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 in the elderly]. (United States)

    Cabezón-Gutiérrez, Luis; Viloria-Jiménez, María Aurora; Pérez-Cajaraville, Juan; Álamo-González, Cecilio; López-Trigo, José Antonio; Gil-Gregorio, Pedro

    Breakthrough pain is defined as an acute exacerbation of pain with rapid onset, short duration and moderate or high intensity, which occurs spontaneously or in connection with a predictable or unpredictable event despite there being stabilised and controlled baseline pain. However, there are doubts about the definition, terminology, epidemiology, and assessment of breakthrough pain, with no clear answers or consensus, especially in the elderly population. This non-systematic review summarises the most important aspects of breakthrough pain in the elderly, based on the limited publications there are in that population group. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. A European survey of oncology nurse breakthrough cancer pain practices

    NARCIS (Netherlands)

    Rustoen, Tone; Geerling, Jenske I.; Pappa, Theodora; Rundstrom, Carina; Weisse, Isolde; Williams, Sian C.; Zavratnik, Bostjan; Kongsgaard, Ulf E.; Wengstrom, Yvonne

    Purpose of the research: 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

  4. Beyond the traditional definition of breakthrough pain: an observational study. (United States)

    Gatti, Antonio; Gentili, Marta; Iorno, Vittorio; Mammucari, Massimo; Tufaro, Giuseppe; Lazzari, Marzia; Sabato, Alessandro Fabrizio


    Breakthrough pain (BTP) is traditionally defined as a transitory pain flare in opioid-treated patients with chronic background pain. This definition has, however, been challenged in recent years. This study aimed to analyze BTP prevalence in different pain conditions. This was a prospective, non-interventional, observational study conducted from June to September 2011 in two Italian pain treatment reference centres. Consecutive patients aged >18 years with oncological or non-oncological pain were eligible for this study; background pain was acute/ subacute (3 months). The characteristics of pain were evaluated by means of a structured interview by physicians, and patients were asked to complete a dedicated clinical study form. The following outcomes were assessed: chronic pain duration (in patients with chronic pain), BTP prevalence, and number and severity of daily BTP episodes. All outcomes were assessed in four populations of patients with: (a) chronic oncological pain; (b) chronic non-oncological pain; (c) non-chronic oncological pain; (d) non-chronic non-oncological pain. The correlation between BTP and gender was also investigated. Of 1,270 patients with chronic pain, 1,086 had non-oncological pain (85.5%). Most patients (68.6%) with non-oncological pain were female (P = 0.001). Pain duration was significantly longer in non-oncological pain versus oncological pain groups (P = 0.002). BTP prevalence was lower in non-oncological patients (P definition. BTP frequency and severity is similar in oncological and non-oncological pain.

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

    DEFF Research Database (Denmark)

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


    consensus on definitions, terminology, and subclassification of transient cancer pain exacerbations. Methods The most frequent authors on BTCP literature were identified using the same search strategy as in a systematic review and invited to participate in a two-round Delphi survey. Topics with a low degree...

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. A survey of Canadian cancer patients' perspectives on the characteristics and treatment of breakthrough pain. (United States)

    Bedard, Gillian; Hawley, Philippa; Zhang, Liying; Slaven, Marissa; Gagnon, Pierre; Bisland, Stuart; Bennett, Margaret; Tardif, Francois; Chow, Edward


    Breakthrough pain is defined as a transient exacerbation of pain that occurs spontaneously or in response to a trigger despite stable and controlled background pain. The purpose of this study was to explore Canadian patients' awareness of and experience with breakthrough pain in cancer (BTPc). Four Canadian cancer centers participated in a non-interventional survey recruiting cancer patients who experienced breakthrough pain. These patients were asked about their pain, its impact on functioning, current management and interest in new treatments of BTPc. Ninety-four Canadian cancer patients participated in this study, with 96% stating that cancer pain impacted their daily living with over half unable to go to work or shopping. Fifty percent of patients said that an episode of BTPc lasted greater than 60 minutes, with the pain score being on average 7.8/10, impacting normal work (7.2/10) and general activity (7.1/10). Only 35% of patients were very satisfied with the speed of relief of their medications. Those who did not take their breakthrough pain medication for every episode stated that was because the pain was not always severe (37%), or they were afraid of becoming tolerant (23%) or addicted (12%). Patients stated that the most important features of a new treatment for BTPc were the ability to relieve pain completely (47%), and quickly (43%). Patients expressed willingness to try transmucosal products (80%) or nasal products (59%). Breakthrough cancer pain in Canadian cancer patients greatly impacts their daily lives. There is room for improvement in the management of BTPc, and the majority of patients would be willing to try new treatments.

  9. [Breakthrough pain treatment with sublingual fentanyl in patients with chronic cutaneous ulcers]. (United States)

    Domingo-Triadó, V; López Alarcón, M D; Villegas Estévez, F; Alba Moratillas, C; Massa Domínguez, B; Palomares Payá, F; Mínguez Martí, A; Debón Vicent, L


    The aim of the study was to assess the efficacy and safety of opioids in the management of pain in those patients with chronic cutaneous ulcers and breakthrough/incidental pain. An open-label, multicentre, prospective, uncontrolled study was conducted in the pain and ulcer units of 5 hospitals across the Comunidad Valenciana. Eligibility criteria were baseline pain 4 in the visual analogue scale or breakthrough procedural pain 4. Exclusion criteria were cognitive impairment, opioid intolerance, or patient refusal to provide informed consent. The protocol scheduled 5 controls: baseline (enrolment), 15 days, one month, 2 months, and 3 months. The main outcome measure of the study was the visual analogue scale score during rest, movement and procedures. Opioids were administered for release of the baseline pain, and sublingual fentanyl for breakthrough pain. A total of 32 patients (86.5%) completed the study. Baseline pain achieved a mean improvement of 3.6 visual analogue scale points (SD 2.3), movement pain improved by 3.9 points (SD 2.5) and procedural pain improved by 4.5 points (SD 2.8), and the mean pain intensity improvement was statistically significant from the first control and at all controls thereafter (PDolor. Published by Elsevier España. All rights reserved.

  10. Efficacy and safety of tramadol/acetaminophen in the treatment of breakthrough pain in cancer patients. (United States)

    Ho, Ming-Lin; Chung, Chih-Yuan; Wang, Chuan-Cheng; Lin, Hsuan-Yu; Hsu, Nicholas C; Chang, Cheng-Shyong


    We evaluated the analgesic efficacy and safety of tramadol 37.5 mg/acetaminophen 325 mg combination tablet, for the treatment of breakthrough pain in cancer patients. This study was conducted at Changhua Christian Hospital, Changhua, Taiwan from January 2006 to February 2007. The single-center and open-label study enrolled 59 opioid-treated cancer patients with at least moderate breakthrough pain (visual analog scale [VAS] score ≥40mm on a 100-mm scale). The efficacy measures included VAS scores and adverse effect assessment 10, 30, and 60 minutes after the administration of tramadol/acetaminophen. Visual analog scale score at time of pain relief was reported. The mean VAS score when the breakthrough pain episode began (0 minute) was 77.8. Analysis showed significant better mean pain VAS scores at 10, 30, and 60 minutes after the administration of tramadol/acetaminophen (p≤0.001 versus 0 min for all 3 time points). The mean time to pain relief was 597.2 seconds and the mean VAS score at time of relief was 43.4. The effective rates, defined by more than 30% reduction of the VAS score, after 10 minutes of administration was 74.6%, 30 minutes 86.4%, and one hour 94.9% (p≤0.001 versus 0 minute for all 3 time points). Two cases of drowsiness were reported. Tramadol/acetaminophen might be efficacious and safe in the treatment of breakthrough pain in cancer.

  11. Efficacy and safety of tramadol/acetaminophen in the treatment of breakthrough pain in cancer patients

    International Nuclear Information System (INIS)

    Ming-Lin Ho; Chih-Yuan Chung


    We evaluated the analgesic efficacy and safety of tramadol 37.5 mg/acetaminophen 325 mg combination tablet, for the treatment of breakthrough pain in cancer patients. This study was conducted at Changhua Christian Hospital, Changhua, Taiwan from January 2006 to February 2007. The single-center and open-label study enrolled 59 opioid-treated cancer patients with at least moderate breakthrough pain (visual analog scale [VAS] score >/=40mm on a 100-mm scale). The efficacy measures included VAS scores and adverse effect assessment 10, 30, and 60 minutes after the administration of tramadol/acetaminophen. Visual analog scale score at time of pain relief was reported. The mean VAS score when the breakthrough pain episode began (0 minute) was 77.8. Analysis showed significant better mean pain VAS scores at 10, 30, and 60 minutes after the administration of tramadol/acetaminophen (p Tramadol/acetaminophen might be efficacious and safe in the treatment of breakthrough pain in cancer (Author).

  12. 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 episodes was 3/day. Forty-four percent patients reported incident-type pain, 39% spontaneous-type pain, and 17% a combination of these pains. The median duration was 60 min, and the median time to peak intensity was 15 min. Three percent patients reported "mild" pain, 37% "moderate" pain, and 60% "severe......" pain. Ninety percent patients stated that the pain interfered with their daily activities. All patients were using opioids as rescue medication (mainly oral morphine/oxycodone), whilst 28% patients were using non-opioids, and 50% patients were using non-pharmacological interventions. Only 55% patients...

  13. 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.

  14. 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.

  15. 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.

  16. How nurses assess breakthrough cancer pain, and the impact of this pain on patients' daily lives - Results of a European survey

    NARCIS (Netherlands)

    Rustoen, Tone; Geerling, Jenske I.; Pappa, Theodora; Rundstrom, Carina; Weisse, Isolde; Williams, Sian C.; Zavratnik, Bostjan; Wengstrom, Yvonne

    Purpose: 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

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

    Directory of Open Access Journals (Sweden)

    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

  18. 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.

  19. [Pain therapy in pediatric oncology: pain experience, drugs and pharmacokinetics]. (United States)

    Mertens, Rolf


    Paediatric cancer patients often experience fear and pain from the disease but also in connection with the necessary diagnostic and therapeutic procedures. The treatment of pain is a priority for all patients, especially for critically ill children because of their vulnerability and limited understanding. The experience of pain is always subjective and depends on the age, the pain experience and the environment.In contrast to adults, it is often difficult to detect character of pain, pain intensity and pain localization in very young patients. Diagnostic and therapeutic procedures are performed in analgosedation for a given drug scheme by a pediatrician experienced in intensive care.In addition, a local anesthetic for an access system/lumbar punctures in the form of EMLA® patch is to be carried out. A rapid and effective treatment of pain and appropriate analgesia can prevent patients from being traumatized.For severe pain, malignancy- or chemotherapy-induced (eg. mucositis WHO grade 3 and 4) initial use of strong opiates is recommended instead of climbing the WHO ladder. For strong opiates, there is no maximum dose, as long as a dose increase leads to clinically observable increase in analgesia, without severe side effects. Patient-controlled analgesia with morphine as continuous subcutaneous or intravenous infusions and the possibility of a bolus injection is suited for children aged 6 years. A measurement of O2-saturation is essential during this infusion. Prophylactic approaches also must be used consistently in regard to the acute side effect of opiate treatment. Good experience, we have also made a non-drug therapy, e.g. personnel/physical affection, cuddling, massage, etc.The choice of analgesia depends on the nature and cause of pain. In neuropathic pain or phantom pain coanalgetics should be used to effectively treat pain in young patients. Different analgesic treatment approaches of the appropriate indications and adverse effects are presented. A

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. Population pharmacokinetic-pharmacodynamic modeling of ketamine-induced pain relief of chronic pain. (United States)

    Dahan, Albert; Olofsen, Erik; Sigtermans, Marnix; Noppers, Ingeborg; Niesters, Marieke; Aarts, Leon; Bauer, Martin; Sarton, Elise


    Pharmacological treatment of chronic (neuropathic) pain is often disappointing. In order to enhance our insight in the complex interaction between analgesic drug and chronic pain relief, we performed a pharmacokinetic-pharmacodynamic (PK-PD) modeling study on the effect of S(+)-ketamine on pain scores in Complex Regional Pain Syndrome type 1 (CRPS-1) patients. Sixty CRPS-1 patients were randomly allocated to received a 100-h infusion of S(+)-ketamine or placebo. The drug infusion rate was slowly increased from 5 mg/h (per 70 kg) to 20 mg/h based upon the effect/side effect profile. Pain scores and drug blood samples were obtained during the treatment phase and pain scores were further obtained weekly for another 11 weeks. A population PK-PD model was developed to analyze the S(+)-ketamine-pain data. Plasma concentrations of S(+)-ketamine and its metabolite decreased rapidly upon the termination of S(+)-ketamine infusion. The chance for an analgesic effect from ketamine and placebo treatment was 67±10% and 23±9% (population value±SE), respectively. The pain data were well described by the PK-PD model with parameters C(50)=10.5±4.8 ng/ml (95% ci 4.37-21.2 ng/ml) and t½ for onset/offset=10.9±4.0 days (5.3-20.5 days). Long-term S(+)-ketamine treatment is effective in causing pain relief in CRPS-1 patients with analgesia outlasting the treatment period by 50 days. These data suggest that ketamine initiated a cascade of events, including desensitization of excitatory receptor systems in the central nervous system, which persisted but slowly abated when ketamine molecules were no longer present. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

  5. 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®.

  6. Different pharmacokinetics of tramadol in mothers treated for labour pain and in their neonates.

    NARCIS (Netherlands)

    Claahsen-van der Grinten, H.L.; Verbruggen, I.; Berg, P.P. van den; Sporken, J.M.J.; Kollee, L.A.A.


    OBJECTIVE: The aim of the present study was to investigate the pharmacokinetic profile of tramadol hydrochloride in neonates, born from mothers who underwent analgesia with tramadol for the relief of labour pain.METHODS: Intramuscular tramadol (100--250 mg) was administered to 22 mothers giving

  7. 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.

  8. Rectal methadone in cancer patients with pain. A preliminary clinical and pharmacokinetic study. (United States)

    Ripamonti, C; Zecca, E; Brunelli, C; Rizzio, E; Saita, L; Lodi, F; De Conno, F


    Cancer pain can be treated in most cases with oral analgesics. However, during their clinical history, 53% to 70% of patients will need alternative routes of opioid administration. The rectal administration of opioids is a simple alternative route for many patients. There are no data in the literature regarding the pharmacodynamics and pharmacokinetics of rectal methadone. We evaluated the analgesia, tolerability and absorption profile of methadone hydrochloride in six opioid-naive cancer patients with pain. A blood sample was collected before administration of a single dose of drug (10 mg) and then again after fixed times. At these fixed times the patients were asked about pain, nausea and drowsiness by means of a visual analogue scale of 0-100 mm (VAS). Pain relief was statistically significant as early as 30 minutes and up to eight hours after methadone administration. None of the patients reported significant side effects. The pharmacokinetics of rectal methadone showed rapid and extensive distribution phases followed by a slow elimination phase. Rectal methadone can be considered an effective analgesic therapy for patients with cancer pain for whom oral and/or parenteral opioids are not indicated or available.

  9. Clinical effectiveness and safety of OROS® hydromorphone in break-through cancer pain treatment: a multicenter, prospective, open-label study in Korean patients. (United States)

    Lee, Kyung Hee; Kim, Min Kyoung; Hyun, Myung Soo; Kim, Jin Young; Park, Keon Uk; Song, Hong Suk; Lee, Sun Ah; Lee, Won Sik; Bae, Sung Hwa; Ryoo, Hun Mo; Cho, Yoon Young


    To evaluate the effectiveness of OROS® hydromorphone in reducing breakthrough pain (BTP) medication frequency in Korean patients with chronic cancer pain. Multicenter, prospective, open-label, phase IV study. Patients with chronic malignant pain using immediate-release oxycodone more than two times per day for BTP. Patients were stabilized on their ongoing drug for 3 days immediately before baseline measurements (day 0). Medication was changed to OROS® hydromorphone at a dose equianalgesic to oxycodone using a 2.5:1 controlled-release oxycodone to hydromorphone hydrochloride conversion ratio; the patients were observed for 7 days. Dose was titrated, if required, and the patients were observed for another 7 days. Effectiveness and safety parameters were measured at baseline, day 7, and day 14. BTP medication frequency on days 7 and 14, compared to baseline. Of the 141 patients screened, 114 received study drug and 98 completed the study. Compared to day 0, daily BTP medication frequency on day 14 decreased from 2.93 to 2.00 (p > 0.0001), daily BTP frequency decreased from 3.67 to 2.44 (p > 0.0001), and end-of-dose pain frequency decreased by 44 percent. Pain was controlled adequately during daytime and night-time. Pain intensity decreased by 11 percent as assessed using the Korean Brief Pain Inventory and by 17 percent as assessed using the numerical rating scale. About 61.2 percent patients and 60.2 percent physicians were satisfied with the treatment. Common adverse events, which occurred in 91.2 percent patients, were constipation, somnolence, and dizziness. Once-daily OROS® hydromorphone is efficient in the reduction of cancer pain-related BTP episodes, including end-of-dose pain.

  10. 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.

  11. 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.

  12. Breakthrough cancer pain (BTcP): a synthesis of taxonomy, pathogenesis, therapy, and good clinical practice in adult patients in Italy. (United States)

    Zucco, Furio; Bonezzi, Cesare; Fornasari, Diego


    Pain presents in 80% of patients with advanced cancer, and 30% have periods of increased pain due to fluctuating intensity, known as breakthrough cancer pain (BTcP). BTcP is high-intensity, short-duration pain occurring in several episodes per day and is non-responsive to treatment. The clinical approach to BTcP is variable. A review of the literature was performed to provide clinicians and practitioners with a rational synthesis of the ongoing scientific debate on BTcP and to provide a basis for optimal clinical approach to BTcP in adult Italian patients. Data show that circadian exacerbations of pain should be carefully monitored, differentiating, if possible, between fluctuations of background pain (BP), end-of-dose effect, and BTcP. BTcP should be monitored in all care contexts in clinical practice and each care facility must have all the medications and products approved for use in BTcP at their disposal. Data show that knowledge about medications for BTcP is lacking: medications for BTcP treatment are not interchangeable, although containing the same active substance; each physician must know the specific characteristics of each medication, its pharmacological properties, limitations in clinical practice, specifics relating to titration and repeatability of administration, and technical specifics relating to the accessibility and delivery. Importantly, before choosing a rapid-onset opioid (ROO), it is essential to deeply understand the status of patient and the characteristics of their family unit/caregivers, taking into account the patient's progressive loss of autonomy and/or cognitive-relational functionality. When BTcP therapy is initiated or changed, special attention must be paid to training the patient and family members/caregivers, providing clear instructions regarding the timing of drug administration. The patient must already be treated effectively with opioids before introducing ROOs for control of BTcP.

  13. 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.

  14. Current understanding on pharmacokinetics, clinical efficacy and safety of progestins for treating pain associated to endometriosis. (United States)

    Barra, Fabio; Scala, Carolina; Ferrero, Simone


    Endometriosis is a chronic estrogen and progestogen responsive inflammatory disease associated with pain symptoms and infertility. The medical therapy of endometriosis aims to induce decidualization within the hormonally dependent ectopic endometrium, and it is often administered to ameliorate women' pain symptoms or to prevent post-surgical disease recurrence. A variety of progestins have been used in monotherapy for the medical management of women with endometriosis. Areas covered: This review aims to offer the reader a complete overview of pharmacokinetic (PK) and clinical efficacy of progestins for the treatment of endometriosis. Expert opinion: Each progestin has a distinct PK parameters and pharmacodynamics affinity not only for progesterone receptor, but also for other steroid receptors, such as estrogen, androgen, and glucocorticoid. Moreover, progestins can also be delivered in different formulations. All these characteristics influence their final biological effect. Randomized, controlled, non-blinded studies support the use of oral progestin-only treatment for pelvic pain associated with endometriosis. Currently, the only two progestins approved by Food and Drug Administration (FDA) for the treatment of endometriosis are norethindrone acetate (NETA) and depot medroxyprogesterone acetate (DMPA).

  15. Pharmacokinetics and analgesic effect of ropivacaine during continuous epidural infusion for postoperative pain relief

    DEFF Research Database (Denmark)

    Erichsen, C J; Sjövall, J; Kehlet, H


    BACKGROUND: The pharmacokinetics and clinical efficacy of ropivacaine (2.5 mg/ml) during a 24-h continuous epidural infusion for postoperative pain relief in 20 patients scheduled for abdominal hysterectomy were characterized using an open-label, increasing-dose design. METHODS: Through an epidural...... catheter inserted at T10-T12, a test dose of 7.5 mg ropivacaine was given 3 min before a bolus dose of 42.5 mg and immediately followed by a 24-h continuous epidural infusion with either 10 or 20 mg/h. Peripheral venous plasma samples were collected up to 48 h after infusion, and urinary excretion...... plasma concentrations of ropivacaine increased markedly and consistently during the 24-h epidural infusion, in contrast to stable unbound concentrations. Both total and unbound plasma concentrations at the end of infusion were proportional to the total dose, although only the latter was proportional...

  16. 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...... a detailed overview of the published human population pharmacokinetic-pharmacodynamic studies for morphine analgesia in addition to basic drug disposition and pharmacological properties of morphine and its analgesic active metabolite, morphine-6-glucuronide, that may help identify future covariates....... Furthermore, based on simulations from key pharmacokinetic-pharmacodynamic models, the contribution of morphine-6-glucuronide to the analgesic response in patients with renal insufficiency was investigated. Simulations were also used to examine the impact of effect-site equilibration half-life on time course...

  17. Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy. (United States)

    Peltoniemi, Marko A; Hagelberg, Nora M; Olkkola, Klaus T; Saari, Teijo I


    Ketamine is a phencyclidine derivative, which functions primarily as an antagonist of the N-methyl-D-aspartate receptor. It has no affinity for gamma-aminobutyric acid receptors in the central nervous system. Ketamine shows a chiral structure consisting of two optical isomers. It undergoes oxidative metabolism, mainly to norketamine by cytochrome P450 (CYP) 3A and CYP2B6 enzymes. The use of S-ketamine is increasing worldwide, since the S(+)-enantiomer has been postulated to be a four times more potent anesthetic and analgesic than the R(-)-enantiomer and approximately two times more effective than the racemic mixture of ketamine. Because of extensive first-pass metabolism, oral bioavailability is poor and ketamine is vulnerable to pharmacokinetic drug interactions. Sublingual and nasal formulations of ketamine are being developed, and especially nasal administration produces rapid maximum plasma ketamine concentrations with relatively high bioavailability. Ketamine produces hemodynamically stable anesthesia via central sympathetic stimulation without affecting respiratory function. Animal studies have shown that ketamine has neuroprotective properties, and there is no evidence of elevated intracranial pressure after ketamine dosing in humans. Low-dose perioperative ketamine may reduce opioid consumption and chronic postsurgical pain after specific surgical procedures. However, long-term analgesic effects of ketamine in chronic pain patients have not been demonstrated. Besides analgesic properties, ketamine has rapid-acting antidepressant effects, which may be useful in treating therapy-resistant depressive patients. Well-known psychotomimetic and cognitive adverse effects restrict the clinical usefulness of ketamine, even though fewer psychomimetic adverse effects have been reported with S-ketamine in comparison with the racemate. Safety issues in long-term use are yet to be resolved.

  18. 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...

  19. 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.

  20. 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...

  1. 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

  2. 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

  3. 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.

  4. Creating breakthroughs at 3M. (United States)

    von Hippel, E; Thomke, S; Sonnack, M


    Most senior managers want their product development teams to create break-throughs--new products that will allow their companies to grow rapidly and maintain high margins. But more often they get incremental improvements to existing products. That's partly because companies must compete in the short term. Searching for breakthroughs is expensive and time consuming; line extensions can help the bottom line immediately. In addition, developers simply don't know how to achieve breakthroughs, and there is usually no system in place to guide them. By the mid-1990s, the lack of such a system was a problem even for an innovative company like 3M. Then a project team in 3M's Medical-Surgical Markets Division became acquainted with a method for developing breakthrough products: the lead user process. The process is based on the fact that many commercially important products are initially thought of and even prototyped by "lead users"--companies, organizations, or individuals that are well ahead of market trends. Their needs are so far beyond those of the average user that lead users create innovations on their own that may later contribute to commercially attractive breakthroughs. The lead user process transforms the job of inventing breakthroughs into a systematic task of identifying lead users and learning from them. The authors explain the process and how the 3M project team successfully navigated through it. In the end, the team proposed three major new product lines and a change in the division's strategy that has led to the development of breakthrough products. And now several more divisions are using the process to break away from incrementalism.

  5. [Major breakthroughs in the medical treatment

    DEFF Research Database (Denmark)

    Kirk, O.; Gerstoft, J.; Lundgren, J.D.


    The introduction of antiretroviral combination therapy for patients with HIV infection is described as an example of a breakthrough within the field of medical treatment. The background for the breakthrough and the phases thereof are described and for comparison, the circumstances of major breakt...... breakthroughs within other medical specialities are mentioned Udgivelsesdato: 2009/3/2......The introduction of antiretroviral combination therapy for patients with HIV infection is described as an example of a breakthrough within the field of medical treatment. The background for the breakthrough and the phases thereof are described and for comparison, the circumstances of major...

  6. Aostra claims major oilsands breakthrough

    International Nuclear Information System (INIS)



    This paper reports that Alberta Oil Sands Technology and Research Authority (Aostra) has completed a horizontal well in-situ steam injection project it calls a major breakthrough in commercially producing bitumen from the bast Athabasca oilsands deposit in Alberta. Aostra the its $71 million (Canadian) proof of concept pilot underground test facility (UTF) near Fort McMurray, achieved a 60% bitumen recovery rate, compared with less than 20% recovery typically achieved with Alberta bitumen. More than 100,000 bbl of bitumen was produced during the project

  7. Advances in translational neuropathic research: example of enantioselective pharmacokinetic-pharmacodynamic modeling of ketamine-induced pain relief in complex regional pain syndrome. (United States)

    Sabia, Michael; Hirsh, Robert A; Torjman, Marc C; Wainer, Irving W; Cooper, Niti; Domsky, Richard; Goldberg, Michael E


    Historically, complex regional pain syndrome (CRPS) was poorly defined, which meant that scientists and clinicians faced much uncertainty in the study, diagnosis, and treatment of the syndrome. The problem could be attributed to a nonspecific diagnostic criteria, unknown pathophysiologic causes, and limited treatment options. The two forms of CRPS still are painful, debilitating disorders whose sufferers carry heavy emotional burdens. Current research has shown that CRPS I and CRPS II are distinctive processes, and the presence or absence of a partial nerve lesion distinguishes them apart. Ketamine has been the focus of various studies involving the treatment of CRPS; however, currently, there is incomplete data from evidence-based studies. The question as to why ketamine is effective in controlling the symptoms of a subset of patients with CRPS and not others remains to be answered. A possible explanation to this phenomenon is pharmacogenetic differences that may exist in different patient populations. This review summarizes important translational work recently published on the treatment of CRPS using ketamine. © Springer Science+Business Media, LLC 2011

  8. 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.

  9. 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.

  10. 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.

  11. 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 ...

  12. 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.

  13. 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.

  14. Orthopedic Health: Targeting Musculoskeletal Pain (United States)

    ... is helping to pioneer breakthroughs in how doctors deal with problems affecting their patients' tendons, ligaments, and ... Pain increases, movement decreases, and something must be done. What's the treatment for crippling osteoarthritis? Dr. Tuan: ...

  15. Flipped Instruction: Breakthroughs in Research and Practice (United States)

    IGI Global, 2017


    The integration of technology into modern classrooms has enhanced learning opportunities for students. With increased access to educational content, students gain a better understanding of the concepts being taught. "Flipped Instruction: Breakthroughs in Research and Practice" is a comprehensive reference source for the latest scholarly…

  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. 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

  18. 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?

  19. Evaluating Nanoparticle Breakthrough during Drinking Water Treatment (United States)

    Chalew, Talia E. Abbott; Ajmani, Gaurav S.; Huang, Haiou


    Background: Use of engineered nanoparticles (NPs) in consumer products is resulting in NPs in drinking water sources. Subsequent NP breakthrough into treated drinking water is a potential exposure route and human health threat. Objectives: In this study we investigated the breakthrough of common NPs—silver (Ag), titanium dioxide (TiO2), and zinc oxide (ZnO)—into finished drinking water following conventional and advanced treatment. Methods: NPs were spiked into five experimental waters: groundwater, surface water, synthetic freshwater, synthetic freshwater containing natural organic matter, and tertiary wastewater effluent. Bench-scale coagulation/flocculation/sedimentation simulated conventional treatment, and microfiltration (MF) and ultrafiltration (UF) simulated advanced treatment. We monitored breakthrough of NPs into treated water by turbidity removal and inductively coupled plasma–mass spectrometry (ICP-MS). Results: Conventional treatment resulted in 2–20%, 3–8%, and 48–99% of Ag, TiO2, and ZnO NPs, respectively, or their dissolved ions remaining in finished water. Breakthrough following MF was 1–45% for Ag, 0–44% for TiO2, and 36–83% for ZnO. With UF, NP breakthrough was 0–2%, 0–4%, and 2–96% for Ag, TiO2, and ZnO, respectively. Variability was dependent on NP stability, with less breakthrough of aggregated NPs compared with stable NPs and dissolved NP ions. Conclusions: Although a majority of aggregated or stable NPs were removed by simulated conventional and advanced treatment, NP metals were detectable in finished water. As environmental NP concentrations increase, we need to consider NPs as emerging drinking water contaminants and determine appropriate drinking water treatment processes to fully remove NPs in order to reduce their potential harmful health outcomes. Citation: Abbott Chalew TE, Ajmani GS, Huang H, Schwab KJ. 2013. Evaluating nanoparticle breakthrough during drinking water treatment. Environ Health Perspect 121

  20. 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.

  1. 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 < 0.001). The outpatients showed more use of short-acting analgesics for breakthrough pain. Sleep quality change was most significantly associated with intervention; other quality of life aspects (e.g., general feelings and life enjoyment) also improved. Pain education also significantly reduced 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.

  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. Spatially varying dispersion to model breakthrough curves. (United States)

    Li, Guangquan


    Often the water flowing in a karst conduit is a combination of contaminated water entering at a sinkhole and cleaner water released from the limestone matrix. Transport processes in the conduit are controlled by advection, mixing (dilution and dispersion), and retention-release. In this article, a karst transport model considering advection, spatially varying dispersion, and dilution (from matrix seepage) is developed. Two approximate Green's functions are obtained using transformation of variables, respectively, for the initial-value problem and for the boundary-value problem. A numerical example illustrates that mixing associated with strong spatially varying conduit dispersion can cause strong skewness and long tailing in spring breakthrough curves. Comparison of the predicted breakthrough curve against that measured from a dye-tracing experiment between Ames Sink and Indian Spring, Northwest Florida, shows that the conduit dispersivity can be as large as 400 m. Such a large number is believed to imply strong solute interaction between the conduit and the matrix and/or multiple flow paths in a conduit network. It is concluded that Taylor dispersion is not dominant in transport in a karst conduit, and the complicated retention-release process between mobile- and immobile waters may be described by strong spatially varying conduit dispersion. Copyright © 2010 The Author(s). Journal compilation © 2010 National Ground Water Association.

  4. Review of extended-release formulations of Tramadol for the management of chronic non-cancer pain: focus on marketed formulations (United States)

    Kizilbash, Arshi; Ngô-Minh, Cường


    Patients with chronic non-malignant pain report impairments of physical, social, and psychological well-being. The goal of pain management should include reducing pain and improving quality of life. Patients with chronic pain require medications that are able to provide adequate pain relief, have minimum dosing intervals to maintain efficacy, and avoid breakthrough pain. Tramadol has proven efficacy and a favourable safety profile. The positive efficacy and safety profile has been demonstrated historically in numerous published clinical studies as well as from post-marketing experience. It is a World Health Organization “Step 2” opioid analgesic that has been shown to be effective, well-tolerated, and valuable, where treatment with strong opioids is not required. A number of extended release formulations of Tramadol are available in Canada and the United States. An optimal extended release Tramadol formulation would be expected to provide consistent pain control with once daily dosing, few sleep interruptions, flexible dosing schedules, and no limitation on taking with meals. Appropriate treatment options should be based on the above proposed attributes. A comparative review of available extended release Tramadol formulations shows that these medications are not equivalent in their pharmacokinetic profile and this may have implications for selecting the optimal therapy for patients with pain syndromes where Tramadol is an appropriate analgesic agent. Differences in pharmacokinetics amongst the formulations may also translate into varied clinical responses in patients. Selection of the appropriate formulation by the health care provider should therefore be based on the patient’s chronic pain condition, needs, and lifestyle. PMID:24711710

  5. 50 Breakthroughs by America's National Labs (United States)


    America's National Laboratory system has been changing and improving the lives of millions for more than 80 years. Born at a time of great societal need, this network of Department of Energy Laboratories has now grown into 17 facilities, working together as engines of prosperity and invention. As this list of 50 Breakthroughs attests, National Laboratory discoveries have spawned industries, saved lives, generated new products, fired the imagination, and helped to reveal the secrets of the universe. Rooted in the need to be the best and bring the best, America's National Laboratories have put an American stamp on the past century of science. With equal ingenuity and tenacity, they are now engaged in winning the future.

  6. Breakthroughs in neuroactive steroid drug discovery. (United States)

    Blanco, Maria-Jesus; La, Daniel; Coughlin, Quinn; Newman, Caitlin A; Griffin, Andrew M; Harrison, Boyd L; Salituro, Francesco G


    Endogenous and synthetic neuroactive steroids (NASs) or neurosteroids are effective modulators of multiple signaling pathways including receptors for the γ-aminobutyric acid A (GABA A ) and glutamate, in particular N-methyl-d-aspartate (NMDA). These receptors are the major inhibitory and excitatory neurotransmitters in the central nervous system (CNS), and there is growing evidence suggesting that dysregulation of neurosteroid production plays a role in numerous neurological disorders. The significant unmet medical need for treatment of CNS disorders has increased the interest for these types of compounds. In this review, we highlight recent progress in the clinical development of NAS drug candidates, in addition to preclinical breakthroughs in the identification of novel NASs, mainly for GABA A and NMDA receptor modulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. 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...

  8. 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

  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. 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.

  11. Breakdown Breakthrough: NREL Finds Easier Ways to Deconstruct Biomass | (United States)

    News | NREL Breakdown Breakthrough: NREL Finds Easier Ways to Deconstruct Biomass Breakdown Breakthrough: NREL Finds Easier Ways to Deconstruct Biomass May 22, 2018 Roman Brunecky (left), Yannick Bomble soften biomass. Photo by Dennis Schroeder, NREL If there's an easier, more efficient method, science will

  12. 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.

  13. 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.

  14. Building breakthrough businesses within established organizations. (United States)

    Govindarajan, Vijay; Trimble, Chris


    Many companies assume that once they've launched a major innovation, growth will soon follow. It's not that simple. High-potential new businesses within established companies face stiff headwinds well after their inception. That's why a company's emphasis must shift: from ideas to execution and from leadership excellence to organizational excellence. The authors spent five years chronicling new businesses at the New York Times Company, Analog Devices, Corning, Hasbro, and other organizations. They found that a breakthrough new business (referred to as NewCo) rarely coexists gracefully with the established business in the company (called CoreCo). The unnatural combination creates three specific challenges--forgetting, borrowing, and learning--that NewCo must meet in order to survive and grow. NewCo must first forget some of what made CoreCo successful. NewCo and CoreCo have elemental differences, so NewCo must leave behind CoreCo's notions about what skills and competencies are most valuable. NewCo must also borrow some of CoreCo's assets--usually in one or two key areas that will give NewCo a crucial competitive advantage. Incremental cost reductions, for example, are never a sufficient justification for borrowing. Finally, NewCo must be prepared to learn some things from scratch. Because strategic experiments are highly uncertain endeavors, NewCo will face several critical unknowns. The more rapidly it can resolve those unknowns--that is, the faster it can learn--the sooner it will zero in on a winning business model or exit a hopeless situation. Managers can accelerate this learning by planning more simply and more often and by comparing predicted and actual trends.

  15. The United States: breakthroughs and waste. (United States)

    Reinhardt, U E


    The health system of the United States is in a paradoxical position. At its best, the system is a magnet for those seeking the latest technical breakthroughs. It can offer that excellence because there have never been effective financial constraints on the imagination; the system has become a major economic frontier, at which professional and other entrepreneurs successfully seek their fortune. At the same time, the system is leaving increasing numbers of Americans frustrated and disillusioned. It is beset by excess capacity in many areas, is needlessly expensive, and often bestows unnecessary health services. Yet only the experts are aware of these flaws; most Americans still express high satisfaction with the quality of the services they receive from their doctors and hospitals. The public's major misgivings arise over the awkward and inequitable way in which American health care is financed. The typical private health insurance policy, for example, is tied to a particular job. If the job is lost, so is the health insurance. Furthermore, these policies are priced on actuarially "fair" principles, so sick individuals are forced to pay higher insurance premiums than relatively healthy ones and chronically ill persons often cannot obtain health insurance coverage at any price. Although there are public programs to catch many persons not privately insured, the coverage tends to be insufficiently extensive and deep. Some 35 million Americans, mostly poor, have no health insurance whatsoever. Unfortunately, at this time there is no political force in the United States strong enough to reform the American health system toward greater social equity and economic efficiency, whereas there are numerous groups powerful enough to block whatever reform might harm their own narrow economic interests. Other nations can learn from America's clinical and organizational innovations in health care delivery. They can also learn what not to do by studying the unseemly way in which

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

    DEFF Research Database (Denmark)

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


    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 ...... studies and clinical condition in patients suffering from visceral pain, and thus constitute the missing link in translational pain research.......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...... facilitate minimizing the gap between knowledge gained in animal and human clinical studies. Combining experimental pain studies and pharmacokinetic studies can improve understanding of the pharmacokinetic-pharmacodynamic relationship of analgesics and, thus, provide valuable insight into optimal clinical...

  17. 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

  18. A Breakthrough for Strengthening Tusi Studies

    Institute of Scientific and Technical Information of China (English)

    Li Liangpin; Peng Furong


    Following the inscription of China’s Tusi ( native officials ) relics onto the list of world cultural heritage in 2015 , Tusi studies has already become a current topic. However, if we ignored the numerous and complicated historical events, the tremendous amount of historical materials and cases with different characteristics, it is difficult to realize a theoretical breakthrough and academic in-novation. Hence, if the academic world intends to find a new breakthrough in Tusi studies, enough attention should be given to the analysis of past e-vents, digging out historical materials, and case studies—only by which can Tusi studies be strengthened. 1 . Analysis of past events Scholarly research of the Tusi in the past has paid more attention to the system, culture ,and ap-plication of Tusi relics for inscription onto the list of world cultural heritage, but has ignored analysis of significant events. Due to the influence of the political right, economic benefit, and cultural in-filtration, there had always been competition be-tween the central government and the Tusi regime during the Yuan, Ming and Qing dynasties. When some conflicts could not be resolved through nego-tiation, large-scale events or battles were the re-sult. Judging from current studies on every small or large battle between the central government and a Tusi regime, we can see that scholars always focus their studies on the background, process, result, historical influence and related evaluations. Up to now, no scholars have written a monograph of these big events closely related to the Tusi, which is doubtlessly a pity when it comes to Tusi studies. We think that three issues should be noticed while analyzing big events related to the Tusi:1 ) taking the overall situation into consideration; 2 ) having theoretical sight; and 3 ) having a theoretical awareness. 2 . Uncovering historical materials The historical materials are especially impor-tant for the study of the Tusi system or Tusi issues

  19. Perioperative pharmacokinetics of methadone in adolescents. (United States)

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


    Methadone is frequently administered to adults experiencing anesthesia and receiving 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. Eligible subjects were children 5-18 yr undergoing general anesthesia and surgery, with an anticipated postoperative inpatient stay exceeding 3 days. Three groups of 10 to 11 patients each received intravenous methadone hydrochloride 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 4 days, 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. 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. Methadone enantiomer disposition in adolescents undergoing surgery was similar to that in healthy adults.

  20. Managing Conversations: The Medium for Achieving "Breakthrough" Results. (United States)

    Bolton, Robert


    Unlike traditional management development, use of conversations in coaching high-performance work teams addresses core processes of speaking and listening. Management of conversations aims to create learning that will lead to breakthroughs in team performance. (SK)

  1. Back Pain and Modic

    DEFF Research Database (Denmark)

    Manniche, Claus; Jordan, Alan; Mikkelsen, Connie

    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...... 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...

  2. 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.

  3. Fear of pain in children and adolescents with neuropathic pain and complex regional pain syndrome. (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. Because of faulty nerve signaling, individuals with neuropathic pain and complex regional pain syndrome 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 downregulate 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, whereas high initial pain-related fear is a risk factor for less treatment responsiveness. An innovative approach to targeting pain-related fear and evidence of a neural response to treatment involving decoupling of the amygdala with key fear circuits in youth with complex regional pain syndrome suggest breakthroughs in our ability to ameliorate these issues.

  4. 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

  5. Lisdexamfetamine: A pharmacokinetic review. (United States)

    Comiran, Eloisa; Kessler, Félix Henrique; Fröehlich, Pedro Eduardo; Limberger, Renata Pereira


    Lisdexamfetamine (LDX) is a d-amphetamine (d-AMPH) pro-drug used to treat Attention Deficit and Hyperactivity Disorder (ADHD) and Binge Eating Disorder (BED) symptoms. The in vivo pharmacodynamics of LDX is the same as that of its active product d-AMPH, although there are a few qualitative and quantitative differences due to pharmacokinetics. Due to the specific pharmacokinetics of the long-acting stimulants, this article revises the pharmacokinetic studies on LDX, the newest amphetamine pro-drug. The Medline/Pubmed, Science Direct and Biblioteca Virtual em Saúde (Lilacs and Ibecs) (2007-2016) databases were searched for articles and their list of references. As for basic pharmacokinetics studies, since LDX is a newly developed medication, there are few results concerning biotransformation, distribution and the use of different biological matrices for analysis. This is the first robust review on this topic, gathering data from all clinical pharmacokinetics studies available in the literature. The particular pharmacokinetics of LDX plays a major role in studying this pro-drug, since this knowledge was essential to understand some reports on clinical effects in literature, e.g. the small likelihood of reducing the effect by interactions, the effect of long duration use and the still questionable reduction of the potential for abuse. In general the already well-known pharmacokinetic properties of amphetamine make LDX relatively predictable, simplifying the use of LDX in clinical practice. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. 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

  7. 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, ...

  8. High-pressure gas-breakthrough apparatus and a procedure for determining the gas-breakthrough pressure of compacted clay

    International Nuclear Information System (INIS)

    Hume, H.B.


    Gas may be produced in a nuclear fuel waste disposal vault. Given that the vault will be sealed with clay-based materials, the fate of the gas is uncertain. Therefore, an instrument was previously built to measure the pressure required to pass gas through compacted clay materials (a gas-breakthrough apparatus). However, the 10 MPa pressure limit of the apparatus was insufficient to test compacted buffer material at the density proposed in the Canadian concept for nuclear fuel waste disposal. Therefore, a high-pressure (50 Wa) gas-breakthrough apparatus was designed, constructed and installed. This report describes the components of the apparatus and the materials and procedures that are used for the gas-breakthrough tests. (author)

  9. 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

  10. 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

  11. Direct Breakthrough Curve Prediction From Statistics of Heterogeneous Conductivity Fields (United States)

    Hansen, Scott K.; Haslauer, Claus P.; Cirpka, Olaf A.; Vesselinov, Velimir V.


    This paper presents a methodology to predict the shape of solute breakthrough curves in heterogeneous aquifers at early times and/or under high degrees of heterogeneity, both cases in which the classical macrodispersion theory may not be applicable. The methodology relies on the observation that breakthrough curves in heterogeneous media are generally well described by lognormal distributions, and mean breakthrough times can be predicted analytically. The log-variance of solute arrival is thus sufficient to completely specify the breakthrough curves, and this is calibrated as a function of aquifer heterogeneity and dimensionless distance from a source plane by means of Monte Carlo analysis and statistical regression. Using the ensemble of simulated groundwater flow and solute transport realizations employed to calibrate the predictive regression, reliability estimates for the prediction are also developed. Additional theoretical contributions include heuristics for the time until an effective macrodispersion coefficient becomes applicable, and also an expression for its magnitude that applies in highly heterogeneous systems. It is seen that the results here represent a way to derive continuous time random walk transition distributions from physical considerations rather than from empirical field calibration.

  12. Husserl's Illumination of the Breakthrough of Logical Investigations

    African Journals Online (AJOL)


    the example Husserl offers of the room where the lights go off in order to illuminate the breakthrough for ... correspondence theory of truth, and his main concern seems to be to ..... The advantage of Husserl's example is that it tries to situate the ...

  13. 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.

  14. Dissolved CO2 Increases 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.

  15. Modeling dust growth in protoplanetary disks: The breakthrough case (United States)

    Drążkowska, J.; Windmark, F.; Dullemond, C. P.


    Context. Dust coagulation in protoplanetary disks is one of the initial steps toward planet formation. Simple toy models are often not sufficient to cover the complexity of the coagulation process, and a number of numerical approaches are therefore used, among which integration of the Smoluchowski equation and various versions of the Monte Carlo algorithm are the most popular. Aims: Recent progress in understanding the processes involved in dust coagulation have caused a need for benchmarking and comparison of various physical aspects of the coagulation process. In this paper, we directly compare the Smoluchowski and Monte Carlo approaches to show their advantages and disadvantages. Methods: We focus on the mechanism of planetesimal formation via sweep-up growth, which is a new and important aspect of the current planet formation theory. We use realistic test cases that implement a distribution in dust collision velocities. This allows a single collision between two grains to have a wide range of possible outcomes but also requires a very high numerical accuracy. Results: For most coagulation problems, we find a general agreement between the two approaches. However, for the sweep-up growth driven by the "lucky" breakthrough mechanism, the methods exhibit very different resolution dependencies. With too few mass bins, the Smoluchowski algorithm tends to overestimate the growth rate and the probability of breakthrough. The Monte Carlo method is less dependent on the number of particles in the growth timescale aspect but tends to underestimate the breakthrough chance due to its limited dynamic mass range. Conclusions: We find that the Smoluchowski approach, which is generally better for the breakthrough studies, is sensitive to low mass resolutions in the high-mass, low-number tail that is important in this scenario. To study the low number density features, a new modulation function has to be introduced to the interaction probabilities. As the minimum resolution


    Understanding the pharmacokinetics of a chemical¯its absorption, distribution, metabolism, and excretion in humans and laboratory animals ¯ is critical to the assessment of its human health risks. For trichloroethylene (TCE), numerous physiologically-based pharmacokinetic (PBPK)...

  17. Association of peak factor VIII levels and area under the curve with bleeding in patients with haemophilia A on every third day pharmacokinetic-guided prophylaxis

    NARCIS (Netherlands)

    Valentino, L. A.; Pipe, S. W.; Collins, P. W.; Blanchette, V. S.; Berntorp, E.; Fischer, K.; Ewenstein, B. M.; Oh, M.; Spotts, G.


    Introduction: We previously showed that pharmacokinetic-guided prophylaxis (PKP) allows the dosing interval to be extended while maintaining a specific trough level. However, the associations of peak factor VIII (FVIII) levels and area under the curve (AUC) with breakthrough bleeding have not been

  18. Clinical pharmacokinetics of melatonin

    DEFF Research Database (Denmark)

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


    was performed in PubMed and Embase databases. The pharmacokinetic variables included maximal plasma/serum concentration (Cmax), time to maximal plasma/serum concentration (Tmax), elimination half-life (T1/2), area-under-the-curve plasma/serum concentrations (AUC), clearance (Cl), volume of distribution (VD......) 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...

  19. A review on Anticipated Breakthrough Technologies of 21st Century


    Aithal P. S.; Shubhrajyotsna Aithal


    This review discuss strategic management of thirteen most anticipated possible technology breakthroughs of 21st century which are substantially affect the life style of living beings in the world like (1) Nanotechnology-based human life comfort, (2) High speed computation through optical computers, (3) Embedded Intelligence, (4) HIV Antivirus, (5) Pseudo Senses - Sensation of existence through virtual reality and through artificial environment, (6) Off Planet Production in micro-gravity, (7) ...

  20. Ten Main Technological Breakthroughs of CNPC in 2009

    Institute of Scientific and Technical Information of China (English)


    @@ Breakthrough in systematic technology for exploration of Qikou oil-enriched depression in Bohai Bay Basin Qikou oil-enriched depression is one of the largest depressions of the Tertiary deposit in Bohai Bay Basin.The oil and gas exploration of this area faces a number of bottlenecks,such as a large proportion of negative structures,complicated distribution of sedimentary sand bodies and diversified types of oil and gas reservoirs.

  1. Breakthrough innovations : The impact of foreign acquisition of knowledge


    Tojeiro Rivero, Damián; Moreno Serrano, Rosina; Badillo Enciso, Erika Raquel


    Based on the Spanish Technological Innovation Panel, this paper explores the role of R+D offshoring on innovation performance from 2004 to 2013. Specifically, we focus our attention on the impact of different types of offshoring governance models on the profitability of developing breakthrough innovations. Using a novel methodology for panel data sets, we control for the heterogeneity of firms as well as for the sample selection and endogeneity. Our study provides evidence that firms developi...

  2. 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.

  3. 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...

  4. The SolarPACES strategy for the solar thermal breakthrough

    Energy Technology Data Exchange (ETDEWEB)

    Burch, G.D. [U.S. Department of Energy, Washington, DC (United States)


    Our national solar thermal research programs and our combined efforts conducted through IEA/SolarPACES have brought about many breakthroughs in the development of solar thermal technology. We have components and systems that are much more efficient, much more reliable, and can be built much more cost-efficiently than just a few years ago. As our technology development proceeds, we undoubtedly will continue to make significant progress, breakthroughs in fact, in all these areas - progress that will bring us even closer to economic parity with more conventional forms of energy. And while this progress is absolutely necessary, the question is whether it will be enough to allow solar thermal to break into the mainstream of global energy supply. Our new IEA/SolarPACES strategy, crafted and approved over the course of the past year, has recognized the changes we must face and given us license to begin to make those changes. We must begin addressing financial hurdles, work to create a more favorable regulatory and tax environment, support development of international partnerships, and expand the visibility and excitement of solar thermal technology to achieve the final breakthroughs we need to allow solar thermal energy to live up to its vast potential. (orig./AKF)

  5. 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 ...

  6. 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...

  7. 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...

  8. Computational opioid prescribing: a novel application of clinical pharmacokinetics. (United States)

    Linares, Oscar A; Linares, Annemarie L


    We implemented a pharmacokinetics-based mathematical modeling technique using algebra to assist prescribers with point-of-care opioid dosing. We call this technique computational opioid prescribing (COP). Because population pharmacokinetic parameter values are needed to estimate drug dosing regimen designs for individual patients using COP, and those values are not readily available to prescribers because they exist scattered in the vast pharmacology literature, we estimated the population pharmacokinetic parameter values for 12 commonly prescribed opioids from various sources using the bootstrap resampling technique. Our results show that opioid dosing regimen design, evaluation, and modification is feasible using COP. We conclude that COP is a new technique for the quantitative assessment of opioid dosing regimen design evaluation and adjustment, which may help prescribers to manage acute and chronic pain at the point-of-care. Potential benefits include opioid dose optimization and minimization of adverse opioid drug events, leading to potential improvement in patient treatment outcomes and safety.

  9. Drugs in space: Pharmacokinetics and pharmacodynamics in astronauts. (United States)

    Kast, Johannes; Yu, Yichao; Seubert, Christoph N; Wotring, Virginia E; Derendorf, Hartmut


    Space agencies are working intensely to push the current boundaries of human spaceflight by sending astronauts deeper into space than ever before, including missions to Mars and asteroids. Spaceflight alters human physiology due to fluid shifts, muscle and bone loss, immune system dysregulation, and changes in the gastrointestinal tract and metabolic enzymes. These alterations may change the pharmacokinetics and/or pharmacodynamics of medications used by astronauts and subsequently might impact drug efficacy and safety. Most commonly, medications are administered during space missions to treat sleep disturbances, allergies, space motion sickness, pain, and sinus congestion. These medications are administered under the assumption that they act in a similar way as on Earth, an assumption that has not been investigated systematically yet. Few inflight pharmacokinetic data have been published, and pharmacodynamic and pharmacokinetic/pharmacodynamic studies during spaceflight are also lacking. Therefore, bed-rest models are often used to simulate physiological changes observed during microgravity. In addition to pharmacokinetic/pharmacodynamic changes, decreased drug and formulation stability in space could also influence efficacy and safety of medications. These alterations along with physiological changes and their resulting pharmacokinetic and pharmacodynamic effects must to be considered to determine their ultimate impact on medication efficacy and safety during spaceflight. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. 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.

  11. 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

  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. The next breakthrough in phonon-mediated superconductivity

    International Nuclear Information System (INIS)

    Pickett, W.E.


    If history teaches us anything, it is that the next breakthrough in superconductivity will not be the result of surveying the history of past breakthroughs, as they have almost always been a matter of serendipity resulting from undirected exploration into new materials. Still, there is reason to reflect on recent advances, work toward higher T c of even an incremental nature, and recognize that it is important to explore avenues currently believed to be unpromising even as we attempt to be rational. In this paper we look at two remarkable new unusually high temperature superconductors (UHTS), MgB 2 with T c = 40 K and (in less detail) high pressure Li with T c = 20 K, with the aim of reducing their unexpected achievements to a simple and clear understanding. We also consider briefly other UHTS systems that provide still unresolved puzzles; these materials include mostly layered structures, and several with strongly bonded C-C or B-C substructures. What may be possible in phonon-coupled superconductivity is reconsidered in the light of the discussion

  14. (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.

  15. 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.

  16. 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 ...

  17. Pharmacokinetics of Snake Venom

    Directory of Open Access Journals (Sweden)

    Suchaya Sanhajariya


    Full Text Available 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, the disposition of snake venom was described by a two-compartment model consisting of a rapid distribution phase and a slow elimination phase, with half-lives of 5 to 48 min and 0.8 to 28 h, respectively, following rapid intravenous injection of the venoms or toxins. When the venoms or toxins were administered intramuscularly or subcutaneously, an initial absorption phase and slow elimination phase were observed. The bioavailability of venoms or toxins ranged from 4 to 81.5% following intramuscular administration and 60% following subcutaneous administration. The volume of distribution and the clearance varied between snake species. For humans, 24 out of 666 initially identified publications contained sufficient information and timed venom concentrations in the absence of antivenom therapy for data extraction. The data were extracted and modelled in NONMEM. A one-compartment model provided the best fit, with an elimination half-life of 9.71 ± 1.29 h. It is intended that the quantitative information provided in this review will provide a useful basis for future studies that address the pharmacokinetics of snakebite in humans.

  18. 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...

  19. 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.

  20. 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. ...

  1. Pharmacotherapy for pain : what to measure, how to measure?

    NARCIS (Netherlands)

    Martini, Christian Hubert


    In this thesis novel techniques are described which are developed to analyze or predict the efficacy of pharmacotherapy for pain. In Chapter 2 an overview is presented on recent pharmacokinetic pharmacodynamic (PKPD) modeling in acute and chronic pain. Chapter 3 describes the analgesic effect of a

  2. 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.

  3. 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.

  4. 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

  5. Insulin aspart pharmacokinetics

    DEFF Research Database (Denmark)

    Rasmussen, Christian Hove; Roge, Rikke Meldgaard; Ma, Zhulin


    Background: Insulin aspart (IAsp) is used by many diabetics as a meal-time insulin to control postprandial glucose levels. As is the case with many other insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics (PD), is associated with clinical variability, both between...... to investigate and quantify the properties of the subcutaneous depot. Data from Brange et al. (1990) are used to determine the effects of insulin chemistry in subcutis on the absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin are used to understand and quantify the systemic...... distribution and elimination (Porksen et al., 1997; Sjostrand et al., 2002). PK and PD profiles for type 1 diabetics from Chen et al. (2005) are analyzed to demonstrate the effects of IAsp antibodies in terms of bound and unbound insulin. PK profiles from Thorisdottir et al. (2009) and Ma et al. (2012b...

  6. Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A. (United States)

    Collins, P W; Blanchette, V S; Fischer, K; Björkman, S; Oh, M; Fritsch, S; Schroth, P; Spotts, G; Astermark, J; Ewenstein, B


    The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level break-through bleeding in patients with severe hemophilia A on prophylaxis. This study analysed data from 44 patients aged 1-6 and 99 patients aged 10-65 years with severe hemophilia A (FVIII safety and efficacy of a recombinant FVIII (Advate). Each patient had pharmacokinetic measurements and FVIII infusions recorded, and these were used to calculate time spent with a FVIII below 1, 2 and 5 IU dL(-1). The data demonstrate that increasing time with a FVIII below 1 IU dL(-1) is associated with increased total bleeds and hemarthroses. Lack of adherence to the intended frequency of FVIII infusion was the most important determinant of low FVIII and increased bleeding. In children aged 1-6 years, the rate of bleeding was also influenced by FVIII half-life and clearance. These data have important implications for the management of patients with severe hemophilia.

  7. 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.

  8. 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…

  9. 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

  10. Pharmacokinetics of clomipramine during pregnancy

    NARCIS (Netherlands)

    Ter Horst, P G J; Proost, J H; Smit, J P; Vries, M T; de Jong-van den Berg, Lolkje; Wilffert, B


    Clomipramine is one of the drugs for depression during pregnancy; however, pharmacokinetic data of clomipramine and its active metabolite desmethylclomipramine in this vulnerable period are lacking. In this study, we describe clomipramine and desmethylclomipramine concentrations including their


    Directory of Open Access Journals (Sweden)

    V. G. Belolipetskaya


    Full Text Available An article gives in a comprehensive manner the main idea of pharmacokinetics, as the science about rules of substances behavior in the internal environment of the organism, as well as of main parameters of pharmacokinetic researches. The article provides vivid and very  persuasive examples of high practical importance of this science both for creating new medical forms of drugs and for choosing the optimal of therapy regime.


    Directory of Open Access Journals (Sweden)

    V. G. Belolipetskaya


    Full Text Available An article gives in a comprehensive manner the main idea of pharmacokinetics, as the science about rules of substances behavior in the internal environment of the organism, as well as of main parameters of pharmacokinetic researches. The article provides vivid and very  persuasive examples of high practical importance of this science both for creating new medical forms of drugs and for choosing the optimal of therapy regime.

  13. 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.

  14. Soil homogeneity evaluation by radionuclide tracer breakthrough curve interpretation

    International Nuclear Information System (INIS)

    Brenizer, J.S. Jr.; Jarrett, A.R.; Jester, W.A.


    Increasing concern about the environmental impact of hazardous waste disposal has made site evaluation and site selection difficult and expensive. Pollutants, assumed to be absorbed by the soil immediately surrounding the burial trench, have been detected far from sites. Discrepancies between predicted migration distances based on indirect methods such as laboratory and computer modeling and those observed at the field site are often significant. The homogeneity of subsurface media, often assumed in laboratory and modeling studies, is seldom found in the field. The use of tracers to determine the flow characteristics of a potential disposal site involves time and expense, but offers a direct evaluation of solute transport and eliminates the assumptions inherent in indirect methods. Current modeling of solute transport in nonhomogeneous porous media is limited by the quantification of input parameters. Several general models can predict solute transport in saturated-unsaturated media from low-level disposal sites if the hydraulic characteristics and chemical reactions expected in each unique water-solute-media system can be defined. The objective of this research was to develop a method of evaluating potential shallow-land burial waste disposal sites by interpreting tracer breakthrough curve structure with respect to the hydrologic properties of the media at the potential disposal site. This methodology will be helpful in evaluating the potential performance of many types of shallow-land waste burial sites such as low-level radioactive waste disposal, surface disposal of flyash, chemical waste disposal, waste sedimentation ponds, and sanitary landfills

  15. 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.

  16. 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.)

  17. 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.

  18. How Students Combine Resources to Make Conceptual Breakthroughs (United States)

    Richards, A. J.; Jones, Darrick C.; Etkina, Eugenia


    We use the framework of cognitive resources to investigate how students construct understanding of a complex physics topic, namely, a photovoltaic cell. By observing students as they learn about how a solar cell functions, we identified over 60 distinct resources that learners may activate while thinking about photovoltaic cells. We classify these resources into three main types: phenomenological primitives, conceptual resources, and epistemological resources. Furthermore, we found a pattern that suggests that when students make conceptual breakthroughs they may be more likely to activate combinations of resources of different types in concert, especially if a resource from each of the three categories is used. This pattern suggests that physics instructors should encourage students to activate multiple types of prior knowledge during the learning process. This can result from instructors deliberately and explicitly connecting new knowledge to students' prior experience both in and outside the formal physics classroom, as well as allowing students to reflect metacognitively on how the new knowledge fits into their existing understanding of the natural world.

  19. 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.

  20. 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.

  1. Parameterizing the Spatial Markov Model from Breakthrough Curve Data Alone (United States)

    Sherman, T.; Bolster, D.; Fakhari, A.; Miller, S.; Singha, K.


    The spatial Markov model (SMM) uses a correlated random walk and has been shown to effectively capture anomalous transport in porous media systems; in the SMM, particles' future trajectories are correlated to their current velocity. It is common practice to use a priori Lagrangian velocity statistics obtained from high resolution simulations to determine a distribution of transition probabilities (correlation) between velocity classes that govern predicted transport behavior; however, this approach is computationally cumbersome. Here, we introduce a methodology to quantify velocity correlation from Breakthrough (BTC) curve data alone; discretizing two measured BTCs into a set of arrival times and reverse engineering the rules of the SMM allows for prediction of velocity correlation, thereby enabling parameterization of the SMM in studies where Lagrangian velocity statistics are not available. The introduced methodology is applied to estimate velocity correlation from BTCs measured in high resolution simulations, thus allowing for a comparison of estimated parameters with known simulated values. Results show 1) estimated transition probabilities agree with simulated values and 2) using the SMM with estimated parameterization accurately predicts BTCs downstream. Additionally, we include uncertainty measurements by calculating lower and upper estimates of velocity correlation, which allow for prediction of a range of BTCs. The simulated BTCs fall in the range of predicted BTCs. This research proposes a novel method to parameterize the SMM from BTC data alone, thereby reducing the SMM's computational costs and widening its applicability.

  2. 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

  3. 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

  4. 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

  5. The 2001 HBR list. Breakthrough ideas for today's business agenda. (United States)


    Business is shaped by ideas. But how do you separate enduring ideas from passing fancies? In this, the first edition of the annual HBR List, our editors spotlight five break-through ideas that are truly shaping the future of business. EVEN A GREAT BUSINESS MODEL IS NOT ENOUGH: The rise and fall of dot-coms left markets reeling and CEOs scratching their heads. The most important lesson of the debacle: squishy thinking about "business models" is no substitute for a distinctive strategy. CHANGE IS CHANGING: In recent years, pundits have urged executives to incite revolutions within their companies. But a growing group of experts now suggests that the best companies actually evolve through incremental change--change that builds on rather than subverts their heritage. EGO MAKES THE LEADER: By looking deeply into executives' psyches, we are beginning to unlock the enigma of leadership. While there will never be a single recipe for successful corporate stewardship, an understanding of the human ego can shed light on leadership's most fundamental components. ONLY CONNECT: In business organizations, what's really important about people is not their individual skills but the relationships they form with one another. By investing in "social capital," companies can often push their performance to a whole new level. THE BIOLOGY CENTURY DAWNS: In the twentieth century, product innovations tended to spring from physics. But in the new century, biology may be the central source of innovation. From genomics to biomimicry, the study of life promises to change what companies sell and even how they operate.

  6. Postoperative pain

    DEFF Research Database (Denmark)

    Kehlet, H; Dahl, J B


    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......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...

  7. 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...

  8. 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

  9. Observational study to analyze patterns of treatment of breakthrough dyspnea in cancer patients in clinical practice. (United States)

    Cabezón-Gutiérrez, Luis; Delgado-Mingorance, Ignacio; Nabal-Vicuña, María; Jiménez-López, Antonio Javier; Cabezón-Álvarez, Ana; Soler-López, Begoña


    Although breakthrough dyspnea is very frequent in cancer patients, there are no precise recommendations for treating it. The main objective of this study was to analyze what treatments are used in clinical practice for the management of breakthrough dyspnea in cancer patients in Spain and the secondary objectives were to describe the characteristics of cancer patients with breakthrough dyspnea and the attributes of the disorder. Cancer patients over 18 years of age, with breakthrough dyspnea and a Karnofsky performance score of ≥30, who were treated at departments of oncology in institutes across Spain were included in this cross-sectional observational study. The characteristics of breakthrough dyspnea, history of treatment, anthropometric variables, Mahler dyspnea index, Borg scale, Edmonton Symptoms Assessment Scale, and patient satisfaction with current breakthrough dyspnea treatment were assessed. The mean age of the 149 included patients was 66 years (95% confidence interval: 64.3 to 67.9), and 53 were females (35.6%). The mean breakthrough dyspnea intensity was 5.85 (95% confidence interval 5.48 to 6.22, Borg scale). A total of 55.1% of the first-choice treatments consisted of opioids, followed by oxygen (17.3%). A total of 119 patients (79.9%) received monotherapy for breakthrough dyspnea. Patients presenting with basal dyspnea received oxygen in a greater proportion of cases (21.1% vs 7.4%; p = 0.07). Patients with predictable dyspnea received a greater proportion of opioids (70.9% vs 44.4%; p = 0.01). Opioids constitute first-line therapy for breakthrough dyspnea in routine clinical practice, though the scientific evidence supporting their use is scarce. Further information derived from controlled clinical trials is needed regarding the comparative efficacy of the different treatments in order to justify their use.

  10. Clinical pharmacokinetics of phenobarbital in neonates

    NARCIS (Netherlands)

    Touw, D J; Graafland, O; Cranendonk, A; Vermeulen, R J; van Weissenbruch, M M


    Demographic and clinical pharmacokinetic data collected from term and preterm neonates who were treated with intravenous phenobarbital have been analysed to evaluate the role of patient characteristics in pharmacokinetic parameters. Significant relationships between total body weight (TBW) or body

  11. 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 [...

  12. Use of pulsed-neutron capture logs to identify steam breakthrough

    International Nuclear Information System (INIS)

    Masse, P.J.; Gosney, T.C.; Long, D.L.


    This paper reports on identification of steam-breakthrough zones in a stacked sand/shale sequence with variable lateral continuity which is difficult. Such identification, however, would allow the modification of field operations to enhance recovery through improved vertical sweep and heat injection. Twenty pulsed-neutron capture (PNC) logs were run to identify the steam-breakthrough zone(s) in a seven-pattern area of Mobil's Middle expansion (MIDX) Steamflood Project in the South Belridge field. These PNC data were combined with data from recent replacement wells and a detailed geologic analysis. Evaluation of this combined information allowed identification of potential steam-breakthrough zone(s), and operations were modified to reduce and eliminate steam breakthrough

  13. 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...

  14. 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.

  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;.


    NARCIS (Netherlands)


    The existing human pharmacokinetic studies have been reviewed and compared with data derived from animals. The earliest study confirms the similarity of rocuronium to vecuronium with respect to the variables derived from the plasma concentration decay curves and the proportion excreted renally.

  17. 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.

  18. 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

  19. Computer model predicting breakthrough febrile urinary tract infection in children with primary vesicoureteral reflux. (United States)

    Arlen, Angela M; Alexander, Siobhan E; Wald, Moshe; Cooper, Christopher S


    Factors influencing the decision to surgically correct vesicoureteral reflux (VUR) include risk of breakthrough febrile urinary tract infection (fUTI) or renal scarring, and decreased likelihood of spontaneous resolution. Improved identification of children at risk for recurrent fUTI may impact management decisions, and allow for more individualized VUR management. We have developed and investigated the accuracy of a multivariable computational model to predict probability of breakthrough fUTI in children with primary VUR. Children with primary VUR and detailed clinical and voiding cystourethrogram (VCUG) data were identified. Patient demographics, VCUG findings including grade, laterality, and bladder volume at onset of VUR, UTI history, presence of bladder-bowel dysfunction (BBD), and breakthrough fUTI were assessed. The VCUG dataset was randomized into a training set of 288 with a separate representational cross-validation set of 96. Various model types and architectures were investigated using neUROn++, a set of C++ programs. Two hundred fifty-five children (208 girls, 47 boys) diagnosed with primary VUR at a mean age of 3.1 years (±2.6) met all inclusion criteria. A total 384 VCUGs were analyzed. Median follow-up was 24 months (interquartile range 12-52 months). Sixty-eight children (26.7%) experienced 90 breakthrough fUTI events. Dilating VUR, reflux occurring at low bladder volumes, BBD, and history of multiple infections/fUTI were associated with breakthrough fUTI (Table). A 2-hidden node neural network model had the best fit with a receiver operating characteristic curve area of 0.755 for predicting breakthrough fUTI. The risk of recurrent febrile infections, renal parenchymal scarring, and likelihood of spontaneous resolution, as well as parental preference all influence management of primary VUR. The genesis of UTI is multifactorial, making precise prediction of an individual child's risk of breakthrough fUTI challenging. Demonstrated risk factors for

  20. Pharmacokinetic-Pharmacodynamic Modelling of the Analgesic and Antihyperalgesic Effects of Morphine after Intravenous Infusion in Human Volunteers

    DEFF Research Database (Denmark)

    Ravn, Pernille; Foster, David J. R.; Kreilgaard, Mads


    Using a modelling approach, this study aimed to (i) examine whether the pharmacodynamics of the analgesic and antihyperalgesic effects of morphine differ; (ii) investigate the influence of demographic, pain sensitivity and genetic (OPRM1) variables on between-subject variability of morphine...... pharmacokinetics and pharmacodynamics in human experimental pain models. The study was a randomized, double-blind, 5-arm, cross-over, placebo-controlled study. The psychophysical cutaneous pain tests, electrical pain tolerance (EPTo) and secondary hyperalgesia areas (2HA) were studied in 28 healthy individuals (15...

  1. Sexual pain. (United States)

    Boardman, Lori A; Stockdale, Colleen K


    Sexual pain is an underrecognized and poorly treated constellation of disorders that significantly impact affected women and their partners. Recognized as a form of chronic pain, sexual pain disorders are heterogeneous and include dyspareunia (superficial and deep), vaginismus, vulvodynia, vestibulitis, and noncoital sexual pain disorder. Women too often tolerate pain in the belief that this will meet their partners' needs. This article provides a review of the terminology and definition of the condition, theories on the pathophysiology, diagnostic considerations, and recommendations on the management of female sexual pain.

  2. 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

  3. Pelvic Pain (United States)

    ... OLPP) Office of Science Policy, Reporting, and Program Analysis (OSPRA) Division of Extramural Research (DER) Extramural Scientific ... treat my pain? Can pelvic pain affect my emotional well-being? How can I cope with long- ...

  4. Neck pain (United States)

    ... cause of neck pain is muscle strain or tension. Most often, everyday activities are to blame. Such ... of a heart attack , such as shortness of breath, sweating, nausea, vomiting, or arm or jaw pain. ...

  5. 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.

  6. Patellofemoral Pain. (United States)

    Dutton, Rebecca A; Khadavi, Michael J; Fredericson, Michael


    Patellofemoral pain is characterized by insidious onset anterior knee pain that is exaggerated under conditions of increased patellofemoral joint stress. A variety of risk factors may contribute to the development of patellofemoral pain. It is critical that the history and physical examination elucidate those risk factors specific to an individual in order to prescribe an appropriate and customized treatment plan. This article aims to review the epidemiology, risk factors, diagnosis, and management of patellofemoral pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 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. ...

  8. 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

  9. 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

  10. 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.

  11. 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....... of the heritable variability in the pharmacokinetics of metoprolol and torsemide remains to be elucidated. This article is protected by copyright. All rights reserved....

  12. 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.

  13. Development of a Pharmacokinetic Model to Describe the Complex Pharmacokinetics of Pazopanib in Cancer Patients

    NARCIS (Netherlands)

    Yu, Huixin; van Erp, Nielka; Bins, Sander; Mathijssen, Ron H J; Schellens, Jan H M; Beijnen, Jos H.; Steeghs, Neeltje; Huitema, Alwin D R

    Background and Objective: Pazopanib is a multi-targeted anticancer tyrosine kinase inhibitor. This study was conducted to develop a population pharmacokinetic (popPK) model describing the complex pharmacokinetics of pazopanib in cancer patients. Methods: Pharmacokinetic data were available from 96

  14. Development of a Pharmacokinetic Model to Describe the Complex Pharmacokinetics of Pazopanib in Cancer Patients

    NARCIS (Netherlands)

    Yu, H.; Erp, N. van; Bins, S.; Mathijssen, R.H.; Schellens, J.H.; Beijnen, J.H.; Steeghs, N.; Huitema, A.D.


    BACKGROUND AND OBJECTIVE: Pazopanib is a multi-targeted anticancer tyrosine kinase inhibitor. This study was conducted to develop a population pharmacokinetic (popPK) model describing the complex pharmacokinetics of pazopanib in cancer patients. METHODS: Pharmacokinetic data were available from 96

  15. Modeling Breakthrough Curves of Citric Acid Adsorption onto Anionic Resins in an Aqueous Solution

    Directory of Open Access Journals (Sweden)

    Sohrabali Ghorbanian


    Full Text Available Breakthrough curves for citric acid adsorption from aqueous solution onto ion-exchange resin at 20, 35, and 55°C have been investigated. To predict breakthrough curves, three mathematical models have been analyzed based on the values of the least square method parameters, Durbin-Watson test, and mean relative percent error and, finally, appropriate models have been achieved. Models are in good agreement with experimental data based on the results. To examine models reliabilities and accuracy, models have been compared by various breakthrough curve data obtained by other investigators. The results show appropriate agreement and in some cases regression errors have been reduced to less than 1.0 percent.

  16. Liquid water breakthrough location distances on a gas diffusion layer of polymer electrolyte membrane fuel cells (United States)

    Yu, Junliang; Froning, Dieter; Reimer, Uwe; Lehnert, Werner


    The lattice Boltzmann method is adopted to simulate the three dimensional dynamic process of liquid water breaking through the gas diffusion layer (GDL) in the polymer electrolyte membrane fuel cell. 22 micro-structures of Toray GDL are built based on a stochastic geometry model. It is found that more than one breakthrough locations are formed randomly on the GDL surface. Breakthrough location distance (BLD) are analyzed statistically in two ways. The distribution is evaluated statistically by the Lilliefors test. It is concluded that the BLD can be described by the normal distribution with certain statistic characteristics. Information of the shortest neighbor breakthrough location distance can be the input modeling setups on the cell-scale simulations in the field of fuel cell simulation.

  17. 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

  18. Pharmacokinetics of drugs in pregnancy. (United States)

    Feghali, Maisa; Venkataramanan, Raman; Caritis, Steve


    Pregnancy is a complex state where changes in maternal physiology have evolved to favor the development and growth of the placenta and the fetus. These adaptations may affect preexisting disease or result in pregnancy-specific disorders. Similarly, variations in physiology may alter the pharmacokinetics or pharmacodynamics that determines drug dosing and effect. It follows that detailed pharmacologic information is required to adjust therapeutic treatment strategies during pregnancy. Understanding both pregnancy physiology and the gestation-specific pharmacology of different agents is necessary to achieve effective treatment and limit maternal and fetal risk. Unfortunately, most drug studies have excluded pregnant women based on often-mistaken concerns regarding fetal risk. Furthermore, over two-thirds of women receive prescription drugs while pregnant, with treatment and dosing strategies based on data from healthy male volunteers and non-pregnant women, and with little adjustment for the complex physiology of pregnancy and its unique disease states. This review will describe basic concepts in pharmacokinetics and their clinical relevance and highlight the variations in pregnancy that may impact the pharmacokinetic properties of medications. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. 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)

  20. 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.


    Makharin, O A; Zhenilo, V M; Patyuchenko, O Yu


    Quality anesthesia during surgery and in the postoperative period remains a topical problem of modern anesthesiology. The study of genetic characteristics of a patient is a goal that may be allow us to develop a personalized approach to solve this problem. The purpose of the review is a synthesis of literature data about the influence of genetic factors on pain perception and its treatment. The review included information obtained from SCOPUS, MedLine, EMBASE. The search keywords were: pain, pharmacogenetics, polymorphism, analgesics.Describe the effect ofgene polymorphisms of OPRM, 5HTRIA, 5HTR2A, COMT GCHI, SCN9A, KCNSI, CACNA2D3, CACNG2, PTGSI, PTGS2, MDRJ/ABCB] on the perception of pain, and CYP2D6, CYP2C9, CYP3A4 on the pharmacokinetics and pharmacodynamics of medi- cations used in the treatment of pain.

  2. 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.

  3. 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....

  4. 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.

  5. 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…

  6. First case of breakthrough pneumonia due to Aspergillus nomius in a patient with acute myeloid leukemia. (United States)

    Caira, Morena; Posteraro, Brunella; Sanguinetti, Maurizio; de Carolis, Elena; Leone, Giuseppe; Pagano, Livio


    We report the first known case of a breakthrough pulmonary infection caused by Aspergillus nomius in an acute myeloid leukemia patient receiving caspofungin therapy. The isolate was identified using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and sequencing-based methods. The organism was found to be fully susceptible, in vitro, to echinocandin antifungal agents.

  7. [Parahisian atrial tachycardia or atrioventricular nodal reentrant tachycardia with tendon of Todaro breakthrough?]. (United States)

    Orczykowski, Michał; Jaworska-Wilczyńska, Maria; Urbanek, Piotr; Bodalski, Robert; Derejko, Paweł; Gajek, Jacek; Hryniewiecki, Tomasz; Szumowski, Lukasz; Walczak, Franciszek


    We present a case of a 61 year-old woman with tachycardia originating close to the His bundle where radiofrequency (RF) ablation may bear potential risk of atrioventricular (AV) block. In this case report we discuss the possibility of a AV nodal reciprocating tachycardia with tendon of Todaro breakthrough. Patient was safely and effectively treated with RF catheter ablation.

  8. 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…

  9. Effect of temperature on the breakthrough of a charcoal tube during vinyl chloride monomer sampling. (United States)

    Roh, J; Park, Y J; Kim, C N; Lim, N G; Lee, S H; Song, J S; Won, J U; Talaska, G


    This study evaluated the effects of temperature on breakthrough of two standard collection media at various concentrations during vinyl chloride monomer (VCM) sampling. The National Institute for Occupational Safety and Health (NIOSH) and Occupational Safety and Health Administration (OSHA) methods were evaluated. To determine whether breakthrough of VCM would occur at the extremes of exposure and temperature that might be encountered in some workplaces, air samples containing 4 ppm (10.24 mg/m3), 8 ppm (20.45 mg/m3), 16 ppm (40.98 mg/m3), and 32 ppm (81.80 mg/m3) of VCM were collected at temperatures of 4, 22, and 40 degrees C. Five liters of air was sampled at the rate of 0.05 L/min for 100 min using the activated charcoal tube recommended by NIOSH. A second tube was added to the sampling train to collect any VCM that might not have been absorbed in the first tube. To collect VCM air samples by the OSHA method, two carbon molecular sieve tubes were connected serially and 3 L of air was sampled at the rate of 0.05 L/min for 60 min. A gas chromatograph with a flame ionization detector and ultra 2 capillary column was used to analyze VCM. Significant breakthrough was found when sampling at higher temperatures with the NIOSH method. No breakthrough was found when samples were collected using the OSHA media at different temperatures and concentrations. Therefore, under hot ambient conditions (>22 degrees C), the possibility of breakthrough should be considered when sampling VCM by the NIOSH method.

  10. 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.

  11. Choreographing Partnerships within an Organizational Structure of Accountability: Maryland State Department of Education's Shift from Compliance Monitor to Breakthrough Partner (United States)

    Strickling, Laura Rutter; Doneker, Karen Lee


    Drawing upon data from twenty-five interviews, this paper examines how the Maryland State Department of Education's Cross-functional Team navigates its changing role from compliance monitor to breakthrough partner in terms of discourse, time, and flexibility, as it carries out the work of the Breakthrough Center. It also examines how the role of…

  12. Ejaculatory pain

    DEFF Research Database (Denmark)

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


    . The psychosexual interview revealed no major psychosexual disturbances and concluded that the pain was of somatic origin. All patients with ejaculatory pain had experienced major negative life changes and deterioration in their overall quality of life and sexual function as a result of the hernia operation...

  13. Breast Pain (United States)

    ... result in the development of breast cysts. Breast trauma, prior breast surgery or other factors localized to the breast can lead to breast pain. Breast pain may also start outside the breast — in the chest wall, muscles, joints or heart, for example — and ...

  14. 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.

  15. 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.

  16. 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, ...

  17. Neck Pain (United States)

    ... Vomiting Nausea and Vomiting in Infants and Children Neck Pain Neck Swelling Shortness of Breath Shortness of Breath ... worse or doesn’t get better. Start OverDiagnosisYour pain may be from DEGENERATIVE CERVICAL ARTHRITIS, a disorder that affects the bones and ...

  18. 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 <5 ng/mL was 49 days after administration. The unusual 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.

  19. 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

  20. A comprehensive physiologically based pharmacokinetic ... (United States)

    Published physiologically based pharmacokinetic (PBPK) models from peer-reviewed articles are often well-parameterized, thoroughly-vetted, and can be utilized as excellent resources for the construction of models pertaining to related chemicals. Specifically, chemical-specific parameters and in vivo pharmacokinetic data used to calibrate these published models can act as valuable starting points for model development of new chemicals with similar molecular structures. A knowledgebase for published PBPK-related articles was compiled to support PBPK model construction for new chemicals based on their close analogues within the knowledgebase, and a web-based interface was developed to allow users to query those close analogues. A list of 689 unique chemicals and their corresponding 1751 articles was created after analysis of 2,245 PBPK-related articles. For each model, the PMID, chemical name, major metabolites, species, gender, life stages and tissue compartments were extracted from the published articles. PaDEL-Descriptor, a Chemistry Development Kit based software, was used to calculate molecular fingerprints. Tanimoto index was implemented in the user interface as measurement of structural similarity. The utility of the PBPK knowledgebase and web-based user interface was demonstrated using two case studies with ethylbenzene and gefitinib. Our PBPK knowledgebase is a novel tool for ranking chemicals based on similarities to other chemicals associated with existi

  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. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ng, C.W.W.; Chen, Z.K.; Coo, J.L. [Department of Civil and Environmental Engineering, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong); Chen, R., E-mail: [Shenzhen Key Laboratory of Urban and Civil Engineering for Disaster Prevention and Mitigation, Harbin Institute of Technology Shenzhen Graduate School, Shenzhen 518055 (China); Zhou, C. [Department of Civil and Environmental Engineering, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong)


    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

  4. Computational Analysis of Pharmacokinetic Behavior of Ampicillin

    Directory of Open Access Journals (Sweden)

    Mária Ďurišová


    Full Text Available orrespondence: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, 841 04 Bratislava, Slovak Republic. Phone + 42-1254775928; Fax +421254775928; E-mail: 84 RESEARCH ARTICLE The objective of this study was to perform a computational analysis of the pharmacokinetic behavior of ampicillin, using data from the literature. A method based on the theory of dynamic systems was used for modeling purposes. The method used has been introduced to pharmacokinetics with the aim to contribute to the knowledge base in pharmacokinetics by including the modeling method which enables researchers to develop mathematical models of various pharmacokinetic processes in an identical way, using identical model structures. A few examples of a successful use of the modeling method considered here in pharmacokinetics can be found in full texts articles available free of charge at the website of the author, and in the example given in the this study. The modeling method employed in this study can be used to develop a mathematical model of the pharmacokinetic behavior of any drug, under the condition that the pharmacokinetic behavior of the drug under study can be at least partially approximated using linear models.

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

    Directory of Open Access Journals (Sweden)

    Marvin Omar Delgado-Guay


    Full Text Available Marvin Omar Delgado-GuayDivision of Geriatrics and Palliative Medicine, The University of Texas, Medical School at Houston, Houston, TX, USAAbstract: 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.Keywords: fentanyl buccal soluble film, cancer pain

  6. Breakthrough bargaining. (United States)

    Kolb, D M; Williams, J


    Unspoken, subtle parts of a bargaining process--also known as the shadow negotiation--can set the tone for a successful negotiation. Deborah Kolb and Judith Williams, whose book The Shadow Negotiation was the starting point for this article, say there are three strategies businesspeople can use to guide these hidden interactions. Power moves are used when two negotiating parties hold unequal power--for instance, subordinates and bosses; new and existing employees; and people of different races, ages, or genders. These strategies, such as casting the status quo in an unfavorable light, can help parties realize that they must negotiate: they will be better off if they do and worse off if they don't. Process moves affect how negotiation issues are received by both sides in the process, even though they do not address substantive issues. Working outside of the actual bargaining process, one party can suggest ideas or marshal support that can shape the agenda and influence how others view the negotiation. Appreciative moves alter the tone or atmosphere so that a more collaborative exchange is possible. They shift the dynamics of the shadow negotiation away from the adversarial--helping parties to save face--and thus build trust and encourage dialogue. These strategic moves don't guarantee that all bargainers will walk away winners, but they help to get stalled negotiations moving--out of the dark of unspoken power plays and into the light of true dialogue.

  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. Mathematical models applied to the Cr(III) and Cr(VI) breakthrough curves. (United States)

    Ramirez C, Margarita; Pereira da Silva, Mônica; Ferreira L, Selma G; Vasco E, Oscar


    Trivalent and hexavalent chromium continuous biosorption was studied using residual brewer Saccharomyces cerevisiae immobilized in volcanic rock. The columns used in the process had a diameter of 4.5 cm and a length of 140 cm, working at an inlet flow rate of 15 mL/min. Breakthrough curves were used to study the yeast biosorption behavior in the process. The saturation time (ts) was 21 and 45 h for Cr(III) and Cr(VI), respectively, and a breakthrough time (tb) of 4 h for Cr(III) and 5 h for Cr(VI). The uptake capacity of the biosorbent for Cr(III) and Cr(VI) were 48 and 60 mg/g, respectively. Two non-diffusional mathematical models with parameters t0 and sigma were used to adjust the experimental data obtained. Microsoft Excel tools were used for the mathematical solution of the two parameters used.

  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. 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.

  11. 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.

  12. 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.

  13. How Is Pain Managed? (United States)

    ... Detection- Goggins Lab Sol Goldman Center Discussion Board Pain Management Pain is a very common symptom in patients ... of pain. Pain Assessment The first step in pain management is a thorough assessment. Your healthcare provider will ...

  14. 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.

  15. 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; Kijak, Gustavo H; 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 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 trials for diverse pathogens.

  16. 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.

  17. Pain Management (United States)

    ... Funding Funding Opportunities (NIH Guide) Forms and Deadlines Electronic Research Admin (eRA) Grants Policy OER News About ... remains the most commonly used pain reliever. The French physician, Dr. Albert Schweitzer, proclaimed in 1931 that, “ ...

  18. 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 ...

  19. Ankle Pain (United States)

    ... home remedies for a while. Seek immediate medical attention if you: Have severe pain or swelling Have ... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization ...

  20. Abdominal Pain (United States)

    ... or pain in your chest Seek immediate medical attention Have someone drive you to urgent care or ... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization ...

  1. Testicle Pain (United States)

    ... is more common in adolescents. Seek immediate medical attention if you have: Sudden, severe testicle pain Testicle ... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization ...

  2. Gastric pain

    African Journals Online (AJOL)

    drugs and drug classes are also linked to a range of mechanisms through which the drugs ... meal, occurring several times per ... Burning or distressing pain, relieved by food ..... antimicrobial agents, and several other drug interactions are.

  3. 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 ) ...

  4. 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 ...

  5. Elbow pain (United States)

    ... the cause, but may involve: Antibiotics Corticosteroid shots Manipulation Pain medicine Physical therapy Surgery (last resort) Alternative ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  6. Knee pain (United States)

    ... Fracture of the kneecap or other bones. Iliotibial band syndrome . Injury to the thick band that runs from your hip to the outside ... of your knee pain. When to Contact a Medical Professional Call your provider if: You cannot bear ...

  7. Abdominal Pain (United States)

    ... I find more information and related topics? Functional Abdominal Pain (English, French or Spanish)—from The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). Gastro Kids , a ...

  8. Flank pain (United States)

    ... how to do these exercises at home. Nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy may be prescribed for flank pain caused by spinal arthritis. Antibiotics are used to treat most kidney infections. You ...

  9. Elbow Pain (United States)

    ... tear damage than are many other joints. Seek emergency care if you have: An obvious deformity in ... . Mayo Clinic Footer Legal Conditions and ...

  10. Arm Pain (United States)

    ... be a sign of a heart attack. Seek emergency treatment if you have: Arm, shoulder or back ... . Mayo Clinic Footer Legal Conditions and ...

  11. Breakthrough analysis for water disinfection using silver nanoparticles coated resin beads in fixed-bed column

    International Nuclear Information System (INIS)

    Mthombeni, Nomcebo H.; Mpenyana-Monyatsi, Lizzy; Onyango, Maurice S.; Momba, Maggie N.B.


    Highlights: ► Performance of silver nanoparticles coated resin in water disinfection is presented. ► Sigmoidal models are used to describe breakthrough curves. ► The performance of the media in water disinfection is affected by process variables. ► Test with environmental water shows the media is effective in water disinfection. - Abstract: This study demonstrates the use of silver nanoparticles coated resin beads in deactivating microbes in drinking water in a column filtration system. The coated resin beads are characterized using X-ray diffraction (XRD), Fourier transform infra-red (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM) and energy dispersive spectroscopy (EDS) to confirm the functional groups, morphology and the presence of silver nanoparticles on the surface of the resin. The performance of the coated resin is evaluated as a function of bed mass, initial bacterial concentration and flow rate using Escherichia coli as model microbial contaminant in water. The survival curves of E. coli are expressed as breakthrough curves (BTCs), which are modeled using sigmoidal regression equations to obtain relevant rate parameters. The number of bed volumes processed at breakthrough point and capacity of the bed are used as performance indicators. Results show that performance increases with a decrease in initial bacterial concentration, an increase in flow rate and an increase in bed mass.

  12. Peak and Tail Scaling of Breakthrough Curves in Hydrologic Tracer Tests (United States)

    Aquino, T.; Aubeneau, A. F.; Bolster, D.


    Power law tails, a marked signature of anomalous transport, have been observed in solute breakthrough curves time and time again in a variety of hydrologic settings, including in streams. However, due to the low concentrations at which they occur they are notoriously difficult to measure with confidence. This leads us to ask if there are other associated signatures of anomalous transport that can be sought. We develop a general stochastic transport framework and derive an asymptotic relation between the tail scaling of a breakthrough curve for a conservative tracer at a fixed downstream position and the scaling of the peak concentration of breakthrough curves as a function of downstream position, demonstrating that they provide equivalent information. We then quantify the relevant spatiotemporal scales for the emergence of this asymptotic regime, where the relationship holds, in the context of a very simple model that represents transport in an idealized river. We validate our results using random walk simulations. The potential experimental benefits and limitations of these findings are discussed.

  13. 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.

  14. 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.

  15. [Pharmacokinetics of crocetin in rats]. (United States)

    Liu, Tong-zheng; Qian, Zhi-yu


    To develop an HPLC method for the determination of crocetin in rat plasma and study the pharmacokinetics in rats. Hypersil C18 column (5 microns, 4.6 mm x 200 mm) was used at column temperature 30 degrees C. The mobile phase consisted of methanol-water-acetic acid (75:24.5:0.5) at the flow rate of 1.0 mL.min-1. The UV detection wave length was 423 nm. The calibration curve was linear (gamma = 0.9996) in the range from 0.49 microgram.mL-1 to 7.87 micrograms.mL-1 for crocetin. The mean recovery was 105.2%. The lowest detectable concentration of crocetin was 0.14 microgram.mL-1 (S/N = 3). The RSDs of within-day and between-day were all less than 5%. The plasma crocetin was steady. The HPLC method of determination of crocetin in the plasma was established. After single dose of 50 ig in 10 rats, the main pharmacokinetic parameters were estimated as follows: T1/2 alpha (30 +/- 6) min, Tmax(65 +/- 16) min, Cmax(5.0 +/- 1.0) microgram.mL-1, AUC0-T(845 +/- 109) microgram.min.mL-1, Vd(5.0 +/- 0.8) Crocetin was shown to be absorbed into the blood through the gastrointestinal tract. This method is quick, precise and reliable. Crocetin was shown to be quickly absorbed in rats.

  16. Glipizide Pharmacokinetics in Healthy and Diabetic Volunteers

    African Journals Online (AJOL)


    Purpose: Disease state may contribute to alteration in drug pharmacokinetics. The purpose of .... dependency or drug abuse, known allergy to ... HPLC analysis of glipizide ... months when stored at 4 0C, protected from .... plasma and urine.

  17. 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...

  18. 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.

  19. 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

  20. Fifteen minute consultation: Practical pain management in paediatric palliative care. (United States)

    Harrop, Emily Jane; Brombley, Karen; Boyce, Katherine


    Pain and distress in the paediatric palliative care population can be very difficult to manage. Clinical scenarios range from the acute management of cancer-related pain at the end of life to the ongoing long-term support of children with complex multimodal pain related to progressive neurological conditions. Understanding the child's underlying condition, possible causes of pain and their preferred mode of communication are important to the delivery of holistic care. Modification of environmental factors, basic care consideration and non-pharmacological measures have a large role to play, alongside conventional analgesics. Medication may also need to be delivered by novel routes such as transdermal patches, continuous subcutaneous infusion of multiple drugs or transmucosal breakthrough analgesic doses. Two cases are used to illustrate approaches to these clinical problems. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. 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

  2. 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

  3. Low back pain - acute (United States)

    Backache; Low back pain; Lumbar pain; Pain - back; Acute back pain; Back pain - new; Back pain - short-term; Back strain - new ... lower back supports most of your body's weight. Low back pain is the number two reason that Americans see ...



    Pashkus N.A; Pashkus V.


    The article discusses the possibility of using active marketing strategies for promoting the results of university’s innovations. Benefits, that can be obtained by university through its strategy of breakthrough positioning explored

  5. 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.

  6. Breakthrough Aspergillus fumigatus and Candida albicans double infection during caspofungin treatment

    DEFF Research Database (Denmark)

    Arendrup, Maiken Cavling; Garcia-Effron, Guillermo; Buzina, Walter


    Caspofungin is used for the treatment of acute invasive candidiasis and as salvage treatment for invasive aspergillosis. We report characteristics of isolates of Candida albicans and Aspergillus fumigatus detected in a patient with breakthrough infection complicating severe gastrointestinal surgery...... without FSK1 resistance mutations in liver and lung tissues. Breakthrough disseminated aspergillosis and candidiasis developed despite an absence of characteristic FKS1 resistance mutations in the Aspergillus isolates. EUCAST and CLSI methodology did not separate the candin-resistant clinical isolate from...

  7. Painful menstrual periods (United States)

    Menstruation - painful; Dysmenorrhea; Periods - painful; Cramps - menstrual; Menstrual cramps ... into two groups, depending on the cause: Primary dysmenorrhea Secondary dysmenorrhea Primary dysmenorrhea is menstrual pain that ...

  8. 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- ...

  9. 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.

  10. 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.

  11. Integrated identification, qualification and quantification strategy for pharmacokinetic profile study of Guizhi Fuling capsule in healthy volunteers


    Yun-Xi Zhong; Xiao-Liang Jin; Shi-Yin Gu; Ying Peng; Ke-Rong Zhang; Bing-Chen Ou-Yang; Yu Wang; Wei Xiao; Zhen-Zhong Wang; Ji-Ye Aa; Guang-Ji Wang; Jian-Guo Sun


    Guizhi Fuling capsule (GZFL), a traditional Chinese medicine formulation, is widely used in China to relieve pain from dysmenorrhea and is now in a Phase II clinical trial in the USA. Due to the low exposure of the five main medicative ingredients (amygdalin, cinnamic acid, gallic acid, paeoniflorin and paeonol) of GZFL in human, a strategy was built to qualitatively and quantitatively identify the possible metabolites of GZFL and to describe the pharmacokinetic profiles of GZFL in human. In ...

  12. Pain Control After Surgery: Pain Medicines (United States)

    ... Emotional Well-Being Mental Health Sex and Birth Control Sex and Sexuality Birth Control Family Health Infants and Toddlers Kids and Teens ... Bracing: What Works? Home Prevention and Wellness Pain Control After Surgery: Pain Medicines Pain Control After Surgery: ...

  13. Procedure and accuracy in the Eurotunnel breakthrough. Vorgehensweise und Genauigkeit beim Durchschlag des Eurotunnels

    Energy Technology Data Exchange (ETDEWEB)

    Korittke, N. (DMT-Gesellschaft fuer Forschung und Pruefung mbH, Essen (Germany, F.R.). Inst. fuer Lagerstaette und Vermessung (ILV))


    After a construction time of about 2.5 years the first link was made in the Eurotunnel between France and England, viz. the service tunnel, on 1 December 1990. Thanks to the accurate Gyromat measurements of the Institute for Mineral Deposits and Surveying of the Deutsche Montan Technologie (DMT) a transverse deviation of only 361 mm, a longitudinal deviation of 69 mm and a vertical deviation of 58 mm were determined in the breakthrough of the 22.3 and 15.6 km long tunnel sections. (orig.).

  14. Epicardial Breakthrough Waves During Sinus Rhythm: Depiction of the Arrhythmogenic Substrate? (United States)

    Mouws, Elisabeth M J P; Lanters, Eva A H; Teuwen, Christophe P; van der Does, Lisette J M E; Kik, Charles; Knops, Paul; Bekkers, Jos A; Bogers, Ad J J C; de Groot, Natasja M S


    Epicardial breakthrough waves (EBW) during atrial fibrillation are important elements of the arrhythmogenic substrate and result from endo-epicardial asynchrony, which also occurs to some degree during sinus rhythm (SR). We examined the incidence and characteristics of EBW during SR and its possible value in the detection of the arrhythmogenic substrate associated with atrial fibrillation. Intraoperative epicardial mapping (interelectrode distances 2 mm) of the right atrium, Bachmann's bundle, the left atrioventricular groove, and the pulmonary vein area was performed during SR in 381 patients (289 male, 67±10 years) with ischemic or valvular heart disease. EBW were referred to as sinus node breakthrough waves if they were the earliest right atrial activated site. A total of 218 EBW and 57 sinus node breakthrough waves were observed in 168 patients (44%). EBW mostly occurred at right atrium (N=105, 48%) and left atrioventricular groove (N=67, 31%), followed by Bachmann's bundle (N=27, 12%) and pulmonary vein area (N=19, 9%; P <0.001). EBW occurred most often in ischemic heart disease patients (N=114, 49%) compared with (ischemic and) valvular heart disease patients (N=26, 17%; P <0.001). EBW electrograms most often consisted of double and fractionated potentials (N=137, 63%). In case of single potentials, an R wave was observed in 88% (N=71) of EBW, as opposed to 21% of sinus node breakthrough waves (N=5; P <0.001). Fractionated EBW potentials were more often observed at the right atrium and Bachmann's bundle ( P <0.001). During SR, EBW are present in over a third of patients, particularly in thicker parts of the atrial wall. Features of SR EBW indicate that muscular connections between endo- and epicardium underlie EBW and that a slight degree of endo-epicardial asynchrony required for EBW to occur is already present in some areas during SR. Hence, an anatomic substrate is present, which may enhance the occurrence of EBW during atrial fibrillation, thereby

  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. 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

  17. The Impact of Breakthrough Therapy Designation on Development Strategies and Timelines for Nononcology Drugs and Vaccines. (United States)

    Poirier, A F; Murphy, W R


    The US Food and Drug Administration (FDA) Safety and Innovation Act (FDASIA, 2012) introduced the Breakthrough Therapy Designation (BTD), a new tool to expedite development of medicines to treat serious or life-threatening diseases. The majority of BTDs have gone to oncology drugs, and a recent publication by Shea et al. 1 reviewed the impact of BTD on oncology drug development. This article reviews the impact of BTD on development strategies and timelines for nononcology drugs. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  18. Breast pain (United States)

    ... that reducing the amount of fat, caffeine, or chocolate in your diet helps reduce breast pain. Vitamin ... harmful, but most studies have not shown any benefit. Talk to your provider before starting any medicine or ... Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA. Review provided by ...

  19. Foot pain (United States)

    ... that you were born with or develops later Injury Shoes that fit poorly or do not have much cushioning Too much walking or other sports activity Trauma The following can cause foot pain: Arthritis and gout . Common in the big toe, which becomes red, swollen, ...

  20. Pain (PDQ) (United States)

    ... intravenous chemotherapy. Mucositis (sores or inflammation in the mouth or other parts of the digestive system ) caused by chemotherapy or targeted therapy. Skin pain, rash, or hand-foot syndrome (redness, tingling, or burning in the palms of the hands and/or ...

  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. [Social pain]. (United States)

    Shimoyama, Naohito; Shimoyama, Megumi


    This chapter focuses on what social pain is and how it should be managed. In order to understand social pain in a cancer patient, it is necessary to recognize the change in the patient's daily life after the diagnosis of cancer. Because the degree of suffering and the relationships with family members and the people he or she worked with differ from patient to patient, it is important to note that the context of social pain is different in each patient. Five points shown below are essential in managing social pain. 1. Economical suffering may be alleviated by utilization of the social security system while taking into account each patient's standard of living. 2. Burdens on family members should be lessened, such as by not having them stay at the patient's bedside every day and letting them go home occasionally. 3. The normal patterns of communication, support, and conflict in the family should be identified, and the extent to which they have been disrupted by the illness should be assessed. 4. It is important to understand the ethnic, cultural, and religious background of the patient and the potential impact of their influence on the individual and the illness. 5. Practical or emotional unfinished business that the patient has needs to be identified, and efforts should be made to support fulfillment.

  3. Leg pain (United States)

    ... in the blood Medicines (such as diuretics and statins) Muscle fatigue or strain from overuse, too much exercise, or holding a muscle in the same position for a long time An injury can also cause leg pain from: A torn or overstretched muscle ( strain ) Hairline ...

  4. Habituating pain

    DEFF Research Database (Denmark)

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


    and pain as unavoidable conditions in construction work. Based on 32 semi-structured interviews performed in eight case studies within four different construction professions, workers’ descriptions of physical strain and its relation to the organizational and social context are analyzed through concepts...

  5. 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.

  6. The pharmacokinetic behaviour of hypoxoside taken orally by ...

    African Journals Online (AJOL)

    measured with a high-performance liquid chromatography . method. For the ... the South African Medicines Control Council to conduct a phase I pharmacokinetic and ... The significance of various factors that influence the pharmacokinetic ...

  7. Orofacial pain

    Directory of Open Access Journals (Sweden)

    Marjolijn Oomens


    Full Text Available In the primary care sector, diagnosis and initial management of orofacial pain are often performed by familydoctors and dentists. Knowledge of the different types of orofacial pain and headache disorders is therefor of great importance. The International Classification of Headache Disorders (ICHD-3 provides an overview of the different types of orofacial pain and will be discussed in this lecture. The main focus will be on trigeminal neuralgia and cluster headache and the current research in this field. Trigeminal Neuralgia (TN is defined as a disorder characterized by recurrent, unilateral, brief, electricshock-like pains, abrupt in onset and termination, limited to the distribution of one or more divisions of thetrigeminal nerve and triggered by innocuous stimuli. Unfortunately, most TN is idiopathic, and the aetiology isnot clear. The guidelines on pharmaceutical TN management published by the American Academy of Neurology (AAN and the European Federation of Neurological Societies (EFNS recommend carbamazepine (CBZ; 200–1200 mg/day or oxcarbazepine (OXC; 600–1800 mg/day as first-line therapy. Both are antiepileptics with well known interactions with other drugs and safety problems. An overview of the currently available literature on the pharmaceutical management of TN patients is discussed. Cluster headache (CH is one of the most painful primary headache disorders. It is characterized by daily or almost daily attacks of unilateral excruciating periorbital pain associated with ipsilateral cranial autonomic symptoms, typically lasting between 15 and 180 minutes if untreated. Cluster headache is caused by the relaesement of neurotransmitters and vasodilators from the sphenopalatine ganglion (SPH. The SPG is a large extracranial parasympathetic ganglion located in the pterygopalatine fossa (PPF. The current treatments for CH attacks are injectable sumatriptan and oxygen inhalation. Both treatments have well known side effects and

  8. 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 ...

  9. Pain Information Brochure (United States)

    ... Library Health Care Systems Research Collaboratory Pain Registries IOM Report: Relieving Pain in America HHS Pathways to ... Library Health Care Systems Research Collaboratory Pain Registries IOM Report: Relieving Pain in America HHS Pathways to ...

  10. NIH Pain Consortium (United States)

    ... Library Health Care Systems Research Collaboratory Pain Registries IOM Report: Relieving Pain in America HHS Pathways to ... Library Health Care Systems Research Collaboratory Pain Registries IOM Report: Relieving Pain in America HHS Pathways to ...

  11. Back pain and sports (United States)

    ... Running - back pain; Weightlifting - back pain; Lumbar pain - sports; Sciatica - sports; Low back pain - sports ... MD, Thompson SR, eds. DeLee and Drez's Orthopaedic Sports Medicine: Principles and Practice . 4th ed. Philadelphia, PA: ...

  12. Back Pain During Pregnancy (United States)

    ... Advocacy For Patients About ACOG Back Pain During Pregnancy Home For Patients Search FAQs Back Pain During ... FAQ115, January 2016 PDF Format Back Pain During Pregnancy Pregnancy What causes back pain during pregnancy? How ...

  13. Pharmacokinetics, pharmacodynamics and toxicology of theranostic nanoparticles (United States)

    Kang, Homan; Mintri, Shrutika; Menon, Archita Venugopal; Lee, Hea Yeon; Choi, Hak Soo; Kim, Jonghan


    Nanoparticles (NPs) are considered a promising tool in both diagnosis and therapeutics. Theranostic NPs possess the combined properties of targeted imaging and drug delivery within a single entity. While the categorization of theranostic NPs is based on their structure and composition, the pharmacokinetics of NPs are significantly influenced by the physicochemical properties of theranostic NPs as well as the routes of administration. Consequently, altered pharmacokinetics modify the pharmacodynamic efficacy and toxicity of NPs. Although theranostic NPs hold great promise in nanomedicine and biomedical applications, a lack of understanding persists on the mechanisms of the biodistribution and adverse effects of NPs. To better understand the diagnostic and therapeutic functions of NPs, this review discusses the factors that influence the pharmacokinetics, pharmacodynamics and toxicology of theranostic NPs, along with several strategies for developing novel diagnostic and therapeutic modalities.

  14. An interactive program for pharmacokinetic modeling. (United States)

    Lu, D R; Mao, F


    A computer program, PharmK, was developed for pharmacokinetic modeling of experimental data. The program was written in C computer language based on the high-level user-interface Macintosh operating system. The intention was to provide a user-friendly tool for users of Macintosh computers. An interactive algorithm based on the exponential stripping method is used for the initial parameter estimation. Nonlinear pharmacokinetic model fitting is based on the maximum likelihood estimation method and is performed by the Levenberg-Marquardt method based on chi 2 criterion. Several methods are available to aid the evaluation of the fitting results. Pharmacokinetic data sets have been examined with the PharmK program, and the results are comparable with those obtained with other programs that are currently available for IBM PC-compatible and other types of computers.

  15. 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.

  16. Breakthrough indicator for aromatic VOCs using needle trap samplers for activated carbon adsorbent. (United States)

    Cheng, Wen-Hsi; Jiang, Jia-Rong; Huang, Yi-Ning; Huang, Shiun-Chian; Yu, Yan-Pin


    Internal circulation cabinets equipped with granular activated carbon (GAC) for adsorbing volatile organic compounds (VOCs) are widely used to store bottles containing organic solvents in universities, colleges, and hospital laboratories throughout Taiwan. This work evaluates the VOC adsorption capacities of GAC using various adsorption times for gas stream mixtures of 100 ppm toluene and 100 ppm o-xylene. Additionally, needle trap sampling (NTS) technology was used to indicate the time for renewing the GAC to avoid VOC breakthrough from adsorbents. Experimental results demonstrate that the proposed models can linearly express toluene and o-xylene adsorption capacities as the natural logarithm of adsorption time (ln(t)) and can accurately simulate the equilibrium adsorption capacities (Qe, g VOCs/g GAC) for gaseous toluene and o-xylene. The NTS, packed with 60-80 mesh divinylbenzene (DVB) particles, was compared in terms of extraction efficiency by simultaneously using the 75-microm Carboxen/polydimethylsiloxane-solid-phase microextraction (Carboxen/PDMS-SPME) fiber for time-weighted average (TWA) sampling, and experimental results indicated that the packed DVB-NTS achieved higher toluene extraction rates. Additionally, the NTS installed in the outlet air stream for adsorbing toluene and o-xylene exhausted through GAC accurately indicated toluene and o-xylene breakthrough times of 4700-5000 min. The GAC-NTS operational instructions to indicate the replacing time of adsorbent in the internal circulation cabinets are also included in this paper.

  17. 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.

  18. 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

  19. Clinical pharmacokinetics of 5-methyltetrahydrohomofolate

    International Nuclear Information System (INIS)

    Loo, T.L.; Jiushi, L.; Lu, K.; Savaraj, N.


    DL-N5-Methyltetrahydrohomofolate (MTHHF; NSC-139490; N- [(4-[(2-(2-amino-3,4,5,6,7,8-hexahydro-4-oxo-5-methyl-6- pteridinyl)ethyl) amino) benzoyl)] -L-glutamate), a new folate antagonist of relatively low toxicity, is active against experimental tumor systems resistant to methotrexate and consequently now in clinical trial. We investigated its clinical pharmacokinetics in six patients; four of them received by rapid i.v. infusion tracer doses of [N5-methyl- 14 C]MTHHF ranging from 13 to 16 mg/sq m, and 2 received 150 mg/sq m; the total radioactivity dose was 100 to 200 mu Ci/patient. MTHHF was assayed by radiochemical and chromatographic techniques. The elimination of MTHHF from the plasma followed a triexponential pattern, with a harmonic mean initial half-life of 20.1 min, an intermediary half-life of 4.5 hr, and a terminal half-life of 74.6 hr. The apparent volume of distribution was 1.6 liters/kg, suggesting rapid and extensive tissue binding. This, together with the low total clearance of 0.2 ml/kg/min, contributed to the long half-life of this agent. Although 68% of the administered dose was excreted in the urine on the first day, only an additional 1% was excreted on the ensuing 3 days. In the two patients who received the higher dose, very little MTHHF was found in the cerebrospinal fluid. In concentrations ranging from 25 to 500 micrograms/ml, the drug was about 50% bound to plasma protein. MTHHF was not metabolized in humans as also reported in animals. These results suggest that MTHHF is excreted in the bile to certain extent. Moreover, since it tends to localize and persist in the body, to forestall cumulative toxicity, frequent administration of this agent should be undertaken only with caution

  20. [Multidisciplinary guideline 'Recognition and treatment of chronic pain in vulnerable elderly people']. (United States)

    Achterberg, Wilco P; de Ruiter, Corinne M; de Weerd-Spaetgens, Chantal M E E; Geels, Paul; Horikx, Annemieke; Verduijn, Monique M


    Chronic pain in vulnerable elderly people is still poorly recognized and treated, both at home and in hospitals and care and nursing homes. Vulnerable elderly people experience and express pain differently to relatively healthy adults, especially when they suffer from cognitive impairment or specific conditions. Determining the nature and severity of the pain requires the use of pain assessment instruments that have been validated for use in vulnerable elderly people. Effective treatment of pain demands careful diagnosis and pharmacological and non-pharmacological interventions that have proven effectiveness in vulnerable elderly people. The combination of multiple morbidity and poly-pharmacy increases the chance of side-effects and complications. In addition, the pharmacokinetic and pharmacodynamic characteristics of many drugs are different in vulnerable elderly people. The advice is to start with a lower dose of pain medication and gradually build up a level on the basis of pain relief and side-effects ('start low, go slow!').

  1. Pharmacokinetics of thiamine derivatives especially of benfotiamine. (United States)

    Loew, D


    Pharmacokinetic data of orally administered lipid-soluble thiamine analogues like benfotiamine are reviewed and assessed. It is quite clear that benfotiamine is absorbed much more better than water-soluble thiamine salts: maximum plasma levels of thiamine are about 5 times higher after benfotiamine, the bioavailability is at maximum about 3.6 times as high as that of thiamine hydrochloride and better than other lipophilic thiamine derivates. The physiological activity (alphaETK) increased only after benfotiamine was given. Due to its excellent pharmacokinetic profile benfotiamine should be preferred in treatment of relevant indications.

  2. 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

  3. 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

  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. Glipizide Pharmacokinetics in Healthy and Diabetic Volunteers

    African Journals Online (AJOL)


    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 ... assayed using a sensitive and validated reverse phase high performance liquid ..... factors may contribute to these variations. [17].

  6. Pharmacological activities and pharmacokinetic study of hyperoside ...

    African Journals Online (AJOL)

    Studies on its pharmacokinetic (PK) properties revealed that it is a stable compound ... attention in drug discovery and food supplement research ... neurotrophic factor (BDNF) and cAMP response element ... antidepressant effect of hyperoside is mediated through .... Saposhnikovia divaricata by high performance counter-.

  7. The role of pharmacokinetics in risk assessment

    International Nuclear Information System (INIS)

    Reitz, R.H.; Fox, T.R.; Watanabe, P.G.


    Pharmacokinetics can aid in the formulation of risk estimations by selection of doses for toxicity studies, by distinguishing between ''internal dose or toxifor concentration'' and ''applied dose,'' by providing a physiological basis for extrapolating between species, and by helping us to visualize the toxicological consequences of processes which we cannot quantify. 10 refs., 6 figs., 2 tabs

  8. 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...

  9. Circadian variation in the pharmacokinetics of verapamil

    DEFF Research Database (Denmark)

    Jespersen, C M; Frederiksen, M; Hansen, J F


    greater bioavailability (AUC) and a prolonged time to peak concentration was found. During the night (24.00 h-06.00 h) the half-life of verapamil was significantly longer than during the day (16.00 h-22.00 h). These differences in pharmacokinetics may be due to reduced hepatic blood flow at night...

  10. [Impact of ECMO on drugs pharmacokinetics]. (United States)

    Hasni, Nesrine; Lemaitre, Florian; Fernandez, Christine; Combes, Alain; Farinotti, Robert


    Extracorporeal membrane oxygenation (ECMO) is a life support system used in the treatment of patients of all ages with severe respiratory or cardiorespiratory failure. Despite the intensive use of drugs in the treatment of patients on ECMO, few studies have been conducted to determine the impact of this device on the pharmacokinetics of drugs. Publications in this field have shown pharmacokinetics changes resulting in an increase in volume of distribution of drugs and/or decreased clearance with consequent increase of their half-life. Reduced plasma concentrations of some drugs due to their adsorption on the different components of the circuit further complicates the determination of pharmacokinetic parameters of patients treated by ECMO. The literature published up to now on the pharmacokinetic changes associated with ECMO provide preliminary support for dosage adjustment. However, more research is needed to identify dosage strategies for this patient population. © 2011 Société Française de Pharmacologie et de Thérapeutique.

  11. Breakthrough curve of H/sub 2/-Ti-sponge adsorption system

    Energy Technology Data Exchange (ETDEWEB)

    Yasufuku, K [Kawasaki Heavy Industries Ltd., Kobe (Japan)


    Experimental work concerning H/sub 2/-Ti-sponge adsorption system has been undertaken at Kawasaki Heavy Industry Co. to obtain necessary data for the design of hydrogen removal tower (Ti-sponge trap) to be used as an purification component of a VHTR plant. In this study, the effects of equilibrium curve, H/sub 2/ inlet concentration, and the ratio of the solid-side capacity factor to the gas-side capacity factor on the breakthrough curve were investigated. The Freundlich's equation with the diffusion model of Carter et al. was numerically solved by the Crank-Nicholson method, and the results of calculations are presented. The flow diagram and the photographs of the facilities for He gas purification experiments are also presented.

  12. Scientific breakthroughs necessary for the commercial success of renewable energy (Invited) (United States)

    Sharp, J.


    In recent years the wind energy industry has grown at an unprecedented rate, and in certain regions has attained significant penetration into the power infrastructure. This growth has been both a result of, and a precursor to, significant advances in the science and business of wind energy. But as a result of this growth and increasing penetration, further advances and breakthroughs will become increasingly important. These advances will be required in a number of different aspects of wind energy, including: resource assessment, operations and performance analysis, forecasting, and the impacts of increased wind energy development. Resource assessment has benefited from the development of tools specifically designed for this purpose. Despite this, the atmosphere is often portrayed in an extremely simplified manner by these tools. New methodologies should rely upon more sophisticated application of the physics of fluid flows. There will need to be an increasing reliance and acceptance of improved measurement techniques (remote sensing, volume rather than point measurements, etc), and more sophisticated and higher-resolution numerical methods for micrositing. The goals of resource assessment will have to include a better understanding of the variability and forecastability of potential sites. Operational and performance analysis are vital to quantifying how well all aspects of the business are being carried out. Operational wind farms generate large amounts of meteorological and mechanical data. Data mining and detailed analysis of this data has proven to be invaluable to shed light upon poorly understood aspects of the science and industry. Future analysis will need to be even more rigorous and creative. Worthy topics of study include the impact of turbine wakes upon downstream turbine performance, how to utilize operational data to improve resource assessment and forecasting, and what the impacts of large-scale wind energy development might be. Forecasting is an

  13. 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

  14. From Bottleneck to Breakthrough: Urbanization and the Future of Biodiversity Conservation. (United States)

    Sanderson, Eric W; Walston, Joseph; Robinson, John G


    For the first time in the Anthropocene, the global demographic and economic trends that have resulted in unprecedented destruction of the environment are now creating the necessary conditions for a possible renaissance of nature. Drawing reasonable inferences from current patterns, we can predict that 100 years from now, the Earth could be inhabited by between 6 and 8 billion people, with very few remaining in extreme poverty, most living in towns and cities, and nearly all participating in a technologically driven, interconnected market economy. Building on the scholarship of others in demography, economics, sociology, and conservation biology, here, we articulate a theory of social-environmental change that describes the simultaneous and interacting effects of urban lifestyles on fertility, poverty alleviation, and ideation. By recognizing the shifting dynamics of these macrodrivers, conservation practice has the potential to transform itself from a discipline managing declines ("bottleneck") to a transformative movement of recovery ("breakthrough").

  15. 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.

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

    Sterling, A.

    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.

  17. Plastic fracture instability analysis of wall breakthrough in a circumferentially cracked pipe subjected to bending loads

    International Nuclear Information System (INIS)

    Zahoor, A.; Kanninen, M.F.


    A method of analyzing internal surface circumferential cracks in ductile reactor piping is presented. The method utilizes an alternate but equivalent definition of the J-integral based on nonlinear structural compliance. The analysis is valid for situations where the cross section containing the crack is fully yielded. Results are obtained for radial and circumferential crack growth for pipes subjected to bending. The stability of radial crack growth (wall breakthrough) is assessed using the J-integral-based tearing modulus approach. The analysis is shown to be in agreement with experimental results on the stability of surface crack growth in Type 304 stainless stee pipes. Example quantitative results for fracture instability assessments for nuclear piping are presented. 23 refs

  18. Plastic fracture instability analysis of wall breakthrough in a circumferentially cracked pipe subjected to bending loads

    Energy Technology Data Exchange (ETDEWEB)

    Zahoor, A.; Kanninen, M.F.


    A method of analyzing internal surface circumferential cracks in ductile reactor piping is presented. The method utilizes an alternate but equivalent definition of the J-integral based on nonlinear structural compliance. The analysis is valid for situations where the cross section containing the crack is fully yielded. Results are obtained for radial and circumferential crack growth for pipes subjected to bending. The stability of radial crack growth (wall breakthrough) is assessed using the J-integral-based tearing modulus approach. The analysis is shown to be in agreement with experimental results on the stability of surface crack growth in Type 304 stainless stee pipes. Example quantitative results for fracture instability assessments for nuclear piping are presented. 23 refs.

  19. 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.

  20. 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.

  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. 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.

  4. Aldosterone breakthrough with benazepril in furosemide-activated renin-angiotensin-aldosterone system in normal dogs. (United States)

    Lantis, A C; Ames, M K; Atkins, C E; DeFrancesco, T C; Keene, B W; Werre, S R


    Pilot studies in our laboratory revealed that furosemide-induced renin-angiotensin-aldosterone system (RAAS) activation was not attenuated by the subsequent co-administration of benazepril. This study was designed to evaluate the effect of benazepril on angiotensin-converting enzyme (ACE) activity and furosemide-induced circulating RAAS activation. Our hypothesis was that benazepril suppression of ACE activity would not suppress furosemide-induced circulating RAAS activation, indicated by urinary aldosterone concentration. Ten healthy hound dogs were used in this study. The effect of furosemide (2 mg/kg p.o., q12h; Group F; n = 5) and furosemide plus benazepril (1 mg/kg p.o., q24h; Group FB; n = 5) on circulating RAAS was determined by plasma ACE activity, 4-6 h posttreatment, and urinary aldosterone to creatinine ratio (UAldo:C) on days -1, -2, 1, 3, and 7. There was a significant increase in the average UAldo:C (μg/g) after the administration of furosemide (Group F baseline [average of days -1 and -2] UAldo:C = 0.41, SD 0.15; day 1 UAldo:C = 1.1, SD 0.56; day 3 UAldo:C = 0.85, SD 0.50; day 7 UAldo:C = 1.1, SD 0.80, P Benazepril suppressed ACE activity (U/L) in Group FB (Group FB baseline ACE = 16.4, SD 4.2; day 1 ACE = 3.5, SD 1.4; day 3 ACE = 1.6, SD 1.3; day 7 ACE = 1.4, SD 1.4, P Benazepril decreased plasma ACE activity but did not prevent furosemide-induced RAAS activation, indicating aldosterone breakthrough (escape). This is particularly noteworthy in that breakthrough is observed at the time of initiation of RAAS suppression, as opposed to developing after months of therapy. © 2014 John Wiley & Sons Ltd.

  5. Breakthrough and prospect of shale gas exploration and development in China

    Directory of Open Access Journals (Sweden)

    Dazhong Dong


    Full Text Available In the past five years, shale gas exploration and development has grown in a leaping-forward way in China. Following USA and Canada, China is now the third country where industrial shale gas production is realized, with the cumulative production exceeding 60 × 108 m3 until the end of 2015. In this paper, the main achievements of shale gas exploration and development in China in recent years were reviewed and the future development prospect was analyzed. It is pointed out that shale gas exploration and development in China is, on the whole, still at its early stage. Especially, marine shale gas in the Sichuan Basin has dominated the recent exploration and development. For the realization of shale gas scale development in China, one key point lies in the breakthrough and industrial production of transitional facies and continental facies shale gas. Low–moderate yield of shale gas wells is the normal in China, so it is crucial to develop key exploration and development technologies. Especially, strictly controlling single well investment and significantly reducing cost are the important means to increase shale gas exploration and development benefits. And finally, suggestions were proposed in five aspects. First, continuously strengthen theoretical and technical researches, actively carry out appraisal on shale gas “sweet spots”, and gradually accumulate development basis. Second, stress on primary evaluation of exploration and development, highlight the effective implementation of shale gas resources, and control the rhythm of appraisal drilling and productivity construction. Third, highlight fine description and evaluation of shale gas reservoirs and increase the overall development level. Fourth, intensify the research on exploration and development technologies in order to stand out simple and practical technologies with low costs. And fifth, summarize the experiences in fast growth of shale gas exploration and development, highlight

  6. 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

  7. Pain and the ethics of pain management. (United States)

    Edwards, R B


    In this article I clarify the concepts of 'pain', 'suffering', 'pains of body', 'pains of soul'. I explore the relevance of an ethic to the clinical setting which gives patients a strong prima facie right to freedom from unnecessary and unwanted pain and which places upon medical professionals two concomitant moral obligations to patients. First, there is the duty not to inflict pain and suffering beyond what is necessary for effective diagnosis, treatment and research. Next, there is the duty to do all that can be done to relieve all the pain and suffering which can be alleviated. I develop in some detail that individuality of pain sensitivity must be taken into account in fulfilling these obligations. I explore the issue of the relevance of informed consent and the right to refuse treatment to the matter of pain relief. And I raise the question of what conditions, if any, should override the right to refuse treatment where pain relief is of paramount concern.

  8. Paediatric pain management

    African Journals Online (AJOL)

    patients is musculoskeletal pain, headache or abdominal pain.2. The pain ... Children older than four years of age can usually talk about their pain; at the age of six to eight years they can use the ... Pain presentation in children normally falls into one of the ... expression, body posture and movement.10 This scale is often.

  9. 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...

  10. 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

  11. Characteristics and clinical implications of the pharmacokinetic profile of ibuprofen in patients with knee osteoarthritis. (United States)

    Gallelli, L; Galasso, O; Urzino, A; Saccà, S; Falcone, D; Palleria, C; Longo, P; Corigliano, A; Terracciano, R; Savino, R; Gasparini, G; De Sarro, G; Southworth, S R


    Ibuprofen is a non-selective cyclo-oxygenase (COX)-1/COX-2 inhibitor used to treat pain conditions and inflammation. Limited data have been published concerning the pharmacokinetic profile and clinical effects of ibuprofen in patients with osteoarthritis (OA). In this paper we compared the pharmacokinetic and clinical profile of ibuprofen (at a dosage of from 800 mg/day to 1800 mg/day) administered in patients affected by severe knee OA. Ibuprofen was administered for 7 days to patients who were scheduled to undergo knee arthroplasty due to OA. After 7 days, the ibuprofen concentration in plasma and synovial fluid was measured through both high-performance liquid chromatography (HPLC)-UV and gas chromatography-mass spectroscopy (GC/MS), while clinical effects were evaluated through both visual analogue scale (VAS) and Western Ontario and McMaster Universities (WOMAC) scores. The Naranjo scale and the WHO causality assessment scale were used for estimating the probability of adverse drug reactions (ADRs). The severity of ADRs was assessed by the modified Hartwig and Siegel scale. Ibuprofen showed a dose-dependent diffusion in both plasma and synovial fluid, which was related to the reduction of pain intensity and improvement of health status, without the development of ADRs. Ibuprofen at higher dosages can be expected to provide better control of OA symptoms as a result of higher tissue distribution.

  12. 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.

  13. Opioids, pain, the brain, and hyperkatifeia: a framework for the rational use of opioids for pain. (United States)

    Shurman, Joseph; Koob, George F; Gutstein, Howard B


    Opioids have relieved more human suffering than any other medication, but their use is still fraught with significant concerns of misuse, abuse, and addiction. This theoretical article explores the hypothesis that opioid misuse in the context of pain management produces a hypersensitivity to emotional distress, termed hyperkatifeia. In the misuse of opioids, neural substrates that mediate positive emotional states (brain reward systems) are compromised, and substrates mediating negative emotional states (brain stress systems) are enhanced. A reflection and early marker of such a nonhomeostatic state may be the development of opioid-induced hyperkatifeia, defined as the increased intensity of the constellation of negative emotional/motivational symptoms and signs observed during withdrawal from drugs of abuse (derived from the Greek "katifeia" for dejection or negative emotional state) and is most likely to occur in subjects in whom the opioid produces a break with homeostasis and less likely to occur when the opioid is restoring homeostasis, such as in effective pain treatment. When the opioid appropriately relieves pain, opponent processes are not engaged. However, if the opioid is administered in excess of need because of overdose, pharmacokinetic variables, or treating an individual without pain, then the body will react to that perturbation by engaging opponent processes in the domains of both pain (hyperalgesia) and negative emotional states (hyperkatifeia). Repeated engagement of opponent processes without time for the brain's emotional systems to reestablish homeostasis will further drive changes in emotional processes that may produce opioid abuse or addiction, particularly in individuals with genetic or environmental vulnerability.

  14. 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...

  15. specific low back pain

    African Journals Online (AJOL)


    Sep 1, 2015 ... SPECIFIC LOW BACK PAIN: IMPLICATION FOR DIRECT HEALTH. CARE COST ... abundant evidence suggesting the benefits of therapeu- tic exercise on pain and ... Exercise and behavioural therapies in chronic pain. 174.

  16. 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 ...

  17. 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 ...

  18. 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.

  19. 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.

  20. A Review on Pharmacokinetic Modeling and the Effects of Environmental Stressors on Pharmacokinetics for Operational Medicine: Operational Pharmacokinetics (United States)


    Manning et al. 1986), which may cause physiological changes. For example, emotional distress may lead to elevated heart rate, blood pressure and...related changes in renal functions were reported during a Stroop word color conflict test (Fauvel, Hadj-Aissa et al. 1991). Emotional stressors could...M. Skee, et al. (2001). "Pharmacokinetics of norelgestromin and ethinyl estradiol delivered by a contraceptive patch (Ortho Evra (TM)/Evra (TM

  1. 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...

  2. 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…

  3. Central Pain Syndrome (United States)

    ... such as neurontin (gabapentin) can be useful. Lowering stress levels appears to reduce pain. View Full Treatment Information Definition Central pain syndrome is a neurological condition caused ...


    Keiper, Naomi L; Cox, Sherry K; Doss, Grayson A; Elsmo, Betsy; Franzen-Klein, Dana; Hartup, Barry K


    To investigate the pharmacokinetics of the nonsteroidal anti-inflammatory drug (NSAID) piroxicam in cranes, three brolgas (Antigone rubicunda) were administered piroxicam as a single oral dose at 0.5 mg/kg and 1.0 mg/kg during separate trials. Serial blood samples were collected for quantification of piroxicam in plasma. Piroxicam was readily absorbed at both dosages, and no adverse effects were observed. Plasma concentrations peaked at 3.67 hr with a concentration of 4.00 μg/ml for the lower dosage, and at 0.83 hr at 8.77 μg/ml for the higher dosage. Piroxicam may exhibit linear kinetics and dose proportionality in brolgas, but will require further study. Mean peak plasma concentrations in brolgas were comparable to concentrations demonstrated to be analgesic in humans. To the authors' knowledge, this study represents the first pharmacokinetic investigation of piroxicam in an avian species.

  5. 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....... Subcutaneous injection of melatonin displayed a rapid absorption rate compared to oral administration. Conclusion: Intranasal administration of melatonin has a large potential, and more research in humans is warranted. Transdermal application of melatonin has a possible use in a local application, due to slow...

  6. Tubocurarine and pancuronium: a pharmacokinetic view. (United States)

    Shanks, C A; Somogyi, A A; Ramzan, M I; Triggs, E J


    This review is an attempt to bring together the pharmacokinetic data on d-tubocurarine and pancuronium with clinical observations on relaxant dosage and effect. The modelling techniques used here represent an oversimplification of the relationships between relaxant plasma concentration and response as they do not predict either the time of onset of paralysis or its peak intensity. However, they do enable calculation of a bolus dose of relaxant required to achieve a particular intensity of paralysis for the average patient once pseudo-distribution equilibrium has been achieved. This has been further extended to predict the cumulation of the relaxants with subsequent dosage in average patients. Suggested regimens incorporating bolus and infusion doses of the relaxants to achieve continuous neuromuscular blockade have been calculated also. Averaged pharmacokinetic parameters derived from patients with renal or hepatic dysfunction have been used to predict the likely duration and intensities of paralysis for the relaxants.

  7. Clinical Pharmacology and Pharmacokinetics of Levetiracetam

    Directory of Open Access Journals (Sweden)

    Chanin Clark Wright


    Full Text Available Status epilepticus and acute repetitive seizures still pose a management challenge despite the recent advances in the field of epilepsy. Parenteral formulations of old anticonvulsants are still a cornerstone in acute seizure management and are approved by the FDA. Intravenous levetiracetam, a second generation anticonvulsant, is approved by the FDA as an adjunctive treatment in patients 16 years or older when oral administration is not available. Data have shown that it has a unique mechanism of action, linear pharmacokinetics and no known drug interactions with other anticonvulsants. In this paper, we will review the current literature about the pharmacology and pharmacokinetics of intravenous levetiracetam and the safety profile of this new anticonvulsant in acute seizure management of both adults and children.

  8. Busted Butte Phase 2: Introduction and Analytical Modeling of Nonreactive Tracer and Lithium Breakthrough

    International Nuclear Information System (INIS)

    Turin, H.J.; Soll, W.E.


    The Busted Butte Unsaturated-Zone Transport Test Facility is located approximately 8 km southeast of Yucca Mountain, and was designed to address uncertainties associated with flow and transport in the UZ site-process models for Yucca Mountain. Busted Butte Phase 2 consisted of a 10m x 10m x 7m test block. From July 1988 through October 2000, complex tracer mixtures were injected continuously at 77 discrete points located along eight parallel 10-m boreholes arranged in two horizontal planes. In August 1999, iodide was added to the tracer mixture to explore the effects of initial hydraulic transients. During the course of the experiment, porewater samples were collected at regular intervals using sorbing-paper collection pads, emplaced into fifteen horizontal and inclined 10-m collection boreholes, oriented perpendicular to the injection boreholes. Potential travel distances ranged from 20 cm to over 500 cm. Nonreactive tracer and weakly sorbing lithium breakthrough was observed at most of the collection points during the injection period. Following termination of injection, approximately 800 rock samples were collected using overcore and mineback techniques, and analyzed for tracer concentration. Rock analyses are discussed in a subsequent paper. To complement complex 3-dimensional finite-element modeling of the entire block, bromide, iodide, and lithium breakthrough onto the collection pads has been modeled with CXTFIT. This simple 1-dimensional analytical code uses a non-linear curve-fitting routine to estimate transport parameters including apparent velocity, dispersivity, and field retardation factors. Preliminary results show that: (1) Bromide and iodide behaved similarly, despite the fact that bromide was injected in a strongly transient flow field, while iodide injection began after flow had approached steady state conditions. (2) With the exception of the closest collection points, tracer velocities remained relatively constant, indicating that transport was

  9. 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

  10. Predicting trace organic compound breakthrough in granular activated carbon using fluorescence and UV absorbance as surrogates. (United States)

    Anumol, Tarun; Sgroi, Massimiliano; Park, Minkyu; Roccaro, Paolo; Snyder, Shane A


    This study investigated the applicability of bulk organic parameters like dissolved organic carbon (DOC), UV absorbance at 254 nm (UV254), and total fluorescence (TF) to act as surrogates in predicting trace organic compound (TOrC) removal by granular activated carbon in water reuse applications. Using rapid small-scale column testing, empirical linear correlations for thirteen TOrCs were determined with DOC, UV254, and TF in four wastewater effluents. Linear correlations (R(2) > 0.7) were obtained for eight TOrCs in each water quality in the UV254 model, while ten TOrCs had R(2) > 0.7 in the TF model. Conversely, DOC was shown to be a poor surrogate for TOrC breakthrough prediction. When the data from all four water qualities was combined, good linear correlations were still obtained with TF having higher R(2) than UV254 especially for TOrCs with log Dow>1. Excellent linear relationship (R(2) > 0.9) between log Dow and the removal of TOrC at 0% surrogate removal (y-intercept) were obtained for the five neutral TOrCs tested in this study. Positively charged TOrCs had enhanced removals due to electrostatic interactions with negatively charged GAC that caused them to deviate from removals that would be expected with their log Dow. Application of the empirical linear correlation models to full-scale samples provided good results for six of seven TOrCs (except meprobamate) tested when comparing predicted TOrC removal by UV254 and TF with actual removals for GAC in all the five samples tested. Surrogate predictions using UV254 and TF provide valuable tools for rapid or on-line monitoring of GAC performance and can result in cost savings by extended GAC run times as compared to using DOC breakthrough to trigger regeneration or replacement. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. 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

  12. The pharmacokinetics of the interstitial space in humans


    Levitt, David G


    Background The pharmacokinetics of extracellular solutes is determined by the blood-tissue exchange kinetics and the volume of distribution in the interstitial space in the different organs. This information can be used to develop a general physiologically based pharmacokinetic (PBPK) model applicable to most extracellular solutes. Methods The human pharmacokinetic literature was surveyed to tabulate the steady state and equilibrium volume of distribution of the solutes mannitol, EDTA, morphi...

  13. 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...

  14. Pharmacokinetics of linezolid in critically ill patients. (United States)

    Sazdanovic, Predrag; Jankovic, Slobodan M; Kostic, Marina; Dimitrijevic, Aleksandra; Stefanovic, Srdjan


    Linezolid is an oxazolidinone antibiotic active against Gram-positive bacteria, and is most commonly used to treat life-threatening infections in critically ill patients. The pharmacokinetics of linezolid are profoundly altered in critically ill patients, partly due to decreased function of vital organs, and partly because life-sustaining drugs and devices may change the extent of its excretion. This article is summarizes key changes in the pharmacokinetics of linezolid in critically ill patients. The changes summarized are clinically relevant and may serve as rationale for dosing recommendations in this particular population. While absorption and penetration of linezolid to tissues are not significantly changed in critically ill patients, protein binding of linezolid is decreased, volume of distribution increased, and metabolism may be inhibited leading to non-linear kinetics of elimination; these changes are responsible for high inter-individual variability of linezolid plasma concentrations, which requires therapeutic plasma monitoring and choice of continuous venous infusion as the administration method. Acute renal or liver failure decrease clearance of linezolid, but renal replacement therapy is capable of restoring clearance back to normal, obviating the need for dosage adjustment. More population pharmacokinetic studies are necessary which will identify and quantify the influence of various factors on clearance and plasma concentrations of linezolid in critically ill patients.

  15. Enantioselective pharmacokinetics of sibutramine in rat. (United States)

    Noh, Keumhan; Bae, Kyoungjin; Min, Bokyoung; Kim, Eunyoung; Kwon, Kwang-il; Jeong, Taecheon; Kang, Wonku


    Racemic sibutramine is widely used to treat obesity owing to its inhibition of serotonin and noradrenaline reuptake in synapses. Although the enantioselective effects of sibutramine and its two active desmethyl-metabolites, monodesmethylsibutramine (MDS) and didesmethylsibutramine (DDS), on anorexia and energy expenditure have been elucidated, the enantioselective pharmacokinetics of sibutramine are still unclear. Therefore, we aimed to characterize the enantioselective pharmacokinetics of sibutramine and its metabolites in plasma and urine following an intravenous and a single oral administration of sibutramine in rats. The absolute bioavailability of sibutramine was only about 7%. The pharmacologically less effective S-isomer of DDS was predominant in the plasma: the C ( max ) and the AUC ( inf ) were 28 and 30 times higher than those of the R-isomer, respectively (psibutramine metabolites MDS and DDS were present at lower concentrations, owing to their rapid biotransformation to hydroxylated and/or carbamoylglucuronized forms and their faster excretion in the urine. The present study is the first to elucidate the enantioselective pharmacokinetics of sibutramine in rats.

  16. Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co-Administered with Intravenous Morphine in Healthy Adult Subjects. (United States)

    Raffa, Robert B; Pawasauskas, Jayne; Pergolizzi, Joseph V; Lu, Luke; Chen, Yin; Wu, Sutan; Jarrett, Brant; Fain, Randi; Hill, Lawrence; Devarakonda, Krishna


    Several features favor paracetamol (acetaminophen) administration by the intravenous rather than the oral route in the postoperative setting. This study compared the pharmacokinetics and bioavailability of oral and intravenous paracetamol when given with or without an opioid, morphine. In this randomized, single-blind, parallel, repeat-dose study in healthy adults, subjects received four repeat doses of oral or intravenous 1000 mg paracetamol at 6-h intervals, and morphine infusions (0.125 mg/kg) at the 2nd and 3rd intervals. Comparisons of plasma pharmacokinetic profiles were conducted before, during, and after opioid co-administrations. Twenty-two subjects were included in the pharmacokinetic analysis. Observed paracetamol peak concentration (C max ) and area under the plasma concentration-time curve over the dosing interval (AUC 0-6 ) were reduced when oral paracetamol was co-administered with morphine (reduced from 11.6 to 7.25 µg/mL and from 31.00 to 25.51 µg·h/mL, respectively), followed by an abruptly increased C max and AUC 0-6 upon discontinuation of morphine (to 13.5 µg/mL and 52.38 µg·h/mL, respectively). There was also a significantly prolonged mean time to peak plasma concentration (T max ) after the 4th dose of oral paracetamol (2.84 h) compared to the 1st dose (1.48 h). However, pharmacokinetic parameters of paracetamol were not impacted when intravenous paracetamol was co-administered with morphine. Morphine co-administration significantly impacted the pharmacokinetics of oral but not intravenous paracetamol. The abrupt release of accumulated paracetamol at the end of morphine-mediated gastrointestinal inhibition following oral but not intravenous administration of paracetamol suggests that intravenous paracetamol provides a better option for the management of postoperative pain. CLINICALTRIALS. NCT02848729.

  17. 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.

  18. 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.

  19. Phytochemicals and the breakthrough of traditional herbs in the management of sexual dysfunctions. (United States)

    Adimoelja, A


    Traditional herbs have been a revolutionary breakthrough in the management of erectile dysfunction and have become known world-wide as an 'instant' treatment. The modern view of the management of erectile dysfunction subscribes to a single etiology, i.e. the mechanism of erection. A large number of pharmacological agents are orally consumed and vasoactive agents inserted intraurethrally or injected intrapenially to regain good erection. Modern phytochemicals have developed from traditional herbs. Phytochemicals focus their mechanism of healing action to the root cause, i.e. the inability to control the proper function of the whole body system. Hence phytochemicals manage erectile dysfunction in the frame of sexual dysfunction as a whole entity. Protodioscin is a phytochemical agent derived from Tribulus terrestris L plant, which has been clinically proven to improve sexual desire and enhance erection via the conversion of protodioscine to DHEA (De-Hydro-Epi-Androsterone). Preliminary observations suggest that Tribulus terrestris L grown on different soils does not consistently produce the active component Protodioscin. Further photochemical studies of many other herbal plants are needed to explain the inconsistent results found with other herbal plants, such as in diversities of Ginseng, Eurycoma longifolia, Pimpinella pruacen, Muara puama, Ginkgo biloba, Yohimbe etc.

  20. 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.

  1. 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.

  2. Stem cell-derived kidney cells and organoids: Recent breakthroughs and emerging applications. (United States)

    Chuah, Jacqueline Kai Chin; Zink, Daniele

    The global rise in the numbers of kidney patients and the shortage in transplantable organs have led to an increasing interest in kidney-specific regenerative therapies, renal disease modelling and bioartificial kidneys. Sources for large quantities of high-quality renal cells and tissues would be required, also for applications in in vitro platforms for compound safety and efficacy screening. Stem cell-based approaches for the generation of renal-like cells and tissues would be most attractive, but such methods were not available until recently. This situation has drastically changed since 2013, and various protocols for the generation of renal-like cells and precursors from pluripotent stem cells (PSC) have been established. The most recent breakthroughs were related to the establishment of various protocols for the generation of PSC-derived kidney organoids. In combination with recent advances in genome editing, bioprinting and the establishment of predictive renal screening platforms this results in exciting new possibilities. This review will give a comprehensive overview over current PSC-based protocols for the generation of renal-like cells, precursors and organoids, and their current and potential applications in regenerative medicine, compound screening, disease modelling and bioartificial organs. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Exploring the role of lipids in intercellular conduits: breakthroughs in the pipeline

    Directory of Open Access Journals (Sweden)

    Elise eDelage


    Full Text Available It has been known for more than a century that most of the plant cells are connected to their neighbors through membranous pores perforating the cell wall, namely plasmodesmata (PDs. The recent discovery of tunneling nanotubes (TNTs, thin membrane bridges established between distant mammalian cells, suggests that intercellular communication mediated through cytoplasmic continuity could be a conserved feature of eukaryotic organisms. Although TNTs differ from PDs in their formation and architecture, both are characterized by a continuity of the plasma membrane between two cells, delimiting a nanotubular channel supported by actin-based cytoskeleton. Due to this unusual membrane organization, lipids are likely to play critical roles in the formation and stability of intercellular conduits like TNTs and PDs, but also in regulating the transfer through these structures. While it is crucial for a better understanding of those fascinating communication highways, the study of TNT lipid composition and dynamics turned out to be extremely challenging. The present review aims to give an overview of the recent findings in this context. We will also discuss some of the promising imaging approaches, which might be the key for future breakthroughs in the field and could also benefit the research on PDs.

  11. Laboratory investigation and simulation of breakthrough curves in karst conduits with pools (United States)

    Zhao, Xiaoer; Chang, Yong; Wu, Jichun; Peng, Fu


    A series of laboratory experiments are performed under various hydrological conditions to analyze the effect of pools in pipes on breakthrough curves (BTCs). The BTCs are generated after instantaneous injections of NaCl tracer solution. In order to test the feasibility of reproducing the BTCs and obtain transport parameters, three modeling approaches have been applied: the equilibrium model, the linear graphical method and the two-region nonequilibrium model. The investigation results show that pools induce tailing of the BTCs, and the shapes of BTCs depend on pool geometries and hydrological conditions. The simulations reveal that the two-region nonequilibrium model yields the best fits to experimental BTCs because the model can describe the transient storage in pools by the partition coefficient and the mass transfer coefficient. The model parameters indicate that pools produce high dispersion. The increased tailing occurs mainly because the partition coefficient decreases, as the number of pools increases. When comparing the tracer BTCs obtained using the two types of pools with the same size, the more appreciable BTC tails that occur for symmetrical pools likely result mainly from the less intense exchange between the water in the pools and the water in the pipe, because the partition coefficients for the two types of pools are virtually identical. Dispersivity values decrease as flow rates increase; however, the trend in dispersion is not clear. The reduced tailing is attributed to a decrease in immobile water with increasing flow rate. It provides evidence for hydrodynamically controlled tailing effects.

  12. 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.

  13. Mathematical modeling and experimental breakthrough curves of carbon dioxide adsorption on metal organic framework CPM-5. (United States)

    Sabouni, Rana; Kazemian, Hossein; Rohani, Sohrab


    It is essential to capture carbon dioxide from flue gas because it is considered one of the main causes of global warming. Several materials and different methods have been reported for CO2 capturing including adsorption onto zeolites and porous membranes, as well as absorption in amine solutions. All such methods require high energy input and high cost. A new class of porous materials called Metal Organic Frameworks (MOFs) exhibited excellent performance in extracting carbon dioxide from a gas mixture. In this study, the breakthrough curves for the adsorption of carbon dioxide on CPM-5 (crystalline porous materials) were obtained experimentally and theoretically using a laboratory-scale fixed-bed column at different experimental conditions such as feed flow rate, adsorption temperature, and feed concentration. It was found that the CPM-5 has a dynamic CO2 adsorption capacity of 11.9 wt % (2.7 mmol/g) (corresponding to 8 mL/min, 298 K, and 25% v/v CO2). The tested CPM-5 showed an outstanding adsorption equilibrium capacity (e.g., 2.3 mmol/g (10.2 wt %) at 298 K) compared to other adsorbents, which can be considered as an attractive adsorbent for separation of CO2 from flue gas.

  14. Atypical Odontalgia (Phantom Tooth Pain) (United States)

    ... atypical facial pain, phantom tooth pain, or neuropathic orofacial pain, is characterized by chronic pain in a tooth ... such as a specialist in oral medicine or orofacial pain. The information contained in this monograph is for ...

  15. Supporting Self-management of Chronic Pain (United States)


    Chronic Pain Syndrome; Chronic Pain; Chronic Pain Due to Injury; Chronic Pain Due to Trauma; Chronic Pain Due to Malignancy (Finding); Chronic Pain Post-Procedural; Chronic Pain Hip; Chronic Pain, Widespread

  16. Paediatric pain management

    African Journals Online (AJOL)

    REVIEW. Introduction. Pain is defined by the International Association for the Study of. Pain (IASP) as ... lasts for a short time, whilst chronic pain normally persists for a much longer ..... on a regular time schedule, i.e. 'by the clock', whereby the medicine is .... combination with a non-opioid (from the first step) for severe pain.

  17. Chest Pain: First Aid (United States)

    First aid Chest pain: First aid Chest pain: First aid By Mayo Clinic Staff Causes of chest pain can vary from minor problems, such as indigestion ... 26, 2018 Original article: . Mayo ...

  18. Chronic pelvic pain. (United States)

    Stein, Sharon L


    Chronic pelvic pain is pain lasting longer than 6 months and is estimated to occur in 15% of women. Causes of pelvic pain include disorders of gynecologic, urologic, gastroenterologic, and musculoskeletal systems. The multidisciplinary nature of chronic pelvic pain may complicate diagnosis and treatment. Treatments vary by cause but may include medicinal, neuroablative, and surgical treatments. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Review of Opioid Pharmacogenetics and Considerations for Pain Management. (United States)

    Owusu Obeng, Aniwaa; Hamadeh, Issam; Smith, Michael


    Opioid analgesics are the standards of care for the treatment of moderate to severe nociceptive pain, particularly in the setting of cancer and surgery. Their analgesic properties mainly emanate from stimulation of the μ receptors, which are encoded by the OPRM1 gene. Hepatic metabolism represents the major route of elimination, which, for some opioids, namely codeine and tramadol, is necessary for their bioactivation into more potent analgesics. The highly polymorphic nature of the genes coding for phase I and phase II enzymes (pharmacokinetics genes) that are involved in the metabolism and bioactivation of opioids suggests a potential interindividual variation in their disposition and, most likely, response. In fact, such an association has been substantiated in several pharmacokinetic studies described in this review, in which drug exposure and/or metabolism differed significantly based on the presence of polymorphisms in these pharmacokinetics genes. Furthermore, in some studies, the observed variability in drug exposure translated into differences in the incidence of opioid-related adverse effects, particularly nausea, vomiting, constipation, and respiratory depression. Although the influence of polymorphisms in pharmacokinetics genes, as well as pharmacodynamics genes (OPRM1 and COMT) on response to opioids has been a subject of intense research, the results have been somehow conflicting, with some evidence insinuating for a potential role for OPRM1. The Clinical Pharmacogenetics Implementation Consortium guidelines provide CYP2D6-guided therapeutic recommendations to individualize treatment with tramadol and codeine. However, implementation guidelines for other opioids, which are more commonly used in real-world settings for pain management, are currently lacking. Hence, further studies are warranted to bridge this gap in our knowledge base and ultimately ascertain the role of pharmacogenetic markers as predictors of response to opioid analgesics. © 2017

  20. Pain, emotion, headache. (United States)

    Bussone, Gennaro; Grazzi, Licia; Panerai, Alberto E


    Pain has been considered as part of a defensive strategy whose specific role is to signal an immediate active danger to the organism. This definition fits well for acute pain. It does not work well, however, for chronic pain that is maintained even in absence of an ongoing, active threat. Currently, acute and chronic pain are considered to be separate conditions. What follows is a review of the different theories about pain and its history. Different hypotheses regarding pain mechanisms are illustrated. New data emerging from scientific research on chronic pain (migraine in particular) involving innovative imaging techniques are reported and discussed. © 2012 American Headache Society.

  1. 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 precluded systematic investigation of specific neuronal and pharmacological alterations that occur in cancer-induced bone pain. In 1999, Schwei et al. described a murine model of cancer-induced bone pain that paralleled the clinical condition in terms of pain development and bone destruction, confined...... to the mouse femur. This model prompted related approaches and we can now state that cancer pain may include elements of inflammatory and neuropathic pains but also unique changes in sensory processing. Cancer induced bone pain results in progressive bone destruction, elevated osteoclast activity...

  2. Multidisciplinary pain management programs.


    Kaiser, Ulrike; Arnold, Bernhard; Pfingsten, Michael; Nagel, Bernd; Lutz, Johannes; Sabatowski, Rainer


    Ulrike Kaiser,1 Bernhard Arnold,2 Michael Pfingsten,3 Bernd Nagel,4 Johannes Lutz,5 Rainer Sabatowski1,61Comprehensive Pain Center, University Hospital “Carl Gustav Carus”, Dresden, 2Department of Pain Management, Klinikum Dachau, Dachau, 3Pain Clinic, University Medicine, University of Göttingen, 4Day Care Unit, DRK Pain Center, Mainz, 5Interdisciplinary Pain Center, Zentralklinik Bad Berka, Bad Berka, 6Department of Anesthesiology and Intensive Care, University ...

  3. Pain perception and modulation in acute and chronic pain states

    NARCIS (Netherlands)

    Oudejans, L.C.J.


    This thesis describes the evaluation of pain perception in acute and chronic pain patients and the strength of the endogenous pain modulation system in chronic pain patients. Additionally, pain phenotypes are determined in patients with chronic pain. The ability of patients with acute pain after

  4. 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,

  5. 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

  6. Dermal pharmacokinetics of microemulsion formulations determined by in vivo microdialysis

    DEFF Research Database (Denmark)

    Kreilgaard, Mads


    To investigate the potential of improving dermal drug delivery of hydrophilic and lipophilic substances by formulation in microemulsion vehicles and to establish a reliable pharmacokinetic model to analyze cutaneous microdialysis data.......To investigate the potential of improving dermal drug delivery of hydrophilic and lipophilic substances by formulation in microemulsion vehicles and to establish a reliable pharmacokinetic model to analyze cutaneous microdialysis data....

  7. Pharmacokinetics of first-line tuberculosis drugs in tanzanian patients

    NARCIS (Netherlands)

    Tostmann, A.; Mtabho, C.M.; Semvua, H.H.; Boogaard, J. van den; Kibiki, G.S.; Boeree, M.J.; Aarnoutse, R.E.


    East Africa has a high tuberculosis (TB) incidence and mortality, yet there are very limited data on exposure to TB drugs in patients from this region. We therefore determined the pharmacokinetic characteristics of first-line TB drugs in Tanzanian patients using intensive pharmacokinetic sampling.

  8. [Pharmacokinetics of digoxin in hyperthyroidism. Effect of methimazole]. (United States)

    Izbicka, Maria; Gasińska, Teresa; Dec, Renata


    Cardiovascular abnormalities may be the only manifestations of overt hyperthyroidism. In patients with heart failure and atrial fibrillation digoxin can be beneficial in controlling the symptoms and signs, but hyperthyroid patients show an impaired response or even resistance to digoxin treatment. The aim of the study is to establish: 1. Are there any differences in the pharmacokinetics of a single oral dose of digoxin between hypertyroid and euthyroid patients? 2. Does simultaneous administration of digoxin and methimazole affect the pharmacokinetics of a single oral dose of dogoxin? 3. Does methimazole-induced euthyroidism change the pharmacokinetics of a single oral dose of digoxin? The subject of the study were 28 patients with hyperthyroidism and 15 healthy persons. We evaluated the pharmacokinetics of a single oral dose of digoxin. Moreover we evaluated pharmacokinetics of a single dose of digoxin after simultaneous administration of digoxin and methimazole in 12 patients and 12 methimazole treated patients werere-assessed once they had become euthyroid. Hyperthyroid patients showed significantly lower serum digoxin concentrations, shorter T1/2 beta and a significantly smaller area under the concentration curve (AUC) that the control group. Administration of methimazole did not affect digoxin pharmacokinetics. In hyperthyroid patients: 1. the pharmacokinetics of a single oral dose of digoxin does differ from that observed in healthy subjects. 2.methimazole do not alter digoxin pharmacokinetics.

  9. 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....

  10. An Allometric Model of Remifentanil Pharmacokinetics and Pharmacodynamics

    NARCIS (Netherlands)

    Eleveld, Douglas J.; Proost, Johannes H.; Vereecke, Hugo; Absalom, Anthony R.; Olofsen, Erik; Vuyk, Jaap; Struys, Michel M. R. F.

    Background: Pharmacokinetic and pharmacodynamic models are used to predict and explore drug infusion schemes and their resulting concentration profiles for clinical application. Our aim was to develop a pharmacokinetic-pharmacodynamic model for remifentanil that is accurate in patients with a wide

  11. Pharmacokinetic Variability of Drugs Used for Prophylactic Treatment of Migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Ågesen, Frederik Nybye; Pavbro, Agniezka


    In this review, we evaluate the variability in the pharmacokinetics of 11 drugs with established prophylactic effects in migraine to facilitate 'personalized medicine' with these drugs. PubMed was searched for 'single-dose' and 'steady-state' pharmacokinetic studies of these 11 drugs. The maximum...

  12. 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.

  13. Common genetic variants are significant risk factors for early menopause: results from the Breakthrough Generations Study. (United States)

    Murray, Anna; Bennett, Claire E; Perry, John R B; Weedon, Michael N; Jacobs, Patricia A; Morris, Danielle H; Orr, Nicholas; Schoemaker, Minouk J; Jones, Michael; Ashworth, Alan; Swerdlow, Anthony J


    Women become infertile approximately 10 years before menopause, and as more women delay childbirth into their 30s, the number of women who experience infertility is likely to increase. Tests that predict the timing of menopause would allow women to make informed reproductive decisions. Current predictors are only effective just prior to menopause, and there are no long-range indicators. Age at menopause and early menopause (EM) are highly heritable, suggesting a genetic aetiology. Recent genome-wide scans have identified four loci associated with variation in the age of normal menopause (40-60 years). We aimed to determine whether theses loci are also risk factors for EM. We tested the four menopause-associated genetic variants in a cohort of approximately 2000 women with menopause≤45 years from the Breakthrough Generations Study (BGS). All four variants significantly increased the odds of having EM. Comparing the 4.5% of individuals with the lowest number of risk alleles (two or three) with the 3.0% with the highest number (eight risk alleles), the odds ratio was 4.1 (95% CI 2.4-7.1, P=4.0×10(-7)). In combination, the four variants discriminated EM cases with a receiver operator characteristic area under the curve of 0.6. Four common genetic variants identified by genome-wide association studies, had a significant impact on the odds of having EM in an independent cohort from the BGS. The discriminative power is still limited, but as more variants are discovered they may be useful for predicting reproductive lifespan.


    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.

  15. 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.

  16. The effect of vapor polarity and boiling point on breakthrough for binary mixtures on respirator carbon. (United States)

    Robbins, C A; Breysse, P N


    This research evaluated the effect of the polarity of a second vapor on the adsorption of a polar and a nonpolar vapor using the Wheeler model. To examine the effect of polarity, it was also necessary to observe the effect of component boiling point. The 1% breakthrough time (1% tb), kinetic adsorption capacity (W(e)), and rate constant (kv) of the Wheeler model were determined for vapor challenges on carbon beds for both p-xylene and pyrrole (referred to as test vapors) individually, and in equimolar binary mixtures with the polar and nonpolar vapors toluene, p-fluorotoluene, o-dichlorobenzene, and p-dichlorobenzene (referred to as probe vapors). Probe vapor polarity (0 to 2.5 Debye) did not systematically alter the 1% tb, W(e), or kv of the test vapors. The 1% tb and W(e) for test vapors in binary mixtures can be estimated reasonably well, using the Wheeler model, from single-vapor data (1% tb +/- 30%, W(e) +/- 20%). The test vapor 1% tb depended mainly on total vapor concentration in both single and binary systems. W(e) was proportional to test vapor fractional molar concentration (mole fraction) in mixtures. The kv for p-xylene was significantly different (p boiling point; however, these differences were apparently of limited importance in estimating 1% tb for the range of boiling points tested (111 to 180 degrees C). Although the polarity and boiling point of chemicals in the range tested are not practically important in predicting 1% tb with the Wheeler model, an effect due to probe boiling point is suggested, and tests with chemicals of more widely ranging boiling point are warranted. Since the 1% tb, and thus, respirator service life, depends mainly on total vapor concentration, these data underscore the importance of taking into account the presence of other vapors when estimating respirator service life for a vapor in a mixture.

  17. 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.

  18. Breakthrough in current-in-plane tunneling measurement precision by application of multi-variable fitting algorithm

    DEFF Research Database (Denmark)

    Cagliani, Alberto; Østerberg, Frederik Westergaard; Hansen, Ole


    We present a breakthrough in micro-four-point probe (M4PP) metrology to substantially improve precision of transmission line (transfer length) type measurements by application of advanced electrode position correction. In particular, we demonstrate this methodology for the M4PP current-in-plane t......We present a breakthrough in micro-four-point probe (M4PP) metrology to substantially improve precision of transmission line (transfer length) type measurements by application of advanced electrode position correction. In particular, we demonstrate this methodology for the M4PP current......-in-plane tunneling (CIPT) technique. The CIPT method has been a crucial tool in the development of magnetic tunnel junction (MTJ) stacks suitable for magnetic random-access memories for more than a decade. On two MTJ stacks, the measurement precision of resistance-area product and tunneling magnetoresistance...

  19. Discovery and development of tramadol for the treatment of pain. (United States)

    Bravo, Lidia; Mico, Juan Antonio; Berrocoso, Esther


    Tramadol is an opioid drug that, unlike classic opioids, also modulates the monoaminergic system by inhibiting noradrenergic and serotoninergic reuptake. For this reason, tramadol is considered an atypical opioid. These special pharmacological characteristics have made tramadol one of the most commonly prescribed analgesic drugs to treat moderate to severe pain. Areas covered: The aim of this review is to provide a historical description of the biochemistry, pharmacokinetics and particularly, the mechanisms of action of tramadol. In addition, a summary is offered of the analgesic effects of tramadol in a variety of animal models of acute and chronic pain. Finally, clinical studies that demonstrate the efficacy and safety of tramadol in the treatment of pain are also assessed. Expert opinion: The discovery that tramadol combines opioid and monoaminergic effects represented a milestone in the evolution of pain treatment. Given its 'mild effect' on opioid receptors, tramadol induces fewer side effects than classic opioids. Tramadol produces satisfactory analgesia against various types of pain and it is currently approved for the treatment of moderate to severe pain. Thus, the combination of monoamine and opioid mechanisms opens new avenues for the design of innovative analgesics.

  20. 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...

  1. 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.

  2. 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.

  3. Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants, a population pharmacokinetic modelling approach. (United States)

    Marsot, Amélie; Brevaut-Malaty, Véronique; Vialet, Renaud; Boulamery, Audrey; Bruguerolle, Bernard; Simon, Nicolas


    Phenobarbital is widely used for treatment of neonatal seizures. Its optimal use in neonates and young infants requires information regarding pharmacokinetics. The objective of this study is to characterize the absolute bioavailability of phenobarbital in neonates and young infants, a pharmacokinetic parameter which has not yet been investigated. Routine clinical pharmacokinetic data were retrospectively collected from 48 neonates and infants (weight: 0.7-10 kg; patient's postnatal age: 0-206 days; GA: 27-42 weeks) treated with phenobarbital, who were administered as intravenous or suspension by oral routes and hospitalized in a paediatric intensive care unit. Total mean dose of 4.6 mg/kg (3.1-10.6 mg/kg) per day was administered by 30-min infusion or by oral route. Pharmacokinetic analysis was performed using a nonlinear mixed-effect population model software). Data were modelled with an allometric pharmacokinetic model, using three-fourths scaling exponent for clearance (CL). The population typical mean [per cent relative standard error (%RSE)] values for CL, apparent volume of distribution (Vd ) and bioavailability (F) were 0.0054 L/H/kg (7%), 0.64 L/kg (15%) and 48.9% (22%), respectively. The interindividual variability of CL, Vd , F (%RSE) and residual variability (%RSE) was 17% (31%), 50% (27%), 39% (27%) and 7.2 mg/L (29%), respectively. The absolute bioavailability of phenobarbital in neonates and infants was estimated. The dose should be increased when switching from intravenous to oral administration. © 2013 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.

  4. Investigating pulmonary and systemic pharmacokinetics of inhaled olodaterol in healthy volunteers using a population pharmacokinetic approach. (United States)

    Borghardt, Jens Markus; Weber, Benjamin; Staab, Alexander; Kunz, Christina; Formella, Stephan; Kloft, Charlotte


    Olodaterol, a novel β2-adrenergic receptor agonist, is a long-acting, once-daily inhaled bronchodilator approved for the treatment of chronic obstructive pulmonary disease. The aim of the present study was to describe the plasma and urine pharmacokinetics of olodaterol after intravenous administration and oral inhalation in healthy volunteers by population pharmacokinetic modelling and thereby to infer its pulmonary fate. Plasma and urine data after intravenous administration (0.5-25 μg) and oral inhalation (2.5-70 μg via the Respimat® inhaler) were available from a total of 148 healthy volunteers (single and multiple dosing). A stepwise model building approach was applied, using population pharmacokinetic modelling. Systemic disposition parameters were fixed to estimates obtained from intravenous data when modelling data after inhalation. A pharmacokinetic model, including three depot compartments with associated parallel first-order absorption processes (pulmonary model) on top of a four-compartment body model (systemic disposition model), was found to describe the data the best. The dose reaching the lung (pulmonary bioavailable fraction) was estimated to be 49.4% [95% confidence interval (CI) 46.1, 52.7%] of the dose released from the device. A large proportion of the pulmonary bioavailable fraction [70.1% (95% CI 66.8, 73.3%)] was absorbed with a half-life of 21.8 h (95% CI 19.7, 24.4 h). The plasma and urine pharmacokinetics of olodaterol after intravenous administration and oral inhalation in healthy volunteers were adequately described. The key finding was that a high proportion of the pulmonary bioavailable fraction had an extended pulmonary residence time. This finding was not expected based on the physicochemical properties of olodaterol. © 2015 The British Pharmacological Society.

  5. [Research progress on current pharmacokinetic evaluation of Chinese herbal medicines]. (United States)

    Li, Guofu; Zhao, Haoru; Yang, Jin


    In order to prove safety and efficacy, herbal medicines must undergo the rigorous scientific researches such as pharmacokinetic and bioavailability, before they are put on the market in the foreign countries. Botanical Drug Products promulgated by the US FDA could guide industry sponsors to develop herbal drugs, which was also an important reference for investigating Chinese herbal medicines. This paper reviews and discusses novel approaches for how to assess systemic exposure and pharmacokinetic of Chinese herbal medicines, which were in line with FDA guidance. This mainly focus on identifying pharmacokinetic markers of botanical products, integral pharmacokinetic study of multiple components, Biopharmaceutics drug disposition classification system, and population pharmacokinetic-pharmacodynamic study in herb-drug interaction.

  6. [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.

  7. Pharmacokinetics of oral terbinafine in adult horses. (United States)

    Younkin, T J; Davis, E G; Kukanich, B


    The primary study objective was to compare the pharmacokinetics of p.o. terbinafine alone to p.o. terbinafine administered with p.o. cimetidine in healthy adult horses. The second objective was to assess the pharmacokinetics of terbinafine when administered per rectum in two different suspensions at 30 mg/kg to adult horses. Six healthy adult horses were included in this crossover study. Plasma terbinafine concentrations were quantified with liquid chromatography and mass spectrometry. The half-life (geometric mean) was 8.38 and 10.76 h, for p.o. alone and p.o. with cimetidine, respectively. The mean maximum plasma concentrations were 0.291 μg/mL at 1.54 h and 0.418 μg/mL at 1.28 h for p.o. alone and p.o. with cimetidine, respectively. Terbinafine with cimetidine had an average C MAX 44% higher and the relative F was 153% compared p.o. terbinafine alone, but was not statistically different (P > 0.05). Terbinafine was infrequently detected when administered per rectum in two different suspensions (water or olive oil). Minor adverse effects included oral irritation, fever, and colic. All resolved spontaneously. More pharmacokinetic studies are indicated assessing drug-drug interactions and using multiple dosing intervals to improve our knowledge of effective oral dosing, the potential for drug accumulation, and systemic adverse effect of terbinafine in horses. © 2016 John Wiley & Sons Ltd.

  8. 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)

  9. Spinal pain in adolescents

    DEFF Research Database (Denmark)

    Aartun, Ellen; Hartvigsen, Jan; Wedderkopp, Niels


    BACKGROUND: The severity and course of spinal pain is poorly understood in adolescents. The study aimed to determine the prevalence and two-year incidence, as well as the course, frequency, and intensity of pain in the neck, mid back, and low back (spinal pain). METHODS: This study was a school......-based prospective cohort study. All 5th and 6th grade students (11-13 years) at 14 schools in the Region of Southern Denmark were invited to participate (N = 1,348). Data were collected in 2010 and again two years later, using an e-survey completed during school time. RESULTS: The lifetime prevalence of spinal pain...... reported their pain as relatively infrequent and of low intensity, whereas the participants with frequent pain also experienced pain of higher intensity. The two-year incidence of spinal pain varied between 40% and 60% across the physical locations. Progression of pain from one to more locations and from...

  10. 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

  11. 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...

  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. Cocrystals and alloys of nitazoxanide: enhanced pharmacokinetics. (United States)

    Suresh, Kuthuru; Mannava, M K Chaitanya; Nangia, Ashwini


    Two isomorphous cocrystals of nitazoxanide (NTZ) with p-aminosalicylic acid (PASA) and p-aminobenzoic acid (PABA) as well as their alloys were prepared by slurry and grinding techniques. The cocrystals exhibit faster dissolution rates and higher pharmacokinetic properties compared to the reference drug, and surprisingly the cocrystal alloy NTZ-PABA : NTZ-PASA (0.75 : 0.25) exhibited 4 fold higher bioavailability of NTZ in Sprague Dawley rats. This study opens the opportunity for cocrystal alloys as improved medicines.

  14. Clinical pharmacokinetics of nisoldipine coat-core. (United States)

    Heinig, R


    Nisoldipine, a calcium antagonist of the dihydropyridine type, is the active ingredient of the controlled release nisoldipine coat-core (CC) formulation. In humans, the absorption from nisoldipine CC occurs across the entire gastrointestinal tract with an increase in bioavailability in the colon because of the lower concentrations of metabolising enzymes in the distal gut wall. Although nisoldipine is almost completely absorbed, its absolute bioavailability from the CC tablet is only 5.5%, as a result of significant first-pass metabolism in the gut and liver. Nisoldipine is a high-clearance drug with substantial interindividual and relatively lower intraindividual variability in pharmacokinetics, dependent on liver blood flow. Nisoldipine is highly (> 99%) protein bound. Its elimination is almost exclusively via the metabolic route and renal excretion of metabolites dominates over excretion in the faeces. Although nisoldipine is administered as a racemic mixture, its plasma concentrations are almost entirely caused by the eutomer as a result of highly stereoselective intrinsic clearance. Nisoldipine CC demonstrates linear pharmacokinetics in the therapeutic dose range and its steady-state pharmacokinetics are predictable from single dose data. Steady-state is reached with the second dose when the drug is given once daily and the peak-trough fluctuations in plasma concentration is minimal. Plasma-concentrations of nisoldipine increase with age. Careful dose titration according to individual clinical response is recommended in the elderly. Nisoldipine CC should not be used in patients with liver cirrhosis, though dosage adjustments in patients with renal impairment are not necessary. Inter-ethnic differences in its pharmacokinetics are not evident. Owing to inhibition of metabolising enzymes, a small dosage adjustment decrement for nisoldipine CC may be required when it is given in combination with cimetidine. Concomitant ingestion of nisoldipine with grapefruit

  15. 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...... dilution technique. The different brands could be divided into three groups. Two gave a high maximum concentration, four a medium, and one a low concentration. The large interbrand variation observed in this study can explain the variations in the results of the treatment and the differing numbers...

  16. 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.

  17. Facilitated pronociceptive pain mechanisms in radiating back pain compared with localized back pain

    DEFF Research Database (Denmark)

    Vaegter, Henrik Bjarke; Palsson, Thorvaldur Skuli; Graven-Nielsen, Thomas


    Facilitated pain mechanisms and impaired pain inhibition are often found in chronic pain patients. This study compared clinical pain profiles, pain sensitivity, as well as pro-nociceptive and anti-nociceptive mechanisms in patients with localized low back pain (n=18), localized neck pain (n=17......), low back and radiating leg pain (n=18), or neck and radiating arm pain (n=17). It was hypothesized that patients with radiating pain had facilitated pain mechanisms and impaired pain inhibition compared with localized pain patients. Cuff algometry was performed on the non-painful lower leg to assess...... threshold (HPT) at the non-painful hand were also assessed. Clinical pain intensity, psychological distress, and disability were assessed with questionnaires. TSP was increased in patients with radiating back pain compared with localized back pain (Ppain or localized low...

  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. Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers. (United States)

    Skulberg, Arne Kristian; Tylleskar, Ida; Nilsen, Turid; Skarra, Sissel; Salvesen, Øyvind; Sand, Trond; Loftsson, Thorsteinn; Dale, Ola


    This study aimed to develop a model for pharmacodynamic and pharmacokinetic studies of naloxone antagonism under steady-state opioid agonism and to compare a high-concentration/low-volume intranasal naloxone formulation 8 mg/ml to intramuscular 0.8 mg. Two-way crossover in 12 healthy volunteers receiving naloxone while receiving remifentanil by a target-controlled infusion for 102 min. The group were subdivided into three different doses of remifentanil. Blood samples for serum naloxone concentrations, pupillometry and heat pain threshold were measured. The relative bioavailability of intranasal to intramuscular naloxone was 0.75. Pupillometry showed difference in antagonism; the effect was significant in the data set as a whole (p < 0.001) and in all three subgroups (p < 0.02-p < 0.001). Heat pain threshold showed no statistical difference. A target-controlled infusion of remifentanil provides good conditions for studying the pharmacodynamics of naloxone, and pupillometry was a better modality than heat pain threshold. Intranasal naloxone 0.8 mg is inferior for a similar dose intramuscular. Our design may help to bridge the gap between studies in healthy volunteers and the patient population in need of naloxone for opioid overdose. : NCT02307721.

  20. Glucosamine sulfate effect on the degenerated patellar cartilage: preliminary findings by pharmacokinetic magnetic resonance modeling

    Energy Technology Data Exchange (ETDEWEB)

    Marti-Bonmati, Luis [Dr Peset University Hospital, Radiology Department, Valencia (Spain); Hospital Quiron Valencia, Radiology Department, Valencia (Spain); Sanz-Requena, Roberto; Alberich-Bayarri, Angel [Hospital Quiron Valencia, Radiology Department, Valencia (Spain); Rodrigo, Jose Luis [Dr Peset University Hospital, Traumatology and Orthopedics Surgery Department, Valencia (Spain); Carot, Jose Miguel [Universidad Politecnica de Valencia, EIO Department, Valencia (Spain)


    Normal and degenerated cartilages have different magnetic resonance (MR) capillary permeability (K{sup trans}) and interstitial interchangeable volume (v{sub e}). Our hypothesis was that glucosamine sulfate treatment modifies these neovascularity abnormalities in osteoarthritis. Sixteen patients with patella degeneration, randomly distributed into glucosamine or control groups, underwent two 1.5-Tesla dynamic contrast-enhanced MR imaging studies (treatment initiation and after 6 months). The pain visual analog scale (VAS) and American Knee Society (AKS) score were used. A two-compartment pharmacokinetic model was used. Percentages of variations (postreatment-pretreatment/pretreatment) were compared (t-test for independent data). In the glucosamine group, pain and functional outcomes statistically improved (VAS: 7.3 {+-} 1.1 to 3.6 {+-} 1.3, p < 0.001; AKS: 18.6 {+-} 6.9 to 42.9 {+-} 2.7, p < 0.01). Glucosamine significantly increased K{sup trans} at 6 months (-54.4 {+-} 21.2% vs 126.7 {+-} 56.9%, p < 0.001, control vs glucosamine). In conclusion, glucosamine sulfate decreases pain while improving functional outcome in patients with cartilage degeneration. Glucosamine sulfate increases K{sup trans}, allowing its proposal as a surrogate imaging biomarker after 6 months of treatment. (orig.)

  1. Loin pain hematuria syndrome. (United States)

    Taba Taba Vakili, Sahar; Alam, Tausif; Sollinger, Hans


    Loin pain hematuria syndrome is a rare disease with a prevalence of ∼0.012%. The most prominent clinical features include periods of severe intermittent or persistent unilateral or bilateral loin pain accompanied by either microscopic or gross hematuria. Patients with loin pain hematuria syndrome initially present with hematuria, flank pain, or most often both hematuria and flank pain. Kidney biopsies from patients with loin pain hematuria typically reveal only minor pathologic abnormalities. Further, loin pain hematuria syndrome is not associated with loss of kidney function or urinary tract infections. Loin pain hematuria syndrome-associated hematuria and pain are postulated to be linked to vascular disease of the kidney, coagulopathy, renal vasospasm with microinfarction, hypersensitivity, complement activation on arterioles, venocalyceal fistula, abnormal ureteral peristalsis, and intratubular deposition of calcium or uric acid microcrystals. Many patients with loin pain hematuria syndrome also meet criteria for a somatoform disorder, and analgesic medications, including narcotics, commonly are used to treat loin pain hematuria syndrome-associated pain. Interventional treatments include renal denervation, kidney autotransplantation, and nephrectomy; however, these methods should be used only as a last resort when less invasive measures have been tried unsuccessfully. In this review article, we discuss and critique current clinical practices related to loin pain hematuria syndrome pathophysiology, diagnosis, treatment, and prognosis. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  2. 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.

  3. 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.

  4. 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

  5. Clinical Population Pharmacokinetics and Toxicodynamics of Linezolid (United States)

    Boak, Lauren M.; Rayner, Craig R.; Grayson, M. Lindsay; Paterson, David L.; Spelman, Denis; Khumra, Sharmila; Capitano, Blair; Forrest, Alan; Li, Jian


    Thrombocytopenia is a common side effect of linezolid, an oxazolidinone antibiotic often used to treat multidrug-resistant Gram-positive bacterial infections. Various risk factors have been suggested, including linezolid dose and duration of therapy, baseline platelet counts, and renal dysfunction; still, the mechanisms behind this potentially treatment-limiting toxicity are largely unknown. A clinical study was conducted to investigate the relationship between linezolid pharmacokinetics and toxicodynamics and inform strategies to prevent and manage linezolid-associated toxicity. Forty-one patients received 42 separate treatment courses of linezolid (600 mg every 12 h). A new mechanism-based, population pharmacokinetic/toxicodynamic model was developed to describe the time course of plasma linezolid concentrations and platelets. A linezolid concentration of 8.06 mg/liter (101% between-patient variability) inhibited the synthesis of platelet precursor cells by 50%. Simulations predicted treatment durations of 5 and 7 days to carry a substantially lower risk than 10- to 28-day therapy for platelet nadirs of linezolid therapy and large between-patient variability, close monitoring of patients for development of toxicity is important. Dose individualization based on plasma linezolid concentration profiles and platelet counts should be considered to minimize linezolid-associated thrombocytopenia. Overall, oxazolidinone therapy over 5 to 7 days even at relatively high doses was predicted to be as safe as 10-day therapy of 600 mg linezolid every 12 h. PMID:24514086

  6. Pharmacokinetics of rilmenidine in healthy subjects

    International Nuclear Information System (INIS)

    Genissel, P.; Bromet, N.; Fourtillan, J.B.; Mignot, A.; Albin, H.


    Rilmenidine is a novel alpha 2-adrenoceptor agonist, used in the treatment of mild or moderate hypertension at the oral dose of 1 mg once or twice daily. The pharmacokinetic parameters were investigated after single or repeated administration in healthy subjects, using labeled and unlabeled compounds. Rilmenidine was rapidly and extensively absorbed, with an absolute bioavailability factor close to 1 and a maximal plasma concentration achieved within 2 hours. Rilmenidine was not subject to presystemic metabolism. Distribution was independent of the free fraction because rilmenidine was weakly bound to plasma proteins (less than 10%). The volume of distribution was approximately 5 (315 liters). Elimination was rapid with a total body plasma clearance of approximately 450 ml.min-1 and an elimination half-life of approximately 8 hours. Renal excretion was the major elimination process (two-thirds of the total clearance). Metabolism was very poor, with a renal elimination of rilmenidine as the parent drug (urinary fraction of rilmenidine was about 65% and no metabolite plasma levels were detected). Linear pharmacokinetics were demonstrated for rilmenidine from 0.5 to 2 mg but, at 3 mg, a slight deviation from linearity was observed. In repeated administration, the linear disposition of rilmenidine with dose was confirmed

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. Chronic Pelvic Pain (United States)

    ... NSAIDs) are helpful in relieving pelvic pain, especially dysmenorrhea . Physical therapy—Acupuncture, acupressure, and nerve stimulation therapies may be useful in treating pain caused by dysmenorrhea. Physical therapy that eases trigger points may give ...

  13. Eldercare at Home: Pain (United States)

    ... or "heaviness" or “misery.” Look for behavior or body language that looks like a response to pain. An ... to communicate about pain in words. Behaviors or body language to look for include facial expressions such as ...

  14. Magnets for Pain Relief (United States)

    ... NCCIH NCCIH At a Glance Mission and Vision Organizational Structure Director's Message Strategic Plans & Reports Budget & ... © Matthew Lester Magnets are often marketed for different types of pain, such as foot or back pain ...

  15. Perspectives in Pancreatic Pain

    Directory of Open Access Journals (Sweden)

    A. S. Salim


    Full Text Available This review describes some of the mechanisms which are thought to be important in the causation of pain in chronic pancreatitis. Both medical and surgical techniques for treating this pain are described.

  16. Diclofenac Topical (osteoarthritis pain) (United States)

    ... gel (Voltaren) is used to relieve pain from osteoarthritis (arthritis caused by a breakdown of the lining ... Diclofenac topical liquid (Pennsaid) is used to relieve osteoarthritis pain in the knees. Diclofenac is in a ...

  17. Physiotherapists' knowledge of pain

    African Journals Online (AJOL)

    To investigate the pain knowledge of sports and orthopaedic manipulative physiotherapists ... may enable more effective treatment and management of clinical ... A person may have severe pain, but appear calm and rational at the same time.

  18. Persistent idiopathic facial pain

    DEFF Research Database (Denmark)

    Maarbjerg, Stine; Wolfram, Frauke; Heinskou, Tone Bruvik


    Introduction: Persistent idiopathic facial pain (PIFP) is a poorly understood chronic orofacial pain disorder and a differential diagnosis to trigeminal neuralgia. To address the lack of systematic studies in PIFP we here report clinical characteristics and neuroimaging findings in PIFP. Methods...... pain 7 (13%), hypoesthesia 23 (48%), depression 16 (30%) and other chronic pain conditions 17 (32%) and a low prevalence of stabbing pain 21 (40%), touch-evoked pain 14 (26%) and remission periods 10 (19%). The odds ratio between neurovascular contact and the painful side was 1.4 (95% Cl 0.4–4.4, p = 0.......565) and the odds ratio between neurovascular contact with displacement of the trigeminal nerve and the painful side was 0.2 (95% Cl 0.0–2.1, p = 0.195). Conclusion: PIFP is separated from trigeminal neuralgia both with respect to the clinical characteristics and neuroimaging findings, as NVC was not associated...

  19. Block That Pain! (United States)

    Skip Navigation Bar Home Current Issue Past Issues Block That Pain! Past Issues / Fall 2007 Table of ... contrast, most pain relievers used for surgical procedures block activity in all types of neurons. This can ...

  20. Science of pain

    National Research Council Canada - National Science Library

    Basbaum, A. I; Bushnell, M. Catherine


    "The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage...

  1. Pain in Down's Syndrome

    Directory of Open Access Journals (Sweden)

    Federica Mafrica


    Full Text Available Pain is a homeostatic mechanism that intervenes to protect the organism from harmful stimuli that could damage its integrity. It is made up of two components: the sensory-discriminative component, which identifies the provenance and characteristics of the type of pain; and the affective-motivational component, on which emotional reflexes, following the painful sensation, depend.There is a system for pain control at an encephalic and spinal level, principally made up of the periaqueductal grey matter, the periventricular area, the nucleus raphe magnus, and the pain-inhibition complex situated in the posterior horns of the spinal cord. Through the activation of these pain-control systems, the nervous system suppresses the afference of pain signals. Endogenous opioids represent another analgesic system.In the course of various studies on pain transmission in Down patients, the reduced tolerance of pain and the incapacity to give a qualitative and quantitative description emerged in a powerful way. All of these aspects cause difficulty in evaluating pain. This is linked to several learning difficulties. However, it cannot be excluded that in these anomalies of pain perception, both the anatomical and the neurotransmitter alteration, typical of this syndrome, may hold a certain importance.This fact may have important clinical repercussions that could affect the choice of therapeutic and rehabilitative schemes for treatment of pathologies in which pain is the dominant symptom, such as postoperative pain. It could influence research on analgesics that are more suitable for these patients, the evaluation of the depth of analgesia during surgical operation, and ultimately, absence of obvious pain manifestations. In conclusion, alterations of the central nervous system, neurotransmitters, pain transmission, and all related problems should be considered in the management of pain in patients with Down's syndrome, especially by algologists and

  2. Pain Examination and Diagnosis. (United States)

    Curtin, Catherine


    Pain is a clinical challenge to health care providers who care for hand disorders. Pathologic pain that prevents recovery leads to dissatisfaction for both patients and providers. Despite pain being common, the root cause is often difficult to diagnose. This article reviews the examination and diagnostic tools that are helpful in identifying pathologic and neuropathic pain. This article provides tools to speed recognition of these processes to allow earlier intervention and better patient outcomes. Published by Elsevier Inc.

  3. Ketogenic Diets and Pain (United States)

    Masino, Susan A.; Ruskin, David N.


    Ketogenic diets are well-established as a successful anticonvulsant therapy. Based on overlap between mechanisms postulated to underlie pain and inflammation, and mechanisms postulated to underlie therapeutic effects of ketogenic diets, recent studies have explored the ability for ketogenic diets to reduce pain. Here we review clinical and basic research thus far exploring the impact of a ketogenic diet on thermal pain, inflammation, and neuropathic pain. PMID:23680946

  4. Ketogenic Diets and Pain


    Masino, Susan A.; Ruskin, David N.


    Ketogenic diets are well-established as a successful anticonvulsant therapy. Based on overlap between mechanisms postulated to underlie pain and inflammation, and mechanisms postulated to underlie therapeutic effects of ketogenic diets, recent studies have explored the ability for ketogenic diets to reduce pain. Here we review clinical and basic research thus far exploring the impact of a ketogenic diet on thermal pain, inflammation, and neuropathic pain.

  5. [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.

  6. The influence of children's pain memories on subsequent pain experience. (United States)

    Noel, Melanie; Chambers, Christine T; McGrath, Patrick J; Klein, Raymond M; Stewart, Sherry H


    Healthy children are often required to repeatedly undergo painful medical procedures (eg, immunizations). Although memory is often implicated in children's reactions to future pain, there is a dearth of research directly examining the relationship between the 2. The current study investigated the influence of children's memories for a novel pain stimulus on their subsequent pain experience. One hundred ten healthy children (60 boys) between the ages of 8 and 12 years completed a laboratory pain task and provided pain ratings. Two weeks later, children provided pain ratings based on their memories as well as their expectancies about future pain. One month following the initial laboratory visit, children again completed the pain task and provided pain ratings. Results showed that children's memory of pain intensity was a better predictor of subsequent pain reporting than their actual initial reporting of pain intensity, and mediated the relationship between initial and subsequent pain reporting. Children who had negatively estimated pain memories developed expectations of greater pain prior to a subsequent pain experience and showed greater increases in pain ratings over time than children who had accurate or positively estimated pain memories. These findings highlight the influence of pain memories on healthy children's expectations of future pain and subsequent pain experiences and extend predictive models of subsequent pain reporting. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  7. Acute pain guidelines

    African Journals Online (AJOL)

    identified the fact that pain is badly managed in all parts of the world, but .... Physiological pain is the activation of nociceptors in response to a noxious ... postsynaptic neuron. ... The basic afferent pain pathway is outlined in Figure 2. 3.2 Neurotransmitters ..... “Crying” is characterised by an utterance of emotion accompanied.

  8. 13. Sacroiliac joint pain

    NARCIS (Netherlands)

    Vanelderen, P.; Szadek, K.M.; Cohen, S.P.; Witte, J.; Lataster, A.; Patijn, J.; Mekhail, N.; van Kleef, M.; van Zundert, J.


    The sacroiliac joint accounts for approximately 16% to 30% of cases of chronic mechanical low back pain. Pain originating in the sacroiliac joint is predominantly perceived in the gluteal region, although pain is often referred into the lower and upper lumbar region, groin, abdomen, and/ or lower

  9. Complex Regional Pain Syndrome (United States)

    Complex regional pain syndrome (CRPS) is a chronic pain condition. It causes intense pain, usually in the arms, hands, legs, or feet. It may happen ... move the affected body part The cause of CRPS is unknown. There is no specific diagnostic test. ...

  10. Knee pain (image) (United States)

    The location of knee pain can help identify the problem. Pain on the front of the knee can be due to bursitis, arthritis, or ... synovial fluid) that forms behind the knee. Overall knee pain can be due to bursitis, arthritis, tears in ...

  11. [Pain in edentulous patients

    NARCIS (Netherlands)

    Baat, C. de


    In daily social life, orofacial pain is strongly associated with teeth. However, edentulousness is no lifetime guarantee of being pain-free in the orofacial region. Common oral pains in edentulous people are caused by denture misfits or occlusal errors, by alveolar ridge atrophy, by (sharp)

  12. 21. Phantom pain.

    NARCIS (Netherlands)

    Wolff, A.P.; Vanduynhoven, E.; Kleef, M. van; Huygen, F.; Pope, J.E.; Mekhail, N.


    Phantom pain is pain caused by elimination or interruption of sensory nerve impulses by destroying or injuring the sensory nerve fibers after amputation or deafferentation. The reported incidence of phantom limb pain after trauma, injury or peripheral vascular diseases is 60% to 80%. Over half the

  13. Medicines for back pain (United States)

    ... You may need to be watched for side effects. NARCOTIC PAIN RELIEVERS Narcotics , also called opioid pain relievers, are used only for pain that is severe and is not helped by other types of painkillers. They work well for short-term relief. Do ...

  14. Pain: Hope through Research (United States)

    ... in drugstores. Chiropractic care may ease back pain, neck pain, headaches, and musculoskeletal conditions. It involves "hands-on" ... together. The peripheral nervous system refers to the cervical, thoracic, ... or dysfunction (such as pain) travel from the brain to the spinal cord ...

  15. Postoperative Pain Management After Primary Total Knee Arthroplasty: The Value of Liposomal Bupivacaine. (United States)

    Sporer, Scott M; Rogers, Thea


    Multimodal pain protocols have been proposed to achieve improved long-acting postoperative analgesia. Controlling postoperative pain after joint arthroplasty is especially important as it relates to patient satisfaction and outcomes. The purpose of this study was to compare the postoperative pain, time to ambulation, and overall narcotic usage between patients who received either a femoral nerve block with a periarticular bupivacaine injection or a periarticular bupivacaine and extended-release liposomal bupivacaine injection after primary total knee arthroplasty. A total of 597 consecutive primary total knee arthroplasties performed between September 1, 2012 and August 31, 2014 received preoperative celecoxib, oxycodone, and transdermal scopolamine. Intraoperatively, patients either received a single-dose bupivacaine femoral nerve block along with 30-mL 0.25% bupivacaine periarticular injection (group A) or a 60-mL periarticular injection alone (20-mL liposomal bupivacaine, 30-mL 0.25% bupivacaine, and 10-mL saline; group B). The postoperative pain scores, narcotic usage, and time to ambulation were retrospectively collected from the electronic medical record. These outcomes were compared between treatment groups. There were 325 patients in group A compared with 272 in group B during the time frame. There was no difference among age, gender, race, and body mass index between the groups. Group B demonstrated a decreased need for breakthrough pain medication (16.9% vs 36.3% P bupivacaine resulted in a decrease need for breakthrough pain medication, improved pain scores at 12 hours, and an earlier time to ambulation compared to a combined femoral nerve block and periarticular bupivacaine injection. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. 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.

  17. Painful Intercourse Is Significantly Associated with Evoked Pain Perception and Cognitive Aspects of Pain in Women with Pelvic Pain

    Directory of Open Access Journals (Sweden)

    Meryl J. Alappattu, DPT, PhD


    Conclusions: Differences in local pain ratings suggest that women with pelvic pain perceive stimuli in this region as more painful than pain-free women although the magnitude of stimuli does not differ. Alappattu MJ, George SZ, Robinson ME, Fillingim RB, Moawad N, LeBrun EW, and Bishop MD. Painful intercourse is significantly associated with evoked pain perception and cognitive aspects of pain in women with pelvic pain. Sex Med 2015;3:14–23.

  18. 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 (Amazon

  19. Children's pain perspectives. (United States)

    Esteve, R; Marquina-Aponte, V


    Previous studies on children's pain perspectives remain limited to English-speaking populations. An exploratory cross-sectional descriptive design was used to investigate the developmental progression of children's pain perspectives, including their pain experience, its definition and attributes, causality and coping. The Children's Pain Perspectives Inventory was applied to 180 healthy Spanish children. A coding system was developed following the content analysis method. Three age groups were compared: 4-6 years, corresponding to the Piagetian pre-operational stage of cognitive development; 7-11 years, corresponding to stage of concrete operations; and 12-14 years, corresponding to the period of early formal operations. In children between 4 and 6, the predominant narratives related to physical injuries, the notion of causality and the definition of pain. In children between 7 and 11, the predominant narratives were those in which pain was described as a sensation in one part of the body. The view of pain as having an emotional basis significantly increased with age and was more frequent in adolescents. In contrast, children between 4-6 and 7-11 indicated that pain occurs spontaneously. The denial of any positive aspects of pain significantly decreased with age; some children between 7 and 11 referred to the 'possibility of relief', while the view that pain is a 'learning experience' was significantly more frequent among adolescents aged between 12 and 14 years. The use of cognitive strategies to control pain significantly increased with age. Between 12 and 14 years of age, adolescents communicate pain by non-verbal behaviour and reported that they do not express demands for relief. There was a progression from concrete to more complex notions of pain as age increased. These results may be of use to health professionals and parents to understand how children at various developmental stages express and cope with pain and to develop tools that effectively assess and

  20. Pain-related worry in patients with chronic orofacial pain. (United States)

    Davis, C Ervin; Stockstill, John W; Stanley, William D; Wu, Qiang


    Pain-related worry is distinct from, but related to, pain catastrophizing (PC) and anxiety. Worry and its relationship with other variables have been studied in people with chronic pain but not in people with chronic orofacial pain. The authors explored the prevalence of trait, general and pain-related worry and the association of worry with higher pain levels and other variables. The authors assessed people who had a diagnosis of chronic orofacial pain by using nonpain-related trait worry, state anxiety, trait anxiety, PC and pain measures. The participants' answers to an open-ended question about what they were most worried about led to the identification of worry domains, including worry about pain. The authors found that worrying about pain was related significantly to worst and least pain levels, pain interference and pain duration, as well as moderated trait worry in predicting pain interference. Although trait worry was not correlated directly with pain, when moderated by PC, it made substantial contributions in predicting pain interference. Participants with chronic orofacial pain reported experiencing substantial levels of trait worry, anxiety, PC and worry about pain that related to pain ratings directly and indirectly. Clinicians should assess pain-related worry in patients with chronic orofacial pain to understand the effects of worry on pain and functioning. Clinicians could treat these patients more effectively by helping them reduce their levels of pain-related worry and focusing on improved coping.

  1. Dancing in pain: pain appraisal and coping in dancers. (United States)

    Anderson, Ruth; Hanrahan, Stephanie J


    This study investigated the relationships between the type of pain experienced (performance pain and injury pain), the cognitive appraisal of pain and pain coping styles in dancers. Fifty-one professional ballet and contemporary dancers (17 males and 34 females), with the mean age of 25.9 years, completed a general pain questionnaire, the Pain Appraisal Inventory, the Survey of Pain Attitudes Control Subscale, and the Sports Inventory for Pain. Multivariate analyses of variance indicated that both the cognitive appraisal of the pain and pain coping styles did not differ according to the type of pain experienced or the pain severity. However, it was found that dancers with performance pain of either low or high severity were more likely to dance in pain than dancers experiencing injury pain. Multiple regression analyses indicated that the appraisal of pain as threatening was predictive of the use of avoidance and catastrophizing pain coping styles. Overall, results indicated that dancers may not differentiate between performance pain and injury pain, or modify their appraisal and coping strategies according to the characteristics of the pain experienced. The study highlighted an opportunity for increased education for dancers in recognizing the difference between pain considered to be a routine aspect of training and pain which is a signal of serious injury.

  2. Neuropathic pain in primary care

    African Journals Online (AJOL)

    The operative difference is that neuropathic pain represents a delayed, ongoing response to damage that is no longer acute ... Postsurgical pain (including post- mastectomy and phantom limb pain). Spinal cord injury pain ... Management of neuropathic pain. Neuropathic pain tends to exhibit a relatively poor response.

  3. Multidisciplinary pain management programs

    Directory of Open Access Journals (Sweden)

    Kaiser U


    Full Text Available Ulrike Kaiser,1 Bernhard Arnold,2 Michael Pfingsten,3 Bernd Nagel,4 Johannes Lutz,5 Rainer Sabatowski1,61Comprehensive Pain Center, University Hospital “Carl Gustav Carus”, Dresden, 2Department of Pain Management, Klinikum Dachau, Dachau, 3Pain Clinic, University Medicine, University of Göttingen, 4Day Care Unit, DRK Pain Center, Mainz, 5Interdisciplinary Pain Center, Zentralklinik Bad Berka, Bad Berka, 6Department of Anesthesiology and Intensive Care, University Hospital “Carl Gustav Carus”, Dresden, Germany

  4. Nutraceuticals and osteoarthritis pain. (United States)

    Wang, Angela; Leong, Daniel J; Cardoso, Luis; Sun, Hui B


    Arthritis is a chronic disease of joints. It is highly prevalent, particularly in the elderly, and is commonly associated with pain that interferes with quality of life. Because of its chronic nature, pharmacological approaches to pain relief and joint repair must be safe for long term use, a quality many current therapies lack. Nutraceuticals refer to compounds or materials that can function as nutrition and exert a potential therapeutic effect, including the relief of pain, such as pain related to arthritis, of which osteoarthritis (OA) is the most common form. Of interest, nutraceuticals have recently been shown to have potential in relieving OA pain in human clinical trials. Emerging evidence indicates nutraceuticals may represent promising alternatives for the relief of OA pain. In this paper, we will overview OA pain and the use of nutraceuticals in OA pain management, focusing on those that have been evaluated by clinical trials. Furthermore, we discuss the biologic and pharmacologic actions underlying the nutraceutical effects on pain relief based on the potential active ingredients identified from traditional nutraceuticals in OA pain management and their potential for drug development. The review concludes by sharing our viewpoints that future studies should prioritize elucidating the mechanisms of action of nutraceuticals in OA and developing nutraceuticals that not only relieve OA pain, but also mitigate OA pathology. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Fantom pain: Case report

    Directory of Open Access Journals (Sweden)

    Marić Sanja S.


    Full Text Available Background Phantom limb pain is a common problem after limb amputation (41-85%. It is described as an extremely painful sensation in the missing part of the body that can last for hours, days or even years. It is considered to arise from cortical reorganization, although many factors can increase the risk of phantom limb pain: pain before surgery, age and sex of the patients, the time elapsed since surgery, stump pain, inadequate prosthesis. Phantom limb pain therapy is very complicated. Case report We reported a case of 80-year-old patient suffering from phantom limb pain and phantom sensation 25 years after the amputation of his left leg due to the injury. The patient has pain at the site of amputation, sensation that he has the leg and that it occupies an unusual position and almost daily exhausting phantom limb pain (6-9 visual analogue scale - VAS with disturbed sleep and mood. We managed to reduce the pain under 4 VAS and decrease the patient suffering by combining drugs from the group of coanalgetics (antidepressants, antiepileptics, non-pharmacological methods (transcutaneous electroneurostimulation - TENS, mirror therapy and femoral nerve block in the place of disarticulation of the left thigh. Conclusion Phantom limb pain therapy is multimodal, exhausting for both the patient and the physician and it is often unsuccessful. The combination of different pharmacological and non-pharmacological modalities can give satisfactory therapeutic response.

  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 tailing becomes heavier. Strong fluctuations occur when the number of samples is limited, due to the effects of subsampling. On the other hand, when the power law model embeds a cutoff (PLCO), the best-fitted exponent (αCO) is insensitive to the degree of tailing and to the effects of subsampling and tends to a 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

  7. Capacitive Sensors and Breakthrough Curves in Automated Irrigation for Water and Soil Conservation (United States)

    Fahmy Hussein, Mohamed


    when such sensors are used in farmers' fields. The second procedure was Breakthrough Curve (BTC) lab-method to follow the fate of chemical composition of water draining out of Ca-saturated soil columns and Exchangeable Sodium Percent, ESP, in soil materials under saturated-flow. The work was run on five packed soil-columns under hydraulic-gradient of about 6 in fine-grained soil materials (Nile clay-sediments) wetted with five NaCl aqueous solutions (10, 25, 50, 75 and 100 mEq/l). The results revealed the removal of 40 to 80% of sodium from irrigation water after 6 to 8 pore volumes flowed out in about 12 hours with the highest removal from the most dilute solution. Rapid increase of ESP was observed when the inlet solution had moderate to high TDS whereas the dilute solution (10 mEq/l) has resulted in no soil chemical degradation. The results were extrapolated to field situation and showed that Nile clayey soil would never get sodic (ESP>15) when wetted with high quality water regardless the water application duration whereas only 1-4 year of irrigation with moderate to poor-quality water (as takes place under perennial irrigation) would result in ESP increase to 15 and much higher values. A secondary but important outcome of BTC experiments was that marginal sediments could be used in multi-column cells (6 to 8 columns) to improve water-quality through removal of Na+ ions from water, whereas anions could be removed by positively-charged resins and the cells could be recycled in a proposed prototype scheme.

  8. The pharmacokinetics and effects of meloxicam, gabapentin, and flunixin in postweaning dairy calves following dehorning with local anesthesia. (United States)

    Glynn, H D; Coetzee, J F; Edwards-Callaway, L N; Dockweiler, J C; Allen, K A; Lubbers, B; Jones, M; Fraccaro, E; Bergamasco, L L; KuKanich, B


    Approved analgesic compounds in cattle are not currently available in the United States due to the lack of validated pain assessment methods and marker residue depletion studies. In this study, we compared the pharmacokinetic parameters and effect of preemptive analgesics administered to calves subjected to dehorning with local anesthesia. Holstein steers were randomly assigned to receive one of the following treatments per os (PO) or intravenously (IV) (n = 8/group): meloxicam (1 mg/kg PO), gabapentin (15 mg/kg PO), meloxicam (1 mg/kg), and gabapentin (15 mg/kg) PO, flunixin (2.2 mg/kg IV), or a placebo. Plasma drug, haptoglobin, substance P (SP) concentrations, serum cortisol concentrations, ocular thermography, mechanical nociceptive threshold (MNT), and average daily gain (ADG) were evaluated. Data were analyzed using mixed-effects models and noncompartmental pharmacokinetic analysis. Meloxicam, gabapentin, and meloxicam with gabapentin at the present doses did not reduce cortisol concentrations. Analgesic-treated calves had significantly lower plasma SP concentrations and improved ADG compared with controls. Flunixin calves had reduced circulating cortisol compared with controls. Meloxicam-treated calves showed an increase in MNT at two horn bud sites compared with the other treatments. Analgesics improved ADG and reduced biomarkers of pain, but effects differed by compound and route of administration. © 2013 John Wiley & Sons Ltd.

  9. Ketamine for pain (United States)

    Jonkman, Kelly; Dahan, Albert; van de Donk, Tine; Aarts, Leon; Niesters, Marieke; van Velzen, Monique


    The efficacy of the N-methyl-D-aspartate receptor antagonist ketamine as an analgesic agent is still under debate, especially for indications such as chronic pain. To understand the efficacy of ketamine for relief of pain, we performed a literature search for relevant narrative and systematic reviews and meta-analyses. We retrieved 189 unique articles, of which 29 were deemed appropriate for use in this review. Ketamine treatment is most effective for relief of postoperative pain, causing reduced opioid consumption. In contrast, for most other indications (that is, acute pain in the emergency department, prevention of persistent postoperative pain, cancer pain, and chronic non-cancer pain), the efficacy of ketamine is limited. Ketamine’s lack of analgesic effect was associated with an increase in side effects, including schizotypical effects. PMID:28979762

  10. The Pain of Labour (United States)

    Labor, Simona


    Labour is an emotional experience and involves both physiological and psychological mechanisms. The pain of labour is severe but despite this its memory diminishes with time. Labour pain has two components: visceral pain which occurs during the early first stage and the second stage of childbirth, and somatic pain which occurs during the late first stage and the second stage. The pain of labour in the first stage is mediated by T10 to L1 spinal segments, whereas that in the second stage is carried by T12 to L1, and S2 to S4 spinal segments. Pain relief in labour is complex and often challenging without regional analgesia. Effective management of labour pain plays a relatively minor role in a woman's satisfaction with childbirth. PMID:26526404

  11. Pain emotion and homeostasis. (United States)

    Panerai, Alberto E


    Pain has always been considered as part of a defensive strategy, whose specific role is to signal an immediate, active danger. This definition partially fits acute pain, but certainly not chronic pain, that is maintained also in the absence of an active noxa or danger and that nowadays is considered a disease by itself. Moreover, acute pain is not only an automatic alerting system, but its severity and characteristics can change depending on the surrounding environment. The affective, emotional components of pain have been and are the object of extensive attention and research by psychologists, philosophers, physiologists and also pharmacologists. Pain itself can be considered to share the same genesis as emotions and as a specific emotion in contributing to the maintenance of the homeostasis of each unique subject. Interestingly, this role of pain reaches its maximal development in the human; some even argue that it is specific for the human primate.

  12. Back Pain in Children

    Directory of Open Access Journals (Sweden)

    Sadi Kayiran ; Sinan Mahir Kayiran;


    Full Text Available Contrary to popular knowledge, back pain is quite frequently seen in children. While very rare in the pre-school age group, frequency reaches 30% in the adolescent period. In many cases, the causes of back pain in childhood cannot be exactly determined and the pain disappears by itself in a short time. It should be remembered that back pain that persists for more than two weeks may be associated with organic causes. Whether or not there have been disruptions in neurological functions should be definitely probed in the medical history. Keeping in mind that back pain could be a part of a systemic disease, a systemic examination should be carried out in cases where there has been long-term back pain. The complaint of childhood back pain should be assessed with a thorough history, a careful physical examination and advanced testing tools. [TAF Prev Med Bull 2011; 10(1.000: 115-118

  13. Avicenna's concept of pain

    Directory of Open Access Journals (Sweden)

    Osama A. Tashani


    Full Text Available Ibn Sina (Latin name – Avicenna, 980–1037 is a famous Muslim physician who wrote The Canon of Medicine. Pain-related writings within The Canon were identified and analysed and compared to Galen and Modern Pain Theory. We found evidence in The Canon that Avicenna challenged Galen's concept of pain. Galen insisted that injuries (breach of continuity were the only cause of pain. In contrast, Avicenna suggested that the true cause of pain was a change of the physical condition (temperament change of the organ whether there was an injury present or not. Avicenna extended Galen's descriptions of 4 to 15 types of pain and used a terminology that is remarkably similar to that used in the McGill Pain Questionnaire.

  14. Experimental investigation of the impact of compound-specific dispersion and electrostatic interactions on transient transport and solute breakthrough (United States)

    Muniruzzaman, Muhammad; Rolle, Massimo


    This study investigates the effects of compound-specific diffusion/dispersion and electrochemical migration on transient solute transport in saturated porous media. We conducted laboratory bench-scale experiments, under advection-dominated regimes (seepage velocity: 0.5, 5, 25 m/d), in a quasi two-dimensional flow-through setup using pulse injection of multiple tracers (both uncharged and ionic species). Extensive sampling and measurement of solutes' concentrations (˜1500 samples; >3000 measurements) were performed at the outlet of the flow-through setup, at high spatial and temporal resolution. The experimental results show that compound-specific effects and charge-induced Coulombic interactions are important not only at low velocities and/or for steady state plumes but also for transient transport under high flow velocities. Such effects can lead to a remarkably different behavior of measured breakthrough curves also at very high Péclet numbers. To quantitatively interpret the experimental results, we used four modeling approaches: classical advection-dispersion equation (ADE), continuous time random walk (CTRW), dual-domain mass transfer model (DDMT), and a multicomponent ionic dispersion model. The latter is based on the multicomponent formulation of coupled diffusive/dispersive fluxes and was used to describe and explain the electrostatic effects of charged species. Furthermore, we determined experimentally the temporal profiles of the flux-related dilution index. This metric of mixing, used in connection with the traditional solute breakthrough curves, proved to be useful to correctly distinguish between plume spreading and mixing, particularly for the cases in which the sole analysis of integrated concentration breakthrough curves may lead to erroneous interpretation of plume dilution.

  15. Clinical and Microbiological Characteristics of Breakthrough Candidemia in Allogeneic Hematopoietic Stem Cell Transplant Recipients in a Japanese Hospital (United States)

    Kimura, Muneyoshi; Yamamoto, Hisashi; Asano-Mori, Yuki; Nakamura, Shigeki; Yamagoe, Satoshi; Ohno, Hideaki; Miyazaki, Yoshitsugu; Abe, Masahiro; Yuasa, Mitsuhiro; Kaji, Daisuke; Kageyama, Kosei; Nishida, Aya; Ishiwata, Kazuya; Takagi, Shinsuke; Yamamoto, Go; Uchida, Naoyuki; Izutsu, Koji; Wake, Atsushi; Taniguchi, Shuichi; Yoneyama, Akiko


    ABSTRACT Few data on breakthrough candidemia (BC), defined as candidemia that develops on administration of antifungal agents (AFAs), in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are available. The medical and microbiological records of recipients of an allo-HSCT obtained between December 2008 and December 2014 were reviewed. Of 768 allo-HSCT cases, 26 developed BC. Among the 26 causative strains, 22 strains were stored and identified by sequencing. The following species were isolated: Candida parapsilosis (9 strains), C. glabrata (4 strains), C. guilliermondii (3 strains), and other Candida species (6 strains). The AFAs being used when BC developed were micafungin (17 cases), liposomal amphotericin B (5 cases), itraconazole (2 cases), and voriconazole (2 cases). All 17 cases who developed BC during micafungin administration were administered 150 mg/day of micafungin. The susceptibilities of the causative Candida species to the administered AFAs when breakthrough occurred ranged from susceptible to resistant. Especially, 85% of the Candida species that caused BC during micafungin administration were susceptible to micafungin. Additionally, 75% of the strains were wild type for susceptibility to the administered AFAs when breakthrough occurred. Systemic steroid administration and a longer severe neutropenic phase (≥5 days) were independent risk factors for BC (P = 0.016 and P = 0.015, respectively). BC developed in allo-HSCT recipients even when they received a sufficient dose of AFA, including micafungin, to which the causative Candida species were susceptible and/or had wild-type susceptibility in vitro. Systemic steroid administration and a longer severe neutropenic phase were host-based factors associated with BC. PMID:28115352

  16. Pharmacokinetics of vinyl chloride in the rat

    International Nuclear Information System (INIS)

    Bolt, H.M.; Laib, R.J.; Kappus, H.; Buchter, A.


    When rats are exposed to [ 14 C]vinyl chloride in a closed system, the vinyl chloride present in the atmosphere equilibrates with the animals' organism within 15 min. The course of equilibration could be determined using rats which had been given 6-nitro-1,2,3-benzothiadiazole. This compound completely blocks metabolism of vinyl chloride. The enzymes responsible for metabolism of vinyl chloride are saturated at an atmospheric concentration of vinyl chloride of 250 ppm. Pharmacokinetic analysis shows that no significant cumulation of vinyl chloride or its major metabolites is to be expected on repeated administration of vinyl chlorides. This may be consistent with the theory that a reactive, shortly living metabolite which occurs in low concentration only, may be responsible for the toxic effects of vinyl chloride

  17. 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...... used in this study. METHODS: Dogs were administered 5 mg/kg intravenously and 10 mg/kg orally (p.o.) of minocycline hydrochloride in separate crossover experiments. In vivo drug concentrations in plasma and in ISF collected by ultrafiltration were measured by high-performance liquid chromatography...

  18. 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.

  19. 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.

  20. A systems approach for tumor pharmacokinetics.

    Directory of Open Access Journals (Sweden)

    Greg Michael Thurber

    Full Text Available Recent advances in genome inspired target discovery, small molecule screens, development of biological and nanotechnology have led to the introduction of a myriad of new differently sized agents into the clinic. The differences in small and large molecule delivery are becoming increasingly important in combination therapies as well as the use of drugs that modify the physiology of tumors such as anti-angiogenic treatment. The complexity of targeting has led to the development of mathematical models to facilitate understanding, but unfortunately, these studies are often only applicable to a particular molecule, making pharmacokinetic comparisons difficult. Here we develop and describe a framework for categorizing primary pharmacokinetics of drugs in tumors. For modeling purposes, we define drugs not by their mechanism of action but rather their rate-limiting step of delivery. Our simulations account for variations in perfusion, vascularization, interstitial transport, and non-linear local binding and metabolism. Based on a comparison of the fundamental rates determining uptake, drugs were classified into four categories depending on whether uptake is limited by blood flow, extravasation, interstitial diffusion, or local binding and metabolism. Simulations comparing small molecule versus macromolecular drugs show a sharp difference in distribution, which has implications for multi-drug therapies. The tissue-level distribution differs widely in tumors for small molecules versus macromolecular biologic drugs, and this should be considered in the design of agents and treatments. An example using antibodies in mouse xenografts illustrates the different in vivo behavior. This type of transport analysis can be used to aid in model development, experimental data analysis, and imaging and therapeutic agent design.

  1. Pharmacokinetics and efficacy of intraocular flurbiprofen. (United States)

    Blazaki, S; Tsika, C; Tzatzarakis, M; Naoumidi, E; Tsatsakis, A; Tsatsanis, C; Tsilimbaris, Miltiadis K


    Intravitreal delivery of non-steroidal anti-inflammatory drugs could be an effective way to treat macular edema caused by posterior segment inflammation. In this study, we evaluated the intravitreal bioavailability and anti-inflammatory efficacy of flurbiprofen in rabbit eyes. For pharmacokinetics, 0.1 ml of 7.66 mg/ml flurbiprofen solution was injected intravitreally and vitreous drug levels were analyzed at specific time points using LC-MS technique. For efficacy, 100 ng lipopolysaccharide of E.coli was injected intravitreally in rabbits to induce inflammation. The animals were separated in three groups and received intraocular flurbiprofen, dexamethasone and PBS to serve as control. Complete ocular examination and total cell count in aqueous fluid were determined to evaluate the extent of inflammation. Eyes were then enucleated for histopathology analysis. The efficacy in the uveitis model was determined by clinical signs of inflammation, total leukocyte count and histology findings. No adverse events were observed during pharmacokinetic assessment. No signs of inflammation, hemorrhage or retina detachment were detected. The recovery of flurbiprofen from vitreous samples was 92.6%. The half-life of flurbiprofen was estimated to be 1.92 h with an elimination constant rate (K) of 0.36. Treatment with intraocular injections of flurbiprofen and dexamethasone significantly reduced total leukocyte count in a manner comparable to dexamethasone [reduction of 96.84% (p flurbiprofen injection compared to control eyes. Flurbiprofen is effective in suppressing inflammation in this experimental uveitis model. In our experimental setting, intravitreal flurbiprofen seem to have a therapeutic result comparable to dexamethasone. However, the half-life of the drug remains short, necessitating further research to prolong its presence in the vitreous cavity.

  2. [Pharmacokinetics of salazosulfapyridine in a hemodialysis patient]. (United States)

    Akiyama, Yuji; Fujimaki, Toshihisa; Sakurai, Yusei


    The patient was a 62-year-old female. Total gastrectomy was performed due to gastric ulcer in 1969. She was diagnosed as rheumatoid arthritis (RA) in 1985 and was developed to amyloidosis in 1991. She was started on hemodialysis (HD) for chronic renal failure in 1996. In 1998, her arthralgia was aggravated, and 100 mg/day of bucillamine was administered on the day of HD. Her arthralgia persisted, and switching to salazosulfapyridine (SASP) was considered. As there were no standards and no reports for the use of SASP in HD patients, we examined the pharmacokinetics of SASP and its metabolites, and compared our patient with the results of phase one study in normal subjects in Japan. In this case, the blood concentration of SASP was similar to that in healthy controls after single administration of 500 mg of SASP on the day of non-HD, while the concentration of sulfapyridine (SP) was higher than that in healthy donors. However, the blood concentrations of SASP, SP, and N4-acetyl-SP (AcSP) at 24 hours after administration were similar to those obtained in healthy men. SASP was not dialyzed, while about half of SP and AcSP, were dialyzed. In a five-day consecutive administration study also, the blood concentrations of these compounds on Day 5 were similar to those of phase one study, suggesting no accumulation. No adverse drug reaction was observed. As this case had the past history of total gastrectomy and amyloidosis, it is possible that this result is influenced by the factors. Therefore it is necessary to examine pharmacokinetics of SASP and its metabolites beforehand when administering this agent to other HD/RA patients.

  3. 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.

  4. Dynamic adsorption of CO2/N2 on cation-exchanged chabazite SSZ-13: A breakthrough analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bower, Jamey K.; Barpaga, Dushyant; Prodinger, Sebastian; Krishna, Rajamani; Schaef, Herbert T.; McGrail, Bernard P.; Derewinski, Miroslaw A.; Motkuri, Radha K.


    Alkali exchanged SSZ-13 adsorbents were investigated for their applicability in separating N2 from CO2 in flue gas streams using a dynamic breakthrough method. In contrast to IAST calculations based on equilibrium isotherms, K+ exchanged SSZ-13 was found to yield the best N2 productivity under dynamic conditions where diffusion properties play a significant role. This was attributed to the selective, partial blockage of access to the CHA cavities enhancing the separation potential in a 15/85 CO2/N2 binary gas mixture.

  5. Breakthrough of the Nordic Bronze Age: Transcultural warriorhood and a Carpathian crossroad in the 16th century BC

    DEFF Research Database (Denmark)

    Vandkilde, Helle


    The breakthrough of the Nordic Bronze Age (NBA) c. 1600 bc as a koiné within Bronze Age Europe can be historically linked to the Carpathian Basin. Nordic distinctiveness entailed an entanglement of cosmology and warriorhood, albeit represented through different media in the hotspot zone (bronze) ...... momentous creativity that drew upon Carpathian originals, contacts and a pool of Carpathian ideas, but ultimately drawing on emergent Mycenaean hegemonies in the Aegean. This provided the incentive for a cosmology-rooted resource from which the NBA could take its starting point....

  6. Chronic female pelvic pain

    Directory of Open Access Journals (Sweden)

    Gaurab Maitra


    Full Text Available Chronic pelvic pain (CPP is defined as nonmalignant pain perceived in the structures related to the pelvis that has been present for more than 6 months or a non acute pain mechanism of shorter duration. Pain in the pelvic region can arise from musculoskeletal, gynaecological, urologic, gastrointestinal and or neurologic conditions. Key gynaecological conditions that contribute to CPP include pelvic inflammatory disease (PID, endometriosis, adnexa pathologies (ovarian cysts, ovarian remnant syndrome, uterine pathologies (leiomyoma, adenomyosis and pelvic girdle pain associated with pregnancy. Several major and minor sexually transmitted diseases (STD can cause pelvic and vulvar pain. A common painful condition of the urinary system is Interstitial cystitis(IC. A second urologic condition that can lead to development of CPP is urethral syndrome. Irritable bowel syndrome (IBS is associated with dysmenorrhoea in 60% of cases. Other bowel conditions contributing to pelvic pain include diverticular disease,Crohn′s disease ulcerative colitis and chronic appendicitis. Musculoskeletal pathologies that can cause pelvic pain include sacroiliac joint (SIJ dysfunction, symphysis pubis and sacro-coccygeal joint dysfunction, coccyx injury or malposition and neuropathic structures in the lower thoracic, lumbar and sacral plexus. Prolonged pelvic girdle pain, lasting more than 6 months postpartum is estimated in 3% to 30% of women. Nerve irritation or entrapment as a cause of pelvic pain can be related to injury of the upper lumbar segments giving rise to irritation of the sensory nerves to the ventral trunk or from direct trauma from abdominal incisions or retractors used during abdominal surgical procedures. Afflictions of the iliohypogastric, ilioinguinal, genitofemoral, pudendal and obturator nerves are of greatest concern in patients with pelvic pain. Patient education about the disease and treatment involved is paramount. A knowledge of the differential

  7. Modeling the onset and offset of dental pain relief by ibuprofen. (United States)

    Li, Hanbin; Mandema, Jaap; Wada, Russell; Jayawardena, Shyamalie; Desjardins, Paul; Doyle, Geraldine; Kellstein, David


    Onset and offset of dental pain relief by ibuprofen following third molar extraction were modeled in a randomized, double-blind, placebo-controlled, parallel-group, 8-hour study of patients receiving either a novel effervescent ibuprofen tablet (400 mg; N = 30), standard ibuprofen tablets (Nurofen(®) 2 × 200 mg; N = 22), or placebo (N = 37). An Emax model was fit to pain relief scores. Linear hazard models were used to analyze the time to first perceptible relief (TFPR), the time to meaningful pain relief (TMPR), and time to remedication (REMD). Nomograms were created to correlate TFPR, TMPR, and REMD with different ibuprofen pharmacokinetic profiles. Effervescent ibuprofen was absorbed rapidly with 95% completion within 15 minutes. Maximum pain relief score by ibuprofen was 1.8 units greater than placebo, with an EC50 (effect-site) for ibuprofen concentration of 10.2 µg·mL(-1). The likelihood to achieve TFPR and TMPR was doubled for every 10 µg·mL(-1) increase in ibuprofen plasma concentration. REMD risk decreased 40-fold as the categorical pain relief score increased from 0 to 3. Rapid absorption of ibuprofen effervescent resulted in an earlier TFPR and TMPR, and a lower REMD rate than standard ibuprofen. The nomograms may be useful in predicting the onset and offset of new faster acting ibuprofen formulations, based on pharmacokinetic profiles.

  8. Effect of Smoking on Pharmacokinetics of Clopidogrel, an ...

    African Journals Online (AJOL)

    ... in patients undergoing PCI. Keywords: Antiplatelet, Clopidogrel, Pharmacokinetics, Smoking, Cigarette ..... regimen of choice to prevent thrombotic complications. [2,16]. ... either the parent drug [19] or the carboxylic acid metabolite as an ...

  9. Pharmacokinetics of Rhodamine 110 and Its Organ Distribution in Rats. (United States)

    Jiang, Shiau-Han; Cheng, Yung-Yi; Huo, Teh-Ia; Tsai, Tung-Hu


    Rhodamine dyes have been banned as food additives due to their potential tumorigenicity. Rhodamine 110 is illegal as a food additive, although its pharmacokinetics have not been characterized, and no accurate bioanalytical methods are available to quantify rhodamine 110. The aim of this study was to develop and validate a fast, stable, and sensitive method to quantify rhodamine 110 using high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) to assess its pharmacokinetics and organ distribution in awake rats. Rhodamine 110 exhibited linear pharmacokinetics and slow elimination after oral administration. Furthermore, its oral bioavailability was approximately 34-35%. The distribution in the liver and kidney suggests that these organs are primarily responsible for rhodamine 110 metabolism and elimination. Our investigation describes the pharmacokinetics and a quantification method for rhodamine 110, improving our understanding of the food safety of rhodamine dyes.

  10. A Comparative Study of the Pharmacokinetics of Conventional and ...

    African Journals Online (AJOL)


    Purpose: To examine the pharmacokinetics of a formulated aceclofenac sustained release ... over 24 h and analyzed by high performance liquid chromatography (HPLC). .... The response factor .... slower drug disposition and prolonged effect.

  11. Pharmacokinetically guided dosing of (high-dose) chemotherapeutic agents

    NARCIS (Netherlands)

    Attema-de Jonge, M.E. (Milly Ellen)


    Due to variation in drug distribution, metabolism and elimination processes between patients, systemic exposure to chemotherapeutic agents may be highly variable from patient to patient after administration of similar doses. This pharmacokinetic variability may explain in part the large variability

  12. Effect of CH4 on the CO2 breakthrough pressure and permeability of partially saturated low-permeability sandstone in the Ordos Basin, China (United States)

    Zhao, Yan; Yu, Qingchun


    The behavior of CO2 that coexists with CH4 and the effect of CH4 on the CO2 stream need to be deeply analyzed and studied, especially in the presence of water. Our previous studies investigated the breakthrough pressure and permeability of pure CO2 in five partially saturated low-permeability sandstone core samples from the Ordos Basin, and we concluded that rocks with a small pore size and low permeability show considerable sealing capacity even under unsaturated conditions. In this paper, we selected three of these samples for CO2-CH4 gas-mixture breakthrough experiments under various degrees of water saturation. The breakthrough experiments were performed by increasing the gas pressure step by step until breakthrough occurred. Then, the effluent gas mixture was collected for chromatographic partitioning analysis. The results indicate that CH4 significantly affects the breakthrough pressure and permeability of CO2. The presence of CH4 in the gas mixture increases the interfacial tension and, thus, the breakthrough pressure. Therefore, the injected gas mixture that contains the highest (lowest) mole fraction of CH4 results in the largest (smallest) breakthrough pressure. The permeability of the gas mixture is greater than that for pure CO2 because of CH4, and the effective permeability decreases with increased breakthrough pressure. Chromatographic partitioning of the effluent mixture gases indicates that CH4 breaks through ahead of CO2 as a result of its weaker solubility in water. Correlations are established between (1) the breakthrough pressure and water saturation, (2) the effective permeability and water saturation, (3) the breakthrough pressure and effective permeability, and (4) the mole fraction of CO2/CH4 in the effluent mixture gases and water saturation. These results deepen our understanding of the multi-phase flow behavior in the porous media under unsaturated conditions, which have implications for formulating emergency response plans for gas

  13. Research design considerations for single-dose analgesic clinical trials in acute pain

    DEFF Research Database (Denmark)

    Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C


    This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials......, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay...... sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable...

  14. Back pain and low back pain

    International Nuclear Information System (INIS)

    Cotta, H.; Niethard, F.U.


    In patients with back pain there is only a poor correlation between clinical and radiological symptoms. Therefore the interpretation of radiological findings is only possible with respect to the natural history of the disease. Indication for radiological examination is given for early diagnosis and treatment of malinformation of the spine; diagnosis and treatment of functional disturbances of the spine with back- and low back pain and diagnosis and treatment of diseases which affect the stability of the vertebrae. (orig.)

  15. Absorption and pharmacokinetics of grapefruit flavanones in beagles


    Mata Bilbao, María de Lourdes; Andrés Lacueva, Ma. Cristina; Roura Carvajal, Elena; Jáuregui Pallarés, Olga; Escribano Ferrer, Elvira; Torre, Celina; Lamuela Raventós, Rosa Ma.


    The present study evaluated the pharmacokinetics of three different grapefruit flavanone forms in dog plasma and demonstrated their absorption after an oral intake of a grapefruit extract; pharmacokinetic parameters of these forms were also determined. Ten healthy beagles were administered 70 mg citrus flavonoids as a grapefruit extract contained in capsules, while two additional dogs were used as controls and given an excipient. The grapefruit flavanone naringin, along with its metabolites n...

  16. Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

    Directory of Open Access Journals (Sweden)

    Hao Jiqing


    Full Text Available Abstract Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms.

  17. Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain (United States)

    Wu, Hongyang; Chen, Zhendong; Sun, Guoping; Gu, Kangsheng; Pan, Yueyin; Hao, Jiqing; Du, Yingying; Ning, Jie


    Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms. PMID:19267934

  18. Maintenance of Pain in Children With Functional Abdominal Pain. (United States)

    Czyzewski, Danita I; Self, Mariella M; Williams, Amy E; Weidler, Erica M; Blatz, Allison M; Shulman, Robert J


    A significant proportion of children with functional abdominal pain develop chronic pain. Identifying clinical characteristics predicting pain persistence is important in targeting interventions. We examined whether child anxiety and/or pain-stooling relations were related to maintenance of abdominal pain frequency and compared the predictive value of 3 methods for assessing pain-stooling relations (ie, diary, parent report, child report). Seventy-six children (7-10 years old at baseline) who presented for medical treatment of functional abdominal pain were followed up 18 to 24 months later. Baseline anxiety and abdominal pain-stooling relations based on pain and stooling diaries and child- and parent questionnaires were examined in relationship to the persistence of abdominal pain frequency. Children's baseline anxiety was not related to persistence of pain frequency. Children who, however, displayed irritable bowel syndrome (IBS) symptoms at baseline maintained pain frequency at follow-up, whereas in children in whom there was no relationship between pain and stooling, pain frequency decreased. Pain and stool diaries and parent report of pain-stooling relations were predictive of pain persistence but child-report questionnaires were not. The presence of IBS symptoms in school-age children with functional abdominal pain appears to predict persistence of abdominal pain over time, whereas anxiety does not. Prospective pain and stooling diaries and parent report of IBS symptoms were predictors of pain maintenance, but child report of symptoms was not.

  19. Pain after earthquake

    Directory of Open Access Journals (Sweden)

    Angeletti Chiara


    Full Text Available Abstract Introduction On 6 April 2009, at 03:32 local time, an Mw 6.3 earthquake hit the Abruzzi region of central Italy causing widespread damage in the City of L Aquila and its nearby villages. The earthquake caused 308 casualties and over 1,500 injuries, displaced more than 25,000 people and induced significant damage to more than 10,000 buildings in the L'Aquila region. Objectives This observational retrospective study evaluated the prevalence and drug treatment of pain in the five weeks following the L'Aquila earthquake (April 6, 2009. Methods 958 triage documents were analysed for patients pain severity, pain type, and treatment efficacy. Results A third of pain patients reported pain with a prevalence of 34.6%. More than half of pain patients reported severe pain (58.8%. Analgesic agents were limited to available drugs: anti-inflammatory agents, paracetamol, and weak opioids. Reduction in verbal numerical pain scores within the first 24 hours after treatment was achieved with the medications at hand. Pain prevalence and characterization exhibited a biphasic pattern with acute pain syndromes owing to trauma occurring in the first 15 days after the earthquake; traumatic pain then decreased and re-surged at around week five, owing to rebuilding efforts. In the second through fourth week, reports of pain occurred mainly owing to relapses of chronic conditions. Conclusions This study indicates that pain is prevalent during natural disasters, may exhibit a discernible pattern over the weeks following the event, and current drug treatments in this region may be adequate for emergency situations.

  20. Chronic Abdominal Wall Pain. (United States)

    Koop, Herbert; Koprdova, Simona; Schürmann, Christine


    Chronic abdominal wall pain is a poorly recognized clinical problem despite being an important element in the differential diagnosis of abdominal pain. This review is based on pertinent articles that were retrieved by a selective search in PubMed and EMBASE employing the terms "abdominal wall pain" and "cutaneous nerve entrapment syndrome," as well as on the authors' clinical experience. In 2% to 3% of patients with chronic abdominal pain, the pain arises from the abdominal wall; in patients with previously diagnosed chronic abdominal pain who have no demonstrable pathological abnormality, this likelihood can rise as high as 30% . There have only been a small number of clinical trials of treatment for this condition. The diagnosis is made on clinical grounds, with the aid of Carnett's test. The characteristic clinical feature is strictly localized pain in the anterior abdominal wall, which is often mischaracterized as a "functional" complaint. In one study, injection of local anesthesia combined with steroids into the painful area was found to relieve pain for 4 weeks in 95% of patients. The injection of lidocaine alone brought about improvement in 83-91% of patients. Long-term pain relief ensued after a single lidocaine injection in 20-30% of patients, after repeated injections in 40-50% , and after combined lidocaine and steroid injections in up to 80% . Pain that persists despite these treatments can be treated with surgery (neurectomy). Chronic abdominal wall pain is easily diagnosed on physical examination and can often be rapidly treated. Any physician treating patients with abdominal pain should be aware of this condition. Further comparative treatment trials will be needed before a validated treatment algorithm can be established.

  1. The Breakthrough Listen Search for Intelligent Life: A Wideband Data Recorder System for the Robert C. Byrd Green Bank Telescope (United States)

    MacMahon, David H. E.; Price, Danny C.; Lebofsky, Matthew; Siemion, Andrew P. V.; Croft, Steve; DeBoer, David; Enriquez, J. Emilio; Gajjar, Vishal; Hellbourg, Gregory; Isaacson, Howard; Werthimer, Dan; Abdurashidova, Zuhra; Bloss, Marty; Brandt, Joe; Creager, Ramon; Ford, John; Lynch, Ryan S.; Maddalena, Ronald J.; McCullough, Randy; Ray, Jason; Whitehead, Mark; Woody, Dave


    The Breakthrough Listen Initiative is undertaking a comprehensive search for radio and optical signatures from extraterrestrial civilizations. An integral component of the project is the design and implementation of wide-bandwidth data recorder and signal processing systems. The capabilities of these systems, particularly at radio frequencies, directly determine survey speed; further, given a fixed observing time and spectral coverage, they determine sensitivity as well. Here, we detail the Breakthrough Listen wide-bandwidth data recording system deployed at the 100 m aperture Robert C. Byrd Green Bank Telescope. The system digitizes up to 6 GHz of bandwidth at 8 bits for both polarizations, storing the resultant 24 GB s‑1 of data to disk. This system is among the highest data rate baseband recording systems in use in radio astronomy. A future system expansion will double recording capacity, to achieve a total Nyquist bandwidth of 12 GHz in two polarizations. In this paper, we present details of the system architecture, along with salient configuration and disk-write optimizations used to achieve high-throughput data capture on commodity compute servers and consumer-class hard disk drives.

  2. Integrated care for patients with a stroke in the Netherlands: results and experiences from a national Breakthrough Collaborative Improvement project

    Directory of Open Access Journals (Sweden)

    M.M.N. Minkman


    Full Text Available Purpose: This article considers the question if measurable improvements are achieved in the quality of care in stroke services by using a Breakthrough collaborative quality improvement model. Context of case: Despite the availability of explicit criteria, evidence based guidelines, national protocols and examples of best practices; stroke care in the Netherlands did not improve substantially yet. For that reason a national collaborative started in 2002 to improve integrated stroke care in 23 self selected stroke services. Data sources: Characteristics of sites, teams, aims and changes were assessed by using a questionnaire and monthly self-reports of teams. Progress in achieving significant quality improvement has been assessed on a five point Likert scale (IHI score. Case description: The stroke services (n=23 formed multidisciplinary teams, which worked together in a collaborative based on the IHI Breakthrough Series Model. Teams received instruction in quality improvement, reviewed self reported performance data, identified bottlenecks and improvement goals, and implemented “potentially better practices” based on criteria from the Edisse study, evidence based guidelines, own ideas and expert opinion. Conclusion and discussion: Quality of care has been improved in most participating stroke services. Eighty-seven percent of the teams have improved their care significantly on at least one topic. About 34% of the teams have achieved significant improvement on all aims within the time frame of the project. The project has contributed to the further development and spread of integrated stroke care in the Netherlands.

  3. Persistent facial pain conditions

    DEFF Research Database (Denmark)

    Forssell, Heli; Alstergren, Per; Bakke, Merete


    Persistent facial pains, especially temporomandibular disorders (TMD), are common conditions. As dentists are responsible for the treatment of most of these disorders, up-to date knowledge on the latest advances in the field is essential for successful diagnosis and management. The review covers...... TMD, and different neuropathic or putative neuropathic facial pains such as persistent idiopathic facial pain and atypical odontalgia, trigeminal neuralgia and painful posttraumatic trigeminal neuropathy. The article presents an overview of TMD pain as a biopsychosocial condition, its prevalence......, clinical features, consequences, central and peripheral mechanisms, diagnostic criteria (DC/TMD), and principles of management. For each of the neuropathic facial pain entities, the definitions, prevalence, clinical features, and diagnostics are described. The current understanding of the pathophysiology...

  4. Spiritual pain and suffering. (United States)

    Brunjes, George B


    Spiritual pain/suffering is commonly experienced by persons with life-limiting illness and their families. Physical pain itself can be exacerbated by non-physical causes such as fear, anxiety, grief, unresolved guilt, depression and unmet spiritual meets. Likewise, the inability to manage physical pain well can be due to emotional and spiritual needs. This is why a holistic, interdisciplinary assessment of pain and suffering is required for each patient and family. The mind, body and spirit are understood in relationship to each other and, in those cases, in relationship to a deity or deities are important to understand. Cultural interpretations of pain and suffering may conflict with the goals of palliative care. Understanding the spiritual framework of the patient and family can help to assure that the physical and spiritual suffering of the patient can be eliminated to provide a peaceful death. Spiritual practices may help in the management of physical pain.

  5. [Cannabinoids in pain medicine]. (United States)

    Karst, M


    The endocannabinoid system (ECS) controls a large number of vital functions. Suboptimal tone of the ECS in certain regions of the nervous system may be associated with disorders that are also associated with pain. Pain and inflammation processes can be modulated by the exogenous supply of cannabinoids. Low-to-moderate pain-relieving effects and in individual cases large pain-relieving effects were observed in randomized, controlled studies of various types of chronic pain. People with chronic neuropathic pain and stress symptoms seem to particularly benefit. The therapeutic range of cannabinoids is small; often small doses are sufficient for clinically significant effects. The "Cannabis-als-Medizin-Gesetz" (cannabis as medicine law) allows the prescription of cannabis preparations under certain conditions. Available data indicate good long-term efficacy and tolerability. However, there is little systematic long-term experience from clinical studies.


    Directory of Open Access Journals (Sweden)

    Aleš Vesnaver


    Full Text Available Background. Chronic unexplained orofacial pain is frequently the cause of prolonged suffering for the patient and an unsolvable problem for the therapist. Pathophysiology of the onset of this type of pain is virtually unknown. Still, it is possible to divide chronic orofacial pain into several separate categories, according to its onset, symptoms and therapy. All forms of this type of pain have a strong psychological component.Methods. A retrograde review was conducted, in which patients’ records, treated in 1994 for chronic unexplained orofacial pain, were followed through a 5 year period. The modalities of treatment then and at present were compared.Conclusions. Except for trigeminal neuralgia, where carbamazepine remains the first choice drug, treatment of chronic facial pain has changed considerably.

  7. Orofacial pain conditions

    DEFF Research Database (Denmark)

    Pedersen, Anne Marie Lynge; Forssell, Heli; Grinde, Bjørn


    Pain of the oral mucosa is a common accompanying symptom of various oral mucosal lesions caused by local and systemic diseases. Pain of the oral mucosa is usually associated with a known cause of tissue damage, e.g. mucosal ulcer or erosion, and it generally responds to adequate treatment...... and dissolves after healing. Chronic pain, on the other hand, persists months and years after apparent tissue healing, and attempts to alleviate pain are challenging. Neuropathic pain occurs due to damage neurogenic structures in the peripheral and/or the central nervous system. It may occur in the absence...... of any obvious noxious stimuli, and in the oral mucosal, the pain is often described as tingling and burning. In the oral cavity, burning mouth syndrome (BMS) is presently considered to have neuropathic background. It is important for dental practitioners to have a clear understanding of the various...

  8. Thoracic spine pain

    Directory of Open Access Journals (Sweden)

    Aleksey Ivanovich Isaikin


    Full Text Available Thoracic spine pain, or thoracalgia, is one of the common reasons for seeking for medical advice. The epidemiology and semiotics of pain in the thoracic spine unlike in those in the cervical and lumbar spine have not been inadequately studied. The causes of thoracic spine pain are varied: diseases of the cardiovascular, gastrointestinal, pulmonary, and renal systems, injuries to the musculoskeletal structures of the cervical and thoracic portions, which require a thorough differential diagnosis. Facet, costotransverse, and costovertebral joint injuries and myofascial syndrome are the most common causes of musculoskeletal (nonspecific pain in the thoracic spine. True radicular pain is rarely encountered. Traditionally, treatment for thoracalgia includes a combination of non-drug and drug therapies. The cyclooxygenase 2 inhibitor meloxicam (movalis may be the drug of choice in the treatment of musculoskeletal pain.

  9. Neonatal pain management

    Directory of Open Access Journals (Sweden)

    Tarun Bhalla


    Full Text Available The past 2-3 decades have seen dramatic changes in the approach to pain management in the neonate. These practices started with refuting previously held misconceptions regarding nociception in preterm infants. Although neonates were initially thought to have limited response to painful stimuli, it was demonstrated that the developmental immaturity of the central nervous system makes the neonate more likely to feel pain. It was further demonstrated that untreated pain can have long-lasting physiologic and neurodevelopmental consequences. These concerns have resulted in a significant emphasis on improving and optimizing the techniques of analgesia for neonates and infants. The following article will review techniques for pain assessment, prevention, and treatment in this population with a specific focus on acute pain related to medical and surgical conditions.

  10. Mental Pain and Suicide

    DEFF Research Database (Denmark)

    Verrocchio, Maria Cristina; Carrozzino, Danilo; Marchetti, Daniela


    ideation than depression. Conclusion: Mental pain is a core clinical factor for understanding suicide, both in the context of mood disorders and independently from depression. Health care professionals need to be aware of the higher suicidal risk in patients reporting mental pain. In this regard......Background: Mental pain, defined as a subjective experience characterized by perception of strong negative feelings and changes in the self and its function, is no less real than other types of grief. Mental pain has been considered to be a distinct entity from depression. We have performed...... a systematic review analyzing the relationship between mental pain and suicide by providing a qualitative data synthesis of the studies. Methods: We have conducted, in accordance with PRISMA guidelines, a systematic search for the literature in PubMed, Web Of Science, and Scopus. Search terms were "mental pain...

  11. Chronic whiplash pain. (United States)

    Seroussi, Richard; Singh, Virtaj; Fry, Adrielle


    Although most patients recover from acute whiplash injuries, those with chronic whiplash syndrome develop signs of central nervous system (CNS) amplification of pain and have a poor prognosis. In this context, specific pain generators from acute whiplash have been identified through clinical, biomechanical, and animal studies. This article gives a clinical perspective on current understanding of these pain generators, including the phenomenon of CNS sensitization. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Ocular pharmacokinetics of 0.45% ketorolac tromethamine. (United States)

    Attar, Mayssa; Schiffman, Rhett; Borbridge, Lisa; Farnes, Quinn; Welty, Devin


    A new carboxymethylcellulose (CMC)-containing ophthalmic formulation of 0.45% ketorolac, pH 6.8 (Acuvail(®)) was recently developed for treatment of inflammation and pain after cataract surgery. This study compared pharmacokinetics of the new formulation with that of a prior formulation, 0.4% ketorolac, pH 7.4 (Acular LS(®)). Ketorolac formulations were administered bilaterally (35 μL) to female New Zealand White rabbits. Samples from aqueous humor and iris-ciliary body were collected at multiple time points, and ketorolac was quantified using liquid chromatography-tandem mass spectrometry. In aqueous humor, the peak concentration (C(max)) and area under the concentration-time curve (AUC(0-τ)) of ketorolac were, respectively, 389 ng/mL and 939 ng·h/mL following administration of the CMC-containing 0.45% ketorolac, pH 6.8, and 211 ng/mL and 465 ng·hr/mL following administration of the 0.4% ketorolac, pH 7.4. In iris-ciliary body, C(max) and AUC(0-τ) of ketorolac were, respectively 450 ng/g and 2040 ng·h/g after administration of the CMC-containing 0.45% ketorolac, pH 6.8, and 216 ng/g and 699 ng·h/g after administration of the 0.4% ketorolac, pH 7.4. PK simulations predicted an AUC(0-τ) of 2910 ng·h/g for twice daily, CMC-containing 0.45% ketorolac, pH 6.8, compared to 725 ng·h/g for 4 times daily, 0.4% ketorolac, pH 7.4. The CMC-containing formulation of 0.45% ketorolac, pH 6.8, increased ketorolac bioavailability by 2-fold in aqueous humor and by 3-fold in iris-ciliary body in comparison to the 0.4% ketorolac, pH 7.4, allowing a reduced dosing schedule from 4 times daily to twice daily.

  13. Imaging of painful scoliosis

    Energy Technology Data Exchange (ETDEWEB)

    Davies, Alun; Saifuddin, Asif [Royal National Orthopaedic Hospital Trust, Department of Radiology, London (United Kingdom)


    Scoliosis is defined as a lateral deviation of the spine from the normal plumb line. Commonly, there is a rotational component and deviation also in the sagittal plane (kyphosis or hyperlordosis). When scoliosis presents in adults, it is often painful. In contrast, back pain in a child is considered rare, and serious underlying pathology should be excluded, particularly since idiopathic scoliosis is typically painless. A painful scoliosis in a child or adolescent, especially if the patient has a left-sided curve, should be examined thoroughly. The aim of this review is to illustrate the causes of a painful scoliosis in children, adolescents and adults. (orig.)

  14. Imaging of painful scoliosis

    International Nuclear Information System (INIS)

    Davies, Alun; Saifuddin, Asif


    Scoliosis is defined as a lateral deviation of the spine from the normal plumb line. Commonly, there is a rotational component and deviation also in the sagittal plane (kyphosis or hyperlordosis). When scoliosis presents in adults, it is often painful. In contrast, back pain in a child is considered rare, and serious underlying pathology should be excluded, particularly since idiopathic scoliosis is typically painless. A painful scoliosis in a child or adolescent, especially if the patient has a left-sided curve, should be examined thoroughly. The aim of this review is to illustrate the causes of a painful scoliosis in children, adolescents and adults. (orig.)

  15. Acute pain assessment

    LENUS (Irish Health Repository)

    Clear, Elaine


    The International Association for the Study of Pain defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage” (IASP, 1997). This definition of pain emphasises that it is neither a sensory nor an emotional experience, but a combination of both. It is a subjective experience influenced by physical, psychological and environmental factors that is assessed from a biopsychosocial perspective. The gold standard in assessing pain however is always what the patient says it is.

  16. Pharmacokinetics of Chinese medicines: strategies and perspectives. (United States)

    Yan, Ru; Yang, Ying; Chen, Yijia


    The modernization and internationalization of Chinese medicines (CMs) are hampered by increasing concerns on the safety and the efficacy. Pharmacokinetic (PK) study is indispensable to establish concentration-activity/toxicity relationship and facilitate target identification and new drug discovery from CMs. To cope with tremendous challenges rooted from chemical complexity of CMs, the classic PK strategies have evolved rapidly from PK study focusing on marker/main drug components to PK-PD correlation study adopting metabolomics approaches to characterize associations between disposition of global drug-related components and host metabolic network shifts. However, the majority of PK studies of CMs have adopted the approaches tailored for western medicines and focused on the systemic exposures of drug-related components, most of which were found to be too low to account for the holistic benefits of CMs. With an area under concentration-time curve- or activity-weighted approach, integral PK attempts to understand the PK-PD relevance with the integrated PK profile of multiple co-existing structural analogs (prototyes/metabolites). Cellular PK-PD complements traditional PK-PD when drug targets localize inside the cells, instead of at the surface of cell membrane or extracellular space. Considering the validated clinical benefits of CMs, reverse pharmacology-based reverse PK strategy was proposed to facilitate target identification and new drug discovery. Recently, gut microbiota have demonstrated multifaceted roles in drug efficacy/toxicity. In traditional oral intake, the presystemic interactions of CMs with gut microbiota seem inevitable, which can contribute to the holistic benefits of CMs through biotransforming CMs components, acting as the peripheral target, and regulating host drug disposition. Hence, we propose a global PK-PD approach which includes the presystemic interaction of CMs with gut microbiota and combines omics with physiologically based

  17. Granular activated carbon adsorption of organic micro-pollutants in drinking water and treated wastewater--Aligning breakthrough curves and capacities. (United States)

    Zietzschmann, Frederik; Stützer, Christian; Jekel, Martin


    Small-scale granular activated carbon (GAC) tests for the adsorption of organic micro-pollutants (OMP) were conducted with drinking water and wastewater treatment plant (WWTP) effluent. In both waters, three influent OMP concentration levels were tested. As long as the influent OMP concentrations are below certain thresholds, the relative breakthrough behavior is not impacted in the respective water. Accordingly, the GAC capacity for OMP is directly proportional to the influent OMP concentration in the corresponding water. The differences between the OMP breakthrough curves in drinking water and WWTP effluent can be attributed to the concentrations of the low molecular weight acid and neutral (LMW) organics of the waters. Presenting the relative OMP concentrations (c/c0) over the specific throughput of the LMW organics (mg LMW organics/g GAC), the OMP breakthrough curves in drinking water and WWTP effluent superimpose each other. This superimposition can be further increased if the UV absorbance at 254 nm (UV254) of the LMW organics is considered. In contrast, using the specific throughput of the dissolved organic carbon (DOC) did not suffice to obtain superimposed breakthrough curves. Thus, the LMW organics are the major water constituent impacting OMP adsorption onto GAC. The results demonstrate that knowing the influent OMP and LMW organics concentrations (and UV254) of different waters, the OMP breakthroughs and GAC capacities corresponding to any water can be applied to all other waters. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Doubling Your Payoff: Winning Pain Relief Engages Endogenous Pain Inhibition (United States)

    Becker, Susanne; Gandhi, Wiebke; Kwan, Saskia; Ahmed, Alysha-Karima; Schweinhardt, Petra


    When in pain, pain relief is much sought after, particularly for individuals with chronic pain. In analogy to augmentation of the hedonic experience ("liking") of a reward by the motivation to obtain a reward ("wanting"), the seeking of pain relief in a motivated state might increase the experience of pain relief when obtained. We tested this hypothesis in a psychophysical experiment in healthy human subjects, by assessing potential pain-inhibitory effects of pain relief "won" in a wheel of fortune game compared with pain relief without winning, exploiting the fact that the mere chance of winning induces a motivated state. The results show pain-inhibitory effects of pain relief obtained by winning in behaviorally assessed pain perception and ratings of pain intensity. Further, the higher participants scored on the personality trait novelty seeking, the more pain inhibition was induced. These results provide evidence that pain relief, when obtained in a motivated state, engages endogenous pain-inhibitory systems beyond the pain reduction that underlies the relief in the first place. Consequently, such pain relief might be used to improve behavioral pain therapy, inducing a positive, perhaps self-amplifying feedback loop of reduced pain and improved functionality.

  19. Population pharmacokinetics of olprinone in healthy male volunteers

    Directory of Open Access Journals (Sweden)

    Kunisawa T


    Full Text Available Takayuki Kunisawa,1 Hidefumi Kasai,2 Makoto Suda,2 Manabu Yoshimura,3 Ami Sugawara,3 Yuki Izumi,3 Takafumi Iida,3 Atsushi Kurosawa,3 Hiroshi Iwasaki3 1Surgical Operation Department, Asahikawa Medical University Hospital, Hokkaido, Japan; 2Clinical Study Management Division, Bell Medical Solutions Inc, Tokyo, Japan; 3Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan Background: Olprinone decreases the cardiac preload and/or afterload because of its vasodilatory effect and increases myocardial contractility by inhibiting phosphodiesterase III. Purpose: The objective of this study was to characterize the population pharmacokinetics of olprinone after a single continuous infusion in healthy male volunteers. Methods: We used 500 plasma concentration data points collected from nine healthy male volunteers for the study. The population pharmacokinetic analysis was performed using the nonlinear mixed effect model (NONMEM® software. Results: The time course of plasma concentration of olprinone was best described using a two-compartment model. The final pharmacokinetic parameters were total clearance (7.37 mL/minute/kg, distribution volume of the central compartment (134 mL/kg, intercompartmental clearance (7.75 mL/minute/kg, and distribution volume of the peripheral compartment (275 mL/kg. The interindividual variability in the total clearance was 12.4%, and the residual error variability (exponential and additive were 22.2% and 0.129 (standard deviation. The final pharmacokinetic model was assessed using a bootstrap method and visual predictive check. Conclusion: We developed a population pharmacokinetic model of olprinone in healthy male adults. The bootstrap method and visual predictive check showed that this model was appropriate. Our results might be used to develop the population pharmacokinetic model in patients. Keywords: phosphodiesterase III inhibitor, men, pharmacokinetic model

  20. Pharmacokinetics of Diclofenac and Hydroxypropyl‐β‐Cyclodextrin (HPβCD) Following Administration of Injectable HPβCD‐Diclofenac in Subjects With Mild to Moderate Renal Insufficiency or Mild Hepatic Impairment


    Hamilton, Douglas A.; Ernst, Cynthia C.; Kramer, William G.; Madden, Donna; Lang, Eric; Liao, Edward; Lacouture, Peter G.; Ramaiya, Atulkumar; Carr, Daniel B.


    Abstract Given their established analgesic properties, nonsteroidal anti‐inflammatory drugs (NSAIDs) represent an important postoperative pain management option. This study investigated: (1) the effects of mild or moderate renal insufficiency and mild hepatic impairment on the pharmacokinetics (PK) of diclofenac and hydroxypropyl‐β‐cyclodextrin (HPβCD) following administration of the injectable NSAID HPβCD‐diclofenac; and (2) the PK of HPβCD following administration of HPβCD‐diclofenac and in...