

    International Nuclear Information System (INIS)

    Papon, P.


    The progress of science and technology has been so rapid in the last few decades that it receives especial attention in forecasting and foresight exercises. But, because they are too greatly in thrall to the dominant paradigms and hence favour a linear perspective, the experts who deal with these questions pay more attention to the future of technologies than to scientific advances and revolutions. The bulk of their work consists, then, in anticipating, by various different methods (Delphi surveys, Road-maps, etc.), at what date a particular technology might be available (without, however, always correctly gauging the conditions for its social appropriation or the applications to which it might be put). In this article, Pierre Papon expounds a much more original and promising approach for attempting to anticipate the discoveries that are likely radically to transform the fields of scientific knowledge by investigating the phenomena that may potentially lead to fundamental revolutions. After reminding us of the premonitory thinking of a number of authors - in the fields, for example, of genetics and computer science -, he endeavors to describe some of the dominant paradigms, particularly in quantum physics and molecular biology. In this way, he shows the advances they have made possible, and also their limitations, and explores what new scientific leaps forward might occur, bringing radically new technological breakthroughs between now and 2050. Papon reminds us, at the same time that, 'as science is not something isolated within society'; it has a duty to contribute to meeting the great challenges that face us - of work, health, nutrition and sustainable development, particularly where energy and climate are concerned. He therefore examines the ways in which future scientific and technological advances might provide solutions and how important it might be to 'translate the questions society poses into scientific questions'. He thus argues implicitly for strategic

  9. Application of the rainfall infiltration breakthrough (RIB) model for ...

    African Journals Online (AJOL)

    Application of the rainfall infiltration breakthrough (RIB) model for groundwater recharge estimation in west coastal South Africa. ... the data from Oudebosch with different rainfall and groundwater abstraction inputs are simulated to explore individual effects on water levels as well as recharge rate estimated on a daily basis.

  10. Technical Breakthroughs in the Wearable Artificial Kidney (WAK)


    Gura, Victor; Macy, Alexandra S.; Beizai, Masoud; Ezon, Carlos; Golper, Thomas A.


    Background: The wearable artificial kidney (WAK) has been a holy grail in kidney failure for decades. Described herein are the breakthroughs that made possible the creation of the WAK V1.0 and its advanced versions V 1.1 and 1.2.

  11. Breakthrough VZV infection after immunization, presenting as herpes zoster.

    NARCIS (Netherlands)

    Schade, R.P.; Bakkers, J.; Cornelissen, M.; Koster-Kamphuis, L.; Melchers, W.J.G.; Galama, J.M.D.


    An immunocompromized, VZV-vaccinated child had a breakthrough infection with VZV, acquired at a day-care centre during a chickenpox outbreak. Interestingly, the infection manifested as herpes zoster of 1 dermatome. Typing showed wild-type virus, which suggests that exogenous reinfection with a new

  12. Dissolved CO2Increases Breakthrough Porosity in Natural Porous Materials. (United States)

    Yang, Y; Bruns, S; Stipp, S L S; Sørensen, H O


    When reactive fluids flow through a dissolving porous medium, conductive channels form, leading to fluid breakthrough. This phenomenon is caused by the reactive infiltration instability and is important in geologic carbon storage where the dissolution of CO 2 in flowing water increases fluid acidity. Using numerical simulations with high resolution digital models of North Sea chalk, we show that the breakthrough porosity is an important indicator of dissolution pattern. Dissolution patterns reflect the balance between the demand and supply of cumulative surface. The demand is determined by the reactive fluid composition while the supply relies on the flow field and the rock's microstructure. We tested three model scenarios and found that aqueous CO 2 dissolves porous media homogeneously, leading to large breakthrough porosity. In contrast, solutions without CO 2 develop elongated convective channels known as wormholes, with low breakthrough porosity. These different patterns are explained by the different apparent solubility of calcite in free drift systems. Our results indicate that CO 2 increases the reactive subvolume of porous media and reduces the amount of solid residual before reactive fluid can be fully channelized. Consequently, dissolved CO 2 may enhance contaminant mobilization near injection wellbores, undermine the mechanical sustainability of formation rocks and increase the likelihood of buoyance driven leakage through carbonate rich caprocks.

  13. Technology breakthrough and clinic application of gemstone CT

    International Nuclear Information System (INIS)

    Wang Jian


    Gemstone CT breaks through the conventional CT development model of expending detector's width over the past decade. By gemstone detector and spectral imaging technology, it could provide higher diagnostic accuracy, quicker diagnosis speed and higher definition of imaging, and better meet comprehensive clinical needs than conventional CT. To summarize technical breakthrough and clinical application of Gemstone CT. (authors)

  14. Breakthrough supplies young fish to a hungry industry | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)


    Oct 28, 2010 ... The technological breakthrough made the industry's growth possible in Southeast Asia. At the time, the Philippines produced about 200,000 tonnes of milkfish. ... for about half of the farmed fish production in the Philippines. An important source of animal protein, it is vital to the country's food security.

  15. Impact of allergic rhinitis and its treatment on the pharmacokinetics of nasally administered fentanyl. (United States)

    Perelman, Michael; Fisher, Anthony N; Smith, Alan; Knight, Alastair


    Fentanyl pectin nasal spray (FPNS, Lazanda® in the US and PecFent® in Europe and Australia) is a novel analgesic approved for the management of breakthrough pain in cancer patients. Given that the fentanyl is nasally administered, it is important to understand whether concomitant allergic rhinitis, or its treatment with a vasoconstrictor, would affect its absorption and, potentially, its efficacy or safety. Subjects with a history of allergic rhinitis were screened to identify subjects who developed at least moderate rhinitis symptoms on exposure to pollen allergen (either ragweed or tree) in an environmental exposure chamber (EEC). These were entered into a randomized, three-way crossover study in which each subject received 100 μg of FPNS under three exposure conditions; Control (no rhinitis), Rhinitis (symptomatic without decongestant), Treated (symptomatic with concomitant oxymetazoline). Blood samples for fentanyl were collected over a 24-hour period. A total of 132 subjects was screened to identify 54 for inclusion in the study; 31 were evaluable for pharmacokinetics. Measures of fentanyl absorption (mean or median) were similar between Control and Rhinitis conditions: Cmax 453.0 vs. 467.8 pg/ml; AUCt 1,292.3 vs. 1,325.4 pg×h/ml, AUC0-∞ 1,430.6 vs. 1,387 pg×h/ml and tmax 20 vs. 17 minutes. When oxymetazoline was co-administered, overall fentanyl absorption was slightly reduced (AUC0-∞ 1,362.4 pg×h/ml); but, more clinically relevant were the delayed rate of absorption (tmax 53 minutes) and reduced Cmax (235.3 pg/ml). Patients treated with FPNS will be unaffected by the development of allergic rhinitis; but, if oxymetazoline is prescribed, the patient would benefit from added supervision when oxymetazoline is started and stopped.

  16. Lumping in pharmacokinetics. (United States)

    Brochot, Céline; Tóth, János; Bois, Frédéric Y


    Pharmacokinetic (PK) models simplify biological complexity by dividing the body into interconnected compartments. The time course of the chemical's amount (or concentration) in each compartment is then expressed as a system of ordinary differential equations. The complexity of the resulting system of equations can rapidly increase if a precise description of the organism is needed. However, difficulties arise when the PK model contains more variables and parameters than comfortable for mathematical and computational treatment. To overcome such difficulties, mathematical lumping methods are new and powerful tools. Such methods aim at reducing a differential system by aggregating several variables into one. Typically, the lumped model is still a differential equation system, whose variables are interpretable in terms of variables of the original system. In practice, the reduced model is usually required to satisfy some constraints. For example, it may be necessary to keep state variables of interest for prediction unlumped. To accommodate such constraints, constrained lumping methods have are also available. After presenting the theory, we study, here, through practical examples, the potential of such methods in toxico/pharmacokinetics. As a tutorial, we first simplify a 2-compartment pharmacokinetic model by symbolic lumping. We then explore the reduction of a 6-compartment physiologically based pharmacokinetic model for 1,3-butadiene with numerical constrained lumping. The lumping methods presented here can be easily automated, and are applicable to first-order ordinary differential equation systems.


    Rowland, Malcolm; Tucker, Geoffrey


    To encourage uniformity in the presentation of pharmacokinetic data, a general nomenclature has been developed. The system has wide application. Flexibility is achieved through the use of general variables, constants, qualifying terms and subscripts. Yet, through the use of implied terms, the symbols describing many common variables and constants are simple.

  18. Symbols in pharmacokinetics. (United States)

    Rowland, M; Tucker, G


    To encourage uniformity in the presentation of pharmacokinetic data, a general nomenclature has been developed. The system has wide application. Flexibility is achieved through the use of general variables, constants, qualifying terms, and subscripts. Yet, through the use of implied terms, the symbols describing many common variables and constants are simple.

  19. Breakthrough candidemia in children: clinical and microbiological characteristics, therapeutic strategies and impact on outcomes. (United States)

    Lai, Mei-Yin; Hsu, Jen-Fu; Chu, Shih-Ming; Wu, I-Hsyuan; Huang, Hsuan-Rong; Lin, Chun-Chih; Lee, I-Ta; Chiang, Ming-Chou; Fu, Ren-Huei; Tsai, Ming-Horng


    To assess the characteristics, treatments, risk factors and outcomes of breakthrough candidemia in children. Episodes of breakthrough candidemia in children were compared with the remaining episodes in a 13-year cohort study. Out of 319 episodes, 45 (14.1%) were breakthrough candidemia. Breakthrough candidemia occurred in patients with more acutely ill conditions, and the majority was caused by non-albicans Candida species (73.3%; 33 episodes). A total of 79.1% of breakthrough candidemia were caused by antifungal-susceptible Candida isolates and emergence of resistance was the mechanism in five cases of patients receiving fluconazole. Episodes of breakthrough candidemia had significantly higher illness severity and higher rates of fungemia-attributable mortality. Breakthrough candidemia independently contributed to unfavorable outcomes, and more aggressive treatment strategies are warranted when breakthrough candidemia is encountered.

  20. Methodology for Examining Potential Technology Breakthroughs for Mitigating CO2 and Application to Centralized Solar Photovoltaics (United States)

    Aggressive reductions in US greenhouse gas emissions will require radical changes in how society generates and uses energy. Technological breakthroughs will be necessary if we are to make this transition cost effectively. With limited resources, understanding the breakthrough pot...

  1. Breakthroughs In Low-Profile Leaky-Wave HPM Antennas (United States)


    YYYY) 18-09-2014 2. REPORT TYPE Quarterly 3. DATES COVERED (From - To) 19 Jun 2014 – 18 Sep 2014 4. TITLE AND SUBTITLE Breakthroughs in Low...Table 1. Types of low-profile, forward-traveling, fast-wave, leaky-wave, HPM antennas Acronym Full Name Identifying Geometry / Feature(s) FAWSEA...more parallel waveguides (aka, channels), with a radiated plane wave that exits the overall aperture at a well-defined angle. Since the FAWSEA aper

  2. Breakthroughs in Photonics 2013: Photoacoustic Tomography in Biomedicine


    Yao, Junjie; Wang, Lihong V.


    Photoacoustic tomography (PAT) is one of the fastest growing biomedical imaging modalities in the last decade. Building on its high scalability and complementary imaging contrast to other mainstream modalities, PAT has gained substantial momentum in both preclinical and clinical studies. In 2013, PAT has grown markedly in both its technological capabilities and biomedical applications. In particular, breakthroughs have been made in super-resolution imaging, deep blood flow measurement, small ...

  3. New AIDA-2020 call for breakthrough detector technologies

    CERN Multimedia


    Physicists, engineers, and industry will be interested in a new proof-of-concept fund for breakthrough projects from the general field of detector development and testing.   Launched in the framework of the European project AIDA-2020, this open call will provide up to 200k€ of seed funding to support innovative and societal applications with a focus on industry-oriented applications. The deadline for applying is 20 October 2016. More information here.

  4. Clinical pharmacokinetics of melatonin

    DEFF Research Database (Denmark)

    Harpsøe, Nathja Groth; Andersen, Lars Peter Holst; Gögenur, Ismail


    PURPOSE: The aim of the review was to provide an overview of studies investigating the pharmacokinetics of exogenous melatonin in humans and if possible, to provide recommendations for clinical use. METHODS: The review was conducted in accordance to PRISMA guidelines. A systematic literature search......), and bioavailability. RESULTS: The literature search identified 392 records. Twenty-two studies were included in the review. Melatonin dosages varied between 0.3 and 100 mg and were administered either orally or intravenously. Cmax ranged from 72.1 (10 ml/h; 0.02 mg, IV) to 101,163 pg/ml (100 mg, oral). Tmax ranged......) and 1602 L (4 mg, oral). Bioavailability of oral melatonin ranged from 9 to 33%. Pharmacokinetics was affected by age, caffeine, smoking, oral contraceptives, feeding status, and fluvoxamine. Critically ill patients displayed accelerated absorption and compromised elimination. CONCLUSIONS: Despite...

  5. Fractional calculus in pharmacokinetics. (United States)

    Sopasakis, Pantelis; Sarimveis, Haralambos; Macheras, Panos; Dokoumetzidis, Aristides


    We are witnessing the birth of a new variety of pharmacokinetics where non-integer-order differential equations are employed to study the time course of drugs in the body: this is dubbed "fractional pharmacokinetics". The presence of fractional kinetics has important clinical implications such as the lack of a half-life, observed, for example with the drug amiodarone and the associated irregular accumulation patterns following constant and multiple-dose administration. Building models that accurately reflect this behaviour is essential for the design of less toxic and more effective drug administration protocols and devices. This article introduces the readers to the theory of fractional pharmacokinetics and the research challenges that arise. After a short introduction to the concepts of fractional calculus, and the main applications that have appeared in literature up to date, we address two important aspects. First, numerical methods that allow us to simulate fractional order systems accurately and second, optimal control methodologies that can be used to design dosing regimens to individuals and populations.

  6. The effects of analgesic prescription and patient adherence on pain in a Dutch outpatient cancer population

    NARCIS (Netherlands)

    Enting, Roeline; Oldenmenger, Wendy H.; Van Gool, Arthur R.; van der Rijt, Carin C. D.; Smitt, Peter A. E. Sillevis


    Insufficient awareness of cancer Pain, including breakthrough pain, inadequate analgesic prescriptions, and nonadherence contribute to inadequate cancer pain management. There are insufficient data about the contribution of each of these factors. In a cross-sectional survey among 915 adult cancer

  7. Pharmacokinetics in older persons. (United States)

    Cusack, Barry J


    Physiologic changes and disease-related alterations in organ function occur with aging. These changes can affect drug pharmacokinetics in older persons. This article reviews age-related changes in pharmacokinetics and their clinical relevance. A PubMed search was conducted using the terms elderly and pharmacokinetics. Other reviews were also included for literature searching. The review includes literature in particular from 1990 through April 2004. Some articles from before 1990 were included to help illustrate principles of age-related pharmacokinetics. There are minor changes in drug absorption with aging. The effect of aging on small-bowel transporter systems is not yet fully established. Bioavailability of highly extracted drugs often is increased with age. Transdermal absorption may be delayed, especially in the case of water-soluble compounds. Fat-soluble drugs may distribute more widely and water-soluble drugs less extensively in older persons. Hepatic drug metabolism shows wide interindividual variation, and in many cases, there is an age-related decline in elimination of metabolized drugs, particularly those eliminated by the cytochrome enzyme system. Any decrement in cytochrome enzyme metabolism appears nonselective. Synthetic conjugation metabolism is less affected by age. Pseudocapillarization of the sinusoidal endothelium in the liver, restricting oxygen diffusion, and the decline in liver size and liver blood flow may influence age-related changes in rate of hepatic metabolism. Frailty, physiological stress, and illness are important predictors of drug metabolism in older individuals. Inhibition of drug metabolism is not altered with aging, but induction is reduced in a minority of studies. Renal drug elimination typically declines with age, commensurate with the fall in creatinine clearance. Renal tubular organic acid transport may decline with age, while the function of the organic base transporter is preserved but may be less responsive to

  8. Tanshinone IIA Exerts an Antinociceptive Effect in Rats with Cancer-induced Bone Pain. (United States)

    Hao, Wei; Chen, Lei; Wu, Li-Fang; Yang, Fan; Niu, Jian-Xiang; Kaye, Alan D; Xu, Shi-Yuan


    Cancer-induced bone pain (CIBP) is a common chronic pain characterized by 2 components, ongoing pain and breakthrough pain. Tanshinone IIA (TSN IIA) is a bioactive constituent of the traditional Chinese medicine Danshen, which has been reported to have an antinociceptive effect on neuropathic and inflammatory pain through downregulation of the late proinflammatory cytokine high-mobility group protein B1 (HMGB1). To assess the antinociceptive effect of TSN IIA on CIBP. A randomized, double-blind, controlled animal trial was performed. University lab in China. A rat CIBP model was established by injecting Walker 256 mammary gland carcinoma cells into the intramedullary cavity of the tibia. Both ongoing pain, e.g., flinching and guarding, and breakthrough pain, e.g., limb use and von Frey threshold, were evaluated. The effects of intraperitoneally administered TSN IIA on pain behavior and the expression levels of spinal HMGB1, interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6 were determined. The effect of TSN IIA on the electrically evoked response of spinal wide-dynamic range (WDR) neurons was performed in vivo. TSN IIA dose-dependently inhibited cancer-induced ongoing pain and breakthrough pain. The expression levels of spinal HMGB1 and other inflammatory factors (IL-1beta, TNF-alpha, and IL-6) were increased in the rat model, but they were suppressed by TSN IIA in a dose-dependent manner. Moreover, TSN IIA significantly inhibited the neuronal responses of WDR neurons in spinal deep layers. Further studies are warranted to ascertain how TSN IIA attenuates cancer-induced ongoing pain. Our results indicate that TSN IIA attenuates cancer-induced ongoing pain and breakthrough pain, possibly via suppression of central sensitization in CIBP rats. Therefore, we have provided strong evidence supporting TSN IIA as a potential and effective therapy for relieving CIBP. Cancer-induced bone pain, high-mobility group protein B1, Tanshinone IIA, ongoing pain

  9. Generating breakthrough new product ideas feeding the innovation funnel

    CERN Document Server

    Cooper, Robert


    Senior executives are experiencing a shortage of game-changing ideas that drive growth. This book explains how to feed the innovation funnel with a steady stream of breakthrough new product ideas, providing numerous examples of the methods, approaches and techniques used by leading companies such as Motorola and Procter & Gamble. Learn more about the impact you can make by leveraging an innovation strategy, voice-of-customer research, external ideas via open innovation, employees? creative talent and fundamental research. Establish a proactive Discovery Stage that focuses on the drivers of innovation performance to transform your organization into an innovation machine.

  10. Tsetse Fly Genome Breakthrough Brings Hope for African Farmers

    International Nuclear Information System (INIS)


    Scientists have cracked the genetic code of the bloodsucking tsetse fly, prompting hope that the breakthrough will help future efforts to control one of the most devastating livestock diseases in sub-Saharan Africa spread by the insect. The tsetse genome was sequenced and annotated during a 10-year international collaborative effort that involved the Insect Pest Control Laboratory run jointly by the United Nations Food and Agriculture Organization (FAO) and the International Atomic Energy Agency (IAEA) in Vienna. The achievement allows scientists to better study the fly's genes and their functions, knowledge that should open the door for researching ways to control the insect

  11. Daratumumab – breakthrough drug in multiple myeloma therapy

    Directory of Open Access Journals (Sweden)

    Artur Jurczyszyn


    Full Text Available Multiple myeloma (MM remains incurable despite important recent advances in treatment. Over the last 2 years, an anti-CD38 monoclonal antibody daratumumab (DARA has emerged as a breakthrough targeted therapy for patients with MM. Early-stage clinical trials have found DARA to be safe and to have encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide as well as stem cell transplant has already failed. This review discusses the preclinical and clinical development of DARA, its pathophysiological basis, and its prospects for future use in MM.

  12. Mini-columns for Conducting Breakthrough Experiments. Design and Construction

    Energy Technology Data Exchange (ETDEWEB)

    Dittrich, Timothy M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Reimus, Paul William [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Ware, Stuart Douglas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    Experiments with moderately and strongly sorbing radionuclides (i.e., U, Cs, Am) have shown that sorption between experimental solutions and traditional column materials must be accounted for to accurately determine stationary phase or porous media sorption properties (i.e., sorption site density, sorption site reaction rate coefficients, and partition coefficients or Kd values). This report details the materials and construction of mini-columns for use in breakthrough columns to allow for accurate measurement and modeling of sorption parameters. Material selection, construction techniques, wet packing of columns, tubing connections, and lessons learned are addressed.

  13. Clinical Pharmacokinetics of Paclitaxel Monotherapy

    DEFF Research Database (Denmark)

    Stage, Tore B; Bergmann, Troels K; Kroetz, Deanna L


    Paclitaxel is an anticancer agent efficacious in the treatment of ovarian, breast, and lung cancer. Due to a strong link between the pharmacokinetics and therapeutic efficacy of paclitaxel, we reviewed the literature on paclitaxel pharmacokinetics. Systematic data mining was performed to extract ...

  14. Pain characteristics and management of inpatients admitted to a comprehensive cancer centre

    DEFF Research Database (Denmark)

    Kurita, G P; Tange, U B; Farholt, H


    prevalence of pain was observed, 65.7%. Thirty-two per cent reported moderate to severe pain when it was at its worst, 96% reported no or mild pain when it was at its least. Nearly 22% reported moderate to severe pain when the pain was categorised as average. Breakthrough pain episodes were reported by 30.......5%. Adjuvant medication was sparsely used and not always correctly indicated. Out of 88 patients with pain, 62.5% were left untreated according to the Electronic Medication System. Higher health-related quality of life was associated with lower pain intensity. The use of opioids with or without adjuvants...... and number of breakthrough episodes; however, analgesic medication seemed to be underused. Measures to improve pain assessment and management are highly required....

  15. Pharmacokinetics of Melatonin

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Holst; Gögenur, Ismail; Rosenberg, Jacob


    Despite widespread clinical application of melatonin, several unanswered questions remain regarding the pharmacokinetics of this drug. This lack of knowledge may contribute to the inconsistency of results in previous clinical studies. Currently, a t max value of 30-45 min and a t ½elimination of 45...... min are well established. Several questions relate to what constitutes a clinically effective plasma concentration, the choice of ideal administration route, and the optimal method of analysis. Furthermore, investigations of melatonin metabolites in humans are urgently needed in order to characterize...

  16. Pharmacokinetic evaluation of pemetrexed

    DEFF Research Database (Denmark)

    Sørensen, Jens Benn


    correlates with renal function and it may be safely used with vitamin supplementation in patients with creatinine clearance ≥ 45 ml/min. The pharmacokinetics of pemetrexed is also largely unchanged in third-space fluids and can be feasibly and safely administered in combination with several other cytotoxic...... or targeted agents. It is the author's opinion that pemetrexed is already a valuable cytotoxic agent which has proved useful in several malignancies. However, future trials might expand on the combined use of pemetrexed with other targeted agents that could be beneficial to other selected patients harboring...

  17. (Mis)understanding Science: The Problem with Scientific Breakthroughs. (United States)

    Evans, James P


    On Saturday morning, February 28, 1953, the mystery of heredity appeared secure. Humans hadn't the faintest idea of how genetic information was transmitted-how the uncanny resemblance between mother and daughter, grandfather and grandson was conveyed across generations. Yet, by that Saturday afternoon, two individuals, James Watson and Francis Crick, had glimpsed the solution to these mysteries. The story of Watson and Crick's great triumph has been told and retold and has rightly entered the pantheon of scientific legend. But Watson and Crick's breakthrough was just that: a rupture and dramatic discontinuity in human knowledge that solved a deep mystery, the likes of which occurs, perhaps, a couple of times each century. And that's the problem. The story is just so good and so irresistible that it has misled generations of scientists about what to expect regarding a life in science. And more damaging, the resulting breakthrough mentality misleads the public, the media, and society's decision-makers about how science really works, all to the detriment of scientific progress and our society's well-being. © 2016 The Hastings Center.

  18. Turning Regenerative Medicine Breakthrough Ideas and Innovations into Commercial Products. (United States)

    Bayon, Yves; Vertès, Alain A; Ronfard, Vincent; Culme-Seymour, Emily; Mason, Chris; Stroemer, Paul; Najimi, Mustapha; Sokal, Etienne; Wilson, Clayton; Barone, Joe; Aras, Rahul; Chiesi, Andrea


    The TERMIS-Europe (EU) Industry committee intended to address the two main critical issues in the clinical/commercial translation of Advanced Therapeutic Medicine Products (ATMP): (1) entrepreneurial exploitation of breakthrough ideas and innovations, and (2) regulatory market approval. Since January 2012, more than 12,000 publications related to regenerative medicine and tissue engineering have been accepted for publications, reflecting the intense academic research activity in this field. The TERMIS-EU 2014 Industry Symposium provided a reflection on the management of innovation and technological breakthroughs in biotechnology first proposed to contextualize the key development milestones and constraints of allocation of financial resources, in the development life-cycle of radical innovation projects. This was illustrated with the biofuels story, sharing similarities with regenerative medicine. The transition was then ensured by an overview of the key identified challenges facing the commercialization of cell therapy products as ATMP examples. Real cases and testimonies were then provided by a palette of medical technologies and regenerative medicine companies from their commercial development of cell and gene therapy products. Although the commercial development of ATMP is still at the proof-of-concept stage due to technology risks, changing policies, changing markets, and management changes, the sector is highly dynamic with a number of explored therapeutic approaches, developed by using a large diversity of business models, both proposed by the experience, pitfalls, and successes of regenerative medicine pioneers, and adapted to the constraint resource allocation and environment in radical innovation projects.

  19. Pharmacokinetics and the analytical chemist. (United States)

    Mehta, A C


    A prerequisite in pharmacokinetic studies is the development of analytical methods to assay the parent drug and its metabolites in biological fluids. For method development and application, a detailed knowledge of pharmacokinetics is not essential, but familiarity with its fundamental principles and terminology is necessary and helps in interpreting assay results and in interacting more effectively with colleagues who may be specialists in medical or related fields. The purpose of this article is to introduce the basic concepts of pharmacokinetics and some of the biological processes associated with it. Areas relevant to the needs of analytical chemists are discussed.

  20. Is a Breakthrough on Climate Change Governance on the Horizon?

    DEFF Research Database (Denmark)

    Figueroa, Maria Josefina

    The recently released Fifth Assessment report of the IPCC has highlighted again with unprecedented scope and insight the urgency of addressing climate change. The international community has pledged to devise the next international agreement on climate change by 2015, while the EU and in particular...... the Scandinavian countries have forged ahead advancing a variety of policies to respond to climate change. Similarly, regions, municipalities, and private actors across the world are also contributing to climate governance. This paper asks whether the world is reaching a tipping point where a breakthrough...... on climate change governance is near?. The answer is approached by contrasting the governance model within which the IPCC operates and the conditions of policy and governance interaction toward the more scientific foundations laid out by IPCC, with the range of multilateral climate governance...

  1. Islet transplantation: lessons learned since the Edmonton breakthrough. (United States)

    Langer, R M


    This work sought to summarize the main issues of the last decade in the field of clinical islet transplantation. Ten years ago in Edmonton, a new protocol initiated for islet transplantation brought a breakthrough to the field. The earlier, rather poor results were in a sharp contrast to the first published results of 100% insulin freedom at 1 year. However, later it became clear that the promising initial results decline with time; at around 5 years, only about 10% of the patients maintain freedom from external insulin. Despite that fact, a milestone was set and intensive research started worldwide. New hopes were raised for patients. Modifications of the original protocol have been implemented to improve clinical results; however, islet transplantation remains an experimental procedure to date.

  2. How to revive breakthrough innovation in the pharmaceutical industry. (United States)

    Munos, Bernard H; Chin, William W


    Over the past 20 years, pharmaceutical companies have implemented conservative management practices to improve the predictability of therapeutics discovery and success rates of drug candidates. This approach has often yielded compounds that are only marginally better than existing therapies, yet require larger, longer, and more complex trials. To fund them, companies have shifted resources away from drug discovery to late clinical development; this has hurt innovation and amplified the crisis brought by the expiration of patents on many best-selling drugs. Here, we argue that more breakthrough therapeutics will reach patients only if the industry ceases to pursue "safe" incremental innovation, re-engages in high-risk discovery research, and adopts collaborative innovation models that allow sharing of knowledge and costs among collaborators.

  3. Serum (1,3)-beta-D-glucan is an inefficient marker of breakthrough candidemia. (United States)

    Abe, Masahiro; Kimura, Muneyoshi; Araoka, Hideki; Taniguchi, Shuichi; Yoneyama, Akiko


    The aim of this study was to evaluate the usefulness of serum (1,3)-beta-D-glucan (BDG) for earlier detection of breakthrough candidemia. We reviewed the medical records of patients with candidemia from January 2008 to March 2013. Serum BDG was measured by Wako turbidimetric assay. During the study period, a total of 147 cases of candidemia were identified, and 31 patients met the criteria for breakthrough candidemia. Serum BDG levels were measured in 25 patients with breakthrough candidemia and 67 patients with nonbreakthrough candidemia. Almost all of the patients with breakthrough candidemia had hematological malignancies. More candidemia were caused by non-C. albicans Candida in the breakthrough group than in the nonbreakthrough group (92.0% vs. 61.8%, p = .005). The median BDG value was significantly lower in breakthrough episodes than in non-breakthrough episodes (18.5 pg/ml vs. 90.4 pg/ml, p = .01). Moreover, BDG values under the cutoff was significantly higher in patients with breakthrough candidemia than in those with nonbreakthrough candidemia (44% vs. 19%, p = .03). In summary, BDG alone was insufficient to detect breakthrough candidemia, and candidemia could occur in patients being treated with antifungal agents, even when the BDG value was under the cutoff value. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail:

  4. Population pharmacokinetic modelling of morphine, gabapentin and their combination in the rat

    DEFF Research Database (Denmark)

    Papathanasiou, Theodoros; Juul, Rasmus Vestergaard; Gabel-Jensen, Charlotte


    Purpose The combination of morphine and gabapentin seems promising for the treatment of postoperative and neuropathic pain. Despite the well characterised pharmacodynamic interaction, little is known about possible pharmacokinetic interactions. The aim of this study was to evaluate whether co......-administration of the two drugs leads to modifications of their pharmacokinetic profiles. Methods The pharmacokinetics of morphine, morphine-3-glucuronide and gabapentin were characterised in rats following subcutaneous injections of morphine, gabapentin or their combination. Non-linear mixed effects modelling was applied...... to describe the pharmacokinetics of the compounds and possible interactions. Results The plasma-concentration-time profiles of morphine and gabapentin were best described using a three- and a one-compartment disposition model respectively. Dose dependencies were found for morphine absorption rate...

  5. Pharmacokinetics of Cannabinoids

    Directory of Open Access Journals (Sweden)

    Iain J McGilveray


    Full Text Available Delta-9-tetrahydrocannabinol (Δ-9-THC is the main psychoactive ingredient of cannabis (marijuana. The present review focuses on the pharmacokinetics of THC, but also includes known information for cannabinol and cannabidiol, as well as the synthetic marketed cannabinoids, dronabinol (synthetic THC and nabilone. The variability of THC in plant material (0.3% to 30% leads to variability in tissue THC levels from smoking, which is, in itself, a highly individual process. THC bioavailability averages 30%. With a 3.55% THC cigarette, a peak plasma level of 152±86.3 ng/mL occured approximately 10 min after inhalation. Oral THC, on the other hand, is only 4% to 12% bioavailable and absorption is highly variable. THC is eliminated from plasma in a multiphasic manner, with low amounts detectable for over one week after dosing. A major active 11-hydroxy metabolite is formed after both inhalation and oral dosing (20% and 100% of parent, respectively. THC is widely distributed, particularly to fatty tissues, but less than 1% of an administered dose reaches the brain, while the spleen and body fat are long-term storage sites. The elimination of THC and its many metabolites (from all routes occurs via the feces and urine. Metabolites persist in the urine and feces for severalweeks. Nabilone is well absorbed and the pharmacokinetics, although variable, appear to be linear from oral doses of 1 mg to 4 mg (these doses show a plasma elimination half-life of approximately 2 h. As with THC, there is a high first-pass effect, and the feces to urine ratio of excretion is similar to other cannabinoids. Pharmacokineticpharmacodynamic modelling with plasma THC versus cardiac and psychotropic effects show that after equilibrium is reached, the intensity of effect is proportional to the plasma THC profile. Clinical trials have found that nabilone produces less tachycardia and less euphoria than THC for a similar antiemetic response.

  6. 75 Breakthroughs by the U.S. Department of Energy's National Laboratories; Breakthroughs 2017

    Energy Technology Data Exchange (ETDEWEB)



    Born at a time when the world faced a dire threat, the National Laboratory System protects America through science and technology. For more than 75 years, the Department of Energy’s national laboratories have solved important problems in science, energy and national security. Partnering with industry and academia, the laboratories also drive innovation to advance economic competitiveness and ensure our nation’s future prosperity. Over the years, America's National Laboratories have been changing and improving the lives of millions of people and this expertise continues to keep our nation at the forefront of science and technology in a rapidly changing world. This network of Department of Energy Laboratories has grown into 17 facilities across the country. As this list of breakthroughs attests, Laboratory discoveries have spawned industries, saved lives, generated new products, fired the imagination and helped to reveal the secrets of the universe.

  7. Chronic Pain (United States)

    ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. × ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. ...

  8. Heel pain (United States)

    Pain - heel ... Heel pain is most often the result of overuse. However, it may be caused by an injury. Your heel ... on the heel Conditions that may cause heel pain include: Swelling and pain in the Achilles tendon ...

  9. Flank pain (United States)

    Pain - side; Side pain ... Flank pain can be a sign of a kidney problem. But, since many organs are in this area, other causes are possible. If you have flank pain and fever , chills, blood in the urine, or ...

  10. Managing neuropathic pain in dogs

    Directory of Open Access Journals (Sweden)

    Sarah A Moore


    Full Text Available Disorders of the somatosensory system such as neuropathic pain are common in people with chronic neurologic and musculoskeletal diseases, yet these conditions remain an underappreciated morbidity in our veterinary patients. This is likely because assessment of neuropathic pain in people relies heavily on self-reporting, something our veterinary patients are not able to do. The development of neuropathic pain is a complex phenomenon, and concepts related to it are frequently not addressed in the standard veterinary medical curriculum such that veterinarians may not recognize this as a potential problem in patients. The goals of this review are to discuss basic concepts in the pathophysiology of neuropathic pain, provide definitions for common clinical terms used in association with the condition, and discuss available medical treatment options for dogs with neuropathic pain. The development of neuropathic pain involves key mechanisms such as ectopic afferent nerve activity, peripheral sensitization, central sensitization, impaired inhibitory modulation, and activation of microglia. Treatments aimed at reducing neuropathic pain are targeted at one or more of these mechanisms. Several drugs are commonly used in the veterinary clinical setting to treat neuropathic pain. These include gabapentin, pregabalin, amantadine, and amitriptyline. Proposed mechanisms of action for each drug, and known pharmacokinetic profiles in dogs are discussed. Strong evidence exists in the human literature for the utility of most of these treatments, but clinical veterinary-specific literature is currently limited. Future studies should focus on objective methods to document neuropathic pain and monitor response to therapy in our veterinary patients.

  11. [Nocioceptive pain, neuropathic pain and pain memory]. (United States)

    Montero-Homs, Jordi


    Pain is a cognitive evaluation. Its appearance in the new functional image systems is promising. Nocioceptive pain, usually acute or persistent, is useful to prevent animals from getting injured. Chronic pain is disease per se: It is due to a sensitisation phenomena and pain memory with an important relationship with emotions. Neuropathic pain is a neurological symptom due to a somatosensorial system dysfunction. In this case, axonal ectopic generation of impulses and synaptic hyperexcitability occurs. In persistent cases, sensitisation phenomenon and memory of pain appear together with neuropathic pain. Pain treatment should be physiopathologicaly orientated. Pain units, specialized in analgesic treatment and some invasive techniques, are usually competent in the treatment of nocioceptive pain. Neuropathic pain should have a neurologic diagnosis and treatment. But neurologist need to be more and more interested in the chronic pain related with memory and sensitisation: better knowledge of the cerebral mechanisms in this phenomenon can add to this pathology in our field.

  12. Fear of pain in children and adolescents with neuropathic pain and CRPS (United States)

    Simons, Laura E.


    A significant proportion of children and adolescents with chronic pain endorse elevated pain-related fear. Pain-related fear is associated with high levels of disability, depressive symptoms, and school impairment. Due to faulty nerve signaling, individuals with neuropathic pain and CRPS may be more prone to develop pain-related fear as they avoid use of and neglect the affected body area(s), resulting in exacerbated symptoms, muscle atrophy, maintenance of pain signaling, and ongoing pain-related disability. Not surprisingly, effective treatments for elevated pain-related fears involve exposure to previously avoided activities to down-regulate incorrect pain signaling. In the context of intensive interdisciplinary pain treatment of youth with neuropathic pain, decreasing pain-related fear is associated with improved physical and psychological functioning, while high initial pain-related fear is a risk factor for less treatment responsiveness. An innovative approach to targeting pain-related fear as well as evidence of a neural response to treatment involving decoupling of the amygdala with key fear circuits in youth with CRPS suggest breakthroughs in our ability to ameliorate these issues. PMID:26785161

  13. A review of factors explaining variability in fentanyl pharmacokinetics; focus on implications for cancer patients

    NARCIS (Netherlands)

    Kuip, E.J.M.; Zandvliet, M.L.; Koolen, S.L.; Mathijssen, R.H.; Rijt, C.C. van der


    Fentanyl is a strong opioid that is available for various administration routes, and which is widely used to treat cancer-related pain. Many factors influence the fentanyl pharmacokinetics leading to a wide inter- and intrapatient variability. This systematic review summarizes multiple studied

  14. Treatment with subcutaneous and transdermal fentanyl: results from a population pharmacokinetic study in cancer patients

    NARCIS (Netherlands)

    Oosten, A.W.; Abrantes, J.A.; Jonsson, S.; Bruijn, P. de; Kuip, E.J.M.; Falcao, A.; Rijt, C.C. van der; Mathijssen, R.H.


    PURPOSE: Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the

  15. Treatment with subcutaneous and transdermal fentanyl: Results from a population pharmacokinetic study in cancer patients

    NARCIS (Netherlands)

    A.W. Oosten (Astrid); J.A. Abrantes (João A.); S. Jönsson (Siv); P. de Bruijn (Peter); E.J.M. Kuip (Evelien); A. Falcão (Amílcar); C.C.D. van der Rijt (Carin); A.H.J. Mathijssen (Ron)


    textabstractPurpose: Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we

  16. The relationship between the pharmacokinetics and pharmacodynamics of spinal opioids. Minireview based on a doctoral thesis. (United States)

    Sjöström, S


    Spinal opioids have been used clinically since the late seventies to treat acute, traumatic, obstetric and chronic pain. In this article the influence of the pharmacokinetics on the dynamics of intrathecal and epidural opioid administration are discussed with reference to current knowledge.

  17. Multiple intravenous doses of paracetamol result in a predictable pharmacokinetic profile in very preterm infants

    NARCIS (Netherlands)

    van Ganzewinkel, C.; Derijks, L.; Anand, K.J.S.; van Lingen, R.A.; Neef, C.; Kramer, B.W.; Andriessen, P.


    AimThe therapeutic options available to treat neonatal pain are limited, and one alternative for nonopioid systemic treatment is paracetamol. However, pharmacokinetic data from prolonged administration of intravenous paracetamol in neonates are limited. The aim of this study was to present

  18. Translational pain research: evaluating analgesic effect in experimental visceral pain models

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Andresen, Trine; Christrup, Lona Louring


    analgesics in detail. In combination with pharmacokinetic studies and objective assessment such as electroencephalography, new information regarding a given drug substance and its effects can be obtained. Results from experimental human visceral pain research can bridge the gap in knowledge between animal......Deep visceral pain is frequent and presents major challenges in pain management, since its pathophysiology is still poorly understood. One way to optimize treatment of visceral pain is to improve knowledge of the mechanisms behind the pain and the mode of action of analgesic substances. This can...... be achieved through standardized experimental human pain models. Experimental pain models in healthy volunteers are advantageous for evaluation of analgesic action, as this is often difficult to assess in the clinic because of confounding factors such as sedation, nausea and general malaise. These pain models...

  19. Calculation of Breakthrough Time in Oil Recovery by the Use of ...

    African Journals Online (AJOL)

    Recent studies indicate that percolation models may be be used to predict breakthrough time by the use of the fractal dimension of the shortest path. The paper shows that better predictions can be made about the breakthrough time when the actual fractal dimension of the boundaries of the oil reservoirs are calculated.

  20. Alternative sample-introduction technique to avoid breakthrough in gradient-elution liquid chromatography of polymers

    NARCIS (Netherlands)

    Reingruber, E.; Bedani, F.; Buchberger, W.; Schoenmakers, P.


    Gradient-elution liquid chromatography (GELC) is a powerful tool for the characterization of synthetic polymers. However, gradient-elution chromatograms often suffer from breakthrough phenomena. Breakthrough can be averted by using a sample solvent as weak as the mobile phase. However, this approach

  1. The New Three Rs: Research, Reading, and Results. Breakthrough to Literacy[TM]. (United States)

    McGraw-Hill Companies, New York, NY. Educational and Professional Publishing Group.

    Research in school districts throughout the United States shows that children who use "Breakthrough to Literacy" achieve significant and lasting improvement in their reading skills. At virtually every site studied where implementation criteria were met, children who participated in "Breakthrough" demonstrated marked increases…

  2. Differences in characteristics between first and breakthrough neutropenic fever after chemotherapy in patients with hematologic disease

    Directory of Open Access Journals (Sweden)

    Eun Young Nam


    Conclusion: It is concluded that the epidemiological profile of breakthrough neutropenic fever is different from that of first episode fever. These data reinforce the view that pooled reporting of neutropenic fever may be misleading, and that clinicians should approach breakthrough fever as a distinct entity.

  3. Recent advances in the use of opioids for cancer pain

    Directory of Open Access Journals (Sweden)

    Joanne Droney


    Full Text Available Joanne Droney, Julia RileyPalliative Medicine Department, Royal Marsden Hospital, London, UKAbstract: Opioids are the mainstay of treatment for moderate to severe cancer pain. In recent years there have been many advances in the use of opioids for cancer pain. Availability and consumption of opioids have increased and opioids other than morphine (including methadone, fentanyl, oxycodone have become more widely used. Inter-individual variation in response to opioids has been identified as a significant challenge in the management of cancer pain. Many studies have been published demonstrating the benefits of opioid switching as a clinical maneuver to improve tolerability. Constipation has been recognized as a significant burden in cancer patients on opioids. Peripherally restricted opioid antagonists have been developed for the prevention and management of opioid induced constipation. The phenomenon of breakthrough pain has been characterized and novel modes of opioid administration (transmucosal, intranasal, sublingual have been explored to facilitate improved management of breakthrough cancer pain. Advances have also been made in the realm of molecular biology. Pharmacogenetic studies have explored associations between clinical response to opioids and genetic variation at a DNA level. To date these studies have been small but future research may facilitate prospective prediction of response to individual drugs.Keywords: opioids, cancer, pain, pharmacogenetics, constipation, breakthrough pain

  4. From Islamicizing the Sciences to Strategizing for Muslims’ Scientific Breakthrough

    Directory of Open Access Journals (Sweden)



    Full Text Available At inception, science and religion were seen as poles apart and so science was vehemently kicked against by religious leaders. Islam later came to bridge the gap between religion and science only to be later hijacked by the Western world and so science was rewritten from a purely materialist point of view; hence, experts in modern science became over-confident and arrogant to have relegated religion to the lowest ebb and looked down upon any knowledge which could not be scientifically proved. However attempts are being made to reconcile religion and science by Muslim reformers. These attempts are not without their shortcomings, hence the need for Islamization of the sciences for them to conform to the Islamic principle of unity of knowledge. However, the present researcher feels that there should be a step forward from the contemporary approaches to Islamicizing the sciences in form of colouring the Western scientific discoveries Islam, to making their own scientific breakthroughs, the type which immortalized Muslim scientists of the Islam’s golden ages. Without this, Muslims will continue to be mere consumers of the Western products. The strategy for the Ummah to achieve this is suggested in this paper.

  5. Structural mechanism of GPCR-arrestin interaction: recent breakthroughs. (United States)

    Park, Ji Young; Lee, Su Youn; Kim, Hee Ryung; Seo, Min-Duk; Chung, Ka Young


    G protein-coupled receptors (GPCRs) are a major membrane receptor family with important physiological and pathological functions. In the classical signaling pathway, ligand-activated GPCRs couple to G proteins, thereby inducing G protein-dependent signaling pathways and phosphorylation by G protein-coupled receptor kinases (GRKs). This leads to an interaction with arrestins, which results in GPCR desensitization. Recently, non-classical GPCR signaling pathways, mediated by GPCR-bound arrestins, have been identified. Consequently, arrestins play important roles in GPCR signaling not only with respect to desensitization but also in relation to G protein-independent signal transduction. These findings have led to efforts to develop functionally biased (i.e. signal transduction biased) GPCR-targeting drugs. One of these efforts is aimed at understanding the structural mechanism of functionally biased GPCR signaling, which includes understanding the G protein-selectivity or arrestin-selectivity of GPCRs. This goal has not yet been achieved; however, great progress has been made during the last 3 years toward understanding the structural mechanism of GPCR-mediated arrestin activation. This review will discuss the recent breakthroughs in the conformational understanding of GPCR-arrestin interaction.

  6. Clean Energy Innovation: Sources of Technical and Commercial Breakthroughs

    Energy Technology Data Exchange (ETDEWEB)

    Perry, T. D., IV; Miller, M.; Fleming, L.; Younge, K.; Newcomb, J.


    Low-carbon energy innovation is essential to combat climate change, promote economic competitiveness, and achieve energy security. Using U.S. patent data and additional patent-relevant data collected from the Internet, we map the landscape of low-carbon energy innovation in the United States since 1975. We isolate 10,603 renewable and 10,442 traditional energy patents and develop a database that characterizes proxy measures for technical and commercial impact, as measured by patent citations and Web presence, respectively. Regression models and multivariate simulations are used to compare the social, institutional, and geographic drivers of breakthrough clean energy innovation. Results indicate statistically significant effects of social, institutional, and geographic variables on technical and commercial impacts of patents and unique innovation trends between different energy technologies. We observe important differences between patent citations and Web presence of licensed and unlicensed patents, indicating the potential utility of using screened Web hits as a measure of commercial importance. We offer hypotheses for these revealed differences and suggest a research agenda with which to test these hypotheses. These preliminary findings indicate that leveraging empirical insights to better target research expenditures would augment the speed and scale of innovation and deployment of clean energy technologies.

  7. Recent breakthroughs on C-2U: Norman’s legacy

    Energy Technology Data Exchange (ETDEWEB)

    Binderbauer, M. W.; Tajima, T.; Tuszewski, M.; Smirnov, A.; Gota, H.; Garate, E.; Barnes, D.; Deng, B. H.; Trask, E.; Yang, X.; Putvinski, S.; Andow, R.; Bolte, N.; Bui, D. Q.; Ceccherini, F.; Clary, R.; Cheung, A. H.; Conroy, K. D.; Dettrick, S. A.; Douglass, J. D. [Tri Alpha Energy, Inc., P.O. Box 7010, Rancho Santa Margarita, CA 92688 (United States); and others


    Conventional field-reversed configurations (FRC) face notable stability and confinement concerns, which can be ameliorated by introducing and maintaining a significant fast ion population in the system. This is the conjecture first introduced by Norman Rostoker multiple decades ago and adopted as the central design tenet in Tri Alpha Energy’s advanced beam driven FRC concept. In fact, studying the physics of such neutral beam (NB) driven FRCs over the past decade, considerable improvements were made in confinement and stability. Next to NB injection, the addition of axially streaming plasma guns, magnetic end plugs, as well as advanced surface conditioning lead to dramatic reductions in turbulence driven losses and greatly improved stability. In turn, fast ion confinement improved significantly and allowed for the build-up of a dominant fast particle population. This recently led to the breakthrough of sustaining an advanced beam driven FRC, thereby demonstrating successful maintenance of trapped magnetic flux, plasma dimensions and total pressure inventory for times much longer than all characteristic system time scales and only limited by hardware and electric supply constraints.

  8. Parameterizing the Spatial Markov Model From Breakthrough Curve Data Alone (United States)

    Sherman, Thomas; Fakhari, Abbas; Miller, Savannah; Singha, Kamini; Bolster, Diogo


    The spatial Markov model (SMM) is an upscaled Lagrangian model that effectively captures anomalous transport across a diverse range of hydrologic systems. The distinct feature of the SMM relative to other random walk models is that successive steps are correlated. To date, with some notable exceptions, the model has primarily been applied to data from high-resolution numerical simulations and correlation effects have been measured from simulated particle trajectories. In real systems such knowledge is practically unattainable and the best one might hope for is breakthrough curves (BTCs) at successive downstream locations. We introduce a novel methodology to quantify velocity correlation from BTC data alone. By discretizing two measured BTCs into a set of arrival times and developing an inverse model, we estimate velocity correlation, thereby enabling parameterization of the SMM in studies where detailed Lagrangian velocity statistics are unavailable. The proposed methodology is applied to two synthetic numerical problems, where we measure all details and thus test the veracity of the approach by comparison of estimated parameters with known simulated values. Our results suggest that our estimated transition probabilities agree with simulated values and using the SMM with this estimated parameterization accurately predicts BTCs downstream. Our methodology naturally allows for estimates of uncertainty by calculating lower and upper bounds of velocity correlation, enabling prediction of a range of BTCs. The measured BTCs fall within the range of predicted BTCs. This novel method to parameterize the SMM from BTC data alone is quite parsimonious, thereby widening the SMM's practical applicability.

  9. Breakthrough characteristics of gas absorption in a packed column

    International Nuclear Information System (INIS)

    Shitanda, Shoji; Fukada, Satoshi; Koto, Kenji; Mitsuishi, Nobuo


    In nuclear industries, the operations to collect or recover various radioactive and non-radioactive gases with a number of absorption or adsorption reagents are practically utilized or planned. Specifically in the operations of recovering hydrogen isotopes, the direct collecting method with active metals such as uranium, zirconium (Zr) and yttrium is watched with keen interest. In this study, the capability of recovering hydrogen by means of Zr was investigated through the estimation of rate-determining step, by flowing the gas mixture of hydrogen and argon after activating metallic Zr under the condition of high temperature and high vacuum, and by determining overall mass transfer coefficient from the absorption breakthrough curves. The details of a packed column and the flowsheet are also described, and the deterioration of Zr powder is considered. That is, the diffusion speed and absorbing reaction speed of hydrogen in Zr particles are supposed to be slow and dominant in mass transfer speed. Further, since gas mixture does not simply diffuse in Zr particles, but the reaction plane seems to move toward the center from the surface in the case of Zr, different from general adsorbents, the moving speed seems to give large effect on the rate-determining step. It is ensured that the hydrogen absorption with Zr powder is so active that hydrogen in gas flow can easily be recovered, and its separation from other gases can be effectively carried out by the desorption of hydrogen from Zr powder by heating it in vacuum. (Wakatsuki, Y.)

  10. Funding breakthrough therapies: A systematic review and recommendation. (United States)

    Hanna, E; Toumi, M; Dussart, C; Borissov, B; Dabbous, O; Badora, K; Auquier, P


    Advanced therapy medicinal products (ATMPs) are innovative therapies likely associated with high prices. Payers need guidance to create a balance between ensuring patient access to breakthrough therapies and maintaining the financial sustainability of the healthcare system. The aims of this study were to identify, define, classify and compare the approaches to funding high-cost medicines proposed in the literature, to analyze their appropriateness for ATMP funding and to suggest an optimal funding model for ATMPs. Forty-eight articles suggesting new funding models for innovative high-cost therapies were identified. The models were classified into 3 groups: financial agreement, health outcomes-based agreement and healthcoin. Financial agreement encompassed: discounts, rebates, price and volume caps, price-volume agreements, loans, cost-plus price, intellectual-based payment and fund-based payment. Health outcomes-based agreements were defined as agreements between manufacturers and payers based on drug performance, and were divided into performance-based payment and coverage with evidence development. Healthcoin described a new suggested tradeable currency used to assign monetary value to incremental outcomes. With a large number of ATMPs in development, it is time for stakeholders to start thinking about new pathways and funding strategies for these innovative high-cost therapies. An "ATMP-specific fund" may constitute a reasonable solution to ensure rapid patient access to innovation without threatening the sustainability of the health care system. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Pharmacokinetic studies of neuromuscular blocking agents: Good Clinical Research Practice (GCRP)

    DEFF Research Database (Denmark)

    Viby-Mogensen, J.; Østergaard, D.; Donati, F.


    Good Clinical Research Practice (GCRP), neuromuscular blocking agents, pharmacokinetics, pharmacokinetic/pharmacodynamic modeling, population pharmacokinetics, statistics, study design......Good Clinical Research Practice (GCRP), neuromuscular blocking agents, pharmacokinetics, pharmacokinetic/pharmacodynamic modeling, population pharmacokinetics, statistics, study design...

  12. Raltegravir Pharmacokinetics during Pregnancy (United States)

    Watts, D. Heather; Stek, Alice; Best, Brookie M.; Wang, Jiajia; Capparelli, Edmund V.; Cressey, Tim R.; Aweeka, Francesca; Lizak, Patty; Kreitchmann, Regis; Burchett, Sandra K.; Shapiro, David E.; Hawkins, Elizabeth; Smith, Elizabeth; Mirochnick, Mark


    Objective We evaluated the pharmacokinetics (pk) of raltegravir in HIV-infected women during pregnancy and postpartum. Methods IMPAACT 1026s is an on-going prospective study of antiretroviral pk during pregnancy (NCT00042289). Women receiving 400 mg raltegravir twice daily in combination antiretroviral therapy had intensive steady state 12-hour pk profiles performed during pregnancy and at 6–12 weeks postpartum. Targets were trough concentration above 0.035 µg/mL, the estimated tenth percentile in non-pregnant historical controls. Results Median raltegravir AUC was 6.6 µg*hr/mL for second trimester (n= 16), 5.4 µg*hr/mL for third trimester (n=41), and 11.6 µg*hr/mL postpartum (n= 38) (p=0.03 pp vs 2nd trimester, p=0.001 pp vs third trimester). Trough concentrations were above the target in 69%, 80%, and 79% of second trimester, third trimester and postpartum subjects respectively, with wide variability (raltegravir concentrations was 1.5. HIV RNA levels were raltegravir AUC was reduced by approximately 50% during pregnancy; trough concentrations were frequently below target both during late pregnancy and postpartum. Raltegravir readily crossed the placenta. High rates of viral suppression at delivery and the lack of a clear relationship between raltegravir concentration and virologic effect in nonpregnant adults suggest that despite the decreased exposure during pregnancy, a higher dose is not necessary. PMID:25162818

  13. Modelling delays in pharmacokinetics

    International Nuclear Information System (INIS)

    Farooqi, Z.H.; Lambrecht, R.M.


    Linear system analysis has come to form the backbone of pharmacokinetics. Natural systems usually involve time delays, thus models incorporating them would be an order closer approximation to the real world compared to those that do not. Delays may be modelled in several ways. The approach considered in this study is to have a discrete-time delay dependent rate with the delay respresenting the duration between the entry of a drug into a compartment and its release in some form (may be as a metabolite) from the compartment. Such a delay may be because of one or more of several physiological reasons, like, formation of a reservoir, slow metabolism, or receptor binding. The mathematical structure this gives rise to is a system of delay-differential equations. Examples are given of simple one and two compartment systems with drugs like bumetanide, carbamazepine, and quinolone-caffeine interaction. In these examples generally a good fit is obtained and the suggested models form a good approximation. 21 refs., 6 figs

  14. Pharmacokinetics of mequindox after intravenous and intramuscular ...

    African Journals Online (AJOL)


    Studies on the pharmacokinetics of quinocetone in pigs and chickens. Acta Veterinaria et Zootechnica Sinica. 34: 94-97. Li JY, Zhou XZ, Li JS, Zhao RC, Miao XL, Zhang JY (2005). The pharmacokinetics of quinocetone in pigs. Chin. J. Vet. Drug, 39: 1-3. Liu CX (2003). Practice pharmacokinetics, 1st ed. China Science and.

  15. Cancer pain

    International Nuclear Information System (INIS)

    Swerdlow, M.; Ventafridda, V.


    This book contains 13 chapters. Some of the chapter titles are: Importance of the Problem; Neurophysiology and Biochemistry of Pain; Assessment of Pain in Patients with Cancer; Drug Therapy; Chemotherapy and Radiotherapy for Cancer Pain; Sympton Control as it Relates to Pain Control; and Palliative Surgery in Cancer Pain Treatment

  16. Technical breakthroughs in the wearable artificial kidney (WAK). (United States)

    Gura, Victor; Macy, Alexandra S; Beizai, Masoud; Ezon, Carlos; Golper, Thomas A


    The wearable artificial kidney (WAK) has been a holy grail in kidney failure for decades. Described herein are the breakthroughs that made possible the creation of the WAK V1.0 and its advanced versions V 1.1 and 1.2. The battery-powered WAK pump has a double channel pulsatile counter phase flow. This study clarifies the role of pulsatile blood and dialysate flow, a high-flux membrane with a larger surface area, and the optimization of the dialysate pH. Flows and clearances from the WAK pump were compared with conventional pumps and with gravity steady flow. Raising dialysate pH to 7.4 increased adsorption of ammonia. Clearances were higher with pulsatile flow as compared with steady flow. The light WAK pump, geometrically suitable for wearability, delivered the same clearances as larger and heavier pumps that cannot be battery operated. Beta(2) microglobulin (beta(2)M) was removed from human blood in vitro. Activated charcoal adsorbed most beta(2)M in the dialysate. The WAK V1.0 delivered an effective creatinine clearance of 18.5 +/- 3.2 ml/min and the WAK V1.1 27.0 +/- 4.0 ml/min in uremic pigs. Half-cycle differences between blood and dialysate, alternating transmembrane pressures (TMP), higher amplitude pulsations, and a push-pull flow increased convective transport. This creates a yet undescribed type of hemodiafiltration. Further improvements were achieved with a larger surface area high-flux dialyzer and a higher dialysate pH. The data suggest that the WAK might be an efficient way of providing daily dialysis and optimizing end stage renal disease (ESRD) treatment.

  17. Enabling Breakthrough Kinetic Simulations of the Magnetosphere Using Petascale Computing (United States)

    Vu, H. X.; Karimabadi, H.; Omelchenko, Y.; Tatineni, M.; Majumdar, A.; Krauss-Varban, D.; Dorelli, J.


    Currently global magnetospheric simulations are predominantly based on single-fluid magnetohydrodynamics (MHD). MHD simulations have proven useful in studies of the global dynamics of the magnetosphere with the goal of predicting eminent features of substorms and other global events. But it is well known that the magnetosphere is dominated by ion kinetic effects, which is ignored in MHD simulations, and many key aspects of the magnetosphere relating to transport and structure of boundaries await global kinetic simulations. We are using our recent innovations in hybrid (electron fluid, kinetic ions) simulations, as being developed in our Hybrid3D (H3D) code, and the power of massively parallel machines to make, breakthrough 3D global kinetic simulations of the magnetosphere. The innovations include (i) multi-zone (asynchronous) algorithm, (ii) dynamic load balancing, and (iii) code adaptation and optimization to large number of processors. In this presentation we will show preliminary results of our progress to date using from 512 to over 8192 cores. In particular, we focus on what we believe to be the first demonstration of the formation of a flux rope in 3D global hybrid simulations. As in the MHD simulations, the resulting flux rope has a very complex structure, wrapping up field lines from different regions and appears to be connected on at least one end to Earth. Magnetic topology of the FTE is examined to reveal the existence of several separators (3D X-lines). The formation and growth of this structure will be discussed and spatial profile of the magnetic and plasma variables will be compared with those from MHD simulations.

  18. [Future directions of neurology - breakthrough to the next stage ]. (United States)

    Tsuji, Shoji


    The 51st Annual Meeting of the Japanese Society of Neurology was held in Tokyo (Tokyo International Forum) from Thursday, May 20 to Saturday, May 22, 2010 with as many as 5,471 attendants. Our Society has been celebrating its 50th anniversary during the period from 2009 through 2010. At the 51st Annual Meeting in 2010, we looked toward the future, as we celebrate our 50th anniversary together with distinguished guests closely related to our Society. The theme for the 51st Annual Meeting was set as "Future of Neurology-Breakthrough to the next stage-." As represented in the theme, I hope that the Annual Meeting provided an excellent opportunity for all of us to look ahead to the future of Neurology and our Society in the next half-century. We have achieved tremendous advances in better understanding neurological diseases and developing more efficacious treatment over the last half century. Great strides have been made in all areas, of which diagnostic imaging, molecular genetics, immunology and physiology are just a few examples, and understanding of diseases has similarly taken a great leap forward. In Japan, the aging of society coupled with the declining birthrate has placed ever-increasing expectations on neurologists to provide better care for dementia, cerebrovascular disorders and neurodegenerative diseases. Given this situation our Society is required to provide outstanding education in both the pre- and post-graduate context, and, furthermore, to ensure that excellent training programs are available for young neurologists preparing for Board certification. Looking towards the future of neurology, we should continue to anticipate new, ground-breaking achievements for better understanding neurological diseases and establishing more effective treatment through our ongoing endeavors.

  19. Pharmacokinetics of macrolides in foals. (United States)

    Villarino, N; Martín-Jiménez, T


    Macrolides are used for treatment of pneumonia and extrapulmonary conditions caused by Rhodococcus equi. In foals, macrolides have an extraordinary capacity to accumulate in different lung tissue compartments. These drugs show unique pharmacokinetic features such as rapid and extensive distribution and long persistence in pulmonary epithelial lining fluid (PELF) and bronchoalveolar lavage (BAL) cells from foals. This article reviews the pharmacokinetic characteristics of erythromycin, azithromycin, clarithromycin, tulathromycin, telithromycin, gamithromycin, and tilmicosin in foals, with emphasis on PELF and BAL cell concentrations. © 2012 Blackwell Publishing Ltd.

  20. Ofloxacin pharmacokinetics in renal failure.


    Fillastre, J P; Leroy, A; Humbert, G


    The pharmacokinetics of ofloxacin were investigated in 12 normal subjects and 21 uremic patients after the administration of a single oral 200-mg dose. An open three-compartment body model was used to calculate ofloxacin pharmacokinetic parameters. In healthy subjects, the peak plasma level averaged 2.24 +/- 0.90 micrograms/ml and was obtained at 0.83 +/- 0.31 h. The absorption rate constant was 4.22 +/- 1.64 h-1. The terminal half-life was 7.86 +/- 1.81 h. The apparent volume of distribution...

  1. Back Pain (United States)

    ... Accessed May 29, 2015. Adult acute and subacute low back pain. Bloomington, Minn.: Institute for Clinical Systems Improvement. Accessed June ...

  2. Abdominal Pain (United States)

    ... to ease your pain. For instance, eat smaller meals if your pain is accompanied by indigestion. Avoid ... . Mayo Clinic Footer Legal Conditions and ...

  3. Knee pain (United States)

    Pain - knee ... Knee pain can have different causes. Being overweight puts you at greater risk for knee problems. Overusing your knee can trigger knee problems that cause pain. If you have a history of arthritis, it ...

  4. Breast pain (United States)

    Pain - breast; Mastalgia; Mastodynia; Breast tenderness ... There are many possible causes for breast pain. For example, changes in the level of of hormones during menstruation or pregnancy often cause breast pain. Some swelling and tenderness just before ...

  5. Foot pain (United States)

    Pain - foot ... Foot pain may be due to: Aging Being on your feet for long periods of time Being overweight A ... sports activity Trauma The following can cause foot pain: Arthritis and gout . Common in the big toe, ...

  6. Eye pain (United States)

    Ophthalmalgia; Pain - eye ... Pain in the eye can be an important symptom of a health problem. Make sure you tell your health care provider if you have eye pain that does not go away. Tired eyes or ...

  7. Wrist pain (United States)

    Pain - wrist; Pain - carpal tunnel; Injury - wrist; Arthritis - wrist; Gout - wrist; Pseudogout - wrist ... Carpal tunnel syndrome: A common cause of wrist pain is carpal tunnel syndrome . You may feel aching, ...

  8. Ankle pain (United States)

    Pain - ankle ... Ankle pain is often due to an ankle sprain. An ankle sprain is an injury to the ligaments, which ... the joint. In addition to ankle sprains, ankle pain can be caused by: Damage or swelling of ...

  9. Postoperative pain

    DEFF Research Database (Denmark)

    Kehlet, H; Dahl, J B


    Treatment of postoperative pain has not received sufficient attention by the surgical profession. Recent developments concerned with acute pain physiology and improved techniques for postoperative pain relief should result in more satisfactory treatment of postoperative pain. Such pain relief may...... also modify various aspects of the surgical stress response, and nociceptive blockade by regional anesthetic techniques has been demonstrated to improve various parameters of postoperative outcome. It is therefore stressed that effective control of postoperative pain, combined with a high degree...

  10. Period Pain (United States)

    ... pain relievers such as nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs include ibuprofen and naproxen. Besides relieving pain, NSAIDs reduce the amount of prostaglandins that your uterus ...

  11. Risk Factors for Breakthrough Pneumocystis carinii Pneumonia on Aerosol Pentamidine Prophylaxis

    Directory of Open Access Journals (Sweden)

    RA McIvor


    Full Text Available OBJECTIVE: To identify baseline characteristics of human immunodeficiency virus (HIV-infected individuals on aerosol pentamidine for Pneumocystis carinii prophylaxis that are predictive of subsequent breakthrough Pneumocystis carinii pneumonia (PCP.

  12. Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes–2

    Directory of Open Access Journals (Sweden)

    Diego Muñoz-Torrero


    Full Text Available Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials, which are published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...

  13. Low cost continuous femoral nerve block for relief of acute severe cancer related pain due to pathological fracture femur

    Directory of Open Access Journals (Sweden)

    Rachel Cherian Koshy


    Full Text Available Pathological fractures in cancer patient cause severe pain that is difficult to control pharmacologically. Even with good pain relief at rest, breakthrough and incident pain can be unmanageable. Continuous regional nerve blocks have a definite role in controlling such intractable pain. We describe two such cases where severe pain was adequately relieved in the acute phase. Continuous femoral nerve block was used as an efficient, cheap and safe method of pain relief for two of our patients with pathological fracture femur. This method was proved to be quite efficient in decreasing the fracture-related pain and improving the level of well being.

  14. Breakthrough disease during interferon-[beta] therapy in MS: No signs of impaired biologic response

    DEFF Research Database (Denmark)

    Hesse, D; Krakauer, M; Lund, H


    Disease activity is highly variable in patients with multiple sclerosis (MS), both untreated and during interferon (IFN)-beta therapy. Breakthrough disease is often regarded as treatment failure; however, apart from neutralizing antibodies (NAbs), no blood biomarkers have been established...... as reliable indicators of treatment response, despite substantial, biologically measurable effects. We studied the biologic response to treatment in a cohort of NAb-negative patients to test whether difference in responsiveness could segregate patients with and without breakthrough disease during therapy....

  15. Statistical characteristics of breakthrough discoveries in science using the metaphor of black and white swans (United States)

    Zeng, Carl J.; Qi, Eric P.; Li, Simon S.; Stanley, H. Eugene; Ye, Fred Y.


    A publication that reports a breakthrough discovery in a particular scientific field is referred to as a ;black swan;, and the most highly-cited papers previously published in the same field ;white swans;. Important scientific progress occurs when ;white swans; meet a ;black swan;, and the citation patterns of the ;white swans; change. This metaphor combines scientific discoveries and scientometric data and suggests that breakthrough scientific discoveries are either ;black swans; or ;grey-black swans;.

  16. Treatment of Breakthrough and Refractory Chemotherapy-Induced Nausea and Vomiting


    Navari, Rudolph M.


    Despite significant progress in the prevention of chemotherapy-induced nausea and vomiting (CINV) with the introduction of new antiemetic agents, 30–50% of patients receiving moderately or highly emetogenic chemotherapy (MEC or HEC) and guideline directed prophylactic antiemetics develop breakthrough CINV. International guidelines recommend the treatment of breakthrough CINV with an agent from a drug class that was not used in the prophylactic antiemetic regimen and recommend using the breakt...

  17. Back Pain with Leg Pain. (United States)

    Vulfsons, Simon; Bar, Negev; Eisenberg, Elon


    The clinical diagnostic dilemma of low back pain that is associated with lower limb pain is very common. In relation to back pain that radiates to the leg, the International Association for the Study of Pain (IASP) states: "Pain in the lower limb should be described specifically as either referred pain or radicular pain. In cases of doubt no implication should be made and the pain should be described as pain in the lower limb." Bogduks' editorial in the journal PAIN (2009) helps us to differentiate and define the terms somatic referred pain, radicular pain, and radiculopathy. In addition, there are other pathologies distal to the nerve root that could be relevant to patients with back pain and leg pain such as plexus and peripheral nerve involvement. Hence, the diagnosis of back pain with leg pain can still be challenging. In this article, we present a patient with back and leg pain. The patient appears to have a radicular pain syndrome, but has no neurological impairment and shows signs of myofascial involvement. Is there a single diagnosis or indeed two overlapping syndromes? The scope of our article encompasses the common diagnostic possibilities for this type of patient. A discussion of treatment is beyond the scope of this article and depends on the final diagnosis/diagnoses made.

  18. [Pharmacokinetics and pharmacodynamics of ceftaroline]. (United States)

    Grau, Santiago; Sorlí, Luisa; Luque, Sonia


    Ceftaroline is administered intravenously in the form of a prodrug, ceftaroline fosamil, which is rapidly hydrolyzed by plasma phosphatases to its active form, ceftaroline. In general, the pharmacokinetics of ceftaroline differ little from those of other cephalosporins. A proportional increase in both the peak plasma concentration (Cmax) and the area under the curve (AUC) have been observed when the drug is administered in increasing doses, which demonstrates its linear pharmacokinetics. Half the dose of ceftaroline is excreted actively through the kidneys. The pharmacokinetic parameters of ceftaroline administered through the intramuscular route in diverse animal species were similar to those observed when the drug was administered intravenously and consequently clinical research into ceftaroline administered through this alternative route would be appropriate. Patients with moderate-severe alterations of renal function and those undergoing hemodialysis require dose adjustments. There is limited experience of the pharmacokinetics of ceftaroline in children, which has given rise to several schedules stratified by age groups. The pharmacodynamics of the drug have been studied in models of animal infection and in in vitro infections caused mainly by Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA], strains with intermediate vancomycin sensitivity [hVISA or hGISA]) and by Streptococcus pneumoniae strains with distinct sensitivities to penicillin. Because ceftaroline is a time-dependent antibiotic, the most widely studied pharmacokinetic/pharmacodynamic (PK/PD) indicator is the time interval during which drug concentrations are maintained above the minimum inhibitory concentration (MIC), calculated both as total drug (T > MIC) and as free fraction of the drug (fT > MIC). The PK/PD simulations carried out in these models, developed on the basis of the concentrations obtained with routine doses in humans, have shown that ceftaroline has a good PK

  19. Prediction of ion-exchange column breakthrough curves by constant-pattern wave approach. (United States)

    Lee, I-Hsien; Kuan, Yu-Chung; Chern, Jia-Ming


    The release of heavy metals from industrial wastewaters represents one of major threats to environment. Compared with chemical precipitation method, fixed-bed ion-exchange process can effectively remove heavy metals from wastewaters and generate no hazardous sludge. In order to design and operate fixed-bed ion-exchange processes successfully, it is very important to understand the column dynamics. In this study, the column experiments for Cu2+/H+, Zn2+/H+, and Cd2+/H+ systems using Amberlite IR-120 were performed to measure the breakthrough curves under varying operating conditions. The experimental results showed that total cation concentration in the mobile-phase played a key role on the breakthrough curves; a higher feed concentration resulted in an earlier breakthrough. Furthermore, the column dynamics was also predicted by self-sharpening and constant-pattern wave models. The self-sharpening wave model assuming local ion-exchange equilibrium could provide a simple and quick estimation for the breakthrough volume, but the predicted breakthrough curves did not match the experimental data very well. On the contrary, the constant-pattern wave model using a constant driving force model for finite ion-exchange rate provided a better fit to the experimental data. The obtained liquid-phase mass transfer coefficient was correlated to the flow velocity and other operating parameters; the breakthrough curves under varying operating conditions could thus be predicted by the constant-pattern wave model using the correlation.

  20. An international survey of cancer pain characteristics and syndromes. IASP Task Force on Cancer Pain. International Association for the Study of Pain. (United States)

    Caraceni, A; Portenoy, R K


    The optimal assessment of cancer pain includes a detailed description of pain characteristics and classification by both syndrome and likely mechanisms. In the clinical setting, the interpretation of this information is aided by knowledge of the available clinical experiences on these aspects of the pain. Unfortunately, existing data are limited. There have been few large surveys of cancer pain characteristics and syndromes, and comparative data from patients in different parts of the world are entirely lacking. To better define the characteristics of cancer pain syndromes the Task Force on Cancer Pain of the International Association for the Study of Pain (IASP) conducted a prospective, cross-sectional, international, multicenter survey of pain specialists and their patients. From a total of 100 clinicians who described themselves as cancer pain practitioners in the IASP membership directory, 51 agreed to participate in the survey and a total of 58 provided data. These clinicians resided in 24 countries and evaluated a total of 1095 patients with severe cancer pain mostly requiring opioid medication, using a combination of patient-rated and observer-rated measures. The patient-rated scales comprised a pain intensity measure chosen from the brief pain inventory. The observer-rated information included demographic and tumor-related data, and responses on checklists of pain syndromes and pathophysiologies. Patients were heterogeneous in terms of demographics and tumor-related information. More than 76% had a Kamofsky performance status score or = 7 on a 10-point numeric scale. The factors that were univariately associated with higher pain intensity included the presence of breakthrough pain, somatic pain or neuropathic pain, age younger than 60 years, and lower performance status score. A multivariate model suggested that the presence of breakthrough pain, somatic pain, and lower performance status were the most important predictors of intense pain. Pains that were

  1. Muscle pain

    African Journals Online (AJOL)

    Key Summary Points. • Muscle pain, known as myalgia, can be in one targeted area or across many muscles, occurring with overexertion or overuse of these muscles. • Pain can be classified as acute or chronic pain and further categorized as nociceptive or neuropathic. • Causes of muscle pain include stress, physical ...

  2. PREFACE: Inverse Problems in Applied Sciences—towards breakthrough (United States)

    Cheng, Jin; Iso, Yuusuke; Nakamura, Gen; Yamamoto, Masahiro


    These are the proceedings of the international conference `Inverse Problems in Applied Sciences—towards breakthrough' which was held at Hokkaido University, Sapporo, Japan on 3-7 July 2006 ( There were 88 presentations and more than 100 participants, and we are proud to say that the conference was very successful. Nowadays, many new activities on inverse problems are flourishing at many centers of research around the world, and the conference has successfully gathered a world-wide variety of researchers. We believe that this volume contains not only main papers, but also conveys the general status of current research into inverse problems. This conference was the third biennial international conference on inverse problems, the core of which is the Pan-Pacific Asian area. The purpose of this series of conferences is to establish and develop constant international collaboration, especially among the Pan-Pacific Asian countries, and to lead the organization of activities concerning inverse problems centered in East Asia. The first conference was held at City University of Hong Kong in January 2002 and the second was held at Fudan University in June 2004. Following the preceding two successes, the third conference was organized in order to extend the scope of activities and build useful bridges to the next conference in Seoul in 2008. Therefore this third biennial conference was intended not only to establish collaboration and links between researchers in Asia and leading researchers worldwide in inverse problems but also to nurture interdisciplinary collaboration in theoretical fields such as mathematics, applied fields and evolving aspects of inverse problems. For these purposes, we organized tutorial lectures, serial lectures and a panel discussion as well as conference research presentations. This volume contains three lecture notes from the tutorial and serial lectures, and 22 papers. Especially at this

  3. [Drug interactions in pain therapy]. (United States)

    Syhr, K M J; Oertel, B G; Geisslinger, G


    Pain is one of the most common reasons for consulting a physician. Chronic pain patients often suffer from a variety of comorbidities, such as depression and anxiety and they are therefore often simultaneously treated with more than one drug. The probability of drug interactions increases with every additional drug. A systematic internet and literature search up to February 2015 was carried out. Systematic lists were included. In addition, the drug prescription information sheets were used and an internet search via Pubmed and was carried out for drugs alone and in combination in order to find substance-specific interactions. A differentiation is made between pharmaceutical, pharmacodynamic and pharmacokinetic drug interactions. Pharmaceutical interactions are caused by chemical, physical or physicochemical incompatibility of drugs or adjuvants used. These can even occur outside the body and during concomitant administration via the same route. A pharmacodynamic interaction in pain management is for example the additive sedative effect of opioids and benzodiazepines when taken together. Pharmacokinetic interactions occur during the absorption, distribution, metabolism and in the elimination phases. Many drug interactions can be avoided by careful and continuous evaluation of pharmacotherapy and if necessary its adaptation; however, a sound knowledge of the underlying pharmacological mechanisms and the properties of currently used analgesics is necessary.

  4. Predicting the Risk of Breakthrough Urinary Tract Infections: Primary Vesicoureteral Reflux. (United States)

    Hidas, Guy; Billimek, John; Nam, Alexander; Soltani, Tandis; Kelly, Maryellen S; Selby, Blake; Dorgalli, Crystal; Wehbi, Elias; McAleer, Irene; McLorie, Gordon; Greenfield, Sheldon; Kaplan, Sherrie H; Khoury, Antoine E


    We constructed a risk prediction instrument stratifying patients with primary vesicoureteral reflux into groups according to their 2-year probability of breakthrough urinary tract infection. Demographic and clinical information was retrospectively collected in children diagnosed with primary vesicoureteral reflux and followed for 2 years. Bivariate and binary logistic regression analyses were performed to identify factors associated with breakthrough urinary tract infection. The final regression model was used to compute an estimation of the 2-year probability of breakthrough urinary tract infection for each subject. Accuracy of the binary classifier for breakthrough urinary tract infection was evaluated using receiver operator curve analysis. Three distinct risk groups were identified. The model was then validated in a prospective cohort. A total of 252 bivariate analyses showed that high grade (IV or V) vesicoureteral reflux (OR 9.4, 95% CI 3.8-23.5, p urinary tract infection (OR 5.3, 95% CI 1.1-24.7, p = 0.034) and female gender (OR 2.6, 95% CI 0.097-7.11, p urinary tract infection. Subgroup analysis revealed bladder and bowel dysfunction was a significant risk factor more pronounced in low grade (I to III) vesicoureteral reflux (OR 2.8, p = 0.018). The estimation model was applied for prospective validation, which demonstrated predicted vs actual 2-year breakthrough urinary tract infection rates of 19% vs 21%. Stratifying the patients into 3 risk groups based on parameters in the risk model showed 2-year risk for breakthrough urinary tract infection was 8.6%, 26.0% and 62.5% in the low, intermediate and high risk groups, respectively. This proposed risk stratification and probability model allows prediction of 2-year risk of patient breakthrough urinary tract infection to better inform parents of possible outcomes and treatment strategies. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights

  5. Pharmacokinetics of gamithromycin in pigs


    Wyns, Heidi; Meyer, Evelyne; Plessers, Elke; Watteyn, Anneleen; De Baere, Siegrid; De Backer, Patrick; Croubels, Siska


    Objectives : Gamithromycin, a 15-membered semi-synthetic macrolide antibiotic of the azalide subclass, has recently been developed for the treatment and prevention of bovine respiratory disease (BRD). Besides the anti-infectious properties, macrolides have frequently been reported to be able to influence various inflammatory processes, such as the production of pro-inflammatory cytokines and mediators. The aim of this study was to determine the pharmacokinetic (PK) parameters of gamithrom...

  6. Population Pharmacokinetics of Intranasal Scopolamine (United States)

    Wu, L.; Chow, D. S. L.; Putcha, L.


    Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS).The bioavailability and pharmacokinetics (PK) was evaluated using data collected in Phase II IND protocols. We reported earlier statistically significant gender differences in PK parameters of INSCOP at a dose level of 0.4 mg. To identify covariates that influence PK parameters of INSCOP, we examined population covariates of INSCOP PK model for 0.4 mg dose. Methods: Plasma scopolamine concentrations versus time data were collected from 20 normal healthy human subjects (11 male/9 female) after a 0.4 mg dose. Phoenix NLME was employed for PK analysis of these data using gender, body weight and age as covariates for model selection. Model selection was based on a likelihood ratio test on the difference of criteria (-2LL). Statistical significance for base model building and individual covariate analysis was set at P less than 0.05{delta(-2LL)=3.84}. Results: A one-compartment pharmacokinetic model with first-order elimination best described INSCOP concentration ]time profiles. Inclusion of gender, body weight and age as covariates individually significantly reduced -2LL by the cut-off value of 3.84(P less than 0.05) when tested against the base model. After the forward stepwise selection and backward elimination steps, gender was selected to add to the final model which had significant influence on absorption rate constant (ka) and the volume of distribution (V) of INSCOP. Conclusion: A population pharmacokinetic model for INSCOP has been identified and gender was a significant contributing covariate for the final model. The volume of distribution and Ka were significantly higher in males than in females which confirm gender-dependent pharmacokinetics of scopolamine after administration of a 0.4 mg dose.

  7. Optimal design of pharmacokinetic studies. (United States)

    Aarons, Leon; Ogungbenro, Kayode


    Experimental design is fundamental to successful scientific investigation. Poorly designed experiments lead to the loss of information, which is costly and potentially unethical. Experiments can be designed in an optimal fashion to maximize the amount of information they provide. Optimal design theory uses prior information about the model and parameter estimates to optimize a function of the Fisher information matrix to obtain the best combination of the design factors. In the case of population pharmacokinetic experiments, this involves the selection and a careful balance of a number of design factors, including the number and location of measurement times and the number of subjects to include in the study. It is expected that as the awareness about the benefits of this approach increases, more people will embrace it and ultimately will lead to more efficient population pharmacokinetic experiments and can also help to reduce both cost and time during drug development. This MiniReview provides an introduction to optimal design using examples taken from different pharmacokinetic experiments.

  8. Extreme Thermal Sensitivity and Pain-Induced Sensitization in a Fibromyalgia Patient

    Directory of Open Access Journals (Sweden)

    Fong Wong


    Full Text Available During the course of a psychophysical study of fibromyalgia syndrome (FMS, one of the subjects with a long history of headache and facial pain displayed an extraordinarily severe thermal allodynia. Her stimulus-response function for ratings of cutaneous heat pain revealed a sensitivity clearly beyond that of normal controls and most FMS subjects. Specially designed psychophysical methods showed that heat sensitivity sometimes increased dramatically within a series of stimuli. Prior exposure to moderate heat pain served as a trigger for allodynic ratings of series of normally neutral thermal stimulation. These observations document a case of breakthrough pain sensitivity with implications for mechanisms of FMS pain.

  9. Intranasal fentanyl in the treatment of acute pain--a systematic review

    DEFF Research Database (Denmark)

    Hansen, M S; Mathiesen, O; Trautner, S


    . No significant analgesic differences between IN fentanyl and intravenous (IV) fentanyl were demonstrated in treatment of acute and post-operative pain. Significant analgesic effect of IN fentanyl was demonstrated in the treatment of breakthrough pain in cancer patients. In the paediatric population, results...... demonstrated some analgesic effect of IN fentanyl following myringotomy, no analgesic effect following voiding cystourethrography, and finally, no significant analgesic difference after long bone fractures, in burns patients, and in post-operative pain relief when compared to IV morphine, oral morphine, or IV...... fentanyl, respectively. Significant analgesic effect of IN fentanyl was demonstrated in the treatment of breakthrough pain in cancer patients. However, the significant deficiencies in trials investigating acute and post-operative pain, and the paediatric population makes firm recommendations impossible....

  10. Alternative sample-introduction technique to avoid breakthrough in gradient-elution liquid chromatography of polymers. (United States)

    Reingruber, Eva; Bedani, Filippo; Buchberger, Wolfgang; Schoenmakers, Peter


    Gradient-elution liquid chromatography (GELC) is a powerful tool for the characterization of synthetic polymers. However, gradient-elution chromatograms often suffer from breakthrough phenomena. Breakthrough can be averted by using a sample solvent as weak as the mobile phase. However, this approach is only applicable to polymers for which a sufficiently strong solvent exists which is at the same time a weak eluent. Finding such a solvent for a given polymer can be laborious or may even be impossible. Besides, when working with comprehensive two-dimensional LC the effluent of the first dimension is the injection solvent of the second dimension. In this case, it is not possible to avoid breakthrough by adjusting the eluent strength of the second-dimension injection solvent. Therefore, another strategy to avert breakthrough has to be implemented. In this work, we successfully avoided breakthrough in GELC by mixing the mobile phase not before, but after the autosampler. This was demonstrated measuring a blend of poly(methyl methacrylate) standards with different molecular-weights as model mixture with comprehensive two-dimensional GELC×size-exclusion chromatography. The strategy is thought to be applicable to all substances with a sufficiently strong dependence of retention on mobile-phase composition. This typically applies to large molecules (synthetic and natural polymers) and allows efficient refocusing. Unretained and barely retained substances are not refocused and therefore suffer in the proposed setup from peak broadening. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Treatment of Breakthrough and Refractory Chemotherapy-Induced Nausea and Vomiting (United States)

    Navari, Rudolph M.


    Despite significant progress in the prevention of chemotherapy-induced nausea and vomiting (CINV) with the introduction of new antiemetic agents, 30–50% of patients receiving moderately or highly emetogenic chemotherapy (MEC or HEC) and guideline directed prophylactic antiemetics develop breakthrough CINV. International guidelines recommend the treatment of breakthrough CINV with an agent from a drug class that was not used in the prophylactic antiemetic regimen and recommend using the breakthrough medication continuously rather than using it on an as needed basis. There have been very few studies on the treatment of breakthrough CINV. A recent double-blind, randomized, phase III study suggested that olanzapine may be an effective agent for the treatment of breakthrough CINV. Refractory CINV occurs when patients develop CINV during subsequent cycles of chemotherapy when antiemetic prophylaxis has not been successful in controlling CINV in earlier cycles. Patients who develop refractory CINV should be considered for a change in their prophylactic antiemetic regimen. If significant anxiety exists, a benzodiazepine may be added to the prophylactic regimen. If a refractory patient is receiving HEC, olanzapine may be added to the prophylactic regimen. If the patient is receiving MEC, olanzapine or an NK-1 receptor antagonist may be added to the prophylactic regimen. PMID:26421294

  12. Treatment of Breakthrough and Refractory Chemotherapy-Induced Nausea and Vomiting

    Directory of Open Access Journals (Sweden)

    Rudolph M. Navari


    Full Text Available Despite significant progress in the prevention of chemotherapy-induced nausea and vomiting (CINV with the introduction of new antiemetic agents, 30–50% of patients receiving moderately or highly emetogenic chemotherapy (MEC or HEC and guideline directed prophylactic antiemetics develop breakthrough CINV. International guidelines recommend the treatment of breakthrough CINV with an agent from a drug class that was not used in the prophylactic antiemetic regimen and recommend using the breakthrough medication continuously rather than using it on an as needed basis. There have been very few studies on the treatment of breakthrough CINV. A recent double-blind, randomized, phase III study suggested that olanzapine may be an effective agent for the treatment of breakthrough CINV. Refractory CINV occurs when patients develop CINV during subsequent cycles of chemotherapy when antiemetic prophylaxis has not been successful in controlling CINV in earlier cycles. Patients who develop refractory CINV should be considered for a change in their prophylactic antiemetic regimen. If significant anxiety exists, a benzodiazepine may be added to the prophylactic regimen. If a refractory patient is receiving HEC, olanzapine may be added to the prophylactic regimen. If the patient is receiving MEC, olanzapine or an NK-1 receptor antagonist may be added to the prophylactic regimen.

  13. Esophageal Acidification During Nocturnal Acid-breakthrough with Ilaprazole Versus Omeprazole in Gastroesophageal Reflux Disease. (United States)

    Karyampudi, Arun; Ghoshal, Uday C; Singh, Rajan; Verma, Abhai; Misra, Asha; Saraswat, Vivek A


    Though nocturnal acid-breakthrough (NAB) is common in gastroesophageal reflux disease (GERD) patients, its clinical importance results from esophageal acidification, which has been shown to be uncommon. Ilaprazole, a long-acting proton pump inhibitor, may cause NAB infrequently. Accordingly, we studied prospectively, (1) frequency and degree of esophageal acidification during NAB, and (2) frequency and severity of NAB while on ilaprazole versus omeprazole. Fifty-eight consecutive patients with GERD on once daily ilaprazole, 10 mg (n = 28) or omeprazole, 20 mg (n = 30) for > one month underwent 24-hour impedance-pH monitoring prospectively. NAB was defined as intra-gastric pH one hour during night, and esophageal acidification as pH < 4 for any duration. Nocturnal symptoms (heartburn, regurgitation, and chest pain) were also recorded. Of the 58 patients (age 35.5 [inter-quartile range 26.5-46.0] years, 38 [65.5%], 42 (72.4%) had NAB. Though patients with NAB had lower nocturnal intra-gastric pH than without (2.8 [1.9-4.1] vs 5.7 [4.6-6.8], P < 0.001), frequency and duration of nocturnal esophageal acidification (17/42 vs 4/16, P = 0.360 and 0.0 [0.0-1.0] vs 0.0 [0.0-0.3] minutes, P = 0.260, respectively) and symptoms were comparable (13/42 vs 6/16, P = 0.750). Though ilaprazole was associated with less NABs (1 [range 1-2, n = 19] vs 1 [range 1-3, n = 23], P = 0.010) than omeprazole, the frequency, duration, and mean intra-gastric pH during NAB were comparable (19/28 vs 23/30, P = 0.560; 117 [0-315] vs 159 [69-287] minutes, P = 0.500; 1.02 [0.7-1.4] vs 1.04 [0.44-1.3], P = 0.620, respectively). Though NAB was common while patients were on a proton pump inhibitor, esophageal acidification was uncommon. Frequency and severity of NAB were comparable among patients on ilaprazole and omeprazole, except for the lesser number of NABs with ilaprazole.

  14. Chronic Pain (United States)

    ... people who have chronic pain may also have low self-esteem, depression, and anger. Symptoms of chronic pain Chronic ... itself often leads to other symptoms. These include low self-esteem, anger, depression, anxiety, or frustration. What causes chronic ...

  15. Ankle Pain (United States)

    ... it follows an injury. Even a relatively benign ankle injury can be quite painful, at least at first. ... improve after several weeks Self-care For many ankle injuries, self-care measures ease the pain. Examples include: ...

  16. Elbow Pain (United States)

    ... pain is often caused by overuse. Many sports, hobbies and jobs require repetitive hand, wrist or arm ... Accessed Jan. 16, 2016. Jan. 11, 2018 Original article: ...

  17. Finger pain (United States)

    Pain - finger ... Nearly everyone has had finger pain at some time. You may have: Tenderness Burning Stiffness Numbness Tingling Coldness Swelling Change in skin color Redness Many conditions, such ...

  18. Habituating pain

    DEFF Research Database (Denmark)

    Ajslev, Jeppe Zielinski Nguyen; Lund, Henrik Lambrecht; Møller, Jeppe Lykke


    the industry reproduce physical strain and the habituation of pain as unquestioned conditions in construction work. The understanding of this mutual reinforcement of the necessity of physically straining, painful, high-paced construction work provides fruitful perspectives on the overrepresentation...

  19. Paracetamol and morphine for infant and neonatal pain; still a long way to go? (United States)

    Baarslag, Manuel A; Allegaert, Karel; Van Den Anker, John N; Knibbe, Catherijne A J; Van Dijk, Monique; Simons, Sinno H P; Tibboel, Dick


    Pharmacologic pain management in newborns and infants is often based on limited scientific data. To close the knowledge gap, drug-related research in this population is increasingly supported by the authorities, but remains very challenging. This review summarizes the challenges of analgesic studies in newborns and infants on morphine and paracetamol (acetaminophen). Areas covered: Aspects such as the definition and multimodal character of pain are reflected to newborn infants. Specific problems addressed include defining pharmacodynamic endpoints, performing clinical trials in this population and assessing developmental changes in both pharmacokinetics and pharmacodynamics. Expert commentary: Neonatal and infant pain management research faces two major challenges: lack of clear biomarkers and very heterogeneous pharmacokinetics and pharmacodynamics of analgesics. There is a clear call for integral research addressing the multimodality of pain in this population and further developing population pharmacokinetic models towards physiology-based models.

  20. Phantom Pain (United States)

    ... Because this is yet another version of tangled sensory wires, the result can be pain. A number of other factors are believed to contribute to phantom pain, including damaged nerve endings, scar tissue at the site of the amputation and the physical memory of pre-amputation pain in the affected area. ...

  1. Chest Pain (United States)

    ... or tightness in your chest Crushing or searing pain that radiates to your back, neck, jaw, shoulders, and one or both arms Pain that lasts ... com. Accessed Sept. 6, 2017. Yelland MJ. Outpatient evaluation of the adult with chest pain. Accessed Sept. ...

  2. Neck Pain (United States)

    ... arms or hands or if you have shooting pain into your shoulder or down your arm. Symptoms Signs and symptoms ... org/search/Pages/results.aspx?k=Chronic neck pain. Accessed June 11, 2015. Isaac Z. Evaluation of the patient with neck pain and cervical ...

  3. Spinal pain

    International Nuclear Information System (INIS)

    Izzo, R.; Popolizio, T.; D’Aprile, P.; Muto, M.


    Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic

  4. Spinal pain

    Energy Technology Data Exchange (ETDEWEB)

    Izzo, R., E-mail: [Neuroradiology Department, A. Cardarelli Hospital, Naples (Italy); Popolizio, T., E-mail: [Radiology Department, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (Fg) (Italy); D’Aprile, P., E-mail: [Neuroradiology Department, San Paolo Hospital, Bari (Italy); Muto, M., E-mail: [Neuroradiology Department, A. Cardarelli Hospital, Napoli (Italy)


    Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic

  5. Breakthrough properties of chloride ions in columns of lead phosphate hydroxide

    International Nuclear Information System (INIS)

    Akiba, Kenichi; Hashimoto, Hiroyuki; Mimura, Hitoshi; Shindo, Manabu.


    Breakthrough properties of chloride ion (Cl - ) have been studied by using columns packed with a granular anion-exchanger of lead phosphate hydroxide (Pb 10 (PO 4 ) 6 (OH) 2 , IXE-1000G). The column utilization of the ratio of breakthrough capacity to total capacity increased with decreasing particle size and increasing temperature. The collection of Cl - from a simulated waste solution was improved by the addition of cation-exchange to IXE-1000G; the adsorption capacity of the column of IXE-1000G/IXE-300G (Sb type cation-exchanger) was over 0.16 mmol Cl - /g, yielding a relatively high column utilization of 75%. (author)

  6. Coupling gravity, electromagnetism and space-time for space propulsion breakthroughs (United States)

    Millis, Marc G.


    spaceflight would be revolutionized if it were possible to propel a spacecraft without rockets using the coupling between gravity, electromagnetism, and space-time (hence called 'space coupling propulsion'). New theories and observations about the properties of space are emerging which offer new approaches to consider this breakthrough possibility. To guide the search, evaluation, and application of these emerging possibilities, a variety of hypothetical space coupling propulsion mechanisms are presented to highlight the issues that would have to be satisfied to enable such breakthroughs. A brief introduction of the emerging opportunities is also presented.

  7. Drug Transport and Pharmacokinetics for Chemical Engineers (United States)

    Simon, Laurent; Kanneganti, Kumud; Kim, Kwang Seok


    Experiments in continuous-stirred vessels were proposed to introduce methods in pharmacokinetics and drug transport to chemical engineering students. The activities can be incorporated into the curriculum to illustrate fundamentals learned in the classroom. An appreciation for the role of pharmacokinetics in drug discovery will also be gained…

  8. Glipizide Pharmacokinetics in Healthy and Diabetic Volunteers

    African Journals Online (AJOL)


    11800, Penang, Malaysia, 4Ministry of Health, Government of Pakistan. Abstract. Purpose: Disease state may contribute to alteration in drug pharmacokinetics. The purpose of this study was to determine the effect of non-insulin dependent diabetes mellitus (NIDDM) on the pharmacokinetics of glipizide. Methods: An open ...

  9. Spontaneous pain attacks: neuralgic pain

    NARCIS (Netherlands)

    de Bont, L.G.


    Paroxysmal orofacial pains can cause diagnostic problems, especially when different clinical pictures occur simultaneously. Pain due to pulpitis, for example, may show the same characteristics as pain due to trigeminal neuralgia would. Moreover, the trigger point of trigeminal neuralgia can either

  10. Ejaculatory pain

    DEFF Research Database (Denmark)

    Aasvang, Eske K; Møhl, Bo; Kehlet, Henrik


    and treatment strategies. METHODS: Ten patients with severe pain-related sexual dysfunction and ejaculatory pain were assessed in detail by quantitative sensory testing and interviewed by a psychologist specialized in evaluating sexual functional disorders and were compared with a control group of 20 patients....... CONCLUSIONS: Postherniotomy ejaculatory pain and pain-related sexual dysfunction is a specific chronic pain state that may be caused by pathology involving the vas deferens and/or nerve damage. Therapeutic strategies should therefore include neuropathic pain treatment and/or surgical exploration.......BACKGROUND: Sexual dysfunction due to ejaculatory and genital pain after groin hernia surgery may occur in approximately 2.5% of patients. However, the specific psychosexological and neurophysiologic characteristics have not been described, thereby precluding assessment of pathogenic mechanisms...

  11. Efficacy of a Targeted Drug Delivery on-Demand Bolus Option for Chronic Pain. (United States)

    Bolash, Robert B; Niazi, Tariq; Kumari, Meera; Azer, Gerges; Mekhail, Nagy


    Intrathecal targeted drug delivery systems historically required physician office visits for dose adjustment to manage fluctuating pain. A wireless device now enables patients to supplement their basal intrathecal infusion with a programmed on-demand bolus dose. We sought to quantify the change in oral breakthrough opioid need associated with the use of an intrathecal bolus in comparison to those treated with the basal infusion alone. Demographic, dosage, bolus usage and longevity data were extracted from the historical medical record of 69 patients (18/51 bolus/nonbolus) followed continuously at our center. Medication consumption and Pain Disability Index measures were obtained at baseline and most recent follow-up. Among patients with the bolus option, only 2 (11%; confidence interval [CI] 0% to 26%) continued to require oral opiates to manage breakthrough pain compared to 29 (57%; CI 43% to 71%) without the bolus option. The Pain Disability Index score decreased by 19% in patients with the bolus option and by 25% in those with the basal infusion. Total daily intrathecal opioid intake was 34% lower in the group with the bolus device. Utilizing an intrathecal bolus to treat incident pain was a safe way to manage unpredictable breakthrough pain and may represent a cost-saving opportunity by eliminating the need for oral analgesic medications. © 2017 World Institute of Pain.

  12. Pain genes.

    Directory of Open Access Journals (Sweden)

    Tom Foulkes


    Full Text Available Pain, which afflicts up to 20% of the population at any time, provides both a massive therapeutic challenge and a route to understanding mechanisms in the nervous system. Specialised sensory neurons (nociceptors signal the existence of tissue damage to the central nervous system (CNS, where pain is represented in a complex matrix involving many CNS structures. Genetic approaches to investigating pain pathways using model organisms have identified the molecular nature of the transducers, regulatory mechanisms involved in changing neuronal activity, as well as the critical role of immune system cells in driving pain pathways. In man, mapping of human pain mutants as well as twin studies and association studies of altered pain behaviour have identified important regulators of the pain system. In turn, new drug targets for chronic pain treatment have been validated in transgenic mouse studies. Thus, genetic studies of pain pathways have complemented the traditional neuroscience approaches of electrophysiology and pharmacology to give us fresh insights into the molecular basis of pain perception.

  13. Cannabinoid Disposition After Human Intraperitoneal Use: An Insight Into Intraperitoneal Pharmacokinetic Properties in Metastatic Cancer. (United States)

    Lucas, Catherine J; Galettis, Peter; Song, Shuzhen; Solowij, Nadia; Reuter, Stephanie E; Schneider, Jennifer; Martin, Jennifer H


    Medicinal cannabis is prescribed under the provision of a controlled drug in the Australian Poisons Standard. However, multiple laws must be navigated in order for patients to obtain access and imported products can be expensive. Dose-response information for both efficacy and toxicity pertaining to medicinal cannabis is lacking. The pharmacokinetic properties of cannabis administered by traditional routes has been described but to date, there is no literature on the pharmacokinetic properties of an intraperitoneal cannabinoid emulsion. A cachectic 56-year-old female with stage IV ovarian cancer and peritoneal metastases presented to hospital with fevers, abdominal distension and severe pain, vomiting, anorexia, dehydration and confusion. The patient reported receiving an intraperitoneal injection, purported to contain 12 g of mixed cannabinoid (administered by a deregistered medical practitioner) two days prior to presentation. Additionally, cannabis oil oral capsules were administered in the hours prior to hospital admission. THC concentrations were consistent with the clinical state but not with the known pharmacokinetic properties of cannabis nor of intraperitoneal absorption. THC concentrations at the time of presentation were predicted to be ~60 ng/mL. Evidence suggests that blood THC concentrations >5 ng/mL are associated with substantial cognitive and psychomotor impairment. The predicted time for concentrations to drop pharmacokinetic properties of the case suggest that there is a large amount unknown about cannabis pharmacokinetic properties. The pharmacokinetic properties of a large amount of a lipid soluble compound given intraperitoneally gave insights into the absorption and distribution of cannabinoids, particularly in the setting of metastatic malignancy. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

  14. Breakthrough disease during interferon-[beta] therapy in MS: No signs of impaired biologic response

    DEFF Research Database (Denmark)

    Hesse, D; Krakauer, M; Lund, H


    as reliable indicators of treatment response, despite substantial, biologically measurable effects. We studied the biologic response to treatment in a cohort of NAb-negative patients to test whether difference in responsiveness could segregate patients with and without breakthrough disease during therapy....

  15. Creative Management as a Strategy for Breakthrough Innovation. Lessons from Basic Research Projects of Japanese Companies. (United States)

    Lee, K. T.


    Japanese science/technology policies emphasize creative research management for strengthening breakthrough innovation. Key lessons include the following: cultivation of creative researchers, clear strategic directions, systematic teamwork and collaboration, focus on strategic industrial relevance, balance between autonomy and control, and the need…

  16. The breakthrough curve combination for xenon sampling dynamics in a carbon molecular sieve column. (United States)

    Shu-jiang, Liu; Zhan-ying, Chen; Yin-zhong, Chang; Shi-lian, Wang; Qi, Li; Yuan-qing, Fan; Huai-mao, Jia; Xin-jun, Zhang; Yun-gang, Zhao


    In the research of xenon sampling and xenon measurements, the xenon breakthrough curve plays a significant role in the xenon concentrating dynamics. In order to improve the theoretical comprehension of the xenon concentrating procedure from the atmosphere, the method of the breakthrough curve combination for sampling techniques should be developed and investigated under pulse injection conditions. In this paper, we describe a xenon breakthrough curve in a carbon molecular sieve column, the combination curve method for five conditions is shown and debated in detail; the fitting curves and the prediction equations are derived in theory and verified by the designed experiments. As a consequence, the curves of the derived equations are in good agreement with the fitting curves by tested. The retention times of the xenon in the column are 61.2, 42.2 and 23.5 at the flow rate of 1200, 1600 and 2000 mL min(-1), respectively, but the breakthrough times are 51.4, 38.6 and 35.1 min.

  17. Chemokine receptors and their crucial role in human immunodeficiency virus infection: major breakthroughs in HIV research

    DEFF Research Database (Denmark)

    Kristiansen, T B; Knudsen, T B; Eugen-Olsen, J


    to a series of breakthroughs in HIV research and knowledge. These include an increased understanding of viral entry, a connection of viral phenotype to specific coreceptor use, and an unequivocal linkage of a single human gene to host susceptibility. All in all these achievements provide a number of promising...... new strategies for combating HIV....

  18. Behind "AIDS breakthrough" headlines, December 2004: important research, not so new. (United States)

    James, John S


    The mid-December press reports about an AIDS drug breakthrough were exaggerated, but the research described is important. It concerns the development of a class of related experimental drugs that work like efavirenz or nevirapine, but appear to be more powerful and much less subject to resistance.

  19. FRB 121102: Detection at 4 - 8 GHz band with Breakthrough Listen backend at Green Bank (United States)

    Gajjar, Vishal,; Siemion, Andrew P. V.; MacMahon, David H. E.; Croft, Steve; Hellbourg, Gregory; Isaacson, Howard; Enriquez, J. Emilio; Price, Danny C.; Lebofsky, Matthew; DeBoer, David; Werthimer, Dan; Hickish, Jack; Brinkman, Casey; Chatterjee, Shami; Ransom, Scott


    On Saturday, August 26 at 13:51:44 UTC we initiated observations of the well-known repeating fast radio burst FRB 121102 [Spitler et al., Nature, 531, 7593 202-205, 2016] using the Breakthrough Listen Digital Backend with the C-band receiver at the Green Bank Telescope.

  20. Pharmacokinetics and dosimetry, an introduction

    International Nuclear Information System (INIS)

    Notari, R.E.


    Classical pharmacokinetic techniques attempt to quantify the time course for drug in the body by assaying samples of blood or urine as a function of time. The mathematical descriptions that have emerged from this approach have proven extremely valuable to both drug research and drug therapy. Since the monitoring of patients' drug blood levels by obtaining a few small blood samples at key times is clinically practical, individualization of dosage regimens has become a reality. This has dramatically altered certain types of drug therapy. These improvements are limited to cases wherein biological response can be related to drug blood levels since the mathematics are capable only of describing the sampled fluids. Non-sampled fluids are considered as additional compartments or pools and described collectively using kinetic equations for mass balance. This limits progress in those areas of research which require assessment of the relationship of specific organ contents to that of the blood. The author suggests that radiopharmaceutical techniques which can provide the time course in specific organs might be coupled with classical pharmacokinetic approaches to provide insight not previously achieved

  1. Pharmacokinetics of metformin during pregnancy. (United States)

    Eyal, Sara; Easterling, Thomas R; Carr, Darcy; Umans, Jason G; Miodovnik, Menachem; Hankins, Gary D V; Clark, Shannon M; Risler, Linda; Wang, Joanne; Kelly, Edward J; Shen, Danny D; Hebert, Mary F


    Our objective was to evaluate the pharmacokinetics of metformin during pregnancy. Serial blood and urine samples were collected over one steady-state dosing interval in women treated with metformin during early to late pregnancy (n = 35) and postpartum (n = 16). Maternal and umbilical cord blood samples were obtained at delivery from 12 women. Metformin concentrations were also determined in breast milk samples obtained over one dosing interval in 6 women. Metformin renal clearance increased significantly in mid (723 +/- 243 ml/min, P pregnancy (625 +/- 130 ml/min, P metformin net secretion clearance (480 +/- 190 ml/min, P pregnancy versus postpartum, respectively. Metformin concentrations at the time of delivery in umbilical cord plasma ranged between nondetectable (metformin through breast milk was 0.13 to 0.28 mg, and the relative infant dose was metformin pharmacokinetics are affected by pregnancy-related changes in renal filtration and net tubular transport and can be roughly estimated by the use of creatinine clearance. At the time of delivery, the fetus is exposed to metformin concentrations from negligible to as high as maternal concentrations. In contrast, infant exposure to metformin through the breast milk is low.

  2. Bone pain

    DEFF Research Database (Denmark)

    Frost, Charlotte Ørsted; Hansen, Rikke Rie; Heegaard, Anne-Marie


    Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology...... of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease...... modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities....

  3. Pharmacokinetic considerations for therapies used to treat interstitial cystitis. (United States)

    Gardella, Barbara; Porru, Daniele; Allegri, Massimo; Bogliolo, Stefano; Iacobone, Anna Daniela; Minella, Cristina; Nappi, Rossella Elena; Ferrero, Simone; Spinillo, Arsenio


    Interstitial cystitis (IC) or bladder pain syndrome (BPS) is defined as supra-pubic pain related to bladder filling. IC is characterized by a particular symptom complex with no identifiable causes; as with bladder hypersensitivity it is usually associated with urinary frequency and urgency with bladder pain. No current treatments have a significant impact on symptoms over time. This systematic review examines the pharmacokinetic aspects and adverse event of present IC therapy to highlight appropriate treatment to improve the symptoms of IC. This article reviews material obtained via Medline, PubMed, and EMBASE literature searches up to October 2013. The correct approach to IC should consider a multidisciplinary team of specialists and a multimodal treatment package that include psychotherapy, behavior change, physical activation, and analgesic treatment. Unfortunately, a single therapeutic target for IC is not yet known. With regard to pathophysiology and therapy, there is more to discover. The first insult damages the bladder urothelium, hence vehicles that lead the drug to penetrate the wall of the bladder might be a novel strategic approach.

  4. Distal Ureteral Diameter Ratio is Predictive of Breakthrough Febrile Urinary Tract Infection. (United States)

    Arlen, Angela M; Leong, Traci; Guidos, P Joseph; Alexander, Siobhan E; Cooper, Christopher S


    Distal ureteral diameter ratio is an objective measure that is prognostic of spontaneous resolution of vesicoureteral reflux. Along with likelihood of resolution, improved identification of children at risk for recurrent febrile urinary tract infections may impact management decisions. We evaluated the usefulness of ureteral diameter ratio as a predictive factor for breakthrough febrile urinary tract infections. Children with primary vesicoureteral reflux and detailed voiding cystourethrogram were identified. Ureteral diameter ratio was computed by measuring largest ureteral diameter within the pelvis and dividing by the distance between L1 and L3 vertebral bodies. Demographics, vesicoureteral reflux grade, laterality, presence/absence of bladder-bowel dysfunction, and ureteral diameter ratio were tested in univariate and multivariable analyses. Primary outcome was breakthrough febrile urinary tract infections. We analyzed 112 girls and 28 boys with a mean ± SD age of 2.5 ± 2.3 years at diagnosis. Vesicoureteral reflux was grade 1 to 2 in 64 patients (45.7%), grade 3 in 50 (35.7%), grade 4 in 16 (11.4%) and grade 5 in 10 (7.2%). Mean ± SD followup was 3.2 ± 2.7 years. A total of 40 children (28.6%) experienced breakthrough febrile urinary tract infections. Ureteral diameter ratio was significantly greater in children with (0.36) vs without (0.25) breakthrough febrile infections (p = 0.004). Controlling for vesicoureteral reflux grade, every 0.1 U increase in ureteral diameter ratio resulted in 1.7 times increased odds of breakthrough infection (95% CI 1.24 to 2.26, p urinary tract infections independent of reflux grade. Ureteral diameter ratio provides valuable prognostic information about risk of recurrent pyelonephritis and may assist with clinical decision-making. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  5. Nalmefene to prevent epidural narcotic side effects in pediatric patients: a pharmacokinetic and safety study. (United States)

    Rosen, D A; Morris, J L; Rosen, K R; Nelson, E R; Steelman, R J; Gustafson, R A; Wilhelm, J A; Chang, C T; Thackara, J W; Frye, R F


    To determine the pharmacokinetics and preliminary efficacy of nalmefene in children in preventing epidural-induced narcotic side effects. Double-blind, placebo-controlled study. University-affiliated children's hospital. Thirty-four children (aged 2-12 yrs) undergoing cardiothoracic surgery with epidural anesthesia. Patients were randomized to receive intravenous bolus nalmefene 1 microg/kg or placebo. Six blood samples (one before nalmefene administration and five from 13 randomly designated time points) from each patient were assayed to determine plasma nalmefene concentrations. Patients were assessed for pain, nausea, vomiting, and urinary retention for 24 hours after administration. Concentration-time data were analyzed by a limited sampling strategy with adult pharmacokinetic parameters used as Bayesian priors. A two-compartment, first-order model was fitted to the data using ADAPT II. Pharmacokinetic parameter estimates in these patients were similar to values reported in adults. The initial disposition half-life (t(1/2alpha)) was 0.36+/-0.11 hour, the terminal elimination half-life (t(1/2beta)) 8.7+/-2.3 hours, clearance 0.729+/-0.172 L/kg/hr, and steady-state volume of distribution 7.21+/-2.49 L/kg. Ability to prevent epidural narcotic-induced side effects could not be documented at the 1-microg/kg dose. No statistically significant differences were noted between study and placebo groups with regard to pain, nausea, vomiting, or urinary retention. Nalmefene has similar pharmacokinetics in children as in adults. It was administered safely to these patients and did not produce unmanageable pain.

  6. Antimicrobial Pharmacokinetics and Pharmacodynamics in Older Adults. (United States)

    Benson, John M


    Antimicrobial use in older adults requires working knowledge of the pharmacokinetics and pharmacodynamics of these drugs, and the alterations known to occur with these models as patients age. A summary of pharmacokinetic principles relevant to antimicrobials and an overview of published medical literature describing pharmacokinetic changes known to correlate with age are presented. Pharmacodynamic models that apply to antibacterial agents are reviewed, as are likely effects of aging on these models. The understanding of how older adults respond in terms of efficacy and toxicity is increasing but limited. Further research into the effects of aging on the actions of antimicrobials in the elderly is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Formulation and pharmacokinetics of diclofenac lipid nanoemulsions for parenteral application. (United States)

    Ramreddy, Srividya; Kandadi, Prabhakar; Veerabrahma, Kishan


    The objective of the present study was to formulate and determine the pharmacokinetics of stable o/w parenteral lipid nanoemulsions (LNEs) of diclofenac acid used to treat arthritic conditions. The LNEs of diclofenac acid with a mean size ranging from 200 to 240 nm and a zeta potential of -29.4 ± 1.04 mV (negatively charged LNEs) and 62.1 ± 3.5 (positively charged LNEs) emulsions were prepared by hot homogenization and ultrasonication process. The influence of formulation variables, such as the change in proportion of cholesterol, was studied, and optimized formulations were developed. The optimized formulations were relatively stable during centrifugal stress, dilution stress, and storage. The drug content and entrapment efficiency were determined using high-performance liquid chromatography. The in vitro drug release was carried out in phosphate-buffered saline pH 7.4 and cumulative amount of drug released was estimated using a UV-visible spectro-photometer. During in vivo pharmacokinetic studies in male Wistar rats, diclofenac serum concentration from LNEs was higher than that of Voveran injection and was detectable up to 12 h. Diclofenac in LNEs showed improved pharmacokinetic profile with increase in area under the curve, elimination half-life and mean residence time in comparison to Voveran. Our aim was to prepare and determine the pharmacokinetics of injectable lipid nanoemulsions of diclofenac acid for treating arthritic conditions by reducing the frequency of dosing and pain at site of injection. The nanoemulsions of diclofenac acid were prepared by homogenization and ultrasonication process. The sizes and charges of oil globules were determined. The effect of cholesterol on stability of emulsion was studied, and an optimized preparation was developed. The optimized formulations were stable during centrifugation, dilution, and storage. The total amount of drug in emulsion and percentage amount of drug present in emulsion globules were determined using

  8. Pain channelopathies (United States)

    Cregg, Roman; Momin, Aliakmal; Rugiero, Francois; Wood, John N; Zhao, Jing


    Pain remains a major clinical challenge, severely afflicting around 6% of the population at any one time. Channelopathies that underlie monogenic human pain syndromes are of great clinical relevance, as cell surface ion channels are tractable drug targets. The recent discovery that loss-of-function mutations in the sodium channel Nav1.7 underlie a recessive pain-free state in otherwise normal people is particularly significant. Deletion of channel-encoding genes in mice has also provided insights into mammalian pain mechanisms. Ion channels expressed by immune system cells (e.g. P2X7) have been shown to play a pivotal role in changing pain thresholds, whilst channels involved in sensory transduction (e.g. TRPV1), the regulation of neuronal excitability (potassium channels), action potential propagation (sodium channels) and neurotransmitter release (calcium channels) have all been shown to be potentially selective analgesic drug targets in some animal pain models. Migraine and visceral pain have also been associated with voltage-gated ion channel mutations. Insights into such channelopathies thus provide us with a number of potential targets to control pain. PMID:20142270

  9. Gastric pain

    African Journals Online (AJOL)

    Intermittent pain and. Not generalised or localised to other abdominal or chest regions and. Not relieved by defecation or passage of flatus and. Not fulfilling the ... retrosternal component. • The pain is commonly induced or relieved by the ingestion of a meal, but may occur during fasting. • Postprandial distress syndrome.

  10. Neuropathic pain

    Directory of Open Access Journals (Sweden)

    Giuseppe Re


    Full Text Available Neuropathic pain is the expression of a dysfunction or primary lesion of a nerve in the peripheral or central nervous system, or both, rather than the biological signal transmitted by the nerve following peripheral nociceptor activation. It represents about 20% of all painful syndromes, with an estimated prevalence of 1.5%, however is actual incidence is hard to pinpoint due to the difficulties encountered in distinguishing it from chronic pain, of which it represents a significant percentage, on account of the not infrequent concurrence of conditions. It is crucial to recognise the variety of symptoms with which it can present: these can be negative and positive and, in turn, motor, sensitive and autonomic. In public health terms, it is important to emphasise that the diagnosis of neuropathic pain does not in most cases require sophisticated procedures and does not therefore weigh on health expenditure. In clinical practice, a validated scale (the LANSS is mentioned is useful for identifying patients presenting neuropathic pain symptoms. Therapy is based on three categories of medication: tricyclic antidepressants, anti-epileptics and opioids at high doses: neuropathic pain has a bad reputation for often resisting common therapeutic approaches and responding less well that nociceptor pain to monotherapy. Therapeutic strategies are all the more adequate the more they are based on symptoms and therefore on the pain generation mechanisms, although the recommendations are dictated more by expert opinions that double-blind randomised trials.

  11. Neck Pain (United States)

    ... vehicle accidents is a common cause of neck pain. The diagnosis of neck pain is determined by a medical history and physical ... qualified health care provider for professional medical advice, diagnosis and treatment of a medical or health condition. ... Links Glossary of Rheumatology Terms ...

  12. Painful shoulder

    Directory of Open Access Journals (Sweden)

    Benno Ejnismann


    Full Text Available Many factors can be involved in the painful shoulder. Beyond articularcauses other pathologies such as artrosis, periarticular diseases as rotadorcuff tears, long head of the biceps tendinitis, adhesive capsulitis, calcifyingtendinitis, degenerative arthritis of the acromioclavicular joint, cervicalradiculopathy and nervous injuries can cause pain in the shoulder.

  13. Orofacial Pain (United States)

    ... aligned teeth can have trouble because the muscles work harder to bring the teeth together, causing strain. Pain also can be caused by clenching or grinding teeth, trauma to the head and neck or poor ergonomics. ; Some people may experience pain in the ears, ...

  14. Pain Management (United States)

    ... NIH About Mission The NIH Director Organization Budget History NIH Almanac Public Involvement Outreach & Education Visitor Information RePORT NIH Fact Sheets Home > Pain Management Small Text Medium Text Large Text Pain Management YESTERDAY Early Greeks and Romans advanced the idea that the brain ...

  15. Chest pain (United States)

    ... pain. The pain may spread to the arm, shoulder, jaw, or back. A tear in the wall of the aorta, the large blood vessel that takes blood from the heart to the rest of the body ( aortic dissection ) causes sudden, severe ...

  16. Gas breakthrough and emission through unsaturated compacted clay in landfill final cover

    International Nuclear Information System (INIS)

    Ng, C.W.W.; Chen, Z.K.; Coo, J.L.; Chen, R.; Zhou, C.


    Highlights: • Explore feasibility of unsaturated clay as a gas barrier in landfill cover. • Gas breakthrough pressure increases with clay thickness and degree of saturation. • Gas emission rate decreases with clay thickness and degree of saturation. • A 0.6 m-thick clay layer may be sufficient to meet gas emission rate limit. - Abstract: Determination of gas transport parameters in compacted clay plays a vital role for evaluating the effectiveness of soil barriers. The gas breakthrough pressure has been widely studied for saturated swelling clay buffer commonly used in high-level radioactive waste disposal facility where the generated gas pressure is very high (in the order of MPa). However, compacted clay in landfill cover is usually unsaturated and the generated landfill gas pressure is normally low (typically less than 10 kPa). Furthermore, effects of clay thickness and degree of saturation on gas breakthrough and emission rate in the context of unsaturated landfill cover has not been quantitatively investigated in previous studies. The feasibility of using unsaturated compacted clay as gas barrier in landfill covers is thus worthwhile to be explored over a wide range of landfill gas pressures under various degrees of saturation and clay thicknesses. In this study, to evaluate the effectiveness of unsaturated compacted clay to minimize gas emission, one-dimensional soil column tests were carried out on unsaturated compacted clay to determine gas breakthrough pressures at ultimate limit state (high pressure range) and gas emission rates at serviceability limit state (low pressure range). Various degrees of saturation and thicknesses of unsaturated clay sample were considered. Moreover, numerical simulations were carried out using a coupled gas–water flow finite element program (CODE-BRIGHT) to better understand the experimental results by extending the clay thickness and varying the degree of saturation to a broader range that is typical at different

  17. Pharmacokinetics of Compounded Intravenous and Oral Gabapentin in Hispaniolan Amazon Parrots ( Amazona ventralis ). (United States)

    Baine, Katherine; Jones, Michael P; Cox, Sherry; Martín-Jiménez, Tomás


    Neuropathic pain is a manifestation of chronic pain that arises with damage to the somatosensory system. Pharmacologic treatment recommendations for alleviation of neuropathic pain are often multimodal, and the few reports communicating treatment of suspected neuropathic pain in avian patients describe the use of gabapentin as part of the therapeutic regimen. To determine the pharmacokinetics of gabapentin in Hispaniolan Amazon parrots ( Amazona ventralis ), compounded gabapentin suspensions were administered at 30 mg/kg IV to 2 birds, 10 mg/kg PO to 3 birds, and 30 mg/kg PO to 3 birds. Blood samples were collected immediately before and at 9 different time points after drug administration. Plasma samples were analyzed for gabapentin concentration, and pharmacokinetic parameters were calculated with both a nonlinear mixed-effect approach and a noncompartmental analysis. The best compartmental, oral model was used to simulate the concentration-time profiles resulting from different dosing scenarios. Mild sedation was observed in both study birds after intravenous injection. Computer simulation of different dosing scenarios with the mean parameter estimates showed that 15 mg/kg every 8 hours would be a starting point for oral dosing in Hispaniolan Amazon parrots based on effective plasma concentrations reported for human patients; however, additional studies need to be performed to establish a therapeutic dose.

  18. Pharmacokinetics of thiamphenicol in dogs. (United States)

    Castells, G; Intorre, L; Franquelo, C; Cristòfol, C; Pérez, B; Martí, G; Arboix, M


    To determine pharmacokinetic parameters of thiamphenicol (TAP) after IV and IM administration in dogs. 6 healthy 2- to 3-year-old male Beagles. IN a crossover design study, 3 dogs were given TAP IV, and 3 dogs were given TAP IM, each at a dosage of 40 mg/kg of body weight. Three weeks later, the same dogs were given a second dose by the opposite route. At preestablished times after TAP administration, blood samples were collected through a catheter placed in the cephalic vein, and TAP concentration was determined by use of a high-performance liquid chromatography. Results-Kinetics of TAP administered IV were fitted by a biexponential equation with a rapid first disposition phase followed by a slower disposition phase. Elimination half-life was short (1.7+/-0.3 hours), volume of distribution at steady state was 0.66+/-0.05 L/kg, and plasma clearance was 5.3+/-0.7 ml/min/kg. After IM administration, absorption was rapid. Peak plasma concentration (25.1+/-10.3 microg/ml) was reached about 45 minutes after drug administration. The apparent elimination half-life after IM administration (5.6+/-4.6 hours) was longer than that after IV administration probably because of the slow absorption rate from the muscle. Mean bioavailability after IM administration was 96+/-7%. The pharmacokinetic profile of TAP in dogs suggests that it may be therapeutically useful against susceptible microorganisms involved in the most common infections in dogs, such as tracheobronchitis, enterocolitis, mastitis, and urinary tract infections.

  19. Clinical Pharmacokinetics of Systemically Administered Antileishmanial Drugs

    NARCIS (Netherlands)

    Kip, Anke E; Schellens, Jan H M; Beijnen, Jos H; Dorlo, Thomas P C

    This review describes the pharmacokinetic properties of the systemically administered antileishmanial drugs pentavalent antimony, paromomycin, pentamidine, miltefosine and amphotericin B (AMB), including their absorption, distribution, metabolism and excretion and potential drug-drug interactions.

  20. Chiral Pesticide Pharmacokinetics: A Range of Values (United States)

    Approximately 30% of pesticides are chiral and used as mixtures of two or more stereoisomers. In biological systems, these stereoisomers can exhibit significantly different pharmacokinetics (absorption, distribution, metabolism, and elimination). In spite of these differences, th...

  1. Pharmacokinetics and pharmacokinetic-pharmacodynamic relationships of monoclonal antibodies in children. (United States)

    Edlund, Helena; Melin, Johanna; Parra-Guillen, Zinnia P; Kloft, Charlotte


    Monoclonal antibodies (mAbs) constitute a therapeutically and economically important drug class with increasing use in both adult and paediatric patients. The rather complex pharmacokinetic and pharmacodynamic properties of mAbs have been extensively reviewed in adults. In children, however, limited information is currently available. This paper aims to comprehensively review published pharmacokinetic and pharmacokinetic-pharmacodynamic studies of mAbs in children. The current status of mAbs in the USA and in Europe is outlined, including a critical discussion of the dosing strategies of approved mAbs. The pharmacokinetic properties of mAbs in children are exhaustively summarised along with comparisons to reports in adults: for each pharmacokinetic process, we discuss the general principles and mechanisms of the pharmacokinetic/pharmacodynamic characteristics of mAbs, as well as key growth and maturational processes in children that might impact these characteristics. Throughout this review, considerable knowledge gaps are identified, especially regarding children-specific properties that influence pharmacokinetics, pharmacodynamics and immunogenicity. Furthermore, the large heterogeneity in the presentation of pharmacokinetic/pharmacodynamic data limited clinical inferences in many aspects of paediatric mAb therapy. Overall, further studies are needed to fully understand the impact of body size and maturational changes on drug exposure and response. To maximise future knowledge gain, we propose a 'Guideline for Best Practice' on how to report pharmacokinetic and pharmacokinetic-pharmacodynamic results from mAb studies in children which also facilitates comparisons. Finally, we advocate the use of more sophisticated modelling strategies (population analysis, physiology-based approaches) to appropriately characterise pharmacokinetic-pharmacodynamic relationships of mAbs and, thus, allow for a more rational use of mAb in the paediatric population.

  2. Clinical rationale for administering fentanyl to cancer pain patients: two Delphi surveys of pain management experts in Denmark. (United States)

    Jacobsen, Ramune; Møldrup, Claus; Christrup, Lona


    To describe the rationale behind the choice of fentanyl administration forms as reported by Danish nurses and physicians specializing in pain management. Sixty nurses and 60 physicians specializing in pain management in Denmark were contacted via an Internet survey system to perform two Delphi surveys. In the brainstorming phase, the main reasons for administering and not administering fentanyl patches and oral transmucosal fentanyl citrate (OTFC) were identified. In the second phase, the nursing and medical experts rated the importance of these reasons on an 11-point Numerical Rating Scale. Responses from 10 pain nurses and 14 pain doctors were used for the final analysis. Impossible or difficult oral intake of analgesia was the most important reason to administer fenantyl patches, whereas patients' dermatological problems and neuropathic pain origin were the most important reasons for not administering fenantyl patches in both panels. OTFC was presented as an alternative or second choice administration form for breakthrough cancer pain by both nurses and doctors. A damaged mouth, the high cost, and energy required for administration of this medication were reported as the main reasons why OTFC was only rarely prescribed to cancer pain patients in Denmark. The reasons for administering fentanyl in different administration forms reported by Danish pain nurses and pain specialists partly differed from those derived from the literature. Studies of pain management traditions could improve the understanding of the reasons for analgesic administration.

  3. Nurse's role in controlling cancer pain. (United States)

    Mahfudh, Salma Said


    Nurses spend more time with patients than any other member of the healthcare team. They play a critical, active and very important part in controlling cancer patients' pain and alleviating suffering. In controlling cancer pain the nurse needs to understand the psychological state of the cancer patient, cancer pain, cancer pain treatment, deleterious effects of unrelieved cancer pain and patient's socio cultural background. She needs to understand that there are two types of pain, nociceptive and neuropathic pains and that 80% of the cancer patients in pain could have 2 or more than 4 different pains at the same time. Nurses' role in controlling cancer pain include believing the patient, assessing pain, identifying the root of the problem, planning the care, administering medication, evaluating effectiveness, ensuring good pain control and individualizing treatment. It also includes nursing interventions such as giving tender nursing care, preventing pain, educating, advocating, communicating, comforting, supporting, and counseling the patient. The nurse must use both pharmacological and non pharmacological treatments to individualize treatment, know all the drugs that are used for the treatment of Cancer Pain, how these drugs relieve pain and what their side effects are. She must use the WHO guidelines to treat pain and must choose the right drug, right dose, given at the right times, with the right intervals and to the right patient. She must evaluate effectiveness of treatment, give PRN doses for breakthrough pain and recommend for specific changes. The role of the nurse is to anticipate the patient's pain needs, advocate for the patient for what feels appropriate for him within his cultural context and incorporate the patient's belief. The nurse can physically relieve pain by promoting comfort, support painful area, gentleness in handling the patient and use nursing treatments. The nurse can recommend physiotherapy, (TENS)/Acupuncture, Occupational therapy

  4. Pharmacokinetics of Botanical Drugs and Plant Extracts. (United States)

    Dominguez More, Gina Paola; Cardenas, Paola Andrea; Costa, Geison M; Simoes, Claudia M O; Aragon, Diana Marcela


    Botanical drugs contain plant extracts, which are complex mixtures of compounds. As with conventional drugs, it is necessary to validate their efficacy and safety through preclinical and clinical studies. However, pharmacokinetic studies for active constituents or characteristic markers in botanical drugs are rare. The objective of this review was to investigate the global state of the art in pharmacokinetic studies of active ingredients present in plant extracts and botanical drugs. A review of pharmacokinetics studies of chemical constituents of plant extracts and botanical drugs was performed, with a total of 135 studies published between January 2004 and February 2015 available in recognized scientific databases. Botanical preparations were mainly found in the form of aqueous extracts of roots and rhizomes. The most widely studied species was Salvia miltiorrhiza Bunge, and the compound most frequently used as a pharmacokinetic marker was berberine. Most studies were performed using the Sprague Dawley rat model, and the preparations were mainly administered orally in a single dose. Quantification of plasma concentrations of pharmacokinetic markers was performed mainly by liquid-liquid extraction, followed by high performance liquid chromatography coupled to mass spectrometry detector. In conclusion, in recent years there has been an increasing interest among researchers worldwide in the study of pharmacokinetics of bioactive compounds in botanical drugs and plant extracts, especially those from the Traditional Chinese Medicine. Copyright© Bentham Science Publishers; For any queries, please email at

  5. Breakthrough on technical and vocational education of Taiwan: Take Oriental Institute of Technology as an example (United States)

    Chang, Horng-jinh; Wang, Whe-min


    Taiwan's economic strength has changed drastically in the past decade because of political and economic reasons; however, in order to cope with international environment, higher education must increase its breakthrough to meet the needs of enterprises. School curriculum also has to be timely changes and adjustments. This study will analyze school learning in several directions, use questionnaire to investigate students' learning stress, to find out where students' pressure lie. Also, outsourcing employers' satisfaction survey to find out what do enterprises wants to solve with the drop problem between school and enterprise. Taking Oriental Institute of Technology (OIT) as an example; over the past ten years, OIT has used overseas internships to help students overcome learning difficulties. Overseas practice courses include Penang Malaysia and Suzhou China had gained tremendous breakthrough.

  6. Heat Sweep Analysis of Thermal Breakthrough at Los Humeros and La Primavera Fields, Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Kruger, P.; Lam, S.; Molinar, R.; Aragon, A.


    Early evaluation of the potential for geothermal breakthrough of reinjected fluids in newly developed geothermal fields can be obtained with the SGP one-dimensional heat sweep model. The model was used to estimate fluid cooldown from wells selected for the first wellhead generating units to be installed at the Los Humeros and La Primavera geothermal fields in Mexico, based on staff-compiled geometric and geologic data, thermal properties of the reservoir rock, and expected production conditions. Geometric considerations were evaluated with respect to known and postulated fault zones and return flow angle of the reinjected fluid. The results show the range of parameter values that affect the rate of thermal breakthrough to an abandonment temperature of 170 ºC corresponding to the minimum inlet pressure to the CFE 5-MW wellhead generator units. 9 figs., 4 tabs., 11 refs.

  7. Breakthrough of toluene vapours in granular activated carbon filled packed bed reactor

    International Nuclear Information System (INIS)

    Mohan, N.; Kannan, G.K.; Upendra, S.; Subha, R.; Kumar, N.S.


    The objective of this research was to determine the toluene removal efficiency and breakthrough time using commercially available coconut shell-based granular activated carbon in packed bed reactor. To study the effect of toluene removal and break point time of the granular activated carbon (GAC), the parameters studied were bed lengths (2, 3, and 4 cm), concentrations (5, 10, and 15 mg l -1 ) and flow rates (20, 40, and 60 ml/min). The maximum percentage removal of 90% was achieved and the maximum carbon capacity for 5 mg l -1 of toluene, 60 ml/min flow rate and 3 cm bed length shows 607.14 mg/g. The results of dynamic adsorption in a packed bed were consistent with those of equilibrium adsorption by gravimetric method. The breakthrough time and quantity shows that GAC with appropriate surface area can be utilized for air cleaning filters. The result shows that the physisorption plays main role in toluene removal.

  8. Breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis are responsive to icatibant

    DEFF Research Database (Denmark)

    Aberer, Werner; Maurer, Marcus; Bouillet, Laurence


    BACKGROUND: Patients with hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) experience recurrent attacks of cutaneous or submucosal edema that may be frequent and severe; prophylactic treatments can be prescribed to prevent attacks. However, despite the use of long......-term prophylaxis (LTP), breakthrough attacks are known to occur. We used data from the Icatibant Outcome Survey (IOS) to evaluate the characteristics of breakthrough attacks and the effectiveness of icatibant as a treatment option. METHODS: Data on LTP use, attacks, and treatments were recorded. Attack...... characteristics, treatment characteristics, and outcomes (time to treatment, time to resolution, and duration of attack) were compared for attacks that occurred with versus without LTP. RESULTS: Data on 3228 icatibant-treated attacks from 448 patients with C1-INH-HAE were analyzed; 30.1% of attacks occurred while...

  9. Electrical breakthrough effect for end pointing in 90 and 45 nm node circuit edit

    International Nuclear Information System (INIS)

    Liu, Kun; Soskov, Alex; Scipioni, Larry; Bassom, Neil; Sijbrandij, Sybren; Smith, Gerald


    The interaction between high-energy Ga + ions and condensed matter is studied for circuit edit applications. A new 'electrical breakthrough effect' due to charging of, and Ga + penetration/doping into, dielectrics is discovered. This new effect is proposed for end pointing in 90 and 45 nm node circuit edits where integrated circuit device dimensions are of a few hundred nanometers. This new end point approach is very sensitive, reliable, and precise. Most importantly, it is not sensitive to device dimensions. A series of circuit edits involving milling holes of high aspect ratio (5-30) and small cross-section area (0.01-0.25 μm 2 ) on real chips has been successfully performed using the electrical breakthrough effect as the end point method

  10. [Hindfoot pain]. (United States)

    Damiano, Joël; Bouysset, Maurice


    The hindfoot is the part of the foot which is proximal to the midtarsal joint. The obvious causes of pain are not considered (post-traumatic etiologies, sprains and fractures but also cutaneous lesions). The main etiologies on the subject are successively exposed by following the localization of the pain. Diffuse pains (ankle arthritis tarsal osteoarthritis, algodystrophy, calcaneo-navicular synostosis but also bone diseases like stress fractures, Paget disease or tumors). Plantar talalgia (Sever's disease, plantar fasciitis and entrapment neuropathies such as (esions of the medial calcaneal nerve, of the first branch of the plantar lateral nerve, medial plantar nerve and lateral plantar nerve). Posterior pains: calcaneal tendinopathy including peritendinitis, tendinosis, retro-calcaneal bursitis and pathology of the postero-lateral talar tuberosity. Medial pains: tendinopathies of the posterior tibial tendon and tendinopathy of the flexor hallucis longus tendon and tarsal tunnel syndrome. Lateral pains: fibularis tendinopathies including split lesions of the fibularis brevis tendon, displacement of the fibularis iongus tendon, sinus tarsi syndrome and finally thickenings of capsules and ligaments and ossifications localized under the tibial malleoli. Anterior pains: antero-inferior tibio-fibular ligament, anterior tibial tendinopathy and anterior impingment syndrome.

  11. Ordovician gas exploration breakthrough in the Gucheng lower uplift of the Tarim Basin and its enlightenment

    Directory of Open Access Journals (Sweden)

    Wang Zhaoming


    Full Text Available A steady high yield natural gas flow was tapped in the Ordovician strata of Well Gucheng 6 drilled in the Gucheng lower uplift in the Tarim Basin in 2012, marking the discovery of another carbonate gas exploration field after the other two fields in the middle and northern Tarim Basin (the so called Tazhong and Tabei in the industry. The exploration in the Gucheng lower uplift has experienced three stages: the first stage, marine facies clastic exploration from 1995 to 2003, focusing on the Devonian Donghe sandstone lithologic traps, the Silurian overlapping lithologic traps, and the Upper Ordovician shelf slope turbidites; the second stage focusing on the reef shoal carbonate reservoirs from 2003 to 2006, during which oil and gas were first discovered in Well Gucheng 4; the third stage can be divided into two periods, in the first period, deeper insight into interbed karstification reservoir exploration, intense research on tricky seismic issues, selection of favorable zones, and 3D seismic deployment in advance laid a robust foundation for breakthroughs in oil and gas exploration; and during 2009–2012, through an in-depth investigation, Well Gucheng 6 was drilled, bringing about the major breakthrough in oil and gas exploration in this study area. This success proves that the Lower Paleozoic carbonate rocks in the Gucheng area have good geological conditions and broad prospect for oil and gas exploration, which give us enlightenment in three aspects: a. new insight into geologic understanding is the prerequisite of exploration breakthrough; b. addressing bottleneck technologies, and acquiring 3D seismic data are the guarantees of exploration breakthrough; and c. emancipation of mind and persistent exploration are key to the findings in new domains.

  12. Developing technology pushed breakthroughs:defining and assessing success factors in ICT industry


    Sarja, J. (Jari)


    Abstract The main task for most development-intensive organisations is to create, develop and commercialise new products and services. The technology push (TP) concept is considered an important competitive advantage for companies trying to create breakthrough products. Because development processes are risky and failure rates are high, especially in the case of technology pushed projects, defined success factors are valuable knowledge for the management of development-intensive firms. ...

  13. The reading-science learning-writing connection: Breakthroughs, barriers, and promises (United States)

    Holliday, William G.; Yore, Larry D.; Alvermann, Donna E.

    This article establishes a broad framework from which to interpret and evaluate the reading-science learning-writing connection. The presentation of breakthroughs, barriers, and promises is intended to outline the established links between, to identify current bottlenecks in thinking about, and to highlight productive inquiries into, print-based languages and scientific understanding. The ideas presented come from various disciplines connected to science education. The ideas are meant to be informative, provocative, integrative, supportive, and without hidden agenda.

  14. The Effect of Velocity Correlation on the Spatial Evolution of Breakthrough Curves in Heterogeneous Media (United States)

    Massoudieh, A.; Dentz, M.; Le Borgne, T.


    In heterogeneous media, the velocity distribution and the spatial correlation structure of velocity for solute particles determine the breakthrough curves and how they evolve as one moves away from the solute source. The ability to predict such evolution can help relating the spatio-statistical hydraulic properties of the media to the transport behavior and travel time distributions. While commonly used non-local transport models such as anomalous dispersion and classical continuous time random walk (CTRW) can reproduce breakthrough curve successfully by adjusting the model parameter values, they lack the ability to relate model parameters to the spatio-statistical properties of the media. This in turns limits the transferability of these models. In the research to be presented, we express concentration or flux of solutes as a distribution over their velocity. We then derive an integrodifferential equation that governs the evolution of the particle distribution over velocity at given times and locations for a particle ensemble, based on a presumed velocity correlation structure and an ergodic cross-sectional velocity distribution. This way, the spatial evolution of breakthrough curves away from the source is predicted based on cross-sectional velocity distribution and the connectivity, which is expressed by the velocity transition probability density. The transition probability is specified via a copula function that can help construct a joint distribution with a given correlation and given marginal velocities. Using this approach, we analyze the breakthrough curves depending on the velocity distribution and correlation properties. The model shows how the solute transport behavior evolves from ballistic transport at small spatial scales to Fickian dispersion at large length scales relative to the velocity correlation length.

  15. Efficacy and Safety of Oral or Nasal Fentanyl for Treatment of Breakthrough Pain in Cancer Patients: A Systematic Review. (United States)

    Rogríguez, Dulce; Urrutia, Gerard; Escobar, Yolanda; Moya, Jordi; Murillo, Maite


    Formulations of fentanyl that use buccal, sublingual, or nasal transmucosal routes of administration have been developed for the treatment of BTP in opioid-tolerant patients with cancer. The purposes of this analysis were to identify and review published data describing the efficacy and safety of different oral or nasal transmucosal fentanyl formulations for treatment of cancer-related BTP, based on a critical analysis of scientific literature. Oral transmucosal or intranasal fentanyl is an effective treatment for management of BTP episodes due to a potent analgesic effect, rapid onset of action, and sustained effect. Furthermore, it is a reasonably safe treatment, causing generally mild adverse events not leading to treatment discontinuation. Nevertheless, further progress in standardizing methodology, definitions, and criteria used both in research and in clinical practice is needed in order to generate quality information allowing a better understanding of the comparable efficacy of available formulations of fentanyl. A more rigorous assessment of long-term safety is also needed to establish a balance between benefits and risks of the available options.

  16. Pharmacokinetic models of morphine and its metabolites in neonates: Systematic comparisons of models from the literature, and development of a new meta-model

    NARCIS (Netherlands)

    K.R. Knøsgaard (Katrine Rørbæk); D.J.R. Foster (David John Richard); M. Kreilgaard (Mads); E. Sverrisdóttir (Eva); R.N. Upton (Richard Neil); J.N. van den Anker (John)


    textabstractMorphine is commonly used for pain management in preterm neonates. The aims of this study were to compare published models of neonatal pharmacokinetics of morphine and its metabolites with a new dataset, and to combine the characteristics of the best predictive models to design a

  17. Compacted artificially cemented soil-acid leachate contaminant interactions: breakthrough curves and transport parameters. (United States)

    Knop, Alexandre; VanGulck, Jamie; Heineck, Karla Salvagni; Consoli, Nilo Cesar


    The transport of contaminants through compacted artificially cemented soil subjected to acid leachate contaminant percolation was analyzed by means of laboratory column tests. The effect of cement content, degree of acidity and hydraulic gradient were evaluated after permeation of several pore volumes of acid leachate contaminant flow through the soil. The pH, electric conductivity and solute breakthrough curves were considered throughout the study. The results showed that the increase of cement content increases the solute pore volumes needed before breakthrough occurred. An increase of the degree of acidity of the percolate and of the hydraulic gradient cause a reduction in the pore volumes needed before breakthrough occurred. The larger the soil cement content, the longer the time required to reach maximum effluent solute concentration. The hydraulic conductivity slightly increased due to cement addition and reduced with increasing degree of acidity of the percolate. Finally, it is possible to state that cement addition to the soil was responsible for increasing retardation coefficient (R) and distribution coefficient (kd) values, meaning that the artificially cemented soils have higher capability to retard the propagation of the contamination and amplified affinity with dissolved acid contaminant.

  18. Carbon dioxide adsorption on polyacrylamide-impregnated silica gel and breakthrough modeling (United States)

    Zhao, Yi; Shen, Yanmei; Bai, Lu; Ni, Shiqing


    Polyacrylamide-impregnated silica gel was prepared to capture CO2 from flue gas. The polymerization of acrylamide was carried out in AN solvent using AIBN as initiator and EGDMA as crosslinker. The adsorbents were characterized by N2 adsorption, FTIR analysis, SEM analysis, and thermal gravimetric analysis. The results showed that the polymer was not only occupying the porosity of the silica, but necessarily surrounding silica particles, and the amide groups was successfully loaded on the support silica. The impregnated silica displayed good thermal-stability at 250 °C. The CO2 adsorption isotherms were measured to examine CO2 adsorption on adsorbents, and the results showed that the capacity was increased significantly after modification. The CO2 isosteric adsorption heats calculated from the isotherms showed that the adsorption interaction of CO2 with the functionalized material may be mainly an intermolecular force or hydrogen bond. Fixed-bed breakthrough model of CO2 adsorption on functionalized silica was successfully developed to describe the breakthrough curves under different adsorption temperature, CO2 concentration, and gas flow rate. The mass transfer coefficients of CO2 were calculated from the breakthrough model, the results showed that adsorption rate could be promoted by increasing temperature, flow rate and CO2 concentration, among which the effect of gas flow rate is the most obvious.

  19. Breakthrough revisited: investigating the requirements for growth of dust beyond the bouncing barrier (United States)

    Booth, Richard A.; Meru, Farzana; Lee, Man Hoi; Clarke, Cathie J.


    For grain growth to proceed effectively and lead to planet formation, a number of barriers to growth must be overcome. One such barrier, relevant for compact grains in the inner regions of the disc, is the `bouncing barrier' in which large grains (˜mm size) tend to bounce off each other rather than sticking. However, by maintaining a population of small grains, it has been suggested that cm-size particles may grow rapidly by sweeping up these small grains. We present the first numerically resolved investigation into the conditions under which grains may be lucky enough to grow beyond the bouncing barrier by a series of rare collisions leading to growth (so-called `breakthrough'). Our models support previous results, and show that in simple models breakthrough requires the mass ratio at which high-velocity collisions transition to growth instead of causing fragmentation to be low, ϕ ≲ 50. However, in models that take into account the dependence of the fragmentation threshold on mass ratio, we find that breakthrough occurs more readily, even if mass transfer is relatively inefficient. This suggests that bouncing may only slow down growth, rather than preventing growth beyond a threshold barrier. However, even when growth beyond the bouncing barrier is possible, radial drift will usually prevent growth to arbitrarily large sizes.

  20. [Rapid release fentanyl administration forms. Comments of the Working Group on Tumor Pain of the German Pain Society]. (United States)

    Wirz, S; Wiese, C H R; Zimmermann, M; Junker, U; Heuser-Grannemann, E; Schenk, M


    The spectrum of indications for rapid release fentanyl preparations is controversial. For this reason the Working Group on Tumor Pain will formulate comments on how to deal with these substances. Breakthrough pain should receive individualized therapy; therefore, the use of opioids of various galenic formulations seems to be advisable. New rapid release fentanyl preparations are suitable for alleviating spontaneous breakthrough pain in tumor patients due to a rapid but short-acting effect. However, a prior optimization of the analgesic basis medication is absolutely necessary. Uncontrolled prescription for non-cancer pain must be criticized due to the problem of addiction. The medical profession should be informed about the benefits of rapid release fentanyl preparations but must also be made aware of the risk of a rapid development of addiction and tolerance. A self-commitment of the pharmaceutical industry to waive advertising for the dangerous off-label use would be desirable. In the opinion of the Working Group on Tumor Pain the use of fentanyl should be openly discussed and further scientific investigations are imperative with the aim of formulating clear recommendations.

  1. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... Learned Going to the ER Communication Tools Pain Management Programs Videos Resources FAQs Glossary Surveys Resource Guide to Chronic Pain Treatments The Art of Pain Management Partners for Understanding Pain Pain Awareness Toolkits September ...

  2. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... Surveys Resource Guide to Chronic Pain Treatments The Art of Pain Management Partners for Understanding Pain Pain ... The physician and the patient are accustomed to deal with acute pain and both naturally expect that ...

  3. Abdominal Pain (United States)

    ... are at greater risk of having anxiety as young adults [2] . Abdominal pain or bellyaches in children What ... can help the overall situation for the child. Teaching kids self-hypnosis [8] or guided imagery [8a] ...

  4. Elbow pain (United States)

    ... are gardening, playing baseball, using a screwdriver, or overusing your wrist and arm. Young children commonly develop " ... Treatment depends on the cause, but may involve: Antibiotics Corticosteroid shots Manipulation Pain medicine Physical therapy Surgery ( ...

  5. Hip Pain (United States)

    ... diagnosis and decision making. In: DeLee & Drez's Orthopaedic Sports Medicine: Principles and Practice. 4th ed. Philadelphia, Pa.: ... . Mayo Clinic Footer Legal Conditions and ...

  6. Pain Control (United States)

    ... of feelings often makes people look for the meaning that cancer and pain have in their life. ... tips: ■■ Ask your doctor if there are generic brands of your medicine available. These usually cost less ...

  7. Phantom Pain (United States)

    ... 16, 2014. Phantom pain Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  8. Urination Pain (United States)

    ... small masses of minerals) in the urinary tract. Urinary tract infections (UTIs) are the most common cause of painful urination. Signs and Symptoms burning or stinging with urination the urge to ...

  9. Joint pain (United States)

    ... or conditions. It may be linked to arthritis , bursitis , and muscle pain . No matter what causes it, ... Autoimmune diseases such as rheumatoid arthritis and lupus Bursitis Chondromalacia patellae Crystals in the joint: Gout (especially ...

  10. Shoulder pain (United States)

    ... This condition is called rotator cuff tendinitis or bursitis. Shoulder pain may also be caused by: Arthritis ... shoulder joint Bone spurs in the shoulder area Bursitis , which is inflammation of a fluid-filled sac ( ...

  11. Heel Pain (United States)

    ... in the big toe joint; an inflamed bursa (bursitis), a small, irritated sac of fluid; a neuroma ( ... sometimes painful deformity generally is the result of bursitis caused by pressure against the shoe and can ...

  12. Neuropathic Pain (United States)

    ... a Plan for an Opioid Emergency Access and Attitudes Globally Arthritis Survey Understanding Clinical Trials Resource Guide ... Guide Tension increases pain. This five-minute relaxation exercise can help you let go of physical stress ...

  13. Pain (PDQ) (United States)

    ... the PDQ summary on Acupuncture for more information. Hypnosis Hypnosis may help you relax and may be combined with other thinking and behavior methods. Hypnosis to relieve pain works best in people who ...

  14. Penis pain (United States)

    Pain - penis ... Bites, either human or insect Cancer of the penis Erection that does not go away (priapism) Genital herpes Infected hair follicles Infected prosthesis of the penis Infection under the foreskin of uncircumcised men ( balanitis ) ...

  15. Anal Pain (United States)

    ... and whole grains, exercising daily, and taking stool softeners, if needed, to facilitate bowel movements, reduce straining and ease pain Sitting in a tub of hot water up to your hips — known as a sitz ...

  16. Abdominal pain (United States)

    ... citrus, high-fat foods, fried or greasy foods, tomato products, caffeine, alcohol, and carbonated beverages. Avoid aspirin, ... especially if bright red, maroon or dark, tarry black) Have chest, neck, or shoulder pain Have sudden, ...

  17. Back Pain (United States)

    ... addition, there doesn't appear to be one type of mattress that's best for people with back pain. It's probably a ... of Nondiscrimination Advertising Mayo Clinic is a not-for-profit organization ...

  18. Leg pain (United States)

    ... to a muscle cramp (also called a charley horse ). Common causes of cramps include: Dehydration or low ... muscle ( strain ) Hairline crack in the bone (stress fracture) Inflamed tendon ( tendinitis ) Shin splints (pain in the ...

  19. Treatment with subcutaneous and transdermal fentanyl: results from a population pharmacokinetic study in cancer patients. (United States)

    Oosten, Astrid W; Abrantes, João A; Jönsson, Siv; de Bruijn, Peter; Kuip, Evelien J M; Falcão, Amílcar; van der Rijt, Carin C D; Mathijssen, Ron H J


    Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the pharmacokinetics of subcutaneous and transdermal fentanyl. Furthermore, we evaluated rotations from the subcutaneous to the transdermal route. Fifty-two patients treated with subcutaneous and/or transdermal fentanyl for moderate to severe cancer-related pain participated. A population pharmacokinetic model was developed and evaluated using non-linear mixed-effects modelling. For rotations from subcutaneous to transdermal fentanyl, a 1:1 dose conversion ratio was used while the subcutaneous infusion was continued for 12 h (with a 50 % tapering after 6 h). A 6-h scheme with 50 % tapering after 3 h was simulated using the final model. A one-compartment model with first-order elimination and separate first-order absorption processes for each route adequately described the data. The estimated apparent clearance of fentanyl was 49.6 L/h; the absorption rate constant for subcutaneous and transdermal fentanyl was 0.0358 and 0.0135 h(-1), respectively. Moderate to large inter-individual and inter-occasion variability was found. Around rotation from subcutaneous to transdermal fentanyl, measured and simulated plasma fentanyl concentrations rose and increasing side effects were observed. We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route.

  20. Efficacy and safety of fentanyl buccal for cancer pain management by administration through a soluble film: an update

    International Nuclear Information System (INIS)

    Delgado-Guay, Marvin Omar


    More than half of patients receiving prescription medicine for cancer pain have been reported to experience inadequate pain relief or breakthrough pain. Buccal administration can deliver lipophilic opioids rapidly to the systemic circulation through the buccal mucosa, limiting gastrointestinal motility and first-pass metabolism. This review updates the safety and efficacy of fentanyl buccal soluble film (FBSF) in patients with cancer pain. Literature was identified through searches of Medline (PubMed). Search terms included combinations of the following: cancer pain, fentanyl, fentanyl buccal soluble film, pharmacology, kinetics, safety, efficacy and toxicity. FBSF is an oral transmucosal form of fentanyl citrate developed as a treatment of breakthrough pain in opioid-tolerant patients with cancer. Studies have shown that it is well tolerated in the oral cavity, with adequate bioavailability and safety in cancer patients. Further studies are warranted to evaluate, in comparison with other short-acting opioids, its efficacy in the management of breakthrough cancer pain, its addictive potential and its economic impact in cancer patients

  1. Pharmacokinetics and pharmacodynamics of suxamethonium. (United States)

    Torda, T A; Graham, G G; Warwick, N R; Donohue, P


    A study was undertaken to determine the time constants of elimination and effect compartment equilibration of suxamethonium and for the slope exponent of the Hill equation. Twelve patients were anaesthetized with thiopentone, fentanyl, and isoflurane in nitrous oxide and oxygen. After allowing conditions to become stable, they were administered three small doses of suxamethonium by rapid intravenous injection. The responses to supramaximal stimulation of the ulnar nerve were recorded by EMG in one and by accelerometry in eleven subjects. Because of failure to recover to control conditions, one subject was deleted from analysis. The recorded drug effect was used in a non-linear curve fitting technique to derive estimates of the pharmacokinetic and pharmacodynamic parameters. The plasma concentration of suxamethonium was adequately represented by a single compartment model. The mean half-life of elimination was 47 s with a 95% confidence interval of 24 to 70 s; that of effect compartment equilibration, 211 s with a 95% confidence range of 139 to 282 s. The average slope exponent was 6.4 and its 95% confidence range was 4.6 to 8.2. The data from the first two doses were used to predict the time taken for the third dose to recover 50%. The predictions showed a mean bias of prediction error greater than 30%.

  2. Pharmacokinetics of miltefosine in Old World cutaneous leishmaniasis patients

    NARCIS (Netherlands)

    Dorlo, Thomas P. C.; van Thiel, Pieter P. A. M.; Huitema, Alwin D. R.; Keizer, Ron J.; de Vries, Henry J. C.; Beijnen, Jos H.; de Vries, Peter J.


    The pharmacokinetics of miltefosine in leishmaniasis patients are, to a great extent, unknown. We examined and characterized the pharmacokinetics of miltefosine in a group of patients with Old World (Leishmania major) cutaneous leishmaniasis. Miltefosine plasma concentrations were determined in

  3. Pharmacokinetics: an analysis of the method. (United States)

    Staubus, A E


    The field of radiology in general, and gastrointestinal radiology in particular, can and has benefited by the application of pharmacokinetic principles in contrast agent research and development. The application of basic pharmacokinetic principles can aid in the design of new synthetic analogues. In many cases, the presence or the absence of certain functional groups in particular locations on the aromatic ring system can predictively influence the binding, clearance and half-life values of these compounds. Detailed pharmacokinetic understanding of gastrointestinal contrast agents, particularly cholecystopaques, hold the key for unlocking the "black box" aspects of hepatic/biliary functions. Specific agents are currently quantitating and characterizing hepatic uptake, enzyme transformations, and biliary excretion functions of the liver. Pharmacokinetic principles can also be applied within the clinical radiology setting. Studies are currently underway to correlate blood iodine levels following iopanoic acid (Telepaque) administration with the causes of gallbladder nonvisualization. In summary, the use of pharmacokinetics has and will continue to assist the gastrointestinal radiologist interested in developmental, basic, and/or clinical research.

  4. Peritoneal Nebulization of Ropivacaine during Laparoscopic Cholecystectomy: Dose Finding and Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    Massimo Allegri


    Full Text Available Background. Intraperitoneal nebulization of ropivacaine reduces postoperative pain and morphine consumption after laparoscopic surgery. The aim of this multicenter double-blind randomized controlled trial was to assess the efficacy of different doses and dose-related absorption of ropivacaine when nebulized in the peritoneal cavity during laparoscopic cholecystectomy. Methods. Patients were randomized to receive 50, 100, or 150 mg of ropivacaine 1% by peritoneal nebulization through a nebulizer. Morphine consumption, pain intensity in the abdomen, wound and shoulder, time to unassisted ambulation, discharge time, and adverse effects were collected during the first 48 hours after surgery. The pharmacokinetics of ropivacaine was evaluated using high performance liquid chromatography. Results. Nebulization of 50 mg of ropivacaine had the same effect of 100 or 150 mg in terms of postoperative morphine consumption, shoulder pain, postoperative nausea and vomiting, activity resumption, and hospital discharge timing (>0.05. Plasma concentrations did not reach toxic levels in any patient, and no significant differences were observed between groups (P>0.05. Conclusions. There is no enhancement in analgesic efficacy with higher doses of nebulized ropivacaine during laparoscopic cholecystectomy. When administered with a microvibration-based aerosol humidification system, the pharmacokinetics of ropivacaine is constant and maintains an adequate safety profile for each dosage tested.

  5. Making synthetic mudstone: Parametric resedimentation studies at high effective stress to determine controls on breakthrough pressure and permeability (United States)

    Guiltinan, E. J.; Cardenas, M. B.; Cockrell, L.; Espinoza, N.


    The geologic sequestration of CO2 is widely considered a potential solution for decreasing anthropogenic atmospheric CO2 emissions. As CO2 rises buoyantly within a reservoir it pools beneath a caprock and a pressure is exerted upon the pores of the caprock proportionally to the height of the pool. The breakthrough pressure is the point at which CO2 begins to flow freely across the caprock. Understanding the mineralogical and grain size controls on breakthrough pressure is important for screening the security of CO2 sequestration sites. However, breakthrough pressure and permeability measurements on caprocks are difficult to conduct in a systematic manner given the variability in and heterogeneity of naturally occurring mudstones and shales causing significant noise and scatter in the literature. Recent work has even revealed the ability for CO2 to pass through thin shale beds at relatively low pressures. To broaden the understanding of shale breakthrough and permeability, we developed an approach that allows for the creation of resedimented mudstones at high effective stresses. Resedimented samples also include calcium carbonate cement. Using this technique, we explore the controls on entry pressure, breakthrough pressure, and permeability of synthetic mudstones. Understanding the effect of mineralogy and grain size on the permeability and breakthrough pressure of mudstones at reservoir stresses will help in the selection and uncertainty quantification of secure CO2 storage sites.

  6. Heritability of metoprolol and torsemide pharmacokinetics

    DEFF Research Database (Denmark)

    Matthaei, Johannes; Brockmöller, Jürgen; Tzvetkov, Mladen


    Genetic variation in the pharmacokinetics of metoprolol and torsemide due to polymorphisms in CYP2D6, CYP2C9 and OATP1B1 has been extensively studied. However, it is still unknown how much of variation in pharmacokinetics of these two clinically important drugs in total is due to genetic factors....... Metoprolol and torsemide were intravenously administered to 44 monozygotic and 14 dizygotic twin pairs. Metoprolol AUC varied 4.7-fold and torsemide AUC 3.5-fold. A very high fraction of AUC variations, 91% of metoprolol and 86% of torsemide, were found to be due to additive genetic effects. However, known...... of the heritable variability in the pharmacokinetics of metoprolol and torsemide remains to be elucidated. This article is protected by copyright. All rights reserved....

  7. Bioavailability and pharmacokinetics of oral meloxicam in llamas

    Directory of Open Access Journals (Sweden)

    Kreuder Amanda J


    Full Text Available Abstract Background South American camelids in the United States have rapidly developed into an important agricultural industry in need of veterinary services. Pain management is challenging in camelids because there are no drugs currently approved by the U.S. Food and Drug Administration for use in these species. Dosage regimens used for many therapeutic drugs have been extrapolated from other ruminants; however, the pharmacokinetics, in camelids, may differ from those of other species. Studies investigating the pharmacokinetics of cyclooxygenase-2 (COX-2 selective non-steroidal anti-inflammatory drugs in camelids are deficient in the published literature. Six adult llamas (121- 168 kg were administered either a 1 mg/kg dose of oral or a 0.5 mg/kg dose of IV meloxicam in a randomized cross-over design with an 11 day washout period between treatments. Plasma samples collected up to 96 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry detection (HPLC-MS followed by non-compartmental pharmacokinetic analysis. Results A mean peak plasma concentration (CMAX of 1.314 μg/mL (Range: 0.826 – 1.776 μg/mL was recorded at 21.4 hours (Range: 12.0 – 24.0 hours with a half-life (T ½ λz of 22.7 hours (Range: 18.0 – 30.8 hours after oral meloxicam administration. In comparison, a half-life (T ½ λz of 17.4 hours (Range: 16.2 – 20.7 hours was demonstrated with IV meloxicam administration. The oral bioavailability (F of meloxicam (dose normalized was 76% (Range: 48 – 92%. No adverse effects associated with either treatment modality were observed in the llamas. Conclusions The mean bioavailability (F of oral meloxicam was 76% indicating a high degree of gastrointestinal absorption. Plasma meloxicam concentrations >0.2 μg/mL were maintained for up to 72 h after oral administration; >0.2 μg/mL is considered to be the concentration of meloxicam required for analgesic effects in

  8. Pharmacokinetics of bisphosphonates in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Luurila, S.; Kautiainnen, S.; Ylitalo, P.; Ylitalo, R. [Univ. of Tamperer, Dept. of Pharmacological Sciences, Tampere (Finland)


    Clodronate, pamidronate and etidronate are commonly used bisphosphonates, which accumulate extensively in arteries and some other tissues. We compared their pharmacokinetics in rabbits with those of tiludronate, the drug newly introduced to clinical use. The {sup 14}C-labelled drugs were given intravenously and plasma drug levels were monitored for up to 24 hr. The dose-related plasma concentrations of tiludronate and etidronate were clearly higher and decreased more slowly than those of clodronate and pamidronate (P<0.001). Already at 5 min., the concentrations of tiludronate and etidronate were higher than those of clodronate and pamidronate (P=0.016). At 24 hr, plasma concentration of tiludronate was 12{+-}6.6%, of etidronate 18{+-}2.5%, of clodronate 0.8{+-}0.2%, and of pamidronate 1.4{+-}0.4% of the dose per body weight. With the same dose (25 mg/kg), absolute AUC{sub 0-24hr} for tiludronate and etidronate was 9-11 times larger than for clodronate. AUC{sub 0-24hr} for pamidronate (2.5 mg/kg) was 11% of that for clodronate. Plasma clearance of tiludronate and etidronate was 9-15 times slower than that of clodronate and pamidronate. At 24 hr, the mean tissue-to-plasma ratio of tiludronate for aorta was 1.2-1.6. For bone, spleen, liver and kidneys the ratio varied from 5.4 to 52.6. The results suggest that 1) tiludronate and etidronate are removed from plasma much slower than clodronate and pamidronate, and 2) the potential of tiludronate to concentrate in arteries and bone is generally smaller than previously found with the other bisphosphonates. (au) 26 refs.

  9. Painful menstrual periods (United States)

    Menstruation - painful; Dysmenorrhea; Periods - painful; Cramps - menstrual; Menstrual cramps ... related activities for a few days during each menstrual cycle. Painful menstruation is the leading cause of ...

  10. Dysmenorrhea: Painful Periods (United States)

    ... Search FAQs Dysmenorrhea: Painful Periods Page Navigation ▼ ACOG Pregnancy Book Dysmenorrhea: Painful Periods Patient Education FAQs Dysmenorrhea: Painful Periods Patient Education Pamphlets - Spanish ...

  11. Back Pain During Pregnancy (United States)

    ... Page Navigation ▼ ACOG Pregnancy Book Back Pain During Pregnancy Patient Education FAQs Back Pain During Pregnancy Patient Education Pamphlets - Spanish Back Pain During Pregnancy FAQ115, January ...

  12. Alternative medicine - pain relief (United States)

    Acupuncture - pain relief; Hypnosis - pain relief; Guided imagery - pain relief ... neck, shoulder, knee, or elbow) Osteoarthritis Rheumatoid arthritis Hypnosis is a focused state of concentration. With self- ...

  13. Shoulder pain. (United States)

    Ramponi, Denise R


    Shoulder pain is a frequent complaint encountered in the emergency setting. A brief review of shoulder anatomy and physical examination sets the foundation for evaluation of shoulder pain. Considerations of patient's age are helpful to predict injuries. Fractured clavicles are often seen in traumatic injuries in children and young adults, whereas fractures of the humeral head are more often seen in the elderly from traumatic injuries. Shoulder dislocations are more common in teens to fourth decade. This article reviews specific acute injuries, chronic conditions, and radiologic considerations of patients with shoulder complaints encountered in emergency settings.

  14. Chest pain

    International Nuclear Information System (INIS)

    Martinez A, Juan Carlos; Saenz M, Oscar; Martinez M, Camilo; Gonzales A Francisco; Nicolas R, Jose; Vergara V, Erika P; Pereira G, Alberto M


    In emergency departments, chest pain is one of the leading motives of consultation. We thus consider it important to review aspects such as its classification, causes, and clinical profiles. Initial assessment should include a full clinical history comprising thorough anamnesis and physical examination. Adequate interpretation of auxiliary tests, ordered in accordance with suspected clinical conditions, should lead to accurate diagnosis. We highlight certain symptoms and clinical signs, ECG and X-ray findings, cardiac bio markers, arterial blood gases, and CT-scanning. Scores of severity and prognosis such as TIMI are assessed. Optimal treatment of the clinical conditions leading to chest pain depends on adequate initial approach and assessment.

  15. Comprehensive sieve analysis of breakthrough HIV-1 sequences in the RV144 vaccine efficacy trial.

    Directory of Open Access Journals (Sweden)

    Paul T Edlefsen


    Full Text Available The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated vaccine efficacy (VE of 31% for protecting low-risk Thai volunteers against acquisition of HIV-1. The impact of vaccine-induced immune responses can be investigated through sieve analysis of HIV-1 breakthrough infections (infected vaccine and placebo recipients. A V1/V2-targeted comparison of the genomes of HIV-1 breakthrough viruses identified two V2 amino acid sites that differed between the vaccine and placebo groups. Here we extended the V1/V2 analysis to the entire HIV-1 genome using an array of methods based on individual sites, k-mers and genes/proteins. We identified 56 amino acid sites or "signatures" and 119 k-mers that differed between the vaccine and placebo groups. Of those, 19 sites and 38 k-mers were located in the regions comprising the RV144 vaccine (Env-gp120, Gag, and Pro. The nine signature sites in Env-gp120 were significantly enriched for known antibody-associated sites (p = 0.0021. In particular, site 317 in the third variable loop (V3 overlapped with a hotspot of antibody recognition, and sites 369 and 424 were linked to CD4 binding site neutralization. The identified signature sites significantly covaried with other sites across the genome (mean = 32.1 more than did non-signature sites (mean = 0.9 (p < 0.0001, suggesting functional and/or structural relevance of the signature sites. Since signature sites were not preferentially restricted to the vaccine immunogens and because most of the associations were insignificant following correction for multiple testing, we predict that few of the genetic differences are strongly linked to the RV144 vaccine-induced immune pressure. In addition to presenting results of the first complete-genome analysis of the breakthrough infections in the RV144 trial, this work describes a set of statistical methods and tools applicable to analysis of breakthrough infection genomes in general vaccine

  16. Determination of hydrogeologic parameters and media nonhomogeneity from nuclear tracer breakthrough curve data

    International Nuclear Information System (INIS)

    Yu, C.; Jester, W.A.; Jarrett, A.R.


    A group transfer model has been developed for the determination of hydrogeologic parameters and medium nonhomogeneity from experimental breakthrough curves. The model is designed to handle the migration of tracers through heterogeneous and homogeneous soil systems under saturated and unsaturated conditions. It divides the medium into groups according to the water velocity in each group. Each group is evaluated in its response to the tracer in terms of flow path distance, pore-water velocity, dispersion coefficient, retardation factor, volumetric water content and mass transfer coefficients. 17 references, 3 figures

  17. Comprehensive Sieve Analysis of Breakthrough HIV-1 Sequences in the RV144 Vaccine Efficacy Trial (United States)

    Edlefsen, Paul T.; Rolland, Morgane; Hertz, Tomer; Tovanabutra, Sodsai; Gartland, Andrew J.; deCamp, Allan C.; Magaret, Craig A.; Ahmed, Hasan; Gottardo, Raphael; Juraska, Michal; McCoy, Connor; Larsen, Brendan B.; Sanders-Buell, Eric; Carrico, Chris; Menis, Sergey; Bose, Meera; Arroyo, Miguel A.; O’Connell, Robert J.; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Rerks-Ngarm, Supachai; Robb, Merlin L.; Kirys, Tatsiana; Georgiev, Ivelin S.; Kwong, Peter D.; Scheffler, Konrad; Pond, Sergei L. Kosakovsky; Carlson, Jonathan M.; Michael, Nelson L.; Schief, William R.; Mullins, James I.; Kim, Jerome H.; Gilbert, Peter B.


    The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated vaccine efficacy (VE) of 31% for protecting low-risk Thai volunteers against acquisition of HIV-1. The impact of vaccine-induced immune responses can be investigated through sieve analysis of HIV-1 breakthrough infections (infected vaccine and placebo recipients). A V1/V2-targeted comparison of the genomes of HIV-1 breakthrough viruses identified two V2 amino acid sites that differed between the vaccine and placebo groups. Here we extended the V1/V2 analysis to the entire HIV-1 genome using an array of methods based on individual sites, k-mers and genes/proteins. We identified 56 amino acid sites or “signatures” and 119 k-mers that differed between the vaccine and placebo groups. Of those, 19 sites and 38 k-mers were located in the regions comprising the RV144 vaccine (Env-gp120, Gag, and Pro). The nine signature sites in Env-gp120 were significantly enriched for known antibody-associated sites (p = 0.0021). In particular, site 317 in the third variable loop (V3) overlapped with a hotspot of antibody recognition, and sites 369 and 424 were linked to CD4 binding site neutralization. The identified signature sites significantly covaried with other sites across the genome (mean = 32.1) more than did non-signature sites (mean = 0.9) (p < 0.0001), suggesting functional and/or structural relevance of the signature sites. Since signature sites were not preferentially restricted to the vaccine immunogens and because most of the associations were insignificant following correction for multiple testing, we predict that few of the genetic differences are strongly linked to the RV144 vaccine-induced immune pressure. In addition to presenting results of the first complete-genome analysis of the breakthrough infections in the RV144 trial, this work describes a set of statistical methods and tools applicable to analysis of breakthrough infection genomes in general vaccine efficacy

  18. Considerations of breakthrough orientation on prospecting uranium resources in southwestern China

    International Nuclear Information System (INIS)

    Sun Zexuan; Kang Youchun


    Based on the study of metallogenic environment, ore control factors, and metallogenic genesis of uranium deposits, combining with regional geological background, 5 uranium metallogenic belts including Gangdise-Tengchong, Sanjiang, northwest of Sichuan, north of Sichuan, middle of Guizhou and 4 uranium metallogenic prospective belts including Gangdise, Changdu, Changtai-Daocheng and Xikang-Yunnan Axis can be classified in southwestern China. The thought of prospecting uranium resources should aim at strengthening regional geological investigation, selecting favorable metallogenic areas, accelerating regional evaluation and implementing uranium resources survey gradually. The breakthrough orientation includes expanding old mining areas, opening up new bases, prospecting new types, and raising comprehensive value for unconventional uranium resources. (authors)

  19. Accelerated approval and breakthrough therapy designation: oncology drug development on speed? (United States)

    Yao, James C; Meric-Bernstam, Funda; Lee, J Jack; Eckhardt, S Gail


    Recent advances in biotechnology have led to discoveries resulting in major improvements in the therapy of refractory malignancies, although most advanced cancers remain incurable. Thus, there is global consensus around the need to streamline the drug approval process for effective agents. Accelerated Approval and Breakthrough Therapy Designation hold the promise of making new treatments available sooner through the use of smaller studies using intermediate endpoints. Here, we consider the inherent limitations of smaller studies and discuss the strategies for hastening oncology drug development while maintaining high-efficacy standards. ©2013 AACR.

  20. So That's How! 2007 Microsoft® Office System Timesavers, Breakthroughs, & Everyday Genius

    CERN Document Server

    Archilla, Evan


    Turn your productivity drains into productivity gains! With this practical (and fun) guide, you'll discover the best ways to tackle your daily work with the 2007 Microsoft Office system. The authors have taught thousands of people to get better results with less effort. Now these efficiency experts let you steal from their "tip jar" full of timesaving shortcuts and other brilliant ideas. You'll explore what's new in your favorite Microsoft Office programs-and transform the way you work. Get timesavers, breakthroughs, & everyday genius to: Take control of your inbox, calendar, and everyday in

  1. Achilles Pain. (United States)

    Connors, G. Patrick

    Five ailments which can cause pain in the achilles tendon area are: (1) muscular strain, involving the stretching or tearing of muscle or tendon fibers; (2) a contusion, inflammation or infection called tenosynovitis; (3) tendonitis, the inflammation of the tendon; (4) calcaneal bursitis, the inflammation of the bursa between the achilles tendon…

  2. Foot pain


    Formosa, Aaron


    Foot complaints are very common in general practice and their incidence increases with age. Three out of four people complain of foot pain during the course of a lifetime, while approximately 20% of people aged 65 years or older complain of non-traumatic foot problems.

  3. Arm Pain (United States)

    ... ed. New York, N.Y.: The McGraw-Hill Companies; 2013. http://accessmedicine. com. Accessed Jan. 16, 2016. Jan. 11, 2018 Original article: . Mayo Clinic Footer Legal Conditions and ...

  4. Pharmacokinetics and pharmacokinetic variability of heroin and its metabolites: review of the literature

    NARCIS (Netherlands)

    Rook, Elisabeth J.; Huitema, Alwin D. R.; van den Brink, Wim; van Ree, Jan M.; Beijnen, Jos H.


    This article reviews the pharmacokinetics of heroin after intravenous, oral, intranasal, intramuscular and rectal application and after inhalation in humans, with a special focus on heroin maintenance therapy in heroin dependent patients. In heroin maintenance therapy high doses pharmaceutically

  5. A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways. (United States)

    Dallmann, André; Ince, Ibrahim; Coboeken, Katrin; Eissing, Thomas; Hempel, Georg


    Physiologically based pharmacokinetic modeling is considered a valuable tool for predicting pharmacokinetic changes in pregnancy to subsequently guide in-vivo pharmacokinetic trials in pregnant women. The objective of this study was to extend and verify a previously developed physiologically based pharmacokinetic model for pregnant women for the prediction of pharmacokinetics of drugs metabolized via several cytochrome P450 enzymes. Quantitative information on gestation-specific changes in enzyme activity available in the literature was incorporated in a pregnancy physiologically based pharmacokinetic model and the pharmacokinetics of eight drugs metabolized via one or multiple cytochrome P450 enzymes was predicted. The tested drugs were caffeine, midazolam, nifedipine, metoprolol, ondansetron, granisetron, diazepam, and metronidazole. Pharmacokinetic predictions were evaluated by comparison with in-vivo pharmacokinetic data obtained from the literature. The pregnancy physiologically based pharmacokinetic model successfully predicted the pharmacokinetics of all tested drugs. The observed pregnancy-induced pharmacokinetic changes were qualitatively and quantitatively reasonably well predicted for all drugs. Ninety-seven percent of the mean plasma concentrations predicted in pregnant women fell within a twofold error range and 63% within a 1.25-fold error range. For all drugs, the predicted area under the concentration-time curve was within a 1.25-fold error range. The presented pregnancy physiologically based pharmacokinetic model can quantitatively predict the pharmacokinetics of drugs that are metabolized via one or multiple cytochrome P450 enzymes by integrating prior knowledge of the pregnancy-related effect on these enzymes. This pregnancy physiologically based pharmacokinetic model may thus be used to identify potential exposure changes in pregnant women a priori and to eventually support informed decision making when clinical trials are designed in this

  6. Ethnic and genetic factors in methadone pharmacokinetics: A population pharmacokinetic study☆ (United States)

    Bart, Gavin; Lenz, Scott; Straka, Robert J.; Brundage, Richard C.


    Background Treatment of opiate use disorders with methadone is complicated by wide interindividual variability in pharmacokinetics. To identify potentially contributing covariates in methadone pharmacokinetics, we used population pharmacokinetic modeling to estimate clearance (CL/F) and volume of distribution (V/F) for each methadone enantiomer in an ethnically diverse methadone maintained population. Methods Plasma levels of the opiate-active R-methadone and opiate-inactive S-methadone were measured in 206 methadone maintained subjects approximately two and twenty-three hours after a daily oral dose of racmethadone. A linear one-compartment population pharmacokinetic model with first-order conditional estimation with interaction (FOCE-I) was used to evaluate methadone CL/F and V/F. The influence of covariates on parameter estimates was evaluated using stepwise covariate modeling. Covariates included ethnicity, gender, weight, BMI, age, methadone dose, and 21 single nucleotide polymorphisms in genes implicated in methadone pharmacokinetics. Results In the final model, for each enantiomer, Hmong ethnicity reduced CL/F by approximately 30% and the rs2032582 (ABCB1 2677G > T/A) GG genotype was associated with a 20% reduction in CL/F. The presence of the rs3745274 minor allele (CYP2B6 515G > T) reduced CL/F by up to 20% for S-methadone only. A smaller effect of age was noted on CL/F for R-methadone. Conclusion This is the first report showing the influence of the rs2032582 and rs3745274 variants on methadone pharmacokinetics rather than simply dose requirements or plasma levels. Population pharmacokinetics is a valuable method for identifying the influences on methadone pharmacokinetic variability. PMID:25456329

  7. When Sex Is Painful (United States)

    ... AQ FREQUENTLY ASKED QUESTIONS GYNECOLOGIC PROBLEMS FAQ020 When Sex Is Painful • How common is painful sex? • What causes pain during sex? • Where is pain during sex felt? • When should ...

  8. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... Surveys Resource Guide to Chronic Pain Treatments The Art of Pain Management Partners for Understanding Pain Pain ... web site was made possible through an unrestricted educational grant from Medtronic Foundation and Purdue Pharma. Medtronic ...

  9. Effect of Relative Humidity on Adsorption Breakthrough of CO2 on Activated Carbon Fibers

    Directory of Open Access Journals (Sweden)

    Yu-Chun Chiang


    Full Text Available Microporous activated carbon fibers (ACFs were developed for CO2 capture based on potassium hydroxide (KOH activation and tetraethylenepentamine (TEPA amination. The material properties of the modified ACFs were characterized using several techniques. The adsorption breakthrough curves of CO2 were measured and the effect of relative humidity in the carrier gas was determined. The KOH activation at high temperature generated additional pore networks and the intercalation of metallic K into the carbon matrix, leading to the production of mesopore and micropore volumes and providing access to the active sites in the micropores. However, this treatment also resulted in the loss of nitrogen functionalities. The TEPA amination has successfully introduced nitrogen functionalities onto the fiber surface, but its long-chain structure blocked parts of the micropores and, thus, made the available surface area and pore volume limited. Introduction of the power of time into the Wheeler equation was required to fit the data well. The relative humidity within the studied range had almost no effects on the breakthrough curves. It was expected that the concentration of CO2 was high enough so that the impact on CO2 adsorption capacity lessened due to increased relative humidity.

  10. Design and optimization of a chronotherapeutic dosage form for treatment of nocturnal acid breakthrough. (United States)

    Agarwal, Vaibhav; Bansal, Mayank


    Present work focuses on the use of tamarind gum to develop a drug delivery system making combined use of floating and pulsatile principles, for the chrono-prevention of nocturnal acid breakthrough. The desired aim was achieved by fabricating a floating delivery system bearing time - lagged coating of Tamarindus indica seed polymer for the programmed release of Famotidine. Response Surface METHODology was the statistical tool that was employed for experiment designing, mathematical model generation and optimization study. A 32 full factorial design was used in designing the experiment. % weight ratio of tamarind gum to ethyl cellulose in the coating combination and the coating weight were the independent variables, whereas the lag time for drug release and the cumulative % drug release in 330 minutes were the observed responses. Results revealed that both the coating composition and the coating weight significantly affected the release of drug from the dosage form. The optimized formulation prepared according to the computer generated software, Design-Expert® deciphered response which were in close proximity with the experimental responses, thus confirming the robustness and accuracy of the predicted model for the utilization of natural polymer like tamarind gum for the chronotherapeutic treatment of nocturnal acid breakthrough.

  11. Hand Hygiene Improvement and Sustainability: Assessing a Breakthrough Collaborative in Western Switzerland. (United States)

    Staines, Anthony; Amherdt, Isabelle; Lécureux, Estelle; Petignat, Christiane; Eggimann, Philippe; Schwab, Marcos; Pittet, Didier


    OBJECTIVE To assess hand hygiene improvement and sustainability associated with a Breakthrough Collaborative. DESIGN Multicenter analysis of hand hygiene compliance through direct observation by trained observers. SETTING A total of 5 publicly funded hospitals in 14 locations, with a total of 1,152 beds, in the County of Vaud, Switzerland. PARTICIPANTS Clinical staff. INTERVENTIONS In total, 59,272 opportunities for hand hygiene were monitored for the duration of the study, for an average of 5,921 per audit (range, 5,449-6,852). An 18-month Hand Hygiene Breakthrough Collaborative was conducted to implement the WHO multimodal promotional strategy including improved access to alcohol-based hand rub, education, performance measurement and feedback, reminders and communication, leadership engagement, and safety culture. RESULTS Overall hand hygiene compliance improved from 61.9% to 88.3% (Pstrategy for content and measurement was associated with significant and substantial improvement in compliance across all professions, all hand hygiene indications, and all participating hospitals. Infect Control Hosp Epidemiol 2017;38:1420-1427.

  12. Proposal to realize a cost breakthrough in carbon-13 production by photochemical separation

    International Nuclear Information System (INIS)

    Marling, J.B.


    A cost breakthrough can now be made in photochemical production of the rare stable isotope carbon-13. This cost breakthrough is achieved by CO 2 laser infrared multiple-photon dissociation of any of several halocarbons (Freon derivatives) such as CF 3 Cl, CF 3 Br, or CF 2 Cl 2 . The single-step carbon-13 enrichment factor for this process is approximately 50, yielding 30% pure C-13 in one step, or up to 97% pure C-13 in two steps. A three-fold carbon-13 cost reduction to below $20/gram is expected to be achieved in a small laboratory-scale demonstration facility capable of producing 4 to 8 kg/year of carbon-13, using presently available pulsed CO 2 TEA lasers at an average power level of 50 watts. Personnel costs dominate the attainable C-13 production costs in a small photochemical enrichment facility. A price reduction to $2/gm carbon-13 is feasible at carbon-13 production levels of 100 to 1000 kg/year, dominated by the Freon raw material costs

  13. First Breakthrough for Future Air-Breathing Magneto-Plasma Propulsion Systems (United States)

    Göksel, B.; Mashek, I. Ch


    A new breakthrough in jet propulsion technology since the invention of the jet engine is achieved. The first critical tests for future air-breathing magneto-plasma propulsion systems have been successfully completed. In this regard, it is also the first time that a pinching dense plasma focus discharge could be ignited at one atmosphere and driven in pulse mode using very fast, nanosecond electrostatic excitations to induce self-organized plasma channels for ignition of the propulsive main discharge. Depending on the capacitor voltage (200-600 V) the energy input at one atmosphere varies from 52-320 J/pulse corresponding to impulse bits from 1.2-8.0 mNs. Such a new pulsed plasma propulsion system driven with one thousand pulses per second would already have thrust-to-area ratios (50-150 kN/m²) of modern jet engines. An array of thrusters could enable future aircrafts and airships to start from ground and reach altitudes up to 50km and beyond. The needed high power could be provided by future compact plasma fusion reactors already in development by aerospace companies. The magneto-plasma compressor itself was originally developed by Russian scientists as plasma fusion device and was later miniaturized for supersonic flow control applications. So the first breakthrough is based on a spin-off plasma fusion technology.

  14. Physiologically-based pharmacokinetic model for Fentanyl in support of the development of Provisional Advisory Levels

    International Nuclear Information System (INIS)

    Shankaran, Harish; Adeshina, Femi; Teeguarden, Justin G.


    Provisional Advisory Levels (PALs) are tiered exposure limits for toxic chemicals in air and drinking water that are developed to assist in emergency responses. Physiologically-based pharmacokinetic (PBPK) modeling can support this process by enabling extrapolations across doses, and exposure routes, thereby addressing gaps in the available toxicity data. Here, we describe the development of a PBPK model for Fentanyl – a synthetic opioid used clinically for pain management – to support the establishment of PALs. Starting from an existing model for intravenous Fentanyl, we first optimized distribution and clearance parameters using several additional IV datasets. We then calibrated the model using pharmacokinetic data for various formulations, and determined the absorbed fraction, F, and time taken for the absorbed amount to reach 90% of its final value, t90. For aerosolized pulmonary Fentanyl, F = 1 and t90 50 human datasets. • Model predictions are in good agreement with the available pharmacokinetic data. • The model can be used for extrapolating across routes, doses and exposure durations. • We illustrate how the model can be used for developing Provisional Advisory Levels

  15. Novel enzyme formulations for improved pharmacokinetic properties and anti-inflammatory efficacies. (United States)

    Yang, Lan; Yan, Shenglei; Zhang, Yonghong; Hu, Xueyuan; Guo, Qi; Yuan, Yuming; Zhang, Jingqing


    Anti-inflammatory enzymes promote the dissolution and excretion of sticky phlegm, clean the wound surface and accelerate drug diffusion to the lesion. They play important roles in treating different types of inflammation and pain. Currently, various formulations of anti-inflammatory enzymes are successfully prepared to improve the enzymatic characteristics, pharmacokinetic properties and anti-inflammatory efficacies. The work was performed by systematically searching all available literature. An overall summary of current research about various anti-inflammatory enzymes and their novel formulations is presented. The original and improved enzymatic characteristics, pharmacokinetic properties, action mechanisms, clinical information, storage and shelf life, treatment efficacies of anti-inflammatory enzymes and their different formulations are summarized. The influencing factors such as enzyme type, source, excipient, pharmaceutical technique, administration route and dosage are analyzed. The combined application of enzymes and other drugs are included in this paper. Anti-inflammatory enzymes were widely applied in treating different types of inflammation and diseases with accompanying edema. Their novel formulations increased enzymatic stabilities, improved pharmacokinetic properties, provided different administration routes, and enhanced anti-inflammatory efficacies of anti-inflammatory enzymes but decreased side effects and toxicity. Novel enzyme formulations improve and expand the usage of anti-inflammatory enzymes. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Pharmacokinetics of a telmisartan, amlodipine and ...

    African Journals Online (AJOL)

    Plasma was prepared by centrifugation of the blood samples at 3,000 rpm for 10 min at 4 °C. Samples were stored at −70 °C in polypropylene tubes until analysis. Pharmacokinetic analysis. Analysis of each drug was performed at. Biosuntek Laboratories Co. (Seongnam, Korea), which is certified by the MFDS as employing.

  17. Pharmacokinetics Of Artemether-Lumefantrine Combination ...

    African Journals Online (AJOL)

    Objectives: The therapeutic effects of artemether monotherapy compared to artemether-lumefantrine combined therapy in malaria based on their pharmacokinetic parameters such as absorption, elimination constants, area under the curve, bioavailability, volume of distribution and half-lives were investigated. Methods: ...

  18. Pharmacokinetic comparison of seven 8-methoxypsoralen brands

    DEFF Research Database (Denmark)

    Menne, T; Andersen, Klaus Ejner; Larsen, E


    The pharmacokinetics of seven 8-MOP brands were evaluated in 7 volunteers using an incomplete bloc design. After a single oral dose the 8-MOP plasma level was followed for 3 hours. The plasma concentration was measured with a gas chromatographic - mass spectrometric method, using an isotopic...

  19. Correlation of Lipophilicity Descriptors with Pharmacokinetic

    African Journals Online (AJOL)

    Dr Olaleye

    Correlation of Lipophilicity Descriptors with Pharmacokinetic. Parameters of Selected Benzodiazepines. Adeyemo M.A1 and Idowu S.O1*. 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria. ABSTRACT. In early-stage drug discovery science, it is often important to reliably ...

  20. Pharmacokinetics and saliva secretion of paracetamol | Babalola ...

    African Journals Online (AJOL)

    A preliminary pharmacokinetic study of paracetamol was carried out in Nigerians for whom it is normal to consume paracetamol or its combination during almost any type of symptoms. After a single oral dose of 1000mg of the drug to eight adult male volunteers, paracetamol was measured in plasma and saliva using ...

  1. Pharmacokinetics of chloroquine in diabetic rabbits | Adelusi ...

    African Journals Online (AJOL)

    The pharmacokinetic parameters derived from diabetic rabbits have been compared to those of normal rabbits. Two sets of rabbits were used, normal rabbits and diabetic rabbits. The diabetic rabbits were obtained by inducing diabetes in rabbits using streptozotocin. Chloroquine at a dose of 10 mg/kg was administered to ...

  2. Pharmacokinetic Studies on Metoprolol - Eudragit Matrix Tablets ...

    African Journals Online (AJOL)

    Purpose: To investigate the pharmacokinetics of of a developed metoprolol and a reference standard (Mepressor®). Methods: Metoprolol tartrate-loaded Eudragit® FS microparticles were formulated and compressed into tablets. The tablets were tested for their physicochemical properties according to United States ...

  3. Buspirone pharmacokinetics in patients with cirrhosis

    DEFF Research Database (Denmark)

    Dalhoff, K; Poulsen, H E; Garred, P


    The pharmacokinetics of a single oral dose of buspirone (20 mg) were determined in 12 patients with cirrhosis and 12 normal subjects. The mean AUC of buspirone was 55 +/- 38 s.d. ng ml-1 h in cirrhotics and 3.5 +/- 2.4 s.d. ng ml-1 h in normals. The time until maximum concentration (tmax) attaine...

  4. Clinical Pharmacokinetics and Pharmacodynamics of Albiglutide

    DEFF Research Database (Denmark)

    Brønden, Andreas; Knop, Filip K; Christensen, Mikkel B


    Albiglutide is a long-acting, glucagon-like peptide-1 receptor agonist for subcutaneous administration with a recommended dose of 30-50 mg once weekly. The aim of this article is to outline the pharmacokinetic and pharmacodynamic properties of albiglutide including the clinical efficacy and safet...

  5. The disposition and pharmacokinetics of Dioscorea nipponica ...

    African Journals Online (AJOL)



    Nov 19, 2008 ... tissues. The radioactivity level was measured to be the highest in the liver, adrenal gland, and wall of the gastrointestinal tract. The radioactivity of TSD was still being detected in blood after 96 h. This showed TSD was ... in human body was few (Lin, 2007), the measurements of pharmacokinetics are difficult ...

  6. The disposition and pharmacokinetics of Dioscorea nipponica ...

    African Journals Online (AJOL)

    This study was aimed to investigate the disposition and pharmacokinetics of the total saponins of dioscorea (TSD) in rats. Male Sprague-Dawley rats were orally administrated with 3H labeled TSD at a single dose ratio of 80 mg TSD per 1 kg rat. Blood samples and feces were collected at different time points to measure the ...


    Michael, O S


    The German Friedrich Hartmut Dost (1910-1985) introduced the word Pharmacokinetics. Clinical pharmacokinetics is the direct application of knowledge regarding a drug's pharmacokinetics to a therapeutic situation in an individual or a population. It is the basis of therapeutic drug monitoring with the ultimate goal of keeping drugs safe. This branch of pharmacology has become the most relevant to the sub-specialty of clinical pharmacology. First reports of Clinical Pharmacokinetics in Nigeria can be credited to two gifted Nigerians, Prof Ayodele O. Iyun and Prof Lateef A. Salako, both of whom were affiliated to the great institutions- University of Ibadan (UI) and the Teaching Hospital, University College Hospital (UCH). Prof A.O Iyun was Nigeria's first home-trained Clinical Pharmacologist, while Prof L.A. Salako played a most significant role in the creation of the Department of Clinical Pharmacology, UCH. This edition of the Chronicles highlights a few of the first reports of this exciting branch of pharmacology in Nigeria. This historical review is based on publications listed on the United States National Library of Medicine database (PUBMED).

  8. Pharmacokinetics of Chloramphenicol in Sheep after Intramuscular ...

    African Journals Online (AJOL)

    The animals were bled at pre-determined time intervals and serum chloramphenicol concentrations monitored using chloramphenicol-ELISA for a period of 30 days post drug administration. Pharmacokinetic evaluation was carried out using a non-compartment analysis. The mean Cmax values obtained in the eight sheep ...

  9. Metabolism and pharmacokinetics of morphine in neonates: A review

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    Full Text Available Morphine is an agonist of the µ and k receptors, whose activation results in analgesia. Morphine-like agonists act through the µ opioid receptors to cause pain relief, sedation, euphoria and respiratory depression. Morphine is glucuronidated and sulfated at positions 3 and 6; the plasma concentration ratios correlate positively with birth weight, which probably reflects increased liver weight with increasing birth weight. Moreover, morphine clearance correlates positively with gestational age and birth weight. Steady-state morphine plasma concentrations are achieved after 24-48 hours of infusion, but the glucuronide metabolite plasma concentrations do not reach steady state before 60 hours. The morphine-3-glucuronide metabolite has lower clearance, a shorter half-life and a smaller distribution volume compared with the morphine-6 metabolite, which is the most active morphine-like agonist. Ordinary doses cause constipation, urinary retention and respiratory depression. Neonatal pain relief may require a blood level of approximately 120 ng/ml, whereas lower levels (20-40 ng/ml seem adequate for children. A bibliographic search was performed using the PubMed database and the keywords “morphine metabolism neonate” and “morphine pharmacokinetics neonate”. The initial and final cutoff points were January 1990 and September 2015, respectively. The results indicate that morphine is extensively glucuronidated and sulfated at positions 3 and 6, and that the glucuronidation rate is lower in younger neonates compared with older infants. Although much is known about morphine in neonates, further research will be required to ensure that recommended therapeutic doses for analgesia in neonates are evidence based.

  10. Pharmacokinetic and pharmacodynamic interactions between antiepileptics and antidepressants. (United States)

    Italiano, Domenico; Spina, Edoardo; de Leon, Jose


    Antiepileptic-antidepressant combinations are frequently used by clinicians; their pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions (DIs) have not been well studied but are frequently likely to be clinically relevant. This article provides a comprehensive review of PK DIs between antiepileptics and antidepressants. In the absence of PD DI studies, PD information on pharmacological mechanisms and studies on efficacy and safety of individual drugs are reviewed. The clinical relevance of the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone and the inhibitory properties of valproic acid and some antidepressants are well understood; correction factors are provided if appropriate DI studies have been completed. More PK studies are needed for: i) antiepileptics with potent inductive effects for all recently approved antidepressants; ii) high doses of mild CYP3A4 inducers, such as clobazam, eslicarbazepine, oxcarbazepine, rufinamide and topiramate for reboxetine and vilazodone; iii) valproate as a possible inhibitor, mild inducer or both a mild inducer and competitive inhibitor of some antidepressants; and iv) inhibitory effects of long-term fluoxetine use on clobazam, lacosamide, phenobarbital, primidone, carbamazepine, felbamate, tiagabine and zonisamide. Possible synergistic or additive beneficial PD DIs in generalized anxiety disorder, chronic pain, migraine prophylaxis, weight control and menopausal symptoms need study.

  11. Ovarian stem cells and neo-oogenesis: A breakthrough in reproductive biology research

    Directory of Open Access Journals (Sweden)

    S Mooyottu1


    Full Text Available The concept of ovarian stem cells which can replenish the ovarian reserve in postnatal mammalian females is a revolutionary breakthrough in reproductive biology. This idea overturned the central dogma existed in female reproductive physiology. Contradicting the popular belief that oogenesis does not occur in post natal life, researchers proved the existence of putative stem cells in ovary, which can supply functional follicles in post natal ovaries. Even though the idea of neo-oogenesis in postnatal ovaries in normal conditions is controversial, the isolation and manipulation of ovarian stem cells have got tremendous application in medical, veterinary and animal production fields. [Veterinary World 2011; 4(2.000: 89-91

  12. Marketization of Collective-owned Rural Land: A Breakthrough in Shenzhen, China

    Directory of Open Access Journals (Sweden)

    Yonghua Zou


    Full Text Available This study focuses on analyzing the ongoing land policy reform that allows collective-owned rural land transactions in the open market in Shenzhen, China. Employing a case study method, we investigate this land policy evolution through description and contextual analysis. We argue that the existing dual-track land administration system, within which the state administers market transactions, has contributed to numerous social problems, such as urban land scarcity, inefficiency of land resource allocation, and exacerbated social injustice. Following the recent actions of the central government, a collective-owned rural land parcel in Shenzhen was officially transferred in November 2013, an action viewed as a landmark step in reforming the current dual-track land system. Though the generalization of Shenzhen’s experiment nationwide faces significant barriers, Shenzhen’s breakthrough in liberalization of the rural land market indicates that China is moving toward a potential new round of land policy revolution.

  13. [Human Primordial Germ Cell Specification--Breakthrough In Culture and Hopes for Therapeutic Utilization]. (United States)

    Magnúsdóttir, Erna


    Germ cells are the precursors to the gametes that carry genetic and epigenetic information between human generations and generate a new individual. Because germ cells are specified early during embryogenesis, at the time of embryo implantation, they are inaccessible for research. Our understanding of their biology has therefore developed slowly since their identification over one hundred years ago. As a result of research into the properties of human and mouse embryonic stem cells and primordial germ cells, scientists have now succeeded in efficiently generating human primordial germ cells in culture by embryonic stem cell and induced pluripotent stem cell culture. In this review we will discuss the state of our knowledge of human primordial germ cells and how research into the pluripotent properties of human and mouse embryonic germ cells has led to this breakthrough. In addition we will discuss the possible utilization of a cell culture system of human primordial germ cells for research into and treatment of germ cell related abnormalities.

  14. Solar Spicules: Prospects for Breakthroughs in Understanding with Solar-B (United States)

    Sterling, A. C.


    Spicules densely populate the lower solar atmosphere; any image or movie of the chromosphere shows a plethora of them or their "cousins," such as mottles or fibrils. Yet despite several decades of effort we still do not know the mechanism that generates them, or how important their contribution is to the material and energy balance of the overall solar atmosphere. Solar-B will provide exciting new chromospheric observations at high time- and spatial-resolution, along with associated quality magnetic field data, that promise to open doors to revolutionary breakthroughs in spicule research. In this presentation we will review the current observational and theoretical status of spicule studies, and discuss prospects for advances in spicule understanding during the Solar-B era.

  15. Trial Design and Efficacy Thresholds for Granting Breakthrough Therapy Designation in Oncology. (United States)

    Kern, Kenneth A


    Breakthrough therapy designation (BTD) is a new approach created by the US Congress and the US Food and Drug Administration (FDA) as part of the FDA Innovation and Safety Act of 2012 to expedite the drug development process for serious illness, including cancer. By law, to qualify for BTD, a new molecular entity must demonstrate substantial clinical improvement over existing therapies. Although the administrative requirements for granting BTD have been made available by the FDA, the actual trial designs, end points, and quantitative therapeutic thresholds involved in the granting process have not been made public. This literature review evaluates nine oncology new molecular entities granted BTD involved in 10 accelerated approvals and summarizes the key factors in clinical trial design leading to successful BTD applications. This information can be used by oncology research teams to set goals for BTD when developing clinical trial designs and thresholds in expedited drug development programs. Copyright © 2016 by American Society of Clinical Oncology.

  16. Posterior reversible encephalopathy syndrome and acute post-streptococcal glomerulonephritis mimicking breakthrough seizures

    Directory of Open Access Journals (Sweden)

    Kamille Abdool


    Full Text Available We report the case of a 14-year-old boy with a past history of primary generalized seizures, who had been seizure-free for 2 years on sodium valproate and presented with generalized tonic clonic seizures suggestive of breakthrough seizures. Examination revealed hypertension, impetiginous lesions of the lower limbs, microscopic hematuria, elevated antistreptolysin O titre and low complement levels consistent with acute post-streptococcal glomerulonephritis. Cranial magnetic resonance imaging (MRI demonstrated changes consistent with posterior reversible encephalopathy syndrome. Hypertension was controlled with intravenous nitroglycerin followed by oral captopril and amlodipine. Brain MRI changes returned normal within 2 weeks. The nephritis went in to remission within 2 months and after 8 months the patient has been seizure free again. Posterior reversible encephalopathy syndrome appeared to have neither short nor intermediate effect on seizure control in this patient. The relationship between posterior reversible encephalopathy syndrome and seizures is reviewed.

  17. Break-through of Mass Integration in Textile Industry through Development of Generic Water Recycle Schemes

    DEFF Research Database (Denmark)

    Wenzel, Henrik


    processing is one of the largest and oldest industries world-wide and responsible for a substantial resource consumption and pollution. Especially the wet processing part of the industry, i.e. pre-treatment, dyeing, printing and finishing, is polluting and resource consuming in terms of both water, energy......As a result of a long term South African – Danish research co-operation on Cleaner Production in textile industry, a number of generic and widely applicable water recycle schemes for textile wet processing has been developed, and the first break-through of water recycling has been achieved. Textile...... and chemicals. It entails a vast variety of water consuming processes, and like in most industries, fresh water is used in all processes with almost no exceptions. Between researchers, it was known for many years that fresh water is not needed by all processes taking place in textile wet treatment. But sound...

  18. Posterior Reversible Encephalopathy Syndrome and Acute Post-Streptococcal Glomerulonephritis Mimicking Breakthrough Seizures. (United States)

    Abdool, Kamille; Ramcharan, Kanterpersad; Bhagwandass, Neal; Persad, Navindra; Temull, Vasant; Seegobin, Karan; Mike, Cassie


    We report the case of a 14-year-old boy with a past history of primary generalized seizures, who had been seizure-free for 2 years on sodium valproate and presented with generalized tonic clonic seizures suggestive of breakthrough seizures. Examination revealed hypertension, impetiginous lesions of the lower limbs, microscopic hematuria, elevated anti-streptolysin O titre and low complement levels consistent with acute post-streptococcal glomerulonephritis. Cranial magnetic resonance imaging (MRI) demonstrated changes consistent with posterior reversible encephalopathy syndrome. Hypertension was controlled with intravenous nitroglycerin followed by oral captopril and amlodipine. Brain MRI changes returned normal within 2 weeks. The nephritis went in to remission within 2 months and after 8 months the patient has been seizure free again. Posterior reversible encephalopathy syndrome appeared to have neither short nor intermediate effect on seizure control in this patient. The relationship between posterior reversible encephalopathy syndrome and seizures is reviewed.

  19. Supply chain optimization: a practitioner's perspective on the next logistics breakthrough. (United States)

    Schlegel, G L


    The objective of this paper is to profile a practitioner's perspective on supply chain optimization and highlight the critical elements of this potential new logistics breakthrough idea. The introduction will briefly describe the existing distribution network, and business environment. This will include operational statistics, manufacturing software, and hardware configurations. The first segment will cover the critical success factors or foundations elements that are prerequisites for success. The second segment will give you a glimpse of a "working game plan" for successful migration to supply chain optimization. The final segment will briefly profile "bottom-line" benefits to be derived from the use of supply chain optimization as a strategy, tactical tool, and competitive advantage.

  20. Chemical beam epitaxy as a breakthrough technology for photovoltaic solar energy applications (United States)

    Yamaguchi, Masafumi; Warabisako, Terunori; Sugiura, Hideo


    Chemical beam epitaxy (CBE) is a possible breakthrough technology for photovoltaic (PV) solar energy applications. This paper reviews the present status of epitaxial technologies for high-efficiency III-V compound semiconductor solar cells. It also discusses the advantages of CBE technology over metalorganic chemical vapor deposition (MOCVD) and molecular beam epitaxy (MBE) for III-V compound solar cell fabrication. CBE and related growth technologies can effectively produce high-efficiency and low-cost multi-junction III-V compound solar cells. Moreover, CBE may possibly reduce solar cell fabrication costs in the future because it utilizes source materials more efficiently than MBE and MOCVD. The cost of solar cell fabrication using CBE are estimated and compared with those using MOCVD and MBE.

  1. On the late-time behavior of tracer test breakthrough curves

    Energy Technology Data Exchange (ETDEWEB)



    The authors investigated the late-time (asymptotic) behavior of tracer test breakthrough curves (BTCs) with rate-limited mass transfer (e.g., in dual or multi-porosity systems) and found that the late-time concentration, c, is given by the simple expression: c = t{sub ad} (c{sub 0}g {minus} m{sub 0}{partial_derivative}g/{partial_derivative}t), for t >> t{sub ad} and t{sub a} >> t{sub ad} where t{sub ad} is the advection time, c{sub 0} is the initial concentration in the medium, m{sub 0} is the 0th moment of the injection pulse; and t{sub a} is the mean residence time in the immobile domain (i.e., the characteristic mass transfer time). The function g is proportional to the residence time distribution in the immobile domain, the authors tabulate g for many geometries, including several distributed (multirate) models of mass transfer. Using this expression they examine the behavior of late-time concentration for a number of mass transfer models. One key results is that if rate-limited mass transfer causes the BTC to behave as a power-law at late-time (i.e., c {approximately} t{sup {minus}k}), then the underlying density function of rate coefficients must also be a power-law with the form a{sup k{minus}}, as a {r_arrow}0. This is true for both density functions of first-order and diffusion rate coefficients. BTCs with k < 3 persisting to the end of the experiment indicate a mean residence time longer than the experiment and possibly infinite, and also suggest an effective rate coefficient that is either undefined or changes as a function of observation time. They apply their analysis to breakthrough curves from Single-Well Injection-Withdrawal tests at the Waste Isolation Pilot Plant, New Mexico.

  2. Accord on “Fire and Building Safety in Bangladesh”: A Breakthrough Agreement?

    Directory of Open Access Journals (Sweden)

    Zillur Rahman


    Full Text Available This discussion aims to review the emergence of the “Accord on Fire and Building Safety in Bangladesh” signed on May 13, 2013, and evaluate if it is an international agreement “breakthrough”. The Accord is signed not only by the global clothing brands and national garment unions but also by international trade union organizations, which is a new development. This raises a question: could this agreement set a new international negotiating precedence in industrial relations between transnational corporations and international trade union organizations? In Bangladesh, globalization has played an important role for booming garment industries. Yet, lack of workers’ rights, weak safety situations, and poor working conditions have continuously been reported. Local and international solidarity movements and garment workers’ welfare associations have been emphasizing workers’ rights and better and safer working environments in workplaces since the beginning of the 1990s. However, their voices were not highly considered even there were some initiatives. Following the ‘Rana Plaza’ garment factory building collapse in April 2013, one of the world’s worst industrial accidents, with more than 1,100 dead workers, some strong measures have been taken—one of these, signing the ‘Accord on Fire and Building Safety in Bangladesh’. This is a strong achievement of a long struggle to take collective action for improving the safety in garment factories in Bangladesh. Although the Accord is understood as a game changer or breakthrough in relation to national and international agreements, do we really know yet if it is a breakthrough or not when it comes to its implementation?

  3. The Breakthrough Listen Search for Intelligent Life: L-Band Data Recovery and Analysis (United States)

    Lifset, Noah


    Breakthrough Listen is a next generation SETI project conducted under the leadership of UC Berkeley. In January 2016, it began collecting data with the Green Bank Telescope in West Virginia. It started a targeted campaign of stars within 50 pc with the L-band receiver (1.1-1.9 GHz). Enriquez et al. (2017) analyzed two thirds of this data comprising an homogeneous sample. The remaining one third of the L-band data taken since then is incomplete in some way, and thus required a different analysis. This project identified all possible issues with this data, and classified it based on its ability to be analyzed. Seven issues were found, and six are able to be accounted for with adapted analysis techniques. The data set consisted of observations of 366 stars within 50 pc, with 297 able to be analyzed and 69 needing to be re-observed. The Breakthrough Listen observation strategy uses 6 five minute observations per target star alternating between ON-target and OFF-target in the form ABACAD, which allows for easier radio-frequency interference identification. The analysis techniques, called turboSETI, search for a narrowband signal with a drifting doppler shift. For this data, a maximum drift rate of 4 Hz/s was chosen, which corresponds to an ET emitter on a planet three times the size of earth rotating three times as fast. An SNR threshold for signal detection of 15 was chosen, which allows for detection of signals with an EIRP (Equivalent Isotropic Radiated Power) of 9.72 x109 W for an emitter at a distance of 10 Ly. A total of 10 candidates signals were found, which were all determined to be either a satellite or another type of RFI. We can infer an upper limit of ~ 5 x108 stars in the milky way transmitting continuously towards earth in the L-band with a EIRP of 1012 W or greater.

  4. Photogravimagnetic assists of light sails: a mixed blessing for Breakthrough Starshot? (United States)

    Forgan, Duncan H.; Heller, René; Hippke, Michael


    Upon entering a star system, light sails are subject to both gravitational forces and radiation pressure, and can use both in concert to modify their trajectory. Moreover, stars possess significant magnetic fields, and if the sail is in any way charged, it will feel the Lorentz force also. We investigate the dynamics of so-called `photogravimagnetic assists' of sailcraft around α Centauri A, a potential first destination en route to Proxima Centauri (the goal of the Breakthrough Starshot programme). We find that a 10-m2 sail with a charge-to-mass ratio of around 10 μC g-1 or higher will need to take account of magnetic field effects during orbital manoeuvres. The magnetic field can provide an extra source of deceleration and deflection, and allow capture on to closer orbits around a target star. However, flipping the sign of the sailcraft's charge can radically change resulting trajectories, resulting in complex loop-de-loops around magnetic field lines and essentially random ejection from the star system. Even on well-behaved trajectories, the field can generate off-axis deflections at α Centauri that, while minor, can result in very poor targeting of the final destination (Proxima) post-assist. Fortunately for Breakthrough Starshot, nanosails are less prone to charging en route than their heavier counterparts, but can still accrue relatively high charge at both the origin and destination, when travelling at low speeds. Photogravimagnetic assists are highly non-trivial, and require careful course correction to mitigate against unwanted changes in trajectory.

  5. Tsetse Fly Genome Breakthrough: The FAO and IAEA Crack the Code

    International Nuclear Information System (INIS)

    Dixit, Aabha


    With the breakthrough in sequencing the genome of the tsetse fly species Glossina morsitans in April 2014, another milestone has been achieved in helping to solve a problem that has had horrendous ramifications for Africa. Finding a solution to the havoc created by tsetse flies to livestock has been a major challenge for the combined scientific efforts of the IAEA and the Food and Agriculture Organization of the United Nations (FAO), as well as for the World Health Organization (WHO), which has focused on combating human sleeping sickness. Joint research over the past decades to block the spread of severe infection from tsetse flies resulted in the introduction by the FAO and IAEA of the environmentally friendly sterile insect technique (SIT), a biologically-based method for the management of key insect pests of agricultural, medical and veterinary importance. A form of insect birth control, the SIT involves releasing mass-bred male flies that have been sterilized by low doses of radiation into infested areas, where they mate with wild females. These do not produce offspring and, as a result, the technique can suppress and, if applied systematically on an area-wide basis, eventually eradicate populations of wild flies. The newly acquired knowledge of the tsetse fly genome provides a wealth of information for the improvement of the entire SIT package and can help unravel interactions between tsetse flies, symbionts and trypanosomes. The decoding of the genome was detailed in a press release issued by the IAEA on 24 April 2014 entitled Tsetse Fly Genome Breakthrough Brings Hope for African Farmers. Tsetse flies were successfully eradicated in 1997 from the Tanzanian island of Zanzibar using the SIT. Ethiopia and Senegal are making significant progress in infested areas with the same method. The FAO and IAEA are helping 14 countries control tsetse populations through applying area-wide integrated pest management approaches

  6. 78 FR 73199 - Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs... (United States)


    ...] Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted... guidance for industry entitled ``Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted... draft guidance for industry entitled ``Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs...

  7. Pharmacokinetics of Alternative Administration Routes of Melatonin

    DEFF Research Database (Denmark)

    Zetner, D.; Andersen, L. P.H.; Rosenberg, J.


    Background: Melatonin is traditionally administered orally but has a poor and variable bioavailability. This study aims to present an overview of studies investigating the pharmacokinetics of alternative administration routes of melatonin. Methods: A systematic literature search was performed...... and included experimental or clinical studies, investigating pharmacokinetics of alternative administration routes of melatonin in vivo. Alternative administration routes were defined as all administration routes except oral and intravenous. Results: 10 studies were included in the review. Intranasal...... administration exhibited a quick absorption rate and high bioavailability. Transdermal administration displayed a variable absorption rate and possible deposition of melatonin in the skin. Oral transmucosal administration of melatonin exhibited a high plasma concentration compared to oral administration...

  8. Metabolism and pharmacokinetics of resveratrol and pterostilbene. (United States)

    Wang, Pei; Sang, Shengmin


    Beneficial properties of resveratrol and pterostilbene, a dimethyl ether analog of resveratrol, have attracted increasing interest in recent years. Resveratrol and pterostilbene exhibit many pharmacological similarities and both of them are generally considered to be safe for human consumption. Beyond the structural and general bioactivity similarities between them, large amounts of data are now available to reveal the metabolic fate and pharmacological differences between them. Pterostilbene was found to be more metabolically stable and usually exhibited stronger pharmacological activities than that of resveratrol. As a contribution to clarify and compare aspects like metabolic stability and pharmacokinetics of resveratrol and pterostilbene, as well as explain the pharmacological similarities and differences between them, this review presents and compares recent data on the metabolism and pharmacokinetics of resveratrol and pterostilbene. © 2018 BioFactors, 44(1):16-25, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  9. Minocycline pharmacokinetics and pharmacodynamics in dogs

    DEFF Research Database (Denmark)

    Maaland, Marit Gaastra; Guardabassi, Luca; Papich, Mark G.


    BACKGROUND: Although minocycline is not licensed for use in dogs, this tetracycline has therapeutic potential against meticillin-resistant Staphylococcus pseudintermedius. HYPOTHESIS/OBJECTIVES: The aim of this study was to establish rational dosage recommendations for minocycline use in dogs....... Specific objectives were to generate and analyse minocycline pharmacokinetic (PK) data on plasma and interstitial fluid (ISF) concentrations, plasma protein binding and pharmacodynamic (PD) data on antimicrobial activity against S. pseudintermedius. ANIMALS: Six healthy dogs from a research colony were....... Pharmacokinetic analysis was performed on plasma and ISF concentrations. PK/PD analysis was completed using in vitro data on plasma protein binding and minocycline susceptibility in 168 S. pseudintermedius isolates. RESULTS: Minocycline distributed to the ISF to a higher degree than predicted by the protein...

  10. Pharmacokinetics of 125I-hirudin in rats and dogs

    International Nuclear Information System (INIS)

    Richter, M.; Cyranka, U.; Nowak, G.; Walsmann, P.


    Hirudin was 125 I-labelled using a modified chloramine-T method. 125 I-hirudin proved to be a suitable marker in pharmacokinetic studies, if unchanged 125 I-hirudin in body fluids was determined by means of a binding assay using immobilized thrombin. In rats and dogs a study was performed on the pharmacokinetic behaviour of hirudin following intravenous and subcutaneous injection, resp., or one-hour infusion and pharmacokinetic parameters were calculated. (author)

  11. Preparation and ocular pharmacokinetics of ganciclovir liposomes


    Shen, Yan; Tu, Jiasheng


    Ophthalmic liposomes of ganciclovir (GCV) were prepared by the reverse phase evaporation method, and their ocular pharmacokinetics in albino rabbits were compared with those obtained after dosing with GCV solution. The in vitro transcorneal permeability of GCV liposomes was found to be 3.9-fold higher than that of the solution. After in vivo instillation in albino rabbits, no difference was found in the precorneal elimination rate of GCV from liposome vs solution dosing. The aqueous humor con...

  12. Gentamicin Pharmacokinetics in the Chicken Inner Ear


    Bunting, Eric C.; Park, Debra L.; Durham, Dianne; Girod, Douglas A.


    Avians have the unique ability to regenerate cochlear hair cells that are lost due to ototoxins or excessive noise. Many methodological techniques are available to damage the hair cells for subsequent scientific study. A recent method utilizes topical application of an ototoxic drug to the round window membrane. The current study examines the pharmacokinetics of gentamicin in the inner ear of chickens following topical application to the round window membrane or a single system...

  13. Eldercare at Home: Pain (United States)

    ... type of pain medicine. New or different pain New pain may need to be evaluated before the next regularly scheduled o ffice visit. If in doubt, call and speak with the doctor or nurse. Side effects of pain medications If the patient cannot tolerate a particular pain ...

  14. Melanocortins and Neuropathic Pain

    NARCIS (Netherlands)

    Vrinten, Dorien Henriëtte


    Neuropathic pain (pain initiated by a lesion or dysfunction of the nervous system) is characterised by symptoms such as allodynia (pain due to a stimulus that does not normally provoke pain) and hyperalgesia (an increased response to a stimulus that is normally painful). It constitutes a major

  15. Pharmacokinetics and biodistribution of genetically-engineered antibodies

    International Nuclear Information System (INIS)

    Colcher, D.; Pavlinkova, G.; Beresford, G.; Booth, B.J.M.; Choudhury, A.; Batra, S.K.; Omaha, Univ. of Nebraska Medical Center, NE


    Genetic manipulations of the immunoglobulin molecules are effective means of altering stability, functional affinity, pharmacokinetics, and biodistribution of the antibodies required for the generation of the 'magic bullet'

  16. Modelling concentration-analgesia relationships for morphine to evaluate experimental pain models

    DEFF Research Database (Denmark)

    Sverrisdóttir, Eva; Foster, David John Richard; Upton, Richard Neil


    The aim of this study was to develop population pharmacokinetic-pharmacodynamic models for morphine in experimental pain induced by skin heat and muscle pressure, and to evaluate the experimental pain models with regard to assessment of morphine pharmacodynamics. In a randomized, double......-blind, placebo-controlled, crossover study, 39 healthy volunteers received an oral dose of 30 mg morphine hydrochloride or placebo. Non-linear mixed effects modelling was used to describe the plasma concentrations of morphine and metabolites, and the analgesic effect of morphine on experimental pain in skin...... and muscle. Baseline pain metrics varied between individuals and occasions, and were described with interindividual and interoccasion variability. Placebo-response did not change with time. For both pain metrics, morphine effect was proportional to baseline pain and was described with a linear model...

  17. Poststroke Pain – but Multiple Pain Mechanisms

    Directory of Open Access Journals (Sweden)

    Vinjamuri Chari


    Full Text Available A 42-year-old man presented with acute left hemiplegia due to a right frontotemporal hemorrhagic stroke and left-sided pain. While the initial presentation suggested central poststroke pain, subsequent investigations also implicated heterotopic ossification of the left hip and amplification of previous low back pain by the new central pain. While heterotopic ossification has been commonly associated with brain injury, spinal cord injury or osseous injury, it is only rarely associated with stroke. Poststroke pain may be multifactorial, and discovering the pain mechanisms has important implications for treatment.

  18. Geopolitics of Quantum Buddhism: Our Pre-Hydrocarbon Tao Future (No Breakthrough at the Rio+20 Summit) (United States)

    Bajrektarevic, Anis


    From Rio to Rio with Kyoto, Copenhagen and Durban in between, the conclusion remains the same: we fundamentally disagree on realities of this planet and the ways we can address them. A decisive breakthrough would necessitate both wider contexts and a larger participatory base so as to identify problems, formulate policies, and broaden and…

  19. Parameterizing the Leaching Surface by Combining Curve-Fitting for Solute Breakthrough and for Spatial Solute Distribution

    NARCIS (Netherlands)

    Bloem, E.; Gee, de M.; Rooij, de G.H.


    Multi-compartment samplers (MCSs) measure unsaturated solute transport in space and time at a given depth. Sorting the breakthrough curves (BTCs) for individual compartments in descending order of total solute amount and plotting in 3D produces the leaching surface. The leaching surface is a useful

  20. Application of the rainfall infiltration breakthrough (RIB) model for groundwater recharge estimation in west coastal South Africa

    CSIR Research Space (South Africa)

    Sun, X


    Full Text Available level fluctuations (WLF) on a monthly basis was proposed in the rainfall infiltration breakthrough (RIB) model for the purpose of groundwater recharge estimation. In this paper, the physical meaning of parameters in the CRD and previous RIB models...

  1. Prediction of Breakthrough Curves for Conservative and Reactive Transport from the Structural Parameters of Highly Heterogeneous Media

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Scott [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Haslauer, Claus P. [Univ. of Tubingen (Germany); Cirpka, Olaf A. [Univ. of Tubingen (Germany); Vesselinov, Velimir Valentinov [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    The key points of this presentation were to approach the problem of linking breakthrough curve shape (RP-CTRW transition distribution) to structural parameters from a Monte Carlo approach and to use the Monte Carlo analysis to determine any empirical error

  2. Pharmacokinetics of a Sustained-release Formulation of Meloxicam After Subcutaneous Administration to Hispaniolan Amazon Parrots (Amazona ventralis). (United States)

    Guzman, David Sanchez-Migallon; Court, Michael H; Zhu, Zhaohui; Summa, Noémie; Paul-Murphy, Joanne R


    Meloxicam has been shown to have a safe and favorable pharmacodynamic profile with individual variability in Hispaniolan Amazon parrots (Amazona ventralis). In the current study, we determined the pharmacokinetics of a sustained-release formulation of meloxicam after subcutaneous administration to Hispaniolan Amazon parrots. Twelve healthy adult parrots, 6 males and 6 females, were used in the study. Blood samples were collected before (time 0) and at 0.5, 1, 2, 6, 12, 24, 48, 72, 96, and 120 hours after a single dose of the sustained-release meloxicam formulation (3 mg/kg SC). Plasma meloxicam concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters were determined by noncompartmental analysis. Plasma concentrations reached a mean C max of 23.4 μg/mL (range, 14.7-46.0 μg/mL) at 1.8 hours (range, 0.5-6 hours), with a terminal half-life of 7.4 hours (range, 1.4-40.9 hours). Individual variation was noticeable, such that some parrots (4 of 12 birds) had very low plasma meloxicam concentrations, similar to the high variability reported in a previous pharmacokinetic study of the standard meloxicam formulation in the same group of birds. Two birds developed small self-resolving scabs at the injection site. On the basis of these results, the sustained-release meloxicam formulation could be administered every 12 to 96 hours in Hispaniolan Amazon parrots to manage pain. Because of these highly variable results, the use of this formulation in this species cannot be recommended until further pharmacokinetic, safety, and pharmacogenomic evaluations are performed to establish accurate dosing recommendations and to understand the high pharmacokinetic variability.

  3. Pain in veterinary medicine in the new millennium. (United States)

    Passantino, Annamaria; Fazio, Alessandra; Quartatone, Valeria


    The practice of veterinary medicine has changed radically over the past two decades, new technology and scientific breakthroughs have occurred, in close association with the field of human medicine. This progress has not only increased the capacity of veterinarians to provide high-quality care, it has also served to increase client awareness and expectations regarding animal care. On the legal front, it has finally given a "voice" to animals, now defined as sentient beings, thus imposing a series of duties upon veterinarians to promote their welfare. Preventing and managing pain has become a fundamental element of patient care quality in veterinary medicine, and pharmacotherapy is the basis of pain management. This paper takes this as a starting point to clarify the concept of pain in veterinary medicine and explores the relevance of an ethic to the clinical setting which gives the animal patient a strong right to freedom from unnecessary pain and thus creating moral obligations towards patients on the part of veterinary professionals. There is the duty not to inflict pain and suffering beyond what is necessary for effective diagnosis and treatment on the one hand and a duty to do all that can be done to relieve all the pain and suffering which can be alleviated on the other.

  4. Chest Pain: First Aid (United States)

    ... injury Short-term, sudden anxiety with rapid breathing Peptic ulcer disease Pain from the digestive tract, such as esophageal reflux, peptic ulcer pain or gallbladder pain that may feel similar ...

  5. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... Going to the ER Communication Tools Pain Management Programs Videos Resources FAQs Glossary Surveys Resource Guide to ... MD, director of the Cleveland Clinic Pain Management Program, explains some of the physiology of pain. Narrator: ...

  6. Low back pain - chronic (United States)

    ... this page: // Low back pain - chronic To use the sharing features on this page, please enable JavaScript. Low back pain refers to pain that you feel in your ...

  7. Palliative care - managing pain (United States)

    ... page, please enable JavaScript. Palliative care is a holistic approach to care that focuses on treating pain ... stressful for you and your family. But with treatment, pain can be managed. How Pain is Measured ...

  8. Buprenorphine Buccal (chronic pain) (United States)

    Buprenorphine (Belbuca) is used to relieve severe pain in people who are expected to need pain medication ... and who cannot be treated with other medications. Buprenorphine (Belbuca) should not be used to treat pain ...

  9. Pain medications - narcotics (United States)

    ... this page: // Pain medications - narcotics To use the sharing features on this page, please enable JavaScript. Narcotics are also called opioid pain relievers. They are only used for pain that ...

  10. Topical Pain Medications (United States)

    ... skin Learn about the various types of topical pain medications available for pain relief. Can they ease your ... hurt even though you take your usual arthritis pain medication. Reluctant to pop another pill, you might wonder ...

  11. Side Effects: Pain (United States)

    Controlling pain is an important part of your cancer treatment plan. Learn how to track levels of pain. Find out how pain, a side effect of cancer treatment, is treated using acupuncture, biofeedback, and physical therapy.

  12. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... acute pain and both naturally expect that some cause will be found, and when it’s found, it ... pain even in the absence of an apparent cause. But chronic pain has a physiological or neurological ...

  13. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... the pain will go away. Part of the problem with chronic pain is that when we start ... is that the presence of a severe pain problem which exists for some period of time can ...

  14. Soul Pain

    Directory of Open Access Journals (Sweden)

    Sarah L. Jirek


    Full Text Available This study extends prior research on vicarious traumatization and emotion management by exploring a deeper, more life-altering effect of working with traumatized clients—namely, “soul pain.” Analyses of in-depth interviews with 29 advocates working with survivors of physical and sexual violence reveal that, as a direct consequence of hearing countless stories of human brutality, some staff members experience a profound wounding of their spirit. This finding expands our understanding of the occupational hazards of the helping professions by revealing another dimension of advocates’ lives—that of the soul or spirit—that may be affected by their work with trauma survivors.

  15. Comparing Adoption of Breakthrough and "Me-too" Drugs among Medicare Beneficiaries: A Case Study of Dipeptidyl Peptidase-4 Inhibitors. (United States)

    Hernandez, Inmaculada; Zhang, Yuting


    "Me-too" drugs are new pharmaceuticals with the mechanism of action of an existing drug and are considered less innovative than breakthrough drugs. The objective of this study was to evaluate whether the adoption patterns of the breakthrough drug sitagliptin and the "me-too" drug saxagliptin differed; and to assess whether the patterns differed between Medicare stand-alone (PDP) and Medicare-Advantage Part D (MA-PD) plans. Pharmacy claims from a 5% random sample of Medicare Part D beneficiaries were used to identify all prescriptions filled for sitagliptin (breakthrough drug) and saxagliptin ("me-too" drug) between October 1, 2006 and December 31, 2011. The number of new sitagliptin and saxagliptin users by month and type of plan were plotted, and Bass diffusion models were constructed to estimate the rate of diffusion. Sitagliptin had a longer adoption life than saxagliptin, and its adoption was quicker among MA-PD than PDP beneficiaries: it peaked at 51 and 66.7 months after its approval, respectively. However, the adoption of saxagliptin did not differ by type of plan: it peaked at 20.5 months in PDP and 22.9 months in MA-PD. At the end of our study, the market share of the innovative drug sitagliptin measured as the cumulative number of users since market entry was almost nine times higher than the "me-too" drug, saxagliptin. The breakthrough drug sitagliptin had a much longer adoption life compared to the "me-too" drug saxagliptin, and the breakthrough drug sitagliptin was adopted quicker among managed care plans compared to PDP plans.

  16. Old Friends With New Faces: Are Sodium Channel Blockers the Future of Adjunct Pain Medication Management? (United States)

    Thomas, Ashley M; Atkinson, Timothy J


    Providers are being asked to decrease the emphasis and overutilization of long-term opioid therapy, but many are left without proper guidance on appropriate utilization of nonopioid therapies. Furthermore, therapeutic options are quite limited and many providers lack confidence in distinguishing available alternatives. When first-line therapy has failed in a patient, there is an apparent lack of knowledge on how to proceed with choosing subsequent therapy. To choose among alternative agents, an understanding of pharmacology, pharmacokinetics, and efficacy in targeting various pain conditions is necessary. This article focuses on the use of the carboxamide class of sodium channel blockers (carbamazepine, oxcarbazepine, eslicarbazepine) for adjunct pain medication management including research updates in pharmacology, pharmacokinetics, and current evidence for pain along with promising areas of research. It is an evidence update for clinical use of sodium channel blockers, clarifies misconceptions regarding their use, and highlights emerging research for improved pain targets that justifies additional study. We performed a complete review of the literature using the search terms, "oxcarbazepine," "carbamazepine," and "eslicarbazepine" in conjunction with "pharmacokinetics," "adverse effects," "pharmacology," "voltage-gated sodium channel subtype," "neuropathic pain," "inflammatory pain," "metabolism," "epoxide metabolite formation," "drug interactions," "CYP450 interactions," "pain phenotype," and "chronic pain management." Databases searched included PubMed and Google Scholar. Package inserts were used for drug structure illustration, adverse reactions, and bioavailability. Pharmacology and pharmacokinetic data were taken from randomized controlled trials evaluating this area as well as in vitro published results. For validity, only peer-reviewed literature was included. Evidence for sodium channel blockers in chronic pain management was limited. This review focuses

  17. Pain Control After Surgery: Pain Medicines (United States)

    ... risks of opioids? Opioids can cause drowsiness, nausea, constipation, or itching. They can affect urination and breathing. ... staff Categories: Prevention and WellnessTags: adult, Drug Safety, elderly, older adults, pain killers, Pain Management, senior September ...

  18. Recent breakthroughs and themes in hydrology, from climate to the water-food-energy nexus (United States)

    Montanari, A.


    The last decades marked a significant change in geosciences. Increasing communication, observations, computing capabilities and opportunities to make dissemination stimulated a rapid increase of the number of publications and scientific forums. On the one hand this development is undoubtedly positive. In fact, it provides more and more opportunities to young and experienced scientists to elaborate innovative ideas and to establish cooperation. On the other hand, the proliferation of information, communication and publications makes the identification of key ideas and contributions definitely more challenging. Notwithstanding the above development, Water Resources Research (WRR) provides an ideal perspective to elaborate a picture of recent breakthroughs in hydrology. In fact, despite the increasing number of submissions and the progress of time, WRR kept a rigorous attitude to assess manuscripts by evaluating their relevance to emerging environmental and societal challenges.To get a long term perspective of breakthroughs in hydrology, it is interesting to compare the two anniversary special sections published so far in WRR, namely, the 50th anniversary special section "Legacy and perspectives for the science of hydrology", and "Trends and Directions in Hydrology", that was edited by Steven Burges in 1986 to celebrate the 20th anniversary of the journal. The above comparison highlights that the traditional break-up of hydrology into sub-disciplines, each focusing on separate components of the water cycle, has given way to a more interconnected, interdisciplinary research on a wide range of spatial and temporal scales, and interactions between water, society, earth and biological systems.This talk will present a voyage through the WRR history to highlight recent advances and topical themes. An attempt to develop a vision for the future of WRR and hydrology will be presented. Water will become more and more the regulator of social dynamics, including economy, politics

  19. Expedited Programs for Serious Conditions: An Update on Breakthrough Therapy Designation. (United States)

    Kwok, Martin; Foster, Theresa; Steinberg, Michael


    Our aim was to describe the regulatory pathways made available by the US Food and Drug Administration (FDA) to expedite the drug development and approval process, with a focus on the benefits and limitations of the Breakthrough Therapy Designation (BTD) pathway. Published materials consisting of journal articles, press releases, government documents, and news articles from pharmaceutical publishers were identified through online databases (ie, Medline and Scopus), the FDA website, and Internet search engines (eg, Google). To encourage pharmaceutical innovation and increase the number of products being approved each year, the FDA has introduced 4 expedited regulatory pathways to accelerate the drug development and approval process. The most recent program, enacted in July 2012, was BTD that is given to drugs that treat a serious or life-threatening disease or condition; and preliminary clinical evidence suggests the potential for these drugs to provide a substantial improvement over the current standard of care. The primary basis for the creation of BTD is to provide patients with serious conditions with earlier access to FDA-approved medications. In 2014, 22% of the new molecular entities approved within the Center for Drug Evaluation and Research had BTD status, as opposed to only 11% in 2013, which indicates both the popularity and success of this expedited pathway. Additionally, the creation of BTD has produced a more collaborative working relationship between the pharmaceutical industry and the FDA because both parties have a vested interest in the drug's success. Some of the more notable concerns surrounding these approved breakthrough therapies have been the abbreviated tolerability and efficacy evidence available from accelerated clinical development programs, ensuring the manufacturing aspects keep pace with these accelerated clinical programs, and finally, managing the strain on resources for both the pharmaceutical companies and the FDA. BTD has already

  20. Solute breakthrough during repeated ponded infiltration into columns of repacked sand and heterogeneous soil (United States)

    Sobotkova, M.; Snehota, M.; Cislerova, M.


    Water flow during recurrent ponded infiltration may be affected by presence of entrapped air in heterogeneous soils. It is likely that presence of entrapped air influences also the solute transport. The aim of this contribution is to experimentally investigate the effect of entrapped air on tracer breakthrough by means of experiments conducted on two large samples in laboratory. A modified recurrent ponded infiltration, conducted on each soil sample consisted of three infiltration runs. The same level of ponding was maintained during each infiltration run at the top of the sample. Water drained freely through the perforated plate at the bottom of the sample. First infiltration run was done into naturally dry soil while two subsequent runs were conducted into wetter soil. It is assumed that infiltration in wet media causes more air trapping and reduced effective saturated hydraulic conductivity in some heterogeneous soils. In order to demonstrate effect of entrapped air dissolution the third infiltration was conducted with partly de-aerated water. The experiments were conducted using an automated set-up with frequent monitoring of pressure heads in three tensiometers, water contents in three TDR probes, cumulative infiltration and outflow, weight of the sample monitored by load cell and concentration of oxygen in the effluent. During each infiltration run the concentration pulse of bromide tracer was applied at the top of the soil core during steady state flow. Bromide breakthrough curve was acquired by electrochemical in-line analysis of bromide ions in the effluent. The results of the experiment conducted on repacked sand show that the steady state outflow rates measured during the first and second infiltration run were similar, while the outflow rates during third infiltration runs were steadily increasing. The shapes of all three BTC’s plotted against the cumulative outflow were nearly identical. In contrast to the repacked sand, steady state outflow rates

  1. Tamoxifen for the treatment of breakthrough bleeding with the etonogestrel implant: a randomized controlled trial. (United States)

    Simmons, Katharine B; Edelman, Alison B; Fu, Rongwei; Jensen, Jeffrey T


    The etonogestrel (ENG) subdermal implant can cause frequent breakthrough bleeding in some users. The objective of this study was to evaluate whether a short course of tamoxifen reduces bleeding/spotting days compared to placebo in ENG implant users. In this double-blind trial, we randomized ENG implant users with frequent or prolonged bleeding or spotting to tamoxifen 10 mg or placebo twice daily for 7 days, to be started after 3 consecutive days of bleeding/spotting. Treatment was repeated as needed up to three times in 180 days. Subjects completed a daily text message bleeding diary. A sample size of 56 provided 80% power to detect a difference of 6 days of bleeding/spotting per 30 days by two-sample t test. Ovulation was monitored by urinary metabolites of progesterone. From March 2014 to February 2015, 56 women enrolled. Fifty-one completed at least 30 days of follow up, and 34 completed 180 days. Compared to women randomized to placebo, women randomized to tamoxifen reported 5 fewer days of bleeding/spotting over 30 days (95% confidence interval [CI] -9.9 to -0.05, p=.05), and 15.2 more continuous bleeding-free days (95% CI 2.8-27.5 days, p=.02) after first use of study drug. Conclusions could not be drawn after 30 days due to higher-than-expected dropout. No ovulation was detected. First use of tamoxifen by ENG implant users reduces bleeding/spotting days and provides a longer cessation of bleeding/spotting than placebo, without compromising ovulation suppression. Further study is needed to determine whether this effect is maintained with repeat use. Women with frequent ENG implant-related breakthrough bleeding may experience a reduction in bleeding/spotting days and an increase in continuous bleeding-free days in the month following first use of tamoxifen. This short course of tamoxifen was well tolerated with bleeding cessation noted within a median of 5 days. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. FRB121102: First detection across 5 - 8 GHz and spectral properties from the Breakthrough Listen instrument (United States)

    Gajjar, Vishal; Siemion, Andrew; MacMohan, David; Croft, Steve; Hellbourg, Greg; Isaacson, Howard; Enriquez, J. Emilio; Price, Daniel; Lebofsky, Matt; De Boer, David; Werthimer, Dan; Hickish, Jack; Brinkman, Casey; Chatterjee, Shami; Ransom, Scott M.; Law, Casey; Hessels, Jason W. T.; Cordes, Jim; Spitler, Laura; Lynch, Ryan; McLaughlin, Maura; Scholz, Paul; Marcote, Benito; Bower, Geoffrey C.; Tendulkar, Shriharsh


    Fast Radio Bursts (FRBs) are some of the most energetic and enigmatic events in the Universe. The origin of these sources is among the most challenging questions of modern-day astrophysics. Thus, it is imperative to understand the properties of these bursts across a range of radio frequencies. Among the known FRBs, FRB121102 is the only source known to show repeated bursts [Spitler et al., Nature, 531, 7593 202-205, 2016], which can allow a detailed investigation of various origin models. In August 2017, we initiated a campaign observing FRB 121102 using the Breakthrough Listen Digital Backend with the C-band receiver at the Robert C. Byrd Green Bank Telescope (GBT). We recorded baseband voltage data across 5.4 GHz of bandwidth, completely covering the C-band receiver's nominal 4-8 GHz band [MacMahon et al. arXiv:1707.06024v2]. The recorded data were searched for dispersed pulses consistent with the known dispersion measure of FRB 121102 (557 pc cm-3) using high-speed GPU software tools. We detected 21 bursts above our detection threshold of 6 sigmas in the first 60-minutes, out of which 18 occurred in the first 30-minutes only. To our knowledge, this is the highest event rate seen for FRB121102 at any observing frequency. These observations are the highest frequency and widest bandwidth detection of bursts from FRB 121102 (or any other FRB) obtained to-date. We note that individual bursts show marked changes in spectral extent ranging from hundreds of MHz to several GHz. We have used high frequency dynamic spectra of these bursts to estimate the characteristic scintillation bandwidth and correlation time-scale. We also found distinctive temporal structures, separated by a few milliseconds, in three of the strongest bursts, with each sub-structure exhibiting varied spectral features. We will discuss our findings and how these detections of FRB 121102 around 8 GHz opens up a new regime in scrutinizing various origin models. We will also highlight the unique

  3. [Benign chronic pain]. (United States)

    Serrie, A; Thurel, C


    Recent data indicate that 25 to 30% of the population in industrialized countries suffers from benign chronic pain. Among these patients, 50 to 75% are professionally incapable for varied lengths of time, from a few days to some weeks or months, or even definitively. The aetiology and clinical presentation of chronic benign pain are enormously varied because this definition includes such different pathologies as headache, pain of rheumatologic, postsurgical, organic, and post-zoster origin, lombalgia, radiculalgia, post-amputation pain, neuropathologic pain, causalgia, algoneurodystrophic pain, psychosomatic and idiopathic pain. Since these syndromes and causes of pain could not be discussed individually, they have been grouped according to their neurophysiology and pathophysiology.

  4. Fighting Chronic Pain (United States)

    ... from clogged arteries Stomach/Digestive: Gallstones, intestinal obstruction, diverticulitis, ulcers, severe indigestion, severe gas pain, inflammatory bowel disease, colitis Urinary/Reproductive: Kidney stones, pelvic pain, vulvodynia, ...

  5. Pain and musculoskeletal pain syndromes in adolescents. (United States)

    Zapata, Aura Ligia; Moraes, Ana Julia Pantoja; Leone, Claudio; Doria-Filho, Ulysses; Silva, Clovis Artur Almeida


    The presence of musculoskeletal pain was evaluated in adolescents. Pain was reported by 40% of respondents, benign joint hypermobility syndrome by 10%, myofascial syndrome by 5%, tendonitis by 2%, and fibromialgia by 1%. Logistical regression analysis indicated that sex and age were predictive of pain.

  6. Population pharmacokinetics and relationship between demographic and clinical variables and pharmacokinetics of gentamicin in neonates

    NARCIS (Netherlands)

    Stolk, L M L; Degraeuwe, P L J; Nieman, F H M; de Wolf, M C; de Boer, A|info:eu-repo/dai/nl/075097346

    Population pharmacokinetic parameter estimates were calculated from 725 routine plasma gentamicin concentrations obtained in 177 neonates of 24 to 42 weeks' gestational age in their first week of life. Kel increases and V/W decreases with increasing gestational age. Almost identical results were

  7. Influence of obesity on propofol pharmacokinetics : derivation of a pharmacokinetic model

    NARCIS (Netherlands)

    Cortinez, L. I.; Anderson, B. J.; Penna, A.; Olivares, L.; Munoz, H. R.; Holford, N. H. G.; Struys, M. M. R. F.; Sepulveda, P.


    The objective of this study was to develop a pharmacokinetic (PK) model to characterize the influence of obesity on propofol PK parameters. Nineteen obese ASA II patients undergoing bariatric surgery were studied. Patients received propofol 2 mg kg(-1) bolus dose followed by a 5-20-40-120 min,

  8. Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach

    NARCIS (Netherlands)

    Yamamoto, Yumi; Valitalo, Pyry A.; Wong, Yin Cheong; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Beukers, Margot W.; Kokki, Hannu; Kokki, Merja; Danhof, Meindert; van Hasselt, Johan G. C.; de Lange, Elizabeth C. M.


    Knowledge of drug concentration-time profiles at the central nervous system (CNS) target-site is critically important for rational development of CNS targeted drugs. Our aim was to translate a recently published comprehensive CNS physiologically-based pharmacokinetic (PBPK) model from rat to human,

  9. The neurologist facing pain in dementia. (United States)

    Álvaro González, Luis Carlos


    . They are attributed to an early lesion in the LC, which reduces its prominent antinociceptive activity. Finally, in the demented patients there is a lack of expectations to analgesic treatments. This means an absence of the placebo effect, which is, alongside the pharmacokinetic action, an inherent part of the analgesic response. The placebo response is related to activity in the ACC and PGS. Giving its lack, higher doses of analgesics are necessary in dementias. The assessment of pain in dementia is rather complex, which is the main reason for the scarcity of the analgesic treatment in dementias. It must be specific and systematic. For this purpose, the pain scales are a useful tool. For communicative patients, simple visual scales are helpful, meanwhile in the non-communicative patients the multidimensional scales are the most suitable. By this means, the expressive, motor, emotional, functional and social interactions are evaluated. Pain may be responsible of progression and cognitive deterioration in dementia. This evolution could be reversible, and consequently it has to be foreseen in order to implement analgesic treatment. Trying to minimize adverse events, it has to be potent but closely monitored. Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  10. The Breakthrough Listen Initiative and the Future of the Search for Intelligent Life (United States)

    Enriquez, J. Emilio; Siemion, Andrew; Croft, Steve; Hellbourg, Greg; Lebofsky, Matt; MacMahon, David; Price, Danny; DeBoer, David; Werthimer, Dan


    Unprecedented recent results in the fields of exoplanets and astrobiology have dramatically increased the interest in the potential existence of intelligent life elsewhere in the galaxy. Additionally, the capabilities of modern Searches for Extraterrestrial Intelligence (SETI) have increased tremendously. Much of this improvement is due to the ongoing development of wide bandwidth radio instruments and the Moore's Law increase in computing power over the previous decades. Together, these instrumentation improvements allow for narrow band signal searches of billions of frequency channels at once.The Breakthrough Listen Initiative (BL) was launched on July 20, 2015 at the Royal Society in London, UK with the goal to conduct the most comprehensive and sensitive search for advanced life in humanity's history. Here we detail important milestones achieved during the first year and a half of the program. We describe the key BL SETI surveys and briefly describe current facilities, including the Green Bank Telescope, the Automated Planet Finder and the Parkes Observatory. We also mention the ongoing and potential collaborations focused on complementary sciences, these include pulse searches of pulsars and FRBs, as well as astrophysically powered radio emission from stars targeted by our program.We conclude with a brief view towards future SETI searches with upcoming next-generation radio facilities such as SKA and ngVLA.

  11. Breakthrough invasive fungal diseases during voriconazole treatment for aspergillosis: A 5-year retrospective cohort study. (United States)

    Kim, Sun Bean; Cho, Sung-Yeon; Lee, Dong-Gun; Choi, Jae-Ki; Lee, Hyo-Jin; Kim, Si-Hyun; Park, Sun Hee; Choi, Su-Mi; Choi, Jung-Hyun; Yoo, Jin-Hong; Lee, Jong-Wook


    Breakthrough invasive fungal diseases (bIFDs) during voriconazole treatment are concerning, as they are associated with high rates of mortality and pathogen distribution. To evaluate the prevalence, incidence, patient characteristics, including IFD events, and overall mortality of bIFDs during voriconazole treatment for invasive aspergillosis (IA). We retrospectively analyzed the medical records of consecutive patients who had undergone voriconazole treatment for IA and who had bIFD events between January 2011 and December 2015. Eleven bIFD events occurred in 9 patients. The prevalence and incidence of bIFDs were 2.25% (9/368) and 0.22 cases per year, respectively. Overall mortality was 44.4% (4/9). The severity of the illness and persistence of immunodeficiency, mixed infection, and low concentration of the treatment drug at the site of infection were identified as possible causes of bIFDs. Seven of 11 events (63.6%) required continued voriconazole treatment with drug level monitoring. In 4 (36.3%) cases, the treatment was changed to liposomal amphotericin B. Two cases resulted in surgical resection (18.2%). Clinicians should be aware that bIFDs during voriconazole treatment for IA can occur, and active therapeutic approaches are required in these cases. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.

  12. Tracking tracer breakthrough in the hyporheic zone using time‐lapse DC resistivity, Crabby Creek, Pennsylvania (United States)

    Nyquist, Jonathan E.; Toran, Laura; Fang, Allison C.; Ryan, Robert J.; Rosenberry, Donald O.


    Characterization of the hyporheic zone is of critical importance for understanding stream ecology, contaminant transport, and groundwater‐surface water interaction. A salt water tracer test was used to probe the hyporheic zone of a recently re‐engineered portion of Crabby Creek, a stream located near Philadelphia, PA. The tracer solution was tracked through a 13.5 meter segment of the stream using both a network of 25 wells sampled every 5–15 minutes and time‐lapse electrical resistivity tomographs collected every 11 minutes for six hours, with additional tomographs collected every 100 minutes for an additional 16 hours. The comparison of tracer monitoring methods is of keen interest because tracer tests are one of the few techniques available for characterizing this dynamic zone, and logistically it is far easier to collect resistivity tomographs than to install and monitor a dense network of wells. Our results show that resistivity monitoring captured the essential shape of the breakthrough curve and may indicate portions of the stream where the tracer lingered in the hyporheic zone. Time‐lapse resistivity measurements, however, represent time averages over the period required to collect a tomographic data set, and spatial averages over a volume larger than captured by a well sample. Smoothing by the resistivity data inversion algorithm further blurs the resulting tomograph; consequently resistivity monitoring underestimates the degree of fine‐scale heterogeneity in the hyporheic zone.

  13. Making Breakthroughs in the Turbulent Decade: China's Space Technology During the Cultural Revolution. (United States)

    Li, Chengzhi; Zhang, Dehui; Hu, Danian


    This article discusses why Chinese space programs were able to develop to the extent they did during the turbulent decade of the Cultural Revolution (1966-1976). It first introduces briefly what China had accomplished in rocket and missile technology before the Cultural Revolution, including the establishment of a system for research and manufacturing, breakthroughs in rocket technology, and programs for future development. It then analyzes the harmful impacts of the Cultural Revolution on Chinese space programs by examining activities of contemporary mass factions in the Seventh Ministry of Machinery Industry. In the third section, this article presents the important developments of Chinese space programs during the Cultural Revolution and explores briefly the significance of these developments for the future and overall progress in space technology. Finally, it discusses the reasons for the series of developments of Chinese space technology during the Cultural Revolution. This article concludes that, although the Cultural Revolution generated certain harmful impacts on the development of Chinese space technology, the Chinese essentially accomplished their scheduled objectives in their space program, both because of the great support of top Chinese leaders, including the officially disgraced Lin Biao and the Gang of Four, and due to the implementation of many effective special measures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Point Climat no. 33 'International Climate Negotiations - COP 19: do not underestimate the MRV breakthrough'

    International Nuclear Information System (INIS)

    Dupont, Marion; Morel, Romain; Bellassen, Valentin; Deheza, Mariana


    Among the publications of CDC Climat Research, 'Climate Briefs' presents, in a few pages, hot topics in climate change policy. This issue addresses the following points: For those who expect 'binding' emission reductions targets in the future international climate agreement to be signed in Paris in 2015, the Warsaw Conference (November 11 to 23, 2013) yielded as much progress as it could. That means little beyond a timetable. However, for those who consider the UNFCCC as the depository of common tools on the monitoring, reporting and verification (MRV) of emissions, actions and financing, Warsaw represents a major breakthrough. For the first time, developing countries - at least those wishing to access climate finance for forests - will abide by MRV procedures similar to those governing the greenhouse gas inventories of industrialized countries. Forestry may be seen as a first sectoral NAMA, and it would be difficult to ignore the Warsaw decisions for the future definition of MRV procedures of NAMAs. In spite of the establishment of the Warsaw International Mechanism for Loss and Damage, low outputs on other issues show that achieving an agreement at COP 21 will require significant political progress during the next 15 months

  15. Breakthrough reactions of iodinated and gadolinium contrast media after oral steroid premedication protocol. (United States)

    Jingu, Akiko; Fukuda, Junya; Taketomi-Takahashi, Ayako; Tsushima, Yoshito


    Adverse reactions to iodinated and gadolinium contrast media are an important clinical issue. Although some guidelines have proposed oral steroid premedication protocols to prevent adverse reactions, some patients may have reactions to contrast media in spite of premedication (breakthrough reaction; BTR).The purpose of this study was to assess the frequency, type and severity of BTR when following an oral steroid premedication protocol. All iodinated and gadolinium contrast-enhanced radiologic examinations between August 2011 and February 2013 for which the premedication protocol was applied in our institution were assessed for BTRs. The protocol was applied to a total of 252 examinations (153 patients, ages 15-87 years; 63 males, 90 females). Of these, 152 were for prior acute adverse reactions to contrast media, 85 were for a history of bronchial asthma, and 15 were for other reasons. There were 198 contrast enhanced CTs and 54 contrast enhanced MRIs. There were nine BTR (4.5%) for iodinated contrast media, and only one BTR (1.9%) for gadolinium contrast media: eight were mild and one was moderate. No patient who had a mild index reaction (IR) had a severe BTR. Incidence of BTRs when following the premedication protocol was low. This study by no means proves the efficacy of premedication, but provides some support for following a premedication protocol to improve safety of contrast-enhanced examinations when prior adverse reactions are mild, or when there is a history of asthma.

  16. Breakthrough reactions of iodinated and gadolinium contrast media after oral steroid premedication protocol

    International Nuclear Information System (INIS)

    Jingu, Akiko; Fukuda, Junya; Taketomi-Takahashi, Ayako; Tsushima, Yoshito


    Adverse reactions to iodinated and gadolinium contrast media are an important clinical issue. Although some guidelines have proposed oral steroid premedication protocols to prevent adverse reactions, some patients may have reactions to contrast media in spite of premedication (breakthrough reaction; BTR). The purpose of this study was to assess the frequency, type and severity of BTR when following an oral steroid premedication protocol. All iodinated and gadolinium contrast-enhanced radiologic examinations between August 2011 and February 2013 for which the premedication protocol was applied in our institution were assessed for BTRs. The protocol was applied to a total of 252 examinations (153 patients, ages 15–87 years; 63 males, 90 females). Of these, 152 were for prior acute adverse reactions to contrast media, 85 were for a history of bronchial asthma, and 15 were for other reasons. There were 198 contrast enhanced CTs and 54 contrast enhanced MRIs. There were nine BTR (4.5%) for iodinated contrast media, and only one BTR (1.9%) for gadolinium contrast media: eight were mild and one was moderate. No patient who had a mild index reaction (IR) had a severe BTR. Incidence of BTRs when following the premedication protocol was low. This study by no means proves the efficacy of premedication, but provides some support for following a premedication protocol to improve safety of contrast-enhanced examinations when prior adverse reactions are mild, or when there is a history of asthma

  17. Do It Yourself (DIY) Earth Science Collaboratories Using Best Practices and Breakthrough Technologies (United States)

    Stephan, E.


    The objective of published earth science study data results and literature on the Web should be to provide a means to integrate discoverable science resources through an open collaborative-Web. At the core of any open science collaborative infrastructure is the ability to discover, manage and ultimately use relevant data accessible to the collaboration. Equally important are the relationships between people, applications, services, and publications, which capture critical contextual knowledge that enable their effective use. While contributions of either irreproducible or costly data can be a great asset the inability of users being able to use the data intelligently or make sense of it, makes these investments not usable. An ability to describe ad-hoc discoverable usage methodologies, provide feedback to data producers, and identify and cite data in a systematic way by leveraging existing Web-enabled off the shelf technology is needed. Fortunately many break-through advancements in data publication best practices and government, open source, and commercial investments support consumers who can provide feedback, share experiences, and contribute back to the earth science ecosystem.

  18. Familial concordance for age at natural menopause: results from the Breakthrough Generations Study. (United States)

    Morris, Danielle H; Jones, Michael E; Schoemaker, Minouk J; Ashworth, Alan; Swerdlow, Anthony J


    Existing estimates of the heritability of menopause age have a wide range. Furthermore, few studies have analyzed to what extent familial similarities might reflect shared environment, rather than shared genes. We therefore analyzed familial concordance for age at natural menopause and the effects of shared genetic and environmental factors on this concordance. Participants were 2,060 individuals comprising first-degree relatives, aged 31 to 90 years, and participating in the UK Breakthrough Generations Study. Menopause data were collected using a self-administered questionnaire and analyzed using logistic regression and variance-components models. Women were at an increased risk of early menopause (≤45 y) if their mother (odds ratio, 6.2; P menopause. Likewise, women had an increased risk of late menopause (≥54 y) if their relative had had a late menopause (mother: odds ratio, 6.1; P menopause age attributed to environmental factors shared by sisters. We confirm that early menopause aggregates within families and show, for the first time, that there is also strong familial concordance for late menopause. Both genes and shared environment were the source of variation in menopause age. Past heritability estimates have not accounted for shared environment, and thus, the effect of genetic variants on menopause age may previously have been overestimated.


    Directory of Open Access Journals (Sweden)

    E.A. Vishneva


    Full Text Available Varicella — is a common viral infection that can cause complications and adverse outcome not only in children at risk, but also in healthy children and adults. Socio-economic burden of disease due to both-direct health care, costs — to seek medical care and treatment,  and indirect — social. The introduction of immunization after the development of live attenuated vaccine has shown impressive results provided high coverage of morbidity and mortality associated with chickenpox declined sharply. However, the development of infection in vaccinated patients — a breakthrough varicella may be related with the deterioration of post-vaccinal immunity with time,  and the primary tolerance and inability to induce an effective immune response. Despite the undeniable progress in the prevention of chicken pox since the early 2000s. the world’s a discussion about the need to move to the two-dose vaccination scheme in national immunization programs has been started. Key words: vaccination, children, chickenpox, varicella, breakout. (Pediatric pharmacology. — 2011; 8 (6: 18–22.

  20. EGOLOGY: psychological spatial breakthrough for social redirection--multidisciplinary spatial focus for individuals/humankind (United States)

    Thompson, Robert A.


    Every age is marked by its physical tools. But today''s Space Age is unique because it is the spatial vantage itself which becomes a tool. It is a mental breakthrough, permitting us to contrast our outward-looking dreams with an inward-focused reality that can psychologically redirect the future for humankind. As the spatial perspective moves our eye from the surface of the earth to a remote point above its surface, our earth-based myopia disappears. We see all former parameters simultaneously, far out as well as close up. Physical differences are minimized, only natural demarcations remain, while similarities and interconnections abound. With the evolution of the Space Age this new awareness stimulated first the ecological movement, raising public consciousness about the physical environment, and then socially about human rights worldwide. From this intellectual quantum jump we realized that planetary interconnections permeated earth''s biosphere and on into the physical-chemical core. Like the ecological shell that identified ecology as the dynamic balance of all organisms interacting with their thermodynamic energy environment, a new outer shell, an egological one, or egoshell, is now needed to deal with multidisciplinary informational dynamics socially (acquisition for educational dissemination and perceptual workplace use). Individuals within their total spatial environment--the conceptual energy/human resource balance identified as EGOLOGY--would then be able to network society, inspiring mental fitness for an individual enlightenment to occur.

  1. Engineering excellence in breakthrough biomedical technologies: bioengineering at the University of California, Riverside. (United States)

    Schultz, Jane S; Rodgers, V G J


    The Department of Bioengineering at the University of California, Riverside (UCR), was established in 2006 and is the youngest department in the Bourns College of Engineering. It is an interdisciplinary research engine that builds strength from highly recognized experts in biochemistry, biophysics, biology, and engineering, focusing on common critical themes. The range of faculty research interests is notable for its diversity, from the basic cell biology through cell function to the physiology of the whole organism, each directed at breakthroughs in biomedical devices for measurement and therapy. The department forges future leaders in bioengineering, mirroring the field in being energetic, interdisciplinary, and fast moving at the frontiers of biomedical discoveries. Our educational programs combine a solid foundation in bio logical sciences and engineering, diverse communication skills, and training in the most advanced quantitative bioengineering research. Bioengineering at UCR also includes the Bioengineering Interdepartmental Graduate (BIG) program. With its slogan Start-Grow-Be-BIG, it is already recognized for its many accomplishments, including being third in the nation in 2011 for bioengineering students receiving National Science Foundation graduate research fellowships as well as being one of the most ethnically inclusive programs in the nation.

  2. Computational tools for Breakthrough Propulsion Physics: State of the art and future prospects

    International Nuclear Information System (INIS)

    Maccone, Claudio


    To address problems in Breakthrough Propulsion Physics (BPP) one needs sheer computing capabilities. This is because General Relativity and Quantum Field Theory are so mathematically sophisticated that the amount of analytical calculations is prohibitive and one can hardly do all of them by hand. In this paper we make a comparative review of the main tensor calculus capabilities of the three most advanced and commercially available 'symbolic manipulator' codes: Macsyma, Maple V and Mathematica. We also point out that currently one faces such a variety of different conventions in tensor calculus that it is difficult or impossible to compare results obtained by different scholars in General Relativity and Quantum Field Theory. Mathematical physicists, experimental physicists and engineers have each their own way of customizing tensors, especially by using the different metric signatures, different metric determinant signs, different definitions of the basic Riemann and Ricci tensors, and by adopting different systems of physical units. This chaos greatly hampers progress toward the chief NASA BPP goal: the design of the NASA Warp Drive. It is thus concluded that NASA should put order by establishing international standards in symbolic tensor calculus and enforcing anyone working in BPP to adopt these NASA BPP Standards

  3. Breakthrough during air sampling with polyurethane foam: What do PUF 2/PUF 1 ratios mean? (United States)

    Bidleman, Terry F; Tysklind, Mats


    Frontal chromatography theory is applied to describe movement of gaseous semivolatile organic compounds (SVOCs) through a column of polyurethane foam (PUF). Collected mass fractions (F C ) are predicted for sample volume/breakthrough volume ratios (τ = V S /V B ) up to 6.0 and PUF bed theoretical plate numbers (N) from 2 to 16. The predictions assume constant air concentrations and temperatures. Extension of the calculations is done to relate the collection efficiency of a 2-PUF train (F C1+2 ) to the PUF 2/PUF 1 ratio. F C1+2 exceeds 0.9 for PUF 2/PUF 1 ≤ 0.5 and lengths of PUF commonly used in air samplers. As the PUF 2/PUF 1 ratio approaches unity, confidence in these predictions is limited by the analytical ability to distinguish residues on the two PUFs. Field data should not be arbitrarily discarded because some analytes broke through to the backup PUF trap. The fractional collection efficiencies can be used to estimate air concentrations from quantities retained on the PUF trap when sampling is not quantitative. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Quinine pharmacokinetics in young children with severe malaria

    NARCIS (Netherlands)

    van Hensbroek, M. B.; Kwiatkowski, D.; van den Berg, B.; Hoek, F. J.; van Boxtel, C. J.; Kager, P. A.


    Children less than two years of age represent a substantial proportion of severe malaria cases in Africa. The standard treatment is parenteral quinine, but little is known about the pharmacokinetics and toxicity of quinine in this age group. We have studied the pharmacokinetics of quinine after

  5. Pharmacokinetics of Single Dose Intravenous Paracetamol in Children

    African Journals Online (AJOL)

    A new intravenous formulation containing paracetamol is now available and widely used in chil-dren, but with limited paediatric pharmacokinetic data. This study was aimed at determining the effects of age on the pharmacokinetics (PK) of this formulation of paracetamol in children. Blood samples were obtained from 24 ...

  6. Effect of mixed film coating on pharmacokinetics of paracetamol tablets

    African Journals Online (AJOL)

    Effect of mixed film coating on pharmacokinetics of paracetamol tablets. ... The main pharmacokinetic parameters were determined using non-compartmental analysis. ... The rate and extent of drug absorption was low in the film-coated tablets compared to the uncoated tablets, demonstrating the ability of the mixed films to ...

  7. Acetaminophen developmental pharmacokinetics in premature neonates and infants

    DEFF Research Database (Denmark)

    Anderson, Brian J; van Lingen, Richard A; Hansen, Tom G


    The aim of this study was to describe acetaminophen developmental pharmacokinetics in premature neonates through infancy to suggest age-appropriate dosing regimens.......The aim of this study was to describe acetaminophen developmental pharmacokinetics in premature neonates through infancy to suggest age-appropriate dosing regimens....

  8. [Advances on pharmacokinetics of traditional Chinese medicine under disease states]. (United States)

    Gong, Zi-peng; Chen, Ying; Zhang, Rui-jie; Yang, Qing; Zhu, Xiao-xin


    In recent years, more and more research shows that the pharmacokinetic parameter of traditional Chinese medicine can be affected by the disease states. It's possible that drug metabolic enzymes, transporters, cell membrane permeability and the change of microbes group could be interfered with physiological and pathological changes, which enables the pharmacokinetics of traditional Chinese medicine in the body to be altered, including the process of absorption, distribution, metabolism and excretion, and then the pharmacokinetic parameters of traditional chinese medicine are altered. It's found that investigating the pharmacokinetic of traditional Chinese medicine in the pathological state is more useful than that of in normal state because the great part of traditional Chinese medicine is mainly used to treat disease. This article reflects the latest research on the pharmacokinetic of traditional Chinese medicine in the disease state such as diabete, cerebral ischemia, liver injury, inflammatory disease, nervous system disorders and fever in order to provide certain reference for clinicians designing reasonable administration dose.

  9. Back pain - returning to work (United States)

    Nonspecific back pain - work; Backache - work; Lumbar pain - work; Pain - back - chronic; Low back pain - work; Lumbago - work ... Exercise helps to prevent future back pain: Exercise a little ... keep your heart healthy and your muscles strong. If walking is ...

  10. Low heritability in pharmacokinetics of talinolol

    DEFF Research Database (Denmark)

    Matthaei, Johannes; Tzvetkov, Mladen V; Gal, Valerie


    BACKGROUND: Efflux transporters like MDR1 and MRP2 may modulate the pharmacokinetics of about 50 % of all drugs. It is currently unknown how much of the variation in the activities of important drug membrane transporters like MDR1 or MRP2 is determined by genetic or by environmental factors...... of talinolol was predefined as the primary parameter. Heritability was analyzed by structural equation modeling and by within- and between-subject variance and talinolol clearance was correlated with polymorphisms in MDR1, MRP2, BCRP, MDR5, OATP1B1, and OCT1. RESULTS: Talinolol clearance varied approximately...

  11. Human pharmacokinetics of proguanil and its metabolites

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Ravn, P; Rønn, A


    The pharmacokinetics of proguanil and its metabolites cycloguanil and p-chlorophenylbiguanide were studied in five healthy volunteers taking 200 mg orally for 14 days. A highly sensitive and specific high-performance liquid chromatographic assay was applied, clearly identifying all three compounds...... of proguanil and cycloguanil appeared after seven hours. Trough concentrations (pre-dose in the morning) of proguanil and cycloguanil were about 200 and 100 nmol/l, respectively. Mean half-life of proguanil was estimated to approximately 20 h. The active metabolite cycloguanil constituted 30% of the total...

  12. Human physiologically based pharmacokinetic model for propofol

    Directory of Open Access Journals (Sweden)

    Schnider Thomas W


    Full Text Available Abstract Background Propofol is widely used for both short-term anesthesia and long-term sedation. It has unusual pharmacokinetics because of its high lipid solubility. The standard approach to describing the pharmacokinetics is by a multi-compartmental model. This paper presents the first detailed human physiologically based pharmacokinetic (PBPK model for propofol. Methods PKQuest, a freely distributed software routine, was used for all the calculations. The "standard human" PBPK parameters developed in previous applications is used. It is assumed that the blood and tissue binding is determined by simple partition into the tissue lipid, which is characterized by two previously determined set of parameters: 1 the value of the propofol oil/water partition coefficient; 2 the lipid fraction in the blood and tissues. The model was fit to the individual experimental data of Schnider et. al., Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60 minutes later by a one hour constant infusion. Results The PBPK model provides a good description of the experimental data over a large range of input dosage, subject age and fat fraction. Only one adjustable parameter (the liver clearance is required to describe the constant infusion phase for each individual subject. In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters. The average weighted residual error (WRE of the PBPK model fit to the both the bolus and infusion phases was 15%; similar to the WRE for just the constant infusion phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental model. Conclusion A PBPK model using standard human parameters and a simple description of tissue binding provides a good description of human propofol kinetics. The major advantage of a

  13. Disclosure of pharmacokinetic drug results to understand nonadherence. (United States)

    van der Straten, Ariane; Montgomery, Elizabeth T; Musara, Petina; Etima, Juliane; Naidoo, Sarita; Laborde, Nicole; Hartmann, Miriam; Levy, Lisa; Bennie, Thola; Cheng, Helen; Piper, Jeanna; Grossman, Cynthia I; Marrazzo, Jeanne; Mensch, Barbara


    In VOICE, a phase IIB trial of daily oral and vaginal tenofovir for HIV prevention, at least 50% of women receiving active products had undetectable tenofovir in all plasma samples tested. MTN-003D, an ancillary study using in-depth interviews (IDIs) and focus group discussions (FGDs), together with retrospective disclosure of plasma tenofovir pharmacokinetic results, explored adherence challenges during VOICE. We systematically recruited participants with pharmacokinetic data (median six plasma samples), categorized as low (0%, N = 79), inconsistent (1-74%, N = 28) or high (≥75%; N = 20) on the basis of frequency of tenofovir detection. Following disclosure of pharmacokinetic results, reactions were captured and adherence challenges systematically elicited; IDIs and FGDs were audio-recorded, transcribed, coded and thematically analysed. We interviewed 127 participants from South Africa, Uganda and Zimbabwe. The most common reactions to pharmacokinetic results included surprise (41%; low pharmacokinetic), acceptance (39%; inconsistent pharmacokinetic) and happiness (65%; high pharmacokinetic). On the basis of participants' explanations, we developed a typology of adherence patterns: noninitiation, discontinuation, misimplementation (resulting from visit-driven use, variable taking, modified dosing or regimen) and adherence. Fear of product side effects/harm was a frequent concern, fuelled by stories shared among participants. Although women with high pharmacokinetic levels reported similar concerns, several described strategies to overcome challenges. Women at all pharmacokinetic levels suggested real-time drug monitoring and feedback to improve adherence and reporting. Retrospective provision of pharmacokinetic results seemingly promoted candid discussions around nonadherence and study participation. The effect of real-time drug monitoring and feedback on adherence and accuracy of reporting should be evaluated in trials.

  14. Lack of genetic association between OCT1, ABCB1, and UGT2B7 variants and morphine pharmacokinetics

    DEFF Research Database (Denmark)

    Nielsen, L M; Sverrisdóttir, E; Stage, T B


    from a double-blinded, randomized, crossover trial in 37 healthy subjects. Pharmacokinetic data were analyzed in NONMEM®, and the time-concentration relationship of morphine, morphine-3-glucuronide, and morphine-6-glucuronide was parameterized as the transit compartment rate constant (ktr), clearance...... (CL), and volume of distribution (VD). The area under the plasma concentration-time curve (AUC0-150min) and the maximum plasma concentration (Cmax) were also calculated. Pharmacodynamic data were measured as pain tolerance thresholds to mechanical stimulation of the rectum and muscle, as well as tonic...

  15. Pain and Nociception

    DEFF Research Database (Denmark)

    Falk, Sarah; Dickenson, Anthony H


    Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditiona...... spinal cord mechanisms of sensitization, and finally address central processing. Our aim is to provide a mechanistic background for the sensory characteristics of cancer-induced bone pain as a basis for better understanding and treating this condition.......Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditional...... therapies are often only partially effective. Until recently, knowledge of cancer pain mechanisms was poor compared with understanding of neuropathic and inflammatory pain states. We now view cancer-induced bone pain as a complex pain state involving components of both inflammatory and neuropathic pain...

  16. Hemiplegic Shoulder Pain. (United States)

    Wilson, Richard D; Chae, John


    Hemiplegic shoulder pain is a common complaint for stroke survivors. Many pathologies are included in the diagnosis of hemiplegic shoulder pain, and many with shoulder pain have a multifactorial cause. This article provides rehabilitation specialists with an approach to evaluation and management of those with hemiplegic shoulder pain. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Cancer Pain Physiology

    DEFF Research Database (Denmark)

    Falk, Sarah; Bannister, Kirsty; Dickenson, Anthony


    Mechanisms of inflammatory and neuropathic pains have been elucidated and translated to patient care by the use of animal models of these pain states. Cancer pain has lagged behind since early animal models of cancer-induced bone pain were based on the systemic injection of carcinoma cells. This ...

  18. Physiotherapists' knowledge of pain

    African Journals Online (AJOL)

    overall pain knowledge. Conclusion. There is an inadequate level of pain knowledge among members of the sports and orthopaedic manipulative physiotherapy ... Improving an individual's coping skills is more important than determining the extent to which there may be a psychological cause of the pain. 0.62. Pain due to ...

  19. Penetration and pharmacokinetics of non-steroidal anti-inflammatory drugs in rat prostate tissue. (United States)

    Yellepeddi, Venkata K; Radhakrishnan, Jayashree; Radhakrishnan, Rajan


    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) involves inflammation of the prostate and affects the quality of life of men of all ages. It is well reported in clinical studies that the treatment for CP/CPPS using nonsteroidal anti-inflammatory drugs (NSAIDs) produced favorable outcomes. However, currently, there are no guidelines on choice of the NSAIDs for the treatment of CP/CPPS. Therefore, in the current research study, we evaluated the prostate tissue penetration of four NSAIDs in rats to provide guidance on choice of NSAIDs for the treatment of CP/CPPS. Male Sprague-Dawley rats were administered orally with four NSAIDs viz. celecoxib, diclofenac, ibuprofen, and naproxen at 500 mg/kg dose. The animals were then sacrificed at various time points, and their prostate tissues were harvested. The NSAIDs were then extracted from the prostate tissues using liquid extraction technique, and their concentration in prostate tissue was quantified using high-performance liquid chromatography (HPLC). The prostate tissue penetration and related pharmacokinetic parameters were evaluated by non-compartmental analysis. The HPLC method for quantifying NSAIDs in prostate tissue resulted in single, sharp peaks without any interference and all validation parameters were within limits. Celecoxib showed the highest area under the curve (AUC) [146.50 ± 2.75 μg/mL*h] of all NSAID's. A two-factor analysis of variance (ANOVA) with replication indicated an overall statistically significant difference in the pharmacokinetic parameters for celecoxib, diclofenac, ibuprofen, and naproxen. This study for the first time reported the relative prostate tissue penetration of four NSAIDs. The pharmacokinetic data indicated that celecoxib has the highest penetration and retention in rat prostate tissues. Therefore, celecoxib may be considered as a better choice for the treatment CP/CPPS involving NSAIDs. © 2017 Wiley Periodicals, Inc.

  20. Pore-scale analysis on the effects of compound-specific dilution on transient transport and solute breakthrough

    DEFF Research Database (Denmark)

    Rolle, Massimo; Kitanidis, Peter

    , a transient flux-related dilution index that allows quantifying the evolution of solute dilution at a given position along the main flow direction. For the different solute transport scenarios we obtained dilution breakthrough curves that complement and add important information to traditional solute......Compound-specific diffusivities significantly impact solute transport and mixing at different scales. Although diffusive processes occur at the small pore scale, their effects propagate and remain important at larger macroscopic scales [1]. In this pore-scale modeling study in saturated porous...... media we show that compound-specific effects are important not only at steady-state and for the lateral displacement of solutes with different diffusivities but also for transient transport and solute breakthrough [2]. We performed flow and transport simulations in two-dimensional pore-scale domains...

  1. Significant interaction between activated charcoal and antiretroviral therapy leading to subtherapeutic drug concentrations, virological breakthrough and development of resistance. (United States)

    Tseng, Alice L; la Porte, Charles; Salit, Irving E


    A 42-year-old, treatment-experienced woman, virologically suppressed on tenofovir/emtricitabine and boosted atazanavir, experienced virological breakthrough, drop in CD4(+) T-cell count and undetectable drug concentrations. Adherence to treatment was confirmed, but repeat testing yielded similar results. After 2 months, the patient stated that she had been taking activated charcoal to manage gastrointestinal symptoms associated with her combination antiretroviral therapy, but she had recently discontinued the charcoal. Atazanavir concentrations were therapeutic but the patient's viral load rebounded and genotype testing revealed new reverse transcriptase mutations. The patient was changed to zidovudine, lamivudine, and boosted darunavir and achieved viral suppression. At 1 year follow-up, her viral load remained activated charcoal and atazanavir/ritonavir leading to virological breakthrough and development of resistance.

  2. Systematic considerations for a multicomponent pharmacokinetic study of Epimedii wushanensis herba: From method establishment to pharmacokinetic marker selection. (United States)

    Wang, Caihong; Wu, Caisheng; Zhang, Jinlan; Jin, Ying


    Prenylflavonoids are major active components of Epimedii wushanensis herba (EWH). The global pharmacokinetics of prenylflavonoids are unclear, as these compounds yield multiple, often unidentified metabolites. This study successfully elucidated the pharmacokinetic profiles of EWH extract and five EWH-derived prenylflavonoid monomers in rats. The study was a comprehensive analysis of metabolic pathways and pharmacokinetic markers. Major plasma compounds identified after oral administration of EWH-derived prototypes or extract included: (1) prenylflavonoid prototypes, (2) deglycosylated products, and (3) glucuronide conjugates. To select appropriate EWH-derived pharmacokinetic markers, a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established to simultaneously monitor 14 major compounds in unhydrolyzed plasma and 10 potential pharmacokinetic markers in hydrolyzed plasma. The pharmacokinetic profiles indicated that the glucuronide conjugates of icaritin were the principle circulating metabolites and that total icaritin accounted for ∼99% of prenylflavonoid exposure after administration of EWH-derived materials to rats. To further investigate icaritin as a prospective pharmacokinetic marker, correlation analysis was performed between total icaritin and its glucuronide conjugates, and a strong correlation (r > 0.5) was found, indicating that total icaritin content accurately reflected changes in the exposure levels of the glucuronide conjugates over time. Therefore, icaritin is a sufficient pharmacokinetic marker for evaluating dynamic prenylflavonoid exposure levels. Next, a mathematical model was developed based on the prenylflavonoid content of EWH and the exposure levels in rats, using icaritin as the pharmacokinetic marker. This model accurately predicted exposure levels in vivo, with similar predicted vs. experimental area under the curve (AUC)(0-96 h) values for total icaritin (24.1 vs. 32.0 mg/L h). Icaritin in

  3. Chronic pain after hysterectomy

    DEFF Research Database (Denmark)

    Brandsborg, B.; Nikolajsen, L.; Kehlet, H.


    BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic...... post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies Udgivelsesdato: 2008/3...

  4. Sensory pain qualities in neuropathic pain. (United States)

    Mackey, Sean; Carroll, Ian; Emir, Birol; Murphy, T Kevin; Whalen, Ed; Dumenci, Levent


    The qualities of chronic neuropathic pain (NeP) may be informative about the different mechanisms of pain. We previously developed a 2-factor model of NeP that described an underlying structure among sensory descriptors on the Short-Form McGill Pain Questionnaire. The goal of this study was to confirm the correlated 2-factor model of NeP. Individual descriptive scores from the Short-Form McGill Pain Questionnaire were analyzed. Confirmatory factor analysis was used to test a correlated 2-factor model. Factor 1 (stabbing pain) was characterized by high loadings on stabbing, sharp, and shooting sensory items; factor 2 (heavy pain) was characterized by high loadings on heavy, gnawing, and aching items. Results of the confirmatory factor analysis strongly supported the correlated 2-factor model. This article validates a model that describes the qualities of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. These data suggest that specific pain qualities may be associated with pain mechanisms or may be useful for predicting treatment response. Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.

  5. Pharmacokinetics and drug metabolism in the elderly. (United States)

    Klotz, Ulrich


    Aging involves progressive impairments in the functional reserve of multiple organs, which might also affect drug metabolism and pharmacokinetics. In addition, the elderly population will develop multiple diseases and, consequently, often has to take several drugs. As the hepatic first-pass effect of highly cleared drugs could be reduced (due to decreases in liver mass and perfusion), the bioavailability of some drugs can be increased in the elderly. Significant changes in body composition occur with advancing age. Lipophilic drugs may have an increased volume of distribution (Vd) with a prolonged half-life, and water-soluble drugs tend to have a smaller Vd. In the elderly, hepatic drug clearance of some drugs can be reduced by up to 30% and CYP-mediated phase I reactions are more likely to be impaired than phase II metabolism, which is relatively preserved in the elderly. Concerning the most important CYP3A4 studies with human liver microsomes and clinical studies with the validated probe, midazolam, it is indicated that there are no significant differences in CYP3A4 activity between young and old populations. Finally, renal excretion is decreased (up to 50%) in about two thirds of elderly subjects, but confounding factors such as hypertension and coronary heart disease account also for a decline in kidney function. In conclusion, age-related physiological and pharmacokinetic changes as well as the presence of comorbidity and polypharmacy will complicate drug therapy in the elderly.

  6. Preparation and ocular pharmacokinetics of ganciclovir liposomes. (United States)

    Shen, Yan; Tu, Jiasheng


    Ophthalmic liposomes of ganciclovir (GCV) were prepared by the reverse phase evaporation method, and their ocular pharmacokinetics in albino rabbits were compared with those obtained after dosing with GCV solution. The in vitro transcorneal permeability of GCV liposomes was found to be 3.9-fold higher than that of the solution. After in vivo instillation in albino rabbits, no difference was found in the precorneal elimination rate of GCV from liposome vs solution dosing. The aqueous humor concentration-time profiles of both liposomes and solution were well described by 2-compartmental pharmacokinetics with first-order absorption. The area under the curve of the aqueous humor concentration-time profiles of GCV liposomes was found to be 1.7-fold higher than that of GCV solution. Ocular tissue distribution of GCV from liposomes was 2 to 10 times higher in the sclera, cornea, iris, lens, and vitreous humor when compared with those observed after solution dosing. These results suggested that liposomes may hold some promise in ocular GCV delivery.

  7. Drug pharmacokinetics and pharmacodynamics: Technological considerations

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J.S.; Volkow, N.D.; Wolf, A.P.


    Additionally, the use of PET to examine drug pharmacokinetics and pharmacadynamics and the relationship of these properties to the behavioral, therapeutic and toxic properties of drugs and substances of abuse is emerging as a powerful new scientific tool. The pharmacokinetic properties of a drug, which comprises all of the biological processes which determine the fraction of the drug available, can be measured using the labeled drug itself. For example, the labeled drug can be used to measure the absolute uptake, regional distribution and kinetics of a drug at its site of action in the body. Additionally the labeled drug and whole body its labeled metabolites and thus provide information an potential toxic effects as well as tissue half lives. On the other hand, different labeled tracers can be used to assess drug pharmacodynamics which include the biological Processes involved in the drug's effects. For example, with appropriate radiotracers, the effects of a drug on metabolism, neurotransmitter activity, blood flew, enzyme activity or other processes can be probed.

  8. Drug pharmacokinetics and pharmacodynamics: Technological considerations

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J.S.; Volkow, N.D.; Wolf, A.P.


    Additionally, the use of PET to examine drug pharmacokinetics and pharmacadynamics and the relationship of these properties to the behavioral, therapeutic and toxic properties of drugs and substances of abuse is emerging as a powerful new scientific tool. The pharmacokinetic properties of a drug, which comprises all of the biological processes which determine the fraction of the drug available, can be measured using the labeled drug itself. For example, the labeled drug can be used to measure the absolute uptake, regional distribution and kinetics of a drug at its site of action in the body. Additionally the labeled drug and whole body its labeled metabolites and thus provide information an potential toxic effects as well as tissue half lives. On the other hand, different labeled tracers can be used to assess drug pharmacodynamics which include the biological Processes involved in the drug`s effects. For example, with appropriate radiotracers, the effects of a drug on metabolism, neurotransmitter activity, blood flew, enzyme activity or other processes can be probed.

  9. Drug pharmacokinetics and pharmacodynamics: Technological considerations

    International Nuclear Information System (INIS)

    Fowler, J.S.; Volkow, N.D.; Wolf, A.P.


    Additionally, the use of PET to examine drug pharmacokinetics and pharmacadynamics and the relationship of these properties to the behavioral, therapeutic and toxic properties of drugs and substances of abuse is emerging as a powerful new scientific tool. The pharmacokinetic properties of a drug, which comprises all of the biological processes which determine the fraction of the drug available, can be measured using the labeled drug itself. For example, the labeled drug can be used to measure the absolute uptake, regional distribution and kinetics of a drug at its site of action in the body. Additionally the labeled drug and whole body its labeled metabolites and thus provide information an potential toxic effects as well as tissue half lives. On the other hand, different labeled tracers can be used to assess drug pharmacodynamics which include the biological Processes involved in the drug's effects. For example, with appropriate radiotracers, the effects of a drug on metabolism, neurotransmitter activity, blood flew, enzyme activity or other processes can be probed

  10. Physiologic and Pharmacokinetic Changes in Pregnancy

    Directory of Open Access Journals (Sweden)

    Maged eCostantine


    Full Text Available Physiologic changes in pregnancy induce profound alterations to the pharmacokinetic properties of many medications. These changes affect distribution, absorption, metabolism, and excretion of drugs, and thus may impact their pharmacodynamic properties during pregnancy. Pregnant women undergo several adaptations in many organ systems. Some adaptations are secondary to hormonal changes in pregnancy, while others occur to support the gravid woman and her developing fetus. Some of the changes in maternal physiology during pregnancy include, for example, increased maternal fat and total body water, decreased plasma protein concentrations, especially albumin, increased maternal blood volume, cardiac output and blood flow to the kidneys and uteroplacental unit, and decreased blood pressure. The maternal blood volume expansion occurs at a larger proportion than the increase in red blood cell mass, which results in physiologic anemia and hemodilution. Other physiologic changes include increased tidal volume, partially compensated respiratory alkalosis, delayed gastric emptying and gastrointestinal motility, and altered activity of hepatic drug metabolizing enzymes. Understating these changes and their profound impact on the pharmacokinetic properties of drugs in pregnancy is essential to optimize maternal and fetal health.

  11. Intravenous buprenorphine and norbuprenorphine pharmacokinetics in humans (United States)

    Huestis, M.A.; Cone, E.J.; Pirnay, S.O.; Umbricht, A.; Preston, K.L.


    Background Prescribed sublingual (SL) buprenorphine is sometimes diverted for intravenous (IV) abuse, but no human pharmacokinetic data are available following high-dose IV buprenorphine. Methods Plasma was collected for 72 h after administration of placebo or 2, 4, 8, 12, or 16 mg IV buprenorphine in escalating order (single-blind, double-dummy) in 5 healthy male non-dependent opioid users. Buprenorphine and its primary active metabolite, norbuprenorphine, were quantified by liquid chromatography tandem mass spectrometry with limits of quantitation of 0.1 μg/L. Results Maximum buprenorphine concentrations (mean ± SE) were detected 10 min after 2, 4, 8, 12, 16 mg IV: 19.3±1.0, 44.5±4.8, 85.2±7.7, 124.6±16.6, and 137.7±18.8 μg/L, respectively. Maximum norbuprenorphine concentrations occurred 10–15 min (3.7±0.7 μg/L) after 16 mg IV administration. Conclusions Buprenorphine concentrations increased in a significantly linear dose-dependent manner up to 12 mg IV buprenorphine. Thus, previously demonstrated pharmacodynamic ceiling effects (over 2–16 mg) are not due to pharmacokinetic adaptations within this range, although they may play a role at doses higher than 12 mg. PMID:23246635

  12. The Pharmacokinetics and Pharmacodynamics of Iron Preparations

    Directory of Open Access Journals (Sweden)

    Susanna Burckhardt


    Full Text Available Standard approaches are not appropriate when assessing pharmacokinetics of iron supplements due to the ubiquity of endogenous iron, its compartmentalized sites of action, and the complexity of the iron metabolism. The primary site of action of iron is the erythrocyte, and, in contrast to conventional drugs, no drug-receptor interaction takes place. Notably, the process of erythropoiesis, i.e., formation of new erythrocytes, takes 3−4 weeks. Accordingly, serum iron concentration and area under the curve (AUC are clinically irrelevant for assessing iron utilization. Iron can be administered intravenously in the form of polynuclear iron(III-hydroxide complexes with carbohydrate ligands or orally as iron(II (ferrous salts or iron(III (ferric complexes. Several approaches have been employed to study the pharmacodynamics of iron after oral administration. Quantification of iron uptake from radiolabeled preparations by the whole body or the erythrocytes is optimal, but alternatively total iron transfer can be calculated based on known elimination rates and the intrinsic reactivity of individual preparations. Degradation kinetics, and thus the safety, of parenteral iron preparations are directly related to the molecular weight and the stability of the complex. High oral iron doses or rapid release of iron from intravenous iron preparations can saturate the iron transport system, resulting in oxidative stress with adverse clinical and subclinical consequences. Appropriate pharmacokinetics and pharmacodynamics analyses will greatly assist our understanding of the likely contribution of novel preparations to the management of anemia.

  13. Pharmacokinetics of procaterol in thoroughbred horses. (United States)

    Kusano, K; Nomura, M; Toju, K; Ishikawa, Y; Minamijima, Y; Yamashita, S; Nagata, S


    Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 ± 0.23 L/kg, and the elimination half-life was 2.85 ± 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses. © 2015 John Wiley & Sons Ltd.

  14. The Breakthrough Listen Search for Intelligent Life: Target Selection of Nearby Stars and Galaxies (United States)

    Isaacson, Howard; Siemion, Andrew P. V.; Marcy, Geoffrey W.; Lebofsky, Matt; Price, Danny C.; MacMahon, David; Croft, Steve; DeBoer, David; Hickish, Jack; Werthimer, Dan; Sheikh, Sofia; Hellbourg, Greg; Enriquez, J. Emilio


    We present the target selection for the Breakthrough Listen search for extraterrestrial intelligence during the first year of observations at the Green Bank Telescope, Parkes Telescope, and Automated Planet Finder. On the way to observing 1,000,000 nearby stars in search of technological signals, we present three main sets of objects we plan to observe in addition to a smaller sample of exotica. We chose the 60 nearest stars, all within 5.1 pc from the Sun. Such nearby stars offer the potential to observe faint radio signals from transmitters that have a power similar to those on Earth. We add a list of 1649 stars drawn from the Hipparcos catalog that span the Hertzprung-Russell diagram, including all spectral types along the main sequence, subgiants, and giant stars. This sample offers diversity and inclusion of all stellar types, but with thoughtful limits and due attention to main sequence stars. Our targets also include 123 nearby galaxies composed of a “morphological-type-complete” sample of the nearest spirals, ellipticals, dwarf spherioidals, and irregulars. While their great distances hamper the detection of technological electromagnetic radiation, galaxies offer the opportunity to observe billions of stars simultaneously and to sample the bright end of the technological luminosity function. We will also use the Green Bank and Parkes telescopes to survey the plane and central bulge of the Milky Way. Finally, the complete target list includes several classes of exotica, including white dwarfs, brown dwarfs, black holes, neutron stars, and asteroids in our solar system.

  15. Treatment of Premenstrual Breakthrough of Depression With Adjunctive Oral Contraceptive Pills Compared With Placebo. (United States)

    Peters, Whitney; Freeman, Marlene P; Kim, Semmie; Cohen, Lee S; Joffe, Hadine


    Two-thirds of women with depressive disorders report reemergence of depression premenstrually, or premenstrual exacerbation (PME), despite effective treatment of the underlying mood disorder during the remainder of the cycle. There is a paucity of studies that rigorously assess treatments targeting PME. Open-label data suggest that augmentation of antidepressants with the oral contraceptive pill (OCP) drospirenone and ethinyl estradiol (DRSP/EE) improves depressive symptoms that break through treatment premenstrually. We now report results of a randomized placebo-controlled OCP augmentation trial. Women with unipolar depressive disorders in remission on stable antidepressant doses with a 30% increase in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from the follicular to luteal phase were randomized to double-blind augmentation of antidepressant with either DRSP/EE or placebo for 2 months. The MADRS and Daily Record of Severity of Problems (DRSP) measures were anchored to the menstrual cycle phase. Of 32 women randomized, 25 (n = 12 DRSP/EE, n = 13 placebo) completed the trial. Premenstrual MADRS scores declined by a median of 43.6% and 38.9% (P = 0.59), and premenstrual DRSP scores declined by a median of 23.5% and 20.9% (P = 0.62) in the DRSP/EE and placebo groups, respectively. There was a trend toward greater improvement in premenstrual DRSP scores for women with fewer lifetime depressive episodes (r = -0.40, P = 0.06). Findings from this small randomized trial suggest that OCP augmentation of antidepressants may not be effective for treating premenstrual breakthrough of depression. Future studies should target women established to have hormonal sensitivity prior to antidepressant therapy and those with fewer lifetime depressive episodes.

  16. Ionic Liquids: Breakthrough Absorption Technology for Post-Combustion CO{sub 2} Capture

    Energy Technology Data Exchange (ETDEWEB)

    Maginn, Edward


    This is the final report for DE-FC26-07NT43091 Ionic Liquids: Breakthrough Absorption Technology for Post-Combustion CO{sub 2} Capture. A detailed summary is provided of the ionic liquid (IL) discovery process, synthesis and testing results, process / systems modeling, lab-scale operational testing, corrosion testing and commercialization possibilities. The work resulted in the discovery of a new class of ionic liquids (ILs) that efficiently react with CO{sub 2} in a 1:1 stoichiometry with no water present and no increase in viscosity. The enthalpy of reaction was tuned to optimize process economics. The IL was found to have excellent corrosion behavior with and without CO{sub 2} present. In lab-scale tests, the IL was able to effectively remove CO{sub 2} from a simulated flue gas stream, although mass transfer was slower than with aqueous monoethanolamine (MEA) due to higher viscosities. The non-volatile nature of the solvent and its high thermal stability, however, make it an intriguing option. An independent systems analysis indicates that the economics of using the best IL discovered to date (NDIL0157), are at least comparable to and potentially slightly better than - the Fluor Econamine FG PlusTM process (DOE Case 12). Further work should be directed at improving mass transfer / lowering viscosity and developing commercial synthesis routes to make these ILs at scale in an inexpensive manner. Demonstration of the process at larger scales is also warranted, as is the exploration of other process configurations that leverage the anhydrous nature of the solvent and its extremely low volatility.


    Directory of Open Access Journals (Sweden)



    Full Text Available The Australian government had funded the National Primary Care Collaborative (NPCC program with funding of $14.6 million over three years. One of the pilots project was the Arthritis and Musculoskeletal Quality Improvement Program (AMQuIP.The study aims to optimize general practitioners (GPs management of patients with osteoarthritis (OA of the hip and knee by identifying gaps between their current practice and best practice. The Breakthrough Series Collaborative methodology with several Plan-Do-Study-Act (PDSA cycles was employed. Participants comprises of 12 GPs/practices from two Victorian Divisions of general Practice (one rural, one metropolitan with 10 patients per GP/practice. GPs/practices attended an orientation and three learning workshops and a videoconference. GPs/practices completed PDSA cycles between workshop and reported results at workshops. GPs/practices reported use of guidelines, change in patient management and change in practice management/systems. All recruited patients completed the SF-12v2 Health Survey and WOMAC OA Index Questionnaire twice. Follow up activities including focus groups and face-to-face interviews were held six months after the final workshop. All GPs/practices used the guidelines/key messages, introduced “new” management strategies to patients, and made positive changes to their practice management/systems. Patient reported positive changes and outcomes. By using a structured methodology and evidence-based guidelines/key messages; GPs can introduce new patient management strategies, and by identifying gaps in practice management systems, positive changes can be achieved.

  18. Watch out for the blue circle: a breakthrough in family planning promotional strategy. (United States)



    Realizing the potential of commercial marketing in changing the attitude and behavior of the target audience in the early years of the 4th 5-year development plan, the National Family Planning Program tried to develop new ventures in communicating the concept of the small family norm to the people. The condom was chosen as the 1st product to be sold through the social marketing project because male awareness about family planning was still low. Based on audience research, the pricing, packaging, and branding of the product was developed. The most accepted brand name was Dua Lima because it has a neutral meaning, is easily remembered, and can be described in sign language. The last reason is very important because most consumers have difficulty communicating about condoms in the sales outlet. Social marketing has proved effective because of strong public relations activities and the involvement of formal and informal leaders. This experiment has convinced family planning management that social marketing is workable for promoting the small family norm. In 1987, under the new program of self-sufficiency in family planning, the private sector is invited to participate by providing family planning services for target audiences, using the principles of self-sufficiency and self-support. There are 2 principal activities; 1) the IEC campaign, and 2) product (contraceptive) selling. IEC activities include a media campaign public relations work. Product selling is done through commercial channels such as pharmaceutical firms, drug stores, private doctors, and midwives. It was decided that the campaign would be aided by a name and logo. The blue circle was chosen because it is unique, communicative, and simple. The social marketing of contraceptives in Indonesia can be considered a breakthrough in communication strategy for a national development program.

  19. Relativistic generalization of the incentive trap of interstellar travel with application to Breakthrough Starshot (United States)

    Heller, René


    As new concepts of sending interstellar spacecraft to the nearest stars are now being investigated by various research teams, crucial questions about the timing of such a vast financial and labour investment arise. If humanity could build high-speed interstellar lightsails and reach α Centauri 20 yr after launch, would it be better to wait a few years, then take advantage of further technology improvements and arrive earlier despite waiting? The risk of being overtaken by a future, faster probe has been described earlier as the incentive trap. Based on 211 yr of historical data, we find that the speed growth of artificial vehicles, from steam-driven locomotives to Voyager 1, is much faster than previously believed, about 4.72 per cent annually or a doubling every 15 yr. We derive the mathematical framework to calculate the minimum of the wait time to launch t plus travel time τ(t) and extend it into the relativistic regime. We show that the t + τ(t) minimum disappears for nearby targets. There is no use of waiting once we can reach an object within about 20 yr of travel, irrespective of the actual speed. In terms of speed, the t + τ(t) minimum for a travel to α Centauri occurs at 19.6 per cent the speed of light (c), in agreement with the 20 per cent c proposed by the Breakthrough Starshot initiative. If interstellar travel at 20 per cent c could be achieved within 45 yr from today and the kinetic energy be increased at a rate consistent with the historical record, then humans can reach the 10 most nearby stars within 100 yr from today.

  20. Stanford test called a net breakthrough - data sent at 3,500 times the speed of broadband

    CERN Multimedia


    Researchers at a Stanford University-affiliated research center have found a way to send data across the Internet more than 3,500 times faster than the typical broadband connection. The technical breakthrough set an Internet speed record too fast to be of use with present-day computers but could open the way for scientists to share and ship massive databases around the world, according to the researchers.

  1. Closed-flow column experiments—Insights into solute transport provided by a damped oscillating breakthrough behavior (United States)

    Ritschel, Thomas; Totsche, Kai Uwe


    Transport studies that employ column experiments in closed-flow mode complement classical approaches by providing new characteristic features observed in the solute breakthrough and equilibrium between liquid and solid phase. Specific to the closed-flow mode is the recirculation of the effluent to the inflow via a mixing vessel. Depending on the ratio of volumes of mixing vessel and water-filled pore space, a damped oscillating solute concentration emerges in the effluent and mixing vessel. The oscillation characteristics, e.g., frequency, amplitude, and damping, allow for the investigation of solute transport in a similar fashion as known for classical open-flow column experiments. However, the closed loop conserves substances released during transport within the system. In this way, solute and porous medium can equilibrate with respect to physicochemical conditions. With this paper, the features emerging in the breakthrough curves of saturated column experiments run in closed-flow mode and methods of evaluation are illustrated under experimental boundary conditions forcing the appearance of oscillations. We demonstrate that the effective pore water volume and the pumping rate can be determined from a conservative tracer breakthrough curve uniquely. In this way, external preconditioning of the material, e.g., drying, can be avoided. A reactive breakthrough experiment revealed a significant increase in the pore water pH value as a consequence of the closed loop. These results highlight the specific impact of the closed mass balance. Furthermore, the basis for the modeling of closed-flow experiments is given by the derivation of constitutive equations and numerical implementation, validated with the presented experiments.

  2. Pharmacokinetics of nalbuphine hydrochloride after intravenous and intramuscular administration to Hispaniolan Amazon parrots (Amazona ventralis). (United States)

    Keller, Dominique L; Sanchez-Migallon Guzman, David; Klauer, Julia M; KuKanich, Butch; Barker, Steven A; Rodríguez-Ramos Fernández, Julia; Paul-Murphy, Joanne R


    To assess the pharmacokinetics of nalbuphine HCl after IV and IM administration to Hispaniolan Amazon parrots (Amazona ventralis). 8 healthy adult Hispaniolan Amazon parrots of unknown sex. Nalbuphine HCl (12.5 mg/kg) was administered IV and IM to all birds in a complete randomized crossover study design; there was a washout period of 21 days between subsequent administrations. Plasma samples were obtained from blood collected at predetermined time points for measurement of nalbuphine concentration by use of liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated by use of computer software. Nalbuphine was rapidly eliminated with a terminal half-life of 0.33 hours and clearance of 69.95 mL/min/kg after IV administration and a half-life of 0.35 hours after IM administration. Volume of distribution was 2.01 L/kg after IV administration. The fraction of the dose absorbed was high (1.03) after IM administration. No adverse effects were detected in the parrots during the study. In Hispaniolan Amazon parrots, nalbuphine appeared to have good bioavailability after IM administration and was rapidly cleared after IV and IM administration. Safety and analgesic efficacy of various nalbuphine treatment regimens in this species require further investigation to determine the potential for clinical palliation of signs of pain in psittacine species.

  3. Pharmacokinetics of long-acting nalbuphine decanoate after intramuscular administration to Hispaniolan Amazon parrots (Amazona ventralis). (United States)

    Sanchez-Migallon Guzman, David; KuKanich, Butch; Heath, Timothy D; Krugner-Higby, Lisa A; Barker, Steven A; Brown, Carolyn S; Paul-Murphy, Joanne R


    To evaluate the pharmacokinetics of nalbuphine decanoate after IM administration to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots of unknown sex. Nalbuphine decanoate (37.5 mg/kg) was administered IM to all birds. Plasma samples were obtained from blood collected before (time 0) and 0.25, 1, 2, 3, 6, 12, 24, 48, and 96 hours after drug administration. Plasma samples were used for measurement of nalbuphine concentrations via liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated with computer software. Plasma concentrations of nalbuphine increased rapidly after IM administration, with a mean concentration of 46.1 ng/mL at 0.25 hours after administration. Plasma concentrations of nalbuphine remained > 20 ng/mL for at least 24 hours in all birds. The maximum plasma concentration was 109.4 ng/mL at 2.15 hours. The mean terminal half-life was 20.4 hours. In Hispaniolan Amazon parrots, plasma concentrations of nalbuphine were prolonged after IM administration of nalbuphine decanoate, compared with previously reported results after administration of nalbuphine hydrochloride. Plasma concentrations that could be associated with antinociception were maintained for 24 hours after IM administration of 37.5 mg of nalbuphine decanoate/kg. Safety and analgesic efficacy of nalbuphine treatments in this species require further investigation to determine the potential for clinical use in pain management in psittacine species.

  4. Clinical efficacy and pharmacokinetics of meloxicam in Mediterranean buffalo calves (Bubalus bubalis). (United States)

    Cagnardi, Petra; Guccione, Jacopo; Villa, Roberto; D'Andrea, Luigi; Di Loria, Antonio; Ferrante, Maria Carmela; Borriello, Giuliano; Zicarelli, Luigi; Ciaramella, Paolo


    The aims of the investigation were to establish for the first time (i) clinical efficacy and (ii) pharmacokinetic profile of meloxicam intravenously (IV) administered in male Mediterranean buffalo calves after surgical orchiectomy. The study was performed on 10 healthy buffalo calves, between 4 and 5 months old and between 127 and 135 kg of body weight (b.w.). An IV injection of 0.5 mg/kg b.w. of meloxicam was administered in six calves (treated group, TG) immediately after surgery; the other four animals were used as untreated control group (CG). The clinical efficacy of meloxicam was evaluated pre- and post-surgery by monitoring respiratory rate (RR), heart rate (HR), rectal temperature (T°C), serum cortisol levels (SCL) and pain score (PS). Significant inter-groups differences were detected at sampling times (T): 4 hour (h) for RR (Pmeloxicam mean concentrations at 96 h was of 0.18 ± 0.14 μg/mL. The volume of distribution and clearance values were quite low, but reasonably homogenous among individuals (Vdss 142.31 ± 55.08 mL/kg and ClB 4.38 ± 0.95 mL/kg/h, respectively). The IV administration of meloxicam in buffalo calves shows encouraging effects represented by significant and prolonged analgesic effects, significant reduction of SCL as well as similar pharmacokinetic profile to bovine calves.

  5. Pharmacokinetics of the novel atypical opioid tapentadol after intravenous, intramuscular and subcutaneous administration in cats. (United States)

    Lee, H-K; Lebkowska-Wieruszewska, B; Kim, T-W; Kowaski, C-J; Giorgi, M


    Drugs that provide effective analgesia in cats are limited. The aim of the present study was to investigate the pharmacokinetics of the novel atypical drug tapentadol (TAP) after intravenous (IV), intramuscular (IM) and subcutaneous (SC) injection in six healthy cats using a 3 × 3 Latin square crossover study design. The dose rate used was 5mg/kg and the concentrations of TAP in plasma were evaluated using high-performance liquid chromatography. Some adverse effects including salivation, agitation and panting, were noted, especially following IV administration. In all three administration groups, TAP concentrations were detectable in plasma for up to 8h. Bioavailability for each route was almost complete, accounting for 94% and 90% after IM and SC administrations, respectively. Drug absorption was faster after IM than SC administration (0.25 h vs. 0.63 h). The half-life of the terminal portion of the plasma concentration curve was not significantly different between the three routes of administrations (2-3h). TAP appears to have some variation in its pharmacokinetic features in cats compared to other animal species. Further studies are needed to evaluate whether TAP would be suitable for use in cats that are experiencing moderate to severe pain, but are sensitive to the adverse effects of commonly prescribed opioids. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Biosorption of uranium(VI) from aqueous solutions by Ca-pretreated Cystoseira indica alga: breakthrough curves studies and modeling. (United States)

    Ghasemi, Morteza; Keshtkar, Ali Reza; Dabbagh, Reza; Jaber Safdari, S


    Uranium(VI) biosorption from aqueous solutions containing 60 mg l(-1) metal concentration by Ca-pretreated Cystoseira indica alga was studied in a packed bed column with 1.5 cm internal diameter. The effect of bed height and flow rate on biosorption process was investigated and the experimental breakthrough curves were obtained. Results showed that by increasing the bed height, the breakthrough and exhaustion times increased and the slope of breakthrough curves decreased. Also, it was observed that the controlled-rate step shifted from external to internal mass transfer limitations, as the flow rate increased. The maximum uptake capacity, 318.15 mg g(-1), and total metal removal, 59.32%, were obtained at flow rate of 2.3 ml min(-1) and bed height of 6 cm. The column was regenerated using 0.1M HCl solution and sorption-desorption studies were carried out for three cycles. The obtained results confirmed that reusability of this biosorbent is possible. The results obtained agreed well with the bed depth service time model. In addition, for estimations of the parameters necessary for the design of a large-scale packed bed column, the experimental data were also fitted to the Thomas, Yan and Belter models and were found to agree with the experimental data fairly well. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Biosorption of uranium(VI) from aqueous solutions by Ca-pretreated Cystoseira indica alga: Breakthrough curves studies and modeling

    Energy Technology Data Exchange (ETDEWEB)

    Ghasemi, Morteza [Faculty of Nuclear Engineering, Shahid Beheshti University, Tehran (Iran, Islamic Republic of); Keshtkar, Ali Reza, E-mail: [Nuclear Fuel Cycle School, Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of); Dabbagh, Reza [Nuclear Science Research School, Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of); Jaber Safdari, S. [Nuclear Fuel Cycle School, Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of)


    Uranium(VI) biosorption from aqueous solutions containing 60 mg l{sup -1} metal concentration by Ca-pretreated Cystoseira indica alga was studied in a packed bed column with 1.5 cm internal diameter. The effect of bed height and flow rate on biosorption process was investigated and the experimental breakthrough curves were obtained. Results showed that by increasing the bed height, the breakthrough and exhaustion times increased and the slope of breakthrough curves decreased. Also, it was observed that the controlled-rate step shifted from external to internal mass transfer limitations, as the flow rate increased. The maximum uptake capacity, 318.15 mg g{sup -1}, and total metal removal, 59.32%, were obtained at flow rate of 2.3 ml min{sup -1} and bed height of 6 cm. The column was regenerated using 0.1 M HCl solution and sorption-desorption studies were carried out for three cycles. The obtained results confirmed that reusability of this biosorbent is possible. The results obtained agreed well with the bed depth service time model. In addition, for estimations of the parameters necessary for the design of a large-scale packed bed column, the experimental data were also fitted to the Thomas, Yan and Belter models and were found to agree with the experimental data fairly well.

  8. Pain in castration-resistant prostate cancer with bone metastases: a qualitative study

    Directory of Open Access Journals (Sweden)

    Gater Adam


    Full Text Available Abstract Background Bone metastases are a common painful and debilitating consequence of castration-resistant prostate cancer (CPRC. Bone pain may predict patients' prognosis and there is a need to further explore CRPC patients' experiences of bone pain in the overall context of disease pathology. Due to the subjective nature of pain, assessments of pain severity, onset and progression are reliant on patient assessment. Patient reported outcome (PRO measures, therefore, are commonly used as key endpoints for evaluating the efficacy of CRPC treatments. Evidence of the content validity of leading PRO measures of pain severity used in CRPC clinical trials is, however, limited. Methods To document patients' experience of CRPC symptoms including pain, and their impact on health-related quality of life (HRQL, semi-structured in-depth qualitative interviews were conducted with 17 patients with CRPC and bone metastases. The content validity of the Present Pain Intensity (PPI scale from the McGill Pain Questionnaire (MPQ, and the 'Average Pain' and 'Worst Pain' items of the Brief Pain Inventory Short-Form (BPI-SF was also assessed. Results Patients with CRPC and bone metastases present with a constellation of symptoms that can have a profound effect on HRQL. For patients in this study, bone pain was the most prominent and debilitating symptom associated with their condition. Bone pain was chronic and, despite being generally well-managed by analgesic medication, instances of breakthrough cancer pain (BTcP were common. Cognitive debriefing of the selected PRO measures of pain severity highlighted difficulties among patients in understanding the verbal response scale (VRS of the MPQ PPI scale. There were also some inconsistencies in the way in which the BPI-SF 'Average Pain' item was interpreted by patients. In contrast, the BPI-SF 'Worst Pain' item was well understood and interpreted consistently among patients. Conclusions Study findings support the

  9. [Discussion about traditional Chinese medicine pharmacokinetics study based on first botanical drug approved by FDA]. (United States)

    Huang, Fanghua


    Pharmacokinetics study is one of main components of pharmaceuticals development. Food and Drug Administration (FDA) approved Veregen as the first botanical drug in 2006. This article introduced FDA's requirement on pharmacokinetics study of botanical drug and pharmacokinetics studies of Veregen, summarized current requirement and status quo of pharmacokinetics study on traditional Chinese medicine (TCM) and natural medicine in China, and discussed about pharmacokinetics study strategy for TCM and natural medicine.

  10. Pharmacokinetics of buprenorphine following intravenous and oral transmucosal administration in dogs. (United States)

    Abbo, Lisa A; Ko, Jeff C H; Maxwell, Lara K; Galinsky, Raymond E; Moody, David E; Johnson, Brenda M; Fang, Wenfang B


    Pharmacokinetic analysis of buprenorphine administered to six healthy dogs via the oral transmucosal (OTM) route at doses of 20 and 120 microg/kg was conducted using liquid chromatography-electrospray ionization-tandem mass spectroscopy (LC-ESI-MS/MS). Bioavailability was 38% plus or minus 12% for the 20 microg/kg dose and 47%+/-16% for the 120 microg/kg dose. Maximum plasma concentrations were similar for buprenorphine doses of 20 microg/kg IV and 120 microg/kg OTM. Sedation and salivation were common side effects, but no bradycardia, apnea, or cardiorespiratory depressive effects were seen. When the two OTM dosing rates were normalized to dose, LC-ESI-MS/MS analysis of buprenorphine and its metabolites detected no significant difference (P>.05), indicating dose proportionality. The results of this study suggest that OTM buprenorphine may be an alternative for pain management in dogs.

  11. Pharmacokinetics and clinical efficacy of long-term epidural ropivacaine infusion in children

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing; Ilett, K F; Lim, S I


    The clinical efficacy and pharmacokinetics of long-term epidural ropivacaine infusion were investigated in 18 postoperative children aged between 0.3 and 7.3 yr. A lumbar or thoracic epidural catheter was inserted after the anaesthetic induction. Sixty minutes following a bolus dose of ropivacaine...... 1 mg kg-1, 0.2% ropivacaine was infused at a fixed rate of 0.4 mg kg-1 h-1 for a mean of 61.3 h (range 36-96 h). Clinical evaluation comprised hourly recording of pain, sedation, motor block, nausea/vomiting, pruritus-scores, SpO2, pulse and respiratory rates, and recording of non-invasive arterial...

  12. Obesity Does Not Affect Propofol Pharmacokinetics During Hypothermic Cardiopulmonary Bypass. (United States)

    El-Baraky, Iman A; Abbassi, Maggie M; Marei, Tarek A; Sabry, Nirmeen A


    Because of the lack of data regarding the impact of obesity on propofol pharmacokinetics in patients undergoing cardiac surgery using hypothermic cardiopulmonary bypass (CPB), the authors sought to explore propofol pharmacokinetics and develop a predictive pharmacokinetic model that characterizes and predicts propofol pharmacokinetics in this population. A prospective, observational study. A teaching hospital. The study comprised 17 obese and 17 control (nonobese) patients undergoing hypothermic CPB. None. Patients mainly underwent valve surgery. On initiation of hypothermic CPB (28°C-32°C), patients received a propofol (1%) bolus (1 mg/kg) immediately followed by a 2 mg/kg/h infusion. Blood samples were withdrawn at the following times: before dosing; 1, 3, 5, and 7 minutes after the propofol bolus dose; every 20 minutes during infusion; just before discontinuation of the infusion; and at 1, 3, 5, 7, 10, 20, 30, and 60 minutes after discontinuation of the infusion. The plasma propofol concentration was determined using high-performance liquid chromatography, and then data were imported into Monolix (Lixoft, Antony, France) for population pharmacokinetic modeling and pharmacokinetic parameters estimation. A 2-compartment pharmacokinetic model with age as a covariate on the peripheral volume of distribution (V2) best described the pooled data. The pooled data was internally evaluated successfully to describe and predict propofol pharmacokinetics in the addressed population. Propofol clearance, intercompartmental clearance, and central volume of distribution were 805 mL/min, 1140 mL/min and 18.8 L, respectively. V2 was calculated as 9.86×exp.(1.88×[age/40]) L. Propofol pharmacokinetic parameters were similar in obese and nonobese patients undergoing hypothermic CPB. Age was the major determinant of propofol V2 in the obese population. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics. (United States)

    Trang, Tuan; Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W; Gutstein, Howard; Cahill, Catherine M


    Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids. Copyright © 2015 the authors 0270-6474/15/3513879-10$15.00/0.

  14. Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics (United States)

    Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W.; Gutstein, Howard


    Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. SIGNIFICANCE STATEMENT Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids. PMID:26468188

  15. Psychological aspects of pain. (United States)

    Gorczyca, Rafał; Filip, Rafał; Walczak, Ewa


    Pain is defined "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage". Pain is a sensation of the body, and is always an unpleasant emotional experience. The role of psychology is auxiliary and supplemental to medicine. This is an aid addressed to the patient, physician and patient's caregivers: professional caregivers, family members and significant others. At each stage of the diagnostic and therapeutic process, psychology offers help, both from the cognitive and practical aspects. The objective of the article is to present important psychological aspects of studies concerning pain, and the psychological methods and techniques of pain treatment. Pain is the leading reason for patients seeking medical care and is one of the most disabling, burdensome, and costly conditions. Pain accompanies many diseases, each one of which generates unique/separate diagnostic, therapeutic and research problems. DEPRESSION AND RELATED PSYCHICAL DISORDERS: There is a significant relationship between depression and pain symptoms, as well as between pain and suicidal thoughts. Patients with a long history of pain disorders also have increased depression and anxiety symptoms, as well as suicidal thoughts. Patients with more severe depression and anxiety symptoms also have an increase in pain problems. The intensity of pain correlates with the intensity of psychopathological symptoms - both with mood lowering and with anxiety symptoms and worry. Active pain coping strategies strive to function in spite of pain, or to distract oneself from pain, are associated with adaptive functioning. Passive strategies involve withdrawal or relinquishing control to an external force or agent and are related to greater pain and depression. Pain catastrophizing is a negatively distorted perception of pain as awful, horrible and unbearable. Catastrophizing is strongly associated with depression and pain. Studies in which

  16. Pain in cancer survivors

    International Nuclear Information System (INIS)

    Mladosievicova, B.


    Pain is a common problem among cancer survivors, especially in the first few years after treatment. In the longer term, approximately 5% to 10% of survivors have chronic severe pain. Overall prevalence of all types pain is about 40% in some cancer survivors with previous specific diagnosis. Until recently, impact of pain in cancer survivors have largely been unexamined. This complication can be predicted by type of malignancy, its therapy, time elapsed from completion of anticancer treatment and effectivity of previous pain interventions. As the purpose of this article is to update readers on more recent data about prevalence of pain in cancer survivors and common treatment-related chronic pain etiologies in patients with a history of cancer who are beyond the acute diagnosis and treatment phase, previously known information about acute pain, pain in terminally ill patients. Some new studies in certain subpopulations of cancer survivors will be explored in more detail. (author)

  17. Pain, objectivity and history: understanding pain stigma. (United States)

    Goldberg, Daniel S


    The primary claim of this paper is that understanding the stigma so commonly endured by chronic pain sufferers today in the USA and the UK is unlikely without proper appreciation of the history of pain. Ameliorating such stigma is an ethical imperative, and yet most approaches eschew even an attempt to trace connections between historical attitudes, practices and beliefs towards pain and the stigmatisation so many pain sufferers currently endure. The manuscript aims to help fill this gap by framing pain in the modern era in context of two crucial intellectual schemes that waxed in the 19th and 20th centuries: mechanical objectivity and somaticism. The analysis explains these frameworks and applies them to exploration of primary sources connected to contested pain conditions such as railway spine. By properly situating the historical roots of what it means to cite the 'subjectivity' of pain as a problem, the modern roots of stigmatising attitudes and practices towards chronic pain sufferers become much clearer. The manuscript concludes by suggesting that interventions expressly intended to target the root causes of such stigma are much more likely to be successful than approaches that proceed in ignorance of the historical forces shaping and driving pain stigma in the present. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  18. Bladder volume at onset of vesicoureteral reflux is an independent risk factor for breakthrough febrile urinary tract infection. (United States)

    Alexander, Siobhan E; Arlen, Angela M; Storm, Douglas W; Kieran, Kathleen; Cooper, Christopher S


    Improved identification of children with vesicoureteral reflux at risk for recurrent febrile urinary tract infection may impact management decisions. We hypothesized that reflux occurring earlier during bladder filling increases the duration of exposure of the kidneys to bacteria, and, therefore, increases the risk of pyelonephritis. Children with vesicoureteral reflux and detailed voiding cystourethrogram data were identified. Bladder volume at onset of reflux was normalized for age. Demographics, reflux grade, laterality, presence/absence of bladder-bowel dysfunction and breakthrough febrile urinary tract infections were assessed. Median followup was 24 months (IQR 12 to 52). A total of 208 girls and 47 boys were analyzed with a mean ± SD age at diagnosis of 3.1 ± 2.6 years. On univariate analysis history of febrile urinary tract infection (HR 2.17, 95% CI 1.33-2.85, p = 0.01), dilating vesicoureteral reflux (HR 1.6, 95% CI 1.05-2.42, p = 0.03) and bladder-bowel dysfunction (HR 1.66, 95% CI 0.99-2.75, p = 0.05) were associated with an increased risk of breakthrough febrile urinary tract infection. Median bladder volume at onset of reflux in children with breakthrough febrile urinary tract infection was significantly less (33.1%) than in those without infection (49.5%, p = 0.003). Reflux onset at 35% predicted bladder capacity or less was associated with a significantly increased risk of breakthrough febrile urinary tract infection on multivariate analysis (HR 1.58, 95% CI 1.05-2.38, p = 0.03). Children with early filling vesicoureteral reflux are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. Bladder volume at onset of reflux should be recorded during cystograms since it provides additional prognostic information about the risk of pyelonephritis and resolution, and may assist with counseling and clinical decision making. Copyright © 2015 American Urological Association Education and Research, Inc. Published by

  19. Population Pharmacokinetics of Tracers: A New Tool for Medical Imaging? (United States)

    Gandia, Peggy; Jaudet, Cyril; Chatelut, Etienne; Concordet, Didier


    Positron emission tomography-computed tomography is a medical imaging method measuring the activity of a radiotracer chosen to accumulate in cancer cells. A recent trend of medical imaging analysis is to account for the radiotracer's pharmacokinetic properties at a voxel (three-dimensional-pixel) level to separate the different tissues. These analyses are closely linked to population pharmacokinetic-pharmacodynamic modelling. Kineticists possess the cultural background to improve medical imaging analysis. This article stresses the common points with population pharmacokinetics and highlights the methodological locks that need to be lifted.

  20. Impact of volume expansion on the efficacy and pharmacokinetics of liposome bupivacaine

    Directory of Open Access Journals (Sweden)

    Hadzic A


    Full Text Available Admir Hadzic,1,2 John A Abikhaled,3 William J Harmon4 1Department of Anesthesiology, The New York School of Regional Anesthesia (NYSORA, New York, NY, USA; 2Department of Anesthesiology, Ziekenhouse Oost Limburgh, Genk, Belgium; 3Austin Surgeons, Austin, TX, 4Urology San Antonio, San Antonio, TX, USA Abstract: Liposome bupivacaine is a prolonged-release liposomal formulation of bupivacaine indicated for single-dose infiltration into the surgical site to produce postsurgical analgesia of longer duration than traditional local anesthetics. This review summarizes the available data on how volume expansion may impact the analgesic efficacy of liposome bupivacaine. The Phase II and III clinical studies that involved surgical site administration of liposome bupivacaine at various concentrations in different surgical settings revealed no apparent concentration–efficacy relationship. A single-center, prospective study comparing the efficacy of transversus abdominis plane infiltration with liposome bupivacaine administered in a lower (266 mg/40 mL vs a higher (266 mg/20 mL dose concentration in subjects undergoing robotic-assisted laparoscopic prostatectomy also reported similar postsurgical pain intensity scores and opioid usage in both treatment groups. The pharmacokinetic profile of liposome bupivacaine following subcutaneous injections in rats was unaltered by differences in drug concentration, dose, or injection volume within the ranges tested. Volume expansion of liposome bupivacaine to a total volume of 300 mL or less does not appear to impact its clinical efficacy or pharmacokinetic profile, thus allowing flexibility to administer the formulation across a wide range of diluent volumes. Keywords: pain, analgesia, liposome bupivacaine, dose, concentration, dilution 

  1. Hormonal and Clinical Predictors for Post-egg Retrieval Pain in Women Undergoing Assisted Reproductive Technology Procedures. (United States)

    Vuilleumier, Pascal H; Dinges, Emily; Ciliberto, Christopher; Ortner, Clemens M; Zarutskie, Paul; Landau, Ruth


    The intensity of post-egg retrieval pain is underestimated, with few studies examining postprocedural pain and predictors to identify women at risk for severe pain. We evaluated the influence of preprocedural hormonal levels, ovarian factors, and mechanical temporal summation (mTS) as predictors for post-egg retrieval pain in women undergoing in vitro fertilization. Eighteen women scheduled for ultrasound-guided egg retrieval under standardized anesthesia and postprocedural analgesia were enrolled. Preprocedural mTS, questionnaires, clinical data related to anesthesia and the procedure itself, postprocedural pain scores, and pain medication for breakthrough pain were recorded. Statistical analysis included Pearson product-moment correlations, Mann-Whitney U tests, and multiple linear regressions. Average peak post-egg retrieval pain during the first 24 hours was 5.0±1.6 on a numerical response scale (0=no pain, 10=worst pain imaginable). Peak post-egg retrieval pain was correlated with basal antimullerian hormone (AMH) (r=0.549, P=0.018), preprocedural peak estradiol (r=0.582, P=0.011), total number of follicles (r=0.517, P=0.028), and number of retrieved eggs (r=0.510, P=0.031). Ovarian hyperstimulation syndrome (n=4) was associated with higher basal AMH (P=0.004), higher peak pain scores (P=0.049), but not with peak estradiol (P=0.13). The mTS did not correlate with peak postprocedural pain (r=0.266, P=0.286), or peak estradiol level (r=0.090, P=0.899). Peak post-egg retrieval pain intensity was higher than anticipated. Our results suggest that post-egg retrieval pain can be predicted by baseline AMH, high peak estradiol, and ovarian hyperstimulation syndrome. Further studies to evaluate intraprocedural and postprocedural pain in this population are needed, as well as clinical trials to assess postprocedural analgesia in women presenting with high hormonal levels.

  2. Management of cancer pain. (United States)

    Lester, P; Gaynor, J S


    Pain secondary to cancer in animals should be promptly addressed to alleviate suffering, stress, and anxiety and to improve quality of life. Uncontrolled cancer pain can have a negative effect on the owners and caregivers of affected animals. The pathophysiology of cancer pain is discussed in this article, along with pain evaluation and monitoring. Treatment of cancer pain should be individualized, and a step-wise approach to the management of cancer pain is presented. The use of opioids, nonsteroidal anti-inflammatory drugs, and adjuvant medications are also reviewed.

  3. Pediatric pain management. (United States)

    Lederhaas, G


    It is now recognized that from the newborn period onwards, children are capable of experiencing pain. This includes the premature infant. The challenge for healthcare providers is to incorporate methods of pain assessment and treatment into their daily practices. The child's understanding of pain closely follows the cognitive and behavioral model developed by Jean Piaget. Based on these developmental stages, pain assessment measures have been developed. Pharmacologic advances have accompanied this improved understanding of infant, child, and adolescent psychology. While acute pain accounts for the majority of children's experiences, recurrent/chronic pain states do occur (e.g. sickle cell related and neuropathic) and can be effectively treated.

  4. Pharmacokinetics of butorphanol after intravenous, intramuscular, and oral administration in Hispaniolan Amazon parrots (Amazona ventralis). (United States)

    Guzman, David Sanchez-Migallon; Flammer, Keven; Paul-Murphy, Joanne R; Barker, Steven A; Tully, Thomas N


    Previous studies have validated the clinical use of opioids with kaap-receptor affinities for pain management in birds. Butorphanol, a kappa opioid receptor agonist and a mu opioid receptor antagonist, is currently considered by many clinicians to be the opioid of choice for this use. However, despite studies reporting the analgesic properties of butorphanol in psittacine birds, dosing intervals have not been established for any psittacine species. The goals of this study in the Hispaniolan Amazon parrot (Amazona ventralis) were to evaluate the pharmacokinetics of butorphanol tartrate after intravenous (IV), intramuscular (IM), and oral (PO) administration and to determine the bioavailability of butorphanol tartrate after oral administration. Twelve Hispaniolan Amazon parrots were used in the study, with a complete-crossover experimental design and a 3-month period separating each part of the study. The birds were randomly assigned to 3 groups (n = 4) for each stage. Butorphanol tartrate was administered once at a dose of 5 mg/kg in the basilic vein or pectoral muscles or as an oral solution delivered via feeding tube into the crop for the IV, IM, and PO studies, respectively. After butorphanol administration, blood samples were collected at 1, 5, 15, 30, 60, 90, 120, 180, and 240 minutes for the IV and IM studies and at 5, 15, 30, 60, 90, 120, 180, 240, and 300 minutes for the PO study. Because of the size limitation of the birds, naive pooling of datum points was used to generate a mean plasma butorphanol concentration at each time point. For each study, birds in each group (n = 4) were bled 3 times after dosing. Plasma butorphanol concentrations were determined by high-performance liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were calculated. Butorphanol tartrate was found to have high bioavailability and rapid elimination following IM administration. In contrast, oral administration resulted in low bioavailability (< 10%), thus

  5. The Breakthrough Listen Search for Intelligent Life: the first SETI results and other future science. (United States)

    Enriquez, J. Emilio; Breakthrough Listen Team


    The Breakthrough Listen (BL) Initiative is the largest campaign in human history on the search for extraterrestrial intelligence. The work presented here is the first BL search for engineered signals. This comprises a sample of 692 nearby stars within 50 pc. We used the Green Bank Telescope (GBT) to conduct observations over 1.1-1.9 GHz (L-band). Our observing strategy allows us to reject most of the detected signals as terrestrial interference. During the analysis, eleven stars show events that passed our thresholding algorithm, but detailed analysis of their properties indicates they are consistent with known examples of anthropogenic radio frequency interference. This small number of false positives and their understood properties give confidence on the techniques used for this search. We conclude that, at the time of our observations none of the observed systems host high-duty-cycle radio transmitters emitting at the observed frequencies with an EIRP of 10^13 W, readily achievable by our own civilization.We can place limits on the presence of engineered signals from putative extraterrestrial civilizations inhabiting the environs of the target stars. Our results suggest that fewer than ~0.1% of the stellar systems within 50 pc possess the type of transmitters searched in this survey. This work provides the most stringent limit on the number of low power radio transmitters around nearby stars to date. We explored several metics to compare our results to previous SETI efforts. We developed a new figure-of-merit that can encompass a wider set of parameters and can be used on future SETI experiments for a meaningful comparison.We note that the current BL state-of-the-art digital backend installed at the Green Bank Observatory is the fastest ever used for a SETI experiment by a factor of a few. Here we will describe the potential use of the BL backend by other groups on complementary science, as well as a mention the ongoing and potential collaborations focused in

  6. Reproducing tailing in breakthrough curves: Are statistical models equally representative and predictive? (United States)

    Pedretti, Daniele; Bianchi, Marco


    Breakthrough curves (BTCs) observed during tracer tests in highly heterogeneous aquifers display strong tailing. Power laws are popular models for both the empirical fitting of these curves, and the prediction of transport using upscaling models based on best-fitted estimated parameters (e.g. the power law slope or exponent). The predictive capacity of power law based upscaling models can be however questioned due to the difficulties to link model parameters with the aquifers' physical properties. This work analyzes two aspects that can limit the use of power laws as effective predictive tools: (a) the implication of statistical subsampling, which often renders power laws undistinguishable from other heavily tailed distributions, such as the logarithmic (LOG); (b) the difficulties to reconcile fitting parameters obtained from models with different formulations, such as the presence of a late-time cutoff in the power law model. Two rigorous and systematic stochastic analyses, one based on benchmark distributions and the other on BTCs obtained from transport simulations, are considered. It is found that a power law model without cutoff (PL) results in best-fitted exponents (αPL) falling in the range of typical experimental values reported in the literature (1.5 constant αCO ≈ 1. In the PLCO model, the cutoff rate (λ) is the parameter that fully reproduces the persistence of the tailing and is shown to be inversely correlated to the LOG scale parameter (i.e. with the skewness of the distribution). The theoretical results are consistent with the fitting analysis of a tracer test performed during the MADE-5 experiment. It is shown that a simple mechanistic upscaling model based on the PLCO formulation is able to predict the ensemble of BTCs from the stochastic transport simulations without the need of any fitted parameters. The model embeds the constant αCO = 1 and relies on a stratified description of the transport mechanisms to estimate λ. The PL fails to

  7. Aldosterone breakthrough in dogs with naturally occurring myxomatous mitral valve disease. (United States)

    Ames, M K; Atkins, C E; Eriksson, A; Hess, A M


    Aldosterone breakthrough (ABT) is the condition in which angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers fail to effectively suppress the activity of the renin angiotensin aldosterone system. The objective of this study was to determine if ABT occurs in dogs with naturally occurring myxomatous mitral valve disease receiving an ACEI, using the urine aldosterone to creatinine ratio (UAldo:C) as a measure of renin angiotensin aldosterone system activation. This study includes 39 dogs with myxomatous mitral valve disease. A UAldo:C cut-off definition (derived from a normal population of healthy, adult, and client-owned dogs) was used to determine the prevalence of ABT in this population. Spearman analysis and univariate logistic regression were used to evaluate the relationship between UAldo:C and ABT (yes/no) and eight variables (age, serum K + concentration, serum creatinine concentration, ACEI therapy duration and ACEI dosage, furosemide therapy duration and furosemide dosage, and urine sample storage time). Finally, the UAldo:C in dogs receiving spironolactone, as part congestive heart failure (CHF) therapy, was compared to dogs with CHF that were not receiving spironolactone. The prevalence of ABT was 32% in dogs with CHF and 30% in dogs without CHF. There was no relationship between either the UAldo:C or the likelihood of ABT and the eight variables. Therapy with spironolactone lead to a significant elevation of the UAldo:C. Using the UAldo:C and a relatively stringent definition of ABT, it appears that incomplete RAAS blockade is common in dogs with MMVD receiving an ACEI. The prevalence of ABT in this canine population mirrors that reported in humans. While the mechanism of ABT is likely multifactorial and still poorly understood, the proven existence of ABT in dogs offers the potential to improve the prognosis for MMVD with the addition of a mineralocorticoid receptor blocker to current therapeutic regimens

  8. Role of voltage-gated sodium channel blockers in the treatment of chronic pain: Potential uses in clinical practice based on available evidence. (United States)

    Alcántara Montero, A; Sánchez Carnerero, C I


    Once patients have failed first line therapy, there is an apparent lack of knowledge on how to proceed with choosing subsequent therapy. To choose amongst alternative agents, an understanding of pharmacology, pharmacokinetics, and available evidence in targeting various pain conditions is necessary. This article focuses on the use of the carboxamide class of voltage-gated sodium channel blockers (carbamazepine, oxcarbazepine, eslicarbazepine acetate) for adjunct pain medication management; including research updates in pharmacology, pharmacokinetics, and evidence for pain along on this therapeutic group with promising future areas of research. Although evidence for voltage-gated sodium channel blockers in chronic pain management is limited, emerging research has identified this area as promising for additional clinical trials to better guide clinical practice. Copyright © 2018 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Extraspinal Percutaneous Osteoplasty for the Treatment of Painful Bony Metastasis. (United States)

    Lee, Jae Heon; Kim, Su Young; Ok, Hwoe Gyeong; Kim, Tae Kyun; Kim, Kyung Hoon


    Extraspinal percutaneous osteoplasties (POPs) are novel techniques for the treatment of painful bony metastasis, which is often the cause of both persistent and incidental breakthrough pain. This retrospective study explored the efficacy and complications of extraspinal POPs. The origin of the cancer metastasis, performed POP sites, necessity of adjacent joint injections, pain and Karnofsky Performance Scale (KPS) scores, complications related to the POPs, and life expectancy were evaluated from the medical records from 2009 to 2016. A total of 47 (M/F = 28/19) patients had received 54 POPs, including costoplasty, scapuloplasty, ilioplasty, humeroplasty, ischioplasty, femoroplasty, sternoplasty, and puboplasty, in order of frequency. The most common sites for the origin of the cancer, in order of frequency, were the lung, liver, breast, colon, and kidney. All patients receiving POPs including scapuloplasty, ilioplasty, humeroplasty, and femoroplasty needed adjacent joint injections before or after the POPs. Pain due to metastatic lesions was reduced significantly immediately after the POPs and the reduction was sustained until the end of their lives. The median KPS was increased from 35.4% to 67.7% immediately after the POPs. There were no complications related to the procedures. The mean life expectancy after performing the POPs, for 35 patients which died afterwards, was 99.3 days, ranging from 1 to 767 days. Even though pain in the isolated POP sites may be difficult to measure due to overlapping systemic pain, the POPs provided immediate local pain relief, and the patients showed better physical performance without procedure-related complications. © 2018 The Korean Academy of Medical Sciences.

  10. [Pharmacokinetics of nitrosomethylurea in oncologic patients]. (United States)

    Korman, D B; Kim, O A; Gor'kov, V A


    Kinetics of blood-nitrosomethylurea (NMU) was studied in 68 patients with lung cancer, malignant melanoma and lymphoma who had received NMU-based combination chemotherapy. The results were used for computing main pharmacokinetic parameters such as logarithm of calculated initial concentration, time of half-elimination from blood, area under the kinetic curve of concentration, volume of distribution in the body and clearance. All those values were shown to significantly differ with individual patients. A longer retention of the drug in blood flow (as evidenced by increased time of half-elimination and area under kinetic curve matched by decreased volume of distribution and clearance) was registered in responders than in non-responders, the difference sometimes reaching statistical significance.

  11. Pharmacokinetics and metabolism of neurotensin in man

    DEFF Research Database (Denmark)

    Pedersen, J H; Andersen, H O; Olsen, P S


    We studied the pharmacokinetics, arteriovenous extraction, and degradation sites of neurotensin (NT) in man during iv infusions of synthetic intact NT [NT-(1-13)] and the NH2-terminal metabolite NT-(1-8) during lipid ingestion and by catheterization of various vascular beds in normal subjects.......6 mL/kg (range, 45.3-281.0). Significant peripheral arteriovenous extraction of NT-(1-13) was found at infusion rates of 144 and 288 pmol/kg.h. Extraction of NH2-terminal immunoreactivity was not significant. Intact NT was identified by gel chromatography in arterial plasma after lipid ingestion...... and iv infusion of NT-(1-13), but postprandially in only low concentrations. In 17 patients with various nonhepatic diseases, plasma intact NT levels were not different in blood sampled from the renal vein, inferior vena cava, brachial artery, or hepatic vein. In contrast, NH2-terminal immunoreactivity...

  12. Dentin hypersensitivity: from diagnosis to a breakthrough therapy for everyday sensitivity relief. (United States)

    Cummins, Diane


    This paper provides an overview of the current knowledge of diagnosis, epidemiology, etiology, and clinical management of dentin hypersensitivity. It summarizes technical approaches to relieve sensitivity in professional and home-use products, with emphasis on the clinical evidence for the efficacy of desensitizing toothpaste, and introduces a new innovative dentifrice technology containing 8% arginine, calcium carbonate, and 1450 ppm fluoride. Dentin hypersensitivity is characterized by short, sharp pain arising from exposed dentin in response to external stimuli which cannot be ascribed to any other form of dental defect or disease. The hydrodynamic theory proposes that pain-producing stimuli cause a change in dentin fluid flow that activates intra-dental nerve fibers, via a mechanoreceptor response, to cause pain. To be hypersensitive, dentin must be exposed and dentin tubules must be open to external stimuli and patent at the pulp. Gingival recession is the primary cause of dentin exposure, and a major predisposing factor for dentin hypersensitivity. Dentin hypersensitivity is a prevalent condition. It has been reported to afflict 15-20% of the adult population, typically 20 to 50-year-olds, with peak incidence between 30 and 39 years. Some studies have reported higher prevalence levels of up to 57%. The incidence of dentin hypersensitivity is expected to rise with changing diets, and as caries and periodontal disease prevention result in improved oral health status, and retention and functionality of the dentition. Treatments to relieve dentin hypersensitivity are based on interruption of the neural response to pain stimuli or occlusion of open tubules to block the hydrodynamic mechanism. Effective and robust dentin occlusion offers the greatest prospect for instant and lasting relief of dentin hypersensitivity. In particular, materials which can coat exposed dentin surfaces, in addition to plugging and sealing open dentin tubules, offer the intriguing

  13. Species differences in pharmacokinetics and drug teratogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nau, H.


    Interspecies differences in regard to the teratogenicity of drugs can be the result of differing pharmacokinetic processes that determine the crucial concentration-time relationships in the embryo. Maternal absorption, as well as distribution, of the drugs does not usually show great species differences. The first-pass effect after oral application is often more pronounced in animals than man (e.g., valproic acid, 13-cis-retinoic acid), although in some cases the reverse was found (e.g., hydrolysis of valpromide). Existing differences can be adjusted by appropriate choice of the administration route and measurements of drug levels. Many variables determine the placental transfer of drugs: developmental stage, type of placenta, properties of the drug. Even closely related drugs (e.g., retinoids) may differ greatly in regard to placental transfer. Maternal protein binding is an important determinant of placental transfer, since only the free concentration in maternal plasma can equilibrate with the embryo during organogenesis; this parameter differs greatly across species. Laboratory animals usually have a much higher rate of drug elimination than man. Drastic drug level fluctuations are therefore present during teratogenicity testing in animals, but not to do the same degree in human therapy. It must, therefore, be investigated if peak concentrations (such as for valproic acid and possibly caffeine) or the area under the concentration-time curve (AUC) (such as for cyclophosphamide and possibly retinoids) correlate with the teratogenic response. Only then is a rational and scientific basis for interspecies comparison possible. It is concluded that the prediction of the human response based on animal studies can be improved by consideration of the appropriate pharmacokinetic determinants.

  14. Pharmacokinetics of topically applied sparfloxacin in rabbits

    Directory of Open Access Journals (Sweden)

    Satia Milan


    Full Text Available PURPOSE: Fluoroquinolones are antimicrobial agents that have a broad spectrum of activity and are widely used against many of the ocular pathogens, responsible for conjunctivitis, blepharitis, corneal ulcers etc. The aim of our study was to evaluate the ocular pharmacokinetics of sparfloxacin (0.3% w/v in the aqueous humour of rabbits. MATERIALS AND METHODS: Pharmacokinetics of topically administered sparfloxacin were determined after a single application of 50 µl topically. The aqueous humour samples were collected at 0, 0.25, 0.5, 1, 2, 3, 4, 5 or 6 hours after instillation. High Performance Thin Layer Chromatographic method was used to analyse the drug concentration in the aqueous humour samples. RESULTS: Fifteen minutes after the instillation of 50 µl of sparfloxacin 0.3% solution, the mean concentration in aqueous humour was found to be 1.4 µg/ml, which reaches the peak level of 3.7 µg/ml after 1.3 hours. At 6 hours, the sparfloxacin aqueous levels were 0.562 µg/ml. The clinical efficacy was predicted based on the Maximum Concentration (Cmax: Minimum Inhibitory Concentration (MIC and Area Under the Concentration-time curve (AUC:MIC ratios. CONCLUSION: The sparfloxacin levels in aqueous humour of rabbits are sufficiently high up to the 6 hours after instillation in the conjunctival sac to provide bactericidal effect against most of the ocular pathogens. Both Cmax:MIC and AUC:MIC ratios are high enough to provide bactericidal effect against most of the ocular pathogens. Sparfloxacin (0.3% ophthalmic preparation has excellent penetration through cornea.

  15. Drug interactions and clinical pharmacokinetics of flumazenil. (United States)

    Klotz, U


    Flumazenil (Ro 15-1788) is a specific benzodiazepine antagonist that can selectively prevent or abolish at the receptor level all centrally mediated effects of benzodiazepines. Following oral administration, flumazenil is absorbed rapidly (peak concentrations are achieved after 20-90 min absorption half-life 0.3 h) but bio-availability is low (16%) owing to significant pre-systemic elimination. As less than 0.2% of an i.v. dose is recovered as unchanged drug in the urine, extensive metabolism must occur and so far three metabolites of flumazenil (N-demethylated and/or hydrolysed products and corresponding glucuronides) have been identified. In the clinical use of flumazenil, rapid onset of action is mandatory. This is facilitated by its fast uptake and regional brain distribution, as verified by positron emission tomography (PET). The limited duration of the benzodiazepine-antagonistic action of flumazenil (2-3 h) is due to its rapid hepatic elimination. This can be characterized either by the short half-life of 0.7-1.3 h or, better, by the high plasma and blood clearance of 520-1300 ml min-1. The low plasma protein binding of flumazenil (about 40%) will not limit its wide distribution (apparent distribution volume 0.6-1 kg) or its partly flow-dependent hepatic elimination. In interaction studies with healthy volunteers, with either midazolam, lormetazepam and flunitrazepam or ethanol, it was found that the disposition of flumazenil was not affected by co-administration of these four drugs. Consequently, pharmacokinetic interactions between benzodiazepines (or alcohol) can be ruled out. So far the pharmacokinetics of the antagonist have been evaluated only in healthy volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Pharmacokinetics of terbutaline in chronic kidney disease. (United States)

    Bastiansen, Anders; Eggert, Sarah; Pedersen, Erland


    In healthy individuals upwards of 90 % of an injected dose of terbutaline is excreted in the urine. The purpose of this study is to determine the pharmacokinetic properties of terbutaline in patients with severe renal impairment as defined by a glomerular filtration rate (GFR) below 30 mL/min. Ten patients were included in the study. GFR was measured with Cr-EDTA clearance. They were given an intravenous injection of 0.500 mg of terbutaline. Blood samples were collected at intervals for 60 h and urine samples were collected for 96 h. The concentration of terbutaline in the blood and in the urine was used to calculate pharmacokinetic parameters. In patients with normal renal function the total clearance of terbutaline is 2.23-3 mL/min/kg. In our population the total clearance of terbutaline was found to be 1.72 (SD: 0.49) mL/min/kg of which approximately 15 % (0.25 mL/min/kg) was renal clearance. We calculated a distribution volume at steady state of 0.74 (SD: 0.22) L/kg with a terminal half-life of 7.93 (SD: 4.06) hours. The mean residence time (MRT) was 8.35 (SD: 4.93) hours. In healthy individuals the excretion of terbutaline is foremost renal but this study shows that severe renal impairment does not lower the total clearance of terbutaline to a degree that might be expected from the Cr-EDTA clearance. However, more research is needed to determine if dosage adjustment is warranted in patients with CKD.

  17. Perinatal pharmacokinetics of azithromycin for cesarean prophylaxis. (United States)

    Sutton, Amelia L; Acosta, Edward P; Larson, Kajal B; Kerstner-Wood, Corenna D; Tita, Alan T; Biggio, Joseph R


    Postpartum infections are polymicrobial and typically include Ureaplasma, an intracellular microbe that is treated by macrolides such as azithromycin. The aim of this study was to evaluate the perinatal pharmacokinetics of azithromycin after a single preincision dose before cesarean delivery. Thirty women who underwent scheduled cesarean delivery were assigned randomly to receive 500 mg of intravenous azithromycin that was initiated 15, 30, or 60 minutes before incision and infused over 1 hour. Serial maternal plasma samples were drawn from the end of infusion up to 8 hours after the infusion. Samples of amniotic fluid, umbilical cord blood, placenta, myometrium, and adipose tissue were collected intraoperatively. Breast milk samples were collected 12-48 hours after the infusion in 8 women who were breastfeeding. Azithromycin was quantified with high performance liquid chromatography separation coupled with tandem mass spectrometry detection. Plasma pharmacokinetic parameters were estimated with the use of noncompartmental analysis and compartmental modeling and simulations. The maximum maternal plasma concentration was reached within 1 hour and exceeded the in vitro minimum inhibitory concentration (MIC50) of 250 ng/mL of Ureaplasma spp in all 30 patients. The concentrations were sustained with a half-life of 6.7 hours. The median concentration of azithromycin in adipose tissue was 102 ng/g, which was below the MIC50. The median concentration in myometrium was 402 ng/g, which exceeded the MIC50. Azithromycin was detectable in both the umbilical cord plasma and amniotic fluid after the single preoperative dose. Azithromycin concentrations in breast milk were high and were sustained up to 48 hours after the single dose. Simulations demonstrated accumulation in breast milk after multiple doses. A single dose of azithromycin achieves effective plasma and tissue concentrations and is transported rapidly across the placenta. The tissue concentrations that are achieved

  18. [Pharmacokinetics of cefoperazone in liver diseases]. (United States)

    Kakiuchi, S; Tagawa, S; Tameda, Y; Kosaka, Y


    To obtain useful informations for determining the optimal dosage of drugs in patients with impaired liver function, pharmacokinetics of cefoperazone (CPZ) was studied in healthy adults (normal control group) and 35 patients with liver disease (liver disease group). CPZ is a new third generation cephalosporin which is mainly excreted into the bile and has serum half-life of about 2 hours. After a rapid intravenous injection of CPZ, peripheral blood and urine samples were obtained at the time according to the protocol of this study. Serum and urine concentrations of CPZ were determined by the bioassay method using Micrococcus luteus ATCC 9341 as the test strain. From the concentrations of CPZ in serum and urine, pharmacokinetic parameters were calculated by means of a "two-compartment open model". After an administration of CPZ, the serum concentration declined more slowly in the liver disease group as compared to the normal control group. At 1 hour after intravenous injection of CPZ, the difference of the serum level was already observed between these 2 groups. The half-life of elimination (T 1/2) was 2 to 4 times longer in the liver disease group. The elimination rate constant (K10) and total clearance (Clt) of CPZ were much lower in the liver disease group than in the control group except for hepatocellular carcinoma. On the other hand, urinary excretion rate (Ur) was lower in the normal control group than in the liver disease group. There was a close correlation between disappearance rate of indocyanine green (KICG) and parameters such as T1/2, K10, Clt and Cler with coefficients of -0.642, 0.723, 0.690 and 0.682, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Cefazolin pharmacokinetics in cats under surgical conditions. (United States)

    Albarellos, Gabriela A; Montoya, Laura; Passini, Sabrina M; Lupi, Martín P; Lorenzini, Paula M; Landoni, María F


    Objectives The aim of this study was to determine the plasma pharmacokinetic profile, tissue concentrations and urine elimination of cefazolin in cats under surgical conditions after a single intravenous dose of 20 mg/kg. Methods Intravenous cefazolin (20 mg/kg) was administered to nine young mixed-breed cats 30 mins before they underwent surgical procedures (ovariectomy or orchiectomy). After antibiotic administration, samples from blood, some tissues and urine were taken. Cefazolin concentrations were determined in all biological matrices and pharmacokinetic parameters were estimated. Results Initial plasma concentrations were high (C p(0) , 134.80 ± 40.54 µg/ml), with fast and moderately wide distribution (distribution half-life [t ½(d) ] 0.16 ± 0.15 h; volume of distribution at steady state [V (d[ss]) ] 0.29 ± 0.10 l/kg) and rapid elimination (body clearance [Cl B ], 0.21 ± 0.06 l/h/kg; elimination half-life [t ½ ], 1.18 ± 0.27 h; mean residence time 1.42 ± 0.36 h). Thirty to 60 mins after intravenous administration, cefazolin tissue concentrations ranged from 9.24 µg/ml (subcutaneous tissue) to 26.44 µg/ml (ovary). The tissue/plasma concentration ratio ranged from 0.18 (muscle) to 0.58 (ovary). Cefazolin urine concentrations were high with 84.2% of the administered dose being eliminated in the first 6 h postadministration. Conclusions and relevance Cefazolin plasma concentrations remained above a minimum inhibitory concentration of ⩽2 µg/ml up to 4 h in all the studied cats. This suggests that a single intravenous dose of 20 mg/kg cefazolin would be adequate for perioperative prophylactic use in cats.

  20. Schumpeterian Patterns of Innovation and the Sources of Breakthrough Inventions: Evidence from a Data-Set of R&D Awards


    Roberto Fontana; Alessandro Nuvolari; Hiroshi Shimitzu; Andrea Vezzulli


    This paper examines the relationship between Schumpeterian patterns of innovation and the generation of breakthrough inventions. Our data source for breakthrough inventions is the “R&D 100 awards” competition organized each year by the magazine Research & Development. Since 1963, this magazine has been awarding this prize to 100 most technologically significant new products available for sale or licensing in the year preceding the judgment. We use instead USPTO patent data to measure the r...